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Cuomo A, Forleo GB, Ghodhbane T, Johnsen J, Montejo AL, Oliveira CV, Pillinger T, Ramos-Quiroga JA, Samara M, Seerden PHB, Thomas Stoeckl T, Fagiolini A. Physical illness in schizophrenia and the role of tolerability in antipsychotic selection: an expert consensus with a focus on cariprazine. Ann Gen Psychiatry 2025; 24:13. [PMID: 40075512 PMCID: PMC11905634 DOI: 10.1186/s12991-025-00550-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 02/12/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Schizophrenia is a highly heterogeneous disease, and a high percentage of patients are at high risk of developing somatic comorbidities, which must be taken into account in disease management and treatment selection. MAIN BODY Antipsychotics are often associated with side effects that worsen the somatic comorbidities. Among the different options, cariprazine is generally safe and usually well tolerated in both acute and long-term treatment and is often a good choice when balancing clinical benefits and side effects. Given the lack of consensus on the priority of symptoms to treat and the reasons for switching therapy based on the balance between side effects and symptom resolution, twelve psychiatrists met for an expert meeting to discuss the most common and worrisome antipsychotic side effects leading to switching, the most important somatic comorbidities, and the best way to address specific symptoms in both the acute and maintenance phases of treatment in schizophrenia. Special attention was given to metabolic comorbidities, sexual dysfunction, and cardiovascular disease. This paper aims to examine the relationship between schizophrenia and specific somatic comorbidities, to discuss how the balance between efficacy and tolerability influences treatment choice in the acute and maintenance treatment of schizophrenia, and how these two variables may have different priorities at different stages of treatment. CONCLUSION The choice of treatment is based primarily on efficacy and tolerability. Cariprazine is beneficial in patients with positive and negative symptoms, and it has a side-effect profile with low rates of metabolic side effects, sedation, and sexual dysfunction.
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Affiliation(s)
- Alessandro Cuomo
- Department of Molecular Medicine, University of Siena School of Medicine, Siena, Italy
| | - Giovanni B Forleo
- Electrophysiology and Cardiac Pacing, University of Milano Ospedale Sacco, Milan, Italy
| | | | - Jon Johnsen
- Blakstad Psychiatric Hospital, Vestre Viken Hospital Trust, Drammen, Norway
| | - Angel L Montejo
- Nursing School, University of Salamanca, Av. Donantes de Sangre SN, Salamanca, 37004, Spain
- Department of Psychiatry, University Hospital of Salamanca, Salamanca, 37007, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), Paseo de San Vicente SN, Salamanca, 37007, Spain
| | | | - Toby Pillinger
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK
- Faculty of Medicine, MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Jose Antonio Ramos-Quiroga
- Department of Mental Health, Hospital Universitari Vall d'Hebron, Barcelona, Catalonia, Spain
- Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain
- Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Catalonia, Spain
- Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain
| | - Myrto Samara
- Department of Psychiatry, Faculty of Medicine, University of Thessaly, Larisa, Greece
| | | | - Thomas Thomas Stoeckl
- Department of Psychiatry and Psychotherapy, Paracelsus Medical University Nuremberg, Nürnberg, Germany
| | - Andrea Fagiolini
- Department of Molecular Medicine, University of Siena School of Medicine, Siena, Italy.
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Gahr M. [Metabolic adverse drug reactions related to psychotropic drugs]. FORTSCHRITTE DER NEUROLOGIE-PSYCHIATRIE 2025; 93:95-103. [PMID: 39313203 DOI: 10.1055/a-2405-5087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/25/2024]
Abstract
Metabolic adverse drug reactions (mADR) related to psychotropic drugs have significant health-related effects including weight gain, impaired glucose tolerance, diabetes mellitus and dyslipidemia as well as economic relevance. Nearly all antipsychotics (AP) and many antidepressants (AD) and mood stabilisers may induce weight gain. Weight development in the first weeks or months after the beginning of the therapy is the strongest predictor for weight gain related to AP and AD. The most important risk factors for mADR are antagonistic effects at H1-, 5-HT2C- und M3-receptors and antidopaminergic effects. However, several other systems are also relevant. Systematic monitoring of metabolic parameters is recommended in all patients treated with substances that are associated with an increased risk of mADR. Lifestyle modification, dietary measures, exercise therapy, dose reduction, change and discontinuation of the substance, and additional treatment with metformin and topiramate are evidence-based treatment options for AP-associated weight gain. GLP-1 receptor agonists such as liraglutide are also promising.
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Affiliation(s)
- Maximilian Gahr
- Krankenhaus für Psychiatrie, Psychotherapie und Psychosomatische Medizin, Schloss Werneck, Werneck, Germany
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Finlay S, Adegboye O, McDermott B, Rudd D, Sarnyai Z. Linking childhood allostatic load, early adversity and the emergence of mental health symptoms in early adulthood: Analysis of the ALSPAC longitudinal birth cohort. Psychoneuroendocrinology 2025; 172:107276. [PMID: 39787866 DOI: 10.1016/j.psyneuen.2024.107276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Revised: 11/28/2024] [Accepted: 12/29/2024] [Indexed: 01/12/2025]
Abstract
BACKGROUND It has been well-established that the allostatic load (AL) index, a cumulative score of multi-system dysregulation in response to chronic stress, is significantly increased at the time of a psychiatric diagnosis. However, no studies have investigated if there is an association between the AL index in childhood and the later development of mental health symptoms in young adults. METHODS Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population cohort from Bristol, United Kingdom, we investigated the AL index at age 9 years and the risks for mental health symptoms at age 24 years. We used multinomial logistic regression analysis to investigate the association between AL threshold (categorised into bottom third: AL index ≤ 7, middle third: AL index = 7.1-9.9, and top third: AL index ≥ 10) and mental health symptoms while adjusting for sex, the age of mother at delivery, and social class. We used a relative risk ratio (RRR) and 95 % confidence interval(CI) for each variable. We further investigated the association between adverse childhood experiences (ACEs) and mental health symptoms. RESULTS We identified a significant association between sex and mental health symptoms, with more females (59 % vs 41 %) showing mental health symptoms than males. We found no direct association between the AL index at age 9 and the later development of mental health symptoms. However, an RRR analysis showed that individuals in the middle and the top third of the AL index had an RRR of 1.99 and 2.20, respectively, to develop mental health symptoms if they were females. We found that individuals who experienced ACE had a much higher risk of developing mental health symptoms as young adults, with the adjusted RRR of 5.39 (95 % CI: 3.00;9.67), 6.79 (95 % CI: 2.55; 18.1), and 2.10 (95 % CI: 0.37;11.8) for neglect, physical and sexual abuse, respectively, in individuals with mood disorder symptoms. The adjusted RRR for neglect and physical and sexual abuse in individuals with psychotic symptoms was 0.99 (95 % CI: 0.37; 2.59), 2.92 (95 % CI: 0.35; 24.4), and 10.5 (95 % CI: 0.99; 112), respectively. CONCLUSION Although the AL index in childhood was not directly associated with the later development of psychotic and mood disorder symptoms in this cohort, females in the higher tertiles of the AL index measured at 9 years of age had an elevated risk of mental health symptoms as young adults. In line with previous work, a strong association was identified between childhood adversity and mental health symptoms in young adulthood. These results highlight the importance of considering the impact of early stress on biological embedding and the later emergence of mental health problems, especially in females.
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Affiliation(s)
- Sabine Finlay
- Laboratory of Psychiatric Neuroscience, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia; College of Medicine and Dentistry, James Cook University, Queensland, Australia
| | - Oyelola Adegboye
- Menzies, School of Health Research, Charles Darwin University, Casuarina, Northern Territory, Australia
| | - Brett McDermott
- Child and Adolescent Mental Health Service, Hobart, Tasmania, Australia; Tasmanian Centre for Mental Health Service Innovation, Hobart, Tasmania, Australia
| | - Donna Rudd
- College of Medicine and Dentistry, James Cook University, Queensland, Australia
| | - Zoltán Sarnyai
- Laboratory of Psychiatric Neuroscience, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia; College of Medicine and Dentistry, James Cook University, Queensland, Australia.
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Li S, Fu Y, Wang W, Qiu J, Huang Y, Li X, Yang K, Yu X, Ma Y, Zhang Y, Zhang M, Li J, Li WD. Olanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway. Curr Neuropharmacol 2025; 23:412-425. [PMID: 39150031 DOI: 10.2174/1570159x22666240815120547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 08/17/2024] Open
Abstract
BACKGROUND Administration of olanzapine (OLA) is closely associated with obesity and glycolipid abnormalities in patients with schizophrenia (SCZ), although the exact molecular mechanisms remain elusive. OBJECTIVE We conducted comprehensive animal and molecular experiments to elucidate the mechanisms underlying OLA-induced weight gain. METHODS We investigated the mechanisms of OLA-induced adipogenesis and lipid storage by employing a real-time ATP production rate assay, glucose uptake test, and reactive oxygen species (ROS) detection in 3T3-L1 cells and AMSCs. Rodent models were treated with OLA using various intervention durations, dietary patterns (normal diets/western diets), and drug doses. We assessed body weight, epididymal and liver fat levels, and metabolic markers in both male and female mice. RESULTS OLA accelerates adipogenesis by directly activating glycolysis and its downstream PI3K signaling pathway in differentiated adipocytes. OLA promotes glucose uptake in differentiated 3T3-L1 preadipocytes. In mouse models with normal glycolipid metabolism, OLA administration failed to increase food intake and weight gain despite elevated GAPDH expression, a marker related to glycolysis and PI3K-AKT. This supports the notion that glycolysis plays a significant role in OLA-induced metabolic dysfunction. CONCLUSION OLA induces glycolysis and activates the downstream PI3K-AKT signaling pathway, thereby promoting adipogenesis.
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Affiliation(s)
- Shen Li
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, 300222, China
| | - Yun Fu
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
- Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, Fuzhou, 350001, China
| | - Wanyao Wang
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Jiali Qiu
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Yepei Huang
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Xuemin Li
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Ke Yang
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Xiawen Yu
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Yanyan Ma
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, 300222, China
| | - Yuan Zhang
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Miaomiao Zhang
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
| | - Jie Li
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, 300222, China
| | - Wei-Dong Li
- Department of Genetics, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China
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Li S, Liu N, Qi D, Niu L, Li Y, Lu C, Dong Y, Wang X, Li J, Zhang X. Sex differences in plasma lipid profiles, but not in glucose metabolism in patients with first-episode antipsychotics-naïve schizophrenia. Brain Res 2024; 1846:149282. [PMID: 39423962 DOI: 10.1016/j.brainres.2024.149282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 10/01/2024] [Accepted: 10/14/2024] [Indexed: 10/21/2024]
Abstract
BACKGROUND First-episode antipsychotics-naïve schizophrenia (FEAN-SCZ) is associated with abnormalities in glucose and lipid metabolism. While sex differences in the incidence and severity of SCZ and metabolic abnormalities have been documented, the specific metabolic abnormalities between the sexes remain unclear. The study aimed to investigate sex-specific differences in plasma glycolipid profiles in FEAN-SCZ patients. METHODS A total of 172 FEAN-SCZ patients (male/female: 83/89) and 31 healthy controls (male/female: 14/17) were recruited. Psychopathology assessment was conducted using the Positive and Negative Syndrome Scale (PANSS). Glycolipid profiles, including oral glucose tolerance test (OGTT), fasting glucose, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were examined in all participants. RESULTS FEAN patients displayed significantly higher fasting and 2-hour glucose levels compared to healthy controls (both p < 0.001). Impaired glucose tolerance (IGT) prevalence in male patients was 24.1 % (n = 20) and 25.9 % (n = 23) in females, contrasting with 0 % (n = 0) in the control group. FEAN patients exhibited elevated blood insulin and TC levels (both p < 0.05) and increased insulin resistance measured by HOMA-IR (p < 0.01). Among male patients, those with IGT had significantly higher TC, TG and LDL levels than non-IGT patients (all p < 0.05), while no significant differences were observed in female patients between IGT and non-IGT groups. Body mass index (BMI), TG and HDL levels were identified as significant predictors of IGT in male FEAN patients. CONCLUSIONS IGT is present in a subset of FEAN-SCZ patients. Male patients with IGT exhibit distinct alterations in plasma lipid profiles compared to non-IGT patients.
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Affiliation(s)
- Shen Li
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Nannan Liu
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Dan Qi
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Lichao Niu
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Yanzhe Li
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Chenghao Lu
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Yeqing Dong
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Xinxu Wang
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China; Brain Assessment & Intervention Laboratory, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China
| | - Jie Li
- Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin 300222, China.
| | - Xiangyang Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
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Madsen NM, Sørensen MA, Danielsen AA, Højlund M, Rohde C, Köhler-Forsberg O. The risk of diabetes and HbA1c deterioration during antipsychotic drug treatment: A Danish two-cohort study among patients with first-episode schizophrenia. Acta Psychiatr Scand 2024. [PMID: 39379169 DOI: 10.1111/acps.13760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 08/04/2024] [Accepted: 09/07/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c). METHODS We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before. RESULTS In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication. CONCLUSION This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES.
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Affiliation(s)
- Nanna M Madsen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
| | - Marc A Sørensen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
| | - Andreas A Danielsen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
| | - Mikkel Højlund
- Department of Psychiatry Aabenraa, Mental Health Services in the Region of Southern Denmark, Aabenraa, Denmark
- Clinical Pharmacology, Pharmacy, and Environmental Medicine, Department of Public Health, University of Southern, Denmark
- Child and Adolescent Mental Health Centre, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark
| | - Christopher Rohde
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Affective Disorders, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
| | - Ole Köhler-Forsberg
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Psychosis Research Unit, Aarhus University Hospital - Psychiatry, Aarhus, Denmark
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Ozkalayci O, Tastekin N. Can simple biomarkers of inflammation guide the diagnosis of psychiatric disorders? Int J Psychiatry Clin Pract 2024:1-7. [PMID: 39373486 DOI: 10.1080/13651501.2024.2412641] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/04/2024] [Accepted: 09/30/2024] [Indexed: 10/08/2024]
Abstract
OBJECTIVE In this study, we wanted to investigate the usability of routine blood samples taken at the beginning of hospitalisation in inpatients to predict the presence of psychotic symptoms in patients. METHODS We divided the hospitalised patients into two groups those with and without psychotic symptoms according to their ICD-10 diagnosis codes. Then, we compared the complete blood count, c-reactive protein (CRP), and fasting glucose levels, which can be used as simple markers of inflammation. RESULTS In this retrospective study, which included 349 patients, we found that blood leukocytes, neutrophils, CRP, and fasting glucose levels were higher in patients with psychotic symptoms than in patients without psychotic symptoms (p = 0.015; p = 0.013; p = 0.002; and p = 0.001, respectively). According to regression analysis, patients with high glucose levels were 4.9 times more likely to have psychotic symptoms than those with low glucose levels. In addition, according to the ROC analysis results; when we used 87 mg/dl as the cut-off value for fasting glucose, it was observed that it predicted psychotic symptoms with approximately 69% sensitivity and 71% specificity. CONCLUSION Although our results still have some limitations, they are promising for the future use of simple biomarkers of inflammation for the differential diagnosis of psychiatric disorders.
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Affiliation(s)
- Ozgur Ozkalayci
- Bolu İzzet Baysal Mental Health and Diseases Hospital, Bolu, Turkey
| | - Nihal Tastekin
- Bolu İzzet Baysal Mental Health and Diseases Hospital, Bolu, Turkey
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Sarnyai Z, Ben-Shachar D. Schizophrenia, a disease of impaired dynamic metabolic flexibility: A new mechanistic framework. Psychiatry Res 2024; 342:116220. [PMID: 39369460 DOI: 10.1016/j.psychres.2024.116220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 09/21/2024] [Accepted: 09/30/2024] [Indexed: 10/08/2024]
Abstract
Schizophrenia is a chronic, neurodevelopmental disorder with unknown aetiology and pathophysiology that emphasises the role of neurotransmitter imbalance and abnormalities in synaptic plasticity. The currently used pharmacological approach, the antipsychotic drugs, which have limited efficacy and an array of side-effects, have been developed based on the neurotransmitter hypothesis. Recent research has uncovered systemic and brain abnormalities in glucose and energy metabolism, focusing on altered glycolysis and mitochondrial oxidative phosphorylation. These findings call for a re-conceptualisation of schizophrenia pathophysiology as a progressing bioenergetics failure. In this review, we provide an overview of the fundamentals of brain bioenergetics and the changes identified in schizophrenia. We then propose a new explanatory framework positing that schizophrenia is a disease of impaired dynamic metabolic flexibility, which also reconciles findings of abnormal glucose and energy metabolism in the periphery and in the brain along the course of the disease. This evidence-based framework and testable hypothesis has the potential to transform the way we conceptualise this debilitating condition and to develop novel treatment approaches.
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Affiliation(s)
- Zoltán Sarnyai
- Laboratory of Psychobiology, Department of Neuroscience, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Department of Psychiatry, Rambam Health Campus, Haifa, Israel; Laboratory of Psychiatric Neuroscience, Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia.
| | - Dorit Ben-Shachar
- Laboratory of Psychobiology, Department of Neuroscience, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Department of Psychiatry, Rambam Health Campus, Haifa, Israel.
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Szoke A, Pignon B, Godin O, Ferchiou A, Tamouza R, Leboyer M, Schürhoff F. Multimorbidity and the Etiology of Schizophrenia. Curr Psychiatry Rep 2024; 26:253-263. [PMID: 38625632 DOI: 10.1007/s11920-024-01500-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/15/2024] [Indexed: 04/17/2024]
Abstract
PURPOSE OF REVIEW A global study of multimorbidity in schizophrenia, especially of the association with physical conditions, might offer much needed etiological insights. RECENT FINDINGS Our review suggests that life-style factors and medication related to schizophrenia are only part of the explanation of the increase in risk for cardiovascular, metabolic, pulmonary disorders, and some cancers. Positive associations with autoimmune disorders (with the exception of rheumatoid arthritis) and epilepsy are promising avenues of research but to date have not been fully exploited. The same holds for the negative comorbidity seen for rheumatoid arthritis and some cancers (e.g., prostate). As a whole, our review suggests that most of the explored conditions have a different prevalence in schizophrenia than in the general population. Several hypotheses emerged from this review such as the role of immune and genetic factors, of sex hormones, and of more general variability factors.
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Affiliation(s)
- A Szoke
- UPEC, Univ Paris Est Creteil, 94000, Créteil, France
- Fondation Fondamental, 94000, Créteil, France
| | - B Pignon
- UPEC, Univ Paris Est Creteil, 94000, Créteil, France.
- DMU IMPACT Psychiatrie Et Addictologie, Hôpital Albert Chenevier, Pavillon Hartmann, 40, Rue de Mesly, 94000, Créteil, France.
- Fondation Fondamental, 94000, Créteil, France.
| | - O Godin
- UPEC, Univ Paris Est Creteil, 94000, Créteil, France
- Fondation Fondamental, 94000, Créteil, France
| | - A Ferchiou
- UPEC, Univ Paris Est Creteil, 94000, Créteil, France
- Fondation Fondamental, 94000, Créteil, France
| | - R Tamouza
- UPEC, Univ Paris Est Creteil, 94000, Créteil, France
- Fondation Fondamental, 94000, Créteil, France
| | - M Leboyer
- UPEC, Univ Paris Est Creteil, 94000, Créteil, France
- Fondation Fondamental, 94000, Créteil, France
| | - F Schürhoff
- UPEC, Univ Paris Est Creteil, 94000, Créteil, France
- Fondation Fondamental, 94000, Créteil, France
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Kanofsky JD, Viswanathan S, Wylie-Rosett J. Lifestyle Coaching May Be an Effective Treatment for Schizophrenia. Am J Lifestyle Med 2024; 18:156-161. [PMID: 38559781 PMCID: PMC10979723 DOI: 10.1177/15598276221142307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/04/2024] Open
Abstract
This commentary critiques the Danish CHANGE trial, which evaluated 3 levels of outpatient intervention intensity, in a group of outpatients with obesity and schizophrenia. Neither adding care coordination with weekly nurse contacts alone nor combining this treatment with assertive community lifestyle coaching as compared to treatment as usual improved outcomes, which included cardiovascular disease risk calculation, cardiorespiratory fitness, weight, and self-reported behaviors such as smoking, physical activity, and diet. The CHANGE trial investigators appear strongly averse to recommending the development and implementation of lifestyle medicine programs as a major component when treating outpatients with severe mental disorders. The potential dismissal of lifestyle medicine as a component of treatment for severe mental disorders is problematic. Valuable lessons can be learned from more thoroughly analyzing secondary outcomes such as medical and psychiatric hospitalization rates and total health care cost. The CHANGE trial data analysis needs to be expanded beyond the focus on changes in weight and serum cholesterol. Insulin resistance and high refined carbohydrate intake may be major factors in determining both the medical and psychiatric clinical course of schizophrenia. Assertive community lifestyle coaching is a novel treatment modality. Evidence strongly suggests assertive community lifestyle coaching substantially decreases both psychiatric and medical hospitalization rates.
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Affiliation(s)
- Jacob Daniel Kanofsky
- Bronx Psychiatric Center, Bronx, NY, USA (JDK); Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA (JDK); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA (SV, JWR); and New York Regional Center for Diabetes Translational Research, Albert Einstein College of Medicine, Bronx, NY, USA (JWR)
| | - Shankar Viswanathan
- Bronx Psychiatric Center, Bronx, NY, USA (JDK); Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA (JDK); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA (SV, JWR); and New York Regional Center for Diabetes Translational Research, Albert Einstein College of Medicine, Bronx, NY, USA (JWR)
| | - Judith Wylie-Rosett
- Bronx Psychiatric Center, Bronx, NY, USA (JDK); Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY, USA (JDK); Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA (SV, JWR); and New York Regional Center for Diabetes Translational Research, Albert Einstein College of Medicine, Bronx, NY, USA (JWR)
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11
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Ma Z, Zhou HX, Chen DC, Wang DM, Zhang XY. Association between suicidal behavior and impaired glucose metabolism in first-episode drug-naïve patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2024; 129:110900. [PMID: 38007210 DOI: 10.1016/j.pnpbp.2023.110900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 11/09/2023] [Accepted: 11/19/2023] [Indexed: 11/27/2023]
Abstract
BACKGROUND Schizophrenia (SZ) patients have been reported to have comorbid suicidal behavior (SB) and impaired glucose metabolism in early psychosis, but it is unclear whether impaired glucose metabolism plays a role in the occurrence of SB in patients with first-episode drug-naïve (FEDN) SZ. Therefore, our main aim was to examine the relationship between SB and glucose metabolism in FEDN SZ patients. METHODS We recruited 319 FEDN SZ patients and collected information on their sociodemographic characteristics, clinical data, and glucose metabolism parameters. Participants' psychotic and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HAMD), respectively. Fasting plasma glucose and insulin levels were also measured. RESULTS The percentage of FEDN SZ patients with SB was 45.5% (145/319). Compared to SZ patients without SB, SZ patients with SB exhibited higher scores on HAMD, PANSS positive subscale, as well as higher levels of fasting plasma glucose, fasting plasma insulin, and homeostasis model assessment of insulin resistance index (all p<0.05). Logistic regression analysis indicated that increased levels of insulin resistance (adjusted OR = 1.920), body mass index (adjusted OR = 0.931), and PANSS general psychopathology (adjusted OR = 1.041) were independently associated with SB. The Receiver Operating Characteristic Curve showed an Area Under Curve value of 0.732 for the combination of three factors in regression model to distinguish between SB and non-SB. CONCLUSIONS Our results indicate that fasting glucose, fasting insulin, and insulin resistance are strongly associated with SB in FEDN SZ patients, suggesting that glucose metabolism abnormalities may be potential biomarkers of SB in SZ patients. Regular monitoring of glucose metabolism variables is essential for suicide prevention.
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Affiliation(s)
- Zheng Ma
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Hui-Xia Zhou
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | - Da-Chun Chen
- Beijing HuiLongGuan Hospital, Peking University, Beijing, China
| | - Dong-Mei Wang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
| | - Xiang-Yang Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
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12
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Wu Q, Long Y, Peng X, Song C, Xiao J, Wang X, Liu F, Xie P, Yang J, Shi Z, Hu Z, McCaig C, St Clair D, Lang B, Wu R. Prefrontal cortical dopamine deficit may cause impaired glucose metabolism in schizophrenia. Transl Psychiatry 2024; 14:79. [PMID: 38320995 PMCID: PMC10847097 DOI: 10.1038/s41398-024-02800-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 11/04/2023] [Accepted: 01/22/2024] [Indexed: 02/08/2024] Open
Abstract
The brain neurotramsmitter dopamine may play an important role in modulating systemic glucose homeostasis. In seven hundred and four drug- naïve patients with first-episode schizophrenia, we provide robust evidence of positive associations between negative symptoms of schizophrenia and high fasting blood glucose. We then show that glucose metabolism and negative symptoms are improved when intermittent theta burst stimulation (iTBS) on prefrontal cortex (PFC) is performed in patients with predominantly negative symptoms of schizophrenia. These findings led us to hypothesize that the prefrontal cortical dopamine deficit, which is known to be associated with negative symptoms, may be responsible for abnormal glucose metabolism in schizophrenia. To explore this, we optogenetically and chemogenetically inhibited the ventral tegmental area (VTA)-medial prefrontal cortex (mPFC) dopamine projection in mice and found both procedures caused glucose intolerance. Moreover, microinjection of dopamine two receptor (D2R) neuron antagonists into mPFC in mice significantly impaired glucose tolerance. Finally, a transgenic mouse model of psychosis named Disc1tr exhibited depressive-like symptoms, impaired glucose homeostasis, and compared to wild type littermates reduced D2R expression in prefrontal cortex.
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Affiliation(s)
- Qiongqiong Wu
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
- Affiliated Mental Health Centre & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310013, China
| | - Yujun Long
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Xingjie Peng
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Chuhan Song
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Jingmei Xiao
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Xiaoyi Wang
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Furu Liu
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Peng Xie
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Jinqing Yang
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Zhe Shi
- Key Laboratory for Quality Evaluation of Bulk Herbs of Hunan Province, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Zhonghua Hu
- Hunan Key Laboratory of Molecular Precision Medicine, Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Colin McCaig
- School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - David St Clair
- School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK
| | - Bing Lang
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China
| | - Renrong Wu
- National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China.
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13
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Morera D, Miller BJ. Meta-analysis of a family history of diabetes in schizophrenia. Schizophr Res 2024; 264:90-94. [PMID: 38118263 DOI: 10.1016/j.schres.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 09/28/2023] [Accepted: 12/05/2023] [Indexed: 12/22/2023]
Abstract
OBJECTIVE Type 2 diabetes (T2DM) is common in patients with schizophrenia and non-affective psychosis. These patients also have an increased prevalence of a family history of T2DM. We performed a systematic review and meta-analysis of the association between a family history of T2DM and schizophrenia. METHOD We searched electronic databases from inception until July 2022 for studies of a family history of T2DM or gestational diabetes in patients with schizophrenia and controls. We performed random effects meta-analysis, calculating odds ratios (ORs) and 95 % confidence intervals (CI) and meta-regression analyses. RESULTS Nine studies were included, comprising 2953 patients with non-affective psychosis and 4484 controls. Schizophrenia was associated with an over two-fold increased odds of a family history of T2DM or gestational diabetes (OR = 2.18, 95 % CI 1.61-2.96, p < 0.01). In meta-regression analyses, age, sex, study quality score, and year of publication were all unrelated to the association. CONCLUSION We found that patients with schizophrenia had a 2.2-fold increased odds of a family history of T2DM versus controls. This association may be relevant to both the pathophysiology of schizophrenia and the reported increased risk of development of diabetes with antipsychotic treatment.
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Affiliation(s)
- Daley Morera
- Medical College of Georgia, Augusta University, Augusta, GA, United States
| | - Brian J Miller
- Department of Psychiatry and Health Behavior, Augusta University, Augusta, GA, United States.
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14
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Petrova NN, Semenova NV. [Metabolic syndrome and antipsychotic therapy of schizophrenia]. Zh Nevrol Psikhiatr Im S S Korsakova 2024; 124:165-170. [PMID: 39690565 DOI: 10.17116/jnevro2024124111165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
The review article discusses the relationship of metabolic disorders with schizophrenia and antipsychotic therapy, the importance of metabolic syndrome for the health of patients with schizophrenia. Risk factors for the development of metabolic syndrome are considered. The metabolic side effects of various antipsychotics are characterized. Options for therapeutic tactics in the development of metabolic syndrome against the background of antipsychotic therapy are described.
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Affiliation(s)
- N N Petrova
- Saint Petersburg State University, St. Petersburg, Russia
| | - N V Semenova
- Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia
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15
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Petrova NN. [Metabolic syndrome in clinical psychiatric practice]. Zh Nevrol Psikhiatr Im S S Korsakova 2024; 124:13-20. [PMID: 39269292 DOI: 10.17116/jnevro202412408113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2024]
Abstract
A literature review in PubMed and Google databases was performed. Inclusion criteria: randomized clinical trials, meta-analyses and systematic reviews, relevant full-text articles on metabolic syndrome (MS) in patients with schizophrenia. Exclusion criteria: articles of poor quality. The terminology of the article corresponds to that used in the publications included in the review. The review substantiates the relevance of the problem of MS, discloses the concept and discusses its criteria, provides data on the prevalence of MS in patients with schizophrenia, discusses the relationship between MS and schizophrenia, MS and cognitive impairment in schizophrenia, and describes metabolic changes in patients with a first episode of psychosis or early stage schizophrenia. Recommendations on therapeutic tactics in the development of metabolic syndrome in patients with schizophrenia are given.
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Affiliation(s)
- N N Petrova
- Saint Petersburg State University, St. Petersburg, Russia
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16
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Xiu M, Hao M, Liu C, Sun M, Lang X. Glucose Metabolism and Sex Hormones in Male Patients with Medication-naïve First-episode Schizophrenia: A Large-scale Cross-sectional Study. Curr Neuropharmacol 2024; 22:2263-2270. [PMID: 38549523 PMCID: PMC11337684 DOI: 10.2174/1570159x22666240212141602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2023] [Revised: 11/23/2023] [Accepted: 12/17/2023] [Indexed: 08/23/2024] Open
Abstract
BACKGROUND Schizophrenia (SCZ) usually begins in early adult life. The underlying molecular mechanisms of SCZ remain unclear. There is evidence for the involvement of abnormalities in metabolic and endocrine systems in SCZ, even in drug-naïve first-episode schizophrenia patients (DNFES). However, the association between impaired regulation of glucose metabolism and sex hormones was not studied in SCZ. This study aimed to evaluate the interrelationship between sex hormones and high fasting glucose levels in male DNFES patients. METHODS A total of 99 patients with SCZ were recruited, and fasting glucose, fasting insulin, the insulin resistance index (HOMA-IR), and sex hormones were measured. RESULTS We found that some male patients with SCZ had abnormal levels in glucose metabolism parameters and gonadal hormones that were not within the normal range. Linear regression analysis adjusted for age, waist circumference, and body mass index showed that testosterone levels were negatively associated with fasting insulin in male patients (β = -0.21, t = -2.2, p = 0.03). CONCLUSION Our findings confirm the abnormalities in glucose metabolism parameters and gonadal hormones at the onset of the illness in male DNFES patients with SCZ. In addition, there was an interaction effect between abnormal glucose metabolism and sex hormones in male patients.
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Affiliation(s)
- Meihong Xiu
- Peking University HuiLongGuan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, China
| | - Meng Hao
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Cai Liu
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Maodi Sun
- North University of China, Taiyuan, China
| | - Xiaoe Lang
- Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China
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17
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Anmella G, Amoretti S, Safont G, Meseguer A, Vieta E, Pons-Cabrera MT, Alfonso M, Hernández C, Sanchez-Autet M, Pérez-Baldellou F, González-Blanco L, García-Portilla MP, Bernardo M, Arranz B. Intestinal permeability and low-grade chronic inflammation in schizophrenia: A multicentre study on biomarkers. Rationale, objectives, protocol and preliminary results. SPANISH JOURNAL OF PSYCHIATRY AND MENTAL HEALTH 2023:S2950-2853(23)00040-6. [PMID: 38591828 DOI: 10.1016/j.sjpmh.2023.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 08/21/2023] [Accepted: 09/18/2023] [Indexed: 04/10/2024]
Abstract
BACKGROUND Altered intestinal permeability and low-grade chronic inflammation disrupt the integrity of the blood-brain barrier (microbiota-gut-brain axis), probably playing a role in the pathophysiology of schizophrenia-spectrum disorders. However, studies assessing the microbiota-gut-brain axis are inconsistent. This article describes the rationale, objectives, protocol, and presents descriptive results for a new project. METHODS The sample of this study came from an observational, cross-sectional and multisite study including four centers in Spain (PI17/00246) recruiting adult patients with DSM-5 schizophrenia-spectrum disorders at any stage of the disease. The aims of the project are to assess the interrelation between intestinal permeability and low-grade chronic inflammation in schizophrenia-spectrum disorders and the role of peripheral biomarkers, diet, exercise, metabolic syndrome, disease severity and functioning as well as cognition. Assessments included the following variables: (1) anthropometric, (2) intestinal permeability, diet, and physical exercise, (3) clinical and functional, (4) neuropsychological and cognitive reserve, and (5) peripheral biomarkers from blood. RESULTS A total of 646 patients were enrolled (257, 39.7% female). Mean age was 43.2±13.6 years, illness duration 15.1±11.5 years. 55.8% consumed tobacco. Positive PANSS score was 13.68±6.55, and 20.38±8.69 in the negative symptoms. CGI was 4.16±2.22 and GAF was 60.00±14.84. CONCLUSION The results obtained by this project are expected to contribute toward the understanding of the physiopathology of schizophrenia-spectrum disorders. This will likely aid to personalize treatments in real-world clinical practice, potentially including variables related to intestinal permeability and inflammation.
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Affiliation(s)
- Gerard Anmella
- Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain; Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, Spain
| | - Silvia Amoretti
- Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain; Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, Spain; Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Barcelona, Catalonia, Spain
| | - Gemma Safont
- Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain; Department of Psychiatry, Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain
| | - Ana Meseguer
- Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain; Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, Spain
| | - Eduard Vieta
- Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain; Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain
| | - Maria Teresa Pons-Cabrera
- Bipolar and Depressive Disorders Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain; Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, Spain
| | - Miqueu Alfonso
- Department of Psychiatry, Hospital Parc Sanitari Sant Joan de Déu, Barcelona, Spain
| | - Carla Hernández
- Department of Psychiatry, Hospital Parc Sanitari Sant Joan de Déu, Barcelona, Spain
| | - Monica Sanchez-Autet
- Department of Psychiatry, Hospital Parc Sanitari Sant Joan de Déu, Barcelona, Spain
| | - Ferran Pérez-Baldellou
- Department of Psychiatry, Hospital Universitari Mutua de Terrassa, Universitat de Barcelona, Barcelona, Spain
| | - Leticia González-Blanco
- Department of Psychiatry, University of Oviedo, Servicio de Salud Mental del Principado de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), INEUROPA, Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Oviedo, Spain
| | - Maria Paz García-Portilla
- Department of Psychiatry, University of Oviedo, Servicio de Salud Mental del Principado de Asturias, Oviedo, Spain; Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), INEUROPA, Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Oviedo, Spain
| | - Miquel Bernardo
- Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain; Barcelona Clinic Schizophrenia Unit, Hospital Clínic de Barcelona, Institute of Neuroscience, University of Barcelona, IDIBAPS, Spain.
| | - Belén Arranz
- Biomedical Research Networking Center for Mental Health Network (CIBERSAM), Barcelona, Spain; Department of Psychiatry, Hospital Parc Sanitari Sant Joan de Déu, Barcelona, Spain
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18
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Zahid U, Hosang GM, de Freitas DF, Mooney R, Bhui K. Ethnic inequality, multimorbidity and psychosis: can a syndemic framework resolve disputed evidence? SCHIZOPHRENIA (HEIDELBERG, GERMANY) 2023; 9:37. [PMID: 37296141 DOI: 10.1038/s41537-023-00367-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 05/02/2023] [Indexed: 06/12/2023]
Abstract
Syndemic theory is described as population-level clustering or co-occurrence of health conditions in the context of shared aetiologies that interact and can act synergistically. These influences appear to act within specific places of high disadvantage. We suggest ethnic inequality in experiences and outcomes of multimorbidity, including psychosis, may be explained through a syndemic framework. We discuss the evidence for each component of syndemic theory in relation to psychosis, using psychosis and diabetes as an exemplar. Following this, we discuss the practical and theoretical adaptations to syndemic theory in order to apply it to psychosis, ethnic inequality and multimorbidity, with implications for research, policy, and practice.
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Affiliation(s)
- Uzma Zahid
- Department of Psychiatry, University of Oxford, Oxford, UK.
- Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
| | - Georgina M Hosang
- Centre for Psychiatry and Mental Health, Wolfson Institute of Population Health, Queen Mary University of London, London, UK
| | - Daniela Fonseca de Freitas
- Department of Psychiatry, University of Oxford, Oxford, UK
- Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
| | - Roisin Mooney
- Department of Psychiatry, University of Oxford, Oxford, UK
| | - Kamaldeep Bhui
- Department of Psychiatry, University of Oxford, Oxford, UK.
- Nuffield Department of Primary Care Health Sciences, Wadham College, University of Oxford, Oxford, UK.
- Queen Mary University London Global Policy Institute, London, UK.
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19
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Huang X, Sun Y, Wu A, Zhang XY. Prevalence and clinical profile of abnormal glucose in first-episode and drug-naïve patients with major depressive disorder with comorbid abnormal thyroid function: a large-scale cross-sectional study. BMC Psychiatry 2023; 23:362. [PMID: 37226146 DOI: 10.1186/s12888-023-04842-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 05/04/2023] [Indexed: 05/26/2023] Open
Abstract
BACKGROUND The associated factors of abnormal glucose in patients with major depressive disorder (MDD) with comorbid abnormal thyroid function (ATF) remain unclear. To the best of our knowledge, this is the first study with a large sample size that examines the risk factors of abnormal glucose in first-episode drug-naïve (FEDN) MDD patients comorbid with ATF and includes clinical correlates and thyroid hormone levels. METHODS A total of 1718 FEDN MDD patients were recruited. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were used to evaluate the symptoms of patients. Fasting blood glucose concentration and thyroid hormone levels were measured. RESULTS The prevalence of abnormal glucose in MDD patients with comorbid ATF was 47.3%, which was 4.25 times higher than that in MDD patients without ATF (17.4%). Compared to those ATF patients without abnormal glucose, ATF patients with abnormal glucose scored higher on HAMD, HAMA and PANSS positive subscale, had a higher rate of suicide attempts, severe anxiety and psychotic symptoms, and had higher levels of thyroid-stimulating hormone (TSH), and thyroid peroxidases antibody (TPOAb) which were also correlated with abnormal glucose in MDD patients comorbid ATF (all P < 0.05). The combination of HAMD score and TSH could differentiate abnormal glucose from ATF. Further, TSH was independence-related with the concentration of fasting blood glucose in MDD patients with comorbid ATF. CONCLUSION Our results demonstrate a high prevalence of abnormal glucose in MDD patients with comorbid ATF. Some clinical and thyroid function-related variables may be associated with abnormal glucose in MDD patients with comorbid ATF.
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Affiliation(s)
- Xiao Huang
- Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Workers' Stadium South Road, Beijing, Chaoyang, 100020, China
| | - Yuan Sun
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Workers' Stadium South Road, Beijing, Chaoyang, 100020, China
| | - Anshi Wu
- Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Workers' Stadium South Road, Beijing, Chaoyang, 100020, China
| | - Xiang-Yang Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China.
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
- Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, 16 Lincui Rd, Beijing, 100101, China.
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20
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Borovcanin MM, Vesic K, Petrovic I, Jovanovic IP, Mijailović NR. Diabetes mellitus type 2 as an underlying, comorbid or consequent state of mental disorders. World J Diabetes 2023; 14:481-493. [PMID: 37273248 PMCID: PMC10236997 DOI: 10.4239/wjd.v14.i5.481] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Revised: 03/21/2023] [Accepted: 04/12/2023] [Indexed: 05/15/2023] Open
Abstract
Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice. Various factors contribute to the development of mental and somatic disorders. Type 2 diabetes mellitus (T2DM) is a significant health burden worldwide, and the prevalence of diabetes in adults is increasing. The comorbidity of diabetes and mental disorders is very common. By sharing a bidirectional link, both T2DM and mental disorders influence each other in various manners, but the exact mechanisms underlying this link are not yet elucidated. The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction, oxidative stress, endothelial dysfunction, and metabolic disturbances. Moreover, diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetes-associated cognitive decline to pre-dementia and dementia. A complex re-lationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production. The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders, emphasizing their complexity and interweaving. We also focused on the cognitive performances and changes in neurodegenerative disorders. The importance of implementing integrated approaches in treating both of these states is highlighted, along with the need for individual therapeutic strategies.
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Affiliation(s)
- Milica M Borovcanin
- Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Katarina Vesic
- Department of Neurology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Ivica Petrovic
- Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Ivan P Jovanovic
- Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
| | - Nataša R Mijailović
- Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34 000, Serbia
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Pillinger T, McCutcheon RA, Howes OD. Variability of glucose, insulin, and lipid disturbances in first-episode psychosis: a meta-analysis. Psychol Med 2023; 53:3150-3156. [PMID: 37449481 PMCID: PMC10235663 DOI: 10.1017/s0033291721005213] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 11/19/2021] [Accepted: 11/30/2021] [Indexed: 11/07/2022]
Abstract
BACKGROUND First-episode psychosis (FEP) is associated with metabolic alterations. However, it is not known if there is heterogeneity in these alterations beyond what might be expected due to normal individual differences, indicative of subgroups of patients at greater vulnerability to metabolic dysregulation. METHODS We employed meta-analysis of variance, indexed using the coefficient of variation ratio (CVR), to compare variability of the following metabolic parameters in antipsychotic naïve FEP and controls: fasting glucose, glucose post-oral glucose tolerance test (OGTT), fasting insulin, insulin resistance, haemoglobin A1c (HbA1c), total-cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. Standardised mean difference in metabolic parameters between groups was also calculated; meta-regression analyses examined physiological/demographic/psychopathological moderators of metabolic change. RESULTS Twenty-eight studies were analysed (1716 patients, 1893 controls). Variability of fasting glucose [CVR = 1.32; 95% confidence interval (CI) 1.12-1.55; p = 0.001], glucose post-OGTT (CVR = 1.43; 95% CI 1.10-1.87; p = 0.008), fasting insulin (CVR = 1.31; 95% CI 1.09-1.58; p = 0.01), insulin resistance (CVR = 1.34; 95% CI 1.12-1.60; p = 0.001), HbA1c (CVR = 1.18; 95% CI 1.06-1.27; p < 0.0001), total-cholesterol (CVR = 1.15; 95% CI 1.01-1.31; p = 0.03), LDL-cholesterol (CVR = 1.28; 95% CI 1.09-1.50; p = 0.002), and HDL-cholesterol (CVR = 1.15; 95% CI 1.00-1.31; p < 0.05), but not triglycerides, was greater in patients than controls. Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients. Increased symptom severity and female sex were associated with worse metabolic outcomes. CONCLUSIONS Patients with FEP present with greater variability in metabolic parameters relative to controls, consistent with a subgroup of patients with more severe metabolic changes compared to others. Understanding determinants of metabolic variability could help identify patients at-risk of developing metabolic syndrome. Female sex and severe psychopathology are associated with poorer metabolic outcomes, with implications for metabolic monitoring in clinical practice.
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Affiliation(s)
- Toby Pillinger
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College of London, London, UK
- Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK
- Faculty of Medicine, Institute of Clinical Sciences, Imperial College London, London, UK
| | - Robert A. McCutcheon
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College of London, London, UK
- Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK
- Faculty of Medicine, Institute of Clinical Sciences, Imperial College London, London, UK
| | - Oliver D. Howes
- Psychiatric Imaging Group, MRC London Institute of Medical Sciences, Hammersmith Hospital, Imperial College London, London, UK
- Faculty of Medicine, Institute of Clinical Sciences, Imperial College London, London, UK
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College of London, London, UK
- H Lundbeck A/s, 3 Abbey View, Everard Close, St Albans AL1 2PS, UK
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22
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Lee J, Costa-Dookhan K, Panganiban K, MacKenzie N, Treen QC, Chintoh A, Remington G, Müller DJ, Sockalingam S, Gerretsen P, Sanches M, Karnovsky A, Stringer KA, Ellingrod VL, Tso IF, Taylor SF, Agarwal SM, Hahn MK, Ward KM. Metabolomic signatures associated with weight gain and psychosis spectrum diagnoses: A pilot study. Front Psychiatry 2023; 14:1169787. [PMID: 37168086 PMCID: PMC10164938 DOI: 10.3389/fpsyt.2023.1169787] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/27/2023] [Indexed: 05/13/2023] Open
Abstract
Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data (n = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.
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Affiliation(s)
- Jiwon Lee
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Kenya Costa-Dookhan
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Kristoffer Panganiban
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Nicole MacKenzie
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Quinn Casuccio Treen
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Araba Chintoh
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Gary Remington
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
| | - Daniel J. Müller
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- Pharmacogenetics Research Clinic, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Sanjeev Sockalingam
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Education, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Philip Gerretsen
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Geriatric Mental Health Services, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Marcos Sanches
- Biostatistics, Centre for Addiction and Mental Health, Toronto, ON, Canada
| | - Alla Karnovsky
- Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Kathleen A. Stringer
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, United States
| | - Vicki L. Ellingrod
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, United States
- Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Ivy F. Tso
- Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, United States
- Department of Psychiatry & Behavioral Health, Ohio State University, Columbus, OH, United States
| | - Stephan F. Taylor
- Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI, United States
| | - Sri Mahavir Agarwal
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada
| | - Margaret K. Hahn
- Schizophrenia Division, Centre for Addiction and Mental Health, Toronto, ON, Canada
- Institute of Medical Science, University of Toronto, Toronto, ON, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON, Canada
- Banting and Best Diabetes Centre, University of Toronto, Toronto, ON, Canada
| | - Kristen M. Ward
- Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, United States
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23
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Aymerich C, Pedruzo B, Pacho M, Laborda M, Herrero J, Pillinger T, McCutcheon RA, Alonso-Alconada D, Bordenave M, Martínez-Querol M, Arnaiz A, Labad J, Fusar-Poli P, González-Torres MÁ, Catalan A. Prolactin and morning cortisol concentrations in antipsychotic naïve first episode psychosis: A systematic review and meta-analysis. Psychoneuroendocrinology 2023; 150:106049. [PMID: 36758330 DOI: 10.1016/j.psyneuen.2023.106049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 01/02/2023] [Accepted: 02/02/2023] [Indexed: 02/05/2023]
Abstract
IMPORTANCE Alterations in prolactin and cortisol levels have been reported in antipsychotic naïve patients with first episode psychosis (FEP). However, it has been studied in very small samples, and inter-group variability has never been studied before. OBJECTIVE To provide estimates of standardized mean differences (SMD) and inter-group variability for prolactin, cortisol awakening response (CAR) and morning cortisol concentrations in antipsychotic naïve FEP (AN-FEP) patients and healthy controls (HC). DATA SOURCES BIOSIS, KCI, MEDLINE, Russian Science Citation Index, SciELO, Cochrane, PsycINFO, Web of Science were searched from inception to February 28, 2022. STUDY SELECTION Peer-reviewed cohort studies that reported on prolactin or cortisol blood concentrations in AN- FEP patients and HC were included. DATA EXTRACTION AND SYNTHESIS Study characteristics, means and standard deviations (SD) were extracted from each article. Inter group differences in magnitude of effect were estimated using Hedges g. Inter-group variability was estimated with the coefficient of variation ratio (CVR). In both cases estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were estimated using meta-regression. PRISMA guideline was followed (No. CRD42022303555). MAIN OUTCOMES AND MEASURES Prolactin, CAR and morning cortisol blood concentrations in AN-FEP group in relation to HC group. RESULTS Fourteen studies for prolactin (N = 761 for AN-FEP group, N = 687 for HC group) and twelve studies for morning cortisol (N = 434 for AN-FEP group, N = 528 for HC group) were included. No studies were found in CAR in AN-FEP patients. Mean SMD for prolactin blood concentration was 0.88 (95% CI 0.57, 1.20) for male and 0.56 (95% CI 0.26, 0.87) for female. As a group, AN-FEP presented greater inter-group variability for prolactin levels than HC (CVR=1.28, 95% CI 1.02, 1.62). SMD for morning cortisol concentrations was non-significant: 0.34 (95% CI -0.01, 0.69) and no inter-group variability significant differences were detected: CVR= 1.05 (95% CI 0.91, 1.20). Meta-regression analyses for age and quality were non-significant. Funnel plots did not suggest a publication bias. CONCLUSIONS AND RELEVANCE Increased prolactin levels were found in AN-FEP patients. A greater inter-group variability in the AN-FEP group suggests the existence of patient subgroups with different prolactin levels. No significant abnormalities were found in morning cortisol levels. Further research is needed to clarify whether prolactin concentrations could be used as an illness biomarker.
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Affiliation(s)
- Claudia Aymerich
- Psychiatry Department, Basurto University Hospital, Basque Health Service (Osakidetza), Bilbao, Spain. Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.
| | - Borja Pedruzo
- Psychiatry Department, Basurto University Hospital, Basque Health Service (Osakidetza), Bilbao, Spain
| | - Malein Pacho
- Psychiatry Department, Basurto University Hospital, Basque Health Service (Osakidetza), Bilbao, Spain
| | - María Laborda
- Psychiatry Department, Basurto University Hospital, Basque Health Service (Osakidetza), Bilbao, Spain
| | - Jon Herrero
- Psychiatry Department, Basurto University Hospital, Basque Health Service (Osakidetza), Bilbao, Spain
| | - Toby Pillinger
- Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; MRC London Institute of Medical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Robert A McCutcheon
- Department of Psychiatry, University of Oxford, UK. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Psychiatric Imaging Group, Medical Research Council, London Institute of Medical Sciences, Hammersmith Hospital, London, UK; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, UK
| | - Daniel Alonso-Alconada
- Department of Cell Biology and Histology, School of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain
| | - Marta Bordenave
- Psychiatry Department, Basurto University Hospital, Basque Health Service (Osakidetza), Bilbao, Spain
| | | | - Ainara Arnaiz
- Erandio Mental Health Center, Basque Health Service (Osakidetza), Erandio, Spain. Biocruces Bizkaia Health Research Institute, Barakaldo, Spain
| | - Javier Labad
- Mental Health Networking Biomedical Research Centre (CIBERSAM), Spain. Salut Mental Taulí, Parc Taulí University Hospital, I3PT, Autonomous University of Barcelona, Sabadell, Barcelona, Spain
| | - Paolo Fusar-Poli
- Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Section of Psychiatry, Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK
| | - Miguel Ángel González-Torres
- Psychiatry Department. Biocruces Bizkaia Health Research Institute, OSI Bilbao-Basurto. School of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain; Centro de Investigación en Red de Salud Mental. (CIBERSAM), Instituto de Salud Carlos III, Plaza de Cruces 12, 48903 Barakaldo, Biscay, Spain
| | - Ana Catalan
- Psychiatry Department. Biocruces Bizkaia Health Research Institute, OSI Bilbao-Basurto. School of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain; Centro de Investigación en Red de Salud Mental. (CIBERSAM), Instituto de Salud Carlos III, Plaza de Cruces 12, 48903 Barakaldo, Biscay, Spain
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24
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Ding H, Xie M, Wang J, Ouyang M, Huang Y, Yuan F, Jia Y, Zhang X, Liu N, Zhang N. Shared genetics of psychiatric disorders and type 2 diabetes:a large-scale genome-wide cross-trait analysis. J Psychiatr Res 2023; 159:185-195. [PMID: 36738649 DOI: 10.1016/j.jpsychires.2023.01.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 12/31/2022] [Accepted: 01/26/2023] [Indexed: 01/29/2023]
Abstract
BACKGROUND Individuals with psychiatric disorders have elevated rates of type 2 diabetes comorbidity. Although little is known about the shared genetics and causality of this association. Thus, we aimed to investigate shared genetics and causal link between different type 2 diabetes and psychiatric disorders. METHODS We conducted a large-scale genome-wide cross-trait association study(GWAS) to investigate genetic overlap between type 2 diabetes and anorexia nervosa, attention deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, obsessive-compulsive disorder, schizophrenia, anxiety disorders and Tourette syndrome. By post-GWAS functional analysis, we identify variants genes expression in various tissues. Enrichment pathways, potential protein interaction and mendelian randomization also provided to research the relationship between type 2 diabetes and psychiatric disorders. RESULTS We discovered that type 2 diabetes and psychiatric disorders had a significant correlation. We identified 138 related loci, 32 were novel loci. Post-GWAS analysis revealed that 86 differentially expressed genes were located in different brain regions and peripheral blood in type 2 diabetes and related psychiatric disorders. MAPK signaling pathway plays an important role in neural development and insulin signaling. In addition, there is a causal relationship between T2D and mental disorders. In PPI analysis, the central genes of the DEG PPI network were FTO and TCF7L2. CONCLUSION This large-scale genome-wide cross-trait analysis identified shared genetics andpotential causal links between type 2 diabetes and related psychiatric disorders, suggesting potential new biological functions in common among them.
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Affiliation(s)
- Hui Ding
- The Affiliated Nanjing Brain Hospital of Nanjing Medical Univesity, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China
| | - Minyao Xie
- The Affiliated Nanjing Brain Hospital of Nanjing Medical Univesity, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China
| | - Jinyi Wang
- The Affiliated Nanjing Brain Hospital of Nanjing Medical Univesity, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China
| | - Mengyuan Ouyang
- The Affiliated Nanjing Brain Hospital of Nanjing Medical Univesity, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China
| | - Yanyuan Huang
- The Affiliated Nanjing Brain Hospital of Nanjing Medical Univesity, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China
| | - Fangzheng Yuan
- School of Psychology, Nanjing Normal University, Nanjing, 210023, PR China
| | - Yunhan Jia
- School of Psychology, Nanjing Normal University, Nanjing, 210023, PR China
| | - Xuedi Zhang
- The Affiliated Nanjing Brain Hospital of Nanjing Medical Univesity, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China
| | - Na Liu
- Department of Medical Psychology, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, PR China.
| | - Ning Zhang
- The Affiliated Nanjing Brain Hospital of Nanjing Medical Univesity, 264 Guangzhou Road, Nanjing, Jiangsu, 210029, PR China.
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25
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Garcia-Rizo C, Cabrera B, Bioque M, Mezquida G, Lobo A, Gonzalez-Pinto A, Diaz-Caneja CM, Corripio I, Vieta E, Baeza I, Garcia-Portilla MP, Gutierrez-Fraile M, Rodriguez-Jimenez R, Garriga M, Fernandez-Egea E, Bernardo M. The effect of early life events on glucose levels in first-episode psychosis. Front Endocrinol (Lausanne) 2022; 13:983792. [PMID: 36545332 PMCID: PMC9762519 DOI: 10.3389/fendo.2022.983792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2022] [Accepted: 10/10/2022] [Indexed: 12/12/2022] Open
Abstract
First episode of psychosis (FEP) patients display a wide variety of metabolic disturbances at onset, which might underlie these patients' increased morbidity and early mortality. Glycemic abnormalities have been previously related to pharmacological agents; however, recent research highlights the impact of early life events. Birth weight (BW), an indirect marker of the fetal environment, has been related to glucose abnormalities in the general population over time. We aim to evaluate if BW correlates with glucose values in a sample of FEP patients treated with different antipsychotics. Two hundred and thirty-six patients were included and evaluated for clinical and metabolic variables at baseline and at 2, 6, 12, and 24 months of follow-up. Pearson correlations and linear mixed model analysis were conducted to analyze the data. Antipsychotic treatment was grouped due to its metabolic risk profile. In our sample of FEP patients, BW was negatively correlated with glucose values at 24 months of follow-up [r=-0.167, p=0.037]. BW showed a trend towards significance in the association with glucose values over the 24-month period (F=3.22; p=0.073) despite other confounders such as age, time, sex, body mass index, antipsychotic type, and chlorpromazine dosage. This finding suggests that BW is involved in the evolution of glucose values over time in a cohort of patients with an FEP, independently of the type of pharmacological agent used in treatment. Our results highlight the importance of early life events in the later metabolic outcome of patients.
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Affiliation(s)
- Clemente Garcia-Rizo
- Barcelona Clínic Schizophrenia Unit, Institute of Neuroscience, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Bibiana Cabrera
- Barcelona Clínic Schizophrenia Unit, Institute of Neuroscience, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
| | - Miquel Bioque
- Barcelona Clínic Schizophrenia Unit, Institute of Neuroscience, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Gisela Mezquida
- Barcelona Clínic Schizophrenia Unit, Institute of Neuroscience, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Antonio Lobo
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Department of Medicine and Psychiatry, University of Zaragoza, Instituto de Investigación Sanitaria Aragón (IIS Aragón), Zaragoza, Spain
| | - Ana Gonzalez-Pinto
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Hospital Universitario de Alava, Servicio de Psiquiatría, BIOARABA, University of the Basque Country, Vitoria, Spain
| | - Covadonga M. Diaz-Caneja
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, School of Medicine, Universidad Complutense, Madrid, Spain
| | - Iluminada Corripio
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Eduard Vieta
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Bipolar and Depressive Disorders Unit, Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - Inmaculada Baeza
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Child and Adolescent Psychiatry and Psychology Department, Hospital Clinic of Barcelona, Institute of Neurosciences, University of Barcelona, Barcelona, Spain
| | - Maria Paz Garcia-Portilla
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Department of Psychiatry, University of Oviedo, Oviedo, Spain. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | - Miguel Gutierrez-Fraile
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Department of Psychiatry, Araba University Hospital, University of the Basque Country (UPV/EHU), Vitoria, Spain
- Neurosciences Department, Araba University Hospital, University of the Basque Country (UPV/EHU), Vitoria, Spain
| | - Roberto Rodriguez-Jimenez
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Instituto de Investigacion Sanitaria, Hospital 12 de Octubre (imas12), Madrid, Spain
| | - Marina Garriga
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Bipolar and Depressive Disorders Unit, Hospital Clinic, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
| | - Emilio Fernandez-Egea
- Department of Psychiatry, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
- Cambridgeshire and Peterborough NHS Foundation Trust, Huntingdon, United Kingdom
| | - Miguel Bernardo
- Barcelona Clínic Schizophrenia Unit, Institute of Neuroscience, Hospital Clínic of Barcelona, University of Barcelona, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
- Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
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26
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Johansen IT, Steen NE, Rødevand L, Werner MCF, Lunding SH, Hjell G, Ormerod MBEG, Agartz I, Melle I, Lagerberg TV, Nerhus M, Andreassen OA. Sex-specific associations between metabolic hormones, severe mental disorders and antipsychotic treatment. Psychoneuroendocrinology 2022; 146:105927. [PMID: 36152455 DOI: 10.1016/j.psyneuen.2022.105927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 09/03/2022] [Accepted: 09/12/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND Metabolic dysregulation has been associated with severe mental disorders (SMD) and with antipsychotic (AP) treatment, but the role of sex is unknown. To identify possible sex-related processes linked to SMD and AP treatment, we investigated sex differences in associations between hormones involved in metabolic regulation in patients with SMD compared to healthy controls (HC) and AP treatment. METHODS We included patients with SMD (N = 1753) and HC (N = 1194) and measured hormones involved in metabolic regulation (insulin, cortisol, thyroid-stimulating hormone (TSH), thyroxine, leptin, adiponectin, testosterone, sex hormone-binding globulin (SHBG), prolactin). Patients were grouped according to use of first-generation AP (N = 163), second-generation AP (N = 1087) or no use of AP (N = 503). Hormones were used one by one as dependent variables in multiple regression analyses with interactions between sex and SMD patients versus HC, and between sex and AP treatment, followed by analyses in males and females separately. RESULTS We found significant interactions between sex and SMD patients versus HC for testosterone, SHBG and adiponectin, with significantly higher testosterone and lower adiponectin levels in females. Furthermore, we found significant interaction between sex and AP groups for TSH, testosterone and insulin, with significantly lower TSH levels in AP-treated females, and lower testosterone and higher insulin levels in AP-treated males. CONCLUSIONS Our findings suggest sex differences in metabolic hormones related to both SMD and AP treatment, indicating sex-dependent mechanisms. Clinicians should be aware of potential sex-specific metabolic changes during AP treatment and experimental studies are warranted to clarify the underlying mechanisms.
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Affiliation(s)
- Ingrid T Johansen
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Nils Eiel Steen
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Linn Rødevand
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Maren C F Werner
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Synve H Lunding
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Gabriela Hjell
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatry, Ostfold Hospital, Graalum, Norway
| | - Monica B E G Ormerod
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Ingrid Agartz
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway; Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institute & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden
| | - Ingrid Melle
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Trine V Lagerberg
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Mari Nerhus
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Akershus University Hospital, Division of Mental Health Services, Department for Special Psychiatry, Lorenskog, Norway
| | - Ole A Andreassen
- NORMENT Centre, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway
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Sormunen E, Saarinen MM, Salokangas RKR, Hutri-Kähönen N, Viikari J, Raitakari OT, Hietala J. Metabolic trajectories in childhood and adolescence: Effects on risk for schizophrenia. SCHIZOPHRENIA (HEIDELBERG, GERMANY) 2022; 8:82. [PMID: 36220836 PMCID: PMC9553975 DOI: 10.1038/s41537-022-00282-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Accepted: 09/03/2022] [Indexed: 11/09/2022]
Abstract
Abnormal glucose and lipid metabolism is common in antipsychotic-naive first-episode patients with schizophrenia, but it is unclear whether these changes can already be seen in premorbid or prodromal period, before the first psychotic episode. We examined insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride trajectories in children and adolescents (9-18 years old), who were later diagnosed with schizophrenia, any non-affective psychosis (NAP) or affective disorder (AD). The study population consisted of a general population-based cohort "The Cardiovascular Risk in Young Finns Study", started in 1980 (n = 3596). Psychiatric diagnoses were derived from the Health Care Register up to the year 2018. Multivariate statistical analysis indicated no significant differences in insulin or lipid levels in children and adolescents who later developed schizophrenia (n = 41) compared to the cohort control group (n = 3202). In addition, no changes in these parameters were seen in the NAP (n = 74) or AD (n = 156) groups compared to the controls, but lower triglyceride levels in childhood/adolescence associated with earlier diagnosis of psychotic disorder in the NAP group. Taken together, our results do not support any gross-level insulin or lipid changes during childhood and adolescence in individuals with later diagnosis of schizophrenia-spectrum disorder. Since changes in glucose and lipid metabolism can be observed in neuroleptic-naive patients with schizophrenia, we hypothesize that the more marked metabolic changes develop during the prodrome closer to the onset of the first psychotic episode. The findings have relevance for studies on developmental hypotheses of schizophrenia.
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Affiliation(s)
- Elina Sormunen
- grid.1374.10000 0001 2097 1371Department of Psychiatry, University of Turku and Turku University Hospital, Turku, Finland
| | - Maiju M. Saarinen
- grid.1374.10000 0001 2097 1371Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
| | - Raimo K. R. Salokangas
- grid.1374.10000 0001 2097 1371Department of Psychiatry, University of Turku and Turku University Hospital, Turku, Finland
| | - Nina Hutri-Kähönen
- grid.502801.e0000 0001 2314 6254Tampere Centre for Skills Training and Simulation, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Jorma Viikari
- grid.410552.70000 0004 0628 215XDepartment of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland
| | - Olli T. Raitakari
- grid.1374.10000 0001 2097 1371Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland ,grid.1374.10000 0001 2097 1371Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland ,grid.410552.70000 0004 0628 215XDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
| | - Jarmo Hietala
- grid.1374.10000 0001 2097 1371Department of Psychiatry, University of Turku and Turku University Hospital, Turku, Finland
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Li S, Chen D, Xiu M, Li J, Zhang XY. Prevalence and clinical correlates of impaired glucose tolerance in first-episode versus chronic patients with schizophrenia. Early Interv Psychiatry 2022; 16:985-993. [PMID: 34743408 DOI: 10.1111/eip.13240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 07/26/2021] [Accepted: 10/19/2021] [Indexed: 11/30/2022]
Abstract
AIM Studies using oral glucose tolerance tests (OGTT) have shown that impaired glucose metabolism presents in the early stages of schizophrenia (SCZ). However, there is a lack of studies on changes in glucose metabolism with the stage of the disease. We first explored the features of glucose metabolic pattern at different phases of male SCZ. METHODS We recruited 83 male first episode drug-naïve patients with SCZ (FEDN-SCZ) and 64 male chronic patients with SCZ (CH-SCZ), as well as 14 male healthy controls. The Positive and Negative Syndrome Scale (PANSS) was used to assess the psychopathology of patients. OGTT, fasting plasma glucose and lipid profiles of all participants were examined. RESULTS While the impaired glucose tolerance (IGT) rate of male SCZ patients was higher than that of HC (P < .05), there was no difference in IGT prevalence between FEDN-SCZ and CH-SCZ. In male FEDN-SCZ, LDL (OR = 2.64, 95% CI = 1.11-6.29, P = .028) and PANSS total score (OR = 1.03, 95% CI = 1.00-1.06, P = .046) were positively correlated with IGT; in male CH-SCZ, BMI (OR = 1.7, 95% CI = 1.08-2.67, P = .023), PANSS total score (OR = 0.82, 95% CI = 0.70-0.96, P = .015) and positive symptoms (OR = 0.45, 95% CI = 0.20-0.99, P = .046) were significantly correlated with IGT. CONCLUSIONS Our findings reflect different glucose metabolism patterns in different stages of SCZ.
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Affiliation(s)
- Shen Li
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China.,Department of Psychiatry, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
| | - Dachun Chen
- Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, China
| | - Meihong Xiu
- Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, China
| | - Jie Li
- Laboratory of Biological Psychiatry, Institute of Mental Health, Tianjin Anding Hospital, Tianjin Medical University, Tianjin, China
| | - Xiang Yang Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.,Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
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Yang Y, Shen M, Li L, Long Y, Wang L, Lang B, Wu R. Olanzapine Promotes the Occurrence of Metabolic Disorders in Conditional TCF7L2-Knockout Mice. Front Cell Dev Biol 2022; 10:890472. [PMID: 35874808 PMCID: PMC9298277 DOI: 10.3389/fcell.2022.890472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 05/16/2022] [Indexed: 11/29/2022] Open
Abstract
Objectives: Schizophrenia (SCZ) patients display higher incidence of metabolic syndrome (MetS) and comorbidity of type II diabetes. Both atypical antipsychotics and genetic variants are believed to predispose the patients with the risk, but their interplay remains largely unknown. TCF7L2 is one of the most common genes strongly associated with glucose homeostasis which also participates in the pathogenesis of schizophrenia. In this study, we aimed to explore the regulatory roles of TCF7L2 in atypical antipsychotics-induced MetS. Methods: Mice with pancreatic β-cell–specific Tcf7l2 deletion (CKO) were generated. The CKO mice and control littermates were subjected to olanzapine (4 mg/kg/day) or saline gavage for 6 weeks. Metabolic indices, β cell mass, and the expressing levels of TCF7L2 and GLP-1R in the pancreatic tissue were closely monitored. Results: Tcf7l2 CKO mice displayed a spectrum of core features of MetS, which included remarkably increased rate of weight gain, higher fasting insulin, higher values of blood lipids (cholesterol, triglyceride, and low-density lipoprotein), impaired glucose tolerance, and hypertrophy of adipocytes. Notably, these effects could be further exacerbated by olanzapine. In addition, Tcf7l2 CKO mice with the olanzapine group showed significantly decreased expressions of GLP-1R protein and a trend of reduced pancreatic β-cell mass. RT-qPCR revealed that the CKO mice presented a significantly less transcription of Sp5, an important element of the Wnt signaling pathway. Conclusion: Our study illustrates that mice with pancreatic β-cell–targeted Tcf7l2 deletion were more vulnerable to suffer metabolic abnormalities after olanzapine administration. This impairment may be mediated by the reduced expression of GLP-1R.
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Affiliation(s)
- Ye Yang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Manjun Shen
- Shenzhen Nanshan Center for Chronic Disease Control, Department of Psychiatry, Shenzhen, China
| | - Li Li
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yujun Long
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Lu Wang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Bing Lang
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
- *Correspondence: Bing Lang, ; Renrong Wu,
| | - Renrong Wu
- National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China
- *Correspondence: Bing Lang, ; Renrong Wu,
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Finlay S, Rudd D, McDermott B, Sarnyai Z. Allostatic load and systemic comorbidities in psychiatric disorders. Psychoneuroendocrinology 2022; 140:105726. [PMID: 35339811 DOI: 10.1016/j.psyneuen.2022.105726] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 02/16/2022] [Accepted: 03/11/2022] [Indexed: 12/11/2022]
Abstract
Psychiatric disorders are complex, disabling, and chronic conditions that are often accompanied by one or more systemic medical comorbidities. In this narrative review, we provide an overview of the allostatic load concept, which represents a multi-system dysregulation in response to chronic stress and link it to systemic comorbidities associated with psychiatric disorders. We synthesized published literature gathered using Medline (Ovid), Scopus, and PsychInfo and identified a high frequency of systemic comorbidities for both mood and psychotic disorders. The identified cardiovascular, metabolic, and immune comorbidities may represent the result of chronic wear and tear caused by a complex interaction between chronic psychosocial stress, health risk behaviors, pharmacological stressors, and the biological systems involved in the development of allostatic load. These findings support the notion that psychiatric disorders should be re-conceptualized as systemic disorders, affecting the brain and systemic biological pathways in an interconnected fashion to result in systemic comorbidities. We suggest that the multi-systemic and multi-dimensional approach that drives the allostatic load concept should be considered for understanding comorbidities in vulnerable psychiatric patients.
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Affiliation(s)
- Sabine Finlay
- Laboratory of Psychiatric Neuroscience, Centre for Molecular Therapeutics, James Cook University, Townsville, Queensland, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia; College of Public Health, Medical & Veterinary Sciences, James Cook University, Queensland, Australia
| | - Donna Rudd
- Laboratory of Psychiatric Neuroscience, Centre for Molecular Therapeutics, James Cook University, Townsville, Queensland, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia; College of Public Health, Medical & Veterinary Sciences, James Cook University, Queensland, Australia
| | - Brett McDermott
- College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia
| | - Zoltán Sarnyai
- Laboratory of Psychiatric Neuroscience, Centre for Molecular Therapeutics, James Cook University, Townsville, Queensland, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, Queensland, Australia; College of Public Health, Medical & Veterinary Sciences, James Cook University, Queensland, Australia.
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Petrikis P, Karampas A, Leondaritis G, Markozannes G, Archimandriti DT, Spyrou P, Georgiou G, Skapinakis P, Voulgari PV. Adiponectin, leptin and resistin levels in first-episode, drug-naïve patients with psychosis before and after short-term antipsychotic treatment. J Psychosom Res 2022; 157:110789. [PMID: 35344816 DOI: 10.1016/j.jpsychores.2022.110789] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 03/04/2022] [Accepted: 03/16/2022] [Indexed: 12/21/2022]
Abstract
OBJECTIVE There is increasing evidence that adiponectin, resistin and leptin may be implicated in the pathophysiology of neuropsychiatric disorders, including schizophrenia. The results of the studies so far remain controversial. Our aim was to compare serum adiponectin, leptin and resistin levels between drug-naïve, first -episode patients with psychosis and healthy controls and in the same group of patients after six weeks of antipsychotic treatment. METHODS Forty first-episode patients with psychosis and 40 matched controls were included in the study. Serum levels of adiponectin, resistin and leptin were measured by enzyme linked immunosorbent assay (ELISA) in both groups. In the patient group, the same adipokines were also measured six weeks after the initiation of antipsychotic treatment. RESULTS Log-transformed serum levels of adiponectin (mean difference = 1.68, 95% confidence interval [CI] = 1.30 to 2.06, U = 157, p < 0.0001), resistin (0.48, 95% CI = 0.36 to 0.59, t = 8.00, p < 0.0001) and leptin (0.66, 95% CI = 0.52 to 0.80, U = 160, p < 0.0001) were significantly higher to the patient group compared to controls. Leptin levels were significantly decreased in the patient group six weeks after the initiation of antipsychotic treatment (mean change = -0.40, 95% CI = -0.59 to -0.21, W = 666; p < 0.0001) while those of adiponectin and resistin levels did not change significantly. CONCLUSION In our study we found higher levels of adiponectin, leptin and resistin in drug-naïve, first-episode patients with normal Body Mass Index (BMI) compared to controls. After six weeks of antipsychotic treatment, there was no change in adiponectin and resistin levels, while leptin levels were reduced compared to baseline.
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Affiliation(s)
- Petros Petrikis
- Department of Psychiatry, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece.
| | - Andreas Karampas
- Department of Psychiatry, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece
| | - George Leondaritis
- Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece; Institute of Biosciences, University Research Center of Ioannina, 45110 Ioannina, Greece
| | - Georgios Markozannes
- Department of Hygiene and Epidemiology, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece
| | - Dimitra T Archimandriti
- Rheumatology Clinic, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece
| | - Polyxeni Spyrou
- Rheumatology Clinic, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece
| | - Georgios Georgiou
- Department of Psychiatry, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece
| | - Petros Skapinakis
- Department of Psychiatry, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece
| | - Paraskevi V Voulgari
- Rheumatology Clinic, Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Ioannina (UOI), P.O. Box 1186, 45110 Ioannina, Greece
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Burghardt KJ, Calme G, Caruso M, Howlett BH, Sanders E, Msallaty Z, Mallisho A, Seyoum B, Qi YA, Zhang X, Yi Z. Profiling the Skeletal Muscle Proteome in Patients on Atypical Antipsychotics and Mood Stabilizers. Brain Sci 2022; 12:259. [PMID: 35204022 PMCID: PMC8870450 DOI: 10.3390/brainsci12020259] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 02/09/2022] [Accepted: 02/10/2022] [Indexed: 02/04/2023] Open
Abstract
Atypical antipsychotics (AAP) are used in the treatment of severe mental illness. They are associated with several metabolic side effects including insulin resistance. The skeletal muscle is the primary tissue responsible for insulin-stimulated glucose uptake. Dysfunction of protein regulation within the skeletal muscle following treatment with AAPs may play a role in the associated metabolic side effects. The objective of this study was to measure protein abundance in the skeletal muscle of patients on long-term AAP or mood stabilizer treatment. Cross-sectional muscle biopsies were obtained from patients with bipolar disorder and global protein abundance was measured using stable isotope labeling by amino acid (SILAC) combined with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Sixteen patients completed muscle biopsies and were included in the proteomic analyses. A total of 40 proteins were significantly different between the AAP group and the mood stabilizer group. In-silico pathway analysis identified significant enrichment in several pathways including glucose metabolism, cell cycle, apoptosis, and folate metabolism. Proteome abundance changes also differed based on protein biological processes and function. In summary, significant differences in proteomic profiles were identified in the skeletal muscle between patients on AAPs and mood stabilizers. Future work is needed to validate these findings in prospectively sampled populations.
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Affiliation(s)
- Kyle J. Burghardt
- Department of Pharmacy Practice, University Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Suite 2190, Detroit, MI 48201, USA; (G.C.); (B.H.H.); (E.S.)
| | - Griffin Calme
- Department of Pharmacy Practice, University Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Suite 2190, Detroit, MI 48201, USA; (G.C.); (B.H.H.); (E.S.)
| | - Michael Caruso
- Department of Pharmaceutical Science, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; (M.C.); (X.Z.); (Z.Y.)
| | - Bradley H. Howlett
- Department of Pharmacy Practice, University Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Suite 2190, Detroit, MI 48201, USA; (G.C.); (B.H.H.); (E.S.)
| | - Elani Sanders
- Department of Pharmacy Practice, University Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Suite 2190, Detroit, MI 48201, USA; (G.C.); (B.H.H.); (E.S.)
| | - Zaher Msallaty
- Division of Endocrinology, School of Medicine, Wayne State University, 4201 St Antoine, Detroit, MI 48201, USA; (Z.M.); (A.M.); (B.S.)
| | - Abdullah Mallisho
- Division of Endocrinology, School of Medicine, Wayne State University, 4201 St Antoine, Detroit, MI 48201, USA; (Z.M.); (A.M.); (B.S.)
| | - Berhane Seyoum
- Division of Endocrinology, School of Medicine, Wayne State University, 4201 St Antoine, Detroit, MI 48201, USA; (Z.M.); (A.M.); (B.S.)
| | - Yue A. Qi
- Center for Alzheimer’s and Related Dementias, National Institutes of Health, Bethesda, MD 20892, USA;
| | - Xiangmin Zhang
- Department of Pharmaceutical Science, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; (M.C.); (X.Z.); (Z.Y.)
| | - Zhengping Yi
- Department of Pharmaceutical Science, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; (M.C.); (X.Z.); (Z.Y.)
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Vázquez-Bourgon J, Gómez-Revuelta M, Mayoral-van Son J, Labad J, Ortiz-García de la Foz V, Setién-Suero E, Ayesa-Arriola R, Tordesillas-Gutiérrez D, Juncal-Ruiz M, Crespo-Facorro B. Pattern of long-term weight and metabolic changes after a first episode of psychosis: Results from a 10-year prospective follow-up of the PAFIP program for early intervention in psychosis cohort. Eur Psychiatry 2022; 65:e48. [PMID: 35971658 PMCID: PMC9486831 DOI: 10.1192/j.eurpsy.2022.2308] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background People with psychosis are at higher risk of cardiovascular events, partly explained by a higher predisposition to gain weight. This has been observed in studies on individuals with a first-episode psychosis (FEP) at short and long term (mainly up to 1 year) and transversally at longer term in people with chronic schizophrenia. However, there is scarcity of data regarding longer-term (above 3-year follow-up) weight progression in FEP from longitudinal studies. The aim of this study is to evaluate the longer-term (10 years) progression of weight changes and related metabolic disturbances in people with FEP. Methods Two hundred and nine people with FEP and 57 healthy participants (controls) were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric, clinical, and sociodemographic data were collected. Results People with FEP presented a significant and rapid increase in mean body weight during the first year of treatment, followed by less pronounced but sustained weight gain over the study period (Δ15.2 kg; SD 12.3 kg). This early increment in weight predicted longer-term changes, which were significantly greater than in healthy controls (Δ2.9 kg; SD 7.3 kg). Weight gain correlated with alterations in lipid and glycemic variables, leading to clinical repercussion such as increments in the rates of obesity and metabolic disturbances. Sex differences were observed, with women presenting higher increments in body mass index than men. Conclusions This study confirms that the first year after initiating antipsychotic treatment is the critical one for weight gain in psychosis. Besides, it provides evidence that weight gain keep progressing even in the longer term (10 years), causing relevant metabolic disturbances.
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Abstract
Depression and psychosis have a developmental component to their origin. Epidemiologic evidence, which we synthesize in this nonsystematic review, suggests that early-life infection, inflammation, and metabolic alterations could play a role in the etiology of these psychiatric disorders. The risk of depression and psychosis is associated with prenatal maternal and childhood infections, which could be mediated by impaired neurodevelopment. Evidence suggests linear dose-response associations between elevated concentrations of circulating inflammatory markers in childhood, particularly the inflammatory cytokine interleukin 6, and the risk for depression and psychosis subsequently in early adulthood. Childhood inflammatory markers are also associated with persistence of depressive symptoms subsequently in adolescence and early adulthood. Developmental trajectories reflecting persistently high insulin levels during childhood and adolescence are associated with a higher risk of psychosis in adulthood, whereas increased adiposity during and after puberty is associated with the risk of depression. Together, these findings suggest that higher levels of infection, inflammation, and metabolic alterations commonly seen in people with depression and psychosis could be a cause for, rather than simply a consequence of, these disorders. Therefore, early-life immuno-metabolic alterations, as well as factors influencing these alterations such as adversity or maltreatment, could represent targets for prevention of these psychiatric disorders. Inflammation could also be an important treatment target for depression and psychosis. The field requires further research to examine sensitive periods when exposure to such immuno-metabolic alterations is most harmful. Interventional studies are also needed to test the potential usefulness of targeting early-life immuno-metabolic alterations for preventing adult depression and psychosis.
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Chan JKN, Wong CSM, Or PCF, Chen EYH, Chang WC. Diabetes complication burden and patterns and risk of mortality in people with schizophrenia and diabetes: A population-based cohort study with 16-year follow-up. Eur Neuropsychopharmacol 2021; 53:79-88. [PMID: 34481187 DOI: 10.1016/j.euroneuro.2021.08.263] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 07/29/2021] [Accepted: 08/17/2021] [Indexed: 10/20/2022]
Abstract
Schizophrenia is associated with increased prevalence of diabetes. However, risk of diabetes complications as well as the impact of complication burden and patterns on subsequent mortality risk in schizophrenia patients with co-existing diabetes is understudied. This population-based, propensity-score matched (1:10) cohort study identified 6991 patients with incident diabetes and pre-existing schizophrenia and 68,682 patients with incident diabetes only (comparison group) between 2001 and 2016 in Hong Kong, using territory-wide medical-record database of public healthcare services. Complications were measured by Diabetes Complications Severity Index (DCSI), which stratified complication burden into 6 levels (DCSI score=0, 1, 2, 3, 4, or ≥5). Associations of diabetes complications, in terms of DCSI scores (complication burden), specific types and two-way combinations of complications (complication patterns), with all-cause mortality rate in schizophrenia were evaluated using Cox proportional-hazards models. Schizophrenia group had comparable macrovascular (adjusted OR 0.99 [95% CI 0.92-1.06]) and lower microvascular (0.79 [0.73-0.86]) complication rates relative to comparison group. Mortality risk ratio for schizophrenia was elevated at all complication burden levels, which conferred incremental impact on excess mortality in both groups. Cardiovascular diseases (1.60 [1.45-1.77]) and cerebrovascular-metabolic diseases (2.74 [1.25-5.99]) were associated with the highest differential mortality in schizophrenia among various specific complications and complication combinations, respectively. Our results indicate that schizophrenia patients with co-existing diabetes are at increased risk of excess mortality relative to those with diabetes alone, regardless of complication burden levels. Implementation of multilevel, targeted interventions is needed to improve diabetes-related outcomes and reduce mortality gap in this vulnerable population.
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Affiliation(s)
- Joe Kwun Nam Chan
- Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong
| | - Corine Sau Man Wong
- Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong
| | - Philip Chi Fai Or
- Department of Psychiatry, Queen Mary Hospital, Hospital Authority, Hong Kong
| | - Eric Yu Hai Chen
- Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong
| | - Wing Chung Chang
- Department of Psychiatry, Queen Mary Hospital, The University of Hong Kong, Pokfulam, Hong Kong; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong.
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Davis-Glurich S, Haas B, Thume K, Braus DF. Primäre Psychose und Typ-2-Diabetes. DIABETOLOGE 2021. [DOI: 10.1007/s11428-021-00799-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Aging biological markers in a cohort of antipsychotic-naïve first-episode psychosis patients. Psychoneuroendocrinology 2021; 132:105350. [PMID: 34271521 DOI: 10.1016/j.psyneuen.2021.105350] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 06/29/2021] [Accepted: 06/30/2021] [Indexed: 11/21/2022]
Abstract
Schizophrenia is a severe and multifactorial disorder with an unknown causative pathophysiology. Abnormalities in neurodevelopmental and aging processes have been reported. Relative telomere length (RTL) and DNA methylation age (DMA), well-known biomarkers for estimating biological age, are both commonly altered in patients with schizophrenia compared to healthy controls. However, few studies investigated these aging biomarkers in first-episode psychosis (FEP) and in antipsychotic-naïve patients. To cover the existing gap regarding DMA and RTL in FEP and antipsychotic treatment, we aimed to verify whether those aging markers could be associated with psychosis and treatment response. Thus, we evaluated these measures in the blood of FEP antipsychotic-naïve patients and healthy controls (HC), as well as the response to antipsychotics after 10 weeks of treatment with risperidone. RTL was measured in 392 subjects, being 80 FEP and 312 HC using qPCR, while DMA was analyzed in a subset of 60 HC, 60 FEP patients (antipsychotic-naïve) and 59 FEP-10W (after treatment) using the "Multi-tissue Predictor"and the Infinium HumanMethylation450 BeadChip Kit. We observed diminished DMA and longer RTL in FEP patients before treatment compared to healthy controls, indicating a decelerated aging process in those patients. We found no statistical difference between responder and non-responder patients at baseline for both markers. An increased DMA was observed in patients after 10 weeks of treatment, however, after adjusting for blood cell composition, no significant association remained. Our findings indicate a decelerated aging process in the early phases of the disease.
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Takayanagi Y, Ishizuka K, Laursen TM, Yukitake H, Yang K, Cascella NG, Ueda S, Sumitomo A, Narita Z, Horiuchi Y, Niwa M, Taguchi A, White MF, Eaton WW, Mortensen PB, Sakurai T, Sawa A. From population to neuron: exploring common mediators for metabolic problems and mental illnesses. Mol Psychiatry 2021; 26:3931-3942. [PMID: 33173197 PMCID: PMC8514126 DOI: 10.1038/s41380-020-00939-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Revised: 10/05/2020] [Accepted: 10/26/2020] [Indexed: 11/24/2022]
Abstract
Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of "from population to neuron", combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling. We accessed the Danish Registry and observed (1) a higher incidence of diabetes in people with SZ or BP and (2) higher incidence of major mental illnesses in people with diabetes in the same large cohort. These epidemiological data suggest the existence of common pathophysiological mediators in both diabetes and major mental illnesses. We hypothesized that molecules associated with insulin resistance might be such common mediators, and then validated the hypothesis by using two independent sets of olfactory neuronal cells biopsied from patients and healthy controls. In the first set, we confirmed an enrichment of insulin signaling-associated molecules among the genes that were significantly different between SZ patients and controls in unbiased expression profiling data. In the second set, olfactory neuronal cells from SZ and BP patients who were not pre-diabetic or diabetic showed reduced IRS2 tyrosine phosphorylation upon insulin stimulation, indicative of insulin resistance. These cells also displayed an upregulation of IRS1 protein phosphorylation at serine-312 at baseline (without insulin stimulation), further supporting the concept of insulin resistance in olfactory neuronal cells from SZ patients. Finally, Irs2 knockout mice showed an aberrant response to amphetamine, which is also observed in some patients with major mental illnesses. The bi-directional relationships between major mental illnesses and diabetes suggest that there may be common pathophysiological mediators associated with insulin resistance underlying these mental and physical conditions.
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Affiliation(s)
- Yoichiro Takayanagi
- Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Koko Ishizuka
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Thomas M. Laursen
- National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Denmark
| | - Hiroshi Yukitake
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Kun Yang
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Nicola G. Cascella
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Shuhei Ueda
- Medical Innovation Center, Kyoto University Graduate School of Medicine, Japan
| | - Akiko Sumitomo
- Medical Innovation Center, Kyoto University Graduate School of Medicine, Japan
| | - Zui Narita
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Yasue Horiuchi
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Minae Niwa
- Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Akiko Taguchi
- Department of Integrative Aging Neuroscience, National Center for Geriatrics and Gerontology, Japan
| | - Morris F. White
- Division of Endocrinology, Department of Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA
| | - William W. Eaton
- Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Preben B. Mortensen
- National Centre for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Denmark,The Lundbeck Foundation’s Initiative for Integrative Research, iPSYCH,Center for Integrated Register-based Research at Aarhus University, CIRRAU, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Takeshi Sakurai
- Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Akira Sawa
- Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA. .,Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. .,Departments of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA. .,Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA. .,Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Abnormal glucose metabolism is associated with clinical symptoms of adolescent-onset patients with first-episode drug-naive schizophrenia. Asian J Psychiatr 2021; 62:102716. [PMID: 34198180 DOI: 10.1016/j.ajp.2021.102716] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/17/2021] [Accepted: 05/25/2021] [Indexed: 02/04/2023]
Abstract
Extensive studies have reported alterations in glucose metabolism in adult-onset patients with schizophrenia, but less attention has been paid to adolescent-onset patients with first-episode drug-naive (FEDN) schizophrenia. The purpose of this study was to compare glucose metabolism between adolescent-onset patients with FEDN schizophrenia and healthy controls and to investigate the relationship between glucose metabolism and clinical symptoms in patients with schizophrenia. This study compared the glycometabolism parameters between 51 adolescents-onset patients with FEDN schizophrenia and 51 age- and sex-matched healthy controls. The Chinese version of the Positive and Negative Syndrome Scale (PANSS), Hamilton Anxiety Rating Scale, and Hamilton Depression Rating Scale were used to assess patients' psychiatric, anxiety, and depressive symptoms. The results showed that compared with healthy controls, the patients had a significantly higher prevalence of impaired fasting glucose and insulin resistance, as well as higher fasting plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index (HOMA-IR) and triglycerides, but lower high-density lipoprotein cholesterol levels. Moreover, HOMA-IR was negatively associated with PANSS general psychopathology, while glucose was positively correlated with depressive symptoms among patients. In sum, adolescent-onset patients with FEDN schizophrenia are more likely to have abnormal glucose metabolism and dyslipidemia than their healthy counterparts. Moreover, abnormal glucose metabolism may be closely related to the psychopathological symptoms of schizophrenia in the early stage of the disease.
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Rukavishnikov GV, Kasyanov ED, Zhilyaeva TV, Mazo GE. [Schizophrenia and cardiometabolic disorders]. Zh Nevrol Psikhiatr Im S S Korsakova 2021; 121:132-138. [PMID: 34283543 DOI: 10.17116/jnevro2021121061132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The aim of this review is to analyze the basic biological mechanisms of comorbidity of schizophrenia and metabolic, cardiovascular diseases, which are not directly associated with external risk factors. The study of the general pathophysiological mechanisms of schizophrenia and metabolic disorders can provide a significant basis not only for the fundamentally novel therapeutic, preventive and diagnostic measures, but also for a better understanding of the etiopathogenesis of these diseases. It seems likely that schizophrenia represents a heterogeneous group with a varying genetic basis for both mental symptoms and neuroendocrine, inflammatory processes that form concomitant somatic disorders. Thus, the new integrated approaches to the study of this problem with the latest methods of genetic and molecular research are relevant.
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Affiliation(s)
- G V Rukavishnikov
- Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia
| | - E D Kasyanov
- Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia
| | - T V Zhilyaeva
- Privolzhsky Research Medical University, Nizhny Novgorod, Russia
| | - G E Mazo
- Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia
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Flintoff J, Kesby JP, Siskind D, Burne TH. Treating cognitive impairment in schizophrenia with GLP-1RAs: an overview of their therapeutic potential. Expert Opin Investig Drugs 2021; 30:877-891. [PMID: 34213981 DOI: 10.1080/13543784.2021.1951702] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Schizophrenia is a neuropsychiatric disorder that affects approximately 1% of individuals worldwide. There are no available medications to treat cognitive impairment in this patient population currently. Preclinical evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve cognitive function. There is a need to evaluate how GLP-1 RAs alter specific domains of cognition and whether they will be of therapeutic benefit in individuals with schizophrenia. AREAS COVERED This paper summarizes the effects of GLP-1 RAs on metabolic processes in the brain and how these mechanisms relate to improved cognitive function. We provide an overview of preclinical studies that demonstrate GLP-1 RAs improve cognition and comment on their potential therapeutic benefit in individuals with schizophrenia. EXPERT OPINION To understand the benefits of GLP-1 RAs in individuals with schizophrenia, further preclinical research with rodent models relevant to schizophrenia symptomology are needed. Moreover, preclinical studies must focus on using a wider range of behavioral assays to understand whether important aspects of cognition such as executive function, attention, and goal-directed behavior are improved using GLP-1 RAs. Further research into the specific mechanisms of how GLP-1 RAs affect cognitive function and their interactions with antipsychotic medication commonly prescribed is necessary.
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Affiliation(s)
- Jonathan Flintoff
- Queensland Brain Institute, the University of Queensland, St Lucia, QLD, Australia
| | - James P Kesby
- Queensland Brain Institute, the University of Queensland, St Lucia, QLD, Australia.,QIMR Berghofer Medical Research Institute, Herston, QLD, Australia
| | - Dan Siskind
- Queensland Centre for Mental Health Research, Wacol, QLD, Australia.,Metro South Addiction and Mental Health Service, Woolloongabba, QLD, Australia
| | - Thomas Hj Burne
- Queensland Brain Institute, the University of Queensland, St Lucia, QLD, Australia.,Queensland Centre for Mental Health Research, Wacol, QLD, Australia
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Misiak B, Pruessner M, Samochowiec J, Wiśniewski M, Reginia A, Stańczykiewicz B. A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals. Front Neuroendocrinol 2021; 62:100930. [PMID: 34171354 DOI: 10.1016/j.yfrne.2021.100930] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 06/10/2021] [Accepted: 06/19/2021] [Indexed: 11/18/2022]
Abstract
Dysregulated cortisol responses and glucose metabolism have been reported in psychosis. We performed a random-effects meta-analysis of cortisol responses in first-episode psychosis (FEP) and psychosis risk states, taking into consideration glucose metabolism. A total of 47 studies were included. Unstimulated blood cortisol levels were significantly higher (g = 0.48, 95 %CI: 0.25-0.70, p < 0.001) in FEP, but not in psychosis risk states (g = 0.39, 95 %CI: -0.42-1.21, p = 0.342), compared to controls. Cortisol awakening response (CAR) was attenuated in FEP (g = -0.40, 95 %CI: -0.68 - -0.12, p = 0.006), but not in psychosis risk states (p = 0.433). Glucose and insulin levels were positively correlated with unstimulated blood cortisol levels in FEP. Our meta-analysis supports previous findings of elevated blood cortisol levels and attenuated CAR in FEP. Future research should focus on identifying the common denominators for alterations in stress hormones and glucose metabolism.
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Affiliation(s)
- Błażej Misiak
- Department of Psychiatry, Division of Consultation Psychiatry and Neuroscience, Wroclaw Medical University, Pasteura 10 Street, 50-367 Wroclaw, Poland.
| | - Marita Pruessner
- Prevention and Early Intervention Program for Psychosis, Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Canada; Department of Clinical Psychology, University of Konstanz, Konstanz, Germany
| | - Jerzy Samochowiec
- Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26 Street, 71-457 Szczecin, Poland
| | | | - Artur Reginia
- Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26 Street, 71-457 Szczecin, Poland
| | - Bartłomiej Stańczykiewicz
- Department of Nervous System Diseases, Wroclaw Medical University, Bartla 5 Street, 51-618 Wroclaw, Poland
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Linnaranta O, Trontti KT, Honkanen J, Hovatta I, Keinänen J, Suvisaari J. Peripheral metabolic state and immune system in first-episode psychosis - A gene expression study with a prospective one-year follow-up. J Psychiatr Res 2021; 137:383-392. [PMID: 33765450 DOI: 10.1016/j.jpsychires.2021.03.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 03/02/2021] [Accepted: 03/05/2021] [Indexed: 12/19/2022]
Abstract
he excess availability of glucose and lipids can also have an impact on the dynamics of activation and regulation of peripheral immune cellsWe aimed at understanding the correlations between peripheral metabolic state and immune system during the first year in first-episode psychosis (FEP). Patients with FEP (n = 67) and matched controls (n = 38), aged 18-40 years, were met at baseline, 2 and 12 months. Fasting peripheral blood samples were collected. We applied the NanoString nCounter in-solution hybridization technology to determine gene expression levels of 178 candidate genes reflecting activation of the immune system. Serum triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and insulin and plasma glucose (fP-Gluc) were measured. We applied Ingenuity Pathway Analysis (IPA) to visualize enrichment of genes to functional classes. Strength of positive or negative regulation of the disease and functional pathways was deduced from IPA activation Z-score at the three evaluation points. We correlated gene expression with plasma glucose, triglycerids and HDL and LDL, and used hierarchical clustering of the pairwise correlations to identify groups of genes with similar correlation patterns with metabolic markers. In patients, initially, genes associated with the innate immune system response pathways were upregulated, which decreased by 12 months. Furthermore, genes associated with apoptosis and T cell death were downregulated, and genes associated with lipid metabolism were increasingly downregulated by 12 months. The immune activation was thus an acute phase during illness onset. At baseline, after controlling for multiple testing, 31/178 genes correlated positively with fasting glucose levels, and 54/178 genes negatively with triglycerides in patients only. The gene clusters showed patterns of correlations with metabolic markers over time. The results suggest a functional link between peripheral immune system and metabolic state in FEP. Metabolic factors may have had an influence on the initial activation of the innate immune system. Future work is necessary to understand the role of metabolic state in the regulation of immune response in the early phases of psychosis.
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Affiliation(s)
- Outi Linnaranta
- Department of Psychiatry, McGill University, Montreal, QC, Canada; Douglas Centre for Sleep and Biological Rhythms, Douglas Mental Health University Institute, 6875 LaSalle Boulevard, H4H 1R3, Montreal, QC, Canada; Department of Public Health Solutions, Mental Health Unit, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland.
| | - Kalevi T Trontti
- Sleep Well Research Program, Faculty of Medicine, P.O. Box 21, FI-00014, University of Helsinki, Finland; Neuroscience Center, Helsinki Institute of Life Science HiLIFE, P.O. Box 21, FI-00014, University of Helsinki, Finland
| | - Jarno Honkanen
- Research Program for Clinical and Molecular Metabolism, P.O. Box 63, FI-00014, University of Helsinki, Helsinki, Finland
| | - Iiris Hovatta
- Sleep Well Research Program, Faculty of Medicine, P.O. Box 21, FI-00014, University of Helsinki, Finland; Neuroscience Center, Helsinki Institute of Life Science HiLIFE, P.O. Box 21, FI-00014, University of Helsinki, Finland; Department of Psychology and Logopedics, Medicum, P.O. Box 21, FI-00014, University of Helsinki, Finland
| | - Jaakko Keinänen
- Department of Public Health Solutions, Mental Health Unit, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland; Department of Psychiatry, University of Helsinki and Helsinki University Hospital, P.O. Box 590, FI-00029, Helsinki, Finland
| | - Jaana Suvisaari
- Department of Public Health Solutions, Mental Health Unit, Finnish Institute for Health and Welfare, P.O. Box 30, FI-00271, Helsinki, Finland
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Çakici N, Sutterland AL, Penninx BWJH, de Haan L, van Beveren NJM. Changes in peripheral blood compounds following psychopharmacological treatment in drug-naïve first-episode patients with either schizophrenia or major depressive disorder: a meta-analysis. Psychol Med 2021; 51:538-549. [PMID: 33653423 PMCID: PMC8020491 DOI: 10.1017/s0033291721000155] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 12/27/2020] [Accepted: 01/13/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND This meta-analysis on peripheral blood compounds in drug-naïve first-episode patients with either schizophrenia or major depressive disorder (MDD) examined which compounds change following psychopharmacological treatment. METHODS The Embase, PubMed and PsycINFO databases were systematically searched for longitudinal studies reporting measurements of blood compounds in drug-naïve first-episode schizophrenia or MDD. RESULTS For this random-effects meta-analysis, we retrieved a total of 31 studies comprising 1818 schizophrenia patients, and 14 studies comprising 469 MDD patients. Brain-derived neurotrophic factor (BDNF) increased following treatment in schizophrenia (Hedges' g (g): 0.55; 95% confidence interval (CI) 0.39-0.70; p < 0.001) and MDD (g: 0.51; CI 0.06-0.96; p = 0.027). Interleukin (IL)-6 levels decreased in schizophrenia (g: -0.48; CI -0.85 to -0.11; p = 0.011), and for MDD a trend of decreased IL-6 levels was observed (g: -0.39; CI -0.87 to 0.09; p = 0.115). Tumor necrosis factor alpha (TNFα) also decreased in schizophrenia (g: -0.34; CI -0.68 to -0.01; p = 0.047) and in MDD (g: -1.02; CI -1.79 to -0.25; p = 0.009). Fasting glucose levels increased only in schizophrenia (g: 0.26; CI 0.07-0.44; p = 0.007), but not in MDD. No changes were found for C-reactive protein, IL-1β, IL-2 and IL-4. CONCLUSIONS Psychopharmacological treatment has modulating effects on BDNF and TNFα in drug-naïve first-episode patients with either schizophrenia or MDD. These findings support efforts for further research into transdiagnostic preventive strategies and augmentation therapy for those with immune dysfunctions.
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Affiliation(s)
- Nuray Çakici
- Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZAmsterdam, the Netherlands
- Parnassia Academy, Parnassia Psychiatric Institute, Kiwistraat 43, 2552 DHThe Hague, the Netherlands
| | - Arjen L. Sutterland
- Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZAmsterdam, the Netherlands
| | - Brenda W. J. H. Penninx
- Department of Psychiatry, Amsterdam Public Health Research Institute and Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit, De Boelelaan 1105, 1081 HVAmsterdam, the Netherlands
| | - Lieuwe de Haan
- Department of Psychiatry and Amsterdam Neuroscience, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZAmsterdam, the Netherlands
| | - Nico J. M. van Beveren
- Parnassia Academy, Parnassia Psychiatric Institute, Kiwistraat 43, 2552 DHThe Hague, the Netherlands
- Department of Psychiatry, Erasmus Medical Center, Doctor Molewaterplein 40, 3015 GDRotterdam, the Netherlands
- Department of Neuroscience, Erasmus Medical Center, Doctor Molewaterplein 40, 3015 GDRotterdam, the Netherlands
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Stogios N, Smith E, Asgariroozbehani R, Hamel L, Gdanski A, Selby P, Sockalingam S, Graff-Guerrero A, Taylor VH, Agarwal SM, Hahn MK. Exploring Patterns of Disturbed Eating in Psychosis: A Scoping Review. Nutrients 2020; 12:E3883. [PMID: 33353080 PMCID: PMC7768542 DOI: 10.3390/nu12123883] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 12/03/2020] [Accepted: 12/09/2020] [Indexed: 12/19/2022] Open
Abstract
Disturbed eating behaviours have been widely reported in psychotic disorders since the early 19th century. There is also evidence that antipsychotic (AP) treatment may induce binge eating or other related compulsive eating behaviours. It is therefore possible that abnormal eating patterns may contribute to the significant weight gain and other metabolic disturbances observed in patients with psychosis. In this scoping review, we aimed to explore the underlying psychopathological and neurobiological mechanisms of disrupted eating behaviours in psychosis spectrum disorders and the role of APs in this relationship. A systematic search identified 35 studies that met our eligibility criteria and were included in our qualitative synthesis. Synthesizing evidence from self-report questionnaires and food surveys, we found that patients with psychosis exhibit increased appetite and craving for fatty food, as well as increased caloric intake and snacking, which may be associated with increased disinhibition. Limited evidence from neuroimaging studies suggested that AP-naïve first episode patients exhibit similar neural processing of food to healthy controls, while chronic AP exposure may lead to decreased activity in satiety areas and increased activity in areas associated with reward anticipation. Overall, this review supports the notion that AP use can lead to disturbed eating patterns in patients, which may contribute to AP-induced weight gain. However, intrinsic illness-related effects on eating behaviors remain less well elucidated, and many confounding factors as well as variability in study designs limits interpretation of existing literature in this field and precludes firm conclusions from being made.
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Affiliation(s)
- Nicolette Stogios
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Institute of Medical Science (IMS), University of Toronto, Toronto, ON M5S 1A8, Canada
| | - Emily Smith
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Institute of Medical Science (IMS), University of Toronto, Toronto, ON M5S 1A8, Canada
| | - Roshanak Asgariroozbehani
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Institute of Medical Science (IMS), University of Toronto, Toronto, ON M5S 1A8, Canada
| | - Laurie Hamel
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
| | - Alexander Gdanski
- Department of Human Biology, University of Toronto, Toronto, ON M5S 3J6, Canada;
| | - Peter Selby
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Department of Family and Community Medicine, University of Toronto, Toronto, ON M5G 1V7, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
| | - Sanjeev Sockalingam
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Institute of Medical Science (IMS), University of Toronto, Toronto, ON M5S 1A8, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
- Bariatric Surgery Program, University Health Network, Toronto, ON M5T 2S8, Canada
| | - Ariel Graff-Guerrero
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Institute of Medical Science (IMS), University of Toronto, Toronto, ON M5S 1A8, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
| | - Valerie H. Taylor
- Department of Psychiatry, University of Calgary, Calgary, AB T2N 1N4, Canada;
| | - Sri Mahavir Agarwal
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Institute of Medical Science (IMS), University of Toronto, Toronto, ON M5S 1A8, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
| | - Margaret K. Hahn
- Centre for Addiction and Mental Health (CAMH), Toronto, ON M6J 1H3, Canada; (N.S.); (E.S.); (R.A.); (L.H.); (P.S.); (S.S.); (A.G.-G.); (S.M.A.)
- Institute of Medical Science (IMS), University of Toronto, Toronto, ON M5S 1A8, Canada
- Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada
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Alameda L, Levier A, Gholam-Rezaee M, Golay P, Vandenberghe F, Delacretaz A, Baumann P, Glatard A, Dubath C, Herane-Vives A, Rodriguez V, Solida A, Do KQ, Eap CB, Conus P. Psychological trauma occurring during adolescence is associated with an increased risk of greater waist circumference in Early Psychosis patients treated with psychotropic medication. PLoS One 2020; 15:e0242569. [PMID: 33270646 PMCID: PMC7714104 DOI: 10.1371/journal.pone.0242569] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 11/04/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND It has been suggested that exposure to Childhood Trauma [CT] may play a role in the risk of obesity in Early Psychosis [EP] patients; however, whether this is independently of age at exposure to CT and the medication profile has yet to be investigated. METHODS 113 EP-patients aged 18-35 were recruited from the Treatment and Early Intervention in Psychosis Program [TIPP-Lausanne]. Body Mass Index [BMI], Weight Gain [WG] and Waist Circumference [WC] were measured prospectively at baseline and after 1, 2, 3, 6 and 12 months of weight gain inducing psychotropic treatment. Patients were classified as Early-Trauma and Late-Trauma if the exposure had occurred before age 12 or between ages 12 and 16 respectively. Generalized Linear Mixed-Models were adjusted for age, sex, socioeconomic status, baseline BMI, medication and for diagnosis of depression. RESULTS Late-Trauma patients, when compared to Non-Trauma patients showed greater WCs during the follow-up [p = 0.013]. No differences were found in any of the other follow-up measures. CONCLUSIONS Exposition to CT during adolescence in EP-patients treated with psychotropic medication is associated with greater WC during the early phase of the disease. Further investigation exploring mechanisms underlying the interactions between peripubertal stress, corticoids responsiveness and a subsequent increase of abdominal adiposity is warranted.
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Affiliation(s)
- Luis Alameda
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
- Service of General Psychiatry, Treatment and Early Intervention in Psychosis, Program [TIPP-Lausanne], Lausanne University Hospital [CHUV], Lausanne, Switzerland
- Department of Psychiatry, Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain
- Instituto de Investigación Sanitaria de Sevilla, IBiS, Sevilla, Spain
- * E-mail:
| | - Axel Levier
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery, Lausanne University Hospital, Prilly, Switzerland
| | - Mehdi Gholam-Rezaee
- Department of Psychiatry, Center for Psychiatric Epidemiology and Psychopathology, Lausanne University Hospital [CHUV], Lausanne, Switzerland
| | - Philippe Golay
- Service of General Psychiatry, Treatment and Early Intervention in Psychosis, Program [TIPP-Lausanne], Lausanne University Hospital [CHUV], Lausanne, Switzerland
- Community Psychiatry Service, Department of Psychiatry, Consultations de Chauderon, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
- Institute of Psychology, faculty of Social and Politic al Science, University of Lausanne, Lausanne, Switzerland
| | - Frederik Vandenberghe
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery, Lausanne University Hospital, Prilly, Switzerland
| | - Aurélie Delacretaz
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery, Lausanne University Hospital, Prilly, Switzerland
| | - Philipp Baumann
- Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital [CHUV], Lausanne, Switzerland
| | - Anaïs Glatard
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery, Lausanne University Hospital, Prilly, Switzerland
| | - Céline Dubath
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery, Lausanne University Hospital, Prilly, Switzerland
| | - Andres Herane-Vives
- Department of Psychological Medicine, Affective Disorders Research Group, Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
- Departamento de Clínicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile
- Affective Disorders Research Group, Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience King’s College London, London, United Kingdom
| | - Victoria Rodriguez
- Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
| | - Alessandra Solida
- Service of General Psychiatry, Treatment and Early Intervention in Psychosis, Program [TIPP-Lausanne], Lausanne University Hospital [CHUV], Lausanne, Switzerland
| | - Kim Q. Do
- Unit for Research in Schizophrenia, Center for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital [CHUV], Lausanne, Switzerland
| | - Chin B. Eap
- Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Hospital of Cery, Lausanne University Hospital, Prilly, Switzerland
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Geneva, Geneva, Switzerland
| | - Philippe Conus
- Service of General Psychiatry, Treatment and Early Intervention in Psychosis, Program [TIPP-Lausanne], Lausanne University Hospital [CHUV], Lausanne, Switzerland
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Noel JM, Jackson CW. ASHP Therapeutic Position Statement on the Use of Antipsychotic Medications in the Treatment of Adults with Schizophrenia and Schizoaffective Disorder. Am J Health Syst Pharm 2020; 77:2114-2132. [PMID: 32871013 PMCID: PMC7499485 DOI: 10.1093/ajhp/zxaa303] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
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Affiliation(s)
- Jason M Noel
- University of Maryland School of Pharmacy, Baltimore, MD
| | - Cherry W Jackson
- Auburn University Harrison School of Pharmacy, Auburn, AL.,Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, School of Medicine, Birmingham, AL
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Bohman H, Agartz I, Mansouri S, Naessen T, Lundberg M. Preclinical atherosclerosis in adolescents with psychotic or bipolar disorders investigated with carotid high-frequency ultrasound. Brain Behav 2020; 10:e01862. [PMID: 32997440 PMCID: PMC7749529 DOI: 10.1002/brb3.1862] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 08/15/2020] [Accepted: 08/28/2020] [Indexed: 11/08/2022] Open
Abstract
OBJECTIVE Early-onset psychosis (EOP) and bipolar disorder (EOBP) (at <18 years of age), are associated with an increased future risk of cardiovascular disease (CVD) and premature death. Yet it is unknown whether the arteries show visible signs of atherosclerosis in EOP and EOBP. This study investigated whether having EOP or EOBP was associated with detectable signs of preclinical atherosclerosis. METHOD By using 22 MHz high-frequency ultrasound, different layers of the arterial wall of the left common carotid artery (LCCA) were assessed in 77 individuals with EOP (n = 25), EOBP (n = 22), and in age-matched healthy controls (n = 30). Conventional CVD confounders were included in the analyses. RESULTS Adolescents with EOP and EOBP, compared to controls, had a significantly thicker LCCA intima thickness (0.132 vs. 0.095 mm, p < .001) and intima/media ratio (0.24 vs. 0.17 p < .001). There was a nonsignificant intima difference between EOP and EOBP. Conventional CVD risk factors did not explain the association between EOP/EOBP and intima thickness. In the group of EOP/EOBP, there was a significant correlation between the dose of current antipsychotic medication and intima thickness; however, the correlation was attenuated to a nonsignificant level when adjusted for global function. CONCLUSIONS Adolescents with EOP or EOBP had an increased LCCA intima thickness, interpreted as a sign of preclinical atherosclerosis. Global function of the disorders was the strongest determinant of intima thickness. The findings, if replicated, might have implications for long-term treatment of EOP and EOBP in order to reduce a future risk of CVD.
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Affiliation(s)
- Hannes Bohman
- Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden.,Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Ingrid Agartz
- NORMENT and K.G. Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.,Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway
| | - Shiva Mansouri
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
| | - Tord Naessen
- Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
| | - Mathias Lundberg
- Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
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Jena M, Mishra A, Mishra BR, Nath S, Maiti R. Effect of lurasidone versus olanzapine on cardiometabolic parameters in unmedicated patients with schizophrenia: a randomized controlled trial. Psychopharmacology (Berl) 2020; 237:3471-3480. [PMID: 32740676 DOI: 10.1007/s00213-020-05628-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 07/27/2020] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Patients with schizophrenia are at higher risk of cardiovascular morbidity and mortality than healthy individuals. This study was conducted to compare the effect of lurasidone and olanzapine on cardiometabolic parameters in unmedicated patients with schizophrenia. METHODS The present study was a randomized open-label, parallel design, active-controlled clinical trial. After recruitment and randomization of 101 patients, a baseline assessment was done by PANSS, SOFAS, lipid profile, fasting blood glucose, HbA1c, serum insulin and serum hs-CRP. HOMA-IR, atherogenic index, coronary risk index and cardiovascular risk indices were calculated as derived parameters. Patients received either lurasidone 80 mg or olanzapine 10 mg as monotherapy and followed up after 6 weeks. RESULTS There was a significant increase in fasting blood glucose (p < 0.001), HbA1c (p < 0.001) and serum insulin (p < 0.001) after 6 weeks of therapy in both the treatment groups but the difference between the groups was not significant (FBS, p = 0.209; HbA1c, p = 0.209; serum insulin, p = 0.720). Olanzapine showed worsening of lipid profile (p < 0.001) while the same improved with lurasidone (p < 0.001) and the difference between the groups was found to be significant (p < 0.001). Serum HDL level decreased in both the treatment groups (olanzapine, p < 0.001; lurasidone, p < 0.001) but the difference between the groups was not significant (p = 0.333). There was an increase in hs-CRP levels in both the treatment groups (olanzapine, p < 0.001; lurasidone, p < 0.001) with no significant difference between them (p = 0.467). Atherogenic index, coronary risk index and cardiovascular risk index increased significantly in the olanzapine group as compared with the lurasidone group (p < 0.001). CONCLUSION Lurasidone showed a favourable effect on lipid profile and cardiovascular risk indices over olanzapine. However, long-term studies are needed to establish and generalize the findings. TRIAL REGISTRATION ClinicalTrials.gov NCT03304457.
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Affiliation(s)
- Monalisa Jena
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
| | - Archana Mishra
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
| | - Biswa Ranjan Mishra
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
| | - Santanu Nath
- Department of Psychiatry, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
| | - Rituparna Maiti
- Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India.
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50
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Lis M, Stańczykiewicz B, Liśkiewicz P, Misiak B. Impaired hormonal regulation of appetite in schizophrenia: A narrative review dissecting intrinsic mechanisms and the effects of antipsychotics. Psychoneuroendocrinology 2020; 119:104744. [PMID: 32534330 DOI: 10.1016/j.psyneuen.2020.104744] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/25/2020] [Accepted: 05/30/2020] [Indexed: 12/14/2022]
Abstract
Cardiometabolic diseases are the main contributor of reduced life expectancy in patients with schizophrenia. It is now widely accepted that antipsychotic treatment plays an important role in the development of obesity and its consequences. However, some intrinsic mechanisms need to be taken into consideration. One of these mechanisms might be related to impaired hormonal regulation of appetite in this group of patients. In this narrative review, we aimed to dissect impairments of appetite-regulating hormones attributable to intrinsic mechanisms and those related to medication effects. Early hormonal alterations that might be associated with intrinsic mechanisms include low levels of leptin and glucagon-like peptide-1 (GLP-1) together with elevated insulin levels in first-episode psychosis (FEP) patients. However, evidence regarding low GLP-1 levels in FEP patients is based on one large study. In turn, multiple-episode schizophrenia patients show elevated levels of insulin, leptin and orexin A together with decreased levels of adiponectin. In addition, patients receiving olanzapine may present with low ghrelin levels. Post mortem studies have also demonstrated reduced number of neuropeptide Y neurons in the prefrontal cortex of patients with schizophrenia. Treatment with certain second-generation antipsychotics may also point to these alterations. Although our understanding of hormonal regulation of appetite in schizophrenia has largely been improved, several limitations and directions for future studies need to be addressed. This is of particular importance since several novel pharmacological interventions for obesity and diabetes have already been developed and translation of these developments to the treatment of cardiometabolic comorbidities in schizophrenia patients is needed.
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Affiliation(s)
- Michał Lis
- Clinical Department of Internal Diseases, Endocrinology and Diabetology, The Central Clinical Hospital of the Ministry of the Interior in Warsaw, Wołoska 137 Street, 02-507 Warsaw, Poland
| | - Bartłomiej Stańczykiewicz
- Department of Nervous System Diseases, Wroclaw Medical University, Bartla 5 Street, 51-618, Wroclaw, Poland
| | - Paweł Liśkiewicz
- Department of Psychiatry, Pomeranian Medical University, Broniewskiego 26 Street, 71-460, Szczecin, Poland
| | - Błażej Misiak
- Department of Genetics, Wroclaw Medical University, Marcinkowskiego 1 Street, 50-368 Wroclaw, Poland.
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