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Barsznica Y, Vandel P, Lambert B, Monnin J, Nicolier M, De Pinho C, Hickel J, Richard-Devantoy S, Morgny C, Szymanska M, Haffen E, Laurent E, Chopard G, Noiret N. Emotional information processing in depressed elderly with suicidal behavior. L'ENCEPHALE 2024:S0013-7006(24)00206-9. [PMID: 39580319 DOI: 10.1016/j.encep.2024.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 09/24/2024] [Accepted: 09/26/2024] [Indexed: 11/25/2024]
Abstract
Elderly suicide is a public health problem, especially in the presence of unipolar depression. Very few tools have been developed to assess suicide risk in the elderly. Suicidal behaviors (SB) are often associated with perturbations of emotional information processing. Recent eye-tracking evidence has indicated specific visual exploration of emotional facial expressions based on age, pathological status, or type of facial emotion expression, which encourage the development of more specific and reliable tools to help in the detection of SB in depressed elderly patients. The aim of this study was to characterize emotional facial information processing in elderly depressed patients with SB vs. patients without SB. We assessed fixation time on their facial expressions (SB n=10 and with noSB n=11). Results showed that depressed SB patients spent more time on emotional regions (i.e. eyes and mouth) of disgust, fear and neutral emotions than did depressed noSB patients. Conversely, fixation time did not differ between the groups for angry, sad and happy emotions. We discuss the difficulties in disengaging attention from emotional information congruent with the patient's emotional state. Specific visual exploration observed in suicidal depressed patients could be used as novel risk factors to more accurately assess and predict suicide risk.
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Affiliation(s)
- Yoan Barsznica
- Université de Franche-Comté, CHU de Besançon, Service de Psychiatrie de l'adulte, 25000 Besançon, France; Université de Franche-Comté, CHU de Besançon, Service de Neurologie, 25000 Besançon, France; Université de Franche-Comté, LINC, 25000 Besançon, France; Université de Franche-Comté, CHU de Besançon, Centre Mémoire Ressources et Recherche (CMRR), 25000 Besançon, France.
| | - Pierre Vandel
- Université de Franche-Comté, CHU de Besançon, Service de Psychiatrie de l'adulte, 25000 Besançon, France; Université de Franche-Comté, LINC, 25000 Besançon, France
| | - Bérénice Lambert
- Observatoire Régional de Santé Bourgogne Franche-Comté, 21000 Dijon, France
| | - Julie Monnin
- Université de Franche-Comté, LINC, 25000 Besançon, France
| | - Magali Nicolier
- Université de Franche-Comté, CHU de Besançon, Service de Psychiatrie de l'adulte, 25000 Besançon, France; Université de Franche-Comté, LINC, 25000 Besançon, France; Université de Franche-Comté, CHU de Besançon, CIC1431 Inserm, 25000 Besançon, France
| | - Claire De Pinho
- Association Hospitalière de Bourgogne Franche-Comté, Intersecteur de Psychiatrie de la Personne âgée 90Z01, 90800 Bavilliers, France
| | - Julia Hickel
- Association Hospitalière de Bourgogne Franche-Comté, Intersecteur de Psychiatrie de la Personne âgée 90Z01, 90800 Bavilliers, France
| | - Stephane Richard-Devantoy
- McGill University, Department of Psychiatry & Douglas Mental Health University, Institute McGill Group for Suicide Studies, Montréal, Canada
| | - Cynthia Morgny
- Observatoire Régional de Santé Bourgogne Franche-Comté, 21000 Dijon, France
| | | | - Emmanuel Haffen
- Université de Franche-Comté, CHU de Besançon, Service de Psychiatrie de l'adulte, 25000 Besançon, France; Université de Franche-Comté, LINC, 25000 Besançon, France; Université de Franche-Comté, CHU de Besançon, CIC1431 Inserm, 25000 Besançon, France; Fondation FondaMental, Créteil, France
| | - Eric Laurent
- Université de Franche-Comté, LINC, 25000 Besançon, France
| | - Gilles Chopard
- Université de Franche-Comté, CHU de Besançon, Service de Psychiatrie de l'adulte, 25000 Besançon, France; Université de Franche-Comté, CHU de Besançon, Service de Neurologie, 25000 Besançon, France; Université de Franche-Comté, LINC, 25000 Besançon, France; Université de Franche-Comté, CHU de Besançon, Centre Mémoire Ressources et Recherche (CMRR), 25000 Besançon, France
| | - Nicolas Noiret
- Université de Poitiers, Université de Tours, CNRS, CeRCA, Poitiers, France
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Wang YF, You GY, Han T, Liu Y, Li J, Ji X, Xie XM. Network analysis of comorbid depression, suicidality and biomarkers on HPA axis among mood disorder patients to psychiatric emergency services. Transl Psychiatry 2023; 13:203. [PMID: 37316541 DOI: 10.1038/s41398-023-02503-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 05/15/2023] [Accepted: 06/01/2023] [Indexed: 06/16/2023] Open
Abstract
Rapid assessment and intervention of suicide risk are common and challenging in psychiatric emergency departments (PED). It is unclear whether distinct pathophysiological processes exist among depressive patients with suicidality. This study examined the network structures of biomarkers on Hypothalamic-Pituitary-Adrenal (HPA) axis, such as Adrenocorticotropic hormone (ACTH) and Corticosterone (Cort), as well as suicidality and depressive symptoms in mood disorder patients in PED. Mood disorder patients in PED were assessed with the measurements of suicidality and depressive symptoms, respectively. A network analysis was performed to identify central symptoms and bridge symptoms of this network and their links to ACTH and Cort. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. A total of 1815 mood disorder patients were recruited. The prevalence of SI was 31.2% (95% CI: 28.15-34.21%), SP was 30.4% (95% CI: 27.39-33.41%), SA was 30.62% (95% CI: 27.61-33.64%) among psychiatric outpatients. The mean score of HAMD-24 was 13.87 ± 8.02. Network analysis revealed that 'Somatic anxiety' had the highest expected centrality, followed by 'Hopelessness' and 'Suicide attempt'. 'Corticosterone' and 'Retardation' may be the main bridge symptoms between depressive symptoms and the suicidality community. The network model showed a high degree of stability. Gender did not significantly influence the network structure. The central symptoms and key bridge symptoms identified could be potential targets for interventions of the HPA axis, which is designed for regular screening of a range of suicidal activity. In the light of this, timely treatment should be provided for psychiatric emergency care.
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Affiliation(s)
- Yi-Fan Wang
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Guang-Yun You
- Department of Psychiatry, The People's Hospital of Juxian County, Juxian, 276500, China
| | - Tian Han
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Yi Liu
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Juan Li
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China
| | - Xiao Ji
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
| | - Xiao-Meng Xie
- Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.
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Karabatsiakis A, de Punder K, Salinas-Manrique J, Todt M, Dietrich DE. Hair cortisol level might be indicative for a 3PM approach towards suicide risk assessment in depression: comparative analysis of mentally stable and depressed individuals versus individuals after completing suicide. EPMA J 2022; 13:383-395. [PMID: 36061827 PMCID: PMC9425778 DOI: 10.1007/s13167-022-00296-z] [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: 07/26/2022] [Accepted: 08/10/2022] [Indexed: 11/24/2022]
Abstract
Depression and suicidal behavior are interrelated, stress-associated mental health conditions, each lacking biological verifiability. Concepts of predictive, preventive, and personalized medicine (3PM) are almost completely missing for both conditions but are of utmost importance. Prior research reported altered levels of the stress hormone cortisol in the scalp hair of depressed individuals, however, data on hair cortisol levels (HCL) for suicide completers (SC) are missing. Here, we aimed to identify differences in HCL between subject with depression (n = 20), SC (n = 45) and mentally stable control subjects (n = 12) to establish the usage of HCL as a new target for 3PM. HCL was measured in extracts of pulverized hair (1-cm and 3-cm hair segments) using ELISA. In 3-cm hair segments, an average increase in HCL for depressed patients (1.66 times higher; p = .011) and SC (5.46 times higher; p = 1.65 × 10−5) compared to that for controls was observed. Furthermore, the average HCL in SC was significantly increased compared to that in the depressed group (3.28 times higher; p = 1.4 × 10−5). A significant correlation between HCL in the 1-cm and the 3-cm hair segments, as well as a significant association between the severity of depressive symptoms and HCL (3-cm segment) was found. To conclude, findings of increased HCL in subjects with depression compared to that in controls were replicated and an additional increase in HCL was seen in SC in comparison to patients with depression. The usage of HCL for creating effective patient stratification and predictive approach followed by the targeted prevention and personalization of medical services needs to be validated in follow-up studies.
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Affiliation(s)
- Alexander Karabatsiakis
- Department of Clinical Psychology II, Institute of Psychology, University of Innsbruck, Innsbruck, Austria
| | - Karin de Punder
- Department of Clinical Psychology II, Institute of Psychology, University of Innsbruck, Innsbruck, Austria
| | | | - Melanie Todt
- Institutes for Forensic Medicine, Hannover Medical School, Hannover, Germany
| | - Detlef E. Dietrich
- AMEOS Clinic for Psychiatry and Psychotherapy, Hildesheim, Germany
- Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany
- Center for Systems Neuroscience Hannover, Hannover Medical School, Hannover, Germany
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Johnston JN, Campbell D, Caruncho HJ, Henter ID, Ballard ED, Zarate CA. Suicide Biomarkers to Predict Risk, Classify Diagnostic Subtypes, and Identify Novel Therapeutic Targets: 5 Years of Promising Research. Int J Neuropsychopharmacol 2022; 25:197-214. [PMID: 34865007 PMCID: PMC8929755 DOI: 10.1093/ijnp/pyab083] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 11/02/2021] [Accepted: 11/30/2021] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Suicide is a global health crisis. However, no objective biomarkers of suicide risk currently exist, and self-reported data can be unreliable, which limits prediction, diagnostic, and treatment efforts. Reliable biomarkers that can differentiate between diagnostic subgroups, predict worsening symptoms, or suggest novel therapeutic targets would be extremely valuable for patients, researchers, and clinicians. METHODS MEDLINE was searched for reports published between 2016 and 2021 using search terms (suicid*) AND (biomarker*) OR (indicat*). Reports that compared biomarkers between suicidal ideation, suicide attempt, death from suicide, or any suicide subgroup against other neuropsychiatric disorders were included. Studies exclusively comparing suicidal behavior or death from suicide with healthy controls were not included to ensure that biomarkers were specific to suicide and not other psychopathology. RESULTS This review summarizes the last 5 years of research into suicide-associated biomarkers and provides a comprehensive guide for promising and novel biomarkers that encompass varying presentations of suicidal ideation, suicide attempt, and death by suicide. The serotonergic system, inflammation, hypothalamic-pituitary-adrenal axis, lipids, and endocannabinoids emerged as the most promising diagnostic, predictive, and therapeutic indicators. CONCLUSIONS The utility of diagnostic and predictive biomarkers is evident, particularly for suicide prevention. While larger-scale studies and further in-depth research are required, the last 5 years of research has uncovered essential biomarkers that could ultimately improve predictive strategies, aid diagnostics, and help develop future therapeutic targets.
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Affiliation(s)
- Jenessa N Johnston
- Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
- Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland,USA
| | - Darcy Campbell
- Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland,USA
| | - Hector J Caruncho
- Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada
- Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland,USA
| | - Ioline D Henter
- Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland,USA
| | - Elizabeth D Ballard
- Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland,USA
| | - Carlos A Zarate
- Experimental Therapeutics and Pathophysiology Branch, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland,USA
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Fernandez-Rodrigues V, Sanchez-Carro Y, Lagunas LN, Rico-Uribe LA, Pemau A, Diaz-Carracedo P, Diaz-Marsa M, Hervas G, de la Torre-Luque A. Risk factors for suicidal behaviour in late-life depression: A systematic review. World J Psychiatry 2022; 12:187-203. [PMID: 35111588 PMCID: PMC8783161 DOI: 10.5498/wjp.v12.i1.187] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 09/17/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Suicide is a leading cause of preventable death worldwide, with its peak of maximum incidence in later life. Depression often puts an individual at higher risk for suicidal behaviour. In turn, depression deserves particular interest in old age due to its high prevalence and dramatic impact on health and wellbeing. AIM To gather integrated evidence on the potential risk factors for suicide behaviour development in depressive older adults, and to examine the effects of depression treatment to tackle suicide behaviour in this population. METHODS A systematic review of empirical studies, published from 2000 onwards, was conducted. Suicidal behaviour was addressed considering its varying forms (i.e., wish to die, ideation, attempt, and completed suicide). RESULTS Thirty-five papers were selected for review, comprising both clinical and epidemiological studies. Most of studies focused on suicidal ideation (60%). The studies consistently pointed out that the risk was related to depressive episode severity, psychiatric comorbidity (anxiety or substance use disorders), poorer health status, and loss of functionality. Reduced social support and loneliness were also associated with suicide behaviour in depressive older adults. Finally, the intervention studies showed that suicidal behaviour was a robust predictor of depression treatment response. Reductions in suicidal ideation were moderated by reductions in risk factors for suicide symptoms. CONCLUSION To sum up, common and age-specific risk factors seem to be involved in suicide development in depressive older adults. A major effort should be made to tackle this serious public health concern so as to promote older people to age healthily and well.
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Affiliation(s)
| | - Yolanda Sanchez-Carro
- Department of Psychiatry, Universidad Autonoma de Madrid, Madrid 28046, Spain
- Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid 28029, Spain
| | - Luisa Natalia Lagunas
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28046, Spain
| | - Laura Alejandra Rico-Uribe
- Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid 28029, Spain
- Department of Psychology, La Rioja International University, Logrono 26006, Spain
| | - Andres Pemau
- Department of Psychology, Universidad Complutense de Madrid, Madrid 28223, Spain
| | | | - Marina Diaz-Marsa
- Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid 28029, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28046, Spain
- Institute of Psychiatry and Mental Health, San Carlos Clinical Hospital, Madrid 28040, Spain
| | - Gonzalo Hervas
- Department of Psychology, Universidad Complutense de Madrid, Madrid 28223, Spain
| | - Alejandro de la Torre-Luque
- Centre for Biomedical Research in Mental Health (CIBERSAM), Madrid 28029, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28046, Spain
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Tan X, Zhang L, Wang D, Guan S, Lu P, Xu X, Xu H. Influence of early life stress on depression: from the perspective of neuroendocrine to the participation of gut microbiota. Aging (Albany NY) 2021; 13:25588-25601. [PMID: 34890365 PMCID: PMC8714134 DOI: 10.18632/aging.203746] [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] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 11/24/2021] [Indexed: 12/17/2022]
Abstract
Depression is the most common mental disorder and has become a heavy burden in modern society. Clinical studies have identified early life stress as one of the high-risk factors for increased susceptibility to depression. Alteration of the hypothalamic-pituitary-adrenal (HPA) axis in response to stress is one of the key risk factors for depression susceptibility related to early life stress. Laboratory animal studies have demonstrated that maternal separation (MS) for extended periods elicits HPA axis changes. These changes persist into adulthood and resemble those present in depressed adult individuals, including hyperactivity of the HPA axis. In addition, there is growing evidence that inflammation plays an important role in depression susceptibility concerned with early life stress. Individuals that have experienced MS have higher levels of pro-inflammatory cytokines and are susceptible to depression. Recently, it has been found that the gut microbiota plays an important role in regulating behavior and is also associated with depression. The translocation of gut microbiota and the change of gut microbiota composition caused by early stress may be a reason. In this review, we discussed the mechanisms by which early life stress contributes to the development of depression in terms of these factors. These studies have facilitated a systematic understanding of the pathogenesis of depression related to early life stress and will provide new ideas for the prevention and treatment of depression.
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Affiliation(s)
- Xi Tan
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Longqing Zhang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Danning Wang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Shaodi Guan
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Pei Lu
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiaolin Xu
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hui Xu
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Lozupone M, Mollica A, Berardino G, Sardone R, Panza F. Could epigenetics play a role in suicidal behavior in older age? Epigenomics 2021; 14:73-79. [PMID: 34784757 DOI: 10.2217/epi-2021-0390] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Tweetable abstract There is growing evidence of a role of environmental exposures in the pathogenesis and epigenetics of suicidal behavior in older age.
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Affiliation(s)
- Madia Lozupone
- Neurodegenerative Disease Unit, Department of Basic Medical Sciences, Neuroscience & Sense Organs, University of Bari Aldo Moro, Bari, 70100, Italy
| | - Anita Mollica
- Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, 71122, Italy
| | - Giuseppe Berardino
- Psychiatric Unit, Department of Clinical & Experimental Medicine, University of Foggia, Foggia, 71122, Italy
| | - Rodolfo Sardone
- Salus In Apulia Study: Frailty Phenotypes Research Unit, National Institute of Gastroenterology 'Saverio de Bellis', Research Hospital, Castellana Grotte Bari, 70013, Italy
| | - Francesco Panza
- Salus In Apulia Study: Frailty Phenotypes Research Unit, National Institute of Gastroenterology 'Saverio de Bellis', Research Hospital, Castellana Grotte Bari, 70013, Italy
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8
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Abstract
After participating in this activity, learners should be better able to:• Identify risk factors for late-life depression• Evaluate strategies to prevent late-life depression ABSTRACT: Late-life depression (LLD) is one of the major sources of morbidity and mortality in the world. Because LLD is related to increased public health burden, excess health care costs and utilization, reduced quality of life, and increased mortality, prevention is a priority. Older adults differ from younger adults with respect to key features, such as their chronicity and lifetime burden of depression and their constellation of comorbidities and risk factors. LLD likely arises from a complex interplay of risk factors, including medical, physiologic, psychosocial, behavioral, and environmental factors. Thus, a comprehensive understanding of LLD risk factors is necessary to inform prevention strategies. In this narrative literature review, we address both the risk architecture of LLD and several potential strategies for prevention. Our description of LLD risk factors and prevention approaches is informed by the framework developed by the National Academy of Medicine (formerly, Institute of Medicine), which includes indicated, selective, and universal approaches to prevention.
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Crump C, Sundquist J, Kendler KS, Edwards AC, Sundquist K. Preterm birth, low fetal growth and risk of suicide in adulthood: a national cohort and co-sibling study. Int J Epidemiol 2021; 50:1604-1614. [PMID: 33693753 DOI: 10.1093/ije/dyab038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 02/15/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Adverse perinatal exposures have been associated with psychiatric disorders and suicidal behaviours later in life. However, the independent associations of gestational age at birth or fetal growth with suicide death, potential sex-specific differences, and causality of these associations are unclear. METHODS A national cohort study was conducted of all 2 440 518 singletons born in Sweden during 1973-98 who survived to age 18 years, who were followed up through 2016. Cox regression was used to compute hazard ratios (HRs) for suicide death associated with gestational age at birth or fetal growth while mutually adjusting for these factors, sociodemographic characteristics and family history of suicide. Co-sibling analyses assessed the influence of unmeasured shared familial (genetic and/or environmental) factors. RESULTS In 31.2 million person-years of follow-up, 4470 (0.2%) deaths by suicide were identified. Early preterm birth (22-33 weeks) was associated with an increased risk of suicide among females [adjusted hazard ratio (HR), 1.97; 95% confidence interval CI), 1.29, 3.01; P = 0.002) but not males (0.90; 0.64, 1.28; P = 0.56), compared with full-term birth (39-41 weeks). Small for gestational age was associated with a modestly increased risk of suicide among females (adjusted HR, 1.27; 95% CI, 1.08, 1.51; P = 0.005) and males (1.14; 1.03, 1.27; P = 0.02). However, these associations were attenuated and non-significant after controlling for shared familial factors. CONCLUSIONS In this large national cohort, preterm birth in females and low fetal growth in males and females were associated with increased risks of suicide death in adulthood. However, these associations appeared to be non-causal and related to shared genetic or prenatal environmental factors within families.
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Affiliation(s)
- Casey Crump
- Departments of Family Medicine and Community Health, and of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jan Sundquist
- Departments of Family Medicine and Community Health, and of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Center for Primary Health Care Research, Lund University, Malmö, Sweden
| | - Kenneth S Kendler
- Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
| | - Alexis C Edwards
- Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
| | - Kristina Sundquist
- Departments of Family Medicine and Community Health, and of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Center for Primary Health Care Research, Lund University, Malmö, Sweden
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10
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The Involvement of Hypothalamus-Pituitary-Adrenal (HPA) Axis in Suicide Risk. Brain Sci 2020; 10:brainsci10090653. [PMID: 32967089 PMCID: PMC7565104 DOI: 10.3390/brainsci10090653] [Citation(s) in RCA: 95] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 09/15/2020] [Accepted: 09/16/2020] [Indexed: 12/12/2022] Open
Abstract
Stress and Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation play a major role in various pathophysiological processes associated with both mood disorders and suicidal behavior. We conducted a systematic review with the primary aim of clarifying the nature and extent of HPA axis activity and suicidal behavior. The second aim of this review was to investigate whether potential biomarkers related to HPA axis abnormalities act as individual susceptibility factors for suicide. The PRISMA statement for reporting systematic reviews was used. Only articles published in English peer-reviewed journals were considered for possible inclusion; we excluded case reports, meta-analyses, and systematic reviews, and studies that did not clearly report statistical analysis, diagnostic criteria, or the number of patients included. Overall, 36 articles on HPA axis and suicide risk met inclusion criteria and were reviewed. Studies that investigated tests detecting biomarkers and the role of early life stressors in suicide risk were also included. We found that HPA axis activity is involved in suicide risk, regardless of the presence or absence of psychiatric conditions. The HPA axis abnormalities, mainly characterized by hyperactivity of the HPA axis, may exert an important modulatory influence on suicide risk. Impaired stress response mechanisms contribute to suicide risk. Targeting HPA axis dysregulation might represent a fruitful strategy for identifying new treatment targets and improving suicide risk prediction.
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11
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Wiersielis KR, Samuels BA, Roepke TA. Perinatal exposure to bisphenol A at the intersection of stress, anxiety, and depression. Neurotoxicol Teratol 2020; 79:106884. [PMID: 32289443 DOI: 10.1016/j.ntt.2020.106884] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 04/04/2020] [Accepted: 04/07/2020] [Indexed: 12/13/2022]
Abstract
Endocrine-disrupting compounds (EDCs) are common contaminants in our environment that interfere with typical endocrine function. EDCs can act on steroid and nuclear receptors or alter hormone production. One particular EDC of critical concern is bisphenol A (BPA) due to its potential harm during the perinatal period of development. Previous studies suggest that perinatal exposure to BPA alters several neurotransmitter systems and disrupts behaviors associated with depression and anxiety in the rodent offspring later in life. Thus, dysregulation in neurotransmission may translate to behavioral phenotypes observed in mood and arousal. Many of the systems disrupted by BPA also overlap with the stress system, although little evidence exists on the effects of perinatal BPA exposure in relation to stress and behavior. The purpose of this review is to explore studies involved in perinatal BPA exposure and the stress response at neurochemical and behavioral endpoints. Although more research is needed, we suggest that perinatal BPA exposure is likely inducing variations in behavioral phenotypes that modulate their action through dysregulation of neurotransmitter systems sensitive to stress and endocrine disruption.
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Affiliation(s)
- Kimberly R Wiersielis
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ. USA.
| | - Benjamin A Samuels
- Department of Psychology, School of Arts and Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ. USA
| | - Troy A Roepke
- Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ. USA
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12
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Cheung S, Woo J, Maes MS, Zai CC. Suicide epigenetics, a review of recent progress. J Affect Disord 2020; 265:423-438. [PMID: 32090769 DOI: 10.1016/j.jad.2020.01.040] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 11/17/2019] [Accepted: 01/11/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND Suicide results in over 800,000 deaths every year, making it a major public health concern worldwide. It is highly complex, with genetic and environmental influences. Epigenetic mechanisms, including DNA methylation, miRNA, and histone modifications, could explain the complex interplay of environmental risk factors with genetic risk factors in the emergence of suicidal behavior. METHODS Here, we review the literature on suicide epigenetics over the past 10 years. RESULTS There has been significant progress in the field of suicide epigenetics, with emerging findings in the brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis genes. LIMITATIONS Studying patient subgroups is needed in order to extract more comparable and reproducible epigenetic findings in suicide. CONCLUSIONS It is crucial to consider suicidal patients or suicide victims' distal and proximal past history e.g., early-life adversity and psychiatric disorder in epigenetic studies of suicidality.
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Affiliation(s)
- Serina Cheung
- Neurogenetics Section, Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada
| | - Julia Woo
- Neurogenetics Section, Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Faculty of Medicine, University of Toronto, Canada
| | - Miriam S Maes
- Neurogenetics Section, Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada
| | - Clement C Zai
- Neurogenetics Section, Tanenbaum Centre for Pharmacogenetics, Molecular Brain Science, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Canada; Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Canada; Institute of Medical Science, University of Toronto, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Canada; Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
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13
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Abstract
Suicide is a global health issue accounting for at least 800,000 deaths per annum. Numerous models have been proposed that differ in their emphasis on the role of psychological, social, psychiatric and neurobiological factors in explaining suicide risk. Central to many models is a stress-diathesis component which states that suicidal behavior is the result of an interaction between acutely stressful events and a susceptibility to suicidal behavior (a diathesis). This article presents an overview of studies that demonstrate that stress and dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, are important additional risk factors for suicide. Evidence for other putative stress-related suicide risk factors including childhood trauma, impaired executive function, impulsivity and disrupted sleep are considered together with the impact of family history of suicide, perinatal and epigenetic influences on suicide risk.
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14
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Alacreu-Crespo A, Olié E, Guillaume S, Girod C, Cazals A, Chaudieu I, Courtet P. Dexamethasone Suppression Test May Predict More Severe/Violent Suicidal Behavior. Front Psychiatry 2020; 11:97. [PMID: 32194449 PMCID: PMC7065044 DOI: 10.3389/fpsyt.2020.00097] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 02/06/2020] [Indexed: 11/13/2022] Open
Abstract
INTRODUCTION Several studies demonstrated that the hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in suicide attempters. Prospective studies found that people with an abnormal response at the dexamethasone suppression test (DST) are more likely to commit suicide. However, whether DST may predict suicide attempts remains less clear. A possible strategy to address this question is to consider the suicide attempt lethality. OBJECTIVES (1) To compare the pre- and post-DST cortisol levels in serious/violent suicide attempters and in non-serious/non-violent suicide attempters, and (2) to investigate whether cortisol level can predict new suicide attempts or their lethality. METHODS The study included 70 recent suicide attempters (25 with a serious or violent attempt) who were followed for two years. Three saliva samples for cortisol measurement were obtained at 8a.m., 3p.m., and 9p.m. before the DST (pre-DST). Then, at 11 p.m., 1 mg of dexamethasone was given orally. The following day (post-DST), three saliva samples were collected at the same hours as before. The post-DST-pre-DST salivary cortisol Δ index was calculated for each collection time. The Risk-Rescue Ratio Scale (RRRS) and the Suicidal Intent Scale (SIS) were used to characterize the suicide attempt at inclusion and those occurring during the follow-up. RESULTS Post-DST cortisol level at 9 p.m. was higher in patients with an initial violent or serious suicide attempt than in non-violent/non-serious attempters (p < .010). Higher post-DST cortisol at 9p.m. was associated with lower RRRS rescue score and higher clinical impression of suicide severity at inclusion. Among the 66 patients who completed the follow-up, 26 attempted suicide again at least once. Higher pre-DST cortisol at 8a.m. predicted new suicide attempts during the follow-up (OR = 2.15 [1.11, 4.15]), and higher cortisol Δ index at 9p.m. was associated with higher suicide intent during the follow-up. CONCLUSIONS Our results suggest that HPA axis hyper-reactivity monitored with the DST is a marker of violent/serious suicide attempt with lower rescue possibility. Furthermore, higher changes between pre-DST and post-DST cortisol levels may predict higher suicide intent. These findings might help to characterize the biological features of nearest suicide phenotypes.
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Affiliation(s)
- Adrián Alacreu-Crespo
- PSNREC, Univ. Montpellier, INSERM, CHU de Montpellier, Montpellier, France.,Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.,FondaMental Foundation, Créteil, France
| | - Emilie Olié
- PSNREC, Univ. Montpellier, INSERM, CHU de Montpellier, Montpellier, France.,Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.,FondaMental Foundation, Créteil, France
| | - Sebastien Guillaume
- PSNREC, Univ. Montpellier, INSERM, CHU de Montpellier, Montpellier, France.,Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.,FondaMental Foundation, Créteil, France
| | - Chloé Girod
- PSNREC, Univ. Montpellier, INSERM, CHU de Montpellier, Montpellier, France.,Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.,FondaMental Foundation, Créteil, France
| | - Aurélie Cazals
- PSNREC, Univ. Montpellier, INSERM, CHU de Montpellier, Montpellier, France.,Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.,FondaMental Foundation, Créteil, France
| | - Isabelle Chaudieu
- Univ. Montpellier, Inserm, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France
| | - Philippe Courtet
- PSNREC, Univ. Montpellier, INSERM, CHU de Montpellier, Montpellier, France.,Department of Emergency Psychiatry and Acute Care, Lapeyronie Hospital, CHU Montpellier, Montpellier, France.,FondaMental Foundation, Créteil, France
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15
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Novel Treatment Targets Based on Insights in the Etiology of Depression: Role of IL-6 Trans-Signaling and Stress-Induced Elevation of Glutamate and ATP. Pharmaceuticals (Basel) 2019; 12:ph12030113. [PMID: 31362361 PMCID: PMC6789839 DOI: 10.3390/ph12030113] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 07/10/2019] [Accepted: 07/26/2019] [Indexed: 12/11/2022] Open
Abstract
Inflammation and psychological stress are risk factors for major depression and suicide. Both increase central glutamate levels and activate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Both factors also affect the function of the chloride transporters, Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2), and provoke interleukin-6 (IL-6) trans-signaling. This leads to measurable increases in circulating corticosteroids, catecholamines, anxiety, somatic and psychological symptoms, and a decline in cognitive functions. Recognition of the sequence of pathological events allows the prediction of novel targets for therapeutic intervention. Amongst others, these include blockade of the big-K potassium channel, blockade of the P2X4 channel, TYK2-kinase inhibition, noradrenaline α2B-receptor antagonism, nicotinic α7-receptor stimulation, and the Sgp130Fc antibody. A better understanding of downstream processes evoked by inflammation and stress also allows suggestions for tentatively better biomarkers (e.g., SERPINA3N, MARCKS, or 13C-tryptophan metabolism).
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16
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Laird KT, Krause B, Funes C, Lavretsky H. Psychobiological factors of resilience and depression in late life. Transl Psychiatry 2019; 9:88. [PMID: 30765686 PMCID: PMC6375932 DOI: 10.1038/s41398-019-0424-7] [Citation(s) in RCA: 122] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 12/28/2018] [Accepted: 01/26/2019] [Indexed: 12/18/2022] Open
Abstract
In contrast to traditional perspectives of resilience as a stable, trait-like characteristic, resilience is now recognized as a multidimentional, dynamic capacity influenced by life-long interactions between internal and environmental resources. We review psychosocial and neurobiological factors associated with resilience to late-life depression (LLD). Recent research has identified both psychosocial characteristics associated with elevated LLD risk (e.g., insecure attachment, neuroticism) and psychosocial processes that may be useful intervention targets (e.g., self-efficacy, sense of purpose, coping behaviors, social support). Psychobiological factors include a variety of endocrine, genetic, inflammatory, metabolic, neural, and cardiovascular processes that bidirectionally interact to affect risk for LLD onset and course of illness. Several resilience-enhancing intervention modalities show promise for the prevention and treatment of LLD, including cognitive/psychological or mind-body (positive psychology; psychotherapy; heart rate variability biofeedback; meditation), movement-based (aerobic exercise; yoga; tai chi), and biological approaches (pharmacotherapy, electroconvulsive therapy). Additional research is needed to further elucidate psychosocial and biological factors that affect risk and course of LLD. In addition, research to identify psychobiological factors predicting differential treatment response to various interventions will be essential to the development of more individualized and effective approaches to the prevention and treatment of LLD.
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Affiliation(s)
- Kelsey T Laird
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA
| | - Beatrix Krause
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA
| | - Cynthia Funes
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA
| | - Helen Lavretsky
- Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior at UCLA, Los Angeles, CA, USA.
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17
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Conejero I, Navucet S, Keller J, Olié E, Courtet P, Gabelle A. A Complex Relationship Between Suicide, Dementia, and Amyloid: A Narrative Review. Front Neurosci 2018; 12:371. [PMID: 29910709 PMCID: PMC5992441 DOI: 10.3389/fnins.2018.00371] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 05/14/2018] [Indexed: 12/26/2022] Open
Abstract
Background: Suicide rates are high among older adults and many conditions have been related to suicide in this population: chronic illnesses, physical disabilities, cancer, social isolation, mental disorders and neurocognitive disorders. Objectives: Among neurocognitive disorders, analysis of the relationships between dementia and suicidal behaviors led to conflicting results and some questions are still without answer. Particularly, it is not known whether (i) Alzheimer's disease (AD) increases the risk of suicidal ideation and suicide attempts (SA) or the frequency of death by suicide; (ii) the presence of suicidal ideation or SA in people older than 65 years of age is an early dementia sign; and (iii) amyloid load in frontal areas facilitates SA by modifying the decision-making pathway. Methods: Therefore, in this narrative review, we searched the PubMed database using the medical subject heading (MeSH) terms (“Suicide” AND “Depression”) OR (“Amyloid” OR “Dementia”) to identify recent (from 2000 to 2017) original studies on the links between suicidal behavior, dementia and brain amyloid load. We also explored the clinical and pathophysiological role of depression in these relationships. Results and Discussion: The findings from these studies suggest that late stage dementia could protect against suicidal ideation and SA. Conversely, the risk of complete suicide is increased during the early phase of cognitive decline. Conclusions: Serious cognitive impairment and decline of executive functions could protect against negative thoughts related to cognitive disability awareness and against suicide planning.Several factors, including brain amyloid load, could be involved in the increased suicide rate early after the diagnosis of dementia.
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Affiliation(s)
- Ismael Conejero
- Department of Psychiatry, Caremeau Hospital, University Hospital of Nîmes, Nîmes, France.,Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, University of Montpellier, Montpellier, France.,Centre de Biochimie Structurale, University of Montpellier, Montpellier, France
| | - Sophie Navucet
- Department of Montpellier, Memory Resources Research Center, Gui De Chauliac Hospital, University of Montpellier, Montpellier, France
| | - Jacques Keller
- Department of Montpellier, Memory Resources Research Center, Gui De Chauliac Hospital, University of Montpellier, Montpellier, France
| | - Emilie Olié
- Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, University of Montpellier, Montpellier, France.,Department of Psychiatric Emergency and Post-Acute Care, Lapeyronie Hospital, University of Montpellier, Montpellier, France
| | - Philippe Courtet
- Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, University of Montpellier, Montpellier, France.,Department of Psychiatric Emergency and Post-Acute Care, Lapeyronie Hospital, University of Montpellier, Montpellier, France
| | - Audrey Gabelle
- Inserm U1061, Neuropsychiatry: Epidemiological and Clinical Research, La Colombière Hospital, University of Montpellier, Montpellier, France.,Department of Montpellier, Memory Resources Research Center, Gui De Chauliac Hospital, University of Montpellier, Montpellier, France
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18
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Ludwig B, Kienesberger K, Carlberg L, Swoboda P, Bernegger A, Koller R, Wang Q, Inaner M, Zotter M, Kapusta ND, Haslacher H, Aigner M, Kasper S, Schosser A. Influence of CRHR1 Polymorphisms and Childhood Abuse on Suicide Attempts in Affective Disorders: A GxE Approach. Front Psychiatry 2018; 9:165. [PMID: 29755375 PMCID: PMC5933260 DOI: 10.3389/fpsyt.2018.00165] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2017] [Accepted: 04/11/2018] [Indexed: 11/18/2022] Open
Abstract
Background: Previous studies have shown that the hypothalamus-pituitary-adrenal-axis (HPA-axis) is closely involved in the development of affective disorders. Given that early life events are also linked to dysregulation of the same system, there might be an association between childhood adversities and suicidal behavior in affective disorders, moderated by HPA-axis genes. We aimed to investigate a potential association between childhood trauma and previous suicide attempts in affective disorder patients, moderated by variants of the corticotropin-releasing hormone receptor 1 (CRHR1) gene. Methods: The current pilot study is part of an ongoing study on suicidal behavior in affective disorders (VieSAD). Two hundred fifty eight Caucasian affective disorder patients were assessed at the Department of Psychiatry and Psychotherapy of the Medical University Vienna and the Karl Landsteiner University for Health and Science. An assemblage of psychiatric interviews was performed (e.g., SCAN, HAMD, SBQ-R, CTQ) and DNA samples of peripheral blood cells were genotyped with TaqMan® SNP Genotyping Assays (rs7209436, rs4792887, rs110402, rs242924, and rs242939). Results: Neither genetic, nor haplotypic associations between CRHR1 polymorphisms and previous suicide attempts could be established for the present sample. Using a binary logistic regression model, significant gene-environment-interactions were found for the single nucleotide polymorphisms (SNPs) rs7209436 and rs110402, reflecting the impact of childhood trauma and CRHR1 polymorphisms on previous suicide attempts. Limitations: A larger sample size will be required to ultimately elucidate the link between childhood trauma and the HPA axis in suicidal behavior. Conclusion: This pilot study presents promising gene-environment-interaction findings in affective disorder patients with a history of suicide attempts.
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Affiliation(s)
- Birgit Ludwig
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Klemens Kienesberger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Laura Carlberg
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Patrick Swoboda
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Alexandra Bernegger
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Romina Koller
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Qingzhong Wang
- UAB Mood Disorder Program, Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Michelle Inaner
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Melanie Zotter
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Nestor D. Kapusta
- Department of Psychoanalysis and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Helmuth Haslacher
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Martin Aigner
- Department of Psychiatry and Psychotherapy, Karl Landsteiner University for Health and Science, Tulln, Austria
| | - Siegfried Kasper
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
| | - Alexandra Schosser
- Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria
- Zentren für Seelische Gesundheit, BBRZ-Med, Vienna, Austria
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19
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Abstract
Suicide is a world health priority. Studies over the last few decades have revealed the complexity underlying the neurobiological mechanisms of suicide. Researchers have found dysregulations in the serotonergic system, the stress system, neural plasticity, lipid metabolism, and cell signaling pathways in relation to suicidal behaviors. These findings have provided more insight into the final path leading to suicide, at which medical intervention should be applied to prevent the action. However, because these molecular mechanisms have been implicated in both depression and suicide, the specificity of the mechanisms has been obscured. In this review, we summarize the main findings of studies on molecular mechanisms of suicidal behavior from the last 2 decades, with particular emphasis on the potential, independent role of each mechanism that is not contingent upon an underlying psychopathology, such as depression. The act of suicide is multifactorial; no single molecular mechanism is sufficient to fully account for the act. Knowledge of the reciprocal interactions among these molecular mechanisms and studying them in the context of brain circuitry by using neuroimaging techniques will provide a better understanding of the neurobiology of suicide.
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Affiliation(s)
- Sangha Kim
- Department of Psychiatry, Yeouido St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Kyoung-Uk Lee
- Department of Psychiatry, Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea
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20
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Costs and benefits of self-efficacy: Differences of the stress response and clinical implications. Neurosci Biobehav Rev 2017; 75:40-52. [PMID: 28143761 DOI: 10.1016/j.neubiorev.2017.01.031] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 12/22/2016] [Accepted: 01/23/2017] [Indexed: 01/17/2023]
Abstract
Encounters with stressors induce diverse idiosyncratic neuroendocrine, behavioral and psychological reactions across people. Perceived self-efficacy can alter autonomic responses and their effects on mental health. The beneficial effects of self-efficacy in buffering physiological arousal, enhancing performance, and diminishing psychopathological symptoms have been observed in diverse contexts. We show that the role of self-efficacy is not uniformly beneficial, and that higher levels of self-efficacy can sometimes lead to increases in neuroendocrine and psychological stress responses and decreases in performance, a phenomenon that has been widely neglected. We discuss specific conditions under which self-efficacy effects do not uniformly ameliorate or prevent the consequences of stress. These conditions suggest that therapeutic interventions need not always promote self-efficacy in principal. Simultaneously, they to do suggest that keeping self-efficacy high might be disadvantageous or detrimental.
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21
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Ambrus L, Lindqvist D, Träskman-Bendz L, Westrin Å. Hypothalamic-pituitary-adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters. Nord J Psychiatry 2016; 70:575-81. [PMID: 27216156 DOI: 10.1080/08039488.2016.1184310] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
INTRODUCTION Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately. METHOD Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items 'Concentration difficulties' and 'Failing memory' were extracted. RESULTS Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = -0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = -0.372, p = 0.020). CONCLUSION The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.
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Affiliation(s)
- Livia Ambrus
- a Department of Clinical Sciences, Psychiatry , Lund University , Lund , Sweden
| | - Daniel Lindqvist
- a Department of Clinical Sciences, Psychiatry , Lund University , Lund , Sweden
| | - Lil Träskman-Bendz
- a Department of Clinical Sciences, Psychiatry , Lund University , Lund , Sweden
| | - Åsa Westrin
- a Department of Clinical Sciences, Psychiatry , Lund University , Lund , Sweden
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22
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Jokinen J, Mattsson P, Nordström P, Samuelsson M. High Early Suicide Risk in Elderly Patients After Self-Poisoning. Arch Suicide Res 2016; 20:683-8. [PMID: 26984396 DOI: 10.1080/13811118.2016.1162239] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
This article reports the findings of a follow-up study of suicide mortality in elderly patients after an index episode of self-poisoning. A total of 222 consecutive patients (143 female) aged 65 years or older (mean age 76.5 years; range 65-100) presenting at the emergency department of the Karolinska University Hospital after self-poisoning during 1994-2000, were followed up for the cause of death by January 1, 2006. Survival analysis was applied to study suicide and death risk. Of the 15 suicides, 13 (87%) occurred during the first year after the index episode of self-poisoning (cumulative suicide risk 6.2%). The risk of dying of all causes during the first year was increased fourfold. Self-poisoning in both elderly men and women is associated with high early suicide risk.
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23
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Chang BP, Franklin JC, Ribeiro JD, Fox KR, Bentley KH, Kleiman EM, Nock MK. Biological risk factors for suicidal behaviors: a meta-analysis. Transl Psychiatry 2016; 6:e887. [PMID: 27622931 PMCID: PMC5048204 DOI: 10.1038/tp.2016.165] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 07/19/2016] [Accepted: 07/20/2016] [Indexed: 01/01/2023] Open
Abstract
Prior studies have proposed a wide range of potential biological risk factors for future suicidal behaviors. Although strong evidence exists for biological correlates of suicidal behaviors, it remains unclear if these correlates are also risk factors for suicidal behaviors. We performed a meta-analysis to integrate the existing literature on biological risk factors for suicidal behaviors and to determine their statistical significance. We conducted a systematic search of PubMed, PsycInfo and Google Scholar for studies that used a biological factor to predict either suicide attempt or death by suicide. Inclusion criteria included studies with at least one longitudinal analysis using a biological factor to predict either of these outcomes in any population through 2015. From an initial screen of 2541 studies we identified 94 cases. Random effects models were used for both meta-analyses and meta-regression. The combined effect of biological factors produced statistically significant but relatively weak prediction of suicide attempts (weighted mean odds ratio (wOR)=1.41; CI: 1.09-1.81) and suicide death (wOR=1.28; CI: 1.13-1.45). After accounting for publication bias, prediction was nonsignificant for both suicide attempts and suicide death. Only two factors remained significant after accounting for publication bias-cytokines (wOR=2.87; CI: 1.40-5.93) and low levels of fish oil nutrients (wOR=1.09; CI: 1.01-1.19). Our meta-analysis revealed that currently known biological factors are weak predictors of future suicidal behaviors. This conclusion should be interpreted within the context of the limitations of the existing literature, including long follow-up intervals and a lack of tests of interactions with other risk factors. Future studies addressing these limitations may more effectively test for potential biological risk factors.
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Affiliation(s)
- B P Chang
- Department of Emergency Medicine, Columbia University Medical Center, New York, NY, USA
| | - J C Franklin
- Department of Psychology, Vanderbilt University, Nashville, TN, USA
- Department of Psychology, Harvard University, Cambridge, MA, USA
| | - J D Ribeiro
- Department of Psychology, Vanderbilt University, Nashville, TN, USA
- Department of Psychology, Harvard University, Cambridge, MA, USA
| | - K R Fox
- Department of Psychology, Harvard University, Cambridge, MA, USA
| | - K H Bentley
- Department of Psychology, Boston University, Boston, MA, USA
| | - E M Kleiman
- Department of Psychology, Harvard University, Cambridge, MA, USA
| | - M K Nock
- Department of Psychology, Harvard University, Cambridge, MA, USA
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Fudalej S, Kopera M, Wołyńczyk-Gmaj D, Fudalej M, Krajewski P, Wasilewska K, Szymański K, Chojnicka I, Podgórska A, Wojnar M, Płoski R. Association between FKBP5 Functional Polymorphisms and Completed Suicide. Neuropsychobiology 2016; 72:126-31. [PMID: 26630184 DOI: 10.1159/000441659] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2015] [Accepted: 10/11/2015] [Indexed: 11/19/2022]
Abstract
OBJECTIVES Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis leads to impaired stress response. FK506-binding protein 51 (FKBP5), which influences HPA axis activity via glucocorticoid receptors, is supposed to play an important role in the regulation of negative feedback and glucocorticoid resistance. Since ineffective stress response mechanisms are considered as a biological background of suicide behavior, we aimed to analyze a possible association between FKBP5 functional polymorphisms and completed suicide. METHODS The selected FKBP5 polymorphisms rs1360780 and rs3800373 were genotyped in a sample of 563 suicide victims and 475 controls. RESULTS A significant association between the high-induction rs3800373 C allele and completed suicide was detected (OR = 1.36, p = 0.007). In this polymorphism, genotype distribution supported a codominant model of inheritance. The analyzed SNPs were in strong linkage disequilibrium (D' = 0.916 and r2 = 0.826) with the rs1360780 (T)-rs3800373 (C) haplotype apparently responsible for the observed association (OR = 1.34, p = 0.010). CONCLUSION The results of the present study indicate that genetic alterations in FKBP5 may influence vulnerability to suicide.
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Affiliation(s)
- Sylwia Fudalej
- Department of Psychiatry, Medical University of Warsaw, Warsaw, Poland
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Abstract
Suicide in the elderly is an underestimated and complex issue that has mainly been explored in sociological, clinical and psychological perspectives. Suicide in non-elderly adults has been associated with diverse neurobiological alterations that may shed light on future predictive markers and more efficient preventative interventions. The aim of this paper was to review studies specifically investigating the neurobiology of elderly suicidal behaviour. We performed a systematic English and French Medline and EMBASE search until 2013. Contrary to literature about the non-elderly, we found a paucity of studies investigating the biomarkers of suicidal risk in elderly adults. Main findings were found in the neurocognitive domain. Studies generally supported the existence of cognitive deficits, notably decision-making impairment and reduced cognitive inhibition, in patients with a history of suicidal act compared to patients without such history. However, replications are needed to confirm findings. Due to several limitations including the small number of available studies, frequent lack of replication and small sample size, no firm conclusions can be drawn. The authors encourage further investigations in this field as insight in the neurobiology of these complex behaviors may limit clichés about end of life and aging, as well as improve future prevention of suicide in the elderly.
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O'Connor DB, Ferguson E, Green JA, O'Carroll RE, O'Connor RC. Cortisol levels and suicidal behavior: A meta-analysis. Psychoneuroendocrinology 2016; 63:370-9. [PMID: 26555430 DOI: 10.1016/j.psyneuen.2015.10.011] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2015] [Revised: 10/03/2015] [Accepted: 10/16/2015] [Indexed: 10/22/2022]
Abstract
Suicide is a major cause of death worldwide, responsible for 1.5% of all mortality. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. This meta-analytic review aimed (i) to estimate the strength and variability of the association between naturally fluctuating cortisol levels and suicidal behavior and (ii) to identify moderators of this relationship. A systematic literature search identified 27 studies (N=2226; 779 suicide attempters and 1447 non-attempters) that met the study eligibility criteria from a total of 417 unique records initially examined. Estimates of effect sizes (r) obtained from these studies were analysed using Comprehensive Meta-Analysis. In these analyses, we compared participants identified as having a past history of suicide attempt(s) to those with no such history. Study quality, mean age of sample and percentage of male participants were examined as potential moderators. Overall, there was no significant effect of suicide group on cortisol. However, significant associations between cortisol and suicide attempts were observed as a function of age. In studies where the mean age of the sample was below 40 years the association was positive (i.e., higher cortisol was associated with suicide attempts; r=.234, p<.001), and where the mean age was 40 or above the association was negative (i.e., lower cortisol was associated with suicide attempts; r=-.129, p<.001). These findings confirm that HPA axis activity, as indicated by age-dependent variations in cortisol levels, is associated with suicidal behavior. The challenge for theory and clinical practice is to explain the complete reversal of the association with age and to identify its clinical implications.
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Affiliation(s)
| | - Eamonn Ferguson
- School of Psychology, University of Nottingham, Nottingham, UK
| | | | | | - Rory C O'Connor
- Suicidal Behaviour Research Laboratory, Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK.
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HPA axis dysregulation in men with hypersexual disorder. Psychoneuroendocrinology 2016; 63:247-53. [PMID: 26519779 DOI: 10.1016/j.psyneuen.2015.10.002] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2015] [Revised: 09/22/2015] [Accepted: 10/05/2015] [Indexed: 12/15/2022]
Abstract
Hypersexual disorder integrating pathophysiological aspects such as sexual desire deregulation, sexual addiction, impulsivity and compulsivity was suggested as a diagnosis for the DSM-5. However, little is known about the neurobiology behind this disorder. A dysregulation of the hypothalamic pituitary adrenal (HPA) axis has been shown in psychiatric disorders but has not been investigated in hypersexual disorder. The aim of this study was to investigate the function of the HPA axis in hypersexual disorder. The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and low dose (0.5mg) dexamethasone suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Non-suppression status was defined with DST-cortisol levels ≥ 138 nmol/l. The Sexual Compulsive scale (SCS), Hypersexual disorder current assessment scale (HD:CAS), Montgomery-Åsberg Depression Scale-self rating (MADRS-S) and Childhood trauma questionnaire (CTQ), were used for assessing hypersexual behavior, depression severity and early life adversity. Patients with hypersexual disorder were significantly more often DST non-suppressors and had significantly higher DST-ACTH levels compared to healthy volunteers. The patients reported significantly more childhood trauma and depression symptoms compared to healthy volunteers. CTQ scores showed a significant negative correlation with DST-ACTH whereas SCS and HD:CAS scores showed a negative correlation with baseline cortisol in patients. The diagnosis of hypersexual disorder was significantly associated DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. The results suggest HPA axis dysregulation in male patients with hypersexual disorder.
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Valiengo LDCL, Stella F, Forlenza OV. Mood disorders in the elderly: prevalence, functional impact, and management challenges. Neuropsychiatr Dis Treat 2016; 12:2105-14. [PMID: 27601905 PMCID: PMC5003566 DOI: 10.2147/ndt.s94643] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Despite the lower prevalence of severe mood disorders in the elderly as compared to younger adults, late-life depression and bipolar disorder (BD) are more strongly associated with negative outcomes related to the presence of medical comorbidities, cognitive deficits, and increased suicide risk and overall mortality. The mechanisms that contribute to these associations are probably multifactorial, involving pathological factors related directly and indirectly to the disease itself, ranging from biological to psychosocial factors. Most of the accumulated knowledge on the nature of these associations derives from naturalistic and observational studies, and controlled data are still scarce. Nonetheless, there has clearly been a recent growth of the scientific interest on late-life BD and geriatric depression. In the present study, we review the most relevant studies on prevalence, clinical presentation, and cognitive/functional impact of mood disorders in elderly. Several clinical-epidemiological studies were dedicated to the study of the prevalence of mood disorders in old age in distinct settings; however, fewer studies investigated the underlying neurobiological findings and treatment specificities in late-life depression and BD. In the present study, we further discuss the implications of these findings on the management of mood disorders in older adults.
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Affiliation(s)
- Leandro da Costa Lane Valiengo
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo
| | - Florindo Stella
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo; Biosciences Institute, Universidade Estadual Paulista, Rio Claro, Brazil
| | - Orestes Vicente Forlenza
- Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Sao Paulo
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29
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Costa LDS, Alencar ÁP, Nascimento Neto PJ, dos Santos MDSV, da Silva CGL, Pinheiro SDFL, Silveira RT, Bianco BAV, Pinheiro RFF, de Lima MAP, Reis AOA, Rolim Neto ML. Risk factors for suicide in bipolar disorder: a systematic review. J Affect Disord 2015; 170:237-54. [PMID: 25261630 DOI: 10.1016/j.jad.2014.09.003] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 08/18/2014] [Accepted: 09/02/2014] [Indexed: 01/27/2023]
Abstract
BACKGROUND Bipolar disorder confers the highest risk of suicide among major psychological disorders. The risk factors associated with bipolar disorder and suicide exist and are relevant to clinicians and researchers. OBJECTIVE The aim of the present study was to conduct a systematic review of articles regarding the suicide risk factors in bipolar disorder. METHODS A systematic review of articles on suicide risk factors in bipolar disorder, published from January 1, 2010 to April 05, 2014, on SCOPUS and PUBMED databases was carried out. Search terms were "Suicide" (medical subject headings [MeSH]), "Risk factors" (MeSH), and "Bipolar" (keyword). Of the 220 retrieved studies, 42 met the eligibility criteria. RESULTS Bipolar disorder is associated with an increased rate death by suicide which contributes to overall mortality rates. Studies covered a wide range of aspects regarding suicide risk factors in bipolar disorder, such as risk factors associated to Sociodemographic conditions, Biological characteristics, Drugs Relationships, Psychological Factors, Genetic Compound, Religious and Spirituals conditions. Recent scientific literature regarding the suicide risk factors in bipolar disorder converge to, directly or indirectly, highlight the negative impacts of risk factors to the affected population quality of life. CONCLUSION This review demonstrated that Bipolar disorders commonly leads to other psychiatric disorders and co-morbidities involving risk of suicide. Thus the risk factors are relevant to have a better diagnosis and prognosis of BD cases involving risk of suicide.
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Affiliation(s)
- Lucas da Silva Costa
- Laboratório de Escrita Científica, Faculdade de Medicina, Universidade Federal do Cariri, UFCA, Barbalha, Ceará, Brazil.
| | - Átila Pereira Alencar
- Laboratório de Escrita Científica, Faculdade de Medicina, Universidade Federal do Cariri, UFCA, Barbalha, Ceará, Brazil
| | | | | | | | | | - Regiane Teixeira Silveira
- Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil
| | - Bianca Alves Vieira Bianco
- Programa de Pós-Graduação em Ciências da Saúde, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil
| | | | | | - Alberto Olavo Advincula Reis
- Programa de Pós-Graduação em Saúde Pública, Faculdade de Saúde Pública, Universidade de São Paulo, USP, São Paulo, São Paulo, Brazil
| | - Modesto Leite Rolim Neto
- Líder de Grupo de Pesquisa em Suicidologia, Universidade Federal do Ceará, UFC/Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq, Faculdade de Medicina, Universidade Federal do Cariri, UFCA, Barbalha, Ceará, Brazil
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Belvederi Murri M, Pariante C, Mondelli V, Masotti M, Atti AR, Mellacqua Z, Antonioli M, Ghio L, Menchetti M, Zanetidou S, Innamorati M, Amore M. HPA axis and aging in depression: systematic review and meta-analysis. Psychoneuroendocrinology 2014; 41:46-62. [PMID: 24495607 DOI: 10.1016/j.psyneuen.2013.12.004] [Citation(s) in RCA: 219] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 12/01/2013] [Accepted: 12/02/2013] [Indexed: 12/31/2022]
Abstract
One of the most consistent findings in the biology of depression is an altered activity of the hypothalamic-pituitary-adrenal (HPA) axis. However, data concerning this issue have never been examined with a focus on the older population. Here we present a systematic review and meta-analysis, based on studies investigating levels of cortisol, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) in depressed participants older than 60 and compared with healthy controls. We found 20 studies, for a total of 43 comparisons on different indices of HPA axis functioning. Depression had a significant effect (Hedges' g) on basal cortisol levels measured in the morning (0.89), afternoon (0.83) and night (1.39), but a smaller effect on cortisol measured continuously (0.51). The effect of depression was even higher on post-dexamethasone cortisol levels (3.22), whereas it was non-significant on morning ACTH and CRH levels. Subgroup analyses indicated that various methodological and clinical factors can influence the study results. Overall, older participants suffering from depression show a high degree of dysregulation of HPA axis activity, with differences compared with younger adults. This might depend on several mechanisms, including physical illnesses, alterations in the CNS and immune-endocrinological alterations. Further studies are needed to clarify the implications of altered HPA axis activity in older patients suffering from depression. Novel pharmacological approaches might be effective in targeting this pathophysiological feature, thus improving the clinical outcomes.
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Affiliation(s)
- Martino Belvederi Murri
- Institute of Psychiatry, Department of Psychological Medicine, King's College London, London, UK; Department of Neurosciences Division of Psychiatry, University of Parma, Parma, Italy.
| | - Carmine Pariante
- Institute of Psychiatry, Department of Psychological Medicine, King's College London, London, UK
| | - Valeria Mondelli
- Institute of Psychiatry, Department of Psychological Medicine, King's College London, London, UK
| | - Mattia Masotti
- Section of Psychiatry, Department of Neuroscience, Oftalmology, Genetics and Infant-Maternal Science, University of Genoa, Genoa, Italy
| | - Anna Rita Atti
- Department of Biomedical and NeuroMotor Sciences - Psychiatry, University of Bologna, Italy
| | - Zefiro Mellacqua
- Institute of Psychiatry, Department of Psychosis Studies, King's College London, London, UK
| | - Marco Antonioli
- Department of Biomedical and NeuroMotor Sciences - Psychiatry, University of Bologna, Italy
| | - Lucio Ghio
- Section of Psychiatry, Department of Neuroscience, Oftalmology, Genetics and Infant-Maternal Science, University of Genoa, Genoa, Italy
| | - Marco Menchetti
- Section of Psychiatry, Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy
| | | | - Marco Innamorati
- Department of Neurosciences Division of Psychiatry, University of Parma, Parma, Italy
| | - Mario Amore
- Section of Psychiatry, Department of Neuroscience, Oftalmology, Genetics and Infant-Maternal Science, University of Genoa, Genoa, Italy
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Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in female patients with major depressive disorder. Psychiatry Res 2013; 210:951-6. [PMID: 24080256 DOI: 10.1016/j.psychres.2013.08.057] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2013] [Revised: 07/08/2013] [Accepted: 08/27/2013] [Indexed: 11/22/2022]
Abstract
Current suicidal ideation and attempts are more commonly found in female patients with major depressive disorder (MDD) than in males. However, little is known about the relationship between activity of female reproductive hormones and suicide. The study population consisted of 490 female MDD patients of age ≥18. They were assessed by the Mini-International Neuropsychiatric Interview. At the same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH), cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant difference among female MDD patients with suicide attempt, those with ideation, and those without within the previous month. Post-hoc analysis also showed that FSH was significantly lower in MDD patients with suicide attempt and ideation than those without, whereas other hormones showed no differences between those with and without attempt. FSH was negatively associated with current suicidality scores after adjustment for age and education years in all age groups. FSH was significantly lower in those with current suicide ideation or attempt than those without in age 45 years or under, but not in other age groups. In conclusion, blood FSH is significantly lower in female MDD patients with current suicide attempt or ideation than those without, especially in age 45 years or under.
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Association, haplotype, and gene-gene interactions of the HPA axis genes with suicidal behaviour in affective disorders. ScientificWorldJournal 2013; 2013:207361. [PMID: 24379738 PMCID: PMC3863451 DOI: 10.1155/2013/207361] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Accepted: 10/22/2013] [Indexed: 02/03/2023] Open
Abstract
Family twin and adoption studies have noted the heritability of specific biological factors that influence suicidal behaviour.
Exposure to stress is one of the factors that strongly contribute to suicide attempts. The biological response
to stress involves the hypothalamic-pituitary-adrenal axis (HPA). Therefore, we found it interesting to study polymorphisms of
genes involved in the HPA axis (CRHR1, NR3C1, and AVPBR1). The study was performed on
597 patients, 225 of whom had a history of suicide attempts. We did not observe any significant differences in the studied
polymorphisms between the group of patients with a history of suicide attempts and the control subjects. Our haplotype analysis
of the AVPR1b gene revealed an association between the GCA haplotype and suicide attempts; however,
this association was not significant after correcting for multiple testing. We did not observe any other association in haplotype
and MDR analysis. We report here a comprehensive analysis of the HPA axis genes and a lack of association for genetic
variations regarding the risk of suicide attempts in affective disorder patients. Nonetheless, the inconsistencies with the previously
published results indicate the importance of the further investigation of these polymorphisms with respect to the risk of suicide attempts.
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Chatzittofis A, Nordström P, Hellström C, Arver S, Åsberg M, Jokinen J. CSF 5-HIAA, cortisol and DHEAS levels in suicide attempters. Eur Neuropsychopharmacol 2013; 23:1280-7. [PMID: 23453639 DOI: 10.1016/j.euroneuro.2013.02.002] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2012] [Revised: 01/26/2013] [Accepted: 02/03/2013] [Indexed: 01/15/2023]
Abstract
The serotonin system and the hypothalamic-pituitary-adrenal (HPA) axis are involved in the biological vulnerability to suicidal behaviour. Altered levels of dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS have been reported in neuropsychiatric conditions. The aim of this study was to investigate CSF levels of 5-Hydroxyindoleacetic acid (5-HIAA) and CSF and plasma levels of cortisol and DHEAS in 28 medication free suicide attempters and 19 healthy volunteers. Another aim was to investigate the relationship between neuroendocrine measures and childhood trauma in suicide attempters. As the study design includes a longitudinal part, we investigated whether CSF cortisol, 5-HIAA or DHEAS would predict subsequent suicide. We hypothesized higher cortisol levels in suicide attempters and lower CSF 5-HIAA levels and higher cortisol levels in suicide victims. Suicide attempters had higher CSF and plasma cortisol levels compared to healthy volunteers. Male suicide attempters had higher CSF DHEAS levels and female suicide attempters had lower CSF 5-HIAA levels compared to male and female healthy volunteers respectively. Exposure to interpersonal violence as a child showed a negative correlation with CSF cortisol/DHEAS ratio adjusted for age, gender and depression severity in a regression analysis. Suicide victims tended to have low CSF 5-HIAA and high CSF cortisol. Abused suicide victims had higher CSF cortisol compared to suicide victims with low exposure to interpersonal violence as a child. The results underlie the important role of the serotonergic system and HPA axis in suicidal behaviour and suggest that CSF DHEAS may be elevated in male suicide attempters.
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Affiliation(s)
- Andreas Chatzittofis
- Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden
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[Anxiety and depression in the elderly]. ZEITSCHRIFT FUR PSYCHOSOMATISCHE MEDIZIN UND PSYCHOTHERAPIE 2013; 58:336-56. [PMID: 23224953 DOI: 10.13109/zptm.2012.58.4.336] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES This paper deals with diagnostics and prevalence of depression and anxiety in the elderly, their biological, psychological, and social risk factors, and the effectiveness of psychotherapy and pharmacotherapy. METHODS The results are based on an overview of the literature reflecting reviews and meta-analyses. RESULTS In the elderly, there is a substantial danger of confounding psychogenic with medical or drug-induced symptoms. Self-assessment scales may be useful for screening, but the results should be confirmed by an expert interview. Based on the available research, we cannot yet be sure whether the prevalence of depression and anxiety in the elderly population is in fact higher, lower, or equal to younger age groups. More women are afflicted with depression or anxiety than men. Pharmacotherapy (preferably antidepressants) and psychotherapy are effective for treating anxiety and depression in the elderly, with medium to high effect sizes. To date it is not possible to provide evidence-based treatment recommendations for the type or the setting of psychotherapy. DISCUSSION More research on this topic is needed.
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McGirr A, Jollant F, Turecki G. Neurocognitive alterations in first degree relatives of suicide completers. J Affect Disord 2013; 145:264-9. [PMID: 22840615 DOI: 10.1016/j.jad.2012.05.062] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2012] [Revised: 05/08/2012] [Accepted: 05/30/2012] [Indexed: 12/24/2022]
Abstract
BACKGROUND Suicide aggregates within families and the relatives of suicide completers are at an increased risk for suicide. Though neurocognitive changes are gaining increasing attention as part of the vulnerability for suicide, the literature on neurocognitive alterations among suicide relatives as possible endophenotypes of suicide is sparse. METHOD Normothymic first-degree relatives (n=14) of suicide completers without personal histories of suicide attempts were compared to individuals without family histories of suicide (n=14) matched for age-, sex- and education. Participants completed the Wisconsin card sorting test, a well validated test of cognitive control in a changing environment. RESULTS First-degree relatives of suicide completers made significantly more perseverative errors and have a lower level of conceptual responses than comparison subjects. CONCLUSION Alterations found in first-degree relatives of suicide completers suggest a decreased responsiveness to changing, yet unambiguous, conditions. These neurocognitive impairments are similar to deficits observed among individuals engaging in suicide attempts. Neurocognitive impairments revealed by the Wisconsin card sorting test may represent a neurocognitive endophenotype of suicide.
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Affiliation(s)
- Alexander McGirr
- McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Blvd., Montreal, QC, Canada H4H 1R3.
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Chistiakov DA, Kekelidze ZI, Chekhonin VP. Endophenotypes as a measure of suicidality. J Appl Genet 2012; 53:389-413. [DOI: 10.1007/s13353-012-0113-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Revised: 08/13/2012] [Accepted: 08/15/2012] [Indexed: 01/07/2023]
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Jokinen J, Chatzittofis A, Hellström C, Nordström P, Uvnäs-Moberg K, Asberg M. Low CSF oxytocin reflects high intent in suicide attempters. Psychoneuroendocrinology 2012; 37:482-90. [PMID: 21852050 DOI: 10.1016/j.psyneuen.2011.07.016] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2011] [Revised: 07/25/2011] [Accepted: 07/25/2011] [Indexed: 12/15/2022]
Abstract
Data from animal studies suggest that oxytocin is an important modulating neuropeptide in regulation of social interaction. One human study has reported a negative correlation between CSF oxytocin levels, life history of aggression and suicidal behaviour. We hypothesized that CSF oxytocin levels would be related to suicidal behaviour, suicide intent, lifetime interpersonal violence and suicide risk. 28 medication free suicide attempters and 19 healthy volunteers participated in this cross sectional and longitudinal study. CSF and plasma morning basal levels of oxytocin were assessed with specific radio-immunoassays. The Beck Suicide Intent Scale (SIS), the Freeman scale and the Karolinska Interpersonal Violence Scale (KIVS) were used to assess suicide intent and lifetime violent behaviour. All patients were followed up for cause of death. The mean follow-up was 21 years. Suicide attempters had lower CSF oxytocin levels compared to healthy volunteers p=0.077. In suicide attempters CSF oxytocin showed a significant negative correlation with the planning subscale of SIS. CSF oxytocin showed a significant negative correlation with suicide intent, the planning subscale of SIS and Freeman interruption probability in male suicide attempters. Correlations between plasma oxytocin levels and the planning subscale of SIS and Freeman interruption probability were significant in male suicide attempters. Lifetime violent behaviour showed a trend to negative correlation with CSF oxytocin. In the regression analysis suicide intent remained a significant predictor of CSF oxytocin corrected for age and gender whereas lifetime violent behaviour showed a trend to be a predictor of CSF oxytocin. Oxytocin levels did not differ significantly in suicide victims compared to survivors. CSF oxytocin may be an important modulator of suicide intent and interpersonal violence in suicide attempters.
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Affiliation(s)
- Jussi Jokinen
- The Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
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Kamali M, Saunders EF, Prossin AR, Brucksch CB, Harrington GJ, Langenecker SA, McInnis MG. Associations between suicide attempts and elevated bedtime salivary cortisol levels in bipolar disorder. J Affect Disord 2012; 136:350-8. [PMID: 22154566 PMCID: PMC3683957 DOI: 10.1016/j.jad.2011.11.027] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2011] [Revised: 10/31/2011] [Accepted: 11/14/2011] [Indexed: 01/25/2023]
Abstract
BACKGROUND Hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been reported in bipolar disorder and also in suicidal behavior, but few studies have examined the relationship between suicidal behaviors and the HPA axis function in bipolar disorder, attending to and minimizing confounding factors. We compare HPA axis activity in bipolar individuals with and without suicidal behavior and unaffected healthy controls through measurement of salivary cortisol. METHOD Salivary cortisol was collected for three consecutive days in 29 controls, 80 bipolar individuals without a history of suicide and 56 bipolar individuals with a past history of suicide. Clinical factors that affect salivary cortisol were also examined. RESULTS A past history of suicide was associated with a 7.4% higher bedtime salivary cortisol level in bipolar individuals. There was no statistical difference between non-suicidal bipolar individuals and controls in bedtime salivary cortisol and awakening salivary cortisol was not different between the three groups. LIMITATIONS The measure of salivary cortisol was a home based collection by the study subjects and the retrospective clinical data was primarily based on their historical account. CONCLUSIONS Bipolar individuals with a past history of suicidal behavior exhibit hyperactivity in the HPA axis. This biological marker remains significant regardless of demographic factors, mood state, severity and course of illness. This finding in bipolar disorder is consistent with the evidence for altered HPA axis functioning in suicide and mood disorders and is associated with a clinical subgroup of bipolar patients at elevated risk for suicide based on their history, and in need of further attention and study.
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Affiliation(s)
- Masoud Kamali
- The University of Michigan, Department of Psychiatry and Depression Center, Ann Arbor, MI 48109-2700, USA.
| | - Erika F.H. Saunders
- The University of Michigan, Department of Psychiatry and Depression Center, MI, USA,Penn State Hershey Medical Center and Penn State College of Medicine, PA, USA
| | - Alan R. Prossin
- The University of Michigan, Department of Psychiatry and Depression Center, MI, USA
| | | | - Gloria J. Harrington
- The University of Michigan, Department of Psychiatry and Depression Center, MI, USA
| | - Scott A. Langenecker
- The University of Michigan, Department of Psychiatry and Depression Center, MI, USA
| | - Melvin G. McInnis
- The University of Michigan, Department of Psychiatry and Depression Center, MI, USA
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Fetal growth, early life circumstances, and risk of suicide in late adulthood. Eur J Epidemiol 2011; 26:571-81. [PMID: 21681547 DOI: 10.1007/s10654-011-9592-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2010] [Accepted: 05/31/2011] [Indexed: 01/21/2023]
Abstract
Recent studies in Sweden and Scotland have found early life conditions to be associated with increased risk of attempted and completed suicide in adolescence and young adulthood. It is not known, however, whether early life conditions affect suicide risk throughout the life course, from adulthood into old age. We examined the effects of early life conditions, including markers of fetal growth, and social and economic characteristics in adulthood, on risk of suicide by violent and non-violent methods in women and men aged 31-87 years using Cox regression. 11,650 women and men born at the Uppsala University Hospital in Sweden between 1915 and 1929 were followed from 1960 until 2002 using linked records from obstetric archives, Census, population and mortality registries. During 435,039 person-years of follow-up 161 completed suicides (104 in males, 57 in females) were observed. An inverse association was found between lower birthweight-for-gestational age and risk of violent suicide in females, although the association did not reach the conventional level of statistical significance (minimally adjusted HR 2.02, 95% CI (0.88-4.63); Table 4). Being male, unmarried, and in the "other or unknown" social class category in adulthood were independently associated with increased rates of suicide. There was a weak association between higher maternal parity and suicide rates. Our findings suggest differences in effects of fetal growth patterns and perinatal circumstances on suicide risk later in life, and suggest that suicide in adults and in the elderly may be influenced by a different combination of factors than those that influence suicide in adolescence and young adulthood.
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Lee BH, Kim YK. Potential peripheral biological predictors of suicidal behavior in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35:842-7. [PMID: 20708058 DOI: 10.1016/j.pnpbp.2010.08.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2010] [Revised: 07/25/2010] [Accepted: 08/02/2010] [Indexed: 01/22/2023]
Abstract
Previous studies have shown that dysfunctions in the serotonin system and hypothalamic-pituitary-adrenal axis (HPA) are associated strongly with suicidal behavior and suicide, especially among individuals with major depressive disorder. Suicidal behavior has been explained using both the stress-diathesis model and the state-trait interaction model. Specifically, diatheses, or trait-dependent risk factors, are associated with dysfunctions in the serotonin system; however, stress responses, or state-dependent factors, are associated with HPA hyperactivity. Decreases in cholesterol and brain-derived neurotrophic factor (BDNF) levels have been associated with impaired brain plasticity among individuals with suicidal behavior. Decreased serotonin functioning has been measured using cerebral spinal fluid (CSF) 5-HIAA, fenfluramine challenge studies, and platelet 5-HT2A receptors. HPA axis dysfunction has been evaluated with the dexamethasone suppression test. Cholesterol and BDNF levels have been measured in blood serum or plasma. Nevertheless, challenges to finding promising and accessible neurobiological predictors of suicide and suicidal behavior remain. As suicide behavior is a complex phenomenon, a combined or multidimensional approach, including each of the aforementioned methods, may be required to predict suicide risk among individuals with major depressive disorder.
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Affiliation(s)
- Bun-Hee Lee
- Department of Psychiatry, College of Medicine, Korea University, Seoul, Republic of Korea
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41
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Animal model and neurobiology of suicide. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35:818-30. [PMID: 21354241 DOI: 10.1016/j.pnpbp.2010.10.027] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2010] [Revised: 10/06/2010] [Accepted: 10/08/2010] [Indexed: 11/20/2022]
Abstract
Animal models are formidable tools to investigate the etiology, the course and the potential treatment of an illness. No convincing animal model of suicide has been produced to date, and despite the intensive study of thousands of animal species naturalists have not identified suicide in nonhuman species in field situations. When modeling suicidal behavior in the animal, the greatest challenge is reproducing the role of will and intention in suicide mechanics. To overcome this limitation, current investigations on animals focus on every single step leading to suicide in humans. The most promising endophenotypes worth investigating in animals are the cortisol social-stress response and the aggression/impulsivity trait, involving the serotonergic system. Astroglia, neurotrophic factors and neurotrophins are implied in suicide, too. The prevention of suicide rests on the identification and treatment of every element increasing the risk.
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McGirr A, Diaconu G, Berlim MT, Turecki G. Personal and family history of suicidal behaviour is associated with lower peripheral cortisol in depressed outpatients. J Affect Disord 2011; 131:368-73. [PMID: 21093058 DOI: 10.1016/j.jad.2010.10.050] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2010] [Revised: 10/13/2010] [Accepted: 10/28/2010] [Indexed: 11/28/2022]
Abstract
BACKGROUND Suicidal behaviour aggregates in families and HPA-axis dysregulation may help explain part of this familial aggregation. Nevertheless, exogenous manipulation of the HPA-axis has yielded mixed results. Naturalistic and non-pharmacological inductions of the HPA-axis do not suggest hyper-responsiveness, yet suggest greater cognitive consequences of stress in individuals at risk for suicide. In this study, we aimed to characterize the relationship between plasma cortisol and an increased risk for suicide, as defined by family history. METHOD Patients (N=148) with depressive disorders underwent psychopathological assessment, including structured investigation of past suicidal behaviour and underwent laboratory blood testing of cortisol. They also completed a family history interview investigating family psychopathology and suicidal behaviour, representing data on 848 first degree relatives. The relationship between plasma cortisol, past suicidal behaviour and suicidal behaviour among first degree relatives was examined. RESULTS Lower levels of plasma cortisol were associated with a personal and family history of suicidal behaviour, as well as a family history of depression among first degree relatives. Multivariate analyses controlling for significant psychopathology replicated the association between lower levels of plasma cortisol, a family history of suicidal behaviour and personal history of suicide attempts, but not a family history of depression. Controlling for personal history of suicide attempts revealed an independent association between plasma cortisol and family history of suicidal behaviour, with an additional contribution by family history of depression in predicting the latter. CONCLUSIONS Lower plasma cortisol is associated with a family history of suicide among depressed outpatients, independent of psychopathology and previous suicide attempts.
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Affiliation(s)
- Alexander McGirr
- McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Canada; University of Toronto, Faculty of Medicine, Toronto, Canada
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Mihaljević S, Vuksan-Ćusa B, Marčinko D, Koić E, Kušević Z, Jakovljević M. Spiritual well-being, cortisol, and suicidality in Croatian war veterans suffering from PTSD. JOURNAL OF RELIGION AND HEALTH 2011; 50:464-473. [PMID: 20694578 DOI: 10.1007/s10943-010-9383-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
We present our preliminary results of work that aims to observe the relationship between the cortisol level, the level of spiritual well-being, and suicidal tendencies in Croatian war veterans suffering from PTSD. The survey was conducted on 17 PTSD veterans who completed the Spiritual Well-Being Scale and the Beck Hopelessness Scale. The plasma cortisol level was obtained by venepuction at 8.00, 12.00, 13.00, 16.00, and 22.00 h. Results showed that veterans with higher spiritual well-being scores had lower cortisol levels, and evening cortisol levels showed significant correlation with suicidal risk. The results of the present study could be a stimulus for further investigation into spiritually based interventions, exploring their impact both on mental status and physical health.
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Affiliation(s)
- Sanea Mihaljević
- Psychiatry Department, General Hospital Virovitica, Gajeva 21, 33 000 Virovitica, Croatia.
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Nyhuis TJ, Sasse SK, Masini CV, Day HEW, Campeau S. Lack of contextual modulation of habituated neuroendocrine responses to repeated audiogenic stress. Behav Neurosci 2011; 124:810-20. [PMID: 21038933 DOI: 10.1037/a0021203] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Exposure to stress reliably activates the hypothalamo-pituitary-adrenocortical (HPA) axis response in rodents, which is significantly reduced (habituated) following repeated exposures. In the current study, it was first established that HPA axis response habituation to repeated loud noise lasted for at least 4 weeks in rats. In the next experiment, a contextual extinction procedure following repeated loud noise exposures failed to restore the habituated HPA axis response. Although an additional study indicated some recovery of responses when the context was modified on a test day following habituation, this effect could be mostly attributed to the familiarity with the contextual cues. A final study confirmed that rats could distinguish between the contexts used and further indicated that context preexposures reduce acute HPA axis responses to loud noise. These studies therefore provide no support for the hypothesis that contextual cues regulate HPA axis response habituation.
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Affiliation(s)
- Tara J Nyhuis
- Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80309, USA.
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45
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Association of FKBP5 gene haplotypes with completed suicide in the Japanese population. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35:252-6. [PMID: 21112363 DOI: 10.1016/j.pnpbp.2010.11.019] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2010] [Revised: 11/08/2010] [Accepted: 11/16/2010] [Indexed: 01/26/2023]
Abstract
BACKGROUND The hypothalamus-pituitary-adrenal (HPA) axis is known to have a role in suicidal behaviors in patients with affective disorders. However, the incomplete overlapping of the genetic factors of suicidal behaviors and the genetic factors of affective disorders suggest that the genes associated with predisposition to suicidal behaviors and affective disorders are different. There is increasing evidence that genes regulating the HPA axis have effects on suicidal behaviors. To test this idea, we examined the association of three HPA axis-related genes (glucocorticoid receptor (NR3C1), mineralocorticoid receptors (NR3C2), and FK506 binding protein 5 (FKBP5)) with suicide. METHODS We selected 3 SNPs of the FKBP5 (rs3800373, rs1360780, and rs2395635), 2 SNPs of the NR3C1 (rs6196 and rs10052957), and 3 SNPs of the NR3C2 genes (rs5525, rs5522, and rs2070951) based on their frequency in the Japanese population. Using TaqMan probe assays, we determined these SNPs in 219 completed suicide victims and 228 age- and gender-matched healthy control subjects. RESULTS No significant differences in genotypic distribution or allelic frequency of any single SNPs between the completed suicide and control groups were observed. The distributions of TT, TC, and GT haplotypes of the FKBP5 gene (comprised of rs3800373 and rs1360780) between the completed suicide and control groups were significantly different (p<0.05 for each haplotype). The TC haplotype withstood correction for multiple comparisons (corrected p = 0.034). CONCLUSION Our results suggest that haplotypes in FKBP5 gene are associated with completed suicide. This finding needs to be confirmed using rigorous SNPs selection in a larger sample.
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Pompili M, Serafini G, Innamorati M, Möller-Leimkühler AM, Giupponi G, Girardi P, Tatarelli R, Lester D. The hypothalamic-pituitary-adrenal axis and serotonin abnormalities: a selective overview for the implications of suicide prevention. Eur Arch Psychiatry Clin Neurosci 2010; 260:583-600. [PMID: 20174927 DOI: 10.1007/s00406-010-0108-z] [Citation(s) in RCA: 108] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2009] [Accepted: 02/05/2010] [Indexed: 12/11/2022]
Abstract
Suicidal behavior and mood disorders are one of the world's largest public health problems. The biological vulnerability for these problems includes genetic factors involved in the regulation of the serotonergic system and stress system. The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates the body's response to stress and has complex interactions with brain serotonergic, noradrenergic and dopaminergic systems. Corticotropin-releasing hormone and vasopressin act synergistically to stimulate the secretion of ACTH that stimulates the biosynthesis of corticosteroids such as cortisol from cholesterol. Cortisol is a major stress hormone and has effects on many tissues, including on mineralocorticoid receptors and glucocorticoid receptors in the brain. Glucocorticoids produce behavioral changes, and one important target of glucocorticoids is the hypothalamus, which is a major controlling center of the HPA axis. Stress plays a major role in the various pathophysiological processes associated with mood disorders and suicidal behavior. Serotonergic dysfunction is a well-established substrate for mood disorders and suicidal behavior. Corticosteroids may play an important role in the relationship between stress, mood changes and perhaps suicidal behavior by interacting with 5-HT1A receptors. Abnormalities in the HPA axis in response to increased levels of stress are found to be associated with a dysregulation in the serotonergic system, both in subjects with mood disorders and those who engage in suicidal behavior. HPA over-activity may be a good predictor of mood disorders and perhaps suicidal behavior via abnormalities in the serotonergic system.
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Affiliation(s)
- Maurizio Pompili
- Department of Psychiatry, Sant'Andrea Hospital, Via di Grottarossa 1035, 00189, Rome, Italy.
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Jokinen J, Ouda J, Nordström P. Noradrenergic function and HPA axis dysregulation in suicidal behaviour. Psychoneuroendocrinology 2010; 35:1536-42. [PMID: 20576361 DOI: 10.1016/j.psyneuen.2010.05.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2010] [Revised: 04/22/2010] [Accepted: 05/23/2010] [Indexed: 01/21/2023]
Abstract
Noradrenergic and HPA axis dysregulation may play a role in suicide risk. Studies of suicide risk have not found consistent relationship to the noradrenaline metabolite 3-methoxy-4-hydroxphenylglycol (MHPG) in the cerebrospinal fluid (CSF). Non-suppression in the dexamethasone test (DST) has been associated with increased risk of suicide in depressed patients. The study sample consisted of 51 mood disorder inpatients admitted to the Department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. Patients underwent lumbar punction and DST and were followed up for the cause of death. The hypothesis was that both CSF MHPG and HPA axis dysregulation are associated with suicidal behaviour. Nine suicide victims had significantly lower CSF MHPG and baseline plasma cortisol than survivors. Using both CSF MHPG and baseline cortisol in ROC analysis for suicide prediction, the positive predictive value was 44% and the area under the curve was 0.88. In conclusion, lower CSF MHPG was associated with suicide risk. Furthermore these results suggest that combined measures of noradrenergic system and HPA axis function may offer better prediction of suicide risk.
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Affiliation(s)
- Jussi Jokinen
- Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
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McGirr A, Diaconu G, Berlim MT, Pruessner JC, Sablé R, Cabot S, Turecki G. Dysregulation of the sympathetic nervous system, hypothalamic-pituitary-adrenal axis and executive function in individuals at risk for suicide. J Psychiatry Neurosci 2010; 35:399-408. [PMID: 20731961 PMCID: PMC2964370 DOI: 10.1503/jpn.090121] [Citation(s) in RCA: 94] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2009] [Revised: 01/31/2010] [Accepted: 03/30/2010] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND Suicidal behaviour aggregates in families, and the hypothalamic-pituitary-adrenal (HPA) axis and noradrenergic dysregulation may play a role in suicide risk. It is unclear whether stress dysregulation is a heritable trait of suicide or how it might increase risk. We investigated stress reactivity of the autonomic nervous system and the HPA axis in suicide predisposition and characterized the effect of this dysregulation on neuropsychologic function. METHODS In this family-based study of first-degree relatives (n = 14) of suicide completers and matched controls with no family or personal history of suicidal behaviour (n = 14), participants underwent the Trier Social Stress Test (TSST). We used salivary α-amylase and cortisol levels to characterize stress reactivity and diurnal variation. We administered a series of neuropsychologic and executive function tests before and after the TSST. RESULTS Despite normal diurnal variation, relatives of suicide completers exhibited blunted cortisol and α-amylase TSST reactivity. Although there were no baseline differences in conceptual reasoning, sustained attention or executive function, the relatives of suicide completers did not improve on measures of inhibition upon repeated testing after TSST. Secondary analyses suggested that these effects were related to suicide vulnerability independent of major depression. LIMITATIONS The sample size was small, and the design prevents us from disentangling our findings from the possible traumatic consequences of losing a relative by suicide. CONCLUSIONS Blunted stress response may be a trait of suicide risk, and impairment of stress-induced executive function may contribute to suicide vulnerability.
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Affiliation(s)
- Alexander McGirr
- McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que
| | - Gabriel Diaconu
- McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que
| | - Marcelo T. Berlim
- McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que
| | - Jens C. Pruessner
- McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que
| | - Rebecca Sablé
- McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que
| | - Sophie Cabot
- McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que
| | - Gustavo Turecki
- McGirr, Giaconu, Berlim, Cabot, Turecki — McGill Group for Suicide Studies; Berlim, Sablé, Turecki — Mood Disorders Program; Pruessner — Centre for Studies on Human Stress, Douglas Mental Health University Institute, McGill University, Montréal, Que
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Nyhuis TJ, Masini CV, Sasse SK, Day HEW, Campeau S. Physical activity, but not environmental complexity, facilitates HPA axis response habituation to repeated audiogenic stress despite neurotrophin mRNA regulation in both conditions. Brain Res 2010; 1362:68-77. [PMID: 20851112 DOI: 10.1016/j.brainres.2010.09.038] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2010] [Revised: 09/03/2010] [Accepted: 09/10/2010] [Indexed: 02/05/2023]
Abstract
Stress exacerbates several physical and psychological disorders. Voluntary exercise can reduce susceptibility to many of these stress-associated disorders. In rodents, voluntary exercise can reduce hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to various stressors as well as upregulate several brain neurotrophins. An important issue regarding voluntary exercise is whether its effect on the reduction of HPA axis activation in response to stress is due to the physical activity itself or simply the enhanced environmental complexity provided by the running wheels. The present study compared the effects of physical activity and environmental complexity (that did not increase physical activity) on HPA axis habituation to repeated stress and modulation of brain neurotrophin mRNA expression. For six weeks, male rats were given free access to running wheels (exercise group), given 4 objects that were repeatedly exchanged (increased environmental complexity group), or housed in standard cages. On week 7, animals were exposed to 11 consecutive daily 30-min sessions of 98-dBA noise. Plasma corticosterone and adrenocorticotropic hormone were measured from blood collected directly after noise exposures. Tissue, including brains, thymi, and adrenal glands was collected on Day 11. Although rats in both the exercise and enhanced environmental complexity groups expressed higher levels of BDNF and NGF mRNA in several brain regions, only exercise animals showed quicker glucocorticoid habituation to repeated audiogenic stress. These results suggest that voluntary exercise, independent from other environmental manipulations, accounts for the reduction in susceptibility to stress.
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Affiliation(s)
- Tara J Nyhuis
- Department of Psychology and Neuroscience, University of Colorado, Boulder, CO 80309, USA.
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50
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Jokinen J, Nordström P. HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients. J Affect Disord 2009; 116:117-20. [PMID: 19054569 DOI: 10.1016/j.jad.2008.10.015] [Citation(s) in RCA: 92] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2008] [Revised: 10/20/2008] [Accepted: 10/21/2008] [Indexed: 11/26/2022]
Abstract
BACKGROUND Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. METHODS The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with (n=18) and without suicide attempt at the index episode. RESULTS The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. CONCLUSIONS The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.
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Affiliation(s)
- Jussi Jokinen
- Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Karolinska University Hospital, Solna, SE-171 76 Stockholm, Sweden.
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