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Ding Z, Chen J, Zhong BL, Liu CL, Liu ZT. Emotional stimulated speech-based assisted early diagnosis of depressive disorders using personality-enhanced deep learning. J Affect Disord 2025; 376:177-188. [PMID: 39914753 DOI: 10.1016/j.jad.2025.01.136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Revised: 01/15/2025] [Accepted: 01/26/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Early diagnosis of depression is crucial, and speech-based early diagnosis of depression is promising, but insufficient data and lack of theoretical support make it difficult to be applied. Therefore, it is valuable to combine psychiatric theories, collect speech recognition data for depression, and develop a practicable recognition method for depression. METHODS In this study, 24 patients with major depressive disorders (MDDs) and 36 healthy controls (HCs) were recruited to participate in a multi-task speech experiment. Descriptive statistics and tests of variance were used to analyze subjects' personality and speech changes. Subsequently, the speech task with the most depressive cues was explored using the Bidirectional Long - Short Term Memory (Bi-LSTM) algorithm, on which a personality-assisted multitasking deep model, i.e., multi-task attentional temporal convolutional network model (TCN-MTA). RESULTS Statistical analyses of speech duration showed that the fable reading, neutral stimulus, and negative stimulus tasks had significant differences on subjects' speech duration, and the negative stimulus task had significant differences between the depressed and control groups (p < 0.001, 0.03, 0.04). Notably, the Big Five personality emotional stability scores were significantly different between the depressed and control groups (0.03). Depression was best identified using Bi-LSTM in negative (Youden index = 0.44) and positive stimulus speech (Youden index = 0.42). Further, the specificity of 0.72 and sensitivity of 0.87 for recognizing depression in negative stimulus speech using our proposed TCN-MTA outperforms existing methods. LIMITATIONS The sample size enrolled in this study is higher than the minimum sample size calculated through G-Power 3.1, but the sample size in this study is still small. CONCLUSION The proposed deep learning-based personality-assisted multitasking method could accurately recognize major depression, which demonstrated the potential of the method based on the fusion of specialized theories and artificial intelligence.
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Affiliation(s)
- Zhong Ding
- School of Education, China University of Geosciences, Lumo Road, Wuhan 430074, Hubei, China; Psychological Science and Health Research Center, China University of Geosciences, Lumo Road, Wuhan 430074, Hubei, China
| | - Jing Chen
- Wuhan Mental Health Center, Jianshe Avenue, Wuhan 430032, Hubei, China; Wuhan Hospital for Psychotherapy, Jianshe Avenue, Wuhan 430032, Hubei, China
| | - Bao-Liang Zhong
- Psychological Science and Health Research Center, China University of Geosciences, Lumo Road, Wuhan 430074, Hubei, China; Wuhan Mental Health Center, Jianshe Avenue, Wuhan 430032, Hubei, China; Wuhan Hospital for Psychotherapy, Jianshe Avenue, Wuhan 430032, Hubei, China.
| | - Chen-Ling Liu
- School of Education, China University of Geosciences, Lumo Road, Wuhan 430074, Hubei, China; Psychological Science and Health Research Center, China University of Geosciences, Lumo Road, Wuhan 430074, Hubei, China.
| | - Zhen-Tao Liu
- Psychological Science and Health Research Center, China University of Geosciences, Lumo Road, Wuhan 430074, Hubei, China; School of Automation, China University of Geosciences, Lumo Road, Wuhan 430074, Hubei, China.
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Boby K, Veerasingam S. Depression diagnosis: EEG-based cognitive biomarkers and machine learning. Behav Brain Res 2025; 478:115325. [PMID: 39515528 DOI: 10.1016/j.bbr.2024.115325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 10/06/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
Depression is a complex mental illness that has significant effects on people as well as society. The traditional techniques for the diagnosis of depression, along with the potential of nascent biomarkers especially EEG-based biomarkers, are studied. This review explores the significance of cognitive biomarkers, offering a comprehensive understanding of their role in the overall assessment of depression. It also investigates the effects of depression on various brain regions, outlines promising areas for future research, and emphasizes the importance of understanding the neurophysiological roots of depression. Furthermore, it elucidates how machine learning and deep learning models are integrated into EEG-based depression diagnosis, emphasizing their importance in optimizing personalized therapeutic protocols and improving diagnostic accuracy with EEG data analysis.
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Affiliation(s)
- Kiran Boby
- Department of Instrumentation and Control Engineering, NIT Tiruchirappalli, Thuvakudi, Tiruchirappalli, Tamil Nadu 620015, India.
| | - Sridevi Veerasingam
- Department of Instrumentation and Control Engineering, NIT Tiruchirappalli, Thuvakudi, Tiruchirappalli, Tamil Nadu 620015, India.
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He Q, Lan X, Ding M, Zhang N. Long-term consumption of hydrogen-rich water provides hepatoprotection by improving mitochondrial biology and quality control in chronically stressed mice. PLoS One 2025; 20:e0317080. [PMID: 39951412 PMCID: PMC11828380 DOI: 10.1371/journal.pone.0317080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 12/20/2024] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Chronic stress has emerged as a prevalent facet of contemporary existence, significantly jeopardizing overall bodily health. The liver, a pivotal organ responsible for metabolic equilibrium, is particularly vulnerable to its adverse effects. This study delves into the hepatoprotective properties of extended consumption of HRW in mice subjected to chronic stress. METHODS Mice subjected to chronic stress via CUMS and HRW administration for seven months underwent liver pathological examination. Key liver function indicators (AST, ALT), oxidative stress markers (SOD, CAT, GSH), and markers related to lipid peroxidation and ferroptosis (MDA, Fe) were measured using standard kits. ELISA determined corticosterone and 4-HNE levels. Immunofluorescence evaluated ROS, Nrf2, and apoptosis in liver tissues. Western blotting analyzed markers for ferroptosis (GPX4, SLC7A11, HO-1, Nrf2), apoptosis (Bax, Bcl-2, Cytc, Caspase-3, Caspase-8), mitochondrial biogenesis (Nrf1, PGC-1α, Tfam), and quality control (Drp1, Fis1, Mfn1, Mfn2, OPA1, PINK1, Parkin, LC3 I/II). RESULTS The findings indicate a noteworthy improvement in liver health among mice exposed to HRW, as evidenced by histological analysis. Furthermore, the consumption of HRW exhibited hepatoprotection, as evidenced by the normalization of AST and ALT levels. Mechanistically, our results indicate that HRW elevates the levels of SOD, CAT, and GSH, while effectively clearing ROS within mitochondria. It was observed led to a regulation in the expression of mitochondrial quality control proteins, consequently improving mitochondrial biogenesis (Nrf1, PGC-1α, Tfam), and increasing ATP production. Furthermore, HRW decreased Cytc, Bax, Caspase-3, and Caspase-8 levels, and increasing the expression of Bcl-2. Additionally, HRW reduced MDA and 4-HNE levels, alleviating ferroptosis through the Nrf2/HO-1 pathway, and upregulating the expression of GPX4 and SLC7A11. By mitigating hepatocyte death through the aforementioned mechanisms, HRW fulfills its crucial role in safeguarding liver health. CONCLUSIONS This study reveals that long-term hydrogen-rich water (HRW) consumption provides significant hepatoprotection in mice under chronic stress. HRW normalizes liver enzyme levels, enhances antioxidant capacity, and reduces lipid peroxidation and ferroptosis. It improves mitochondrial biogenesis, function, and ATP production, and attenuates apoptosis by modulating related proteins. Behavioral tests show HRW alleviates stress-induced anxiety and enhances exploratory behavior. These findings suggest HRW is a promising non-invasive intervention for preventing and treating stress-related liver disorders by targeting oxidative stress and mitochondrial dysfunction.
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Affiliation(s)
- Qi He
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Northeast Agricultural University, Harbin, China
| | - Xiang Lan
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Northeast Agricultural University, Harbin, China
| | - Mengyuan Ding
- College of Veterinary Medicine, Northeast Agricultural University, Harbin, China
- Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine, Northeast Agricultural University, Harbin, China
| | - Na Zhang
- The Key Laboratory of Dairy Science of Education Ministry, Northeast Agricultural University, Harbin, China
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Xu N, He Y, Wei YN, Bai L, Wang L. Possible antidepressant mechanism of acupuncture: targeting neuroplasticity. Front Neurosci 2025; 19:1512073. [PMID: 40018358 PMCID: PMC11865234 DOI: 10.3389/fnins.2025.1512073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 02/03/2025] [Indexed: 03/01/2025] Open
Abstract
Major depressive disorder (MDD) is a highly prevalent and severely disabling psychiatric disorder that decreases quality of life and imposes substantial economic burden. Acupuncture has emerged as an effective adjunctive treatment for depression, it regulates neurotransmitters involved in mood regulation and modulates the activity of specific brain regions associated with emotional processing, as evidenced by neuroimaging and biochemical studies. Despite these insights, the precise neuroplastic mechanisms through which acupuncture exerts its antidepressant effects remain not fully elucidated. This review aims to summarize the current knowledge on acupuncture's modulation of neuroplasticity in depression, with a focus on the neuroplasticity-based targets associated with acupuncture's antidepressant effects. We encapsulate two decades of research into the neurobiological mechanisms underpinning the efficacy of acupuncture in treating depression. Additionally, we detail the acupoints and electroacupuncture parameters used in the treatment of depression to better serve clinical application.
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Affiliation(s)
- Ning Xu
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yue He
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yong-Nan Wei
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Lu Bai
- Department of First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, China
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Long Wang
- First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
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Gao G, Ge H, Rong B, Sun L, Si L, Huang J, Li C, Huang J, Wu L, Zhao H, Zhou M, Xie Y, Xiao L, Wang G. Serum KNG and FVIII may serve as potential biomarkers for depression. Behav Brain Res 2025; 482:115454. [PMID: 39880101 DOI: 10.1016/j.bbr.2025.115454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2024] [Revised: 01/19/2025] [Accepted: 01/22/2025] [Indexed: 01/31/2025]
Abstract
BACKGROUND The global burden of major depressive disorder (MDD) is rising, with current diagnostic methods hindered by significant subjectivity and low inter-rater reliability. Several studies have implied underlying link between coagulation-related proteins, such as kininogen (KNG) and coagulation factor VIII (FVIII), and depressive symptoms, offering new insights into the exploration of depression biomarkers. This study aims to elucidate the roles of KNG and FVIII in depression, potentially providing a foundational basis for biomarker research in this field. METHODS A three-part experiment was conducted: (1) we measured serum levels of KNG and FVIII in the chronic unpredictable mild stress (CUMS) model; (2) KNG adeno-associated-virus overexpression (KNG-AAV-OE) model was constructed to further investigate the roles of KNG and FVIII. Meanwhile, quantity PCR, western blotting and immunofluorescence staining detected the KNG-FVIII pathway. (3) Peripheral blood samples were gathered from healthy control (HC, N = 21), as well as first-episode drug-naive patients with MDD (FEDN-MDD, N = 21), to further confirm the association between KNG, FVIII and depression. RESULTS Firstly, serum KNG and FVIII levels were significantly elevated in the CUMS model. Then, the rats exhibited pronounced depressive-like behaviors in the KNG-AAV-OE model, with corresponding increases in serum KNG and FVIII. Lastly, clinical data showed increased KNG and FVIII levels in FEDN-MDD compared to HC. Furthermore, KNG and FVIII levels exhibited a strong positive correlation with the scores of the 24-item Hamilton Depression Scale and the 14-item Hamilton Anxiety Scale. CONCLUSION To sum up, this study highlights critical roles of serum KNG and FVIII in depression and the KNG-AAV-OE may lead the augment of FVIII in serum. Consequently, our research may offer new evidence and foundation for depression biomarkers research in the future.
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Affiliation(s)
- Guoqing Gao
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
| | - Hailong Ge
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
| | - Bei Rong
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Limin Sun
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Lujia Si
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Junjie Huang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Chen Li
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Junhua Huang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Lan Wu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Haomian Zhao
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Mingzhe Zhou
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China
| | - Yinping Xie
- Department of Psychiatry and Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
| | - Ling Xiao
- Department of Psychiatry and Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China.
| | - Gaohua Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China; Department of Psychiatry and Institute of Neuropsychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, PR China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, PR China.
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Luo Y, Tang M, Fan X. Meta analysis of resting frontal alpha asymmetry as a biomarker of depression. NPJ MENTAL HEALTH RESEARCH 2025; 4:2. [PMID: 39820155 PMCID: PMC11739517 DOI: 10.1038/s44184-025-00117-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 01/06/2025] [Indexed: 01/19/2025]
Abstract
This meta-analysis investigated resting frontal alpha asymmetry (FAA) as a potential biomarker for major depressive disorder (MDD). Studies included articles utilizing FAA measure involving EEG electrodes (F3/F4, F7/F8, or Fp1/Fp2) and covering both MDD and controls. Hedges' d was calculated from FAA means and standard deviations (SDs). A systematic search of PubMed through July 2023 identified 23 studies involving 1928 MDD participants and 2604 controls. The analysis revealed a small but significant grand mean effect size (ES) for FAA (F4 - F3), suggesting limited diagnostic value of FAA in MDD. Despite the presence of high heterogeneity across studies, subgroup analyses did not identify significant differences based on calculation formula, reference montage, age, or depression severity. The findings indicate that FAA may have limited standalone diagnostic utility but could complement existing clinical assessments for MDD, highlighting the need for a multifaceted approach to depression diagnosis and prognosis.
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Affiliation(s)
- Yiwen Luo
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, 200124, China
| | - Mingcong Tang
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, 200124, China
| | - Xiwang Fan
- Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai, 200124, China.
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More S, Kaleem M, Kharwade R, Almutairy AF, Shahzad N, Ali Mujtaba M, Taha M, Pise A, Zafar A, Mahmood D. Depression unveiled: Insights into etiology and animal models for behavioral assessment, exploring the multifactorial nature and treatment of depression. Brain Res 2025; 1847:149313. [PMID: 39515744 DOI: 10.1016/j.brainres.2024.149313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 10/27/2024] [Accepted: 11/04/2024] [Indexed: 11/16/2024]
Abstract
Over the past century, significant shifts in daily living have led to an increased prevalence of mental disorders, often linked to hormonal imbalances. Among these, anxiety and depression stand out as prevalent diagnoses, particularly in industrialized nations. Depression, according to the DSM-5, is a heterogeneous condition that affects emotional, cognitive, and physical functioning, with symptoms including insomnia, sexual dysfunction, and weight changes. Cognitive theories of depression highlight its impact on judgment, decision-making, thinking, and focus. Depression's multifaceted nature means that no two patients experience identical symptoms, risk factors, or treatment responses. The COVID-19 pandemic has exacerbated mental health issues, with social isolation, restricted contact, and altered daily routines contributing to increased anxiety and depression, especially among adolescents and young adults. The pandemic's psychological toll underscores the need for effective treatment strategies for mental disorders. The physical manifestations of major depressive disorder (MDD) are associated with a heightened risk of developing various medical conditions, including metabolic disorders, cardiovascular disease, stroke, epilepsy, and dementia. This review provides a comprehensive exploration of depression and anxiety, covering their different types, epidemiology, potential causes, diagnostic criteria, and available treatment options. It delves into the role of pharmacological interventions and examines recent advancements to enhance therapeutic outcomes. Additionally, the review assesses the therapeutic potential of drugs, offering insights into their efficacy in treating these complex mental health disorders. By targeting the multifactorial etiology of depression through drug repurposing and new drug development, researchers aim to enhance treatment efficacy and achieve better outcomes for patients with depression.
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Affiliation(s)
- Sachin More
- Department of Pharmacology, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India
| | - Mohammed Kaleem
- Department of Pharmacology, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India
| | - Rohini Kharwade
- Department of Pharmaceutics, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India
| | - Ali F Almutairy
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia
| | - Naiyer Shahzad
- Department of Pharmacology and Toxicology, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Md Ali Mujtaba
- Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Arar, Saudi Arabia; Center for Health Research, Northern Border University, Arar, Saudi Arabia.
| | - Murtada Taha
- Department of Clinical Laboratory Science, Prince Sultan military college of health sciences, Dhahran, Saudi Arabia
| | - Ajay Pise
- Department of Regulatory Affairs, Dadasaheb Balpande College of Pharmacy, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur 440037, Maharashtra, India
| | - Ameeduzzafar Zafar
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka 72341, Al-Jouf, Saudi Arabia
| | - Danish Mahmood
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia
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Fennema D, Barker GJ, O’Daly O, Godlewska BR, Carr E, Goldsmith K, Young AH, Moll J, Zahn R. Neural signatures of emotional biases predict clinical outcomes in difficult-to-treat depression. RESEARCH DIRECTIONS. DEPRESSION 2024; 1:e21. [PMID: 40028885 PMCID: PMC11869767 DOI: 10.1017/dep.2024.6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 03/05/2025]
Abstract
Background Neural predictors underlying variability in depression outcomes are poorly understood. Functional MRI measures of subgenual cortex connectivity, self-blaming and negative perceptual biases have shown prognostic potential in treatment-naïve, medication-free and fully remitting forms of major depressive disorder (MDD). However, their role in more chronic, difficult-to-treat forms of MDD is unknown. Methods Forty-five participants (n = 38 meeting minimum data quality thresholds) fulfilled criteria for difficult-to-treat MDD. Clinical outcome was determined by computing percentage change at follow-up from baseline (four months) on the self-reported Quick Inventory of Depressive Symptomatology (16-item). Baseline measures included self-blame-selective connectivity of the right superior anterior temporal lobe with an a priori Brodmann Area 25 region-of-interest, blood-oxygen-level-dependent a priori bilateral amygdala activation for subliminal sad vs happy faces, and resting-state connectivity of the subgenual cortex with an a priori defined ventrolateral prefrontal cortex/insula region-of-interest. Findings A linear regression model showed that baseline severity of depressive symptoms explained 3% of the variance in outcomes at follow-up (F[3,34] = .33, p = .81). In contrast, our three pre-registered neural measures combined, explained 32% of the variance in clinical outcomes (F[4,33] = 3.86, p = .01). Conclusion These findings corroborate the pathophysiological relevance of neural signatures of emotional biases and their potential as predictors of outcomes in difficult-to-treat depression.
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Affiliation(s)
- Diede Fennema
- Centre of Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
| | - Gareth J. Barker
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
| | - Owen O’Daly
- Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
| | - Beata R. Godlewska
- Psychopharmacology Research Unit, University Department of Psychiatry, University of Oxford, Oxford, UK
- Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK
| | - Ewan Carr
- Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
| | - Kimberley Goldsmith
- Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
| | - Allan H. Young
- Centre of Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
- National Service for Affective Disorders, South London and Maudsley NHS Foundation Trust, London, UK
| | - Jorge Moll
- Cognitive and Behavioral Neuroscience Unit, D’Or Institute for Research and Education (IDOR), Pioneer Science Program, Rio de Janeiro, Brazil
| | - Roland Zahn
- Centre of Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
- National Service for Affective Disorders, South London and Maudsley NHS Foundation Trust, London, UK
- Cognitive and Behavioral Neuroscience Unit, D’Or Institute for Research and Education (IDOR), Pioneer Science Program, Rio de Janeiro, Brazil
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Ma S, Li R, Gong Q, Lv H, Deng Z, Wang B, Yao L, Kang L, Xiang D, Yang J, Liu Z. Using Data-Driven Algorithms with Large-Scale Plasma Proteomic Data to Discover Novel Biomarkers for Diagnosing Depression. J Proteome Res 2024; 23:4043-4054. [PMID: 39150755 DOI: 10.1021/acs.jproteome.4c00389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/17/2024]
Abstract
Given recent technological advances in proteomics, it is now possible to quantify plasma proteomes in large cohorts of patients to screen for biomarkers and to guide the early diagnosis and treatment of depression. Here we used CatBoost machine learning to model and discover biomarkers of depression in UK Biobank data sets (depression n = 4,479, healthy control n = 19,821). CatBoost was employed for model construction, with Shapley Additive Explanations (SHAP) being utilized to interpret the resulting model. Model performance was corroborated through 5-fold cross-validation, and its diagnostic efficacy was evaluated based on the area under the receiver operating characteristic (AUC) curve. A total of 45 depression-related proteins were screened based on the top 20 important features output by the CatBoost model in six data sets. Of the nine diagnostic models for depression, the performance of the traditional risk factor model was improved after the addition of proteomic data, with the best model having an average AUC of 0.764 in the test sets. KEGG pathway analysis of 45 screened proteins showed that the most significant pathway involved was the cytokine-cytokine receptor interaction. It is feasible to explore diagnostic biomarkers of depression using data-driven machine learning methods and large-scale data sets, although the results require validation.
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Affiliation(s)
- Simeng Ma
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Ruiling Li
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Qian Gong
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Honggang Lv
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Zipeng Deng
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Beibei Wang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Lihua Yao
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Lijun Kang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Dan Xiang
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
| | - Jun Yang
- School of Information Engineering, Wuhan University of Technology, Wuhan 430070, China
| | - Zhongchun Liu
- Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430071, China
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10
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de Deus M, Petit C, Schwitzer T. ElectroRetinoGraphy toward an exploration of the therapeutic potential of antidepressants in patients with major depressive disorder: A scoping review of the literature. Neurosci Biobehav Rev 2024; 164:105833. [PMID: 39089420 DOI: 10.1016/j.neubiorev.2024.105833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Revised: 07/07/2024] [Accepted: 07/27/2024] [Indexed: 08/04/2024]
Abstract
Major Depressive Disorder (MDD) is characterized by at least one major depressive episode. It requires medical attention typically involving the prescription of antidepressants. Remission in MDD patients is often difficult to achieve because of the limited effectiveness of these drugs. Nowadays, numerous patients undergo various antidepressant treatments, with subjective changes in their personal experiences being regularly monitored. Therefore, it is essential to find clinical and objective tools that offer a more tailored approach to antidepressant selection. The neurochemistry of the retina being similar to the brain, one promising approach would be to use ElectroRetinoGraphy (ERG) measurements on MDD patients requiring antidepressant treatment. Thus, the aim of this scoping review is to highlight effects of different classes of antidepressants on retinal function evaluated by full-field ERG (ffERG), Pattern ERG (PERG) and multifocal ERG (mfERG) waveforms in MDD patients. These ERG measurements could serve as pivotal indicators in defining patient profiles, facilitating a more objective and personalized approach to therapeutic interventions, thereby advancing precision psychiatry.
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Affiliation(s)
- Marie de Deus
- Pôle Hospitalo-Universitaire de Psychiatrie d'Adulte et d'Addictologie du Grand Nancy, Centre Psychothérapique de Nancy, 1, rue du Docteur Archambault, Laxou 54 520, France
| | - Charlotte Petit
- Pôle Hospitalo-Universitaire de Psychiatrie d'Adulte et d'Addictologie du Grand Nancy, Centre Psychothérapique de Nancy, 1, rue du Docteur Archambault, Laxou 54 520, France
| | - Thomas Schwitzer
- Pôle Hospitalo-Universitaire de Psychiatrie d'Adulte et d'Addictologie du Grand Nancy, Centre Psychothérapique de Nancy, 1, rue du Docteur Archambault, Laxou 54 520, France.
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11
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Pan X, Gao Y, Guan K, Chen J, Ji B. Ghrelin/GHSR System in Depressive Disorder: Pathologic Roles and Therapeutic Implications. Curr Issues Mol Biol 2024; 46:7324-7338. [PMID: 39057075 PMCID: PMC11275499 DOI: 10.3390/cimb46070434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/03/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024] Open
Abstract
Depression is the most common chronic mental illness and is characterized by low mood, insomnia, and affective disorders. However, its pathologic mechanisms remain unclear. Numerous studies have suggested that the ghrelin/GHSR system may be involved in the pathophysiologic process of depression. Ghrelin plays a dual role in experimental animals, increasing depressed behavior and decreasing anxiety. By combining several neuropeptides and traditional neurotransmitter systems to construct neural networks, this hormone modifies signals connected to depression. The present review focuses on the role of ghrelin in neuritogenesis, astrocyte protection, inflammatory factor production, and endocrine disruption in depression. Furthermore, ghrelin/GHSR can activate multiple signaling pathways, including cAMP/CREB/BDNF, PI3K/Akt, Jak2/STAT3, and p38-MAPK, to produce antidepressant effects, given which it is expected to become a potential therapeutic target for the treatment of depression.
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Affiliation(s)
- Xingli Pan
- School of Biological Sciences, Jining Medical University, Jining 272067, China;
| | - Yuxin Gao
- School of Clinical Medicine, Jining Medical University, Jining 272067, China; (Y.G.); (K.G.)
| | - Kaifu Guan
- School of Clinical Medicine, Jining Medical University, Jining 272067, China; (Y.G.); (K.G.)
| | - Jing Chen
- Neurobiology Institute, Jining Medical University, Jining 272067, China
- Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Bingyuan Ji
- Institute of Precision Medicine, Jining Medical University, Jining 272067, China
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12
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Herman RJ, Schmidt HD. Targeting GLP-1 receptors to reduce nicotine use disorder: Preclinical and clinical evidence. Physiol Behav 2024; 281:114565. [PMID: 38663460 PMCID: PMC11128349 DOI: 10.1016/j.physbeh.2024.114565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 04/18/2024] [Accepted: 04/22/2024] [Indexed: 04/30/2024]
Abstract
Nicotine use disorder (NUD) remains a leading cause of preventable death in the U.S. Unfortunately, current FDA-approved pharmacotherapies for smoking cessation have limited efficacy and are associated with high rates of relapse. One major barrier to long-term smoking abstinence is body weight gain during withdrawal. Nicotine withdrawal-induced body weight gain can also lead to development of chronic disease states like obesity and type II diabetes mellitus. Therefore, it is critical to identify novel pharmacotherapies for NUD that decrease relapse and nicotine withdrawal symptoms including body weight gain. Recent studies demonstrate that glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate voluntary nicotine taking and seeking and prevent withdrawal-induced hyperphagia and body weight gain. Emerging evidence also suggests that GLP-1R agonists improve cognitive deficits, as well as depressive- and anxiety-like behaviors, which contribute to smoking relapse during withdrawal. While further studies are necessary to fully characterize the effects of GLP-1R agonists on NUD and understand the mechanisms by which GLP-1R agonists decrease nicotine withdrawal-mediated behaviors, the current literature supports GLP-1R-based approaches to treating NUD.
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Affiliation(s)
- Rae J Herman
- Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
| | - Heath D Schmidt
- Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, United States; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
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13
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Zierer C, Behrendt C, Lepach-Engelhardt AC. Digital biomarkers in depression: A systematic review and call for standardization and harmonization of feature engineering. J Affect Disord 2024; 356:438-449. [PMID: 38583596 DOI: 10.1016/j.jad.2024.03.163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 03/21/2024] [Accepted: 03/28/2024] [Indexed: 04/09/2024]
Abstract
BACKGROUND General physicians misclassify depression in more than half of the cases. Researchers have explored the feasibility of leveraging passively collected data points, also called digital biomarkers, to provide more granular understanding of depression phenotypes as well as a more objective assessment of disease. METHOD This paper provides a systematic review following the PRISMA guidelines (Page et al., 2021) to understand which digital biomarkers might be relevant for passive screening of depression. Pubmed and PsycInfo were systematically searched for studies published from 2019 to early 2024, resulting in 161 records assessed for eligibility. Excluded were intervention studies, studies focusing on a different disease or those with a lack of passive data collection. 74 studies remained for a quality assessment, after which 27 studies were included. RESULTS The review shows that depressed participants' real-life behavior such as reduced communication with others can be tracked by passive data. Machine learning models for the classification of depression have shown accuracies up to 0.98, surpassing the quality of many standardized assessment methods. LIMITATIONS Inconsistency of outcome reporting of current studies does not allow for drawing statistical conclusions regarding effectiveness of individual included features. The Covid-19 pandemic might have impacted the ongoing studies between 2020 and 2022. CONCLUSION While digital biomarkers allow real-life tracking of participant's behavior and symptoms, further work is required to align the feature engineering of digital biomarkers. With shown high accuracies of assessments, connecting digital biomarkers with clinical practice can be a promising method of detecting symptoms of depression automatically.
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Affiliation(s)
- Carolin Zierer
- Department of Psychology, PFH Private University of Applied Sciences, Göttingen, Lower Saxony, Germany
| | - Corinna Behrendt
- Department of Psychology, PFH Private University of Applied Sciences, Göttingen, Lower Saxony, Germany.
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14
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Tian H, Gao S, Xu M, Yang M, Shen M, Liu J, Li G, Zhuang D, Hu Z, Wang C. tiRNA-Gly-GCC-001 in major depressive disorder: Promising diagnostic and therapeutic biomarker. Br J Pharmacol 2024; 181:1952-1972. [PMID: 38439581 DOI: 10.1111/bph.16319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 01/03/2024] [Accepted: 01/04/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND AND PURPOSE In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA-derived small ribonucleic acids (tsRNAs) have been established as promising non-invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development. EXPERIMENTAL APPROACH Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA-Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed. KEY RESULTS In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up-regulated and 4 down-regulated). qRT-PCR was used to validate the expression of six tsRNAs that were up-regulated in MDD (tiRNA-1:20-chrM.Ser-GCT, tiRNA-1:33-Gly-GCC-1, tRF-1:22-chrM.Ser-GCT, tRF-1:31-Ala-AGC-4-M6, tRF-1:31-Pro-TGG-2 and tRF-1:32-chrM.Gln-TTG). Interestingly, serum tiRNA-Gly-GCC-001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA-Gly-GCC-001 is predicted to suppress brain-derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA-Gly-GCC-001 down-regulation was evident following an 8-week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy. CONCLUSION AND IMPLICATIONS Our current work reports for the first time that tiRNA-Gly-GCC-001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy.
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Affiliation(s)
- Haihua Tian
- Zhejiang Key Laboratory of Pathophysiology, Health Center, Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Shugui Gao
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Miaomiao Xu
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Mei Yang
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Mengyuan Shen
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Jimeng Liu
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Guangxue Li
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Dingding Zhuang
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Zhenyu Hu
- Department of Psychiatry, Affiliated Kangning Hospital of Ningbo University, Ningbo, Zhejiang, China
- Department of Psychiatry, Ningbo Kangning Hospital, Ningbo, Zhejiang, China
| | - Chuang Wang
- Zhejiang Key Laboratory of Pathophysiology, Health Center, Ningbo University, Ningbo, Zhejiang, China
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15
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Rajkumar RP. Are There Biological Correlates of Response to Yoga-Based Interventions in Depression? A Critical Scoping Review. Brain Sci 2024; 14:543. [PMID: 38928543 PMCID: PMC11201983 DOI: 10.3390/brainsci14060543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 05/22/2024] [Accepted: 05/23/2024] [Indexed: 06/28/2024] Open
Abstract
Depression is the most common mental disorder worldwide. Both antidepressants and psychotherapy are effective in treating depression, but the response to these treatments is often incomplete. Yoga-based interventions (YBIs) have been advocated by some researchers as a promising form of alternative treatment for depression. Recent research has attempted to identify the biological mechanisms associated with the antidepressant actions of YBIs. In this scoping review, conducted according to the PRISMA-ScR guidelines, the PubMed and Scopus databases were searched to retrieve research on biomarkers of response to YBIs in patients with depression. These studies were also critically reviewed to evaluate their methodological quality and any sources of bias. Nineteen studies were included in the review. Based on these studies, there is preliminary evidence that YBIs may be associated with increased serum brain-derived neurotrophic factor (BDNF) and reduced serum cortisol and interleukin-6 (IL-6) in patients with depression. However, many of these changes were also observed in the control arms, and the overall quality of the research was low. At present, it cannot be concluded that there are reliable biomarkers of response to YBIs in depression, though there are some potential biological correlates. Further advances in this field will depend critically on improvements in study design, particularly the minimization of sources of bias and the selection of more specific and sensitive biomarkers based on existing evidence from other treatment modalities.
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Affiliation(s)
- Ravi Philip Rajkumar
- Department of Psychiatry, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Pondicherry 605 006, India
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16
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Bagarić T, Mihaljević-Peleš A, Skočić Hanžek M, Živković M, Kozmar A, Rogić D. Serum Levels of Zinc, Albumin, Interleukin-6 and CRP in Patients with Unipolar and Bipolar Depression: Cross Sectional Study. Curr Issues Mol Biol 2024; 46:4533-4550. [PMID: 38785543 PMCID: PMC11119144 DOI: 10.3390/cimb46050275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/02/2024] [Accepted: 05/07/2024] [Indexed: 05/25/2024] Open
Abstract
Unipolar (UD) and bipolar depression (BDD) show a high degree of similarity in clinical presentations, which complicates the differential diagnosis of these disorders. The aim of this study was to investigate the serum levels of interleukin 6 (IL-6), C-reactive protein (CRP), albumin (Alb), and zinc (Zn) in patients with UD, BDD, and healthy controls (HC). A total of 211 samples were collected: 131 patient samples (65 UD and 68 BDD) and 80 HC. The Montgomery-Asberg Depression Rating Scale (MADRS), along with the Hamilton Depression Rating Scale (HAMD-17), were administered to patient groups to evaluate symptoms. A cross-sectional study was performed to analyse the serum levels of IL-6, CRP, albumin, and zinc. The concentration of CRP was determined using the immunoturbidimetry method, zinc using the colorimetric method, and albumin using the colorimetric method with bromocresol green on the Alinity c device. IL-6 cytokine concentration in serum samples was ascertained using a commercial enzyme immunoassay, ELISA. We found no significant differences in serum concentrations of zinc, albumin, CRP, and IL-6 between the groups of patients with unipolar and bipolar depression. There was a significant statistical difference (p < 0.001) between serum levels of all investigated parameters in both groups of depressed patients in comparison with HC. Furthermore, correlations with specific items on HAMD-17; (namely, hypochondrias, work and activities, somatic symptoms-general, and weight loss) and on MADRS (concentration difficulties, lassitude) were observed in both patient groups. These findings confirm the presence of low-grade inflammation in depression, thus adding better insight into the inflammation hypothesis directed to explain the aetiology of depressive disorders. Our results do not indicate potential biomarkers for distinguishing between unipolar and bipolar depression.
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Affiliation(s)
- Tihana Bagarić
- Department for Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
| | - Alma Mihaljević-Peleš
- Department for Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Milena Skočić Hanžek
- Department for Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Maja Živković
- Department for Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
- School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Ana Kozmar
- Department for Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
| | - Dunja Rogić
- Department for Psychiatry and Psychological Medicine, University Hospital Centre Zagreb, 10000 Zagreb, Croatia
- Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia
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17
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Hu Y, Chen J, Chen J, Wang W, Zhao S, Hu X. An Ensemble Classification Model for Depression Based on Wearable Device Sleep Data. IEEE J Biomed Health Inform 2024; 28:2602-2612. [PMID: 37030745 DOI: 10.1109/jbhi.2023.3258601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/10/2023]
Abstract
Depression is one of the most common mental disorders, with sleep disturbances as typical symptoms. With the popularity of wearable devices increasing in recent years, more and more people wear portable devices to track sleep quality. Based on this, we believe that depression detection through wearable sleep data is more intelligent and economical. However, the majority of wearable devices face the problem of missing data during the data collection process. Otherwise, most existing studies of depression identification focus on the utilization of complex data, making it difficult to generalize and susceptible to noise interference. To address these issues, we propose a systematic ensemble classification model for depression (ECD). For the missing data problem of wearable devices, we design an improved GAIN method to further control the generation range of interpolated values, which can achieve a more reasonable treatment of missing values. Compared with the original GAIN approach, the improved method shows a 28.56% improvement when using MAE as the metric. For depression recognition, we use ensemble learning to construct a depression classification model which combines five classification models, including SVM, KNN, LR, CBR, and DT. Ensemble learning can improve the model's robustness and generalization. The voting mechanism is used in several places to improve noise immunity. The final classification model performed great on the dataset, with a precision of 92.55% and a recall of 91.89%. These results illustrate how efficient this method is in automatically detecting depression.
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18
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Wang Y, Cai X, Ma Y, Yang Y, Pan CW, Zhu X, Ke C. Metabolomics on depression: A comparison of clinical and animal research. J Affect Disord 2024; 349:559-568. [PMID: 38211744 DOI: 10.1016/j.jad.2024.01.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 12/13/2023] [Accepted: 01/04/2024] [Indexed: 01/13/2024]
Abstract
BACKGROUND Depression is a major cause of suicide and mortality worldwide. This study aims to conduct a systematic review to identify metabolic biomarkers and pathways for major depressive disorder (MDD), a prevalent subtype of clinical depression. METHODS We searched for metabolomics studies on depression published between January 2000 and January 2023 in the PubMed and Web of Science databases. The reported metabolic biomarkers were systematically evaluated and compared. Pathway analysis was implemented using MetaboAnalyst 5.0. RESULTS We included 26 clinical studies on MDD and 78 metabolomics studies on depressive-like animal models. A total of 55 and 77 high-frequency metabolites were reported consistently in two-thirds of clinical and murine studies, respectively. In the comparison between murine and clinical studies, we identified 9 consistently changed metabolites (tryptophan, tyrosine, phenylalanine, methionine, fumarate, valine, deoxycholic acid, pyruvate, kynurenic acid) in the blood, 1 consistently altered metabolite (indoxyl sulfate) in the urine and 14 disturbed metabolic pathways in both types of studies. These metabolic dysregulations and pathways are mainly implicated in enhanced inflammation, impaired neuroprotection, reduced energy metabolism, increased oxidative stress damage and disturbed apoptosis, laying solid molecular foundations for MDD. LIMITATIONS Due to unavailability of original data like effect-size results in many metabolomics studies, a meta-analysis cannot be conducted, and confounding factors cannot be fully ruled out. CONCLUSIONS This systematic review delineated metabolic biomarkers and pathways related to depression in the murine and clinical samples, providing opportunities for early diagnosis of MDD and the development of novel diagnostic targets.
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Affiliation(s)
- Yibo Wang
- Suzhou Medical College of Soochow University, Suzhou, China
| | - Xinyi Cai
- Suzhou Medical College of Soochow University, Suzhou, China
| | - Yuchen Ma
- Suzhou Medical College of Soochow University, Suzhou, China
| | - Yang Yang
- Suzhou Medical College of Soochow University, Suzhou, China
| | - Chen-Wei Pan
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China
| | - Xiaohong Zhu
- Suzhou Centers for Disease Control and Prevention, Suzhou, China.
| | - Chaofu Ke
- School of Public Health, Suzhou Medical College of Soochow University, Suzhou, China.
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19
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Jaiswal A, Goyal N, Shreekantiah U. High-Definition Transcranial Direct Current Stimulation-Primed Intermittent Theta Burst Stimulation in Treatment-Resistant Depression: A Controlled Study. J ECT 2024; 40:41-46. [PMID: 38411577 DOI: 10.1097/yct.0000000000000952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/28/2024]
Abstract
OBJECTIVES The aim of this study was to evaluate whether high-definition transcranial direct current stimulation (HDtDCS) priming improves the efficacy of intermittent theta burst stimulation (iTBS) in improving TRD. METHODOLOGY A prospective hospital-based, randomized control study where the participants were divided into active or sham HDtDCS-primed iTBS stimulation groups for a total of 10 sessions and were assessed on clinical parameters at baseline, end of week 1, and end of week 2 was done. Primary outcome of the study was the difference in Hamilton Depression Rating Scale (HDRS) scores over 2 weeks of HDtDCS-primed iTBS. RESULT A significant effect of time was seen over HDRS scores in both active and sham groups with a large effect size. Significant effect of time was also found over the Clinical Global Impressions-Severity Scale scores of patients with a large effect size. The difference in the improvement in depressive severity as measured using HDRS and Clinical Global Impressions-Severity Scale scores between active and sham groups was also found to be significant with large effect sizes. CONCLUSION High-definition tDCS-primed iTBS is superior to normal iTBS in patients with depression who have failed a trial of 2 antidepressants, whereas both mechanisms are of benefit to the patients.
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Affiliation(s)
- Alankrit Jaiswal
- From the Central Institute of Psychiatry, Ranchi, Jharkhand, India
| | - Nishant Goyal
- Central Institute of Psychiatry, Ranchi, Jharkhand, India
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20
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Kang S, Kim W, Nam J, Li K, Kang Y, Bae B, Chun KH, Chung C, Lee J. Non-Targeted Metabolomics Investigation of a Sub-Chronic Variable Stress Model Unveils Sex-Dependent Metabolic Differences Induced by Stress. Int J Mol Sci 2024; 25:2443. [PMID: 38397124 PMCID: PMC10889542 DOI: 10.3390/ijms25042443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/16/2024] [Accepted: 02/18/2024] [Indexed: 02/25/2024] Open
Abstract
Depression is twice as prevalent in women as in men, however, most preclinical studies of depression have used male rodent models. This study aimed to examine how stress affects metabolic profiles depending on sex using a rodent depression model: sub-chronic variable stress (SCVS). The SCVS model of male and female mice was established in discovery and validation sets. The stress-induced behavioral phenotypic changes were similar in both sexes, however, the metabolic profiles of female plasma and brain became substantially different after stress, whereas those of males did not. Four stress-differential plasma metabolites-β-hydroxybutyric acid (BHB), L-serine, glycerol, and myo-inositol-could yield biomarker panels with excellent performance to discern the stressed individuals only for females. Disturbances in BHB, glucose, 1,5-anhydrosorbitol, lactic acid, and several fatty acids in the plasma of stressed females implied a systemic metabolic shift to β-oxidation in females. The plasma levels of BHB and corticosterone only in stressed females were observed not only in SCVS but also in an acute stress model. These results collectively suggest a sex difference in the metabolic responses by stress, possibly involving the energy metabolism shift to β-oxidation and the HPA axis dysregulation in females.
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Affiliation(s)
- Seulgi Kang
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; (S.K.); (K.L.); (Y.K.); (B.B.)
| | - Woonhee Kim
- Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea; (W.K.); (J.N.); (C.H.C.)
| | - Jimin Nam
- Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea; (W.K.); (J.N.); (C.H.C.)
| | - Ke Li
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; (S.K.); (K.L.); (Y.K.); (B.B.)
| | - Yua Kang
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; (S.K.); (K.L.); (Y.K.); (B.B.)
| | - Boyeon Bae
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; (S.K.); (K.L.); (Y.K.); (B.B.)
| | - Kwang-Hoon Chun
- Gachon Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, Incheon 21936, Republic of Korea;
| | - ChiHye Chung
- Department of Biological Sciences, Konkuk University, Seoul 05029, Republic of Korea; (W.K.); (J.N.); (C.H.C.)
| | - Jeongmi Lee
- School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea; (S.K.); (K.L.); (Y.K.); (B.B.)
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21
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Lee D, Woo CW, Heo H, Ko Y, Jang JS, Na S, Kim N, Woo DC, Kim KW, Lee DW. Mapping Changes in Glutamate with Glutamate-Weighted MRI in Forced Swim Test Model of Depression in Rats. Biomedicines 2024; 12:384. [PMID: 38397986 PMCID: PMC10887078 DOI: 10.3390/biomedicines12020384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 02/01/2024] [Accepted: 02/06/2024] [Indexed: 02/25/2024] Open
Abstract
Chemical exchange saturation transfer with glutamate (GluCEST) imaging is a novel technique for the non-invasive detection and quantification of cerebral Glu levels in neuromolecular processes. Here we used GluCEST imaging and 1H magnetic resonance spectroscopy (1H MRS) to assess in vivo changes in Glu signals within the hippocampus in a rat model of depression induced by a forced swim test. The forced swimming test (FST) group exhibited markedly reduced GluCEST-weighted levels and Glu concentrations when examined using 1H MRS in the hippocampal region compared to the control group (GluCEST-weighted levels: 3.67 ± 0.81% vs. 5.02 ± 0.44%, p < 0.001; and Glu concentrations: 6.560 ± 0.292 μmol/g vs. 7.133 ± 0.397 μmol/g, p = 0.001). Our results indicate that GluCEST imaging is a distinctive approach to detecting and monitoring Glu levels in a rat model of depression. Furthermore, the application of GluCEST imaging may provide a deeper insight into the neurochemical involvement of glutamate in various psychiatric disorders.
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Affiliation(s)
- Donghoon Lee
- Faculty of Health Sciences, Higher Colleges of Technology, Fujairah P.O. Box 1626, United Arab Emirates;
| | - Chul-Woong Woo
- Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea; (C.-W.W.); (D.-C.W.)
| | - Hwon Heo
- Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea;
| | - Yousun Ko
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea;
| | - Ji Sung Jang
- Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea; (J.S.J.); (S.N.)
| | - Seongwon Na
- Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea; (J.S.J.); (S.N.)
| | - Nari Kim
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
| | - Dong-Cheol Woo
- Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea; (C.-W.W.); (D.-C.W.)
- Department of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea;
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
| | - Kyung Won Kim
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea;
- Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea;
| | - Do-Wan Lee
- Department of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea;
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22
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Lan L, Peng S, Zhang R, He H, Yang Y, Xi B, Zhang J. Serum proteomic biomarker investigation of vascular depression using data-independent acquisition: a pilot study. Front Aging Neurosci 2024; 16:1341374. [PMID: 38384936 PMCID: PMC10879412 DOI: 10.3389/fnagi.2024.1341374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Accepted: 01/22/2024] [Indexed: 02/23/2024] Open
Abstract
Background Vascular depression (VaD) is a depressive disorder closely associated with cerebrovascular disease and vascular risk factors. It remains underestimated owing to challenging diagnostics and limited information regarding the pathophysiological mechanisms of VaD. The purpose of this study was to analyze the proteomic signatures and identify the potential biomarkers with diagnostic significance in VaD. Methods Deep profiling of the serum proteome of 35 patients with VaD and 36 controls was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Functional enrichment analysis of the quantified proteins was based on Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Reactome databases. Machine learning algorithms were used to screen candidate proteins and develop a protein-based model to effectively distinguish patients with VaD. Results There were 29 up-regulated and 31 down-regulated proteins in the VaD group compared to the controls (|log2FC| ≥ 0.26, p ≤ 0.05). Enrichment pathways analyses showed that neurobiological processes related to synaptic vesicle cycle and axon guidance may be dysregulated in VaD. Extrinsic component of synaptic vesicle membrane was the most enriched term in the cellular components (CC) terms. 19 candidate proteins were filtered for further modeling. A nomogram was developed with the combination of HECT domain E3 ubiquitin protein ligase 3 (HECTD3), Nidogen-2 (NID2), FTO alpha-ketoglutarate-dependent dioxygenase (FTO), Golgi membrane protein 1 (GOLM1), and N-acetylneuraminate lyase (NPL), which could be used to predict VaD risk with favorable efficacy. Conclusion This study offers a comprehensive and integrated view of serum proteomics and contributes to a valuable proteomics-based diagnostic model for VaD.
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Affiliation(s)
- Liuyi Lan
- Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Sisi Peng
- Department of Neuropsychology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ran Zhang
- Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Haoying He
- Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China
| | - Yong Yang
- SpecAlly Life Technology Co., Ltd., Wuhan, China
| | - Bing Xi
- SpecAlly Life Technology Co., Ltd., Wuhan, China
| | - Junjian Zhang
- Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China
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23
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Videtta G, Squarcina L, Prunas C, Brambilla P, Delvecchio G. White matter integrity and medication response to antidepressants in major depressive disorder: a review of the literature. Front Psychiatry 2024; 14:1335706. [PMID: 38361831 PMCID: PMC10867229 DOI: 10.3389/fpsyt.2023.1335706] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 12/27/2023] [Indexed: 02/17/2024] Open
Abstract
Major Depressive Disorder (MDD) is a severe psychiatric disorder characterized by selective impairments in mood regulation, cognition and behavior. Although it is well-known that antidepressants can effectively treat moderate to severe depression, the biochemical effects of these medications on white matter (WM) integrity are still unclear. Therefore, the aim of the study is to review the main scientific evidence on the differences in WM integrity in responders and non-responders to antidepressant medications. A record search was performed on three datasets (PubMed, Scopus and Web of Science) and ten records matched our inclusion criteria. Overall, the reviewed studies highlighted a good efficacy of antidepressants in MDD treatment. Furthermore, there were differences in WM integrity between responders and non-responders, mainly localized in cingulate cortices, hippocampus and corpus callosum, where the former group showed higher fractional anisotropy and lower axial diffusivity values. Modifications in WM integrity might be partially explained by branching and proliferation as well as neurogenesis of axonal fibers mediated by antidepressants, which in turn may have positively affected brain metabolism and increase the quantity of the serotonergic neurotransmitter within synaptic clefts. However, the reviewed studies suffer from some limitations, including the heterogeneity in treatment duration, antidepressant administration, medical posology, and psychiatric comorbidities. Therefore, future studies are needed to reduce confounding effects of antidepressant medications and to adopt longitudinal and multimodal approaches in order to better characterize the differences in WM integrity between responders and non-responders.
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Affiliation(s)
- Giovanni Videtta
- Department of Biomedical Sciences for Health, University of Milan, Milan, Italy
| | - Letizia Squarcina
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Cecilia Prunas
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Paolo Brambilla
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giuseppe Delvecchio
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
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24
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Zhang J, Liu D, Xiang J, Yang M. Combining Glial Fibrillary Acidic Protein and Neurofilament Light Chain for the Diagnosis of Major Depressive Disorder. Anal Chem 2024; 96:1693-1699. [PMID: 38231554 DOI: 10.1021/acs.analchem.3c04825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
Major depressive disorder (MDD) is a prevalent brain disorder affecting more than 2% of the world's population. Due to the lack of well-specific biomarkers, it is difficult to distinguish MDD from other diseases with similar clinical symptoms (such as Alzheimer's disease and cerebral thrombosis). In this work, we provided a strategy to address this issue by constructing a combinatorial biomarker of serum glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL). To achieve the convenient and sensitive detection of two proteins, we developed an electrochemical immunosandwich sensor using two metal-ion-doped carbon dots (Pb-CDs and Cu-CDs) as probes for signal output. Each probe contains approximately 300 Pb2+ or 200 Cu2+, providing excellent signal amplification. This method achieved detection limits of 0.3 pg mL-1 for GFAP and 0.2 pg mL-1 for NFL, lower than most of the reported detection limits. Analysis of real serum samples showed that the concentration ratio of GFAP to NFL, which is associated with the relative degree of brain inflammation and neurodegeneration, is suitable for not only distinguishing MDD from healthy individuals but also specifically distinguishing MDD from Alzheimer's disease and cerebral thrombosis. The good specificity gives the combinatorial GFAP/NFL biomarker broad application prospects in the screening, diagnosis, and treatment of MDD.
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Affiliation(s)
- JinXia Zhang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Dan Liu
- Eye Center of Xiangya Hospital, Central South University, Changsha 410083, P. R. China
| | - Juan Xiang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
| | - Minghui Yang
- College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P. R. China
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25
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Jaber M, Kahwaji H, Nasr S, Baz R, Kim YK, Fakhoury M. Precision Medicine in Depression: The Role of Proteomics and Metabolomics in Personalized Treatment Approaches. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1456:359-378. [PMID: 39261438 DOI: 10.1007/978-981-97-4402-2_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
Depression, or major depressive disorder (MDD), is a widespread mental health condition marked by enduring feelings of sorrow and loss of interest. Treatment of depression frequently combines psychotherapy, medication, and lifestyle modifications. However, the occurrence of treatment resistance in certain individuals makes it difficult for physicians to effectively manage this disorder, calling for the implementation of alternative therapeutic strategies. Recently, precision medicine has gained increased attention in the field of mental health, paving the way for more personalized and effective therapeutic interventions in depression. Also known as personalized medicine, this approach relies on genetic composition, molecular profiles, and environmental variables to customize therapies to individual patients. In particular, precision medicine has offered novel viewpoints on depression through two specific domains: proteomics and metabolomics. On one hand, proteomics is the thorough study of proteins in a biological system, while metabolomics focuses on analyzing the complete set of metabolites in a living being. In the past few years, progress in research has led to the identification of numerous depression-related biomarkers using proteomics and metabolomics techniques, allowing for early identification, precise diagnosis, and improved clinical outcome. However, despite significant progress in these techniques, further efforts are required for advancing precision medicine in the diagnosis and treatment of depression. The overarching goal of this chapter is to provide the current state of knowledge regarding the use of proteomics and metabolomics in identifying biomarkers related to depression. It also highlights the potential of proteomics and metabolomics in elucidating the intricate processes underlying depression, opening the door for tailored therapies that could eventually enhance clinical outcome in depressed patients. This chapter finally discusses the main challenges in the use of proteomics and metabolomics and discusses potential future research directions.
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Affiliation(s)
- Mohamad Jaber
- School of Medicine, American University of Beirut, Beirut, Lebanon
| | - Hamza Kahwaji
- School of Medicine, Lebanese American University, Byblos, Lebanon
| | - Sirine Nasr
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Reine Baz
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Yong-Ku Kim
- Department of Psychiatry, Korea University College of Medicine, Seoul, Republic of Korea
| | - Marc Fakhoury
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon.
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26
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Wang L, Lu Z, Teng Y, Pan W, Li Y, Su S, Chang J, Zhao M. Cognitive impairment is associated with BDNF-TrkB signaling mediating synaptic damage and reduction of amino acid neurotransmitters in heart failure. FASEB J 2024; 38:e23351. [PMID: 38085181 DOI: 10.1096/fj.202301699rr] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 11/14/2023] [Accepted: 11/21/2023] [Indexed: 12/18/2023]
Abstract
Heart failure (HF) is often accompanied by cognitive impairment (CI). Brain-derived neurotrophic factor (BDNF) deficiency is closely associated with CI. However, the role and mechanism of BDNF in HF with CI is still not fully understood. Here, the case-control study was designed including 25 HF without CI patients (HF-NCI) and 50 HF with CI patients (HF-CI) to investigate the predictive value of BDNF in HF-CI while animal and cell experiments were used for mechanism research. Results found that BDNF levels in serum neuronal-derived exosomes were downregulated in HF-CI patients. There was no significant difference in serum BDNF levels among the two groups. HF rats showed obvious impairment in learning and memory; also, they had reduced thickness and length of postsynaptic density (PSD) and increased synaptic cleft width. Expression of BDNF, TrkB, PSD95, and VGLUT1 was significantly decreased in HF rats brain. In addition, compared with sham rats, amino acids were significantly reduced with no changes in the acetylcholine and monoamine neurotransmitters. Further examination showed that the number of synaptic bifurcations and the expression of BDNF, TrkB, PSD95, and VGLUT1 were all decreased in the neurons that interfered with BDNF-siRNA compared with those in the negative control neurons. Together, our results demonstrated that neuronal-derived exosomal BDNF act as effective biomarkers for prediction of HF-CI. The decrease of BDNF in the brain triggers synaptic structural damage and a decline in amino acid neurotransmitters via the BDNF-TrkB-PSD95/VGLUT1 pathway. This discovery unveils a novel pathological mechanism underlying cognitive impairment following heart failure.
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Affiliation(s)
- Lei Wang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Ziwen Lu
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yu Teng
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Weibing Pan
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Yang Li
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Sha Su
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jingling Chang
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Mingjing Zhao
- Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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27
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McNaughton BA, Burrows K, Choquette E, Poplin T, Kuplicki R, Paulus MP, Ironside M, Stewart JL. Impaired eating behaviors but intact metabolic hormone levels in individuals with major depressive disorder and generalized anxiety disorder. J Psychiatr Res 2023; 168:193-203. [PMID: 37918032 PMCID: PMC10842703 DOI: 10.1016/j.jpsychires.2023.10.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 10/23/2023] [Accepted: 10/25/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND Major depressive disorder (MDD) and generalized anxiety disorder (GAD) contribute significantly to global health burdens. Identifying disease markers for these comorbid disorders can increase understanding of pathogenesis and improve screening and intervention strategies. This study examined the association of physical health factors with MDD and MDD + GAD, across sexes. METHODS Two samples of participants from the Tulsa-1000 study (exploratory cohort: N = 136; confirmatory cohort: N = 185) completed body composition measurements, eating behavior (Three Factor Eating Questionnaire [TFEQ], Eating Disorder Diagnostic Scale [EDDS]), exercise questionnaires, and a blood draw. Metabolic hormone concentrations (leptin, insulin, and adiponectin) were analyzed from blood samples. Within each cohort, a two-way analysis of variance compared three groups (MDD, MDD + GAD, and healthy controls [HC]), sex, and their interaction on dependent variables. Hedges g was calculated to reflect effect size magnitude. RESULTS Medium-to-large group main effects across cohorts indicated that compared to HC: (1) MDD (g = 1.71/0.57) and MDD + GAD (g = 0.93/0.69) reported higher TFEQ Disinhibition scores; (2) MDD endorsed higher TFEQ Hunger scores (g = 0.66/0.48); and (3) MDD (g = 1.60/1.30) and MDD + GAD (g = 0.92/1.72) reported greater EDDS scores. Large sex main effects across cohorts indicated that females exhibited higher levels than males for percent body fat (g = 1.07/1.17), leptin (g = 1.27/1.12), and adiponectin (g=0.82/0.88). LIMITATIONS The power to detect group*sex interactions was limited due to a greater number of females (than males) in the study, and over half of clinical participants were taking medications. CONCLUSIONS Individuals with MDD and MDD + GAD demonstrate difficulties in regulating eating behaviors, potentially contributing to functional impairment and increased disease burden.
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Affiliation(s)
| | | | | | - Tate Poplin
- Laureate Institute of Brain Research, Tulsa, OK, USA
| | | | - Martin P Paulus
- Laureate Institute of Brain Research, Tulsa, OK, USA; The University of Tulsa, Tulsa, OK, USA
| | - Maria Ironside
- Laureate Institute of Brain Research, Tulsa, OK, USA; The University of Tulsa, Tulsa, OK, USA
| | - Jennifer L Stewart
- Laureate Institute of Brain Research, Tulsa, OK, USA; The University of Tulsa, Tulsa, OK, USA.
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28
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Lee YR, Lee J, Kang HG. Discovery and validation of a protein biomarker for the diagnosis and classification of disease severity of major depressive disorder. Clin Chim Acta 2023; 549:117555. [PMID: 37709115 DOI: 10.1016/j.cca.2023.117555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/10/2023] [Accepted: 09/11/2023] [Indexed: 09/16/2023]
Abstract
BACKGROUND AND AIMS Diagnosis and classification of disease severity of major depressive disorder (MDD) are determined through a doctor's consultation and questionnaire-based rating scale. This study aimed to identify and validate a serum protein biomarker for diagnosing and classifying the disease severity of MDD. MATERIALS AND METHODS Based on the Hamilton Depression Rating Scale (HAMD) score, participants were divided into control, mild, moderate, and severe groups. Samples prepared from collected sera were analyzed using non-targeted qualitative and targeted quantitative tools to identify potential biomarkers. RESULTS Four proteins were selected as biomarker candidates, which showed statistically significant consistent tendencies depending on MDD severity. Among them, tetranectin was the only validated protein in the quantitative analysis that showed the same decreasing tendency as that in the qualitative analysis. Furthermore, tetranectin showed fair discrimination performance between the control and MDD group. CONCLUSIONS Tetranectin may be a novel potential biomarker for diagnosing and classifying the severity of MDD, though further verification and validation studies of its efficacy are needed.
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Affiliation(s)
- You-Rim Lee
- Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu, 11759, Republic of Korea.
| | - Jiyeong Lee
- Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Uijeongbu, 11759, Republic of Korea; Department of Biomedical Laboratory Science, Graduate School, Eulji University, Uijeongbu, 11759, Republic of Korea.
| | - Hee-Gyoo Kang
- Department of Senior Healthcare, Graduate School, Eulji University, Uijeongbu, 11759, Republic of Korea; Department of Biomedical Laboratory Science, Graduate School, Eulji University, Uijeongbu, 11759, Republic of Korea; Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Seongnam, 13135, Republic of Korea.
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29
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Rimti FH, Shahbaz R, Bhatt K, Xiang A. A review of new insights into existing major depressive disorder biomarkers. Heliyon 2023; 9:e18909. [PMID: 37664743 PMCID: PMC10469054 DOI: 10.1016/j.heliyon.2023.e18909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2022] [Revised: 07/19/2023] [Accepted: 08/02/2023] [Indexed: 09/05/2023] Open
Abstract
As major depressive disorder (MDD) is such a diverse condition, there are currently no clear ways for determining its severity, endophenotype, or therapy response. The distinctive nature of depression, the variability of analysis in literature and the large number of conceptually complicated biomarkers are some of the many reasons for the lack of progress. Markers are involved in the process of neurotrophic, metabolic, and inflammation as well as neuroendocrine and neurotransmitter systems' components. Some clinical indicators are strong enough so that can be measured using assessments of proteomic, genetic, metabolomics, neuroimaging, epigenetic and transcriptomic. Markers of oxidative stress, endocrine, inflammatory, proteomic, and growth indicators are currently among the promising biologic systems/markers identified in this analysis. This narrative review examines succinct studies which investigated cytokines of inflammatory factors, peripheral factors of development, metabolic and endocrine markers as pathophysiological biomarkers of MDD, and treatment responses. Endocrine and metabolic alterations have also been linked to MDD in various studies. So, this study summarizes all of the numerous biomarkers that are significant in the detection or treatment of MDD patients. The paper also provides an overview of various biomarkers which are important for the regulation and its effects on MDD.
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Affiliation(s)
| | | | - Kunj Bhatt
- McMaster University, Ontario, 00000, Canada
| | - Alex Xiang
- McMaster University, Ontario, 00000, Canada
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30
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Song J, Lee E. Awareness and related factors of depressive symptoms in breastfeeding people in South Korea: a survey-based cross-sectional study. BMJ Open 2023; 13:e068282. [PMID: 37500267 PMCID: PMC10387636 DOI: 10.1136/bmjopen-2022-068282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/29/2023] Open
Abstract
OBJECTIVES This study identifies depressive symptoms and the factors that could explain its presence in breastfeeding people. DESIGN This study is a cross-sectional study from national survey data. SETTING AND PARTICIPANTS Data were derived from the 2019 Korean Community Health Survey. The study subjects were breastfeeding people under the age of 50. PRIMARY OUTCOME MEASURES Depressive symptoms in breastfeeding people were classified according to the Patient Health Questionnaire-9 (PHQ-9) score. Physical and health behaviours were considered as factors related to depressive symptoms. A multilevel logistic regression analysis was used. RESULTS Among 497 participants, 19.4% (n=97) of breastfeeding people were depressed. We found that depressive symptoms were associated with age (31-35, OR: 0.79, 95% CI: 0.67 to 0.94; 35-49, OR: 0.42, 95% CI: 0.32 to 0.56), rural setting (OR: 0.62, 95% CI: 0.51 to 0.76), economic activity (OR: 0.75, 95% CI: 0.61 to 0.91) and physical health (diabetus mellitus or hypertension, OR: 5.17, 95% CI: 3.78 to 7.06). CONCLUSIONS This study implies that socioeconomic factors, physical health and health behaviours may influence depressive symptoms in breastfeeding people. These findings should be used as descriptive data to support the development of education programmes to help breastfeeding people.
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Affiliation(s)
- Jiyoung Song
- Department of Nursing, Hoseo University, Asan, Korea (the Republic of)
| | - Eunwon Lee
- Department of Nursing, Doowon University of Technology, Anseong, Korea (the Republic of)
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31
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Zheng Y, Liu C, Lai NYG, Wang Q, Xia Q, Sun X, Zhang S. Current development of biosensing technologies towards diagnosis of mental diseases. Front Bioeng Biotechnol 2023; 11:1190211. [PMID: 37456720 PMCID: PMC10342212 DOI: 10.3389/fbioe.2023.1190211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 06/16/2023] [Indexed: 07/18/2023] Open
Abstract
The biosensor is an instrument that converts the concentration of biomarkers into electrical signals for detection. Biosensing technology is non-invasive, lightweight, automated, and biocompatible in nature. These features have significantly advanced medical diagnosis, particularly in the diagnosis of mental disorder in recent years. The traditional method of diagnosing mental disorders is time-intensive, expensive, and subject to individual interpretation. It involves a combination of the clinical experience by the psychiatrist and the physical symptoms and self-reported scales provided by the patient. Biosensors on the other hand can objectively and continually detect disease states by monitoring abnormal data in biomarkers. Hence, this paper reviews the application of biosensors in the detection of mental diseases, and the diagnostic methods are divided into five sub-themes of biosensors based on vision, EEG signal, EOG signal, and multi-signal. A prospective application in clinical diagnosis is also discussed.
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Affiliation(s)
- Yuhan Zheng
- Faculty of Science and Engineering, University of Nottingham Ningbo China, Ningbo, China
- Ningbo Research Center, Ningbo Innovation Center, Zhejiang University, Ningbo, China
- Robotics Institute, Ningbo University of Technology, Ningbo, China
| | - Chen Liu
- Faculty of Science and Engineering, University of Nottingham Ningbo China, Ningbo, China
- Ningbo Research Center, Ningbo Innovation Center, Zhejiang University, Ningbo, China
| | - Nai Yeen Gavin Lai
- Faculty of Science and Engineering, University of Nottingham Ningbo China, Ningbo, China
| | - Qingfeng Wang
- Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, China
| | - Qinghua Xia
- Ningbo Research Center, Ningbo Innovation Center, Zhejiang University, Ningbo, China
| | - Xu Sun
- Faculty of Science and Engineering, University of Nottingham Ningbo China, Ningbo, China
- Nottingham Ningbo China Beacons of Excellence Research and Innovation Institute, University of Nottingham Ningbo China, Ningbo, China
| | - Sheng Zhang
- Faculty of Science and Engineering, University of Nottingham Ningbo China, Ningbo, China
- Ningbo Research Center, Ningbo Innovation Center, Zhejiang University, Ningbo, China
- School of Mechanical Engineering, Zhejiang University, Hangzhou, China
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32
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Khan Z, Gupta GD, Mehan S. Cellular and Molecular Evidence of Multiple Sclerosis Diagnosis and Treatment Challenges. J Clin Med 2023; 12:4274. [PMID: 37445309 DOI: 10.3390/jcm12134274] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Revised: 06/19/2023] [Accepted: 06/21/2023] [Indexed: 07/15/2023] Open
Abstract
Multiple sclerosis (MS) is a chronic autoimmune disease that impacts the central nervous system and can result in disability. Although the prevalence of MS has increased in India, diagnosis and treatment continue to be difficult due to several factors. The present study examines the difficulties in detecting and treating multiple sclerosis in India. A lack of MS knowledge among healthcare professionals and the general public, which delays diagnosis and treatment, is one of the significant issues. Inadequate numbers of neurologists and professionals with knowledge of MS management also exacerbate the situation. In addition, MS medications are expensive and not covered by insurance, making them inaccessible to most patients. Due to the absence of established treatment protocols and standards for MS care, India's treatment techniques vary. In addition, India's population diversity poses unique challenges regarding genetic variations, cellular and molecular abnormalities, and the potential for differing treatment responses. MS is more difficult to accurately diagnose and monitor due to a lack of specialized medical supplies and diagnostic instruments. Improved awareness and education among healthcare professionals and the general public, as well as the development of standardized treatment regimens and increased investment in MS research and infrastructure, are required to address these issues. By addressing these issues, it is anticipated that MS diagnosis and treatment in India will improve, leading to better outcomes for those affected by this chronic condition.
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Affiliation(s)
- Zuber Khan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, IK Gujral Punjab Technical University, Jalandhar 144603, India
| | - Ghanshyam Das Gupta
- Department of Pharmaceutics, ISF College of Pharmacy, IK Gujral Punjab Technical University, Jalandhar 144603, India
| | - Sidharth Mehan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, IK Gujral Punjab Technical University, Jalandhar 144603, India
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33
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Zhou R, Zhang H, He S, Li Y, Xu G, Huang J, Wang H, Wang Q, Li B, Wang X, Chen N, Li F, Li X, Liu M, Peng D. A Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD): study protocol for a randomized clinical trial and prognosis study. Trials 2023; 24:308. [PMID: 37143128 PMCID: PMC10161548 DOI: 10.1186/s13063-023-07317-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 04/19/2023] [Indexed: 05/06/2023] Open
Abstract
BACKGROUND Major depressive disorder (MDD) with atypical features, namely depression with atypical features (AFD), is one of the most common clinical specifiers of MDD, closely associated with bipolar disorder (BD). However, there is still a lack of clinical guidelines for the diagnosis, treatment, and prognosis of AFD. Our study mainly focuses on three issues about how to identify AFD, what is the appropriate individualized treatment for AFD, and what are the predictive biomarkers of conversion to BD. METHODS The Study of Individualized Diagnosis and Treatment for Depression with Atypical Features (iDoT-AFD) is a multicenter, prospective, open-label study consisting of a 12-week randomized controlled trial (RCT) and a continued follow-up until 4 years or reaching the study endpoint. It is enrolling 480 patients with AFD (120 per treatment arm), 100 patients with BD, and 100 healthy controls (HC). Multivariate dimension information is collected including clinical features, cognitive function, kynurenine pathway metabolomics, and multimodal magnetic resonance imaging (MRI) data. Firstly, multivariate informatics analyses are performed to recognize patients with AFD from participants including the first-episode and recurrent atypical depression, patients with BD, and patients with HC. Secondly, patients with atypical depression are randomly allocated to one of the four treatment groups including "single application of selective serotonin reuptake inhibitor (SSRI) or serotonin-noradrenaline reuptake inhibitor (SNRI)", "SSRI/SNRI combined with mood stabilizer," "SSRI/SNRI combined with quetiapine (≥ 150 mg/day)," or "treatment as usual (TAU)" and then followed up 12 weeks to find out the optimized treatment strategies. Thirdly, patients with atypical depression are followed up until 4 years or switching to BD, to explore the risk factors of conversion from atypical depression to BD and eventually build the risk warning model of conversion to BD. DISCUSSION The first enrolment was in August 2019. The iDoT-AFD study explores the clinical and biological markers for the diagnosis, treatment, and prognosis of AFD and further provides evidence for clinical guidelines of AFD. TRIAL REGISTRATION ClinicalTrials.gov NCT04209166. Registered on December 19, 2019.
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Affiliation(s)
- Rubai Zhou
- Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wan Ping Road, Shanghai, 200030, China
| | - Huifeng Zhang
- Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wan Ping Road, Shanghai, 200030, China
| | - Shen He
- Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wan Ping Road, Shanghai, 200030, China
| | - Yi Li
- Wuhan Mental Health Center, Wuhan, Hubei, China
| | - Guiyun Xu
- Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jinsong Huang
- Dalian Seventh People's Hospital, Dalian, Liaoning, China
| | - Huaning Wang
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Qian Wang
- School of Biomedical Engineering, ShanghaiTech University, Shanghai, China
| | - Biao Li
- Wuhan Mental Health Center, Wuhan, Hubei, China
| | | | - Ningning Chen
- Department of Affective Disorders, Guangzhou Brain Hospital, Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Fang Li
- Dalian Seventh People's Hospital, Dalian, Liaoning, China
| | - Xiaosa Li
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China
| | - Mengjun Liu
- School of Biomedical Engineering, Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China
| | - Daihui Peng
- Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 600 South Wan Ping Road, Shanghai, 200030, China.
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Medina-Rodriguez EM, Watson J, Reyes J, Trivedi M, Beurel E. Th17 cells sense microbiome to promote depressive-like behaviors. MICROBIOME 2023; 11:92. [PMID: 37106375 PMCID: PMC10142784 DOI: 10.1186/s40168-022-01428-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 11/16/2022] [Indexed: 05/12/2023]
Abstract
BACKGROUND Microbiome alterations have been associated with depression, and fecal transfer of depressed patients' microbiomes is sufficient to enhance despair behaviors in rodents. Yet little is known about the potential mechanisms, whereby microbes modulate depressive-like behaviors. RESULTS In this study, we showed that certain bacteria known to induce Th17 cells are increased in depressed patients and mice exhibiting learned helplessness. Fecal transfers of human depressed patients' microbiomes into germ-free-like mice were sufficient to decrease sociability and increased susceptibility to the learned helplessness paradigm, confirming that the microbiome is sufficient to confer depressive-like behaviors. This microbial effect was dependent on the presence of Th17 cells in the recipient, as germ-free-like recipient mice deficient in Th17 cells were resistant to the behavioral changes induced by the microbiome of depressed patients. CONCLUSION Altogether, these findings suggest a crucial role of the microbiome/Th17 cell axis in regulating depressive-like behaviors. Video Abstract.
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Affiliation(s)
- Eva M Medina-Rodriguez
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Jowan Watson
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Juliana Reyes
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA
| | - Madhukar Trivedi
- Department of Psychiatry, Center for Depression Research and Clinical Care, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
| | - Eléonore Beurel
- Department of Psychiatry and Behavioral Sciences, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
- Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
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Integrating functional neuroimaging and serum proteins improves the diagnosis of major depressive disorder. J Affect Disord 2023; 325:421-428. [PMID: 36642308 DOI: 10.1016/j.jad.2023.01.034] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 12/25/2022] [Accepted: 01/08/2023] [Indexed: 01/15/2023]
Abstract
BACKGROUND The lack of effective objective diagnostic biomarkers for major depressive disorder (MDD) leads to high misdiagnosis. Compared with healthy controls (HC), abnormal brain functions and protein levels are often observed in MDD. However, it is unclear whether combining these changed multidimensional indicators could help improve the diagnosis of MDD. METHODS Sixty-three MDD and eighty-one HC subjects underwent resting-state fMRI scans, among whom 37 MDD and 45 HC provided blood samples. Amplitudes of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and serum levels of brain-derived neurotrophic factor (BDNF), cortisol, and multiple cytokines were measured and put into the linear discriminant analysis (LDA) to construct corresponding MDD diagnostic models. The area under the receiver operating characteristic curve (AUC) of 5-fold cross-validation was calculated to evaluate each model's performance. RESULTS Compared with HC, MDD patients' spontaneous brain activity, serum BDNF, cortisol, interleukin (IL)-4, IL-6, and IL-10 levels changed significantly. The combinations of unidimensional multi-indicator had better diagnostic performance than a single one. The model consisted of multidimensional multi-indicator further exhibited conspicuously superior diagnostic efficiency than those constructed with unidimensional multi-indicator, and its AUC, sensitivity, specificity, and accuracy of 5-fold cross-validation were 0.99, 92.0 %, 100.0 %, and 96.3 %, respectively. LIMITATIONS This cross-sectional study consists of relatively small samples and should be replicated in larger samples with follow-up data to optimize the diagnostic model. CONCLUSIONS MDD patients' neuroimaging features and serum protein levels significantly changed. The model revealed by LDA could diagnose MDD with high accuracy, which may serve as an ideal diagnostic biomarker for MDD.
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Inhibition of Microglial GSK3β Activity Is Common to Different Kinds of Antidepressants: A Proposal for an In Vitro Screen to Detect Novel Antidepressant Principles. Biomedicines 2023; 11:biomedicines11030806. [PMID: 36979785 PMCID: PMC10045655 DOI: 10.3390/biomedicines11030806] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 02/17/2023] [Accepted: 03/04/2023] [Indexed: 03/09/2023] Open
Abstract
Depression is a major public health concern. Unfortunately, the present antidepressants often are insufficiently effective, whilst the discovery of more effective antidepressants has been extremely sluggish. The objective of this review was to combine the literature on depression with the pharmacology of antidepressant compounds, in order to formulate a conceivable pathophysiological process, allowing proposals how to accelerate the discovery process. Risk factors for depression initiate an infection-like inflammation in the brain that involves activation microglial Toll-like receptors and glycogen synthase kinase-3β (GSK3β). GSK3β activity alters the balance between two competing transcription factors, the pro-inflammatory/pro-oxidative transcription factor NFκB and the neuroprotective, anti-inflammatory and anti-oxidative transcription factor NRF2. The antidepressant activity of tricyclic antidepressants is assumed to involve activation of GS-coupled microglial receptors, raising intracellular cAMP levels and activation of protein kinase A (PKA). PKA and similar kinases inhibit the enzyme activity of GSK3β. Experimental antidepressant principles, including cannabinoid receptor-2 activation, opioid μ receptor agonists, 5HT2 agonists, valproate, ketamine and electrical stimulation of the Vagus nerve, all activate microglial pathways that result in GSK3β-inhibition. An in vitro screen for NRF2-activation in microglial cells with TLR-activated GSK3β activity, might therefore lead to the detection of totally novel antidepressant principles with, hopefully, an improved therapeutic efficacy.
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Ahmed T, Qassem M, Kyriacou PA. Measuring stress: a review of the current cortisol and dehydroepiandrosterone (DHEA) measurement techniques and considerations for the future of mental health monitoring. Stress 2023; 26:29-42. [PMID: 36625303 DOI: 10.1080/10253890.2022.2164187] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Psychological stress and its inevitable trajectory toward mental health deteriorations such as clinical and major depression has become an unprecedented global burden. The diagnostic procedures involved in the characterization of mental illnesses commonly follow qualitative and subjective measures of stress, often leading to greater socioeconomic burdens due to misdiagnosis and poor understanding of the severity of such illnesses, further fueled by the stigmatization surrounding mental health. In recent years, the application of cortisol and stress hormone measurements has given rise to an alternative, quantifiable approach for the psychological evaluation of stress and depression. This review comprehensively evaluates the current state-of-the-art technology for measuring cortisol and dehydroepiandrosterone (DHEA) and their applications within stress monitoring in humans. Recent advancements in these fields have shown the importance of measuring stress hormones for the characterization of stress manifestation within the human body, and its relevance in mental health decline. Preliminary results from studies considering multimodal approaches toward stress monitoring have showcased promising developments, emphasizing the need for further technological advancement in this field, which consider both neurochemical and physiological biomarkers of stress, for global benefit.
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Affiliation(s)
- Tashfia Ahmed
- Research Centre of Biomedical Engineering, University of London, London, UK
| | - Meha Qassem
- Research Centre of Biomedical Engineering, University of London, London, UK
| | - Panicos A Kyriacou
- Research Centre of Biomedical Engineering, University of London, London, UK
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Suseelan S, Pinna G. Heterogeneity in major depressive disorder: The need for biomarker-based personalized treatments. Adv Clin Chem 2022; 112:1-67. [PMID: 36642481 DOI: 10.1016/bs.acc.2022.09.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Major Depressive Disorder (MDD) or depression is a pathological mental condition affecting millions of people worldwide. Identification of objective biological markers of depression can provide for a better diagnostic and intervention criteria; ultimately aiding to reduce its socioeconomic health burden. This review provides a comprehensive insight into the major biomarker candidates that have been implicated in depression neurobiology. The key biomarker categories are covered across all the "omics" levels. At the epigenomic level, DNA-methylation, non-coding RNA and histone-modifications have been discussed in relation to depression. The proteomics system shows great promise with inflammatory markers as well as growth factors and neurobiological alterations within the endocannabinoid system. Characteristic lipids implicated in depression together with the endocrine system are reviewed under the metabolomics section. The chapter also examines the novel biomarkers for depression that have been proposed by studies in the microbiome. Depression affects individuals differentially and explicit biomarkers identified by robust research criteria may pave the way for better diagnosis, intervention, treatment, and prediction of treatment response.
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Affiliation(s)
- Shayam Suseelan
- The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States
| | - Graziano Pinna
- The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States; UI Center on Depression and Resilience (UICDR), Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States.
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Siddique R, Awan FM, Nabi G, Khan S, Xue M. Chronic jet lag-like conditions dysregulate molecular profiles of neurological disorders in nucleus accumbens and prefrontal cortex. Front Neuroinform 2022; 16:1031448. [PMID: 36582489 PMCID: PMC9792783 DOI: 10.3389/fninf.2022.1031448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 11/22/2022] [Indexed: 12/14/2022] Open
Abstract
Background Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease including, cancer, psychiatric, and related brain diseases. Results In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice's brain. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the quantitative PCR (qPCR) analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL. Conclusion Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.
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Affiliation(s)
- Rabeea Siddique
- Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China,Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou, Henan, China
| | - Faryal Mehwish Awan
- Department of Medical Lab Technology, The University of Haripur, Haripur, Pakistan
| | - Ghulam Nabi
- Institute of Nature Conservation, Polish Academy of Sciences, Kraków, Poland
| | - Suliman Khan
- Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China,Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou, Henan, China,Department of Medical Lab Technology, The University of Haripur, Haripur, Pakistan,*Correspondence: Suliman Khan, ;
| | - Mengzhou Xue
- Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China,Henan Medical Key Laboratory of Translational Cerebrovascular Diseases, Zhengzhou, Henan, China,Mengzhou Xue,
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Nunes FDD, Ferezin LP, Pereira SC, Figaro-Drumond FV, Pinheiro LC, Menezes IC, Baes CVW, Coeli-Lacchini FB, Tanus-Santos JE, Juruena MF, Lacchini R. The Association of Biochemical and Genetic Biomarkers in VEGF Pathway with Depression. Pharmaceutics 2022; 14:pharmaceutics14122757. [PMID: 36559251 PMCID: PMC9785844 DOI: 10.3390/pharmaceutics14122757] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/29/2022] [Accepted: 12/05/2022] [Indexed: 12/13/2022] Open
Abstract
VEGF is an important neurotrophic and vascular factor involved in mental disorders. The objective of this study was to verify the effect of genetic polymorphisms in the VEGF pathway on the risk for depression, symptom intensity, and suicide attempts. To examine the association between the VEGF pathway and depression, we genotyped polymorphisms and measured the plasma concentrations of VEGF, KDR, and FLT1 proteins. The participants were 160 patients with depression and 114 healthy controls. The questionnaires that assessed the clinical profile of the patients were the MINI-International Neuropsychiatric Interview, GRID-HAMD21, CTQ, BSI, and the number of suicide attempts. Genotyping of participants was performed using the real-time PCR and protein measurements were performed using the enzyme-linked immunosorbent assay (ELISA). VEGF and its inhibitors were reduced in depression. Individuals with depression and displaying the homozygous AA of the rs699947 polymorphism had higher plasma concentrations of VEGF (p-value = 0.006) and were associated with a greater number of suicide attempts (p-value = 0.041). Individuals with depression that were homozygous for the G allele of the FLT1 polymorphism rs7993418 were associated with lower symptom severity (p-value = 0.040). Our results suggest that VEGF pathway polymorphisms are associated with the number of suicide attempts and the severity of depressive symptoms.
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Affiliation(s)
- Fernanda Daniela Dornelas Nunes
- Department of Psychiatric Nursing and Human Sciences, Ribeirão Preto College of Nursing, University of Sao Paolo, Sao Paulo 14040-902, Brazil
| | - Letícia Perticarrara Ferezin
- Department of Psychiatric Nursing and Human Sciences, Ribeirão Preto College of Nursing, University of Sao Paolo, Sao Paulo 14040-902, Brazil
| | - Sherliane Carla Pereira
- Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paolo 14049-900, Brazil
| | - Fernanda Viana Figaro-Drumond
- Department of Psychiatric Nursing and Human Sciences, Ribeirão Preto College of Nursing, University of Sao Paolo, Sao Paulo 14040-902, Brazil
| | - Lucas Cézar Pinheiro
- Department of Psychiatric Nursing and Human Sciences, Ribeirão Preto College of Nursing, University of Sao Paolo, Sao Paulo 14040-902, Brazil
| | - Itiana Castro Menezes
- Department of Neuroscience and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo 14049-900, Brazil
| | - Cristiane von Werne Baes
- Department of Neuroscience and Behavior, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo 14049-900, Brazil
| | - Fernanda Borchers Coeli-Lacchini
- Blood Center Foundation, Clinics Hospital of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paolo 14051-060, Brazil
| | - José Eduardo Tanus-Santos
- Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paolo 14049-900, Brazil
| | - Mário Francisco Juruena
- Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London and South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, Monks Orchard Road, Beckenham BR3 3BX, UK
| | - Riccardo Lacchini
- Department of Psychiatric Nursing and Human Sciences, Ribeirão Preto College of Nursing, University of Sao Paolo, Sao Paulo 14040-902, Brazil
- Correspondence: ; Tel.: +16-33153447
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Zhang X, Zhang Z, Diao W, Zhou C, Song Y, Wang R, Luo X, Liu G. Early-diagnosis of major depressive disorder: From biomarkers to point-of-care testing. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Kotzaeroglou A, Tsamesidis I. The Role of Equilibrium between Free Radicals and Antioxidants in Depression and Bipolar Disorder. MEDICINES (BASEL, SWITZERLAND) 2022; 9:57. [PMID: 36422118 PMCID: PMC9694953 DOI: 10.3390/medicines9110057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 11/04/2022] [Accepted: 11/07/2022] [Indexed: 06/16/2023]
Abstract
Background: Increasing evidence suggests that the presence of oxidative stress and disorders of the antioxidant defense system are involved in a wide range of neuropsychiatric disorders, such as bipolar disorder, schizophrenia and major depression, but the exact mechanism remains unknown. This review focuses on a better appreciation of the contribution of oxidative stress to depression and bipolar disorder. Methods: This review was conducted by extracting information from other research and review studies, as well as other meta-analyses, using two search engines, PubMed and Google Scholar. Results: As far as depression is concerned, there is agreement among researchers on the association between oxidative stress and antioxidants. In bipolar disorder, however, most of them observe strong lipid peroxidation in patients, while regarding antioxidant levels, opinions are divided. Nevertheless, in recent years, it seems that on depression, there are mainly meta-analyses and reviews, rather than research studies, unlike on bipolar disorder. Conclusions: Undoubtedly, this review shows that there is an association among oxidative stress, free radicals and antioxidants in both mental disorders, but further research should be performed on the exact role of oxidative stress in the pathophysiology of these diseases.
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Affiliation(s)
- Anastasia Kotzaeroglou
- Department of Biomedical Sciences, Metropolitan College, Campus of Thessaloniki, 54624 Thessaloniki, Greece
| | - Ioannis Tsamesidis
- Department of Biomedical Sciences, Metropolitan College, Campus of Thessaloniki, 54624 Thessaloniki, Greece
- School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
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Microalgae extract induces antidepressant-like activity via neuroinflammation regulation and enhances the neurotransmitter system. Food Chem Toxicol 2022; 170:113508. [DOI: 10.1016/j.fct.2022.113508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 10/15/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022]
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Bayes J, Schloss J, Sibbritt D. The effect of a Mediterranean diet on the symptoms of depression in young males (the "AMMEND: A Mediterranean Diet in MEN with Depression" study): a randomized controlled trial. Am J Clin Nutr 2022; 116:572-580. [PMID: 35441666 DOI: 10.1093/ajcn/nqac106] [Citation(s) in RCA: 65] [Impact Index Per Article: 21.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 04/05/2022] [Accepted: 04/18/2022] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Depression is a common mental health condition that affects 1 in 8 males each year, especially young adults. Young adulthood offers an opportunity for early dietary interventions, with research suggesting that a Mediterranean diet (MD) could be beneficial in treating depression. OBJECTIVES This study aimed to determine if an MD can improve depressive symptoms in young males with clinical depression. METHODS A 12-wk, parallel-group, open-label, randomized controlled trial was conducted to assess the effect of an MD intervention in the treatment of moderate to severe depression in young males (18-25 y). Befriending therapy was chosen for the control group. Assessments were taken at baseline, week 6, and week 12. MD adherence was measured with the Mediterranean Diet Adherence Score (MEDAS). The primary outcome measure was the Beck Depression Inventory Scale-version II (BDI-II) and secondary outcome was quality of life (QoL). RESULTS A total of 72 participants completed the study. After 12 wk, the MEDAS scores were significantly higher in the MD group compared with the befriending group (mean difference: 7.8; 95% CI: 7.23, 8.37; P < 0.001). The mean change in BDI-II score was significantly higher in the MD group compared with the befriending group at week 12 (mean difference: 14.4; 95% CI: 11.41, 17.39; P < 0.001). The mean change in QoL score was also significantly higher in the MD group compared with the befriending group at week 12 (mean difference: 12.7; 95% CI: 7.92, 17.48; P < 0.001). CONCLUSIONS Our results demonstrate that compared with befriending, an MD intervention leads to significant increases in MEDAS, decreases in BDI-II score, and increases in QoL scores. These results highlight the important role of nutrition for the treatment of depression and should inform advice given by clinicians to this specific demographic population.The trial was registered with Australia and New Zealand Clinical Trials Registry (trial ID ACTRN12619001545156) and has also been registered with the WHO International Clinical Trials Registry Platform (Universal Trial Number U1111-1242-5215).
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Affiliation(s)
- Jessica Bayes
- School of Public Health, Faculty of Health, University of Technology Sydney, New South Wales, Australia
| | - Janet Schloss
- National Centre for Naturopathic Medicine, Southern Cross University, Lismore, New South Wales, Australia
| | - David Sibbritt
- School of Public Health, Faculty of Health, University of Technology Sydney, New South Wales, Australia
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Kim JM, Kang HJ, Kim JW, Jhon M, Choi W, Lee JY, Kim SW, Shin IS, Kim MG, Stewart R. Prospective associations of multimodal serum biomarkers with 12-week and 12-month remission in patients with depressive disorders receiving stepwise psychopharmacotherapy. Brain Behav Immun 2022; 104:65-73. [PMID: 35618226 DOI: 10.1016/j.bbi.2022.05.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 05/13/2022] [Accepted: 05/20/2022] [Indexed: 11/26/2022] Open
Abstract
Prognostic biomarkers for depression treatment outcomes have yet to be elucidated. This study sought to evaluate whether a multi-modal serum biomarker panel was prospectively associated with 12-week and 12-month remission in outpatients with depressive disorders receiving stepwise psychopharmacotherapy. At baseline, 14 serum biomarkers and socio-demographic/clinical characteristics were evaluated in 1094 patients. They received initial antidepressant monotherapy followed, as required by a protocol of successive alternative pharmacological strategies administered in 3-week steps during the acute (3-12 week) phase (N = 1086), and in 3-month steps during the continuation (6-12 month) phase (N = 884). Remission was defined as a Hamilton Depression Rating Scale score of ≤ 7. Remission was achieved in 490 (45.1%) over the 12-week, and in 625 (70.7%) over the 12-month, treatment periods. Combination scores of four serum biomarkers (high-sensitivity C-reactive protein, interleukin-1 beta, interleukin-6, and leptin) were prospectively associated with 12-week remission; and four (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, and brain-derived neurotrophic factor) were prospectively associated with 12-month remission in a clear gradient manner (P-values < 0.001) and after adjustment for relevant covariates. These associations were evident after the Step 1 treatment monotherapy but weakened with increasing treatment steps, falling below statistical significance after 4 + treatment steps. Application of combined multiple serum biomarkers, particularly on inflammatory markers, could improve predictability of remission at acute and continuation treatment phases for depressive disorders. Patients with unfavourable biomarkers might require alternative treatment regimes for better outcomes.
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Affiliation(s)
- Jae-Min Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea.
| | - Hee-Ju Kang
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Ju-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Min Jhon
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Wonsuk Choi
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
| | - Ju-Yeon Lee
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Sung-Wan Kim
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Il-Seon Shin
- Department of Psychiatry, Chonnam National University Medical School, Gwangju, Korea
| | - Min-Gon Kim
- Gwangju Institute of Science and Technology, Gwangju, South Korea
| | - Robert Stewart
- Department of Psychological Medicine, King's College London (Institute of Psychiatry, Psychology and Neuroscience), UK; South London and Maudsley NHS Foundation Trust, London, UK.
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Prognostic Significance of Blood-Based Baseline Biomarkers in Treatment-Resistant Depression: A Literature Review of Available Studies on Treatment Response. Brain Sci 2022; 12:brainsci12070940. [PMID: 35884746 PMCID: PMC9317233 DOI: 10.3390/brainsci12070940] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 07/16/2022] [Accepted: 07/17/2022] [Indexed: 12/04/2022] Open
Abstract
Major depressive disorder is a leading cause of disability worldwide and a major contributor to the overall global burden of disease. While there are several options for antidepressant treatment, only about 40–60% of patients respond to initial monotherapy, while 30–40% of patients may even show resistance to treatment. This article offers a narrative review of those studies evaluating the predictive properties of various blood-based baseline biomarkers regarding treatment responses to the pharmacological, stimulation, or behavioral treatment of patients with treatment-resistant depression (TRD). Our results show that overall, there is only a very limited number of studies assessing baseline peripheral biomarkers regarding treatment response in TRD. Although there is some evidence for the predictive significance of particular biomarkers (e.g., IL-6, CRP, BDNF), the majority of the results are either single-study reports or studies with conflicting results. This may contribute to the wide variety of treatment protocols and different TRD definition criteria, the small number of patients included, and the existence of different biological phenotypes of the disorder used within the various studies. Taken together, there does not yet appear to be any specific baseline peripheral biomarker with sufficient discriminative predictive validity that can be used in the routine clinical practice of TRD. The discovery of new biomarkers and the better clinical characterization of known biomarkers could support the better classification and staging of TRD, the development of personalized treatment algorithms with higher rates of remission and fewer side effects, and the development of new precision drugs for specific subgroups of patients.
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Lee B, Shin E, Song I, Chang B. Depression in Adolescence and Brain-Derived Neurotrophic Factor. Front Mol Neurosci 2022; 15:947192. [PMID: 35875661 PMCID: PMC9302599 DOI: 10.3389/fnmol.2022.947192] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 06/20/2022] [Indexed: 12/27/2022] Open
Abstract
The incidence of depression among adolescents has been rapidly increasing in recent years. Environmental and genetic factors have been identified as important risk factors for adolescent depression. However, the mechanisms underlying the development of adolescent depression that are triggered by these risk factors are not well understood. Clinical and preclinical studies have focused more on adult depression, and differences in depressive symptoms between adolescents and adults make it difficult to adequately diagnose and treat adolescent depression. Brain-derived neurotrophic factor (BDNF) is known to play a critical role in the pathophysiology of many psychiatric disorders, including depression. However, there are still few studies on adolescent depression. Therefore, in this review paper, the causes and treatment of adolescent depression and the function of BDNF are investigated.
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Hersey M, Reneaux M, Berger SN, Mena S, Buchanan AM, Ou Y, Tavakoli N, Reagan LP, Clopath C, Hashemi P. A tale of two transmitters: serotonin and histamine as in vivo biomarkers of chronic stress in mice. J Neuroinflammation 2022; 19:167. [PMID: 35761344 PMCID: PMC9235270 DOI: 10.1186/s12974-022-02508-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Accepted: 06/01/2022] [Indexed: 12/12/2022] Open
Abstract
Background Stress-induced mental illnesses (mediated by neuroinflammation) pose one of the world’s most urgent public health challenges. A reliable in vivo chemical biomarker of stress would significantly improve the clinical communities’ diagnostic and therapeutic approaches to illnesses, such as depression. Methods Male and female C57BL/6J mice underwent a chronic stress paradigm. We paired innovative in vivo serotonin and histamine voltammetric measurement technologies, behavioral testing, and cutting-edge mathematical methods to correlate chemistry to stress and behavior. Results Inflammation-induced increases in hypothalamic histamine were co-measured with decreased in vivo extracellular hippocampal serotonin in mice that underwent a chronic stress paradigm, regardless of behavioral phenotype. In animals with depression phenotypes, correlations were found between serotonin and the extent of behavioral indices of depression. We created a high accuracy algorithm that could predict whether animals had been exposed to stress or not based solely on the serotonin measurement. We next developed a model of serotonin and histamine modulation, which predicted that stress-induced neuroinflammation increases histaminergic activity, serving to inhibit serotonin. Finally, we created a mathematical index of stress, Si and predicted that during chronic stress, where Si is high, simultaneously increasing serotonin and decreasing histamine is the most effective chemical strategy to restoring serotonin to pre-stress levels. When we pursued this idea pharmacologically, our experiments were nearly identical to the model’s predictions. Conclusions This work shines the light on two biomarkers of chronic stress, histamine and serotonin, and implies that both may be important in our future investigations of the pathology and treatment of inflammation-induced depression. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-022-02508-9.
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Affiliation(s)
- Melinda Hersey
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA.,Department of Pharmacology, Physiology, & Neuroscience, University of South Carolina School of Medicine, Columbia, SC, 29209, USA
| | - Melissa Reneaux
- Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK
| | - Shane N Berger
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Sergio Mena
- Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK
| | - Anna Marie Buchanan
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Yangguang Ou
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Navid Tavakoli
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA
| | - Lawrence P Reagan
- Department of Pharmacology, Physiology, & Neuroscience, University of South Carolina School of Medicine, Columbia, SC, 29209, USA.,Columbia VA Health Care Systems, Columbia, SC, 29208, USA
| | - Claudia Clopath
- Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK
| | - Parastoo Hashemi
- Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC, 29208, USA. .,Department of Bioengineering, Imperial College London, London, SW7 2AZ, UK.
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Bobo WV, Grossardt BR, Virani S, St Sauver JL, Boyd CM, Rocca WA. Association of Depression and Anxiety With the Accumulation of Chronic Conditions. JAMA Netw Open 2022; 5:e229817. [PMID: 35499825 PMCID: PMC9062691 DOI: 10.1001/jamanetworkopen.2022.9817] [Citation(s) in RCA: 48] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
IMPORTANCE Longitudinal associations between comorbid depression and anxiety with the accumulation of chronic illnesses are unclear, and questions remain about the contributions associated with each condition in the increasing prevalence of multimorbidity. OBJECTIVE To compare the risk and rate of accumulating chronic conditions in people with depression, anxiety, and comorbid depression and anxiety vs individuals with neither depression nor anxiety. DESIGN, SETTING, AND PARTICIPANTS This cohort study used the Rochester Epidemiology Project medical records-linkage system to identify residents of Olmsted County, Minnesota, from January 1, 2005, to December 31, 2014, with follow-up ending December 31, 2017. The sample was divided into cohorts anchored at birthday ages of 20, 40, and 60 years. Individuals were classified at anchoring birthday age as having depression alone, anxiety alone, comorbid depression and anxiety, or neither depression nor anxiety (reference group), using electronically extracted diagnosis codes from the International Classification of Diseases, Ninth Revision (ICD-9) in the 5 years before each anchoring birthday. Data were analyzed from August 2020 through November 2021. EXPOSURES Depression alone, anxiety alone, comorbid depression and anxiety, or neither depression nor anxiety (reference group). MAIN OUTCOMES AND MEASURES The main outcome was sex-specific risk, calculated as hazard ratios (HRs) and rates of accumulation, calculated as mean annual incidence rates per 100 person-years, of 15 common chronic conditions within each birthday age cohort through the end of study. RESULTS Among the 40 360 individuals included across all 3 age cohorts, 21 516 (53.3%) were women. After balancing cohorts on race, Hispanic ethnicity, education level, body mass index, smoking status, and calendar year at index birthday, the risk of accumulating chronic conditions was significantly increased among women with depression alone (cohort aged 20 years: HR, 1.20 [95% CI, 1.02-1.42]; cohort aged 40 years: HR, 1.20 [95% CI, 1.10-1.31]; cohort aged 60 years: HR, 1.09 [95% CI, 1.02-1.16]) and women with comorbid depression and anxiety (cohort aged 20 years: HR, 1.60 [95% CI, 1.28-1.99]; cohort aged 40 years: HR, 1.41 [95% CI, 1.21-1.65]; cohort aged 60 years: HR, 1.29 [95% CI, 1.15-1.44]) compared with referent women in the same birthday cohorts and in men with comorbid depression and anxiety compared with referent men in the cohort aged 20 years (HR, 1.77 [95% CI, 1.08-2.91]). For women, the rates of accumulation of conditions were significantly higher across birthday cohorts in the comorbid depression and anxiety group compared with the depression alone group (eg, cohort aged 20 years: difference, 1.2 [95% CI, 0.2-2.1] per 100 person-years) and reference group (eg, cohort aged 20 years: difference, 1.7 [95% CI, 0.9-2.6] per 100 person-years). For men, compared with the reference group, the rates of accumulation of conditions were significantly higher in men with comorbid depression and anxiety in the cohort aged 20 years (difference, 1.4 [95% CI, 0.1-2.6] per 100 person-years) and in men with depression in the cohort aged 40 years (difference, 2.0 [95% CI, 0.8-3.2] per 100 person-years). CONCLUSIONS AND RELEVANCE In this cohort study, the risk of accumulating chronic conditions was increased with depression and comorbid depression and anxiety in women across the age span and in younger men with comorbid depression and anxiety. Compared with women without depression or anxiety, there was a more rapid rate of accumulation of chronic conditions in women with depression and anxiety individually and an even higher rate when depression and anxiety cooccurred.
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Affiliation(s)
- William V. Bobo
- Department of Psychiatry and Psychology, Mayo Clinic Florida, Jacksonville
| | - Brandon R. Grossardt
- Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
| | - Sanya Virani
- Department of Psychiatry and Human Behavior, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island
| | - Jennifer L. St Sauver
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
- The Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota
| | - Cynthia M. Boyd
- Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Walter A. Rocca
- Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, Minnesota
- Department of Neurology, Mayo Clinic, Rochester, Minnesota
- Women’s Health Research Center, Mayo Clinic, Rochester, Minnesota
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50
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Kim SJ, Woo Y, Kim HJ, Goo BS, Nhung TTM, Lee SA, Suh BK, Mun DJ, Kim JH, Park SK. Retinoic acid-induced protein 14 controls dendritic spine dynamics associated with depressive-like behaviors. eLife 2022; 11:77755. [PMID: 35467532 PMCID: PMC9068211 DOI: 10.7554/elife.77755] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/24/2022] [Indexed: 11/24/2022] Open
Abstract
Dendritic spines are the central postsynaptic machinery that determines synaptic function. The F-actin within dendritic spines regulates their dynamic formation and elimination. Rai14 is an F-actin-regulating protein with a membrane-shaping function. Here, we identified the roles of Rai14 for the regulation of dendritic spine dynamics associated with stress-induced depressive-like behaviors. Rai14-deficient neurons exhibit reduced dendritic spine density in the Rai14+/- mouse brain, resulting in impaired functional synaptic activity. Rai14 was protected from degradation by complex formation with Tara, and accumulated in the dendritic spine neck, thereby enhancing spine maintenance. Concurrently, Rai14 deficiency in mice altered gene expression profile relevant to depressive conditions and increased depressive-like behaviors. Moreover, Rai14 expression was reduced in the prefrontal cortex of the mouse stress model, which was blocked by antidepressant treatment. Thus, we propose that Rai14-dependent regulation of dendritic spines may underlie the plastic changes of neuronal connections relevant to depressive-like behaviors.
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Affiliation(s)
- Soo Jeong Kim
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Youngsik Woo
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Hyun Jin Kim
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Bon Seong Goo
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Truong Thi My Nhung
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Seol-Ae Lee
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Bo Kyoung Suh
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Dong Jin Mun
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Joung-Hun Kim
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Sang Ki Park
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
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