Pub Date : 2025-09-08DOI: 10.1038/s44220-025-00496-2
Alec J. Jamieson, Trevor Steward, Christopher G. Davey, Sevil Ince, James A. Agathos, Bradford A. Moffat, Rebecca K. Glarin, Kim L. Felmingham, Ben J. Harrison
Depressive and anxiety disorders are characterized by altered connectivity within and between the default mode network (DMN) and salience network. Basal forebrain subdivisions, critical for regulating network activity, remain understudied across these conditions. To address this gap, we analyzed 7-Tesla resting-state functional magnetic resonance imaging data from a transdiagnostic sample (n = 70), primarily with depressive and anxiety disorders, and healthy controls (n = 77). We used spectral dynamic causal modeling to assess effective connectivity between the medial septum/diagonal band (Ch1–3), nucleus basalis of Meynert (Ch4), ventral pallidum, and DMN and salience network. Healthy participants showed excitatory connectivity from Ch1–3 to the DMN and from Ch4 to the anterior insula. By contrast, clinical participants exhibited greater inhibitory Ch4 to DMN connectivity and increased excitatory connectivity from Ch4 to the anterior insula. Widespread Ch4 connectivity dysfunction may implicate the cholinergic system as a mechanistic and therapeutic target for depressive and anxiety disorders. Using 7T resting-state functional MRI data, the authors investigate the effective connectivity of basal forebrain areas in a transdiagnostic sample of patients with anxiety and depression and healthy controls.
{"title":"Altered basal forebrain regulation of intrinsic brain networks in depressive and anxiety disorders","authors":"Alec J. Jamieson, Trevor Steward, Christopher G. Davey, Sevil Ince, James A. Agathos, Bradford A. Moffat, Rebecca K. Glarin, Kim L. Felmingham, Ben J. Harrison","doi":"10.1038/s44220-025-00496-2","DOIUrl":"10.1038/s44220-025-00496-2","url":null,"abstract":"Depressive and anxiety disorders are characterized by altered connectivity within and between the default mode network (DMN) and salience network. Basal forebrain subdivisions, critical for regulating network activity, remain understudied across these conditions. To address this gap, we analyzed 7-Tesla resting-state functional magnetic resonance imaging data from a transdiagnostic sample (n = 70), primarily with depressive and anxiety disorders, and healthy controls (n = 77). We used spectral dynamic causal modeling to assess effective connectivity between the medial septum/diagonal band (Ch1–3), nucleus basalis of Meynert (Ch4), ventral pallidum, and DMN and salience network. Healthy participants showed excitatory connectivity from Ch1–3 to the DMN and from Ch4 to the anterior insula. By contrast, clinical participants exhibited greater inhibitory Ch4 to DMN connectivity and increased excitatory connectivity from Ch4 to the anterior insula. Widespread Ch4 connectivity dysfunction may implicate the cholinergic system as a mechanistic and therapeutic target for depressive and anxiety disorders. Using 7T resting-state functional MRI data, the authors investigate the effective connectivity of basal forebrain areas in a transdiagnostic sample of patients with anxiety and depression and healthy controls.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 10","pages":"1202-1213"},"PeriodicalIF":8.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1038/s44220-025-00494-4
Sarah E. Woronko, Mohan Li, Jason N. Scott Jr, Manuel Kuhn, Shiba M. Esfand, Mario Bogdanov, Brian W. Boyle, Samantha R. Linton, Lauren R. Borchers, Peter Zhukovsky, Courtney Miller, Paula Bolton, Shuang Li, Robert C. Meisner, Ty Lees, Diego A. Pizzagalli
Historically, aperiodic neural activity (the 1/f exponent and offset of electroencephalogram power spectra) has been treated as neural noise. However, recent work has highlighted associations among aperiodic activity, aging, cognition and psychopathology. Although depression has been associated with cognitive deficits and dysregulation of excitatory–inhibitory neural mechanisms linked to aperiodic activity, so far, few studies have compared aperiodic activity in adults with and without depression, and none have evaluated aperiodic activity as a function of depressive chronicity. Here individuals with depression (n = 72) and healthy controls (n = 34) completed a resting state electroencephalography recording from which aperiodic activity estimates were extracted. We show significant group differences in aperiodic exponent and offset across central and posterior regions, such that, as hypothesized, these parameters were lower for depressed individuals relative to controls. Follow-up analyses clarified that this effect was driven by the number of lifetime depressive episodes experienced. Future research is needed to understand how depression heterogeneity impacts aperiodic activity. This research investigates aperiodic neural activity in depressed individuals versus healthy controls using resting state electroencephalography recordings. Findings reveal significant differences in aperiodic exponent and offset, influenced by lifetime depressive episodes, highlighting the relationship between depression heterogeneity and neural mechanisms.
{"title":"Alterations in aperiodic neural activity associated with major depressive disorder","authors":"Sarah E. Woronko, Mohan Li, Jason N. Scott Jr, Manuel Kuhn, Shiba M. Esfand, Mario Bogdanov, Brian W. Boyle, Samantha R. Linton, Lauren R. Borchers, Peter Zhukovsky, Courtney Miller, Paula Bolton, Shuang Li, Robert C. Meisner, Ty Lees, Diego A. Pizzagalli","doi":"10.1038/s44220-025-00494-4","DOIUrl":"10.1038/s44220-025-00494-4","url":null,"abstract":"Historically, aperiodic neural activity (the 1/f exponent and offset of electroencephalogram power spectra) has been treated as neural noise. However, recent work has highlighted associations among aperiodic activity, aging, cognition and psychopathology. Although depression has been associated with cognitive deficits and dysregulation of excitatory–inhibitory neural mechanisms linked to aperiodic activity, so far, few studies have compared aperiodic activity in adults with and without depression, and none have evaluated aperiodic activity as a function of depressive chronicity. Here individuals with depression (n = 72) and healthy controls (n = 34) completed a resting state electroencephalography recording from which aperiodic activity estimates were extracted. We show significant group differences in aperiodic exponent and offset across central and posterior regions, such that, as hypothesized, these parameters were lower for depressed individuals relative to controls. Follow-up analyses clarified that this effect was driven by the number of lifetime depressive episodes experienced. Future research is needed to understand how depression heterogeneity impacts aperiodic activity. This research investigates aperiodic neural activity in depressed individuals versus healthy controls using resting state electroencephalography recordings. Findings reveal significant differences in aperiodic exponent and offset, influenced by lifetime depressive episodes, highlighting the relationship between depression heterogeneity and neural mechanisms.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 10","pages":"1181-1190"},"PeriodicalIF":8.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-04DOI: 10.1038/s44220-025-00482-8
P. Murali Doraiswamy, Jon Andoni Duñabeitia, Carlos Rodriguez, Davangere P. Devanand
Digital cognitive twins could transform cognitive training into a personalized, clinically grounded and ethically governed modality for preventive use.
数字认知双胞胎可以将认知训练转变为一种个性化、临床基础和道德管理的预防模式。
{"title":"Digital cognitive twins in mental health","authors":"P. Murali Doraiswamy, Jon Andoni Duñabeitia, Carlos Rodriguez, Davangere P. Devanand","doi":"10.1038/s44220-025-00482-8","DOIUrl":"10.1038/s44220-025-00482-8","url":null,"abstract":"Digital cognitive twins could transform cognitive training into a personalized, clinically grounded and ethically governed modality for preventive use.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 10","pages":"1106-1108"},"PeriodicalIF":8.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-02DOI: 10.1038/s44220-025-00488-2
Eve Griffin, Selena O’Connell, Karl Andriessen, Ella Arensman, Fiona Tuomey
In this Comment, we describe the design, conduct and impact of a collaborative co-produced national study of suicide bereavement, including people with lived or living experience in the research. We highlight crucial gaps and challenges that need to be addressed.
{"title":"A co-produced national study of suicide bereavement: from experience to evidence","authors":"Eve Griffin, Selena O’Connell, Karl Andriessen, Ella Arensman, Fiona Tuomey","doi":"10.1038/s44220-025-00488-2","DOIUrl":"10.1038/s44220-025-00488-2","url":null,"abstract":"In this Comment, we describe the design, conduct and impact of a collaborative co-produced national study of suicide bereavement, including people with lived or living experience in the research. We highlight crucial gaps and challenges that need to be addressed.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 9","pages":"966-968"},"PeriodicalIF":8.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1038/s44220-025-00493-5
Paola Magioncalda, Abhishek Yadav, Matteo Martino
Schizophrenia is a chronic psychotic syndrome with elusive neurobiological underpinnings, partly owing to heterogeneity and inconsistency of existing data. Here, to address this, we conduct an umbrella review of meta-analyses of neuroimaging studies to identify the most consistent brain alterations in schizophrenia. A systematic PubMed search (until October 2022) identified 50 articles reporting high-resolution neuroimaging meta-analyses examining brain structure and function—gray matter, white matter, intrinsic activity and task-based activation—by comparing brain alterations between individuals with prodromal symptoms or schizophrenia (distinguishing early and chronic stages) and healthy controls, or by correlating brain alterations with schizophrenia symptoms. The synthesis uncovers a core spatiotemporal set of brain alterations. The prodromal stage shows gray matter deficits in midline structures (especially the medial prefrontal cortex), alongside central executive network dysfunction. The first-episode/early psychosis stage features additional gray matter damage to the operculum (insula, superior temporal gyrus and adjacent cortices) and white matter disruptions in fronto-temporal regions near the lateral ventricles (affecting the fornix, cingulum and long-range fasciculi), alongside default-mode network dysfunction. The chronic/deteriorative stage involves widespread alterations, prominently affecting the thalamus and lateral prefrontal cortex. Damage to opercular areas (especially the superior temporal gyrus/auditory cortex) correlates with auditory hallucinations, while default-mode network dysfunction correlates with delusions and hallucinations. These alterations may be limited to prototypical schizophrenia. Integrating these findings, we developed a conceptual framework that links the spatiotemporal pattern of brain alterations to pathophysiology and psychopathology, forming the basis for a working model of schizophrenia. In this umbrella review of meta-analyses of neuroimaging studies in schizophrenia, the authors identify a core pattern of brain alterations for prodromal, early and chronic stages, and propose a conceptual framework linking these brain alterations to the pathophysiology and psychopathology of the disorder.
{"title":"An umbrella review of neuroimaging studies and conceptual framework linking pathophysiology and psychopathology in schizophrenia","authors":"Paola Magioncalda, Abhishek Yadav, Matteo Martino","doi":"10.1038/s44220-025-00493-5","DOIUrl":"10.1038/s44220-025-00493-5","url":null,"abstract":"Schizophrenia is a chronic psychotic syndrome with elusive neurobiological underpinnings, partly owing to heterogeneity and inconsistency of existing data. Here, to address this, we conduct an umbrella review of meta-analyses of neuroimaging studies to identify the most consistent brain alterations in schizophrenia. A systematic PubMed search (until October 2022) identified 50 articles reporting high-resolution neuroimaging meta-analyses examining brain structure and function—gray matter, white matter, intrinsic activity and task-based activation—by comparing brain alterations between individuals with prodromal symptoms or schizophrenia (distinguishing early and chronic stages) and healthy controls, or by correlating brain alterations with schizophrenia symptoms. The synthesis uncovers a core spatiotemporal set of brain alterations. The prodromal stage shows gray matter deficits in midline structures (especially the medial prefrontal cortex), alongside central executive network dysfunction. The first-episode/early psychosis stage features additional gray matter damage to the operculum (insula, superior temporal gyrus and adjacent cortices) and white matter disruptions in fronto-temporal regions near the lateral ventricles (affecting the fornix, cingulum and long-range fasciculi), alongside default-mode network dysfunction. The chronic/deteriorative stage involves widespread alterations, prominently affecting the thalamus and lateral prefrontal cortex. Damage to opercular areas (especially the superior temporal gyrus/auditory cortex) correlates with auditory hallucinations, while default-mode network dysfunction correlates with delusions and hallucinations. These alterations may be limited to prototypical schizophrenia. Integrating these findings, we developed a conceptual framework that links the spatiotemporal pattern of brain alterations to pathophysiology and psychopathology, forming the basis for a working model of schizophrenia. In this umbrella review of meta-analyses of neuroimaging studies in schizophrenia, the authors identify a core pattern of brain alterations for prodromal, early and chronic stages, and propose a conceptual framework linking these brain alterations to the pathophysiology and psychopathology of the disorder.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 10","pages":"1241-1255"},"PeriodicalIF":8.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29DOI: 10.1038/s44220-025-00492-6
Ana Donnelly
In this Q&A, we speak to Lakshmi Vijayakumar, a psychiatrist, researcher and founder of SNEHA , a suicide-prevention organization in India. Over the past four decades, her work — from tackling youth suicides to shaping laws and working with refugees — has saved countless lives, mainly because of her unshakeable belief in change. Here she speaks candidly about her journey, the challenges of changing minds, and the urgency of treating suicide as both a mental health and social issue.
{"title":"Saving lives, one voice at a time","authors":"Ana Donnelly","doi":"10.1038/s44220-025-00492-6","DOIUrl":"10.1038/s44220-025-00492-6","url":null,"abstract":"In this Q&A, we speak to Lakshmi Vijayakumar, a psychiatrist, researcher and founder of SNEHA , a suicide-prevention organization in India. Over the past four decades, her work — from tackling youth suicides to shaping laws and working with refugees — has saved countless lives, mainly because of her unshakeable belief in change. Here she speaks candidly about her journey, the challenges of changing minds, and the urgency of treating suicide as both a mental health and social issue.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 9","pages":"961-962"},"PeriodicalIF":8.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29DOI: 10.1038/s44220-025-00487-3
Olivia Remes
{"title":"Understanding the ‘silent crisis’ of suicide in the construction industry and the way forward","authors":"Olivia Remes","doi":"10.1038/s44220-025-00487-3","DOIUrl":"10.1038/s44220-025-00487-3","url":null,"abstract":"","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 9","pages":"959-960"},"PeriodicalIF":8.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29DOI: 10.1038/s44220-025-00491-7
Daiane B. Machado
Despite decades of scientific advances, suicide remains a global public health challenge shaped by deep social, economic and cultural inequalities. Although substantial resources have been allocated to prevention efforts, these strategies have overwhelmingly been designed, tested and implemented based on evidence generated in high-income countries. As a result, the models and interventions commonly adopted worldwide often fail to adequately capture the diverse realities of the global south. Here we argue that the global south offers critical insights for rethinking suicide prevention, illustrating how socioeconomic factors, cultural practices and community connection and resilience shape mental health outcomes and suicide risk. Rather than relying exclusively on individual-centered, clinical approaches, a broader and more context-sensitive framework is necessary, one that integrates structural determinants, promotes social justice and values epistemological diversity. Through an analysis of epidemiological trends, mental health constructs, cultural practices, theoretical frameworks and public policy interventions, this Perspective proposes a reconceptualization of suicide-prevention strategies that move beyond traditional paradigms. This Perspective challenges the traditional approaches to suicide prevention research, which are often rooted in studies from high-income countries. It advocates for culturally informed, community-based strategies, drawing on successful examples from the global south.
{"title":"Rethinking suicide prevention: insights from the global south for a new global agenda","authors":"Daiane B. Machado","doi":"10.1038/s44220-025-00491-7","DOIUrl":"10.1038/s44220-025-00491-7","url":null,"abstract":"Despite decades of scientific advances, suicide remains a global public health challenge shaped by deep social, economic and cultural inequalities. Although substantial resources have been allocated to prevention efforts, these strategies have overwhelmingly been designed, tested and implemented based on evidence generated in high-income countries. As a result, the models and interventions commonly adopted worldwide often fail to adequately capture the diverse realities of the global south. Here we argue that the global south offers critical insights for rethinking suicide prevention, illustrating how socioeconomic factors, cultural practices and community connection and resilience shape mental health outcomes and suicide risk. Rather than relying exclusively on individual-centered, clinical approaches, a broader and more context-sensitive framework is necessary, one that integrates structural determinants, promotes social justice and values epistemological diversity. Through an analysis of epidemiological trends, mental health constructs, cultural practices, theoretical frameworks and public policy interventions, this Perspective proposes a reconceptualization of suicide-prevention strategies that move beyond traditional paradigms. This Perspective challenges the traditional approaches to suicide prevention research, which are often rooted in studies from high-income countries. It advocates for culturally informed, community-based strategies, drawing on successful examples from the global south.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 9","pages":"982-990"},"PeriodicalIF":8.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44220-025-00491-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1038/s44220-025-00477-5
Malvika Sridhar, Wiebke Struckmann, Noriah D. Johnson, Martin Tik, Cammie E. Rolle, Ian H. Kratter, Nolan R. Williams
Major depressive disorder (MDD) is a prevalent psychiatric illness marked by notable changes in mood, behavior and cognition. Emerging evidence indicates that depression can differ by sex in terms of onset, symptoms and treatment response. While modern psychiatry acknowledges sex differences in epidemiology, we are yet to identify biomarkers that could guide sex-specific interventions. Recent discoveries in MDD research point towards alterations in functional brain network patterns. This Perspective highlights the rationale for using resting-state functional magnetic resonance imaging (rs-fMRI) to identify sex differences in MDD. We present preliminary evidence for sex-based differences in depression from the limited existing rs-fMRI literature. Although limited and heterogeneous in their design, the results point towards the need for larger research studies. Furthermore, in female individuals, hormonal fluctuations during specific life phases pose a substantial risk for the onset of depressive episodes. We advocate that future studies integrate sex as an essential factor in MDD research and utilize resting-state functional connectivity to identify sex-specific neural features and biomarkers. We finally recommend ways to incorporate menstrual and reproductive cycle data into depression research to develop better diagnostic tools and personalized treatment strategies. Major depressive disorder (MDD) exhibits sex-specific differences in onset, symptoms and treatment response, yet biomarkers for guiding sex-specific interventions remain unidentified. Here the authors propose the use of resting-state functional magnetic resonance imaging to uncover sex-based neural differences in MDD, advocating for larger studies to enhance diagnostic tools and personalized treatments.
{"title":"Functional neuroimaging highlights sex as a critical variable in depression research","authors":"Malvika Sridhar, Wiebke Struckmann, Noriah D. Johnson, Martin Tik, Cammie E. Rolle, Ian H. Kratter, Nolan R. Williams","doi":"10.1038/s44220-025-00477-5","DOIUrl":"10.1038/s44220-025-00477-5","url":null,"abstract":"Major depressive disorder (MDD) is a prevalent psychiatric illness marked by notable changes in mood, behavior and cognition. Emerging evidence indicates that depression can differ by sex in terms of onset, symptoms and treatment response. While modern psychiatry acknowledges sex differences in epidemiology, we are yet to identify biomarkers that could guide sex-specific interventions. Recent discoveries in MDD research point towards alterations in functional brain network patterns. This Perspective highlights the rationale for using resting-state functional magnetic resonance imaging (rs-fMRI) to identify sex differences in MDD. We present preliminary evidence for sex-based differences in depression from the limited existing rs-fMRI literature. Although limited and heterogeneous in their design, the results point towards the need for larger research studies. Furthermore, in female individuals, hormonal fluctuations during specific life phases pose a substantial risk for the onset of depressive episodes. We advocate that future studies integrate sex as an essential factor in MDD research and utilize resting-state functional connectivity to identify sex-specific neural features and biomarkers. We finally recommend ways to incorporate menstrual and reproductive cycle data into depression research to develop better diagnostic tools and personalized treatment strategies. Major depressive disorder (MDD) exhibits sex-specific differences in onset, symptoms and treatment response, yet biomarkers for guiding sex-specific interventions remain unidentified. Here the authors propose the use of resting-state functional magnetic resonance imaging to uncover sex-based neural differences in MDD, advocating for larger studies to enhance diagnostic tools and personalized treatments.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 9","pages":"974-981"},"PeriodicalIF":8.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-22DOI: 10.1038/s44220-025-00471-x
Joëlle A. Pasman, Jacob Bergstedt, Arvid Harder, Tong Gong, Ying Xiong, Sara Hägg, Fang Fang, Jorien L. Treur, Karmel W. Choi, Patrick F. Sullivan, Yi Lu
Major depressive disorder (MDD) is a prevalent and debilitating disorder whose causes and consequences remain insufficiently understood. Genetic variants can be used to study causal relationships with other traits. Here we reviewed 201 MDD-associated traits and performed genetic correlation analyses for 115 traits, two-sample Mendelian randomization for 89 of them, and one-sample Mendelian randomization for an additional 43 outcomes, applying sensitivity tests and power analyses. We show that MDD liability increases risk for poorer circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic and suicide outcomes. Most associations were bidirectional, although with weaker evidence for diet, disease and endocrine traits causing MDD risk. These findings provide a systematic overview of traits putatively causally linked to MDD—confirming known links and identifying new ones—and underscore MDD as a cross-cutting risk factor across medical, functional and psychosocial domains. The authors analyze genetic correlations and perform Mendelian randomization to reveal bidirectional links between major depressive disorder and various traits, highlighting its role as an important risk factor across medical, functional and psychosocial domains and identifying potential causal relationships.
{"title":"An encompassing Mendelian randomization study of the causes and consequences of major depressive disorder","authors":"Joëlle A. Pasman, Jacob Bergstedt, Arvid Harder, Tong Gong, Ying Xiong, Sara Hägg, Fang Fang, Jorien L. Treur, Karmel W. Choi, Patrick F. Sullivan, Yi Lu","doi":"10.1038/s44220-025-00471-x","DOIUrl":"10.1038/s44220-025-00471-x","url":null,"abstract":"Major depressive disorder (MDD) is a prevalent and debilitating disorder whose causes and consequences remain insufficiently understood. Genetic variants can be used to study causal relationships with other traits. Here we reviewed 201 MDD-associated traits and performed genetic correlation analyses for 115 traits, two-sample Mendelian randomization for 89 of them, and one-sample Mendelian randomization for an additional 43 outcomes, applying sensitivity tests and power analyses. We show that MDD liability increases risk for poorer circadian, cognitive, diet, medical disease, endocrine, functional, inflammatory, metabolic, mortality, physical activity, reproduction, risk behavior, social, socioeconomic and suicide outcomes. Most associations were bidirectional, although with weaker evidence for diet, disease and endocrine traits causing MDD risk. These findings provide a systematic overview of traits putatively causally linked to MDD—confirming known links and identifying new ones—and underscore MDD as a cross-cutting risk factor across medical, functional and psychosocial domains. The authors analyze genetic correlations and perform Mendelian randomization to reveal bidirectional links between major depressive disorder and various traits, highlighting its role as an important risk factor across medical, functional and psychosocial domains and identifying potential causal relationships.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 9","pages":"1002-1011"},"PeriodicalIF":8.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12417207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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