Valerie Voon, Luis Manssuer, Yi-Jie Zhao, Qiong Ding, Ying Zhao, Linbin Wang, Tao Wang, Peng Huang, Yixin Pan, Bomin Sun, Dianyou Li
{"title":"Modeling impulsivity and risk aversion in the subthalamic nucleus with deep brain stimulation","authors":"Valerie Voon, Luis Manssuer, Yi-Jie Zhao, Qiong Ding, Ying Zhao, Linbin Wang, Tao Wang, Peng Huang, Yixin Pan, Bomin Sun, Dianyou Li","doi":"10.1038/s44220-024-00289-z","DOIUrl":"10.1038/s44220-024-00289-z","url":null,"abstract":"Risk evaluation is ubiquitous in decisions. Deep brain stimulation of the subthalamic nucleus is effective for Parkinson’s disease and obsessive–compulsive disorder, and can be associated with impulsivity and hypomania. Subthalamic stimulation has seemingly contrasting effects on impulsivity enhancing conflict-induced impulsivity but decreasing risk taking. Here, using a card gambling task paired with intracranial recordings (n = 25) and within-subject case control acute stimulation (n = 15) of the right subthalamic nucleus, we dissociated objective risk and uncertainty and subjective physiological markers of risk. Acute stimulation decreased risk taking (P = 0.010, Cohen’s d = 0.72) and increased subthalamic theta activity (P < 0.001, Cohen’s d = 0.72). Critically, stimulation negatively shifted the relationship between subthalamic physiology and a measure of evidence accumulation similar to observations with stimulation-induced conflict processing. This highlights the phenotypic and physiological heterogeneity of impulsivity, yet linking mechanisms underlying stimulation-induced conflict and risk. Finally, stimulation-induced risk seeking implicates the ventral subthalamic nucleus and dissociating anatomical and functional connectivity with the mesial prefrontal cortex. Our findings have implications for conceptualizations of impulsivity, and clinical relevance for neuropsychiatric disorders. Using a card gambling task paired with intracranial recordings and deep brain stimulation of the right subthalamic nucleus, the authors dissociate objective and subjective markers of risk taking and demonstrate the role of stimulation localization on risk-related behavior.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 9","pages":"1084-1095"},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44220-024-00289-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141821833","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}
Zhiyang Wang, Stephanie Zellers, Alyce M. Whipp, Marja Heinonen-Guzejev, Maria Foraster, Jordi Júlvez, Irene van Kamp, Jaakko Kaprio
{"title":"Author Correction: The effect of environment on depressive symptoms in late adolescence and early adulthood: an exposome-wide association study and twin modeling","authors":"Zhiyang Wang, Stephanie Zellers, Alyce M. Whipp, Marja Heinonen-Guzejev, Maria Foraster, Jordi Júlvez, Irene van Kamp, Jaakko Kaprio","doi":"10.1038/s44220-024-00295-1","DOIUrl":"10.1038/s44220-024-00295-1","url":null,"abstract":"","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 8","pages":"999-999"},"PeriodicalIF":0.0,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44220-024-00295-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141825559","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}
Tomáš Formánek, Danni Chen, Zdeněk Šumník, Karolína Mladá, James Hughes, Stephen Burgess, Nicholas J. Wareham, Graham K. Murray, Peter B. Jones, Benjamin I. Perry
{"title":"Childhood-onset type 1 diabetes and subsequent adult psychiatric disorders: a nationwide cohort and genome-wide Mendelian randomization study","authors":"Tomáš Formánek, Danni Chen, Zdeněk Šumník, Karolína Mladá, James Hughes, Stephen Burgess, Nicholas J. Wareham, Graham K. Murray, Peter B. Jones, Benjamin I. Perry","doi":"10.1038/s44220-024-00280-8","DOIUrl":"10.1038/s44220-024-00280-8","url":null,"abstract":"Childhood-onset type 1 diabetes (T1D) is associated with substantial psychiatric morbidity in later life, but it remains unknown whether these associations are due to common underlying biological mechanisms or the impacts of living with the condition and its treatment. Here, using Czech national register data, we identified children with T1D aged ≤14 years between 1994 and 2007 and estimated the risk of psychiatric disorders up to 24 years later. We found that children diagnosed with T1D had an elevated risk of developing substance use, mood, anxiety and personality disorders, and behavioral syndromes. Conversely, we found that children with T1D had a lower risk of developing psychotic disorders. In Mendelian randomization analysis, we found an association with schizophrenia, which, however, did not persist following multiple testing adjustment. The combined observational and Mendelian randomization evidence suggests that T1D diagnosis in childhood predisposes to far-reaching, extensive psychiatric morbidity, which is unlikely to be explicable by common underlying biological mechanisms. The findings of this study highlight that monitoring and addressing the mental health needs of children with T1D is imperative, whereas glucose dysregulation and/or inflammation implicated in schizophrenia pathogenesis warrants future research. In this study, analyzing Czech national register-based data and using genome-wide Mendelian randomization, the authors report elevated risk for developing substance use, mood, anxiety and personality disorders in individuals with childhood-onset type 1 diabetes, and show that these associations are unlikely to be explicable by common underlying biological mechanisms.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 9","pages":"1062-1070"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44220-024-00280-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141827877","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}
Joane Matta, Baptiste Pignon, Sofiane Kab, Emmanuel Wiernik, Olivier Robineau, Fabrice Carrat, Gianluca Severi, Mathilde Touvier, Hélène Blanché, Jean-François Deleuze, Clément Gouraud, Charles Ouazana Vedrines, Victor Pitron, Sarah Tebeka, Brigitte Ranque, Nicolas Hoertel, Marcel Goldberg, Marie Zins, Cédric Lemogne
{"title":"Depressive symptoms and sex differences in the risk of post-COVID-19 persistent symptoms: a prospective population-based cohort study","authors":"Joane Matta, Baptiste Pignon, Sofiane Kab, Emmanuel Wiernik, Olivier Robineau, Fabrice Carrat, Gianluca Severi, Mathilde Touvier, Hélène Blanché, Jean-François Deleuze, Clément Gouraud, Charles Ouazana Vedrines, Victor Pitron, Sarah Tebeka, Brigitte Ranque, Nicolas Hoertel, Marcel Goldberg, Marie Zins, Cédric Lemogne","doi":"10.1038/s44220-024-00290-6","DOIUrl":"10.1038/s44220-024-00290-6","url":null,"abstract":"Women are unexplainedly more affected than men by post-COVID-19 persistent symptoms. Depressive symptoms may partially explain these sex differences. In the French population-based CONSTANCES cohort, depressive symptoms were measured with the nine-item Patient Health Questionnaire between April 6 and May 4, 2020. Between December 2020 and January 2021, among 2,093 infected participants (mean (s.d.) age, 43.0 years (11.9); 55.3% women), 453 (21.6%) reported ≥1 new persistent symptom that emerged from March 2020. Accounting for several confounders, women were more likely than men to have ≥1 symptom (odds ratio (95% confidence interval), 1.45 (1.17–1.80)). Further adjusting for the nine-item Patient Health Questionnaire, participants in the highest (versus lowest) quartile were more likely to have ≥1 symptom (2.97 (2.09–4.23)), while the association with female sex substantially dropped (1.28 (1.02–1.60)). Depressive symptoms mediated 41.5–45.4% of this association. A biopsychosocial model, integrating gender and mental health, is warranted to understand long COVID and inform preventive and therapeutic strategies. In this cohort study, the authors find that depressive symptoms at the beginning of the pandemic may partially explain why women participants who had a COVID-19 episode were more likely than their male counterparts to report at least one post-COVID-19 persistent symptom seven to ten months later.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 9","pages":"1053-1061"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141828606","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}
Trine Tollerup Nielsen, Jinjie Duan, Daniel F. Levey, G. Bragi Walters, Emma C. Johnson, Thorgeir Thorgeirsson, VA Million Veteran Program, Thomas Werge, Preben Bo Mortensen, Hreinn Stefansson, Kari Stefansson, David M. Hougaard, Arpana Agrawal, Joel Gelernter, Jakob Grove, Anders D. Børglum, Ditte Demontis
{"title":"Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD","authors":"Trine Tollerup Nielsen, Jinjie Duan, Daniel F. Levey, G. Bragi Walters, Emma C. Johnson, Thorgeir Thorgeirsson, VA Million Veteran Program, Thomas Werge, Preben Bo Mortensen, Hreinn Stefansson, Kari Stefansson, David M. Hougaard, Arpana Agrawal, Joel Gelernter, Jakob Grove, Anders D. Børglum, Ditte Demontis","doi":"10.1038/s44220-024-00277-3","DOIUrl":"10.1038/s44220-024-00277-3","url":null,"abstract":"Cannabis use disorder (CUD) and cannabis use (CU) are prevalent conditions co-occurring with attention-deficit hyperactivity disorder (ADHD). Here we report results from a cross-disorder genome-wide association study of ADHD and CUD or CU. We identified 36 concordant genome-wide significant loci for ADHD–CUD and ten loci for ADHD–CU. DRD2 was identified as an ADHD–CUD risk gene. ADHD–CUD risk genes showed high expression across brain tissues and brain developmental stages, which was not observed for ADHD–CU genes. ADHD–CUD and ADHD–CU showed similar genetic correlations with substance use, whereas they differed for substance-use disorders. Individuals with ADHD–CUD had increased polygenic scores (PGS) for psychiatric disorders compared with those with ADHD without CUD and increased burden of rare deleterious variants. Stratification of individuals with ADHD by their CUD PGS revealed an absolute risk of 22% for comorbid CUD in the highest CUD-PGS bin—much higher than 1.6% risk among controls. Sex-specific differences were substantial with an approximately 10% higher CUD risk among men in the highest CUD-PGS bin. In this study, the authors use a combination of genetic methodologies to investigate the genetic associations between attention-deficit/hyperactivity disorder, cannabis use disorder and cannabis use.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 9","pages":"1071-1083"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141829671","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}
Sam Ereira, Sheena Waters, Adeel Razi, Charles R. Marshall
{"title":"Author Correction: Early detection of dementia with default-mode network effective connectivity","authors":"Sam Ereira, Sheena Waters, Adeel Razi, Charles R. Marshall","doi":"10.1038/s44220-024-00296-0","DOIUrl":"10.1038/s44220-024-00296-0","url":null,"abstract":"","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 8","pages":"1000-1000"},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44220-024-00296-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141968563","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}
Zhiyan Wang, Chao Jiang, Lingxiao Guan, Lei Zhao, Tengteng Fan, Jian Wang, Xiaodong Cai, Yingli Zhang, Chen Yao, Bo Peng, Feixue Wang, Chunhua Hu, Zhiqiang Cui, Yiheng Tu, Luming Li
{"title":"Deep brain stimulation of habenula reduces depressive symptoms and modulates brain activities in treatment-resistant depression","authors":"Zhiyan Wang, Chao Jiang, Lingxiao Guan, Lei Zhao, Tengteng Fan, Jian Wang, Xiaodong Cai, Yingli Zhang, Chen Yao, Bo Peng, Feixue Wang, Chunhua Hu, Zhiqiang Cui, Yiheng Tu, Luming Li","doi":"10.1038/s44220-024-00286-2","DOIUrl":"10.1038/s44220-024-00286-2","url":null,"abstract":"The habenula (Hb) is a phylogenetically old structure connecting forebrain and brainstem monoaminergic nuclei that has been implicated in the pathogenesis of depression. Here, to investigate the clinical efficacy and neural mechanisms of stimulating the Hb for alleviating depression symptoms in humans, we bilaterally implanted electrodes in six patients with treatment-resistant depression and delivered high-frequency stimulation. Compared to baseline, we observed a substantial reduction in Hamilton Depression Rating Scale scores: 62.1% at 1-month, 64.0% at 3-month and 66.2% at 6-month follow-up. Local field potential data showed that acute Hb stimulation increased theta-band power, especially in the right side, which was related to the following clinical remission. Moreover, functional magnetic resonance imaging data showed that acute Hb stimulation enhanced blood oxygen level-dependent responses of the medial orbitofrontal cortex, raphe and substantia nigra, which are important components of the dopaminergic and serotonergic systems. Our findings demonstrated that Hb stimulation can alleviate depressive symptoms and modulate the activity of the medial orbitofrontal cortex, raphe and substantia nigra in treatment-resistant depression patients. This trial was registered under the clinical trial numbers NCT03667872 and ChiCTR2100045363. Using deep brain stimulation of the habenula with implanted electrodes in patients with treatment-resistant depression, this study found a substantial reduction in depression scores at follow-up over multiple time points.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 9","pages":"1045-1052"},"PeriodicalIF":0.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141652935","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}
{"title":"Circadian disruptions and brain clock dysregulation in mood disorders","authors":"Jorge Mendoza","doi":"10.1038/s44220-024-00260-y","DOIUrl":"10.1038/s44220-024-00260-y","url":null,"abstract":"The circadian system, composed of a network of brain and peripheral 24-hour clocks and oscillators, allows organisms to anticipate and synchronize to natural daily events. The day–night cycle is the dominant timing signal to align circadian clocks to the external time. Thereby, exposure to aberrant light–dark cycles leads to disruptions of the circadian system, evoking different health issues, including mental or affective ones. Humans with circadian misalignments, such as those observed in jet-lag-exposed people or shift workers, and animal models of clock disturbances show mood alterations such as anxiety and depressive-like behaviors. The mechanisms underlying the physiopathology of mood disorders in circadian disruption may imply an altered functioning of the main clock in the suprachiasmatic nucleus, from other central oscillators, or a loss of internal synchrony between them. This Review outlines the current knowledge on the link between circadian perturbations and mood disorders in humans and animal models, and the possible neurobiological mechanisms involved. This Review explores the link between mood disorders and circadian disruptions, including social jet lag and shift work, and offers new perspectives for therapeutic development in future chronobiology research.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 7","pages":"749-763"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141608138","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}
{"title":"Diffuse glioma location is associated with extremes of depressive symptoms","authors":"","doi":"10.1038/s44220-024-00276-4","DOIUrl":"10.1038/s44220-024-00276-4","url":null,"abstract":"Mood dysfunction is more common in people with brain tumors than in those with other tumor types, but the reasons for this association are unclear. Using various methods for lesion–symptom mapping, we identified brain locations in patients with diffuse glioma that are related to severe depressive symptoms or an absence of depressive symptoms.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 7","pages":"747-748"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141608125","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}
Maisa N. G. van Genderen, Vera Belgers, Johanna M. Niers, Linda Douw, Jantine G. Röttgering, Maxine Gorter, Marieke E. C. Blom, Frederik Barkhof, Martin Klein, Roelant S. Eijgelaar, Philip C. De Witt Hamer
{"title":"Tumor location is associated with mood dysfunction in patients with diffuse glioma","authors":"Maisa N. G. van Genderen, Vera Belgers, Johanna M. Niers, Linda Douw, Jantine G. Röttgering, Maxine Gorter, Marieke E. C. Blom, Frederik Barkhof, Martin Klein, Roelant S. Eijgelaar, Philip C. De Witt Hamer","doi":"10.1038/s44220-024-00275-5","DOIUrl":"10.1038/s44220-024-00275-5","url":null,"abstract":"Gliomas are primary brain tumors that can cause neuropsychiatric symptoms, including severe depressive symptoms (SDS; in 14%) and an absence of depressive symptoms (ADS; in 29%), determined by Center for Epidemiologic Studies Depression (CES-D) scores. We examined the association between both SDS and ADS and brain tumor location in 201 patients with diffuse glioma before surgery. Tumors and white matter disconnectomes did not relate to CES-D using sparse canonical correlation analysis. SDS were associated with tumors in the right corticospinal tract, fornix, and inferior fronto-occipital fasciculus and the left uncinate fasciculus, whereas ADS was associated with tumors in the left uncinate fasciculus and first segment of the superior longitudinal fasciculus and the right temporal cingulum and thalamus using Bayesian regression analyses. ADS occurs even more frequently in patients with diffuse glioma than does SDS, which is explained partly by tumor location. This research aids the understanding of gliomas and mood dysfunction in general. The authors report how the anatomical location of diffuse gliomas is related to the occurrence of severe depressive symptoms or the absence of depressive symptoms.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"2 7","pages":"853-864"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44220-024-00275-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141608123","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}