Pub Date : 2025-10-30DOI: 10.1038/s44220-025-00534-z
Ralf C. Buckley, Ruth Bishop, Bronwyn Paynter, Meisha Liddon, Paula Brough
{"title":"Occupational therapy as an allied health avenue for clinical nature-based mental healthcare","authors":"Ralf C. Buckley, Ruth Bishop, Bronwyn Paynter, Meisha Liddon, Paula Brough","doi":"10.1038/s44220-025-00534-z","DOIUrl":"10.1038/s44220-025-00534-z","url":null,"abstract":"","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1296-1297"},"PeriodicalIF":8.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450108","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 : 2025-10-21DOI: 10.1038/s44220-025-00521-4
S. L. Harper, A. Cunsolo, B. Aylward, S. Clayton, M. Lin, K. Minor, R. Vriezen, M. Banuet-Martinez, H. L. Bayne
Although feeling anxious can be a normal and healthy response to climate change, more severe forms of climate change anxiety can reach clinical relevance, persist for long periods of time and impact daily functioning. Here we leveraged the disciplinary strengths of psychology and epidemiology to examine these more severe manifestations of climate change anxiety in Canada. Using a national population-based cross-sectional survey—using a multistage, multistratified random probability sampling method—we applied the Climate Change Anxiety Scale and collected sociodemographic data (n = 2,476). The prevalence of climate change anxiety (symptoms that reach clinical relevance) was 2.35% (95% confidence interval 1.49–3.68%). Across demographic groups, the prevalence of climate change anxiety was the highest among Indigenous Peoples; prevalence estimates were also relatively elevated for women, those living in Northern Canada and those with household incomes <$60,000 CAD per year. Our interdisciplinary approach permitted more accurate prevalence estimates than in previous studies that use convenience samples globally. Harper et al. used data from a national population-based cross-sectional survey to assess the prevalence, magnitude and distribution of climate change anxiety in Canada.
{"title":"Prevalence, magnitude and distribution of climate change anxiety in Canada: an interdisciplinary study","authors":"S. L. Harper, A. Cunsolo, B. Aylward, S. Clayton, M. Lin, K. Minor, R. Vriezen, M. Banuet-Martinez, H. L. Bayne","doi":"10.1038/s44220-025-00521-4","DOIUrl":"10.1038/s44220-025-00521-4","url":null,"abstract":"Although feeling anxious can be a normal and healthy response to climate change, more severe forms of climate change anxiety can reach clinical relevance, persist for long periods of time and impact daily functioning. Here we leveraged the disciplinary strengths of psychology and epidemiology to examine these more severe manifestations of climate change anxiety in Canada. Using a national population-based cross-sectional survey—using a multistage, multistratified random probability sampling method—we applied the Climate Change Anxiety Scale and collected sociodemographic data (n = 2,476). The prevalence of climate change anxiety (symptoms that reach clinical relevance) was 2.35% (95% confidence interval 1.49–3.68%). Across demographic groups, the prevalence of climate change anxiety was the highest among Indigenous Peoples; prevalence estimates were also relatively elevated for women, those living in Northern Canada and those with household incomes <$60,000 CAD per year. Our interdisciplinary approach permitted more accurate prevalence estimates than in previous studies that use convenience samples globally. Harper et al. used data from a national population-based cross-sectional survey to assess the prevalence, magnitude and distribution of climate change anxiety in Canada.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1384-1394"},"PeriodicalIF":8.7,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450113","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 : 2025-10-20DOI: 10.1038/s44220-025-00525-0
Isaac N. Treves, Madelynn S. Park, Jamaal Spence, Nigel Jaffe, Kristina Pidvirny, Anna O. Tierney, Aaron K. Kucyi, John D. E. Gabrieli, Randy P. Auerbach, Christian A. Webb
Rumination, or perseverative negative self-referential thinking, is a hallmark of depression. In adults, a dynamic resting-state functional magnetic resonance imaging model of trait rumination was recently identified through predictive modeling. In adolescents, a development period during which rumination and depression increase, the neurobiological correlates of ruminative thinking are less clear. Here, in the current preregistered study, we examine dynamic connectivity correlates of self-reported rumination in a large sample of adolescents (n = 443, containing clinical and nonclinical individuals). Notably, the adult model failed to generalize to our sample. In addition, linear models trained on default-mode network (DMN) connectivity, as well as whole-brain connectome models, failed to generalize to held-out data. In an exploratory random forest analysis, we found significant prediction performance of a model in which increased variability between DMN–cerebellum, DMN–dorsal attention network and DMN–DMN connections was nominally associated with higher rumination. However, the model did not generalize to an external sample with lower rumination scores and a distinct scanner protocol. Our findings illustrate the difficulty of characterizing the neurodevelopment of risk factors for depression. Here the authors explore dynamic connectivity associated with rumination in a large adolescent cohort, revealing that adult models do not generalize, while exploratory analyses suggest that variability in default-mode network connections may predict rumination, highlighting challenges in understanding depression risk factors.
{"title":"Limited generalizability of dynamic fMRI correlates of adolescent rumination","authors":"Isaac N. Treves, Madelynn S. Park, Jamaal Spence, Nigel Jaffe, Kristina Pidvirny, Anna O. Tierney, Aaron K. Kucyi, John D. E. Gabrieli, Randy P. Auerbach, Christian A. Webb","doi":"10.1038/s44220-025-00525-0","DOIUrl":"10.1038/s44220-025-00525-0","url":null,"abstract":"Rumination, or perseverative negative self-referential thinking, is a hallmark of depression. In adults, a dynamic resting-state functional magnetic resonance imaging model of trait rumination was recently identified through predictive modeling. In adolescents, a development period during which rumination and depression increase, the neurobiological correlates of ruminative thinking are less clear. Here, in the current preregistered study, we examine dynamic connectivity correlates of self-reported rumination in a large sample of adolescents (n = 443, containing clinical and nonclinical individuals). Notably, the adult model failed to generalize to our sample. In addition, linear models trained on default-mode network (DMN) connectivity, as well as whole-brain connectome models, failed to generalize to held-out data. In an exploratory random forest analysis, we found significant prediction performance of a model in which increased variability between DMN–cerebellum, DMN–dorsal attention network and DMN–DMN connections was nominally associated with higher rumination. However, the model did not generalize to an external sample with lower rumination scores and a distinct scanner protocol. Our findings illustrate the difficulty of characterizing the neurodevelopment of risk factors for depression. Here the authors explore dynamic connectivity associated with rumination in a large adolescent cohort, revealing that adult models do not generalize, while exploratory analyses suggest that variability in default-mode network connections may predict rumination, highlighting challenges in understanding depression risk factors.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1407-1416"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450100","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 : 2025-10-20DOI: 10.1038/s44220-025-00497-1
Ilina Singh, Essi Viding, Lucienne Spencer, Charlotte Austin, Zeba R. Kokan, Argyris Stringaris
There is an urgent need for a rigorous science of patient and public participation, involvement and engagement (PPIE) in child and adolescent mental health research. In this Perspective we argue that current PPIE practices lack solid theoretical foundations and require systematic evaluation of their epistemic and ethical impacts. We call for the development of clear concepts of ‘lived experience’ and ‘voice’ and the establishment of a shared framework to assess the value of PPIE in advancing discovery science. We end with ten initial questions to advance open, multi-stakeholder dialogue and debate on PPIE in the field. In this Perspective, Singh et al. examine the growing role of patient and public participation, involvement and engagement in discovery science, highlighting the need for clearer guidance in the context of youth mental health research.
{"title":"The need for a science of patient and public involvement and participation in child and adolescent mental health research","authors":"Ilina Singh, Essi Viding, Lucienne Spencer, Charlotte Austin, Zeba R. Kokan, Argyris Stringaris","doi":"10.1038/s44220-025-00497-1","DOIUrl":"10.1038/s44220-025-00497-1","url":null,"abstract":"There is an urgent need for a rigorous science of patient and public participation, involvement and engagement (PPIE) in child and adolescent mental health research. In this Perspective we argue that current PPIE practices lack solid theoretical foundations and require systematic evaluation of their epistemic and ethical impacts. We call for the development of clear concepts of ‘lived experience’ and ‘voice’ and the establishment of a shared framework to assess the value of PPIE in advancing discovery science. We end with ten initial questions to advance open, multi-stakeholder dialogue and debate on PPIE in the field. In this Perspective, Singh et al. examine the growing role of patient and public participation, involvement and engagement in discovery science, highlighting the need for clearer guidance in the context of youth mental health research.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1311-1317"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450094","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 : 2025-10-20DOI: 10.1038/s44220-025-00517-0
Le Wang, Yifei Lin, Tingting Fu, Yuhuan Xie, Yong Yang, Nanyan Xiang, Shiqi Su, Huan Song, Donghao Lu, Jin Huang
Depression is a global health challenge, and recent attention has been given to the influence of hematological biomarkers in predicting its onset. In this study, we assessed the relationship between 32 blood cell-related biomarkers and depression risk among 87,493 participants (45.9% female; mean age at baseline 43.47 years, s.d. 10.59) with repeated measures over a median follow-up of 2 years (range 1–8 years) from a population-based cohort, the West-China Hospital Alliance Longitudinal Epidemiology Wellness Study. Adjusted Poisson regression models revealed significant associations between lymphocyte biomarkers (CD4, CD8 and ratios) and depression risk (all false discovery rate <0.05). Red-cell distribution width was significantly associated with depression in female participants (adjusted risk ratio 1.171, 95% confidence interval 1.063–1.29, false discovery rate 0.013). Trajectory analysis, using latent class mixed modeling, revealed that monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio trajectories were found to be predictive of depression, with monocyte-to-lymphocyte ratio and lymphocyte count patterns particularly associated with increased risk among male participants. These findings provide insights into the role of sex-specific hematological biomarker trajectories in depression risk, emphasizing the need for further exploration of targeted prevention and intervention strategies based on biomarker patterns. Wang et al. analyzed data from a large population-based cohort study in China to examine the relationship between blood cell biomarkers and the risk of depression.
{"title":"Blood cell biomarker trajectories and depression risk in a sex-stratified 10-year longitudinal cohort analysis","authors":"Le Wang, Yifei Lin, Tingting Fu, Yuhuan Xie, Yong Yang, Nanyan Xiang, Shiqi Su, Huan Song, Donghao Lu, Jin Huang","doi":"10.1038/s44220-025-00517-0","DOIUrl":"10.1038/s44220-025-00517-0","url":null,"abstract":"Depression is a global health challenge, and recent attention has been given to the influence of hematological biomarkers in predicting its onset. In this study, we assessed the relationship between 32 blood cell-related biomarkers and depression risk among 87,493 participants (45.9% female; mean age at baseline 43.47 years, s.d. 10.59) with repeated measures over a median follow-up of 2 years (range 1–8 years) from a population-based cohort, the West-China Hospital Alliance Longitudinal Epidemiology Wellness Study. Adjusted Poisson regression models revealed significant associations between lymphocyte biomarkers (CD4, CD8 and ratios) and depression risk (all false discovery rate <0.05). Red-cell distribution width was significantly associated with depression in female participants (adjusted risk ratio 1.171, 95% confidence interval 1.063–1.29, false discovery rate 0.013). Trajectory analysis, using latent class mixed modeling, revealed that monocyte-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio trajectories were found to be predictive of depression, with monocyte-to-lymphocyte ratio and lymphocyte count patterns particularly associated with increased risk among male participants. These findings provide insights into the role of sex-specific hematological biomarker trajectories in depression risk, emphasizing the need for further exploration of targeted prevention and intervention strategies based on biomarker patterns. Wang et al. analyzed data from a large population-based cohort study in China to examine the relationship between blood cell biomarkers and the risk of depression.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1438-1451"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44220-025-00517-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450112","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 : 2025-10-20DOI: 10.1038/s44220-025-00522-3
Adyasha Khuntia, David Popovic, Elif Sarisik, Madalina O. Buciuman, Mads L. Pedersen, Lars T. Westlye, Ole A. Andreassen, Andreas Meyer-Lindenberg, Joseph Kambeitz, Raimo K. R. Salokangas, Jarmo Hietala, Alessandro Bertolino, Stefan Borgwardt, Paolo Brambilla, Rachel Upthegrove, Stephen J. Wood, Rebekka Lencer, Eva Meisenzahl, Peter Falkai, Emanuel Schwarz, Ariane Wiegand, Nikolaos Koutsouleris
Understanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. Using brain scans from healthy individuals (n = 1,504), we trained a model to predict body mass index (BMI) and applied it to individuals with schizophrenia (n = 146), clinical high-risk states for psychosis (n = 213) and recent-onset depression (ROD, n = 200). We computed BMIgap (BMIpredicted − BMImeasured), interrogated its brain-level overlaps with schizophrenia and explored whether BMIgap predicted weight gain at the 1-year and 2-year follow-ups. Schizophrenia (BMIgap = 1.05 kg m−2) and clinical high-risk individuals (BMIgap = 0.51 kg m−2) showed increased BMIgap and individuals with ROD (BMIgap = −0.82 kg m−2) showed decreased BMIgap. Shared brain patterns of BMI and schizophrenia were linked to illness duration, disease onset and hospitalization frequency. Higher BMIgap predicted future weight gain, particularly in younger individuals with ROD, and at 2-year follow-up. Here we show that BMIgap can serve as a potential brain-derived measure to stratify at-risk individuals and deliver tailored interventions for better metabolic risk control. This research investigates the neurobiological factors influencing weight gain, using brain scans from diverse cohorts to develop a predictive model. The findings indicate that BMIgap correlates with psychiatric conditions, suggesting its potential for identifying at-risk individuals and guiding personalized interventions.
了解体重增加的神经生物学基础可以降低过高的死亡率，改善精神疾病的长期轨迹。利用健康个体（n = 1,504）的脑部扫描，我们训练了一个预测身体质量指数（BMI）的模型，并将其应用于精神分裂症患者（n = 146）、精神病临床高危状态患者（n = 213）和新近发病的抑郁症患者（n = 200）。我们计算了BMIgap （bmi预测- bmi测量），询问了其与精神分裂症的脑水平重叠，并探讨了BMIgap是否在1年和2年的随访中预测了体重增加。精神分裂症（BMIgap = 1.05 kg m−2）和临床高危人群（BMIgap = 0.51 kg m−2）BMIgap升高，ROD患者（BMIgap = - 0.82 kg m−2）BMIgap降低。BMI和精神分裂症的共同大脑模式与疾病持续时间、疾病发作和住院频率有关。较高的BMIgap预示着未来的体重增加，特别是在年轻的ROD患者和2年随访中。本研究表明，BMIgap可以作为一种潜在的脑源性测量方法，对高危个体进行分层，并提供量身定制的干预措施，以更好地控制代谢风险。这项研究调查了影响体重增加的神经生物学因素，利用来自不同人群的大脑扫描来建立一个预测模型。研究结果表明，BMIgap与精神疾病相关，表明其在识别高危个体和指导个性化干预方面的潜力。
{"title":"The BMIgap tool to quantify transdiagnostic brain signatures of current and future weight","authors":"Adyasha Khuntia, David Popovic, Elif Sarisik, Madalina O. Buciuman, Mads L. Pedersen, Lars T. Westlye, Ole A. Andreassen, Andreas Meyer-Lindenberg, Joseph Kambeitz, Raimo K. R. Salokangas, Jarmo Hietala, Alessandro Bertolino, Stefan Borgwardt, Paolo Brambilla, Rachel Upthegrove, Stephen J. Wood, Rebekka Lencer, Eva Meisenzahl, Peter Falkai, Emanuel Schwarz, Ariane Wiegand, Nikolaos Koutsouleris","doi":"10.1038/s44220-025-00522-3","DOIUrl":"10.1038/s44220-025-00522-3","url":null,"abstract":"Understanding the neurobiological underpinnings of weight gain could reduce excess mortality and improve long-term trajectories of psychiatric disorders. Using brain scans from healthy individuals (n = 1,504), we trained a model to predict body mass index (BMI) and applied it to individuals with schizophrenia (n = 146), clinical high-risk states for psychosis (n = 213) and recent-onset depression (ROD, n = 200). We computed BMIgap (BMIpredicted − BMImeasured), interrogated its brain-level overlaps with schizophrenia and explored whether BMIgap predicted weight gain at the 1-year and 2-year follow-ups. Schizophrenia (BMIgap = 1.05 kg m−2) and clinical high-risk individuals (BMIgap = 0.51 kg m−2) showed increased BMIgap and individuals with ROD (BMIgap = −0.82 kg m−2) showed decreased BMIgap. Shared brain patterns of BMI and schizophrenia were linked to illness duration, disease onset and hospitalization frequency. Higher BMIgap predicted future weight gain, particularly in younger individuals with ROD, and at 2-year follow-up. Here we show that BMIgap can serve as a potential brain-derived measure to stratify at-risk individuals and deliver tailored interventions for better metabolic risk control. This research investigates the neurobiological factors influencing weight gain, using brain scans from diverse cohorts to develop a predictive model. The findings indicate that BMIgap correlates with psychiatric conditions, suggesting its potential for identifying at-risk individuals and guiding personalized interventions.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1395-1406"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44220-025-00522-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450095","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 : 2025-10-20DOI: 10.1038/s44220-025-00518-z
Angela Song-Chase, Jennifer Dykxhoorn, Anna-Clara Hollander, Cecilia Magnusson, Christina Dalman, James B. Kirkbride
Social capital—the trust and cohesion within communities—has been linked to mental health, yet longitudinal evidence remains scarce. Here we show that neighborhood-level personal trust predicts the incidence of severe mental illness in a large, population-based cohort in Stockholm County, Sweden. Among 1.47 million Swedish-born residents followed over 15 years, higher personal trust at baseline was associated with reduced rates of non-affective psychotic disorder and bipolar disorder without psychosis over the follow-up period, but only among individuals of Swedish or European heritage. In contrast, the same exposure increased incidence rates among those of North African, Middle Eastern or Sub-Saharan African heritage. Political and welfare trust showed no consistent associations. These findings suggest that social capital may confer mental health benefits or risks depending on one’s own social position, highlighting the need for nuanced public mental health strategies that consider structural and cultural contexts in promoting mental wellbeing. The authors present data demonstrating that neighborhood-level personal trust influences severe mental illness incidence in a large cohort in Sweden, varying by heritage, emphasizing tailored public health strategies for mental wellbeing.
{"title":"Longitudinal association between neighborhood-level social capital and incidence of major psychiatric disorders in a cohort of 1.4 million people in Sweden","authors":"Angela Song-Chase, Jennifer Dykxhoorn, Anna-Clara Hollander, Cecilia Magnusson, Christina Dalman, James B. Kirkbride","doi":"10.1038/s44220-025-00518-z","DOIUrl":"10.1038/s44220-025-00518-z","url":null,"abstract":"Social capital—the trust and cohesion within communities—has been linked to mental health, yet longitudinal evidence remains scarce. Here we show that neighborhood-level personal trust predicts the incidence of severe mental illness in a large, population-based cohort in Stockholm County, Sweden. Among 1.47 million Swedish-born residents followed over 15 years, higher personal trust at baseline was associated with reduced rates of non-affective psychotic disorder and bipolar disorder without psychosis over the follow-up period, but only among individuals of Swedish or European heritage. In contrast, the same exposure increased incidence rates among those of North African, Middle Eastern or Sub-Saharan African heritage. Political and welfare trust showed no consistent associations. These findings suggest that social capital may confer mental health benefits or risks depending on one’s own social position, highlighting the need for nuanced public mental health strategies that consider structural and cultural contexts in promoting mental wellbeing. The authors present data demonstrating that neighborhood-level personal trust influences severe mental illness incidence in a large cohort in Sweden, varying by heritage, emphasizing tailored public health strategies for mental wellbeing.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1425-1437"},"PeriodicalIF":8.7,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44220-025-00518-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450107","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 : 2025-10-16DOI: 10.1038/s44220-025-00515-2
Lucas M. Marques, Sara B. Franco
{"title":"Solastalgia as a warning sign for mental health in a changing environment","authors":"Lucas M. Marques, Sara B. Franco","doi":"10.1038/s44220-025-00515-2","DOIUrl":"10.1038/s44220-025-00515-2","url":null,"abstract":"","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1298-1299"},"PeriodicalIF":8.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450096","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 : 2025-10-13DOI: 10.1038/s44220-025-00510-7
Laura M. Hack, Jenna Jubeir, Rachel Hilton, Leonardo Tozzi, Leyla Boyar, Xue Zhang, Timothy Lyons, Booil Jo, Ruth O’Hara, Alan F. Schatzberg, Leanne M. Williams
Cognitive impairments are a major contributor to psychosocial dysfunction in major depressive disorder, yet mechanistically selective treatments targeting these impairments are lacking. Here, in line with a precision medicine approach, we evaluated guanfacine immediate release (GIR), an α2A receptor agonist, as a novel treatment aimed at enhancing cognitive control circuit function and behavioral performance in a neurobiologically defined subtype of depression, the cognitive biotype NCT04181736 . This biotype was prospectively identified based on impairments in both cognitive control circuitry and associated behavioral performance. Seventeen participants with major depressive disorder meeting these prospective criteria completed 6−8 weeks of GIR treatment (target dose of 2 mg per night), consistent with our preregistered per-protocol analysis plan. GIR significantly increased activation and connectivity within the cognitive control circuit. The clinical response (defined as a ≥50% reduction on the 17-item Hamilton Depression Rating Scale (HDRS)) was achieved by 76.5%, of patients, exceeding conventional antidepressant response rates, and 84.6% also achieved remission (HDRS score of ≤7). GIR also led to significant improvements in cognitive control performance, global life satisfaction and quality of life. Here we demonstrate both clinical efficacy and circuit target engagement of GIR as a mechanistically selective treatment for the cognitive biotype of depression. This study demonstrates that guanfacine immediate release enhances cognitive control circuit function and behavioral performance in a neurobiologically defined cognitive biotype of depression, achieving a 76.5% clinical response rate and improving life satisfaction, marking a promising advance in precision medicine.
{"title":"A stratified precision medicine trial targeting α2A-adrenergic receptor agonism as a treatment for the cognitive biotype of depression","authors":"Laura M. Hack, Jenna Jubeir, Rachel Hilton, Leonardo Tozzi, Leyla Boyar, Xue Zhang, Timothy Lyons, Booil Jo, Ruth O’Hara, Alan F. Schatzberg, Leanne M. Williams","doi":"10.1038/s44220-025-00510-7","DOIUrl":"10.1038/s44220-025-00510-7","url":null,"abstract":"Cognitive impairments are a major contributor to psychosocial dysfunction in major depressive disorder, yet mechanistically selective treatments targeting these impairments are lacking. Here, in line with a precision medicine approach, we evaluated guanfacine immediate release (GIR), an α2A receptor agonist, as a novel treatment aimed at enhancing cognitive control circuit function and behavioral performance in a neurobiologically defined subtype of depression, the cognitive biotype NCT04181736 . This biotype was prospectively identified based on impairments in both cognitive control circuitry and associated behavioral performance. Seventeen participants with major depressive disorder meeting these prospective criteria completed 6−8 weeks of GIR treatment (target dose of 2 mg per night), consistent with our preregistered per-protocol analysis plan. GIR significantly increased activation and connectivity within the cognitive control circuit. The clinical response (defined as a ≥50% reduction on the 17-item Hamilton Depression Rating Scale (HDRS)) was achieved by 76.5%, of patients, exceeding conventional antidepressant response rates, and 84.6% also achieved remission (HDRS score of ≤7). GIR also led to significant improvements in cognitive control performance, global life satisfaction and quality of life. Here we demonstrate both clinical efficacy and circuit target engagement of GIR as a mechanistically selective treatment for the cognitive biotype of depression. This study demonstrates that guanfacine immediate release enhances cognitive control circuit function and behavioral performance in a neurobiologically defined cognitive biotype of depression, achieving a 76.5% clinical response rate and improving life satisfaction, marking a promising advance in precision medicine.","PeriodicalId":74247,"journal":{"name":"Nature mental health","volume":"3 11","pages":"1363-1373"},"PeriodicalIF":8.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44220-025-00510-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450099","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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