Pub Date : 2025-11-19DOI: 10.1016/j.bpsgos.2025.100656
Sherod E. Haynes , Anthony Lacagnina , Hyun Seong Seo , Fang Li , Xiao Yang , Muhammad Furqan Afzal , Carole Morel , Aurelie Menigoz , Kanaka Rajan , Roger L. Clem , Barbara Juarez , Helen S. Mayberg , Donald G. Rainnie , Larry J. Young , Ming-Hu Han
Background
Cumulative stress is a major risk factor for developing major depressive disorder (MDD), but not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point or by what mechanism a trajectory of stable resiliency emerges.
Methods
Utilizing a 10-day repeated social defeat stress (RSDS) model for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible male mice. Cell-type selective electrophysiology, chemogenetics, optogenetics, and RNA quantification were used to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience.
Results
In response to ongoing stress, corticotropin-releasing factor (CRF+, but not CRF−) neurons of the BNSTov displayed a sustained increased firing rate in resilient but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history.
Conclusions
Our study reveals a novel process by which individuals may persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.
{"title":"Stress History Modulates Corticotropin-Releasing Factor Neurons to Establish Resilience","authors":"Sherod E. Haynes , Anthony Lacagnina , Hyun Seong Seo , Fang Li , Xiao Yang , Muhammad Furqan Afzal , Carole Morel , Aurelie Menigoz , Kanaka Rajan , Roger L. Clem , Barbara Juarez , Helen S. Mayberg , Donald G. Rainnie , Larry J. Young , Ming-Hu Han","doi":"10.1016/j.bpsgos.2025.100656","DOIUrl":"10.1016/j.bpsgos.2025.100656","url":null,"abstract":"<div><h3>Background</h3><div>Cumulative stress is a major risk factor for developing major depressive disorder (MDD), but not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point or by what mechanism a trajectory of stable resiliency emerges.</div></div><div><h3>Methods</h3><div>Utilizing a 10-day repeated social defeat stress (RSDS) model for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible male mice. Cell-type selective electrophysiology, chemogenetics, optogenetics, and RNA quantification were used to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience.</div></div><div><h3>Results</h3><div>In response to ongoing stress, corticotropin-releasing factor (CRF<sup>+</sup>, but not CRF<sup>−</sup>) neurons of the BNSTov displayed a sustained increased firing rate in resilient but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history.</div></div><div><h3>Conclusions</h3><div>Our study reveals a novel process by which individuals may persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100656"},"PeriodicalIF":3.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038037","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 : 2025-11-17DOI: 10.1016/j.bpsgos.2025.100641
Deepak K. Sarpal
{"title":"Artificial Intelligence Meets Ultra-High-Field Neuroimaging to Examine Psychosis","authors":"Deepak K. Sarpal","doi":"10.1016/j.bpsgos.2025.100641","DOIUrl":"10.1016/j.bpsgos.2025.100641","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100641"},"PeriodicalIF":3.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571562","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 : 2025-11-13DOI: 10.1016/j.bpsgos.2025.100655
Noam Goldway , Taly Markovits , Naomi Fine , Tom Fruchtman-Steinbok , Guy Gurevitch , Gustavo Deco , Haggai Sharon , Talma Hendler
Background
Dissociation, an altered state of consciousness in which individuals feel detached from their body, environment, and sense of self, is a common feature of posttraumatic stress disorder (PTSD). Despite its significance, the neurocognitive processes underlying dissociation remain poorly understood, potentially limiting diagnostic precision and treatment efficacy in PTSD.
Methods
To address this gap, we applied network control theory to resting-state functional magnetic resonance imaging to examine neural dynamics during dissociative states in 2 contexts: healthy volunteers (n = 30) undergoing intravenous administration of ketamine, an anesthetic known to induce dissociative states, and patients with PTSD receiving an intervention aimed at alleviating dissociative symptoms (a secondary analysis of data from 78 patients who participated in previously conducted clinical trials).
Results
Ketamine administration led to resting-state brain dynamics resembling those observed in patients with PTSD before treatment, characterized by an increased dominance of a default mode network (DMN) meta-state and a decreased dominance of a somatomotor network (SOM) meta-state. Posttreatment reduction in the dominance of the DMN meta-state correlated with a decrease in dissociative symptoms in patients with PTSD. Computational modeling analysis revealed that after treatment, patients with PTSD exhibited a more organized and less entropic brain state. However, contrary to our hypothesis, ketamine administration did not lead to significant changes in these entropy-related indices.
Conclusions
Dissociative states, whether induced by pharmacological manipulation or clinical condition, are accompanied by increased dominance of the DMN meta-state and reduced dominance of the SOM meta-state.
{"title":"Brain State Dynamics in Ketamine-Induced Dissociation Resemble Those in Posttraumatic Stress Disorder","authors":"Noam Goldway , Taly Markovits , Naomi Fine , Tom Fruchtman-Steinbok , Guy Gurevitch , Gustavo Deco , Haggai Sharon , Talma Hendler","doi":"10.1016/j.bpsgos.2025.100655","DOIUrl":"10.1016/j.bpsgos.2025.100655","url":null,"abstract":"<div><h3>Background</h3><div>Dissociation, an altered state of consciousness in which individuals feel detached from their body, environment, and sense of self, is a common feature of posttraumatic stress disorder (PTSD). Despite its significance, the neurocognitive processes underlying dissociation remain poorly understood, potentially limiting diagnostic precision and treatment efficacy in PTSD.</div></div><div><h3>Methods</h3><div>To address this gap, we applied network control theory to resting-state functional magnetic resonance imaging to examine neural dynamics during dissociative states in 2 contexts: healthy volunteers (<em>n</em> = 30) undergoing intravenous administration of ketamine, an anesthetic known to induce dissociative states, and patients with PTSD receiving an intervention aimed at alleviating dissociative symptoms (a secondary analysis of data from 78 patients who participated in previously conducted clinical trials).</div></div><div><h3>Results</h3><div>Ketamine administration led to resting-state brain dynamics resembling those observed in patients with PTSD before treatment, characterized by an increased dominance of a default mode network (DMN) meta-state and a decreased dominance of a somatomotor network (SOM) meta-state. Posttreatment reduction in the dominance of the DMN meta-state correlated with a decrease in dissociative symptoms in patients with PTSD. Computational modeling analysis revealed that after treatment, patients with PTSD exhibited a more organized and less entropic brain state. However, contrary to our hypothesis, ketamine administration did not lead to significant changes in these entropy-related indices.</div></div><div><h3>Conclusions</h3><div>Dissociative states, whether induced by pharmacological manipulation or clinical condition, are accompanied by increased dominance of the DMN meta-state and reduced dominance of the SOM meta-state.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100655"},"PeriodicalIF":3.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885158","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 : 2025-11-12DOI: 10.1016/j.bpsgos.2025.100639
Mary M. Torregrossa
{"title":"Harnessing Analysis of Individual Differences in Behavior to Identify Novel Mechanisms Relevant to Neuropsychiatric Disorders","authors":"Mary M. Torregrossa","doi":"10.1016/j.bpsgos.2025.100639","DOIUrl":"10.1016/j.bpsgos.2025.100639","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100639"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520846","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 : 2025-11-12DOI: 10.1016/j.bpsgos.2025.100653
Mariah DeSerisy , Huiyu Yang , Jacob W. Cohen , Juan Sanchez-Peña , David Semanek , Hajer Nakua , Gaurav H. Patel , David Pagliaccio , Amy E. Margolis
Background
Irritability is transdiagnostic and associated with considerable impairment. The behavioral presentation of irritability may vary with age, sex, and diagnosis. Although inconsistent, clinical evidence indicates that irritability may present as temper tantrums associated with neurodevelopmental disorders in young boys, whereas irritability in girls may manifest in adolescence associated with negative mood. Functional activation of subcortical regions is characteristic of irritability, but the structural correlates of irritability in these regions are underexplored. We hypothesized that age, sex, and diagnosis would modify subcortical correlates of irritability.
Methods
False discovery rate–corrected regression models tested whether associations between irritability and subcortical structures were moderated by sex, age, or diagnosis in 1792 youths from the Healthy Brain Network dataset (release 11.0), a cohort weighted for psychiatric problems. Irritability was measured via the Affective Reactivity Index. FreeSurfer 6.0.1 extracted subcortical structures.
Results
Effect modification by sex indicated higher irritability associated with smaller reward-related volumes (right nucleus accumbens, bilateral caudate) in boys and with larger threat-related volumes (left amygdala) in girls. Effect modification by age or diagnosis was not significant.
Conclusions
Sex-specific subcortical correlates may explain sex-specific differences in the behavioral presentation of irritability. In models of irritability, the subcortex governs initiation of angry responses, which are dampened by prefrontal cortices. The altered volumes in reward-related regions in boys and threat-related regions in girls reported herein may be markers of early risk for irritability and/or possible targets for brain-informed interventions. Girls may benefit from irritability treatments targeting threat-based pathways, and boys may benefit from treatments targeting reward-based pathways.
{"title":"Sex-Specific Associations of Irritability With Subcortical Brain Volumes","authors":"Mariah DeSerisy , Huiyu Yang , Jacob W. Cohen , Juan Sanchez-Peña , David Semanek , Hajer Nakua , Gaurav H. Patel , David Pagliaccio , Amy E. Margolis","doi":"10.1016/j.bpsgos.2025.100653","DOIUrl":"10.1016/j.bpsgos.2025.100653","url":null,"abstract":"<div><h3>Background</h3><div>Irritability is transdiagnostic and associated with considerable impairment. The behavioral presentation of irritability may vary with age, sex, and diagnosis. Although inconsistent, clinical evidence indicates that irritability may present as temper tantrums associated with neurodevelopmental disorders in young boys, whereas irritability in girls may manifest in adolescence associated with negative mood. Functional activation of subcortical regions is characteristic of irritability, but the structural correlates of irritability in these regions are underexplored. We hypothesized that age, sex, and diagnosis would modify subcortical correlates of irritability.</div></div><div><h3>Methods</h3><div>False discovery rate–corrected regression models tested whether associations between irritability and subcortical structures were moderated by sex, age, or diagnosis in 1792 youths from the Healthy Brain Network dataset (release 11.0), a cohort weighted for psychiatric problems. Irritability was measured via the Affective Reactivity Index. FreeSurfer 6.0.1 extracted subcortical structures.</div></div><div><h3>Results</h3><div>Effect modification by sex indicated higher irritability associated with smaller reward-related volumes (right nucleus accumbens, bilateral caudate) in boys and with larger threat-related volumes (left amygdala) in girls. Effect modification by age or diagnosis was not significant.</div></div><div><h3>Conclusions</h3><div>Sex-specific subcortical correlates may explain sex-specific differences in the behavioral presentation of irritability. In models of irritability, the subcortex governs initiation of angry responses, which are dampened by prefrontal cortices. The altered volumes in reward-related regions in boys and threat-related regions in girls reported herein may be markers of early risk for irritability and/or possible targets for brain-informed interventions. Girls may benefit from irritability treatments targeting threat-based pathways, and boys may benefit from treatments targeting reward-based pathways.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100653"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798695","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 : 2025-11-12DOI: 10.1016/j.bpsgos.2025.100654
Hassan Jubair
Dissociative disorders (DDs), including dissociative identity disorder and depersonalization disorder, are complex and often misdiagnosed psychiatric conditions due to their overlapping symptoms with other mental illnesses. Electroencephalography (EEG), a low-cost and noninvasive neuroimaging tool, is a valuable means of examining the neurophysiological signatures associated with DDs. In this review, we aim to systematically evaluate how machine learning (ML) and deep learning (DL) methods are applied to EEG data for the diagnosis and monitoring of DDs, highlighting their effectiveness, limitations, and future research directions. We reviewed and synthesized studies involving EEG-based ML and DL models applied to DD-related data. The analysis focused on EEG biomarkers, model architecture (e.g., support vector machines, convolutional neural networks [CNNs], recurrent neural networks [RNNs]), feature types (raw vs. handcrafted), performance metrics, and reported challenges. Findings indicate that DL models, especially CNN and RNN, outperform traditional ML models by learning complex spatiotemporal EEG patterns. Key EEG biomarkers identified include altered frontal EEG power, disrupted theta and alpha rhythms, and attenuated P300 components. Hybrid and raw feature–based DL approaches yielded the highest classification accuracies (up to 98.3%) in related neuropsychiatric tasks. EEG-based DL techniques offer promising advancements in diagnosing DDs. However, challenges such as data scarcity, model interpretability, and generalizability persist. Future research should focus on explainable artificial intelligence, multimodal integration, transfer learning, and personalized EEG biomarkers to bridge the gap between research and clinical application.
{"title":"Electroencephalography-Based Machine and Deep Learning Approaches for the Diagnosis of Dissociative Disorders: A Comprehensive Review","authors":"Hassan Jubair","doi":"10.1016/j.bpsgos.2025.100654","DOIUrl":"10.1016/j.bpsgos.2025.100654","url":null,"abstract":"<div><div>Dissociative disorders (DDs), including dissociative identity disorder and depersonalization disorder, are complex and often misdiagnosed psychiatric conditions due to their overlapping symptoms with other mental illnesses. Electroencephalography (EEG), a low-cost and noninvasive neuroimaging tool, is a valuable means of examining the neurophysiological signatures associated with DDs. In this review, we aim to systematically evaluate how machine learning (ML) and deep learning (DL) methods are applied to EEG data for the diagnosis and monitoring of DDs, highlighting their effectiveness, limitations, and future research directions. We reviewed and synthesized studies involving EEG-based ML and DL models applied to DD-related data. The analysis focused on EEG biomarkers, model architecture (e.g., support vector machines, convolutional neural networks [CNNs], recurrent neural networks [RNNs]), feature types (raw vs. handcrafted), performance metrics, and reported challenges. Findings indicate that DL models, especially CNN and RNN, outperform traditional ML models by learning complex spatiotemporal EEG patterns. Key EEG biomarkers identified include altered frontal EEG power, disrupted theta and alpha rhythms, and attenuated P300 components. Hybrid and raw feature–based DL approaches yielded the highest classification accuracies (up to 98.3%) in related neuropsychiatric tasks. EEG-based DL techniques offer promising advancements in diagnosing DDs. However, challenges such as data scarcity, model interpretability, and generalizability persist. Future research should focus on explainable artificial intelligence, multimodal integration, transfer learning, and personalized EEG biomarkers to bridge the gap between research and clinical application.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100654"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798707","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 : 2025-11-12DOI: 10.1016/j.bpsgos.2025.100628
Christal N. Davis
{"title":"Using Genetics to Shed Light on the Scientific Gray Zone of Functional Seizures","authors":"Christal N. Davis","doi":"10.1016/j.bpsgos.2025.100628","DOIUrl":"10.1016/j.bpsgos.2025.100628","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100628"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520847","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 : 2025-11-10DOI: 10.1016/j.bpsgos.2025.100652
Gudmundur Einarsson , Hannes K. Arnason , Rosa S. Gisladottir , Gyda Bjornsdottir , Thorgeir E. Thorgeirsson , Astros Skuladottir , G. Bragi Walters , Saedis Saevarsdottir , Magnus K. Magnusson , Gisli H. Halldorsson , Audunn S. Snaebjarnarson , Hafsteinn Einarsson , Gardar Sveinbjornsson , Hannes Helgason , Vinicius Tragante , Gudrun A. Jonsdottir , Hildur M. Aegisdottir , Ingileif Jonsdottir , Thorarinn Gislason , Gudmar Thorleifsson , Kari Stefansson
Background
Zopiclone and zolpidem are widely prescribed hypnotic medications for insomnia, sharing similar efficacy but differing in side-effect profiles, particularly concerning taste disturbances. Identifying genetic predictors of intolerance to these medications could inform personalized treatment strategies.
Methods
We conducted a genome-wide association study to identify genetic variants associated with switching between zopiclone and zolpidem in 57,669 Icelanders, using electronic prescription data from Iceland (2003–2020), and 6590 British individuals from the UK Biobank (1990–2017). We included individuals who had received at least 3 prescriptions of either drug. We also investigated data on bitter taste perception using quinine taste test data from 2238 Icelandic individuals.
Results
A common sequence variant, rs6488335-G, within the TAS2R∗ bitter taste receptor gene locus on chromosome 12, was associated with an increased likelihood of switching from zopiclone to zolpidem (Iceland: odds ratio [OR], 1.29; 95% CI, 1.24 to 1.35; United Kingdom: OR, 1.34; 95% CI, 1.12 to 1.59) and a decreased likelihood of switching in the reverse direction. The effect was more pronounced in women (ORfemales, 1.36; 95% CI, 1.29 to 1.44) than in men (ORmales, 1.19; 95% CI, 1.11 to 1.27). While the variant is associated with bitter taste perception of quinine, conditional analyses suggest that the pharmacogenetic association with drug switching is independent of taste perception.
Conclusions
Our findings indicate that carriers of the rs6488335-G variant, particularly homozygous women, were more likely to switch from zopiclone to zolpidem, potentially due to heightened sensitivity to taste-related side effects. Preemptive genetic testing could guide clinicians in prescribing zolpidem over zopiclone for individuals at risk, thereby reducing health care visits and improving treatment adherence.
{"title":"Variant in a Taste Receptor Locus Tied to Changes in the Use of Insomnia Medication","authors":"Gudmundur Einarsson , Hannes K. Arnason , Rosa S. Gisladottir , Gyda Bjornsdottir , Thorgeir E. Thorgeirsson , Astros Skuladottir , G. Bragi Walters , Saedis Saevarsdottir , Magnus K. Magnusson , Gisli H. Halldorsson , Audunn S. Snaebjarnarson , Hafsteinn Einarsson , Gardar Sveinbjornsson , Hannes Helgason , Vinicius Tragante , Gudrun A. Jonsdottir , Hildur M. Aegisdottir , Ingileif Jonsdottir , Thorarinn Gislason , Gudmar Thorleifsson , Kari Stefansson","doi":"10.1016/j.bpsgos.2025.100652","DOIUrl":"10.1016/j.bpsgos.2025.100652","url":null,"abstract":"<div><h3>Background</h3><div>Zopiclone and zolpidem are widely prescribed hypnotic medications for insomnia, sharing similar efficacy but differing in side-effect profiles, particularly concerning taste disturbances. Identifying genetic predictors of intolerance to these medications could inform personalized treatment strategies.</div></div><div><h3>Methods</h3><div>We conducted a genome-wide association study to identify genetic variants associated with switching between zopiclone and zolpidem in 57,669 Icelanders, using electronic prescription data from Iceland (2003–2020), and 6590 British individuals from the UK Biobank (1990–2017). We included individuals who had received at least 3 prescriptions of either drug. We also investigated data on bitter taste perception using quinine taste test data from 2238 Icelandic individuals.</div></div><div><h3>Results</h3><div>A common sequence variant, rs6488335-G, within the <em>TAS2R</em><em>∗</em> bitter taste receptor gene locus on chromosome 12, was associated with an increased likelihood of switching from zopiclone to zolpidem (Iceland: odds ratio [OR], 1.29; 95% CI, 1.24 to 1.35; United Kingdom: OR, 1.34; 95% CI, 1.12 to 1.59) and a decreased likelihood of switching in the reverse direction. The effect was more pronounced in women (OR<sub>females</sub>, 1.36; 95% CI, 1.29 to 1.44) than in men (OR<sub>males</sub>, 1.19; 95% CI, 1.11 to 1.27). While the variant is associated with bitter taste perception of quinine, conditional analyses suggest that the pharmacogenetic association with drug switching is independent of taste perception.</div></div><div><h3>Conclusions</h3><div>Our findings indicate that carriers of the rs6488335-G variant, particularly homozygous women, were more likely to switch from zopiclone to zolpidem, potentially due to heightened sensitivity to taste-related side effects. Preemptive genetic testing could guide clinicians in prescribing zolpidem over zopiclone for individuals at risk, thereby reducing health care visits and improving treatment adherence.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100652"},"PeriodicalIF":3.7,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746984","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 : 2025-11-10DOI: 10.1016/j.bpsgos.2025.100625
Jon E. Grant
{"title":"Rethinking Trichotillomania","authors":"Jon E. Grant","doi":"10.1016/j.bpsgos.2025.100625","DOIUrl":"10.1016/j.bpsgos.2025.100625","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100625"},"PeriodicalIF":3.7,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520841","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 : 2025-11-07DOI: 10.1016/j.bpsgos.2025.100651
Huanqing Yang , Sowmya Narayan , Joeri Bordes , Lotte van Doeselaar , Carlo De Donno , Matthias Eder , Danusa Menegaz , Rosa-Eva Huettl , Lea-Maria Brix , Shiladitya Mitra , Margherita Springer , Marianne B. Müller , Alon Chen , Jan M. Deussing , Juan Pablo Lopez , Mathias V. Schmidt
Background
Exposure to stressful life events is a major risk factor for many psychiatric disorders. The mineralocorticoid receptor (MR) is a key regulator of the hypothalamic-pituitary-adrenal axis, a central stress response component. Stress-related mental disorders, such as anxiety and depression, are associated with MR dysfunction in the brain, but its cell type–specific contributions to emotional behavior and cognitive function remain unclear.
Methods
Using a mouse model with a specific deletion of MR in forebrain glutamatergic neurons, we tested the behavioral, structural, and functional impact of MR in this neuronal population (n = 9–14 for behavioral and n = 3–4 for structural and functional analyses).
Results
We revealed a specific function of MR in regulating baseline anxiety in male but not female mice. This distinct behavioral phenotype was associated with hippocampal structural and functional alterations. Furthermore, we identified a previously unrecognized downstream target of MR, the actin-bundling factor Fam107a, whose expression is tightly regulated by MR. Overexpression of Fam107a in the hippocampus was sufficient to rescue the increased anxiety phenotype of glutamatergic MR knockout mice.
Conclusions
Together, our results underline the central role of MR as a potential target in understanding the intricate interplay between stress, resilience, and mental health.
暴露于压力生活事件是许多精神疾病的主要危险因素。矿化皮质激素受体（MR）是下丘脑-垂体-肾上腺轴的关键调节因子，是应激反应的中心成分。与压力相关的精神障碍，如焦虑和抑郁，与大脑的核磁共振功能障碍有关，但其细胞类型特异性对情绪行为和认知功能的贡献尚不清楚。方法使用前脑谷氨酸能神经元特异性MR缺失的小鼠模型，我们测试了MR对该神经元群体的行为、结构和功能影响（n = 9-14, n = 3-4）。结果我们发现MR在雄性小鼠而非雌性小鼠中具有调节基线焦虑的特定功能。这种独特的行为表型与海马结构和功能改变有关。此外，我们发现了一个以前未被识别的MR下游靶点，即肌动蛋白捆绑因子Fam107a，其表达受到MR的严格调控，在海马中过度表达Fam107a足以挽救谷氨酸能MR敲除小鼠增加的焦虑表型。总之，我们的研究结果强调了MR在理解压力、恢复力和心理健康之间错综复杂的相互作用方面的核心作用。
{"title":"Mineralocorticoid Receptor in Glutamatergic Neurons Modulates Anxiety Exclusively in Male Mice Via Regulation of the Actin-Bundling Factor Fam107a","authors":"Huanqing Yang , Sowmya Narayan , Joeri Bordes , Lotte van Doeselaar , Carlo De Donno , Matthias Eder , Danusa Menegaz , Rosa-Eva Huettl , Lea-Maria Brix , Shiladitya Mitra , Margherita Springer , Marianne B. Müller , Alon Chen , Jan M. Deussing , Juan Pablo Lopez , Mathias V. Schmidt","doi":"10.1016/j.bpsgos.2025.100651","DOIUrl":"10.1016/j.bpsgos.2025.100651","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to stressful life events is a major risk factor for many psychiatric disorders. The mineralocorticoid receptor (MR) is a key regulator of the hypothalamic-pituitary-adrenal axis, a central stress response component. Stress-related mental disorders, such as anxiety and depression, are associated with MR dysfunction in the brain, but its cell type–specific contributions to emotional behavior and cognitive function remain unclear.</div></div><div><h3>Methods</h3><div>Using a mouse model with a specific deletion of MR in forebrain glutamatergic neurons, we tested the behavioral, structural, and functional impact of MR in this neuronal population (<em>n</em> = 9–14 for behavioral and <em>n</em> = 3–4 for structural and functional analyses).</div></div><div><h3>Results</h3><div>We revealed a specific function of MR in regulating baseline anxiety in male but not female mice. This distinct behavioral phenotype was associated with hippocampal structural and functional alterations. Furthermore, we identified a previously unrecognized downstream target of MR, the actin-bundling factor Fam107a, whose expression is tightly regulated by MR. Overexpression of Fam107a in the hippocampus was sufficient to rescue the increased anxiety phenotype of glutamatergic MR knockout mice.</div></div><div><h3>Conclusions</h3><div>Together, our results underline the central role of MR as a potential target in understanding the intricate interplay between stress, resilience, and mental health.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100651"},"PeriodicalIF":3.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885178","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}
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