{"title":"Individualized gray matter morphological abnormalities unveil two neuroanatomical obsessive-compulsive disorder subtypes.","authors":"Baohong Wen, Keke Fang, Qiuying Tao, Ya Tian, Lianjie Niu, Wenqing Shi, Zijun Liu, Jin Sun, Liang Liu, Xiaopan Zhang, Ruiping Zheng, Hui-Rong Guo, Yarui Wei, Yong Zhang, Jingliang Cheng, Shaoqiang Han","doi":"10.1038/s41398-025-03226-5","DOIUrl":"10.1038/s41398-025-03226-5","url":null,"abstract":"<p><p>Obsessive-compulsive disorder (OCD) is a highly heterogeneous disorder, with notable variations among cases in structural brain abnormalities. To address this heterogeneity, our study aimed to delineate OCD subtypes based on individualized gray matter morphological differences. We recruited 100 untreated, first-episode OCD patients and 106 healthy controls for structural imaging scans. Utilizing normative models of gray matter volume, we identified subtypes based on individual morphological abnormalities. Sensitivity analyses were conducted to validate the reproducibility of clustering outcomes. To gain deeper insights into the connectomic and molecular underpinnings of structural brain abnormalities in the identified subtypes, we investigated their associations with normal brain network architecture and the distribution of neurotransmitter receptors/transporters. Our findings revealed two distinct OCD subtypes exhibiting divergent patterns of structural brain abnormalities. Sensitivity analysis results confirmed the robustness of the identified subtypes. Subtype 1 displayed significantly increased gray matter volume in regions including the frontal gyrus, precuneus, insula, hippocampus, parahippocampal gyrus, amygdala, and temporal gyrus, while subtype 2 exhibited decreased gray matter volume in the frontal gyrus, precuneus, insula, superior parietal gyrus, temporal gyrus, and fusiform gyrus. When considering all patients collectively, structural brain abnormalities nullified. The identified subtypes were characterized by divergent disease epicenters. Specifically, subtype 1 showed disease epicenters in the middle frontal gyrus, while subtype 2 displayed disease epicenters in the striatum, thalamus and hippocampus. Furthermore, structural brain abnormalities in these subtypes displayed distinct associations with neurotransmitter receptors/transporters. The identified subtypes offer novel insights into nosology and the heterogeneous nature of OCD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"23"},"PeriodicalIF":5.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giuseppe Fanelli, Emanuel Raschi, Gaye Hafez, Silke Matura, Carmen Schiweck, Elisabetta Poluzzi, Carlotta Lunghi
{"title":"The interface of depression and diabetes: treatment considerations.","authors":"Giuseppe Fanelli, Emanuel Raschi, Gaye Hafez, Silke Matura, Carmen Schiweck, Elisabetta Poluzzi, Carlotta Lunghi","doi":"10.1038/s41398-025-03234-5","DOIUrl":"10.1038/s41398-025-03234-5","url":null,"abstract":"<p><p>This state-of-the-art review explores the relationship between depression and diabetes, highlighting the two-way influences that make treatment challenging and worsen the outcomes of both conditions. Depression and diabetes often co-occur and share genetic, lifestyle, and psychosocial risk factors. Lifestyle elements such as diet, physical activity, and sleep patterns play a role on the development and management of both conditions, highlighting the need for integrated treatment strategies. The evidence suggests that traditional management strategies focusing on either condition in isolation fall short of addressing the intertwined nature of diabetes and depression. Instead, integrated care models encompassing psychological support and medical management are recommended to improve treatment efficacy and patient adherence. Such models require collaboration across multiple healthcare disciplines, including endocrinology, psychiatry, and primary care, to offer a holistic approach to patient care. This review also identifies significant patient-related barriers to effective management, such as stigma, psychological resistance, and health literacy, which need to be addressed through patient-centered education and support systems. Future directions for research include longitudinal studies in diverse populations to further elucidate causal relationships and the exploration of novel therapeutic targets, as well as the effectiveness of healthcare models aimed at preventing the onset of one condition in individuals diagnosed with the other.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"22"},"PeriodicalIF":5.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christa Hohoff, Nicole Kerkenberg, Mingyue Zhang, Weronika Palkowska, Lydia Wachsmuth, Maja Peng, Lena Stiehl, Christiane Schettler, Johannes C S Zang, Andreas Huge, Evgeni Ponimaskin, Cornelius Faber, Bernhard T Baune, Weiqi Zhang
{"title":"Deficiency of the palmitoyl acyltransferase ZDHHC7 modulates depression-like behaviour in female mice after a mild chronic stress paradigm.","authors":"Christa Hohoff, Nicole Kerkenberg, Mingyue Zhang, Weronika Palkowska, Lydia Wachsmuth, Maja Peng, Lena Stiehl, Christiane Schettler, Johannes C S Zang, Andreas Huge, Evgeni Ponimaskin, Cornelius Faber, Bernhard T Baune, Weiqi Zhang","doi":"10.1038/s41398-025-03240-7","DOIUrl":"10.1038/s41398-025-03240-7","url":null,"abstract":"<p><p>Chronic stress (CS) is a debilitating condition that negatively affects body and brain. In mice, CS effects range from changes in behaviour and brain microstructure down to the level of gene expression. These effects are partly mediated by sex and sex steroid hormones, which in turn are affected by the palmitoyl acyltransferase ZDHHC7. ZDHHC7 might modulate also the response to CS via palmitoylation of sex steroid hormone receptors and other proteins critical for neuronal structure and functions. Therefore, we aimed to investigate the role of ZDHHC7 in response to CS on different system levels in a mouse model of Zdhhc7-deficiency. Female and male Zdhhc7-knockout (KO) and -wildtype (WT) mice underwent a four-week-mild CS paradigm or non-stress control (C) condition. After C or CS, behaviours, hippocampal microstructures (via MRI-based diffusion tensor imaging) and brain gene expression profiles (via mRNA-seq transcriptomics) were investigated. Analyses focused on effects of genotype (KO vs. WT) or condition (C vs. CS) separately in both sexes. Our results revealed significant effects particularly in females. Female KOs displayed increased locomotion and reduced depression-like behaviour after CS (KO vs. WT, C vs. CS: p<sub>all</sub> < 0.05). Hippocampal fibres were reduced in female KOs after C (KO vs. WT: p<sub>all</sub> < 0.05) but in female WTs after CS (C vs. CS: p<sub>all</sub> < 0.05). Furthermore, female KOs showed increased cortistatin expression after CS (C vs. CS: mRNAseq and qPCR p<sub>all</sub> < 0.05). In sum, Zdhhc7-deficiency reduced depression-like behaviours, prevented hippocampal fibre reduction and upregulated cortistatin after CS. It seemed to be related to a sex-specific stress response and may reveal genetic factors of CS-resilience in female mice.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"20"},"PeriodicalIF":5.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The left amygdala is genetically sexually-dimorphic: multi-omics analysis of structural MRI volumes.","authors":"Yuanyuan Gui, Geyu Zhou, Shuya Cui, Hongyu Li, Hui Lu, Hongyu Zhao","doi":"10.1038/s41398-025-03223-8","DOIUrl":"10.1038/s41398-025-03223-8","url":null,"abstract":"<p><p>Brain anatomy plays a key role in complex behaviors and mental disorders that are sexually divergent. While our understanding of the sex differences in the brain anatomy remains relatively limited, particularly of the underlying genetic and molecular mechanisms that contribute to these differences. We performed the largest study of sex differences in brain volumes (N = 33,208) by examining sex differences both in the raw brain volumes and after controlling the whole brain volumes. Genetic correlation analysis revealed sex differences only in the left amygdala. We compared transcriptome differences between males and females using data from GTEx and characterized cell-type compositions using GTEx bulk amygdala RNA-seq data and LIBD amygdala single-cell reference profiles. We also constructed polygenic risk scores (PRS) to investigate sex-specific genetic correlations between left amygdala volume and mental disorders (N = 25,576~105,318) of Psychiatric Genomics Consortium and other traits of UKB (N = 347,996). Although there were pronounced sex differences in brain volumes, there was no difference in the heritability between sexes. There was a significant sex-specific genetic correlation between male and female left amygdala. We identified sex-differentiated genetic effects of PRSs for schizophrenia on left amygdala volume, as well as significant sex-differentiated genetic correlations between PRSs of left amygdala and six traits in UKB. We also found several sex-differentially expressed genes in the amygdala. These findings not only advanced the current knowledge of genetic basis of sex differences in brain anatomy, but also presented an important clue for future research on the mechanism of sex differences in mental disorders and targeted treatments.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"17"},"PeriodicalIF":5.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Klara Mareckova, Ana Paula Mendes-Silva, Martin Jáni, Anna Pacinkova, Pavel Piler, Vanessa F Gonçalves, Yuliya S Nikolova
{"title":"Mitochondrial DNA variants and their impact on epigenetic and biological aging in young adulthood.","authors":"Klara Mareckova, Ana Paula Mendes-Silva, Martin Jáni, Anna Pacinkova, Pavel Piler, Vanessa F Gonçalves, Yuliya S Nikolova","doi":"10.1038/s41398-025-03235-4","DOIUrl":"10.1038/s41398-025-03235-4","url":null,"abstract":"<p><p>The pace of biological aging varies between people independently of chronological age and mitochondria dysfunction is a key hallmark of biological aging. We hypothesized that higher functional impact (FI) score of mitochondrial DNA (mtDNA) variants might contribute to premature aging and tested the relationships between a novel FI score of mtDNA variants and epigenetic and biological aging in young adulthood. A total of 81 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort had good quality genetic data as well as blood-based markers to estimate biological aging in the late 20. A subset of these participants (n = 69) also had epigenetic data to estimate epigenetic aging in the early 20s using Horvath's epigenetic clock. The novel FI score was calculated based on 7 potentially pathogenic mtDNA variants. Greater FI score of mtDNA variants was associated with older epigenetic age in the early 20s and older biological age in the late 20s. These medium to large effects were independent of sex, current BMI, cigarette smoking, cannabis, and alcohol use. These findings suggest that elevated FI score of mtDNA variants might contribute to premature aging in young adulthood.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"16"},"PeriodicalIF":5.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoqian Ma, Nana Feng, Lena Palaniyappan, Luolong Cao, Zixin Gu, Jujiao Kang, Liu Yuan, Lijun Ouyang, Yujue Wang, Chunwang Li, Ke Jin, Xiaogang Chen, Jianfeng Feng, Ying He, Qiang Luo
{"title":"Neuroimaging stratification reveals the striatal vulnerability to stress as a risk for schizophrenia.","authors":"Xiaoqian Ma, Nana Feng, Lena Palaniyappan, Luolong Cao, Zixin Gu, Jujiao Kang, Liu Yuan, Lijun Ouyang, Yujue Wang, Chunwang Li, Ke Jin, Xiaogang Chen, Jianfeng Feng, Ying He, Qiang Luo","doi":"10.1038/s41398-025-03237-2","DOIUrl":"10.1038/s41398-025-03237-2","url":null,"abstract":"<p><p>The striatum, a core brain structure relevant for schizophrenia, exhibits heterogeneous volumetric changes in this illness. Due to this heterogeneity, its role in the risk of developing schizophrenia following exposure to environmental stress remains poorly understood. Using the putamen (a subnucleus of the striatum) as an indicator for convergent genetic risk of schizophrenia, 63 unaffected first-degree relatives of patients (22.08 ± 4.80 years) with schizophrenia (UFR-SZ) were stratified into two groups. Compared with healthy controls (HC; n = 59), voxel-based and brain-wide volumetric changes and their associations with stressful life events (SLE) were tested. These stratified associations were validated using two large population-based cohorts (the ABCD study; n = 1680, 11.92 ± 0.62 years; and UK Biobank, n = 20547, 55.38 ± 7.43 years). Transcriptomic analysis of brain tissues was used to identify the biological processes associated with the brain mediation effects on the SLE-psychosis relationship. The stratified UFR-SZ subgroup with smaller right putamen had a smaller volume in the left caudate when compared to HC; this caudate volume was associated with both a higher level of SLE and more psychotic symptoms. This caudate-SLE association was replicated in two independent large-scale cohorts, when individuals were stratified by both a higher polygenic burden for schizophrenia and smaller right putamen. In UFR-SZ, the caudate cluster mediated the relationship between SLE and more psychotic symptoms. This mediation was associated with the genes enriched in both glutamatergic synapses and response to oxidative stress. The stratified association between the striatum and stress highlights the differential vulnerability to stress, contributing to the complexity of the gene-by-environment etiology of schizophrenia.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"18"},"PeriodicalIF":5.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wei Du, Biqiu Tang, Senhao Liu, Wenjing Zhang, Su Lui
{"title":"Causal associations between iron levels in subcortical brain regions and psychiatric disorders: a Mendelian randomization study.","authors":"Wei Du, Biqiu Tang, Senhao Liu, Wenjing Zhang, Su Lui","doi":"10.1038/s41398-025-03231-8","DOIUrl":"10.1038/s41398-025-03231-8","url":null,"abstract":"<p><p>Despite observational studies linking brain iron levels to psychiatric disorders, the exact causal relationship remains poorly understood. This study aims to examine the relationship between iron levels in specific subcortical brain regions and the risk of psychiatric disorders. Utilizing two-sample Mendelian randomization (MR) analysis, this study investigates the causal associations between iron level changes in 16 subcortical nuclei and eight major psychiatric disorders, including schizophrenia (SCZ), major depressive disorder (MDD), autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and insomnia. The genetic instrumental variables linked to iron levels and psychiatric disorders were derived from the genome-wide association studies data of the UK Biobank Brain Imaging and Psychiatric Genomics Consortium. Bidirectional causal estimation was primarily obtained using the inverse variance weighting (IVW) method. Iron levels in the left substantia nigra showed a negative association with the risk of MDD (OR<sub>IVW</sub> = 0.94, 95% CI = 0.91-0.97, p < 0.001) and trends with risk of SCZ (OR<sub>IVW</sub> = 0.90, 95% CI = 0.82-0.98, p = 0.020). Conversely, iron levels in the left putamen were positively associated with the risk of ASD (OR<sub>IVW</sub> = 1.11, 95% CI = 1.04-1.19, p = 0.002). Additionally, several bidirectional trends were observed between subcortical iron levels and the risk for psychiatric disorders. Lower iron levels in the left substantia nigra may increase the risk of MDD, and potentially increase the risk of SCZ, indicating a potential shared pathogenic mechanism. Higher iron levels in the left putamen may lead to the development of ASD. The observed bidirectional trends between subcortical iron levels and psychiatric disorders, indicate the importance of the underlying biomechanical interactions between brain iron regulation and these disorders.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"19"},"PeriodicalIF":5.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Developing multifactorial dementia prediction models using clinical variables from cohorts in the US and Australia.","authors":"Caitlin A Finney, David A Brown, Artur Shvetcov","doi":"10.1038/s41398-025-03247-0","DOIUrl":"10.1038/s41398-025-03247-0","url":null,"abstract":"<p><p>Existing dementia prediction models using non-neuroimaging clinical measures have been limited in their ability to identify disease. This study used machine learning to re-examine the diagnostic potential of clinical measures for dementia. Data was sourced from the Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing (AIBL) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Clinical variables included 21 measures across medical history, hematological and other blood tests, and APOE genotype. Tree-based machine learning algorithms and artificial neural networks were used. APOE genotype was the best predictor of dementia cases and healthy controls. Our results, however, demonstrated that there are limitations when using publicly accessible cohort data that may limit the generalizability and interpretability of such predictive models. Future research should examine the use of routine APOE genetic testing for dementia diagnostics. It should also focus on clearly unifying data across clinical cohorts.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"15"},"PeriodicalIF":5.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marina Eni, Yaniv Zigel, Michal Ilan, Analya Michaelovski, Hava M Golan, Gal Meiri, Idan Menashe, Ilan Dinstein
{"title":"Reliably quantifying the severity of social symptoms in children with autism using ASDSpeech.","authors":"Marina Eni, Yaniv Zigel, Michal Ilan, Analya Michaelovski, Hava M Golan, Gal Meiri, Idan Menashe, Ilan Dinstein","doi":"10.1038/s41398-025-03233-6","DOIUrl":"10.1038/s41398-025-03233-6","url":null,"abstract":"<p><p>Several studies have demonstrated that the severity of social communication problems, a core symptom of Autism Spectrum Disorder (ASD), is correlated with specific speech characteristics of ASD individuals. This suggests that it may be possible to develop speech analysis algorithms that can quantify ASD symptom severity from speech recordings in a direct and objective manner. Here we demonstrate the utility of a new open-source AI algorithm, ASDSpeech, which can analyze speech recordings of ASD children and reliably quantify their social communication difficulties across multiple developmental timepoints. The algorithm was trained and tested on the largest ASD speech dataset available to date, which contained 99,193 vocalizations from 197 ASD children recorded in 258 Autism Diagnostic Observation Schedule, Second edition (ADOS-2) assessments. ASDSpeech was trained with acoustic and conversational features extracted from the speech recordings of 136 children, who participated in a single ADOS-2 assessment, and tested with independent recordings of 61 additional children who completed two ADOS-2 assessments, separated by 1-2 years. Estimated total ADOS-2 scores in the test set were significantly correlated with actual scores when examining either the first (r(59) = 0.544, P < 0.0001) or second (r(59) = 0.605, P < 0.0001) assessment. Separate estimation of social communication and restricted and repetitive behavior symptoms revealed that ASDSpeech was particularly accurate at estimating social communication symptoms (i.e., ADOS-2 social affect scores). These results demonstrate the potential utility of ASDSpeech for enhancing basic and clinical ASD research as well as clinical management. We openly share both algorithm and speech feature dataset for use and further development by the community.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"14"},"PeriodicalIF":5.8,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marina Ivanova, Ksenia Germanova, Dmitry S Petelin, Aynur Ragimova, Grigory Kopytin, Beatrice A Volel, Vadim V Nikulin, Maria Herrojo Ruiz
{"title":"Frequency-specific changes in prefrontal activity associated with maladaptive belief updating in volatile environments in euthymic bipolar disorder.","authors":"Marina Ivanova, Ksenia Germanova, Dmitry S Petelin, Aynur Ragimova, Grigory Kopytin, Beatrice A Volel, Vadim V Nikulin, Maria Herrojo Ruiz","doi":"10.1038/s41398-025-03225-6","DOIUrl":"10.1038/s41398-025-03225-6","url":null,"abstract":"<p><p>Bipolar disorder (BD) involves altered reward processing and decision-making, with inconsistencies across studies. Here, we integrated hierarchical Bayesian modelling with magnetoencephalography (MEG) to characterise maladaptive belief updating in this condition. First, we determined if previously reported increased learning rates in BD stem from a heightened expectation of environmental changes. Additionally, we examined if this increased expectation speeds up belief updating in decision-making, associated with modulation of rhythmic neural activity within the prefrontal, orbitofrontal, and anterior cingulate cortex (PFC, OFC, ACC). Twenty-two euthymic BD and 27 healthy control (HC) participants completed a reward-based motor decision-making task in a volatile setting. Hierarchical Bayesian modelling revealed BD participants anticipated greater environmental volatility, resulting in a more stochastic mapping from beliefs to actions and paralleled by lower win rates and a reduced tendency to repeat rewarded actions than HC. Despite this, BD individuals adjusted their expectations of action-outcome contingencies more slowly, but both groups invigorated their actions similarly. On a neural level, while healthy individuals exhibited an alpha-beta suppression and gamma increase during belief updating, BD participants showed dampened effects, extending across the PFC, OFC, and ACC regions. This was accompanied by an abnormally increased beta-band directed information flow in BD. Overall, the results suggest euthymic BD individuals anticipate environmental change without adequately learning from it, contributing to maladaptive belief updating. Alterations in frequency-domain amplitude and functional connectivity within the PFC, OFC, and ACC during belief updating underlie the computational effects and could serve as potential indicators for predicting relapse in future research.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"13"},"PeriodicalIF":5.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}