Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Imbalance of thalamocortical structural connectivity in adolescents with early-onset schizophrenia","authors":"Yonghui Xiang ,&nbsp;Shuting Chen ,&nbsp;Jinqiang Zhang ,&nbsp;Guowei Wu ,&nbsp;Xuan Ouyang ,&nbsp;Zhening Liu ,&nbsp;Chen Tan ,&nbsp;Can Xu ,&nbsp;Lange Zheng ,&nbsp;Xinran Xu ,&nbsp;Lena Palaniyappan ,&nbsp;Weidan Pu","doi":"10.1016/j.pnpbp.2025.111423","DOIUrl":"10.1016/j.pnpbp.2025.111423","url":null,"abstract":"<div><h3>Background</h3><div>Thalamocortical circuit imbalance, characterized by decreased prefrontal-thalamic connectivity and increased sensorimotor-thalamic connectivity, has been well-documented in adult-onset schizophrenia. We have previously demonstrated functional imbalance of this circuit in adolescents with early-onset schizophrenia (EOS). We now investigate whether this functional imbalance stems from the thalamocortical structural connectivity in EOS, thereby further establishing its relevance to the neurodevelopmental modeling of psychosis.</div></div><div><h3>Methods</h3><div>The study included 212 adolescents (145 EOS patients and 67 healthy controls). To further control the medication effect, the patients were divided into two subgroups (drug-naive vs drug-treated). Fourteen bilateral cortical regions of interest and bilateral thalamus were used as targets and seeds respectively for probabilistic tractography to quantify structural connectivity of the thalamocortical circuit.</div></div><div><h3>Results</h3><div>Compared to healthy controls, in EOS, structural connectivity of the thalamus with the dorsolateral prefrontal (dlPFC) and parietal cortices was decreased, while connectivity with the sensorimotor cortices was increased. We also observed an unexpected increase in connectivity of the medial prefrontal cortex (mPFC) with thalamus in EOS. The imbalance pattern was replicated in two subgroups regardless of medication status. Further correlation analysis showed that the thalamic hypoconnectivity with the dlPFC and the hyperconnectivity with the mPFC were both related with higher individual symptom burden in patients.</div></div><div><h3>Conclusions</h3><div>The functional thalamocortical circuit imbalance in adolescents with schizophrenia is underwritten by a similar imbalance in the structural connectivity. A specific thalamocortical structural hyperconnectivity involving the mPFC, previously unobserved in adult-onset patients, may contribute to the distinct clinical manifestations in EOS.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111423"},"PeriodicalIF":5.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel multidimensional, perinatal social and material deprivation paradigm induces aggressive behavior and cortical gene expression reprogramming in young adult mice","authors":"Bruno G. Berardino ,&nbsp;María Belén Cardillo ,&nbsp;Rocío Priegue ,&nbsp;Hugo C. Perez ,&nbsp;Sergio I. Nemirovsky ,&nbsp;Micaela Salvochea ,&nbsp;Verónica Cantarelli ,&nbsp;Marina F. Ponzio ,&nbsp;Mariela Chertoff ,&nbsp;Eduardo T. Cánepa","doi":"10.1016/j.pnpbp.2025.111432","DOIUrl":"10.1016/j.pnpbp.2025.111432","url":null,"abstract":"<div><div>Poverty is a complex, multidimensional stressor that affects both physical and mental health outcomes. Current animal models often isolate single aspects of socioeconomic adversity, limiting their translational relevance. This study introduces a novel murine model of social and material deprivation (SMD) designed to simulate the co-occurrence of environmental impoverishment and social stress observed in real-world settings.</div><div>During gestation and lactation pregnant mice and their litters were exposed to a combination of reduced nesting/bedding material, lack of cage enrichment, maternal separation with early weaning, and threat from a dominant male. Behavioral tests, brain morphology assessments, and prefrontal cortex gene expression analyses were performed in the offspring, considering sex as a biological variable throughout.</div><div>SMD dams displayed increased depressive-like behavior and maladaptive coping strategies, along with reduced maternal care. Offspring exhibited delayed neurodevelopment, increased anxiety-like behavior and aggression in males, and structural brain alterations, including reduced dorsal (females) and ventral (both sexes) hippocampal area, and increased prefrontal cortex width in both sexes.</div><div>Transcriptomic analyses of the prefrontal cortex revealed sex-specific patterns: in males, genes involved in neuronal development and immune function were predominantly upregulated; in females, chromatin remodeling genes were upregulated, while immune-related genes were downregulated.</div><div>The SMD model recapitulates key behavioral, morphological, and molecular features associated with early-life adversity and socioeconomic disadvantage, offering a valuable tool to investigate sex-specific neurobiological responses to complex stress exposure during sensitive developmental windows.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111432"},"PeriodicalIF":5.3,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-chain fatty acids in mood and schizophrenia spectrum disorders: Evidence in the field and translational perspectives","authors":"Julia Karska ,&nbsp;Karolina Skonieczna-Żydecka ,&nbsp;Natalia Jakubiak ,&nbsp;Wiktoria Czarnecka ,&nbsp;Błażej Misiak","doi":"10.1016/j.pnpbp.2025.111430","DOIUrl":"10.1016/j.pnpbp.2025.111430","url":null,"abstract":"<div><div>The etiology of mood and schizophrenia spectrum disorders remains largely unknown. In recent years, several studies have focused on the role of the microbiome-gut-brain-axis (MGBA) in its etiology, providing several novel insights. The communication within MGBA involves various pathways leading through the vagus nerve and the bloodstream mediators. The latter are represented by short-chain fatty acids (SCFAs), produced by gut microbiota from dietary fiber. To date, several physiological and pathophysiological roles in the periphery and the central nervous system for SCFAs have been suggested. Studies investigating gut microbiota have consistently reported a decreased abundance of bacteria-producing SCFAs in people with mood and schizophrenia spectrum disorders. Yet, studies investigating faecal and blood levels of SCFAs have provided mixed findings. The present article provides a narrative review of studies examining the physiological roles of SCFAs, along with animal model and human studies addressing the involvement of SCFAs in mood and schizophrenia spectrum disorders, formulates future directions and provides translational perspectives.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111430"},"PeriodicalIF":5.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144469940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-lasting behavioral, molecular and functional connectivity alterations after chronic THC exposure during adolescence in mice","authors":"Laura Gómez-Acero ,&nbsp;Federico Varriano ,&nbsp;Nuria Sánchez-Fernández ,&nbsp;Francisco Ciruela ,&nbsp;Guadalupe Soria ,&nbsp;Ester Aso","doi":"10.1016/j.pnpbp.2025.111422","DOIUrl":"10.1016/j.pnpbp.2025.111422","url":null,"abstract":"<div><div>Heavy and daily use of cannabis with high contents of Δ⁹-tetrahydrocannabinol (THC) during adolescence is associated with an increased risk of developing psychotic disorders later in life. Here, we treated mice with THC during adolescence and found that this exposure impaired social interaction and increased vulnerability to develop sensorimotor gating deficiencies comparable to those previously described among heavy cannabis consumers. Importantly, we provide evidence on long-term cortico-striatal dysconnectivity induced by exposure to THC during adolescence and its correlation with impaired social interactions occurring later in adulthood. Moreover, we have observed long-lasting molecular alterations in key elements that regulate the mesolimbic dopaminergic system, namely on the balance between dopamine D₂, adenosine A_2A, and cannabinoid CB₁ receptors in the striatum of treated mice. Together, these findings contribute to a better understanding of the neurobiological bases of the deleterious effects associated with cannabis abuse during adolescence.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111422"},"PeriodicalIF":5.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of nonhuman primate models of depressive disorder","authors":"Yu Bao ,&nbsp;Di Luan ,&nbsp;Zhiqiang Meng","doi":"10.1016/j.pnpbp.2025.111421","DOIUrl":"10.1016/j.pnpbp.2025.111421","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a common mental disorder that affects people worldwide. It has been challenging to apply findings from basic research using rodents to clinical research. Many treatments that target the monoamine system are not effective. Nonhuman primates (NHPs) play an important role in both basic and translational research, but their use in research has been limited, and it is difficult to measure moods or thoughts in NHPs. In this evaluation, we focus on the depression model and behavior assessments in NHPs to understand their unique contributions to depression research. We also examine depression-like behavior in NHPs that aligns with the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) and provide an overview of insights from studies using nonhuman monkey models and behavioral assessments in the development of new and effective treatments for depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111421"},"PeriodicalIF":5.3,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-dependent effects of cumulative methylphenidate exposure on brain structure and symptom amelioration in youth with ADHD: A longitudinal MRI study","authors":"Jung-Chi Chang ,&nbsp;Hsiang-Yuan Lin ,&nbsp;Susan Shur-Fen Gau","doi":"10.1016/j.pnpbp.2025.111429","DOIUrl":"10.1016/j.pnpbp.2025.111429","url":null,"abstract":"<div><div>Methylphenidate is known to alleviate attention-deficit/hyperactivity disorder (ADHD) symptoms. However, methylphenidate's age-dependent effects on brain structure have not been well studied. This longitudinal MRI study investigated the effect of cumulative methylphenidate exposure on brain structure and ADHD-related symptoms. Eighty-nine individuals with DSM-5 ADHD and 91 typically developing controls (TDC) were assessed with MRI for brain structure and the parent-rated SNAP-IV questionnaire for ADHD-related symptoms at baseline and follow-up. The average follow-up interval was 4.86 years. Participants were divided into two age-based groups at a baseline age cutoff of 12 years. In the early-exposure subgroup (baseline age &lt; 12 years), distinct developmental differences were noted between the ADHD and TDC groups in various frontal regions. Increased cumulative methylphenidate dosage was associated with increased gray matter volumes in several frontal areas, such as the right paracentral, caudal middle frontal, superior frontal, lateral orbitofrontal, rostral middle frontal, precentral cortices, left pars opercularis, paracentral, and superior frontal cortices in the early-exposure subgroup. Additionally, greater volumetric increases in specific frontal regions, including the right rostral middle frontal, right paracentral, right superior frontal, and left paracentral cortices, correlated with more significant improvements in oppositional symptoms. Conversely, the late-exposure subgroup (baseline age &gt; 12 years) showed no significant differences in cortical development or associations between methylphenidate and brain structure. Our findings indicate that early methylphenidate exposure may affect frontal brain morphology and its association with symptom improvement in ADHD. These age-dependent patterns of psychostimulants on brain structure provide further insight into treatment response and disorder progression monitoring.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111429"},"PeriodicalIF":5.3,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural basis of the association between future time perspective and ADHD characteristics: functional connectivity between Left inferior parietal lobule and mPFC","authors":"Mingzhen Ding ,&nbsp;Rong Zhang ,&nbsp;Tingyong Feng","doi":"10.1016/j.pnpbp.2025.111427","DOIUrl":"10.1016/j.pnpbp.2025.111427","url":null,"abstract":"<div><div>ADHD is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity, leading to ongoing challenges in academic, career, and social adaptation. Previous research indicated that individuals with higher levels of future time perspective (FTP) tend to exhibit lower ADHD traits. However, little is known about the neural substrates between the relationship of FTP and ADHD traits. To address this question, we adopted voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analyses in a sample of 240 participants to investigate the neural substrates involved in the relationship between FTP and ADHD traits. Behavioral results demonstrated FTP was significantly negatively correlated with attention deficit (AD), hyperactivity-impulsivity disorder (HD) traits respectively. VBM analysis revealed a significant positive correlation between FTP and gray matter volume (GMV) in the superior medial frontal gyrus (SMFG) and left precentral gyrus (PG), while FTP was negatively related to GMV in the left inferior parietal lobule (IPL) and left superior temporal gyrus (STG). Furthermore, RSFC results indicated individuals with higher levels of FTP exhibited greater functional connectivity between the IPL and both the dorsomedial prefrontal cortex (dmPFC) and the ventromedial prefrontal cortex (vmPFC). More importantly, mediation analysis revealed that FTP fully mediated the relationship between the functional connectivity of IPL-dmPFC and IPL-vmPFC with AD traits, and the relationship between the functional connectivity of IPL-vmPFC and HD traits. Overall, this study highlights the crucial role of brain circuits involved in planning regulation, goal execution, and value evaluation in the relationship between FTP and ADHD symptoms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111427"},"PeriodicalIF":5.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dopamine D3 receptor gene is associated with obsessive-compulsive disorder and antidepressant response","authors":"Gwyneth Zai ,&nbsp;Clement C. Zai ,&nbsp;Eliza Burroughs ,&nbsp;Paul D. Arnold ,&nbsp;James L. Kennedy ,&nbsp;Margaret A. Richter","doi":"10.1016/j.pnpbp.2025.111428","DOIUrl":"10.1016/j.pnpbp.2025.111428","url":null,"abstract":"<div><h3>Background</h3><div>Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with a strong genetic component. Previous studies have suggested a role for the dopamine receptor genes in OCD with the dopamine D3 receptor (<em>DRD3</em>) gene being relatively overlooked. There is neurobiological evidence that D3 may be involved in the striatal-cortical circuits that affect compulsive behaviour and anxiety. Thus, we investigated genetic variants of <em>DRD3</em> in association with OCD and serotonin reuptake inhibitor (SRI) response.</div></div><div><h3>Methods</h3><div>We examined nine polymorphisms across <em>DRD3</em> in 318 individuals with OCD (comprised of 129 small nuclear families, and 196 independent singleton cases) compared to 196 healthy controls matched for age, gender, and ethnicity using the family-based association test (FBAT) and case-control analysis respectively. Quantitative analyses were performed with age at onset (AAO) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) severity scores.</div></div><div><h3>Results</h3><div>Nominally significant biased transmission of alleles in polymorphic sites rs2399504, rs7611535, rs1394016, Ser9Gly, rs167770, and rs2087017 was observed with FBAT. The rs2399504, rs7611535, rs1394016, Ser9Gly, and rs167770 polymorphisms were associated with AAO but not with Y-BOCS scores using FBAT. Five polymorphisms (rs2399504, rs7611535, rs1394016, Ser9Gly, and rs167770) showed a trend in case-control analyses for allele/genotype distributions. Haplotype analyses of the polymorphisms using Haploview revealed several combinations of markers associated with OCD. Nominally positive association between rs167770 and rs11721264 and sertraline response remained significant after correction for multiple testing.</div></div><div><h3>Conclusion</h3><div>This is the first report to our knowledge of involvement of <em>DRD3</em> in OCD, which requires further research.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111428"},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auditory and visual oddball stimulus processing deficits in clinical high risk for psychosis: Forecasting psychosis risk with N200 and P300","authors":"Yawen Hong ,&nbsp;Lihua Xu ,&nbsp;Xiaochen Tang ,&nbsp;Dan Zhang ,&nbsp;Wensi Zheng ,&nbsp;Zhenying Qian ,&nbsp;Jinyang Zhao ,&nbsp;Yingying Tang ,&nbsp;Min Su ,&nbsp;Liying Huang ,&nbsp;Yong Ye ,&nbsp;Tianhong Zhang ,&nbsp;Xiong Jiao ,&nbsp;Jijun Wang","doi":"10.1016/j.pnpbp.2025.111426","DOIUrl":"10.1016/j.pnpbp.2025.111426","url":null,"abstract":"<div><h3>Background</h3><div>Individuals at clinical high risk (CHR) for psychosis exhibit reduced P300 responses, particularly in auditory tasks. While N200 abnormalities have been reported in CHR individuals, findings are inconsistent, and research on visual oddball tasks is limited. This study compares event-related potentials (ERPs) in auditory and visual oddball paradigms between CHR individuals and healthy controls (HC), aiming to explore these components as potential biomarkers for CHR and its clinical outcomes.</div></div><div><h3>Methods</h3><div>Baseline auditory and visual oddball N200 and P300 were obtained from CHR participants (<em>N</em> = 96) and HC participants (<em>N</em> = 60). All CHR participants were followed up for five years and stratified into CHR converters and non-converters. The differences in N200 and P300 amplitude in auditory and visual oddball tasks were compared between the clinical outcome subgroups and HC participants. Prediction models were developed using Cox proportional hazards regression to identify baseline predictors.</div></div><div><h3>Results</h3><div>CHR converters showed significantly reduced N200 and P300 amplitudes in both oddball paradigms relative to CHR non-converters and HC participants. Furthermore, Prediction models including visual N200 amplitudes (β = −0.233, <em>p</em> = 0.012) and auditory P300 amplitudes (β = 0.219, <em>p</em> = 0.039) demonstrated effective discrimination between CHR converters and non-converters.</div></div><div><h3>Conclusion</h3><div>These results suggest that N200 and P300 amplitude deficits across auditory and visual modalities precede the onset of full psychosis. Moreover, the combined assessment of visual N200 and auditory P300 amplitudes may serve as a more sensitive prognostic biomarker for predicting clinical outcomes in individuals at clinical high risk.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111426"},"PeriodicalIF":5.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multivariate associations between structural brain changes and cognitive impairment in partially or fully remitted persons with bipolar disorder","authors":"Johanna Mariegaard Schandorff ,&nbsp;Anne Bügel Fisker Madsen ,&nbsp;Viktoria Damgaard ,&nbsp;Bethany Little ,&nbsp;Anjali Sankar ,&nbsp;Julian Macoveanu ,&nbsp;Vibe G. Frokjaer ,&nbsp;Lars Vedel Kessing ,&nbsp;Martin Balslev Jørgensen ,&nbsp;Gitte Moos Knudsen ,&nbsp;Peter Gallagher ,&nbsp;Kamilla Woznica Miskowiak","doi":"10.1016/j.pnpbp.2025.111425","DOIUrl":"10.1016/j.pnpbp.2025.111425","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive impairment across cognitive domains and brain structure alterations are well documented in persons with bipolar disorder (BD) but the association between them is still unclear. Previous studies have generally applied univariate models to investigate brain-cognition correlations, which limits the discovery of complex association patterns. The aim of this study was to apply canonical correlation analysis (CCA) to identify multivariate associations between brain structure and cognitive impairment in BD.</div></div><div><h3>Methods</h3><div>Cognitively impaired persons with BD (<em>n</em> = 169) in full or partial remission were included from four prior pro-cognitive intervention studies. We included healthy controls (HC, <em>n</em> = 40) for the calculation of covariate-adjusted brain and cognition <em>z</em>-scores. All participants underwent structural magnetic resonance imaging and an extensive cognitive test battery. We conducted principal component analysis on the brain data within the BD group to reduce the number of variables in the dataset. We then applied CCA to investigate multivariate associations between brain structure and cognition in the BD cohort.</div></div><div><h3>Results</h3><div>Poorer performance across working memory, psychomotor speed, executive functions, and verbal learning and memory correlated with lower grey matter volume in frontotemporal regions, the right hippocampus, and the left caudate nucleus, and with larger frontotemporal and right posterior cingulate gyral thickness.</div></div><div><h3>Conclusions</h3><div>The association between cognition, reduced grey matter volume and larger thickness in frontotemporal and posterior cingulate regions suggests that cognitive impairment originates from dysregulated, rather than simply reduced, neuroplasticity processes. Aberrant volume and thickness measures in these regions are potential treatment targets to promote cognition in BD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"140 ","pages":"Article 111425"},"PeriodicalIF":5.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144280198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}