Biological Psychiatry最新文献

{"title":"A cross-generational methylomic signature of infant maltreatment in newborn rhesus macaques.","authors":"Roy Lardenoije, Michelle N C A Smulders, Elyse L Morin, Brittany R Howell, Dora Guzman, Jerrold S Meyer, Kerry J Ressler, Mar Sánchez, Torsten Klengel","doi":"10.1016/j.biopsych.2025.02.901","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.901","url":null,"abstract":"<p><strong>Background: </strong>Early life adversity (ELA) result in detrimental physical and mental health outcomes. The impact of ELA can reverberate across generations, with epigenetic modifications being one of the proposed biological correlates of exposure to ELA. Here we bridge the translational gap between rodent models and clinical studies by utilizing a nonhuman primate model to study the cross-generational epigenetic and functional footprints of physical maltreatment and neglect.</p><p><strong>Methods: </strong>Methylomic profiling was performed using the Illumina MethylationEPIC array platform, adapted for rhesus macaques. 339,081 individual methylation sites were compared between newborn offspring of maltreated (n = 14, 8 female) and non-maltreated (n = 12, 5 female) mothers.</p><p><strong>Results: </strong>We identified 409 differentially methylated positions (DMPs) and 7 differentially methylated regions associated with the cross-generational impact of infant maltreatment. A subsequent pathway enrichment analysis revealed 78 enriched pathways. Neonatal blood cortisol levels were significantly lower in animals with a maltreated mother (maltreated n = 13, 7 female; control n = 9, 4 female). Out of the 409 DMPs, 46 showed an association with blood cortisol levels, of which 19 were found to potentially mediate the association between ancestral infant maltreatment and decreased blood cortisol levels. Finally, 137 of the DMPs were associated with a human trait in the EWAS Atlas, including child abuse and glucocorticoid exposure.</p><p><strong>Conclusions: </strong>These findings provide a deeper insight into the role of epigenetic alterations across generations after environmental insults and how this may impact the development of phenotypic alterations in offspring of maltreatment exposed individuals.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of the KCNQ (Kv7) Channel Opener Ezogabine on Resting-State Functional Connectivity of Striatal Brain Reward Regions, Depression and Anhedonia in Major Depressive Disorder: Results from a Randomized Controlled Trial.","authors":"Avijit Chowdhury, Sarah Boukezzi, Sara Costi, Sara Hameed, Yael Jacob, Ramiro Salas, Dan V Iosifescu, Ming-Hu Han, Alan Swann, Sanjay J Mathew, Laurel Morris, James W Murrough","doi":"10.1016/j.biopsych.2025.02.897","DOIUrl":"10.1016/j.biopsych.2025.02.897","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.</p><p><strong>Methods: </strong>A double-blind, randomized, placebo-controlled clinical trial in individuals aged 18 to 65 with MDD compared daily dosing with ezogabine (n=19) to placebo (n=21) for five weeks. Functional magnetic resonance imaging (fMRI) assessed RSFC of the brain's key reward regions (ventral caudate, nucleus accumbens) at baseline and post-treatment. Clinical symptoms were measured using the Snaith-Hamilton Pleasure Scale (SHAPS), Montgomery-Åsberg Depression Rating Scale (MADRS), and other clinical symptom scales.</p><p><strong>Results: </strong>Ezogabine significantly reduced RSFC between the reward seeds and the posterior cingulate cortex (PCC)/precuneus compared to placebo, which was associated with a reduction in depression severity. Improvements in anhedonia (SHAPS) and depressive symptoms (MADRS) with ezogabine compared to placebo were also associated with decreased connectivity between the reward seeds and mid/posterior cingulate regions (MCC, PCC, precuneus).</p><p><strong>Conclusions: </strong>The findings suggest that ezogabine's antidepressant effects are mediated through modulation of striatal-mid/posterior cingulate connectivity, indicating a potential therapeutic mechanism for KCNQ-targeted drugs for MDD and anhedonia. Future studies should validate these results in larger trials.</p><p><strong>Clinicaltrials: </strong>gov identifier: NCT03043560.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative genomics approach identifies glial transcriptomic dysregulation and risk in the cortex of individuals with Alcohol Use Disorder.","authors":"Anna S Warden, Nihal A Salem, Eric Brenner, Greg T Sutherland, Julia Stevens, Manav Kapoor, Alison M Goate, R Dayne Mayfield","doi":"10.1016/j.biopsych.2025.02.895","DOIUrl":"10.1016/j.biopsych.2025.02.895","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorder (AUD) is a prevalent neuropsychiatric disorder that is a major global health concern, affecting millions of people worldwide. Past studies of AUD used underpowered single cell analysis or bulk homogenates of postmortem brain tissue, which obscures gene expression changes in specific cell types. Therefore, we sought to conduct the largest-to-date single-nuclei RNAseq (snRNA-seq) postmortem brain study in AUD to elucidate transcriptomic pathology with cell type-specific resolution.</p><p><strong>Methods: </strong>Here we performed snRNA-seq and high dimensional network analysis of 73 post-mortem samples from individuals with AUD (N=36, N_nuclei= 248,873) and neurotypical controls (N=37, N_nuclei= 210,573) in the dorsolateral prefrontal cortex from both male and female donors. Additionally, we performed analysis for cell type-specific enrichment of aggregate genetic risk for AUD as well as integration of the AUD proteome for secondary validation.</p><p><strong>Results: </strong>We identified 32 distinct cell clusters and found widespread cell type-specific transcriptomic changes across the cortex in AUD, particularly affecting glial populations. We found the greatest dysregulation in novel microglial and astrocytic subtypes that accounted for the majority of differential gene expression and co-expression modules linked to AUD. Differential gene expression was secondarily validated by integration of a publicly available AUD proteome. Finally, analysis for aggregate genetic risk for AUD identified subtypes of glia as potential key players not only affected by but causally linked to the progression of AUD.</p><p><strong>Conclusions: </strong>These results highlight the importance of cell type-specific molecular changes in AUD and offer opportunities to identify novel targets for treatment on the single-nuclei level.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amygdala hyperactivity in PTSD: disentangling predisposing from consequential factors in a prospective longitudinal design.","authors":"Lycia D de Voogd, Mahur M Hashemi, Wei Zhang, Reinoud Kaldewaij, Saskia B J Koch, Vanessa A van Ast, Floris Klumpers, Karin Roelofs","doi":"10.1016/j.biopsych.2025.02.894","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.894","url":null,"abstract":"<p><strong>Background: </strong>Substantial inter-individual differences exist in the vulnerability to develop post-traumatic stress disorder (PTSD) symptoms following trauma exposure. Identification of neurocognitive risk markers for PTSD-symptoms could aid early assessment and identification of preventive intervention-targets for PTSD, particularly in high-risk professionals. Therefore, large prospective longitudinal studies with pre-trauma measurements are essential to disentangle whether previously observed neurobiological alterations in PTSD are a cause or consequence of trauma exposure or PTSD symptoms.</p><p><strong>Methods: </strong>In police recruits (n=221) without current trauma symptoms but at high risk for trauma exposure, we employed functional magnetic resonance imaging (fMRI) to disentangle predictive and acquired neural markers of post-traumatic stress symptoms. Using an experimental paradigm, we investigated anticipatory threat responses and the switch into defensive action.</p><p><strong>Results: </strong>Those recruits who showed relatively heightened dorsal amygdala responses and heightened amygdala-precuneus coupling during threat anticipation demonstrated relatively stronger increase in PTSD symptoms after trauma exposure. While the experience of traumatic events, independent of PTSD symptoms, was associated with increased lateral amygdala activation in response to the aversive stimulus (i.e. receiving an electrical shock).</p><p><strong>Conclusions: </strong>This prospective longitudinal study shows a predictive role for dorsal amygdala responsivity during threat anticipation for the development of trauma symptoms, while lateral amygdala responding to aversive events after trauma may reflect a failure to regulate. Our findings not only inform neurobiological theories of PTSD risk and vulnerability but also provide a starting point for prediction and intervention studies.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emergence and dynamics of delusions and hallucinations across stages in early psychosis.","authors":"Catalina Mourgues-Codern, David Benrimoh, Jay Gandhi, Emily A Farina, Raina Vin, Tihare Zamorano, Deven Parekh, Ashok Malla, Ridha Joober, Martin Lepage, Srividya N Iyer, Jean Addington, Carrie E Bearden, Kristin S Cadenhead, Barbara Cornblatt, Matcheri Keshavan, William S Stone, Daniel H Mathalon, Diana O Perkins, Elaine F Walker, Tyrone D Cannon, Scott W Woods, Jai L Shah, Albert R Powers","doi":"10.1016/j.biopsych.2025.02.891","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.891","url":null,"abstract":"<p><strong>Background: </strong>Hallucinations and delusions are often grouped together within the positive symptoms of psychosis. However, recent evidence suggests they may be driven by distinct computational and neural mechanisms. Examining the time course of their emergence may provide insights into the relationship between these underlying mechanisms.</p><p><strong>Methods: </strong>Participants from the second (N = 719) and third (N = 699) iterations of the North American Prodrome Longitudinal Study (NAPLS 2,3) were assessed for timing of CHR-P-level delusion and hallucination onset. Pre-onset symptom patterns in first-episode psychosis patients (FEP) from the Prevention and Early Intervention Program for Psychosis (PEPP-Montréal; N = 694) were also assessed. Symptom onset was determined at baseline assessment and the evolution of symptom patterns examined over 24 months.</p><p><strong>Results: </strong>In all three samples, participants were more likely to report the onset of attenuated/subthreshold delusions prior to attenuated/subthreshold hallucinations (odds ratios (OR): NAPLS 2=4.09; NAPLS 3=4.14; PEPP, Z=7.01, P < 0.001) and to present with only attenuated/subthreshold delusions compared to only attenuated/subthreshold hallucinations (OR: NAPLS 2=5.6; NAPLS 3=11.11; PEPP=42.75). Re-emergence of attenuated/subthreshold delusions after remission was also more common than re-emergence of attenuated/subthreshold hallucinations (Ps < 0.05), which more often resolved first (Ps < 0.001). In both CHR-P samples, ratings of delusional ideation fell with the onset of attenuated hallucinations (P = 0.007).</p><p><strong>Conclusions: </strong>Attenuated/subthreshold delusions tend to emerge before attenuated/subthreshold hallucinations and may play a role in their development. Further work should examine the relationship between the mechanisms driving these symptoms and its utility for diagnosis and treatment.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting Schizophrenia Biology Using Pleiotropy with Cognitive Genomics.","authors":"Upasana Bhattacharyya, Jibin John, Todd Lencz, Max Lam","doi":"10.1016/j.biopsych.2025.02.890","DOIUrl":"10.1016/j.biopsych.2025.02.890","url":null,"abstract":"<p><strong>Background: </strong>Given the increasingly large number of loci discovered by psychiatric GWAS, specification of the key biological pathways underlying these loci has become a priority for the field. We have previously leveraged the pleiotropic genetic relationships between schizophrenia and two cognitive phenotypes (educational attainment and cognitive task performance) to differentiate two subsets of illness-relevant SNPs: (1) those with \"concordant\" alleles, which are associated with reduced cognitive performance and educational attainment and increased schizophrenia risk; and (2) those with \"discordant\" alleles linked to reduced educational and/or cognitive levels but lower schizophrenia susceptibility.</p><p><strong>Methods: </strong>In the present study, we extend our prior work, utilizing larger input GWAS datasets and a more powerful statistical approach to pleiotropic meta-analysis, the Pleiotropic Locus Exploration and Interpretation using Optimal test (PLEIO).</p><p><strong>Results: </strong>Our pleiotropic meta-analysis of schizophrenia and the two cognitive phenotypes revealed 768 significant loci (166 novel). Among these, 347 loci harbored concordant SNPs, 270 encompassed discordant SNPs, and 151 \"dual\" loci contained concordant and discordant SNPs. Competitive gene-set analysis using MAGMA linked concordant SNP loci with neurodevelopmental pathways (e.g., neurogenesis), whereas discordant loci were associated with mature neuronal synaptic functions. These distinctions were also observed in BrainSpan analysis of temporal enrichment patterns across developmental periods, with concordant loci containing more prenatally expressed genes than discordant loci. Dual loci were enriched for genes related to mRNA translation initiation, representing a novel finding in the schizophrenia literature.</p><p><strong>Conclusions: </strong>Pleiotropic analysis permits not only enhanced statistical power for locus discovery, but also the ability to parse distinct biological processes associated with endophenotypes.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Neuropsychiatric Checklist for Autoimmune Psychosis: A Narrative Review.","authors":"Ludger Tebartz van Elst, Kimon Runge, Philipp T Meyer, Horst Urbach, Nils Venhoff, Harald Prüss","doi":"10.1016/j.biopsych.2025.02.889","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.889","url":null,"abstract":"<p><p>Autoimmune encephalitis is a rapidly evolving topic in both neurology and psychiatry. A recent international consensus paper defined criteria for possible, probable and definite autoimmune psychosis (AP) inspired by the principles established in neurology for the definition of autoimmune encephalitis (AE). This has stimulated much clinical research on AP, but also criticism of the validity of the criteria for possible AP, justifying further clinical investigation such as lumbar puncture. In clinical practice, it is often difficult to decide how far diagnostic procedures such as lumbar punctures and immunotherapies should go in unclear cases. Against this background, this review has three aims: First, we summarize and compare the available concepts for the diagnosis of AP in a systematic literature review. Second, we present an overview of typical specific and non-specific findings that can be obtained in laboratory, electroencephalography, magnetic resonance imaging, cerebrospinal fluid, and [¹⁸F]fluorodeoxyglucose positron emission tomography studies in the context of AP. Thirdly, we summarize these findings and present the Neuropsychiatric Checklist for AP (NEPCAP) as a tool for clinical assessment of the likelihood of AP, with reference to the typical red flag symptoms and the specific and many unspecific findings that can be identified in additional investigations. We suggest that this instrument might be a useful tool for a comprehensive, possibly uniform and standardized case assessment in the context of possible AP.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating polygenic liability and family history for predicting psychiatric diseases in the Taiwan biobank.","authors":"Shi-Heng Wang, Yen-Chen A Feng, Mei-Chen Lin, Chi-Fung Cheng, Mei-Hsin Su, Chia-Yen Chen, Chi-Shin Wu, Chun Chieh Fan","doi":"10.1016/j.biopsych.2025.02.888","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.888","url":null,"abstract":"<p><strong>Background: </strong>This study investigated the interplay between molecular measures of polygenic risk score (PRS) and conventional measures of family history (FH) on the risk of four psychiatric disorders: schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD) in community samples of East Asian populations. We examined the individual and joint associations and relative contributions of PRS and FH and evaluated the potential of combining transdiagnostic PRSs and FHs to improve risk prediction.</p><p><strong>Methods: </strong>The genotyping of 106,581 unrelated participants from the Taiwan Biobank was linked to the National Health Insurance Research Database to retrieve information on ICD-defined diseases and FH. A logistic regression model was used to examine the association between PRS and FH in fathers, mothers, and siblings with a risk of psychiatric disorders.</p><p><strong>Results: </strong>The PRS for SCZ, BPD, MDD, and OCD explained 2.0%, 0.4%, 0.6%, and 0.6%, respectively, and FH explained 1.3%, 1.4%, 2.3%, and 3.4%, respectively, of the variance in the corresponding disease. Incorporating PRS and FH increased the explained variances in SCZ, BPD, MDD, and OCD by 3.2%, 1.7%, 2.8%, and 4.1%, respectively. The effect sizes for PRS and FH in the PRS/FH alone and PRS-FH combined models were generally similar. Simultaneously incorporating the four PRSs and FHs increased the explained variances of SCZ, BPD, MDD, and OCD to 4.7%, 4.7%, 3.3%, and 7.3%, respectively.</p><p><strong>Conclusions: </strong>PRS and FH provide independent and complementary information for the identification of psychiatric disorders. The incorporation of transdiagnostic PRSs and FHs improved risk identification.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Methodological and Interpretational Issues in the PsyRiskMR Database.","authors":"Xiaoyan Li, Junfeng Xia","doi":"10.1016/j.biopsych.2025.02.887","DOIUrl":"10.1016/j.biopsych.2025.02.887","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurobiological perturbations in bipolar disorder compared to schizophrenia - evidence from cell cultures and brain organoids.","authors":"Ibrahim A Akkouh, Jordi Requena Osete, Attila Szabo, Ole A Andreassen, Srdjan Djurovic","doi":"10.1016/j.biopsych.2025.02.012","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.02.012","url":null,"abstract":"<p><p>Bipolar disorder (BD) and schizophrenia (SCZ) are uniquely human disorders with a complex pathophysiology which involves adverse neuropathological events in brain development. High disease polygenicity and limited access to live human brain tissue make these disorders exceedingly challenging to study mechanistically. Cellular cultures and brain organoids generated from human-derived pluripotent stem cells preserve the genetic background of the donor cells and recapitulate some of the defining characteristics of human brain architecture and early spatiotemporal development. These model systems have already proven successful in deciphering some of the neuropathological perturbations in BD and SCZ, and methodological advancements, such as the functional integration of two or more region-specific organoids and organoid transplantation in animals, promise to deliver increasingly refined insights. Here we review a selection of recent discoveries achieved by stem cell-based models, with a particular focus on patterns of cellular and molecular convergence and divergence between BD and SCZ. We first provide a brief overview of the evidence from glial and neuronal cell cultures and brain organoids, centering our discussion on several key functional domains, including neuroinflammation, neuronal excitability, and mitochondrial function. We then review recent findings demonstrating the power of integrating stem cell-based systems with gene editing technologies to elucidate the functional consequences of risk variants identified through genetic association studies. We end with a discussion of current challenges and some promising avenues for future research.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}