Biological psychiatry global open science最新文献

{"title":"Peripheral MicroRNA Expression Patterns as Biomarkers for Adolescent Depression","authors":"Brunno Rocha Levone, Gerhard Schratt","doi":"10.1016/j.bpsgos.2025.100571","DOIUrl":"10.1016/j.bpsgos.2025.100571","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100571"},"PeriodicalIF":3.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886395","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}

{"title":"Effects of Shared and Nonshared Schizophrenia and Bipolar Disorder Alleles on Cognition and Educational Attainment in the UK Biobank","authors":"Alexander L. Richards ,&nbsp;Eilidh Fenner ,&nbsp;Nicholas E. Clifton ,&nbsp;Darren Cameron ,&nbsp;Claire E. Tume ,&nbsp;Nicholas J. Bray ,&nbsp;Sophie E. Legge ,&nbsp;James T.R. Walters ,&nbsp;Peter A. Holmans ,&nbsp;Michael C. O’Donovan ,&nbsp;Michael J. Owen","doi":"10.1016/j.bpsgos.2025.100601","DOIUrl":"10.1016/j.bpsgos.2025.100601","url":null,"abstract":"<div><h3>Background</h3><div>Cognitive impairment is typically more severe in schizophrenia (SZ) than bipolar disorder (BD). We explored the underlying genetics and biology of this difference and its relationship to educational attainment (EA) using genomic structural equation modeling.</div></div><div><h3>Methods</h3><div>Shared and differentiating fractions of liability for SZ and BD were derived and tested for their association with general intelligence (<em>n</em> = 93,541), fluid intelligence (<em>n</em> = 160,465), and EA (<em>n</em> = 354,609) in the UK Biobank. Liabilities were tested for enrichment in genes with high expression specificity (HES) for developmental stages, cell types, and functional categories.</div></div><div><h3>Results</h3><div>Shared liability was associated with poorer cognition but higher EA. The SZ differentiating fraction (SZ_diff) was associated with poorer cognition and lower EA. When we adjusted for cognition, the effects of SZ_diff on EA were attenuated but still significant. The differentiating fraction was enriched for HES genes for young adulthood (20–30 years), mid-adulthood (30–60 years), and the dentate gyrus.</div></div><div><h3>Conclusions</h3><div>Shared liability for SZ and BD is enriched for alleles that confer risk for poorer cognitive function in the general population but is associated with noncognitive traits that enhance EA. In contrast, SZ_diff is enriched for alleles that confer risk for poorer EA through both cognitive and noncognitive mechanisms, which has implications for interventions. The enrichment of the differentiating fraction for HES genes in early and mid-adulthood and in the dentate gyrus highlights developmental stages and cell types important for future research.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100601"},"PeriodicalIF":3.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220166","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}

{"title":"Decreased Mitochondrial DNA Integrity and Elevated Inflammatory Markers in Late-Life Depression: A Longitudinal Study","authors":"Ana Paula Mendes-Silva ,&nbsp;Perla El-Ahmad ,&nbsp;Ana Paula Costa ,&nbsp;Lloyd Cenon Balbuena ,&nbsp;Yuliya Stoycheva Nikolova ,&nbsp;Tarek Rajji ,&nbsp;James Lowery Kennedy ,&nbsp;Erica Leandro Vieira ,&nbsp;Vanessa Faria Gonçalves ,&nbsp;Breno Satler Diniz","doi":"10.1016/j.bpsgos.2025.100598","DOIUrl":"10.1016/j.bpsgos.2025.100598","url":null,"abstract":"<div><h3>Background</h3><div>Late-life depression (LLD) is a prevalent and severe mental disorder. The biological mechanisms underlying LLD are not fully understood, but increasing evidence suggests that mitochondria play a significant role. Impaired mitochondrial function leads to excessive production of reactive oxygen species and the release of circulating cell-free mitochondrial DNA (ccf-mtDNA). The ccf-mtDNA activates the toll-like receptor system, which triggers a systemic proinflammatory response. However, there is limited understanding of the impact of ccf-mtDNA integrity, such as deletions, on LLD pathological conditions.</div></div><div><h3>Methods</h3><div>We included 90 older individuals (50 LLDs, 40 nondepressed healthy control participants [HCs]), with a subset of individuals followed up at 30 months (13 LLDs, 13 HCs). Plasma was separated from blood, and DNA was extracted. Mitochondrial genes MT-ND2 and MT-ND4 were targeted to evaluate ccf-mtDNA levels and deletion using real-time quantitative polymerase chain reaction. Plasma interleukins (ILs) 1β, 5, and 6 were quantified via multiplex immunoassay.</div></div><div><h3>Results</h3><div>LLD was linked to increased ccf-mtDNA instability at baseline (deletion: <em>F</em>_88,1 = 7.105, <em>p</em> = .009; levels: <em>F</em>_88,1 = 6.885, <em>p</em> = .01), which was associated with more severe depressive symptoms and greater medical comorbidity burden. Longitudinal analysis revealed significant effects of diagnosis and time on ccf-mtDNA levels and the deletion rate. Additionally, higher deletion rates at baseline predicted IL-5 and IL-6 levels at 30 months (<em>p</em>_adjusted = .13, <em>p</em>_adjusted = .12, respectively).</div></div><div><h3>Conclusions</h3><div>Increased ccf-mtDNA instability may heighten vulnerability to emotional dysregulation and medical burden in individuals with LLD. Further research is needed to validate our findings and elucidate the mechanisms that connect mitochondrial instability and inflammation in LLD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100598"},"PeriodicalIF":3.7,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158125","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}

{"title":"Glutamate, Contextual Insensitivity, and Disorganized Speech in First-Episode Schizophrenia: A 7T Magnetic Resonance Spectroscopy Study","authors":"Yingqi Laetitia Wang ,&nbsp;Victoria Sharpe ,&nbsp;Michael Mackinley ,&nbsp;Gina R. Kuperberg ,&nbsp;Kaustubh Supekar ,&nbsp;Jean Theberge ,&nbsp;Lena Palaniyappan","doi":"10.1016/j.bpsgos.2025.100593","DOIUrl":"10.1016/j.bpsgos.2025.100593","url":null,"abstract":"<div><h3>Background</h3><div>In people with schizophrenia, formal thought disorder is a core symptom that emerges early and persists into chronic stages despite treatments. It manifests as disorganized speech and is often associated with poor long-term outcomes. A key feature of this disorganization is an impairment in the buildup and use of context provided by preceding words when choosing upcoming words. Recent work has shown that spoken words are less predictable based on global linguistic context in schizophrenia, but the neural basis of this remains unknown. Glutamate dysfunction in the anterior cingulate cortex has long been implicated in schizophrenia, but its connection to behavioral impairments remains unclear.</div></div><div><h3>Methods</h3><div>In this study, we investigated the relationship between linguistic contextual sensitivity and glutamate level in the dorsal anterior cingulate cortex in 39 patients with first-episode psychosis (33 men) and 33 sociodemographically matched healthy control participants (22 men). Contextual sensitivity was measured using a large language model (GPT-3), and glutamate levels were measured using 7T magnetic resonance spectroscopy.</div></div><div><h3>Results</h3><div>We found a significant interaction between diagnosis and glutamate level in predicting contextual sensitivity: Patients with lower glutamate levels had poor contextual sensitivity, a relationship not seen in healthy control participants. Glutamate variation was specifically explained by contextual sensitivity after controlling for other clinical and language variables, underscoring the robustness and specificity of this association.</div></div><div><h3>Conclusions</h3><div>These results highlight a potential glutamatergic basis for disorganized speech in schizophrenia and suggest that contextual sensitivity in speech could reflect anterior cingulate glutamate variations in early psychosis.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100593"},"PeriodicalIF":3.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121205","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}

{"title":"Increasing SOX10 Expression Overcomes Schizophrenia-Associated Early Oligodendrocyte Growth Deficits In Vitro","authors":"Donna L. McPhie ,&nbsp;Juan Antonio García-León ,&nbsp;Catherine M. Verfaillie ,&nbsp;Suzann M. Babb ,&nbsp;Bruce M. Cohen","doi":"10.1016/j.bpsgos.2025.100592","DOIUrl":"10.1016/j.bpsgos.2025.100592","url":null,"abstract":"<div><h3>Background</h3><div>Individuals with schizophrenia (SZ) tend to have lower than average brain myelin content. Gene-set analyses suggest that aberrant oligodendrocyte (OL) development is an underlying cause of this abnormality. Previously, we observed that cells from patients with SZ, reprogrammed to neural lines, had substantially reduced OL production. Furthermore, OLs produced in culture correlated strongly with myelin content observed in the brains of the donors of the lines. In the current study, we tested whether increasing expression of <em>SOX10</em>, crucial in determining commitment to oligodendrocyte fate, can overcome the SZ-associated deficit in OL production.</div></div><div><h3>Methods</h3><div>Fibroblasts from 6 participants with SZ and 6 healthy control participants were reprogrammed to neural lines. Quantitative reverse transcription polymerase chain reactions were run to determine the expression of <em>SOX10</em>. In addition, expression was measured for several other genes (<em>OLIG2</em>, <em>SOX9</em>, <em>QK</em><em>I</em>, and <em>FEZ1</em>) that are associated with risk for SZ and also interact with SOX10 in determining OL development. Finally, using an inducible lentiviral system, <em>SOX10</em> was expressed in neural precursor cells and the effect of increased SOX10 expression on the production of OLs was quantified.</div></div><div><h3>Results</h3><div><em>SOX10</em> expression was significantly reduced in cells from patients with SZ. Reductions in expression of <em>SOX9</em> and <em>QK</em><em>I</em> were also seen. Increasing <em>SOX10</em> gene and resulting protein expression overcame the SZ-associated deficit in OL production.</div></div><div><h3>Conclusions</h3><div>Evidence from these studies, together with previous results, suggests that reduced SOX10 is a critical determinant of deficient OL production and, thereby, a contributing determinant of abnormal brain myelination in SZ. This abnormality could be a target for therapeutic interventions.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100592"},"PeriodicalIF":3.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145220167","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}

{"title":"Transcriptomic Architecture of Weak Versus Strong Contextual Fear Extinction Learning Uncovers Extinction-Suppressive Role of TIA1","authors":"Maria I. Bonilla ,&nbsp;Hae-Lim Lee ,&nbsp;Stephen Foster ,&nbsp;In-Jung Kim ,&nbsp;Andrii Rudenko","doi":"10.1016/j.bpsgos.2025.100591","DOIUrl":"10.1016/j.bpsgos.2025.100591","url":null,"abstract":"<div><h3>Background</h3><div>Extinction, the capacity for an individual to inhibit or diminish fear memories, is a critical aspect of fear processing. In humans, weak extinction learning is often observed in anxiety and fear-related disorders such as posttraumatic stress disorder. However, the mechanisms behind regulating extinction and determining individual variability in extinction learning remain poorly understood.</div></div><div><h3>Methods</h3><div>To investigate the molecular basis of interindividual and sex-related differences in the ability to extinguish fear, extinction learning was analyzed in inbred wild-type male and female mice. Contextual fear conditioning and extinction were combined with profiling of the hippocampal transcriptomes associated with weak and strong extinction learning and genetic manipulations to extend our transcriptomic findings.</div></div><div><h3>Results</h3><div>We identified significant sex-dependent and -independent differences in hippocampal gene expression between weak and strong extinction learner animals. Very high transcriptomic overlap between weak learner males and females was especially surprising, showing upregulation of multiple genes associated with neurotoxic insult and cellular stress, including a gene encoding a major stress regulator, a prion-like TIA1. Overexpression of <em>Tia1</em> in the dorsal hippocampus caused sex-independent dysregulation of microglia and diminished fear extinction learning in animals of both sexes.</div></div><div><h3>Conclusions</h3><div>We demonstrated the brain-based transcriptomic architecture associated with weak versus strong fear extinction learning in male and female mammalian subjects and identified the sex-independent extinction-suppressive role of hippocampal TIA1 upregulation. Our results should help to develop a better understanding of the mechanisms that underlie individual and sex-dependent differences in extinction and could inform novel therapeutic targets for pharmacological extinction augmentation strategies in fear-related disorders.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100591"},"PeriodicalIF":3.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158123","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}

{"title":"Functional Coupling and Longitudinal Outcome Prediction in First-Episode Psychosis","authors":"Isaac Z. Pope ,&nbsp;Sidhant Chopra ,&nbsp;Alexander Holmes ,&nbsp;Shona M. Francey ,&nbsp;Brian O’Donoghue ,&nbsp;Vanessa L. Cropley ,&nbsp;Barnaby Nelson ,&nbsp;Hok Pan Yuen ,&nbsp;Kelly Allott ,&nbsp;Mario Alvarez-Jimenez ,&nbsp;Susy Harrigan ,&nbsp;Christos Pantelis ,&nbsp;Andrew Thompson ,&nbsp;Stephen J. Wood ,&nbsp;Patrick D. McGorry ,&nbsp;Alex Fornito","doi":"10.1016/j.bpsgos.2025.100589","DOIUrl":"10.1016/j.bpsgos.2025.100589","url":null,"abstract":"<div><h3>Background</h3><div>Clinical outcomes following the first episode of psychosis (FEP) are highly heterogeneous across patients. The identification of prognostic biomarkers would greatly facilitate personalized treatments. Patients with psychosis often display brainwide disruptions of interregional functional coupling (FC), with some being linked to symptom severity and remission. Thus, FC may have prognostic potential for people experiencing psychosis.</div></div><div><h3>Methods</h3><div>Fifty-five antipsychotic-naïve patients with FEP (51% female, ages 15–25 years) were randomized to receive either antipsychotic or placebo tablets for 6 months alongside psychosocial interventions. Functional magnetic resonance imaging was conducted at baseline and after 3 months to evaluate whether baseline FC or 3-month change in FC could predict 6- and 12-month changes in symptoms and functioning, quantified using the Brief Psychiatric Rating Scale and the Social and Occupational Functioning Assessment Scale, respectively. We considered 3 different cross-validated prediction algorithms: 1) connectome-based predictive modeling, 2) kernel ridge regression, and 3) multilayer meta-matching. Each prediction model comprised 35 to 49 individuals.</div></div><div><h3>Results</h3><div>All models showed poor performance in predicting patients’ 6- and 12-month changes in symptoms and functioning (all <em>r</em><em>_mean</em> &lt; 0.3), and no model achieved significance via permutation testing (all <em>p</em> &gt; .05).</div></div><div><h3>Conclusions</h3><div>Our findings suggest that brainwide measures of FC may not be suitable for predicting extended clinical outcomes over a 6- to 12-month period in patients with FEP.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100589"},"PeriodicalIF":3.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121126","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}

{"title":"Understanding the Comorbidities Among Psychiatric Disorders, Chronic Low Back Pain, and Spinal Degenerative Disease Using Observational and Genetically Informed Analyses","authors":"Dan Qiu ,&nbsp;Eleni Friligkou ,&nbsp;Jun He ,&nbsp;Brenda Cabrera-Mendoza ,&nbsp;Mihaela Aslan ,&nbsp;Mihir Gupta ,&nbsp;Renato Polimanti","doi":"10.1016/j.bpsgos.2025.100588","DOIUrl":"10.1016/j.bpsgos.2025.100588","url":null,"abstract":"<div><h3>Background</h3><div>Psychiatric disorders and symptoms are associated with differences in pain perception and sensitivity. These differences can have important implications in treating spinal degenerative disease (SDD) and chronic low back pain (CLBP).</div></div><div><h3>Methods</h3><div>Leveraging UK Biobank (UKB) (<em>n</em> = 402,072) and All of Us Research Program (AoU) (<em>n</em> = 157,415) data, we investigated the effects linking psychiatric disorders to SDD and CLBP. We applied multinominal regression models, polygenic risk scoring, and one-sample Mendelian randomization (MR) to triangulate the effects underlying the observed associations. We also performed gene ontology and drug-repurposing analyses to dissect the biology shared among mental illnesses, SDD, and CLBP.</div></div><div><h3>Results</h3><div>When we compared individuals affected only by SDD, those affected only by CLBP, and those affected by both conditions with control participants, observational and genetically informed analyses highlighted that the strongest effects across the 3 case groups were observed for alcohol use disorder, anxiety, depression, and posttraumatic stress disorder. Additionally, schizophrenia and its polygenic risk score appeared to have an inverse relationship with CLBP, SDD, and their comorbidity. One-sample MR highlighted a potential direct effect of internalizing disorders on the outcomes investigated that was particularly strong on SDD. Our drug repurposing analyses identified histone deacetylase inhibitors as targeting molecular pathways shared by psychiatric disorders, SDD, and CLBP.</div></div><div><h3>Conclusions</h3><div>These findings support that the comorbidity among psychiatric disorders, SDD, and CLBP is due to the contribution of direct effects and shared biology linking these health outcomes. These pleiotropic mechanisms, together with sociocultural factors, play a key role in shaping the SDD-CLBP comorbidity patterns that have been observed across the psychopathology spectrum.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100588"},"PeriodicalIF":3.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095555","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}

{"title":"Epigenetic and Structural Brain Aging and Their Associations With Major Depressive Disorder","authors":"Eileen Y. Xu ,&nbsp;Claire Green ,&nbsp;Daniel L. McCartney ,&nbsp;Laura K.M. Han ,&nbsp;Kathryn L. Evans ,&nbsp;Rosie M. Walker ,&nbsp;Danni A. Gadd ,&nbsp;Douglas Steele ,&nbsp;Gordon Waiter ,&nbsp;Archie Campbell ,&nbsp;Stephen M. Lawrie ,&nbsp;James H. Cole ,&nbsp;Andrew M. McIntosh ,&nbsp;Xueyi Shen ,&nbsp;Heather C. Whalley","doi":"10.1016/j.bpsgos.2025.100577","DOIUrl":"10.1016/j.bpsgos.2025.100577","url":null,"abstract":"<div><h3>Background</h3><div>A growing body of evidence suggests that major depressive disorder (MDD) may be associated with premature biological aging. However, most studies reported to date have examined brain-based (BrainAge) and DNA methylation (DNAm)–based measures (DNAmAge) of biological age (BioAge) in isolation.</div></div><div><h3>Methods</h3><div>We investigated 2 well-studied BioAge measures in lifetime and current MDD: BrainAge and DNAmAge (4 separate DNAmAge measures based on Horvath, Hannum, GrimAge, and PhenoAge clocks). We used cross-sectional cohort data from GS:STRADL (Generation Scotland: STratifying Resilience and Depression Longitudinally) (BrainAge <em>n</em> = 833; DNAmAge <em>n</em> = 587; age range 26–76 years) and used UK Biobank (UKB) data to test for replication of BrainAge associations with MDD (BrainAge <em>n</em> = 12,018, age range 45–80 years). Premature brain and DNAm aging were operationalized as predicted age difference (PAD), and analyses controlled for age, sex, smoking, and alcohol intake. We also tested individual and additive associations of brain- and DNAm-based PADs to lifetime/current MDD using logistic regression.</div></div><div><h3>Results</h3><div>Individuals with lifetime MDD showed significantly higher BrainAge and DNAmAge in GS, ranging from 1.60 to 2.45 years, than individuals without MDD for all measures except for Horvath age. No differences were found for BrainAge in the UKB. In terms of PAD, lifetime MDD was significantly associated with GrimAge-PAD, PhenoAge-PAD, and Brain-PAD, ranging from odds ratio (OR) = 1.21−1.30 (and in UKB, Brain-PAD OR = 1.05). DNAm-PAD and Brain-PAD demonstrated shared and distinctive associations with lifetime MDD, where PhenoAge-PAD plus Brain-PAD explained maximum variance (area under the curve = 0.69, <em>R</em>² = 9%). No significant associations were found for current MDD.</div></div><div><h3>Conclusions</h3><div>Our findings highlight shared and distinct associations of premature brain and DNAm aging in lifetime MDD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100577"},"PeriodicalIF":3.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019370","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}

{"title":"Recruitment of Neuronal Populations in the Paraventricular Thalamus of Alcohol-Seeking Rats With Withdrawal-Related Learning Experience","authors":"Hermina Nedelescu ,&nbsp;Elias Meamari ,&nbsp;Nami Rajaei ,&nbsp;Alexus Grey ,&nbsp;Ryan Bullard ,&nbsp;Nathan O’Connor ,&nbsp;Nobuyoshi Suto ,&nbsp;Friedbert Weiss","doi":"10.1016/j.bpsgos.2025.100578","DOIUrl":"10.1016/j.bpsgos.2025.100578","url":null,"abstract":"<div><h3>Background</h3><div>Stimulus-reactive neuronal populations are groups of neurons that become activated by environmental stimuli. These sparsely activated neuronal assemblies are implicated in encoding associations between environmental contexts and subjectively rewarding or aversive experiences that regulate behavior. How positive or negative hedonic states are represented in brain neurocircuits is a fundamental question relevant for understanding the processing of emotionally meaningful stimuli that drive appropriate versus maladaptive behavior. It is well known that animals avoid noxious stimuli and experiences. However, little is known about how the conditioning of environmental stimuli to behavior that leads to amelioration of dysphoric states establishes powerful associations that lead to compulsive maladaptive behavior.</div></div><div><h3>Methods</h3><div>Here, we sought to identify stimulus-reactive neurons that may mediate the conditioned effects of environmental stimuli associated with the reversal of dysphoric alcohol withdrawal states using a dependent withdrawal-related learning (WDL) experimental condition (DEP-WDL) (<em>N</em> = 13) and 3 controls: nondependent WDL (NDEP-WDL) (<em>N</em> = 12), dependent no-WDL (DEP-NWDL) (<em>N</em> = 9), NDEP-NWDL (<em>N</em> = 9).</div></div><div><h3>Results</h3><div>The results document a role for clusters of neurons in the paraventricular nucleus of the thalamus (<em>N</em> = 8), the central nucleus of the amygdala (<em>N</em> = 8), and the dorsal striatum (<em>N</em> = 9) in this conditioned negative reinforcement process.</div></div><div><h3>Conclusions</h3><div>These findings suggest that associations between reversal of negative hedonic states and environmental contexts are encoded in distinct neuronal populations that may serve as a neural substrate of compulsive alcohol seeking and vulnerability to relapse associated with reward dysregulation and hedonic allostasis.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100578"},"PeriodicalIF":3.7,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145095554","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}