Biological psychiatry global open science最新文献

{"title":"Predictive Processing in Autism Spectrum Disorder: The Atypical Iterative Prior Updating Account","authors":"Zhuanghua Shi ,&nbsp;Fredrik Allenmark ,&nbsp;Laura A. Theisinger ,&nbsp;Rasmus L. Pistorius ,&nbsp;Stefan Glasauer ,&nbsp;Hermann J. Müller ,&nbsp;Christine M. Falter-Wagner","doi":"10.1016/j.bpsgos.2025.100468","DOIUrl":"10.1016/j.bpsgos.2025.100468","url":null,"abstract":"<div><h3>Background</h3><div>The nature of predictive-processing differences between individuals with autism spectrum disorder (ASD) and typically developing (TD) individuals remains contested. Some studies have reported impaired predictive processing in ASD, while others have suggested intact but atypical learning dynamics.</div></div><div><h3>Methods</h3><div>We investigated duration reproduction tasks under high- and low-volatility settings to examine the updating dynamics of prior beliefs and sensory estimate updating in individuals with ASD (<em>n</em> = 32) and TD counterparts (<em>n</em> = 32). Using a two-state Bayesian model, we analyzed how the participants updated their prior beliefs and perceptual estimates and how these updates affected their behavior over time.</div></div><div><h3>Results</h3><div>Individuals with ASD integrated prior knowledge similarly to TD control participants for perceptual estimates. However, they relied more heavily on sensory input for iteratively updating their prior beliefs, perceiving events as less interconnected. This heightened reliance on sensory inputs led to the initial underweighting of priors in perceptual estimates, resulting in a weaker central tendency early in sessions. Over time, ASD participants adapted, reaching integration weights comparable to those of TD control participants by the end of the session. These findings suggest that predictive processing in ASD is characterized by distinct updating dynamics, not an inability to form or use prior effectively.</div></div><div><h3>Conclusions</h3><div>Our study highlights a unique interplay between sensory inputs and prior beliefs in ASD, where greater reliance on sensory inputs during prior updating influences adaptation speed and intertrial dynamics. This process clarifies inconsistencies in the literature and underscores the role of interactive updating in predictive processing differences between individuals with ASD and TD individuals.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100468"},"PeriodicalIF":4.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143726221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposome-Wide Gene-By-Environment Interaction Study of Psychotic Experiences in the UK Biobank","authors":"Bochao Danae Lin ,&nbsp;Lotta-Katrin Pries ,&nbsp;Angelo Arias-Magnasco ,&nbsp;Boris Klingenberg ,&nbsp;David E.J. Linden ,&nbsp;Gabriëlla A.M. Blokland ,&nbsp;Dennis van der Meer ,&nbsp;Jurjen J. Luykx ,&nbsp;Bart P.F. Rutten ,&nbsp;Sinan Guloksuz","doi":"10.1016/j.bpsgos.2025.100460","DOIUrl":"10.1016/j.bpsgos.2025.100460","url":null,"abstract":"<div><h3>Background</h3><div>A previous study successfully identified 148 of 23,098 exposures associated with any psychotic experiences (PEs) in the UK Biobank using an exposome-wide association study (XWAS). Furthermore, research has shown that the polygenic risk score for schizophrenia (PRS-SCZ) is associated with PEs. However, the interaction of these exposures with PRS-SCZ remains unknown.</div></div><div><h3>Method</h3><div>To systematically investigate possible gene-by-environment interactions underlying PEs through data-driven agnostic analyses, we conducted 1) conditional XWAS adjusting for PRS-SCZ to estimate the main effects of the exposures and of PRS-SCZ, 2) exposome-wide interaction study (XWIS) to estimate multiplicative and additive interactions between PRS-SCZ and exposures, and 3) correlation analyses between PRS-SCZ and exposures. The study included 148,502 participants from the UK Biobank.</div></div><div><h3>Results</h3><div>In the conditional XWAS models, significant effects of PRS-SCZ and 148 exposures on PEs remained statistically significant. In the XWIS model, we found significant multiplicative (multiplicative scale, 1.23; 95% CI, 1.10–1.37; <em>p</em> = 4.0 × 10⁻⁴) and additive (relative excess risk due to interaction, 0.55; 95% CI, 0.32–0.77; synergy index, 0.22; 95% CI, 0.14–0.30; and attributable proportion, 1.59; 95% CI, 1.30–1.91; all <em>p</em>s &lt; .05/148) interactions of PRS-SCZ and the variable serious medical conditions/disability with PEs. We additionally identified 6 additive gene-by-environment interactions for mental distress, help-/treatment-seeking behaviors (3 variables), sadness, and sleep problems. In the correlation test focused on 7 exposures that exhibited significant interactions with PRS-SCZ, nonsignificant or small (<em>r</em> &lt; 0.04) gene-by-environment correlations were observed.</div></div><div><h3>Conclusions</h3><div>These findings reveal evidence for gene-by-environment interactions underlying PEs and suggest that intertwined pathways of genetic vulnerability and exposures may contribute to psychosis risk.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100460"},"PeriodicalIF":4.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Variations in Daily Cortisol Pattern and Long-Term Cortisol Output on Hippocampal Subfield Volumes in the Adult Human Brain","authors":"Nikolai Malykhin ,&nbsp;Joseph Serrano ,&nbsp;Béla Reiz ,&nbsp;Kathleen Hegadoren ,&nbsp;Wojciech Pietrasik ,&nbsp;Randy Whittal","doi":"10.1016/j.bpsgos.2025.100458","DOIUrl":"10.1016/j.bpsgos.2025.100458","url":null,"abstract":"<div><h3>Background</h3><div>Animal models of adult chronic stress indicate that the cornu ammonis 1–3 (CA1–3) and dentate gyrus (DG) hippocampal subfields are most susceptible to cellular changes associated with prolonged psychogenic stressors and glucocorticoid overexposure. However, no study reported to date has examined associations between long-term cortisol output, chronic stress, and hippocampal subfield volumes in healthy adults experiencing different levels of chronic stress. The main goal of the current study was to test whether higher long-term cortisol output measured by hair cortisol concentration would be associated with atrophy of CA1–3 and DG hippocampal subfields.</div></div><div><h3>Methods</h3><div>We examined associations between short- and long-term cortisol output and hippocampal subfield volumes in healthy adults (<em>N</em> = 40). High-resolution structural magnetic resonance imaging datasets were acquired together with diurnal salivary cortisol and hair cortisol measures. Hair cortisol concentration was analyzed using the high-resolution liquid chromatography–mass spectrometry method.</div></div><div><h3>Results</h3><div>Higher hair cortisol concentration was associated with smaller volumes of all hippocampal subfields in the anterior hippocampus and smaller DG volumes in both the anterior and posterior hippocampus. We found that a larger increase in morning cortisol level after awakening was associated with smaller DG and CA1–3 volumes, while a smaller decrease in cortisol level in the afternoon from awakening was associated with smaller CA1–3 volume in the anterior hippocampus. The observed associations between cortisol and hippocampal subfield volumes were not predicted by individual chronic stress levels or history of childhood trauma.</div></div><div><h3>Conclusions</h3><div>Our results suggest that both increased hair cortisol concentration and daily cortisol fluctuations can have a negative impact on the CA1–3 and DG subfields.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100458"},"PeriodicalIF":4.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigative Approaches to Resilient Emotion Regulation Neurodevelopment in a South African Birth Cohort","authors":"Tristan Yates ,&nbsp;Siphumelele Sigwebela ,&nbsp;Soraya Seedat ,&nbsp;Michael Milham ,&nbsp;Stefan du Plessis ,&nbsp;Lior Abramson ,&nbsp;Erica Niemiec ,&nbsp;Carol Worthman ,&nbsp;Mary Jane Rotheram-Borus ,&nbsp;Giovanni Salum ,&nbsp;Alexandre Franco ,&nbsp;Arianna Zuanazzi ,&nbsp;Fatima Ahmed ,&nbsp;Kelly Gemmell ,&nbsp;Joan Christodoulou ,&nbsp;Nomandla Mhlaba ,&nbsp;Noluncedo Mqhele ,&nbsp;Nomfusi Ngalimane ,&nbsp;Akhona Sambudla ,&nbsp;Nim Tottenham ,&nbsp;Mark Tomlinson","doi":"10.1016/j.bpsgos.2025.100457","DOIUrl":"10.1016/j.bpsgos.2025.100457","url":null,"abstract":"<div><div>Understanding the neurobiology of resilient emotion regulation following adversities is critical for addressing mental health problems globally. However, the functional neurobiology of resilience has rarely been studied in low- and middle-income countries, which comprise 90% of the world’s population and experience more consistent adversities. Here, we describe how we are investigating the neurodevelopment of resilient emotion regulation in adolescents (anticipated <em>N</em> = 525) from a South African birth cohort recruited from a low-income, high-adversity township. Across 2 longitudinal time points (13–14 and 15–16 years), magnetic resonance imaging, behavior, and self-report measures from adolescents and their caregivers are collected. These data are complemented by existing developmental histories (from the prenatal period to 8 years). The culturally adapted measures, protocols, and analytic plans for investigating resilient emotion regulation are presented. By characterizing neurodevelopmental correlates of adolescent resilience from an understudied low- and middle-income country, this research will provide deeper insights into mental health globally.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100457"},"PeriodicalIF":4.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diminished Social Memory and Hippocampal Correlates of Social Interactions in Chronic Social Defeat Stress Susceptibility","authors":"Amanda Larosa ,&nbsp;Tian Rui Zhang ,&nbsp;Alice S. Wong ,&nbsp;Cyrus Y.H. Fung ,&nbsp;Xiong Ling Yun (Jenny) Long ,&nbsp;Prabhjeet Singh ,&nbsp;Benjamin C.M. Fung ,&nbsp;Tak Pan Wong","doi":"10.1016/j.bpsgos.2025.100455","DOIUrl":"10.1016/j.bpsgos.2025.100455","url":null,"abstract":"<div><h3>Background</h3><div>Susceptibility to chronic stress has been associated with depression, a mood disorder that highly implicates the hippocampus. Hippocampal contribution to stress susceptibility has been supported by findings in mice following chronic social defeat stress (CSDS). However, little is known about the role of hippocampal activity in determining the development of stress susceptibility.</div></div><div><h3>Methods</h3><div>We used the UCLA Miniscope to longitudinally measure the activity of dorsal CA1 hippocampal neurons during CSDS. In addition to examining the representation of social information by these neurons, we compared social memory in mice that were either susceptible or resilient to CSDS.</div></div><div><h3>Results</h3><div>We observed more stable dorsal CA1 correlates of social interaction and social memory in CSDS-resilient mice. Such changes were absent in CSDS-susceptible mice and accompanied by greater social memory impairments.</div></div><div><h3>Conclusions</h3><div>CSDS susceptibility may be supported by hippocampal social cognitive processes, as reflected in diminished hippocampal representations of social information and greater impairment in social memory in suspectible compared with resilient mice.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100455"},"PeriodicalIF":4.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the Microbiome in Relation to Mental Distress Across Two Points During Pregnancy: Data From U.S. and Swedish Cohorts","authors":"Mary Kimmel ,&nbsp;Bangzhuo Tong ,&nbsp;Alfons Edbom Devall ,&nbsp;Richelle D. Björvang ,&nbsp;Ina Schuppe-Koistinen ,&nbsp;Lars Engstrand ,&nbsp;Emma Fransson ,&nbsp;Alkistis Skalkidou ,&nbsp;Luisa W. Hugerth","doi":"10.1016/j.bpsgos.2025.100453","DOIUrl":"10.1016/j.bpsgos.2025.100453","url":null,"abstract":"<div><h3>Background</h3><div>In this study, we aimed to characterize the gut microbiome and its potential functioning in 2 populations at 2 time points during pregnancy in relation to mental distress.</div></div><div><h3>Methods</h3><div>During the second and third trimester, individuals from the United States and Sweden completed the Edinburgh Postnatal Depression Scale and provided fecal samples for whole-genome metagenomics. A total of 832 and 161 samples were sequenced and analyzed from the Swedish cohort and the U.S. cohort, respectively. Multiple characterizations of the microbial community were analyzed in relation to distress measured using the Edinburgh Postnatal Depression Scale. Principal coordinate analysis and distance-based redundancy analysis assessed variation in functional gut-brain modules. For the U.S. cohort, the Trier Social Stress Test was administered 8 weeks postpartum while collecting salivary cortisol.</div></div><div><h3>Results</h3><div>Principal coordinate analysis identified 4 sample clusters based on the gut-brain modules distinguished by functions such as short-chain fatty acid synthesis and cortisol degradation. While with distance-based redundancy analysis, mental distress subtypes did not significantly contribute to variation in gut-brain modules (<em>p</em> = .085 for Sweden, <em>p</em> = .23 for the U.S.), a U.S. sample cluster distinguished by lower cortisol degradation from another cluster with higher gut microbial cortisol degradation abundance had significantly higher odds of being associated with depression (<em>p</em> = .024). The U.S. sample cluster with lower gut microbial cortisol degradation abundance also had significantly higher cortisol levels after a postpartum social stressor.</div></div><div><h3>Conclusions</h3><div>Further studies are warranted to investigate the potential for the gut microbiome to serve as biomarkers of gut-brain axis health during pregnancy across disparate populations.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100453"},"PeriodicalIF":4.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prepartal Stress, Prepartal and Postpartal Hair Glucocorticoid Concentrations, and Symptoms of Postpartum Depression 3 Days and 12 Weeks After Delivery","authors":"Dena Sadeghi-Bahmani ,&nbsp;Serge Brand ,&nbsp;Gunther Meinlschmidt ,&nbsp;Marion Tegethoff ,&nbsp;Jennifer Kurath ,&nbsp;Nicole Bürki ,&nbsp;Irene Hösli ,&nbsp;Thorsten Mikoteit","doi":"10.1016/j.bpsgos.2025.100454","DOIUrl":"10.1016/j.bpsgos.2025.100454","url":null,"abstract":"<div><h3>Background</h3><div>Postpartum depression (PPD) is a serious mental health problem that affects about 17% of mothers. The aims of the current study were to observe the associations between prenatal stress, self- and expert-rated PPD, and prepartal and postpartal hair cortisol and cortisone concentrations as proxies for altered hypothalamic-pituitary-adrenal axis activity (HPA-AA).</div></div><div><h3>Methods</h3><div>A total of 129 mothers (mean age 33.1 years) completed the Edinburgh Postnatal Depression Scale 3 days (baseline) and 12 weeks (study end) postpartum. At the end of the study, participants reported on prepartum stressful life events, experts rated participants’ symptoms of depression, and participants provided 6 cm of hair strands for analysis of hair glucosteroid levels 12 weeks before and 12 weeks after delivery.</div></div><div><h3>Results</h3><div>Prepartal stress was associated with higher scores for self- and expert-rated PPD and with lower hair cortisone concentrations as a proxy for less adaptive HPA-AA. Higher prepartal and postpartal hair cortisol/cortisone ratios (i.e., higher cortisol/lower cortisone concentrations) were associated with higher PPD symptom scores.</div></div><div><h3>Conclusions</h3><div>Women with prepartal stress were at increased risk of experiencing PPD 12 weeks after delivery. Altered hair steroid levels (lower cortisone concentrations) as a proxy for altered HPA-AA further substantiated this association. Results suggest that 1) both prepartal stress and the suppression of HPA-AA appear to be involved in the development of PPD; 2) hair steroid analysis can be used to predict PPD; and 3) women with prepartal stressful life events may benefit from timely support and relief to decrease their risk of developing PPD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100454"},"PeriodicalIF":4.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Hidden Mark of a Troubled Past: Neuroimaging and Transcriptomic Analyses Reveal Interactive Effects of Maternal Immune Activation and Adolescent THC Exposure Suggestive of Increased Neuropsychiatric Risk","authors":"Mario Moreno-Fernández ,&nbsp;Víctor Luján ,&nbsp;Shishir Baliyan ,&nbsp;Celia Poza ,&nbsp;Roberto Capellán ,&nbsp;Natalia de las Heras-Martínez ,&nbsp;Miguel Ángel Morcillo ,&nbsp;Marta Oteo ,&nbsp;Emilio Ambrosio ,&nbsp;Marcos Ucha ,&nbsp;Alejandro Higuera-Matas","doi":"10.1016/j.bpsgos.2025.100452","DOIUrl":"10.1016/j.bpsgos.2025.100452","url":null,"abstract":"<div><h3>Background</h3><div>Maternal exposure to infections during gestation has been shown to predispose individuals to neuropsychiatric disorders. Additionally, clinical data suggest that cannabis use may trigger the onset of schizophrenia in vulnerable individuals. However, the direction of causality remains unclear.</div></div><div><h3>Methods</h3><div>To elucidate this issue, we utilized a rat model of maternal immune activation combined with exposure to increasing doses of Δ⁹-tetrahydrocannabinol during adolescence in both male and female rats. We investigated several behaviors in adulthood relevant for neuropsychiatric disorders, including impairments in working memory, deficits in sensorimotor gating, alterations in social behavior, anhedonia, and potential changes in implicit learning (conditioned taste aversion). Furthermore, we conducted a longitudinal positron emission tomography study to target affected brain regions and, subsequently, collected brain samples of one such region (the orbitofrontal cortex) for RNA sequencing analyses, which were also performed on peripheral blood mononuclear cells to identify peripheral biomarkers.</div></div><div><h3>Results</h3><div>While adolescent Δ⁹-tetrahydrocannabinol did not unmask latent behavioral disruptions, positron emission tomography scans revealed several brain alterations dependent on the combination of both hits. Additionally, the transcriptomic studies demonstrated that maternal immune activation affected dopaminergic, glutamatergic, and serotoninergic genes, with the combination of both exposures in most cases shifting the expression from downregulation to upregulation. In peripheral cells, interactive effects were observed on inflammatory pathways, and some genes were proposed as biomarkers.</div></div><div><h3>Conclusions</h3><div>These results suggest that the combination of these 2 vulnerability factors leaves a lasting mark on the body, potentially predisposing individuals to neuropsychiatric disorders even before behavioral alterations manifest.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100452"},"PeriodicalIF":4.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruptions in Reward-Guided Decision-Making Functions Are Predictive of Greater Oral Oxycodone Self-Administration in Male and Female Rats","authors":"Kaitlyn LaRocco ,&nbsp;Peroushini Villiamma ,&nbsp;Justin Hill ,&nbsp;Mara A. Russell ,&nbsp;Ralph J. DiLeone ,&nbsp;Stephanie M. Groman","doi":"10.1016/j.bpsgos.2025.100450","DOIUrl":"10.1016/j.bpsgos.2025.100450","url":null,"abstract":"<div><h3>Background</h3><div>Problematic opioid use that emerges in a subset of individuals may be due to preexisting disruptions in the biobehavioral mechanisms that regulate drug use. The identity of these mechanisms is not known, but emerging evidence suggests that suboptimal decision making that is observable prior to drug use may contribute to the pathology of addiction.</div></div><div><h3>Methods</h3><div>The current study investigated the relationship between decision-making phenotypes and opioid-taking behaviors in male and female Long Evans rats. Adaptive decision-making processes were assessed using a probabilistic reversal learning task and oxycodone- (or vehicle, as a control) taking behaviors assessed daily in 32 sessions using a saccharin fading procedure that promoted dynamic intake of oxycodone. Tests of motivation, extinction, and reinstatement were also performed.</div></div><div><h3>Results</h3><div>Computational analyses of decision-making data identified data-driven metrics that predicted self-administration of oxycodone and addiction-relevant behaviors. Moreover, preexisting impairments in reward-guided decision making observed in female rats were associated with greater addiction-relevant behaviors when compared with males.</div></div><div><h3>Conclusions</h3><div>These results provide new insights into the biobehavioral mechanisms that regulate opiate-taking behaviors and offer a novel phenotypic approach for interrogating sex differences in addiction susceptibility and opioid use disorders.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100450"},"PeriodicalIF":4.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143465067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Transcriptomic Signature of Depressive Symptoms in Late Life","authors":"Stuart Matan-Lithwick ,&nbsp;Melissa C. Misztal ,&nbsp;Mu Yang ,&nbsp;Thomas DeLong ,&nbsp;Shreejoy Tripathy ,&nbsp;Jeffrey T. Dunn ,&nbsp;David A. Bennett ,&nbsp;Philip L. De Jager ,&nbsp;Yanling Wang ,&nbsp;Daniel W. Fisher ,&nbsp;Hongxin Dong ,&nbsp;Daniel Felsky","doi":"10.1016/j.bpsgos.2025.100448","DOIUrl":"10.1016/j.bpsgos.2025.100448","url":null,"abstract":"<div><h3>Background</h3><div>Depressive symptoms in late life can impair daily function and accompany cognitive decline. However, the molecular mechanisms that underlie these changes in the brain remain poorly understood.</div></div><div><h3>Methods</h3><div>Differential expression analysis was performed on bulk-tissue RNA sequencing data generated from dorsolateral prefrontal cortex samples of elderly participants in ROS/MAP (Religious Orders Study and Memory and Aging Project; <em>N</em> = 998, mean age at death = 89.7 years). Bulk tissue RNA sequencing was analyzed against depressive symptoms measured prior to death, controlling for Alzheimer’s disease neuropathology, medication status, and lifestyle factors. Sex-stratified models were also tested.</div></div><div><h3>Results</h3><div>Increased abundance of the Prader-Willi syndrome–associated gene <em>PWAR1</em> (corrected <em>p</em> = 5.47 × 10⁻³) and <em>CTDSPL2</em> (corrected <em>p</em> = .03) were associated with a higher burden of depressive symptoms in the combined sample. An additional 14 genes showed suggestive associations, including several with known links to neuropsychiatric illness (e.g., <em>ACVR2B-AS1</em>, <em>COL19A1</em>). Functional enrichment analysis revealed downregulation of aerobic metabolism and upregulation of both amino acid catabolism and DNA modification processes. Differential expression signatures were poorly correlated between males and females (Pearson <em>r</em> = 0.12; 95% CI, 0.10 to 0.13), and only the male group showed independently significant differential expression. Little overlap was found with previously published analyses of major depressive disorder.</div></div><div><h3>Conclusions</h3><div>Building on recently published single-nucleus profiling, we present the largest-ever study of transcriptomic correlates of depressive symptoms in late life, revealing new insights into sex-specific regulators. <em>PWAR1</em> and <em>CTDSPL2</em> were identified as putative markers of late-life depression in the dorsolateral prefrontal cortex and warrant further study.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100448"},"PeriodicalIF":4.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}