Biological psychiatry global open science最新文献

{"title":"Atypical Neural Activation During Emotional but Not Nonemotional Response Inhibition in Healthy Young People Exposed to Childhood Maltreatment and Peer Victimization","authors":"Lena Lim ,&nbsp;Keith M. Shafritz","doi":"10.1016/j.bpsgos.2025.100497","DOIUrl":"10.1016/j.bpsgos.2025.100497","url":null,"abstract":"<div><h3>Background</h3><div>Early-life interpersonal stress, particularly childhood maltreatment (CM), is associated with neurobiological abnormalities and atypical emotion regulation. However, few studies have investigated the neural effects of peer victimization (PV). We examined neural alterations in emotional and nonemotional response inhibition in carefully matched healthy CM and PV groups.</div></div><div><h3>Methods</h3><div>Functional magnetic resonance imaging data were collected from 113 age- and sex-matched nonclinical/community youths (38 CM, 39 PV, and 36 control) during an emotional (fearful/happy) and nonemotional (letter) Go/NoGo task.</div></div><div><h3>Results</h3><div>There were no significant group differences in behavioral performance. However, during fearful face inhibition, the CM group exhibited hyperactivation compared with the PV group in a cluster comprising the bilateral calcarine, cuneus, and lingual gyri, which was related to higher parental antipathy in the CM group. Hyperactivation also occurred in limbic-striatal, middle temporal, and cerebellar regions, although at a more liberal threshold. Additionally, there was a trend of PV-specific underactivation in the left middle temporal gyrus during happy inhibition. Despite no significant group differences in nonemotional response inhibition, both the CM and PV groups exhibited greater activation than the control group in default mode network regions during the cognitively low-load LetterGo condition.</div></div><div><h3>Conclusions</h3><div>These findings suggest that early-life interpersonal stress is associated with atypical neural activation during emotionally driven decision making but not during nonemotional response inhibition, underscoring the importance of examining both “hot” and “cold” decision-making processes. The atypical activation of key emotion-visual processing regions may be a potential mechanism to cope with aversive experiences and may reflect the brain’s attempt to facilitate emotional inhibitory control, particularly in resilient maltreated youths.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100497"},"PeriodicalIF":4.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856121","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":"Exposure to Fine Particulate Matter During Pregnancy Is Associated With Hippocampal Development in Offspring","authors":"Jessica L. Buthmann ,&nbsp;Tarik Benmarhnia ,&nbsp;Jonathan Y. Huang ,&nbsp;Pei Huang ,&nbsp;Jonas G. Miller ,&nbsp;Jessica P. Uy ,&nbsp;Peter D. Gluckman ,&nbsp;Marielle V. Fortier ,&nbsp;Yap-Seng Chong ,&nbsp;Ai Peng Tan ,&nbsp;Michael J. Meaney ,&nbsp;Ian H. Gotlib","doi":"10.1016/j.bpsgos.2025.100490","DOIUrl":"10.1016/j.bpsgos.2025.100490","url":null,"abstract":"<div><h3>Background</h3><div>As the global climate crisis persists, it becomes increasingly important to understand how exposure to environmental toxins can affect the developing brain. Although researchers are beginning to document links between prenatal exposure to air pollution and brain structure, it is not clear when these associations emerge.</div></div><div><h3>Methods</h3><div>We leveraged data from the GUSTO (Growing Up Toward Healthy Outcomes in Singapore) longitudinal birth cohort study to examine prenatal exposure to air pollution and brain development during childhood. Spatiotemporally interpolated prenatal exposure to particulate matter &lt;2.5 μm was averaged across each prenatal week. Structural magnetic resonance imaging data were obtained when children were ages 4.5, 6.0, 7.5, and 10.5 years (<em>N</em> = 325, 47.7% female) and segmented with FreeSurfer 7.1. A subset of parents completed the Child Behavior Checklist at the final assessment (<em>n</em> = 195, 46.7% female). We used latent growth modeling to estimate a slope of hippocampal volume growth in each hemisphere from ages 4.5 to 10.5 years, adjusted for intracranial volume.</div></div><div><h3>Results</h3><div>Distributed lag models indicated that late gestational exposure (during weeks 36–40) was associated with slower hippocampal growth in both hemispheres. Importantly, we also found that faster hippocampal volume growth in the right hemisphere was associated with more externalizing and attention problems at 10.5 years.</div></div><div><h3>Conclusions</h3><div>Future research should examine mechanisms that may underlie or contribute to these associations. These findings underscore the importance of efforts to reduce pollution, particularly for pregnant people and their children.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100490"},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847859","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":"Mediation Analyses Link Cardiometabolic Factors and Liver Fat With White Matter Hyperintensities and Cognitive Performance: A UK Biobank Study","authors":"Daniel E. Askeland-Gjerde ,&nbsp;Lars T. Westlye ,&nbsp;Patrik Andersson ,&nbsp;Max Korbmacher ,&nbsp;Ann-Marie de Lange ,&nbsp;Dennis van der Meer ,&nbsp;Olav B. Smeland ,&nbsp;Sigrun Halvorsen ,&nbsp;Ole A. Andreassen ,&nbsp;Tiril P. Gurholt","doi":"10.1016/j.bpsgos.2025.100488","DOIUrl":"10.1016/j.bpsgos.2025.100488","url":null,"abstract":"<div><h3>Background</h3><div>Liver fat is associated with cardiometabolic disease, cerebrovascular disease, and dementia. Cerebrovascular disease, most often cerebral small vessel disease, identified by magnetic resonance imaging as white matter hyperintensities (WMHs) often contributes to dementia. However, liver fat’s role in the relationship between cardiometabolic risk, WMHs, and cognitive performance is unclear.</div></div><div><h3>Methods</h3><div>In the UK Biobank cohort (<em>N</em> = 32,461, 52.6% female; mean age 64.2 ± 7.7 years; <em>n</em> = 23,354 in the cognitive performance subsample), we used linear regression to investigate associations between cardiometabolic factors measured at baseline and liver fat, WMHs, and cognitive performance measured at follow-up, which was 9.3 ± 2.0 years later on average. We used structural equation modeling to investigate whether liver fat mediated associations between cardiometabolic factors and WMHs and whether WMHs mediated associations between liver fat and cognitive performance.</div></div><div><h3>Results</h3><div>Nearly all cardiometabolic factors were significantly associated with liver fat (|<em>r</em>| range = 0.03–0.41, <em>p</em> = 3.4 × 10⁻⁸ to 0) and WMHs (|<em>r</em>| = 0.04–0.15, <em>p</em> = 5.8 × 10⁻¹³ to 7.0 × 10⁻¹⁵⁹) in regression models. Liver fat was associated with WMHs (<em>r</em> = 0.11, <em>p</em> = 4.3 × 10⁻⁸²) and cognitive performance (<em>r</em> = −0.03, <em>p</em> = 1.6 × 10⁻⁷). Liver fat mediated the associations between cardiometabolic factors and WMHs (|β_mediation| = 0.003–0.027, <em>p</em>_mediation = 1.9 × 10⁻⁸ to 0), and WMHs mediated the associations between liver fat and cognitive performance (β_mediation = −0.01, <em>p</em>_mediation = 0).</div></div><div><h3>Conclusions</h3><div>Our findings indicate that liver fat mediates associations between cardiometabolic factors and WMHs and that WMHs mediate the association between liver fat and cognitive performance. This suggests that liver fat may be important for understanding the effects of cardiometabolic factors on cerebrovascular disease and cognitive function. Experimental studies are warranted to determine relevant targets for preventing vascular-driven cognitive impairment.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100488"},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851775","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":"Early-Life Adversity–Induced Epigenetic Reprogramming of Prefrontal Cortex in Rats Subjected to Maternal Separation","authors":"Aleena Francis ,&nbsp;Lauren Allen McKibben ,&nbsp;Yogesh Dwivedi","doi":"10.1016/j.bpsgos.2025.100487","DOIUrl":"10.1016/j.bpsgos.2025.100487","url":null,"abstract":"<div><h3>Background</h3><div>Early-life adversity (ELA) can lead to long-lasting behavioral and neurobiological changes through epigenetic mechanisms. In this study, we comprehensively mapped genome-wide DNA methylation in the prefrontal cortex of rats following maternal separation (MS).</div></div><div><h3>Methods</h3><div>Rat pups were separated from their mother for 180 minutes/day from postnatal days (PNDs) 1 to 14 and tested for depressive- and anxiety-like behavior during adulthood (PNDs 80–89). Genome-wide DNA methylation, corresponding functional analyses, and transcription factor binding sites (TFBSs) were performed using reduced-representation bisulfite sequencing, focusing on differentially methylated cytosines (DMCs), differentially methylated regions (DMRs), and non-CpG sites.</div></div><div><h3>Results</h3><div>Both male and female MS rats showed a significant decrease in sucrose preference. Principal component and multidimensional scaling analyses did not show differences in the methylation data between male and female rats, prompting us to combine them in subsequent analyses. A total of 33,905 DMCs and 151 DMRs were identified in the MS group. The functional analysis of the dysregulated genes by DMCs and DMRs in the promoter or gene body revealed gene enrichment involved in neurodevelopment, synaptic plasticity, and stress response. Key genes with altered methylation included <em>Dnmt3a/b</em>, <em>Notch1</em>, <em>Mapk14</em>, and calcium channel subunits. Gene network analysis revealed interactions among ribosomal, MAPK (mitogen-activated protein kinase), and glutamatergic pathway genes. An enrichment of Elk1 TFBSs was particularly noted within the DMR. Additionally, differential non-CpG methylation, specifically at CHH (H = C/T/A) sites, dysregulated the Wnt pathway genes.</div></div><div><h3>Conclusions</h3><div>Our findings expand our understanding of the molecular mechanisms that underlie the long-term effects of ELA and identify potential biomarkers for stress-related psychiatric disorders.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100487"},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869559","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":"Transformative Effects of Mindfulness Meditation Training on the Dynamic Reconfiguration of Executive and Default Mode Networks in Internet Gaming Disorder","authors":"Shuang Li ,&nbsp;Anhang Jiang ,&nbsp;Xuefeng Ma ,&nbsp;Zhengjie Zhang ,&nbsp;Haosen Ni ,&nbsp;Huabin Wang ,&nbsp;Chang Liu ,&nbsp;Xiaolan Song ,&nbsp;Guang-Heng Dong","doi":"10.1016/j.bpsgos.2025.100485","DOIUrl":"10.1016/j.bpsgos.2025.100485","url":null,"abstract":"<div><h3>Background</h3><div>Internet gaming disorder (IGD) is a pervasive global mental health issue, and finding effective treatments for the disorder has been challenging. Mindfulness meditation (MM), recognized for its holistic approach that involves integrating mental and physical facets, holds promise for addressing the multifaceted nature of addiction. Nevertheless, the effect of MM on IGD and its associated neural networks, particularly in terms of their dynamic characteristics, remains elusive.</div></div><div><h3>Methods</h3><div>A total of 61 eligible participants with IGD (30 in the MM group, 31 in the progressive muscle relaxation [PMR] group) completed the experimental protocol, which involved pretest, an 8-session MM/PMR training regimen, and posttests. The 142 brain regions of interest were categorized into 5 brain networks using dynamic network reconfiguration analysis based on Shen’s functional template. A comparative analysis of network dynamic features, including recruitment and integration coefficients, was performed across different groups and tests using resting-state functional magnetic resonance imaging data.</div></div><div><h3>Results</h3><div>While clinically nonspecific effects were observed in the PMR group, the MM group exhibited a significant reduction in addiction severity and cravings. In the dynamic brain network, MM training increased the recruitment coefficient within the frontoparietal network (FPN) and basal ganglia network (BGN) but decreased it within the default mode network (DMN). Furthermore, MM training increased the integration coefficient in the FPN-DMN and DMN–limbic network (LN).</div></div><div><h3>Conclusions</h3><div>MM has demonstrated pronounced efficacy in treating IGD. MM may enhance top-down control functions, cognitive and emotional functions, and reward-system processing, potentially through the reconfiguration of the FPN-DMN pathway, DMN-LN pathway, and BGN.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100485"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143851774","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":"Transient Inhibition of the Mediodorsal Thalamus During Early Adolescence Induces Hypofrontality and Social Memory Deficits in Young Adulthood","authors":"Sha-Sha Yang ,&nbsp;Quansheng He ,&nbsp;Xinyang Gu ,&nbsp;Shoupei Liu ,&nbsp;Wei Ke ,&nbsp;Liang Chen ,&nbsp;Bo Li ,&nbsp;Yousheng Shu ,&nbsp;Wen-Jun Gao","doi":"10.1016/j.bpsgos.2025.100486","DOIUrl":"10.1016/j.bpsgos.2025.100486","url":null,"abstract":"<div><h3>Background</h3><div>Dysconnectivity between the mediodorsal thalamus (MD) and medial prefrontal cortex (mPFC) during adolescence is linked to developmental and psychiatric disorders, as well as social behavioral deficits. However, the precise mechanisms that underlie these impairments remain elusive.</div></div><div><h3>Methods</h3><div>We transiently inhibited MD activity with inhibitory DREADDs (HM4Di) in adolescent mice. Then, we examined the social behavior performance by a three-chamber social behavioral paradigm and neural excitability in both MD and mPFC neurons in adulthood with multiple approaches.</div></div><div><h3>Results</h3><div>We revealed that this transient MD inhibition during adolescence led to impaired social memory in adulthood. The neuronal excitability of both MD and mPFC excitatory neurons decreased. Meanwhile, excitatory synaptic transmission in excitatory pyramidal neurons in the mPFC was impaired. In vivo calcium imaging showed a persistent reduction of general calcium activity in the mPFC. Unexpectedly, there were significant alterations in intrinsic excitability and synaptic function changes in somatostatin but not in parvalbumin interneurons.</div></div><div><h3>Conclusions</h3><div>Our findings provide insights into the role of MD input activity in shaping the circuit and functional maturation of the mPFC that is critical for the normal development of social memory and abnormal deficits in psychiatric disorders.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100486"},"PeriodicalIF":4.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143858904","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":"Eating Disorders and Later Incidence of Cancer: A Nationwide Longitudinal Study in Denmark","authors":"Gabrielle E. Cooper ,&nbsp;Natalie M. Papini ,&nbsp;Katrine Holde ,&nbsp;Cynthia M. Bulik ,&nbsp;Zeynep Yilmaz ,&nbsp;Liselotte V. Petersen","doi":"10.1016/j.bpsgos.2025.100483","DOIUrl":"10.1016/j.bpsgos.2025.100483","url":null,"abstract":"<div><h3>Background</h3><div>We examined the incidence of cancer types among individuals with eating disorders (EDs).</div></div><div><h3>Methods</h3><div>A nationwide longitudinal study of 6,807,731 individuals born between 1940 and 2015 was conducted using the Danish National Registries. Cox models with ED diagnosis as exposure and cancer diagnoses as outcomes were used to estimate hazard ratios (HRs) and 95% CIs while adjusting for sex, birth year, and comorbidities. The primary analysis comprised ICD-8 and ICD-10 codes for anorexia nervosa (AN) and other ED (OED). The secondary analysis comprised ICD-10 codes and included AN, bulimia nervosa (BN), and eating disorders not otherwise specified (EDNOS).</div></div><div><h3>Results</h3><div>AN was associated with a reduced incidence of breast cancer while adjusting for sex and birth year (HR, 0.80; 95% CI, 0.66–0.97) and elevated incidence of respiratory (HR, 1.59; 95% CI, 1.24–2.04), cervical (HR, 1.45; 95% CI, 1.05–1.98), and esophageal (HR, 4.77; 95% CI, 2.82–8.06) cancers. OED was associated with an elevated incidence of respiratory (HR, 1.57; 95% CI, 1.20–2.06) and cervical (HR, 1.60; 95% CI, 1.20–2.14) cancers. ICD-10–only analyses confirmed the association of AN with reduced incidence of breast cancer and elevated incidence of respiratory and cervical cancers. BN was associated with reduced incidence of breast cancer in sensitivity analysis. EDNOS was associated with reduced incidence of breast cancer and elevated incidence of respiratory and cervical cancers.</div></div><div><h3>Conclusions</h3><div>All EDs were associated with a reduced incidence of breast cancer. All EDs except BN were associated with a higher incidence of respiratory and cervical cancers. AN was associated with a higher incidence of esophageal cancer.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100483"},"PeriodicalIF":4.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828294","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":"Fear Synchrony of Mouse Dyads: Interaction of Sex Composition and Stress","authors":"Wataru Ito ,&nbsp;Andrew Holmes ,&nbsp;Alexei Morozov","doi":"10.1016/j.bpsgos.2025.100484","DOIUrl":"10.1016/j.bpsgos.2025.100484","url":null,"abstract":"<div><h3>Background</h3><div>Socially coordinated threat responses support a group’s survival. Given the distinct social roles of each sex, social coordination can differ between males and females and mixed-sex groups. We investigated how the sex composition of mouse dyads affected one form of social coordination, the synchronization of conditioned freezing, and assessed how emotional state and social context influenced synchronization by exposure to stress and altering the partner’s familiarity, respectively.</div></div><div><h3>Methods</h3><div>Mice were fear conditioned individually to an auditory stimulus and tested in same- or opposite-sex dyads with familiar or unfamiliar partners. Independent cohorts were tested after 5 minutes of restraint stress or with prefrontal inactivation by muscimol. Time-series data on freezing bouts were used to compute the synchrony index, freezing properties, and state transitions based on a Markov model.</div></div><div><h3>Results</h3><div>In same-sex dyads, males exhibited higher synchrony than females. State transition analysis revealed sex-specific synchronization strategies: Males maintained a congruent freezing state primarily by following their partners’ state transitions, whereas females did so by reversing their own. Stress disrupted synchrony in males, which was prevented by prefrontal inactivation, while stress enhanced synchrony in females. Partner’s unfamiliarity reduced synchrony in males but had no effect on females. Conversely, opposite-sex dyads exhibited high levels of synchrony and a unique resilience to stress and unfamiliarity without preferred synchronization strategies.</div></div><div><h3>Conclusions</h3><div>Mice display sex composition–specific synchronization of threat response and its modulation by stress and social context, providing insights into neuropsychiatric disorders characterized by abnormal threat responses in social contexts with same- and opposite-sex groups.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100484"},"PeriodicalIF":4.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847858","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":"Integration of Metabolomic and Brain Imaging Data Highlights Pleiotropy Among Posttraumatic Stress Disorder, Glycoprotein Acetyls, and Pallidum Structure","authors":"Solveig Løkhammer ,&nbsp;Markos Tesfaye ,&nbsp;Brenda Cabrera-Mendoza ,&nbsp;Kristoffer Sandås ,&nbsp;Gita A. Pathak ,&nbsp;Eleni Friligkou ,&nbsp;Stéphanie Le Hellard ,&nbsp;Renato Polimanti","doi":"10.1016/j.bpsgos.2025.100482","DOIUrl":"10.1016/j.bpsgos.2025.100482","url":null,"abstract":"<div><h3>Background</h3><div>The development of posttraumatic stress disorder (PTSD) is attributable to the interplay between exposure to severe traumatic events, environmental factors, and biological characteristics. Blood and brain imaging markers have been associated with PTSD. However, to our knowledge, no study has systematically investigated the genetic relationship between PTSD, metabolic biomarkers, and brainwide imaging.</div></div><div><h3>Methods</h3><div>We integrated genome-wide data informative of PTSD, 233 metabolic biomarkers, and 3935 brain imaging-derived phenotypes (IDPs). Pleiotropy was assessed by applying global and local genetic correlation, colocalization, and genetically inferred causality.</div></div><div><h3>Results</h3><div>We observed significant genetic overlap between PTSD and glycoprotein acetyls (GlycA) (a stable inflammatory biomarker) in 2 independent cohorts (discovery <em>r</em>_g = 0.26, <em>p</em> = 1.00 × 10⁻⁴; replication <em>r</em>_g = 0.23, <em>p</em> = 5.99 × 10⁻¹⁹). Interestingly, there was no genetic correlation between anxiety and GlycA (<em>p</em> = .33). PTSD and GlycA were both genetically correlated with median T2∗ in the left pallidum (IDP-1444: <em>r</em>_g = 0.14, <em>p</em> = 1.39 × 10⁻⁵; <em>r</em>_g = −0.38, <em>p</em> = 2.50 × 10⁻³, respectively). Local genetic correlation between PTSD and GlycA was observed in 7 genetic regions (<em>p</em> &lt; 2.0 × 10⁻⁵), mapping genes related to immune and stress response, inflammation, and metabolic processes. Furthermore, we identified 1 variant, rs12048743, with evidence of horizontal pleiotropy linking GlycA and IDP-1444 (<em>z</em>_IDP-1444 = 17.14, <em>z</em>_GlycA = −6.07, theta <em>p</em> = 2.06 × 10⁻⁸). Regional colocalization was observed among GlycA, IDP-1444, and tissue-specific transcriptomic regulation for brain frontal cortex and testis (rs12048743—chr1q32.1; posterior probability &gt; 0.8). While we also tested causality between PTSD, metabolomic biomarkers, and brain IDPs, these were not consistent across different genetically informed causal inference methods.</div></div><div><h3>Conclusions</h3><div>Our findings highlight a new putative pleiotropic mechanism that links systemic inflammation and pallidum structure to PTSD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100482"},"PeriodicalIF":4.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821421","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":"Peripheral Blood Cytokines as Markers of Longitudinal Change in White Matter Microstructure Following Inpatient Treatment for Opioid Use Disorders","authors":"Eduardo R. Butelman ,&nbsp;Yuefeng Huang ,&nbsp;Sarah G. King ,&nbsp;Pierre-Olivier Gaudreault ,&nbsp;Ahmet O. Ceceli ,&nbsp;Greg Kronberg ,&nbsp;Flurin Cathomas ,&nbsp;Panos Roussos ,&nbsp;Scott J. Russo ,&nbsp;Eric L. Garland ,&nbsp;Rita Z. Goldstein ,&nbsp;Nelly Alia-Klein","doi":"10.1016/j.bpsgos.2025.100480","DOIUrl":"10.1016/j.bpsgos.2025.100480","url":null,"abstract":"<div><h3>Background</h3><div>Opioid use disorder (OUD) causes major public health morbidity and mortality. Although standard-of-care treatment with medications for OUD (MOUDs) is available, there are few biological markers of the clinical process of recovery. Neurobiological aspects of recovery can include normalization of brain white matter (WM) microstructure, which is sensitive to cytokine signaling. Here, we determined whether blood-based cytokines can be markers of change in WM microstructure following MOUD.</div></div><div><h3>Methods</h3><div>Inpatient individuals with heroin use disorder (iHUDs) (<em>n</em> = 21) with methadone or buprenorphine MOUD underwent magnetic resonance imaging (MRI) scans with diffusion tensor imaging (DTI) and provided ratings of drug cue–induced craving, arousal, and valence earlier in treatment (MRI1) and ≈14 weeks thereafter (MRI2). Healthy control participants (HCs) (<em>n</em> = 24) also underwent 2 MRI scans during a similar time interval. At MRI2, participants provided a peripheral blood sample for multiplex quantification of serum cytokines. We analyzed the correlation of a multitarget biomarker score (from a principal component analysis of 19 cytokines that differed significantly between iHUDs and HCs) with treatment-related change in DTI metrics (ΔDTI; MRI2 − MRI1).</div></div><div><h3>Results</h3><div>The cytokine biomarker score was negatively correlated with ΔDTI metrics in frontal, frontoparietal, and corticolimbic WM tracts in iHUDs but not in HCs. Also, serum levels of specific cytokines in the cytokine biomarker score, including the interleukin-related oncostatin M (OSM), similarly correlated with ΔDTI metrics in iHUDs but not in HCs. Serum levels of other specific cytokines were negatively correlated with changes in cue-induced craving and arousal in the iHUDs.</div></div><div><h3>Conclusions</h3><div>Specific serum cytokines, studied alone or as a group, may serve as accessible biomarkers of WM microstructure changes and potential recovery in iHUDs undergoing treatment with MOUD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 3","pages":"Article 100480"},"PeriodicalIF":4.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791630","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}