Biological psychiatry global open science最新文献

{"title":"Autism-Associated PTCHD1 Missense Variants Bind to the SNARE-Associated Protein SNAPIN but Exhibit Impaired Subcellular Trafficking","authors":"Stephen F. Pastore ,&nbsp;Connie T.Y. Xie ,&nbsp;Roya Derwish ,&nbsp;Tahir Muhammad ,&nbsp;Tereza Blahova ,&nbsp;Sierra C. El-masri ,&nbsp;Paul W. Frankland ,&nbsp;Paul A. Hamel ,&nbsp;John B. Vincent","doi":"10.1016/j.bpsgos.2025.100492","DOIUrl":"10.1016/j.bpsgos.2025.100492","url":null,"abstract":"<div><h3>Background</h3><div><em>PTCHD1</em> is a susceptibility gene for autism spectrum disorder and intellectual disability. Its function in brain development and neurotransmission remains elusive. Studies have sought to characterize PTCHD1 function by elucidating its neural network of interacting proteins. However, given the current paucity of functional information, many PTCHD1 missense variants in clinical databases are classified as variants of uncertain significance (VUSs), severely limiting the health care resources available to patients and families.</div></div><div><h3>Methods</h3><div>A yeast 2-hybrid assay was used to identify synaptic PTCHD1-interacting proteins. Candidate binding partners were validated by cloning; transient overexpression in human embryonic kidney (HEK) 293T cells, followed by co-immunoprecipitation and immunoblotting; and immunocytochemistry in differentiated P19 cells. Site-directed mutagenesis was used to evaluate the pathogenicity of clinical missense variants, followed by transient overexpression and immunocytochemistry in non-neuronal (HEK293T) and neuronal (Neuro-2a cells) systems.</div></div><div><h3>Results</h3><div>A novel interaction was identified between the first lumenal loop of PTCHD1 and the SNARE-associated protein SNAPIN, which is implicated in synaptic vesicle exocytosis. Clinically associated missense variants within this region did not disrupt SNAPIN binding, indicating that the pathoetiology of these variants is unrelated to this interaction. However, 6 of the 12 missense variants tested exhibited pronounced retention within the endoplasmic reticulum and impaired neuronal and non-neuronal trafficking to the plasma membrane.</div></div><div><h3>Conclusions</h3><div>These data yield insights into the role of PTCHD1 in neurodevelopment and neurotransmission and suggest a neuropathological mechanism for missense variants. These findings provide a platform for diagnostic assay and VUS interpretation, allowing for clinical reclassification of these variants.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100492"},"PeriodicalIF":4.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906770","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":"Posttraumatic Stress Disorder-Related Differences in Neural Connectivity Among Female Trauma Survivors","authors":"Natalie C. Noble ,&nbsp;Mohammad S.E. Sendi ,&nbsp;Julia B. Merker ,&nbsp;Samantha R. Linton ,&nbsp;Theresa K. Webber ,&nbsp;Russell T. Toll ,&nbsp;Amit Etkin ,&nbsp;Wei Wu ,&nbsp;Kerry J. Ressler ,&nbsp;Antonia V. Seligowski","doi":"10.1016/j.bpsgos.2025.100491","DOIUrl":"10.1016/j.bpsgos.2025.100491","url":null,"abstract":"<div><h3>Background</h3><div>Posttraumatic stress disorder (PTSD) is a debilitating condition that disproportionately impacts females. Prior research indicates that males with PTSD exhibit hypoconnectivity of frontal brain regions measured with resting electroencephalography (EEG). In the current study, we examined functional connectivity among females with PTSD and trauma-exposed control females, as well as the impact of sex hormones.</div></div><div><h3>Methods</h3><div>Participants included 61 females (mean age = 31.41 years, SD = 8.64) who endorsed criterion A trauma exposure. Resting-state EEG data were recorded for 5 minutes in the eyes-open position. Using a linear mixed-effects model, functional connectivity of the theta band (4–7 Hz) served as the response variable.</div></div><div><h3>Results</h3><div>Compared with the control group, the PTSD group showed hyperconnectivity between visual brain regions and the rest of the cerebral cortex (false discovery rate–corrected <em>p</em> [<em>p</em>_FDR] &lt; .05). Additionally, participants with PTSD demonstrated enhanced connectivity between the default mode network and frontoparietal control network compared with control participants (<em>p</em>_FDR &lt; .05), as well as increased connectivity between the ventral attention network and the rest of the cerebral cortex (<em>p</em>_FDR &lt; .05). Estradiol was associated with higher connectivity, while progesterone was associated with lower connectivity, but these associations did not survive correction.</div></div><div><h3>Conclusions</h3><div>The results are consistent with prior research indicating that PTSD is associated with altered connectivity in visual brain regions, which may reflect disrupted visual processing related to reexperiencing symptoms (e.g., intrusive memories). Our findings provide additional support for the relevance of the theta frequency range in PTSD given its role in fear learning and regulation processes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100491"},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879258","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":"Association of Psychological Resilience With Decelerated Brain Aging in Cognitively Healthy World Trade Center Responders","authors":"Saren H. Seeley ,&nbsp;Rachel Fremont ,&nbsp;Zoe Schreiber ,&nbsp;Laurel S. Morris ,&nbsp;Leah Cahn ,&nbsp;James W. Murrough ,&nbsp;Daniela Schiller ,&nbsp;Dennis S. Charney ,&nbsp;Robert H. Pietrzak ,&nbsp;M. Mercedes Perez-Rodriguez ,&nbsp;Adriana Feder","doi":"10.1016/j.bpsgos.2025.100489","DOIUrl":"10.1016/j.bpsgos.2025.100489","url":null,"abstract":"<div><h3>Background</h3><div>Despite their exposure to potentially traumatic stressors, the majority of World Trade Center (WTC) responders—those who worked on rescue, recovery, and cleanup efforts on or following September 11, 2001—have shown psychological resilience, never developing long-term psychopathology. Psychological resilience may be protective against the earlier age-related cognitive changes associated with posttraumatic stress disorder (PTSD) in this cohort. In the current study, we calculated the difference between estimated brain age from structural magnetic resonance imaging (MRI) data and chronological age in WTC responders who participated in a parent functional MRI study of resilience (<em>N</em> = 97). We hypothesized that highly resilient responders would show the least brain aging and explored associations between brain aging and psychological and cognitive measures.</div></div><div><h3>Method</h3><div>WTC responders screened for the absence of cognitive impairment were classified into 3 groups: a WTC-related PTSD group (<em>n</em> = 32), a Highly Resilient group without lifetime psychopathology despite high WTC-related exposure (<em>n</em> = 34), and a Lower WTC-Exposed control group also without lifetime psychopathology (<em>n</em> = 31). We used <em>BrainStructureAges</em>, a deep learning algorithm that estimates voxelwise age from T1-weighted MRI data to calculate decelerated (or accelerated) brain aging relative to chronological age.</div></div><div><h3>Results</h3><div>Globally, brain aging was decelerated in the Highly Resilient group and accelerated in the PTSD group, with a significant group difference (<em>p</em> = .021, Cohen’s <em>d</em> = 0.58); the Lower WTC-Exposed control group exhibited no significant brain age gap or group difference. Lesser brain aging was associated with resilience-linked factors including lower emotional suppression, greater optimism, and better verbal learning.</div></div><div><h3>Conclusions</h3><div>Cognitively healthy WTC responders show differences in brain aging related to resilience and PTSD.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 4","pages":"Article 100489"},"PeriodicalIF":4.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906769","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}