Translational Psychiatry最新文献

{"title":"The relationship between hair cortisol and trauma sequelae in motor vehicle crash survivors: the role of childhood trauma experiences.","authors":"Ileana Schmalbach, Susann Steudte-Schmiedgen, Vanessa Renner, Philipp Drees, Katja Petrowski","doi":"10.1038/s41398-025-03295-6","DOIUrl":"https://doi.org/10.1038/s41398-025-03295-6","url":null,"abstract":"<p><p>Previous research highlights inconsistent associations between premorbid hair cortisol concentrations (HCC) and posttraumatic stress disorder (PTSD) symptoms, often neglecting the critical role of childhood trauma (CT) in civilian populations. To address this gap, our study investigates the predictive value of HCC for PTSD symptoms following a motor vehicle crash (MVC), extending our prior findings by assessing CT as a moderator within a sample that includes participants with and without CT. We hypothesize that pre-MVC HCC is positively associated with PTSD risk and that this relationship is moderated by early adversity. We examined N = 272 participants with a traumatic brain injury aged 18-65 years who experienced a MVC between 2010 and 2020. Cortisol concentrations were determined in 3 cm scalp-near segments of hair samples that were obtained at the emergency room shortly after the MVC (t1). Participants completed measuring instruments capturing symptoms of posttraumatic stress (Posttraumatic Diagnostic Scale [PDS]; Impact of Event Scale-Revised [IES-R]) and Childhood Trauma Questionnaire (CTQ). PDS and IES-R were re-collected three months post-MVC (t2). Elevated pre-MVC HCC predicted PTSD symptoms (p < 0.05), emphasizing the role of chronic stress and HPA axis dysregulation in PTSD. Contrary to our hypothesis, CT did not moderate this relationship, suggesting that HCC's impact on PTSD is independent of early adverse experiences. In this context, CT emerged as an independent predictor of PTSD at the 3-month follow-up, underscoring its lasting influence on psychological trauma vulnerability, particular in the face of recent adversity. Our study confirmed that elevated pre-MVC HCC levels predict PTSD symptoms. Although childhood trauma did not moderate this relationship, it independently predicted PTSD at follow-up. These findings underscore the lasting impact of early adversity on mental health, highlighting the importance of considering both HPA axis regulation and trauma history to develop targeted interventions for adults exposed to new stressors.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"88"},"PeriodicalIF":5.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlations of blood and brain NMR metabolomics with Alzheimer's disease mouse models.","authors":"Franz Knörnschild, Ella J Zhang, Rajshree Ghosh Biswas, Marta Kobus, Jiashang Chen, Jonathan X Zhou, Angela Rao, Joseph Sun, Xiaoyu Wang, Wei Li, Isabella H Muti, Piet Habbel, Johannes Nowak, Zhongcong Xie, Yiying Zhang, Leo L Cheng","doi":"10.1038/s41398-025-03293-8","DOIUrl":"https://doi.org/10.1038/s41398-025-03293-8","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex, progressive neurodegenerative disorder, impacting millions of geriatric patients globally. Unfortunately, AD can only be diagnosed post-mortem, through the analysis of autopsied brain tissue in human patients. This renders early detection and countering disease progression difficult. As AD progresses, the metabolomic profile of the brain and other organs can change. These alterations can be detected in peripheral systems (i.e., blood) such that biomarkers of the disease can be identified and monitored with minimal invasion. In this work, High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is used to correlate biochemical changes in mouse brain tissues, from the cortex and hippocampus, with blood plasma. Ten micrograms of each brain tissue and ten microliters of blood plasma were obtained from 5XFAD Tg AD mice models (n = 15, 8 female, 7 male) and female C57/BL6 wild-type mice (n = 8). Spectral regions-of-interest (ROI, n = 51) were identified, and 121 potential metabolites were assigned using the Human Metabolome Database and tabulated according to their trends (increase/decrease, false discovery rate significance). This work identified several metabolites that impact glucose oxidation (lactic acid, pyruvate, glucose-6-phosphate), allude to oxidative stress resulting in brain dysfunction (L-cysteine, galactitol, propionic acid), as well as those interacting with other neural pathways (taurine, dimethylamine). This work also suggests correlated metabolomic changes within blood plasma, proposing an avenue for biomarker detection, ideally leading to improved patient diagnosis and prognosis in the future.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"87"},"PeriodicalIF":5.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the shared genetic architecture between schizophrenia and sex hormone traits.","authors":"Xiaoyan He, Qingyan Ma, Jing Liu, Pu Lei, Huan Peng, Wen Lu, Yixin Liu, Xianyan Zhan, Bin Yan, Xiancang Ma, Jian Yang","doi":"10.1038/s41398-025-03305-7","DOIUrl":"10.1038/s41398-025-03305-7","url":null,"abstract":"<p><p>Sex hormones are involved in schizophrenia pathogenesis; however, their direction and genetic overlap remain unknown. By leveraging summary statistics from large-scale genome-wide association studies, we quantified the shared genetic architecture between schizophrenia and four sex hormone traits. Linkage disequilibrium score regression and bivariate causal mixture modeling strategies showed significant positive correlations between sex hormone-binding globulin (SHBG), total testosterone, and schizophrenia, while bioavailable testosterone and schizophrenia were negatively correlated. Estradiol showed a weak positive correlation with schizophrenia, with little polygenic overlap. The conjunctional false discovery rate method identified 303 lead single-nucleotide polymorphisms (SNPs) in jointly shared genomic loci between schizophrenia and SHBG, with 130, 52, and 9 SNPs shared between schizophrenia and total testosterone, bioavailable testosterone, and estradiol, respectively. Functional annotation suggests that mitotic sister chromatid segregation and N-glycan biosynthesis may be involved in common mechanisms underlying sex hormone regulation and schizophrenia onset. In conclusion, this study clarified the inherent relationships between schizophrenia and sex hormone traits, highlighted the roles of mitotic sister chromatid segregation and N-glycan biosynthesis in the pathogenesis of schizophrenia, and delivered potential targets for further validation.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"83"},"PeriodicalIF":5.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spotlight on mechanism of sudden unexpected death in epilepsy in Dravet syndrome.","authors":"WeiHui Shao, Lu Liu, JiaXuan Gu, Yue Yang, YaXuan Wu, ZhuoYue Zhang, Qing Xu, YuLing Wang, Yue Shen, LeYuan Gu, Yuan Cheng, HongHai Zhang","doi":"10.1038/s41398-025-03304-8","DOIUrl":"10.1038/s41398-025-03304-8","url":null,"abstract":"<p><p>Dravet syndrome (DS) is a severe and catastrophic epilepsy with childhood onset. The incidence and prevalence of sudden unexpected death in epilepsy (SUDEP) are significantly higher in DS patients than in general epileptic populations. Although extensive research conducted, the underlying mechanisms of SUDEP occurring in DS patients remain unclear. This review focuses on the link between DS and SUDEP and analyzes the potential pathogenesis. We summarize the genetic basis of DS and SUDEP and elucidate the pathophysiological mechanisms of SUDEP in DS. Furthermore, given the drug-resistant nature of this disorder, the pharmacological approach has limited efficacy and often causes side effects, therefore, the non-pharmacological approaches and precise treatment can reduce the risk of SUDEP in this condition, open a new window to cure this disease, and provide a widened landscape of treatment options for patients.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"84"},"PeriodicalIF":5.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemogenetic induction of CA1 hyperexcitability triggers indistinguishable autistic traits in asymptomatic mice differing in Ambra1 expression and sex.","authors":"Margherita De Introna, Paraskevi Krashia, Annamaria Sabetta, Livia La Barbera, Annalisa Nobili, Marcello D'Amelio, Francesco Cecconi, Martine Ammassari-Teule, Annabella Pignataro","doi":"10.1038/s41398-025-03271-0","DOIUrl":"10.1038/s41398-025-03271-0","url":null,"abstract":"<p><p>Among the genomic alterations identified as risk factors in mice models of autism spectrum disorders (ASD), heterozygous deletion of Ambra1 (Activating Molecule in Beclin1-Regulated Autophagy) triggers an ASD phenotype associated with hippocampal hyperexcitability exclusively in the female sex although Ambra1 protein is comparably expressed in the hippocampus of symptomatic females and asymptomatic males. Given the intricate relationship between Ambra1 deficiency and sex in the etiology of ASD, we took advantage of asymptomatic mice including Ambra1^+/- males and wild-type (Wt) mice of both sexes to investigate whether their non-pathogenic variations in Ambra1 levels could underlie a differential susceptibility to exhibit ASD-like traits in response to experimental elevation of hippocampal excitability. Here we report that selective activation of inhibitory DREADD in CA1 parvalbumin-positive interneurons (PV-IN) reduces GABAergic currents onto pyramidal neurons (PN), causes social and attentional deficits, and augments the proportion of immature/thin spines in CA1 PN dendrites to the same extent in Ambra1^+/- males and Wt mice of both sexes. Our findings show that the substantial hippocampal variations in pro-autophagic Ambra1 gene product shown by asymptomatic mice differing in mutation and/or sex do not underlie a differential reactivity to chemogenetic induction of idiopathic ASD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"82"},"PeriodicalIF":5.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Over-integration of visual network in major depressive disorder and its association with gene expression profiles.","authors":"Mingrui Zhu, Yifan Chen, Junjie Zheng, Pengfei Zhao, Mingrui Xia, Yanqing Tang, Fei Wang","doi":"10.1038/s41398-025-03265-y","DOIUrl":"10.1038/s41398-025-03265-y","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a common psychiatric condition associated with aberrant functional connectivity in large-scale brain networks. However, it is unclear how the network dysfunction is characterized by imbalance or derangement of network modular interaction in MDD patients and whether this disruption is associated with gene expression profiles. We included 262 MDD patients and 297 healthy controls, embarking on a comprehensive analysis of intrinsic brain activity using resting-state functional magnetic resonance imaging (R-fMRI). We assessed brain network integration by calculating the Participation Coefficient (PC) and conducted an analysis of intra- and inter-modular connections to reveal the dysconnectivity patterns underlying abnormal PC manifestations. Besides, we explored the potential relationship between the above graph theory measures and clinical symptoms severity in MDD. Finally, we sought to uncover the association between aberrant graph theory measures and postmortem gene expression data sourced from the Allen Human Brain Atlas (AHBA). Relative to the controls, alterations in systemic functional connectivity were observed in MDD patients. Specifically, increased PC within the bilateral visual network (VIS) was found, accompanied by elevated functional connectivities (FCs) between VIS and both higher-order networks and Limbic network (Limbic), contrasted by diminished FCs within the VIS and between the VIS and the sensorimotor network (SMN). The clinical correlations indicated positive associations between inter-VIS FCs and depression symptom, whereas negative correlations were noted between intra-VIS FCs with depression symptom and cognitive disfunction. The transcriptional profiles explained 21-23.5% variance of the altered brain network system dysconnectivity pattern, with the most correlated genes enriched in trans-synaptic signaling and ion transport regulation. These results highlight the modular connectome dysfunctions characteristic of MDD and its linkage with gene expression profiles and clinical symptomatology, providing insight into the neurobiological underpinnings and holding potential implications for clinical management and therapeutic interventions in MDD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"86"},"PeriodicalIF":5.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive neural processing of self-generated hand and tool actions in patients with schizophrenia spectrum disorders and healthy individuals.","authors":"Christina V Schmitter, Mareike Pazen, Lukas Uhlmann, Bianca M van Kemenade, Tilo Kircher, Benjamin Straube","doi":"10.1038/s41398-025-03306-6","DOIUrl":"10.1038/s41398-025-03306-6","url":null,"abstract":"<p><p>Schizophrenia spectrum disorders (SSD) have been linked to dysfunctions in the predictive neural suppression of sensory input elicited by one's own actions. Such motor predictions become particularly challenging during tool use and when feedback from multiple sensory modalities is present. In this study, we investigated the neural correlates and potential dysfunctions of action feedback processing in SSD during tool use actions and bimodal sensory feedback presentation. Patients with SSD (N_Total = 42; schizophrenia N_F20 = 34; schizoaffective disorder N_F25 = 6; other N = 2) and healthy controls (HC, N = 27) performed active or passive hand movements with or without a tool and received unimodal (visual; a video of their hand movement) or bimodal (visual and auditory) feedback with various delays (0, 83, 167, 250, 333, 417 ms). Subjects reported whether they detected a delay. A subgroup (N_SSD = 20; N_HC = 20) participated in an identical fMRI experiment. Both groups reported fewer delays in active than passive conditions and exhibited neural suppression in all conditions in occipital and temporoparietal regions, cerebellum, and SMA. Group differences emerged in right cuneus, calcarine, and middle occipital gyrus, with reduced active-passive differences in patients during tool use actions and in bimodal trials during actions performed without a tool. These results demonstrate for the first time that, although patients and HC show similarities in neural suppression, higher-level visual processing areas fail to adequately distinguish between self- and externally generated sensory input in patients, particularly in complex action feedback scenarios involving bimodal action feedback and feedback elicited by tool use actions.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"85"},"PeriodicalIF":5.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143650970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential locations for non-invasive brain stimulation in treating ADHD: Results from a cross-dataset validation of functional connectivity analysis.","authors":"Yue Yang, Sitong Yuan, Huize Lin, Yi Han, Binlong Zhang, Jinna Yu","doi":"10.1038/s41398-025-03303-9","DOIUrl":"10.1038/s41398-025-03303-9","url":null,"abstract":"<p><p>Noninvasive brain stimulation (NIBS) has emerged as a promising therapeutic approach for attention-deficit/hyperactivity disorder (ADHD), yet the inaccurate selection of stimulation sites may constrain its efficacy. This study aimed to identify novel NIBS targets for ADHD by integrating meta-analytic findings with cross-dataset validation of functional connectivity patterns. A meta-analysis including 124 functional magnetic resonance imaging (fMRI) studies was first conducted to delineate critical brain regions associated with ADHD, which were defined as regions of interest (ROIs). Subsequently, functional connectivity (FC) analysis was performed using resting-state fMRI data from two independent databases comprising 116 patients with ADHD. Surface brain regions exhibiting consistent FC patterns with the ADHD-related ROIs across both datasets were identified as candidate NIBS targets. These targets were then translated to scalp-level stimulation sites using the 10-20 system and continuous proportional coordinates (CPC). Key regions mapped to the scalp included the bilateral dorsolateral prefrontal cortex, right inferior frontal gyrus, bilateral inferior parietal lobule, supplementary motor area (SMA), and pre-SMA. These findings propose a set of precise stimulation location for NIBS interventions in ADHD, potentially broadening the scope of neuromodulation strategies for this disorder. The study emphasized the utility of cross-dataset functional connectivity analysis in refining NIBS target selection and highlights novel brain targets that warrant further investigation in clinical trials.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"81"},"PeriodicalIF":5.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11910651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Surviving and Thriving\": evidence for cortical GABA stabilization in cognitively-intact oldest-old adults.","authors":"Mark K Britton, Greg Jensen, Richard Ae Edden, Nicolaas Aj Puts, Sara A Nolin, Stacy Suzanne Merritt, Roxanne F Rezaei, Megan Forbes, Keyanni Joy Johnson, Pradyumna K Bharadwaj, Mary Kathryn Franchetti, David A Raichlen, Cortney J Jessup, G Alex Hishaw, Emily J Van Etten, Aaron T Gudmundson, Saipavitra Murali-Manohar, Hannah Cowart, Theodore P Trouard, David S Geldmacher, Virginia G Wadley, Noam Alperin, Bonnie E Levin, Tatjana Rundek, Kristina M Visscher, Adam J Woods, Gene E Alexander, Ronald A Cohen, Eric C Porges","doi":"10.1038/s41398-025-03302-w","DOIUrl":"10.1038/s41398-025-03302-w","url":null,"abstract":"<p><p>Age-related alterations in GABAergic function, including depletion of cortical GABA concentrations, is likely associated with declining cognitive performance in normative aging. However, the extent to which GABAergic function is perturbed in the highest-functioning stratum of the oldest-old (85+) population is unknown. For the first time, we report the stability of cortical GABA in this population. We extend our previously-reported Individual Participant Data Meta-Analysis of GABA levels across the lifespan, integrating four large cross-sectional datasets sampling cognitively-intact oldest-old adults. Within our lifespan model, the slope of age-related GABA differences in cognitively-intact oldest-old adults flattens after roughly age 80; within oldest-old adults only, inclusion of age does not improve the fit of models predicting GABA. We interpret these findings as an effect of survivorship: inclusion in the study required intact cognition, and too great a reduction of GABA levels may not be compatible with neurophysiological function needed for intact cognition. This work contributes to a growing body of evidence suggesting that successful cognitive aging may require intact GABAergic function, as well as further characterizing successful aging amongst oldest-old adults and emphasizing GABA as a potential target for interventions to prolong cognitive health in aging.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"79"},"PeriodicalIF":5.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in cerebral resting state functional connectivity associated with social anxiety disorder and early life adversities.","authors":"Melina Leypoldt, Ariane Wiegand, Matthias Munk, Sanja Drohm, Andreas J Fallgatter, Vanessa Nieratschker, Benjamin Kreifelts","doi":"10.1038/s41398-025-03301-x","DOIUrl":"10.1038/s41398-025-03301-x","url":null,"abstract":"<p><p>Social Anxiety Disorder (SAD) involves fear of negative evaluation and social avoidance, impacting quality of life. Early life adversities (ELA) are recognized as risk factors for SAD. Previous research indicated inconsistent alterations in resting state functional connectivity (RSFC) in SAD, particularly in the prefrontal cortex and precuneus. This study investigated the interaction between SAD and ELA at the RSFC level. Functional magnetic resonance imaging (fMRI) was conducted on 120 participants (aged 19-48). Four groups were formed: low/ high ELA controls (n = 49, n = 22) and low/ high ELA SAD participants (n = 30, n = 19). Seed-based correlation analyses (SCA) and multi-voxel pattern analysis (MVPA) were applied. A network in which ELA moderates the neural correlates of SAD during the resting state was identified, involving key nodes like the subgenual anterior cingulate cortex, left middle frontal gyrus, and an area in the calcarine fissure/precuneus. Five distinct interaction patterns of SAD and ELA were observed, showcasing opposite RSFC patterns in individuals with SAD based on ELA experience. Results remained significant when controlled for general anxiety and depression measures. Emotional aspects of ELA played a significant role in these interactions. These findings stress the necessity of considering primarily emotional ELA as covariate in neuroimaging studies investigating SAD and potentially also other psychiatric disorders, addressing inconsistencies in prior research. The left middle frontal gyrus emerges as a link in the SAD-ELA interaction during resting state and anxiety-relevant stimulation. Longitudinal studies, starting from childhood, are needed to understand ELA's impact on brain function and to identify potential neuromarkers for SAD predisposition post-ELA exposure.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"80"},"PeriodicalIF":5.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}