Translational Psychiatry最新文献

{"title":"Intravenous psilocybin induces dose-dependent changes in functional network organization in rat cortex.","authors":"Brian H Silverstein, Nicholas Kolbman, Amanda Nelson, Tiecheng Liu, Peter Guzzo, Jim Gilligan, UnCheol Lee, George A Mashour, Giancarlo Vanini, Dinesh Pal","doi":"10.1038/s41398-025-03308-4","DOIUrl":"10.1038/s41398-025-03308-4","url":null,"abstract":"<p><p>Psilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in cortical networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on cortex-wide network dynamics. Previous electroencephalographic studies of psychedelics in rodents have primarily used sparse electrode arrays with limited spatial resolution, precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in this study, we used electroencephalographic recordings from 27 sites/electrodes across rat cortex (n = 6 male, 6 female) to characterize the effect of psilocybin (0.1, 1, and 10 mg/kg delivered over an hour) on brain network organization as inferred through changes in node degree (an index of network density) and connection strength (via weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p < 0.05], 2) increased frontal high gamma connectivity [p < 0.05] and posterior theta connectivity [p ≤ 0.049], and 3) increased frontal high gamma [p < 0.05] and posterior theta [p ≤ 0.046] network density. The behavioral activity and the medium gamma frontoparietal connectivity showed an inverted-U relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"93"},"PeriodicalIF":5.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11933319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701567","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":"Multi-omics insight into the molecular networks of mental disorder related genetic pathways in the pathogenesis of inflammatory bowel disease.","authors":"Meng Zhang, Jianhui Zhao, Haosen Ji, Yuqian Tan, Siyun Zhou, Jing Sun, Yuan Ding, Xue Li","doi":"10.1038/s41398-025-03299-2","DOIUrl":"10.1038/s41398-025-03299-2","url":null,"abstract":"<p><p>Mental disorders are associated with inflammatory bowel disease (IBD), but the genetic pathophysiology is not fully understood. We obtained data on mental disorder-related gene methylation, expression, protein levels, and summary statistics of IBD, and performed Summary data-based Mendelian randomization and colocalization analyses to explore the causal associations and shared causal genetic variants between multiple molecular traits and IBD. Integrating multi-omics data, we found QDPR, DBI and MAX are associated with ulcerative colitis (UC) risk, while HP is linked to IBD risk. Inverse associations between gene methylation (cg0880851 and cg26689483) and expression are observed in QDPR, consistent with their detrimental role in UC. Methylation of DBI (cg11066750) protects against UC by enhancing expression. Higher levels of DBI (OR = 0.79, 95%CI = 0.69-0.90) and MAX (OR = 0.74, 95%CI = 0.62-0.90) encoded proteins are inversely associated with UC risk, while higher QDPR (OR = 1.17, 95%CI = 1.07-1.28) and HP (OR = 1.09, 95%CI = 1.04-1.14) levels increase UC and IBD risk. Our findings advance the understanding of IBD's pathogenic mechanisms and gut-brain interaction.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"91"},"PeriodicalIF":5.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677256","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":"The characteristics of anhedonia in depression: a review from a clinically oriented perspective.","authors":"Congchong Wu, Qingli Mu, Weijia Gao, Shaojia Lu","doi":"10.1038/s41398-025-03310-w","DOIUrl":"10.1038/s41398-025-03310-w","url":null,"abstract":"<p><p>Anhedonia, as one of the core symptoms of major depressive disorder (MDD), has been regarded as a potential endophenotype of the disease. Multiple studies have evaluated the potential mechanisms of anhedonia in MDD, and found that MDD patients with anhedonia showed different functions in clinical features. In this review, we focus on the clinical research to explore the differences between MDD patients with and without anhedonia in the clinical manifestations and biological alterations, and elaborate the treatments and prognosis of anhedonia. It is demonstrated that anhedonia is associated with adverse outcomes including more severe depressive episode and suicidality, and poor prognosis in patients with MDD. At the biological level, MDD patients with anhedonia seem to present higher levels of inflammatory factors, abnormal metabolic function and hypermetabolism of BDNF. In brain imaging studies, there are some structural and/ or functional changes in multiple brain regions of subcortical and cortical areas, as well as the limbic system in MDD patients with anhedonia. Meanwhile, preliminary research findings have also indicated that there are associations between intestinal flora imbalance and anhedonia. Moreover, evidence indicated the benefit of some selective serotonin reuptake inhibitors seemed limited on anhedonia, and other treatments including psychotherapy, physical therapy and probiotic interventions has remained to be explored but has interesting potential. Therefore, increased awareness of the anhedonic symptoms and the unique clinical features would benefit improved early diagnosis and therapeutic effects in MDD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"90"},"PeriodicalIF":5.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677267","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":"Suprachiasmatic nucleus dysfunction induces anxiety- and depression-like behaviors via activating the BDNF-TrkB pathway of the striatum.","authors":"Xiaotao Liang, Yuewen Ding, Xiaoyu Zhu, Jing Qiu, Xiaoqin Shen, Yifan Xiong, Jieli Zhou, Xiaoshan Liang, Wei Xie","doi":"10.1038/s41398-025-03313-7","DOIUrl":"10.1038/s41398-025-03313-7","url":null,"abstract":"<p><p>The circadian rhythm system consists of a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks dispersed throughout other brain areas (including striatum, Str) as well as various tissues and organs. Circadian rhythm disturbance is a major risk factor and common comorbidity for mood disorders, especially anxiety and depression. Bmal1 is one of the fundamental clock protein genes that is required to maintain circadian rhythm. Recent research has revealed a link between suprachiasmatic nucleus dysfunction and anxiety and depression, but the underlying mechanisms remain to be fully elucidated. This study aimed to investigate how circadian rhythm disturbance may lead to anxiety- and depression-like behaviors. Through behavioral tests, virus tracing, molecular biology and other techniques, we found neural connection from the suprachiasmatic nucleus to the striatum. SCN lesions and Bmal1^flox/flox + pAAV-hSyn-Cre-GFP (conditional knockout, cKO) mice exhibited disruptions in core body temperature rhythm, as well as anxiety- and depression-like behaviors. Importantly, these mice displayed altered expression patterns of clock protein genes and an upregulation of the Brain-Derived Neurotrophic Factor (BDNF) - Tyrosine Kinase receptor B (TrkB) signaling pathway within the striatum. Microinjection of the TrkB inhibitor ANA-12 can effectively reverse anxiety- and depression-like behaviors. These findings indicate that suprachiasmatic nucleus dysfunction may contribute to the pathogenesis of anxiety and depression through upregulation of the BDNF-TrkB pathway in the striatum, potentially mediated by neural projections from the SCN. Bmal1 gene within SCN may represent a novel therapeutic target for mood disorders.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"92"},"PeriodicalIF":5.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677262","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":"Dopaminergic changes in the subgenual cingulate cortex in dementia with lewy bodies associates with presence of depression.","authors":"Lina Gliaudelytė, Steven P Rushton, Rolando Berlinguer-Palmini, Alan J Thomas, Christopher M Morris","doi":"10.1038/s41398-025-03298-3","DOIUrl":"10.1038/s41398-025-03298-3","url":null,"abstract":"<p><p>In addition to the core clinical features of fluctuating cognition, visual hallucinations, and parkinsonism, individuals with dementia with Lewy bodies (DLB) frequently experience chronic and debilitating major depression. Treatment of depression in DLB is hampered by a lack of available effective therapies and standard serotonergic medication for major depressive disorder (MDD) is typically ineffective. Dysfunction of dopaminergic neurotransmission contributing to anhedonia and loss of motivation has been described in MDD. The subgenual anterior cingulate cortex (sgACC) is important in mood regulation and in the symptomatic expression of depression, displaying structural, functional and metabolic abnormalities in MDD. To assess dopaminergic and serotonergic synaptic changes in DLB, post mortem sgACC tissue from DLB donors with and without depression was investigated using high-resolution stimulated emission depletion (STED) microscopy, as well as Western and dot blotting techniques. STED imaging demonstrated the presence of α-synuclein within individual dopaminergic terminals in the sgACC, α-synuclein presence showing a significant positive correlation with increased synaptosomal associated protein 25 kDa (SNAP25) volumes in depressed DLB cases. A reduction in dopaminergic innervation in the sgACC was observed in DLB cases with depression compared to controls (p < 0.001), but not in non-depressed DLB donors, along with reduced levels of multiple dopaminergic markers and receptors. Limited alterations were observed in serotonergic markers. Our work demonstrates a role for dopaminergic neurotransmission in the aetiology of depression in DLB. Careful and selective targeting of dopaminergic systems in the sgACC may be a therapeutic option for treatment of depression in DLB.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"89"},"PeriodicalIF":5.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671067","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":"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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923047/pdf/","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":"OA","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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920067/pdf/","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":"OA","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}