Translational Psychiatry最新文献

{"title":"Causal relationship between Alzheimer's disease and cerebral small vessel disease: a Mendelian randomization study.","authors":"Renjie Liu, Lanlan Chen, Xuan Chen","doi":"10.1038/s41398-025-03560-8","DOIUrl":"https://doi.org/10.1038/s41398-025-03560-8","url":null,"abstract":"<p><p>Observational studies have produced inconsistent findings regarding the relationship between Alzheimer's disease (AD) and cerebral small vessel disease (CSVD) risk. Residual confounding and potential reverse causality are inevitable in such conventional observational studies. We tried to examine the causal relationship between AD and CSVD-related phenotypes using genetic methods. Genetic instruments for each AD and CSVD-related phenotypes (cerebral microbleeds, white matter hyperintensity, and lacunar stroke) were derived from large-scale genome-wide association studies. In this study, two-sample Mendelian randomization (MR) tested potential causal associations between AD and CSVD-related phenotypes, followed by a colocalization analysis to corroborate MR findings and explain possible mechanisms. Using univariable MR, we observed that genetic liability to AD was associated with an increased risk of cerebral microbleeds (CMBs) [odds ratio (OR) = 1.149; 95% confidence interval (CI) = 1.070-1.235, P < 0.001], and a modest increase in white matter hyperintensities (WMHs) volume (β = 0.031 mm³, 95% CI = 0.009-0.054 mm³, P = 0.005). In multivariable MR, the causal effect of genetic liability for AD on CMBs and WMHs remained after adjusting for risk factors, with the estimate across the IVW method. Colocalization results provided evidence for a shared causal variant between AD with CMBs (PPH4 = 0.996) and WMHs (PPH4 = 0.657), suggesting that the MR estimates were not confounded by linkage disequilibrium. Our MR analyses provided robust evidence for the causal effects of genetic liability for AD on an increased risk of CMBs and WMHs. More work is warranted to confirm the mechanisms of association between AD and CSVD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"317"},"PeriodicalIF":6.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970633","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":"Deep adversarial learning identifies ADHD-specific associations between apoptotic genes and white matter microstructure in frontal-striatum-cerebellum circuit.","authors":"Yilu Zhao, Xiangyu Zheng, Xuping Gao, Ning Wang, Zhao Fu, Junbin Tian, Kangfuxi Zhang, Peng Wang, ShaoXian Li, Jichang Zhang, XueTong Ding, Hui Zhang, Li Sun, Binrang Yang, Shuyu Li, Suhua Chang, Qingjiu Cao, Yufeng Wang, Li Yang","doi":"10.1038/s41398-025-03493-2","DOIUrl":"https://doi.org/10.1038/s41398-025-03493-2","url":null,"abstract":"<p><p>Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by genetic predisposition and alterations in brain structural connectivity. While existing studies have established associations between genetic variants and neuroanatomical features, the specific relationships in ADHD remained poorly understood. To address this gap, we developed adversarial deep canonical correlation analysis models (A-DCCA) to disentangle ADHD-specific and non-specific \"gene-white matter\" association patterns. Utilizing diffusion tensor imaging and genotype data from six-hundred ADHD and typically developed children in a Chiese cohort, the current study revealed ADHD-specific correlations between the right cerebral peduncle, right posterior limb of the internal capsule, and genes regulating neural apoptotic processes (CAMK1D, METTL15, and MAP2K4). In contrast, associations involving the left cerebral peduncle, left posterior limb of the internal capsule, right superior longitudinal fasciculus, and right posterior thalamic radiation with genes related to early neural development (FYN, PHF2, ZSCAN31, and CD82) presented associations shared by ADHD and non-ADHD groups. Incorporating interpretable deep learning models, the current study unveiled white matter regions vulnerable to genetic influences in ADHD-specific and non-specific ways, shedding light on the understanding of biological substrates of ADHD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"320"},"PeriodicalIF":6.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970555","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":"Differential trajectories of corticostriatal structural connectivity in individuals at clinical high risk for psychosis according to functional outcome.","authors":"Eugenie Choe, Hyungyou Park, Jiseon Jang, Minah Kim, Jun Soo Kwon","doi":"10.1038/s41398-025-03567-1","DOIUrl":"https://doi.org/10.1038/s41398-025-03567-1","url":null,"abstract":"<p><p>Dysconnectivity in the corticostriatal pathway, which is central to psychosis pathophysiology, is also known to be present in individuals at clinical high risk for psychosis (CHR-P). Considering that the corticostriatal pathway actively matures until adulthood and that neuroanatomical maturation is suggested to be related to functional outcomes in individuals at CHR-P, longitudinal studies on the corticostriatal structural pathway in individuals at CHR-P are warranted. To characterize the longitudinal trajectory of corticostriatal structural connectivity, diffusion-weighted images were collected from 23 individuals at CHR-P and 20 healthy controls (HCs) at baseline and at a 2-year follow-up visit. Probabilistic tractography was performed to segment the pathways between seven cortical regions and the striatum. The relative connectivity between each cortical region and associated striatal subregion was calculated. The CHR-P group was divided into subgroups according to the functional outcome of the modified Global Assessment of Functioning score at follow-up. A significant group‒time interaction between the left orbitofrontal cortex and its associated striatal subregion was found, with a negative slope in the CHR-P group and positive slope in the HC group. In the left orbitofrontal corticostriatal relative connectivity, the group‒time interaction between HCs and individuals at CHR-P with poor functional outcomes at follow-up was statistically significant, whereas that between HCs and individuals at CHR-P with good functional outcomes at follow-up was not. These findings indicate abnormal white matter maturation of the orbitofrontal corticostriatal pathway in individuals at CHR-P. Abnormal neuroanatomical maturation of the orbitofrontal corticostriatal pathway may reflect prognosis for functional outcomes in these individuals.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"319"},"PeriodicalIF":6.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970581","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":"Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.","authors":"Vanessa Budny, Iván Ruminot, Maha Wybitul, Valerie Treyer, L Felipe Barros, Christian Tackenberg","doi":"10.1038/s41398-025-03550-w","DOIUrl":"https://doi.org/10.1038/s41398-025-03550-w","url":null,"abstract":"<p><p>The human brain has high energy demands and tightly regulated mechanisms ensure its activity-dependent energy supply. Glucose hypometabolism is associated with brain aging and has also been linked to neurodegenerative diseases such as Alzheimer's disease (AD). The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for AD while APOE2 reduces the risk and APOE3 has been referred to as risk neutral allele. APOE is a major lipid carrier in the brain and is not only involved in the build-up of the two AD hallmark pathologies, β-amyloid (Aβ) plaques and neurofibrillary tangles, but also in several other (patho-)physiological processes including immune response, neuronal growth, synaptic plasticity and energy metabolism. Although there has been recent progress in understanding APOE biology, the exact mechanisms of how APOE (especially APOE4) affects brain energy metabolism are still largely unclear. This review highlights the recent evidence of how APOE isoforms differentially affect the bioenergetic homeostasis of the brain, thereby affecting AD etiology and pathophysiology, and identifies critical questions and emerging topics that require further investigation.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"316"},"PeriodicalIF":6.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970258","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":"iPSC-derived cerebral organoids reveal mitochondrial, inflammatory and neuronal vulnerabilities in bipolar disorder.","authors":"Dana El Soufi El Sabbagh, Alencar Kolinski Machado, Lauren Pappis, Erika Leigh Beroncal, Delphine Ji, George Nader, Prathyusha Ravi Chander, Jaehyoung Choi, Angela Duong, Hyunjin Jeong, Bruna Panizzutti, Chiara Cristina Bortolasci, Andrea Szatmari, Peter Carlen, Margaret Hahn, Liliana Attisano, Michael Berk, Ken Walder, Ana Cristina Andreazza","doi":"10.1038/s41398-025-03529-7","DOIUrl":"https://doi.org/10.1038/s41398-025-03529-7","url":null,"abstract":"<p><p>Bipolar disorder (BD) is increasingly recognized as a disease with both mitochondrial dysfunction and heightened inflammatory reactivity, yet contribution to neuronal activity remains unclear. To address these gaps, this study utilizes iPSC-derived cerebral organoids (COs) from BD patients and healthy controls to model disease-specific metabolic and inflammatory dysfunction in a more physiologically relevant system. BD COs exhibited mitochondrial impairment, dysregulated metabolic function, and increased nod-leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome activation sensitivity. Treatment with MCC950, a selective NLRP3 inhibitor, effectively rescued mitochondrial function and reduced inflammatory activation in both BD and control COs. The effect of a Bioactive Flavonoid Extract (BFE), a potential therapeutic, was also explored and yielded a partial rescue of inflammasome activation. These findings highlight a mitochondria-inflammasome axis in BD pathophysiology and establish a novel platform for studying BD-associated cellular mechanisms, ultimately bridging the gap between molecular dysfunction and therapeutic development.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"315"},"PeriodicalIF":6.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970444","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":"Modulation of neuroimmune cytokine networks by antidepressants: implications in mood regulation.","authors":"Roseane Galdioli Nava, Anny Silva Adri, Igor Salerno Filgueiras, Adriel Leal Nóbile, Pedro Marçal Barcelos, Yohan Lucas Gonçalves Corrêa, Sergio Felipe de Oliveira, Gustavo Cabral-Miranda, Haroldo Dutra Dias, Lena F Schimke, René de Araújo Gleizer, Rodrigo Juliani Siqueira Dalmolin, Helder I Nakaya, Rafael Machado Rezende, Otavio Cabral-Marques","doi":"10.1038/s41398-025-03532-y","DOIUrl":"https://doi.org/10.1038/s41398-025-03532-y","url":null,"abstract":"<p><p>Major Depressive Disorder (MDD) is increasingly recognized as a neuroinflammatory condition characterized by dysregulated cytokine networks. This comprehensive review examines the immunomodulatory effects of antidepressant medications, revealing their significant impact on Th1/Th2 cytokine balance beyond their classical neurotransmitter actions. Clinical data show that diverse antidepressant classes consistently demonstrate immunomodulatory properties that extend beyond their classical neurotransmitter effects. These medications reduce pro-inflammatory markers (IFN-γ, TNF-α, IL-6) while enhancing anti-inflammatory cytokines (IL-10, TGF-β), effects particularly relevant for treatment-resistant cases with elevated baseline inflammation. The therapeutic potential of these immunoregulatory effects is supported by emerging interventions, including low-dose IL-2 immunotherapy, vagus nerve stimulation, and microbiota-targeted therapies, which show promise for specific depression subtypes. Importantly, these approaches appear most effective when guided by inflammatory biomarkers, suggesting a path toward personalized treatment strategies. By integrating findings from clinical studies and translational research, this work establishes immune modulation as a fundamental component of antidepressant action. The review provides a framework for developing next-generation treatments that target neuroimmune pathways in MDD, with particular emphasis on practical applications for treatment-resistant cases. These insights bridge the gap between neuropharmacology and clinical psychiatry, offering new therapeutic possibilities for patients with inflammation-associated depression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"314"},"PeriodicalIF":6.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970374","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":"Transcutaneous auricular vagus nerve stimulation alleviates anxiety-like behaviors in mice with post-traumatic stress disorder by regulating glutamatergic neurons in the anterior cingulate cortex.","authors":"Zhijun Diao, Yan Zuo, Jinming Zhang, Ke Chen, Yongbin Liu, Yuwei Wu, Feng Miao, Haifa Qiao","doi":"10.1038/s41398-025-03535-9","DOIUrl":"https://doi.org/10.1038/s41398-025-03535-9","url":null,"abstract":"<p><p>Vagus nerve stimulation has been certified to be an effective therapeutic modality for emotional disorders, especially anxiety triggered by post-traumatic stress disorder (PTSD). Nevertheless, the neural mechanisms underlying the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) remain poorly understood. In this study, we aimed to elucidate whether and how taVNS influences anxiety-like behaviors elicited by PTSD, focusing on synaptic plasticity in taVNS-activated neurons (TANs) of the anterior cingulate cortex (ACC). Our findings substantiate that taVNS significantly mitigates anxiety-like behaviors in PTSD-like male mice via activating specific glutamatergic neurons in the ACC. Notably, these glutamatergic TANs^ACC exhibited marked enhancements in presynaptic excitatory transmission relative to those non-activated glutamatergic neurons in the ACC. This enhancement of presynaptic release further prevented the induction of presynaptic long-term potentiation (pre-LTP), manifesting as presynaptic depotentiation. Furthermore, inhibiting these glutamatergic TANs^ACC weakened the positive effects of taVNS on anxiety-like behaviors in PTSD-like male mice. Conversely, activating these glutamatergic TANs^ACC did not further amplify the effects of taVNS on anxiety-like behaviors. Collectively, our results reveal that the upregulation of presynaptic transmission in glutamatergic TANs^ACC is responsible for the positive effects of taVNS on anxiety-like behaviors in PTSD-like male mice, providing new insights into functional and activity patterns of the specific brain regions involved in the effects of taVNS.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"313"},"PeriodicalIF":6.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970511","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":"Identifying individuals at clinical high risk for psychosis using a battery of tasks sensitive to symptom mechanisms.","authors":"Trevor F Williams, James M Gold, James A Waltz, Jason Schiffman, Lauren M Ellman, Gregory P Strauss, Elaine F Walker, Scott W Woods, Albert R Powers, Joshua Kenney, Minerva K Pappu, Philip R Corlett, Tanya Tran, Steven M Silverstein, Richard E Zinbarg, Vijay A Mittal","doi":"10.1038/s41398-025-03539-5","DOIUrl":"https://doi.org/10.1038/s41398-025-03539-5","url":null,"abstract":"<p><p>The clinical high risk for psychosis (CHR-P) population is important for understanding disease progression and treatment; however, standard approaches to identifying CHR-P individuals are expensive and labor-intensive. Focusing on neurocognitive mechanisms that underlie individual psychosis symptoms (positive, negative, and disorganization) may improve screening and identification. The present study examines whether a behavioral task battery that assays symptom mechanisms can identify CHR-P individuals and predict risk severity. Participants (N = 621) were recruited from clinics and the community as part of the Computerized Assessment of Psychosis Risk (CAPR) consortium study. Structured clinical interviews, a dimensional risk calculator, and behavioral tasks were administered. Clinical interviews identified the following groups: (a) CHR-P (n = 273), (b) non-CHR-P individuals with limited psychosis like experiences (PLEs; n = 120), (c) participants with mental disorders and no PLEs (CLN; n = 82), and (d) healthy controls (HC; n = 146). Multinomial logistic regression indicated that the task battery differentiated groups (p < 0.001), with utility for identifying CHR-P individuals (Sensitivity = 0.87, PPV = 0.51, NPV = 0.77), though with high false positives that varied based on comparison group (Specificity = 0.21-0.43). Tasks also predicted psychosis risk calculator scores (Adjusted R² = 0.12), with the two unique predictors being positive symptom task variables associated with updating beliefs regarding environmental volatility. Overall, symptom mechanism tasks differentiated CHR-P individuals from control groups, suggesting their potential as novel screening tools. Using tasks to more efficiently identify CHR-P individuals (e.g., enrich samples), may lower barriers and identify individuals that may otherwise be missed.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"311"},"PeriodicalIF":6.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970416","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":"Endocannabinoid and N-acylethanolamine concentrations in hair of female patients with posttraumatic stress disorder - associations with clinical symptoms and outcomes following multimodal trauma-focused inpatient treatment.","authors":"L Bergunde, M L Woud, L Shkreli, L Schindler-Gmelch, S Garthus-Niegel, S E Blackwell, C Kirschbaum, H Kessler, S Steudte-Schmiedgen","doi":"10.1038/s41398-025-03476-3","DOIUrl":"https://doi.org/10.1038/s41398-025-03476-3","url":null,"abstract":"<p><p>While psychotherapeutic treatments for posttraumatic stress disorder (PTSD) show in general good responses in affected individuals, 30-40% of patients show limited improvement. On a biological level, the endocannabinoid system of the body may play a role in the aftermath of trauma, in PTSD, and in extinction processes. This study is a secondary analysis of a randomized-controlled trial including patients with PTSD over the course of trauma-focused inpatient treatment. It aimed to investigate whether endocannabinoid system alterations are associated with symptom severity and treatment response. Fifty-four female inpatients with PTSD provided hair samples and completed psychometric questionnaires at pre-treatment, post-treatment, and 3-month follow-up. Endocannabinoid (EC: AEA, 1-AG/2-AG) and N-acylethanolamine (NAE: SEA, PEA, OEA) concentrations were measured in scalp-near 3-cm hair segments, reflecting cumulative concentrations in the 3 months prior to sampling. At pre-treatment, higher depressive and anxiety symptoms were significantly associated with lower hair AEA levels, whereas higher PTSD symptoms (when controlling for depressive symptoms) and more traumatic experiences were significantly associated with higher hair AEA and NAE levels respectively. PTSD symptoms improved across treatment, remaining stable at 3-month follow-up, but were predicted neither by pre-treatment hair ECs/NAEs nor their changes across treatment and follow-up, which was confirmed in subgroup analyses. Our findings suggest that hair ECs/NAEs may be distinctly linked with trauma-related and affective and anxiety symptoms, however, do not predict treatment response in PTSD. This challenges expectations and highlights the complexity of endocannabinoid system alterations in stress-related psychopathology. Given the study's limitations, including a female-only sample and lack of a control group, larger studies with control groups and multiple biomarkers are needed to identify intervention-related biomarkers in PTSD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"312"},"PeriodicalIF":6.2,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970251","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":"Cannabinoid 1 receptor availability in posttraumatic stress disorder: A positron emission tomography study.","authors":"Nachshon Korem, Anahita Bassir Nia, Ansel T Hillmer, Deepak D'Souza, Nabeel Nabulsi, Jim Ropchan, Yiyun Huang, Kelly Cosgrove, Ifat Levy, Robert H Pietrzak, Ilan Harpaz-Rotem","doi":"10.1038/s41398-025-03519-9","DOIUrl":"https://doi.org/10.1038/s41398-025-03519-9","url":null,"abstract":"<p><p>The endocannabinoid system (ECS) plays a critical role in fear learning and maintenance and may, therefore, be implicated in the pathophysiology of posttraumatic stress disorder (PTSD). The exact role of cannabinoid receptor 1 (CB1R), a key component of the ECS, remains unclear. Although preclinical studies largely suggest CB1R downregulation in PTSD, the only prior study of CB1R availability in individuals with PTSD reported higher levels than in controls. In this study, we investigated the relationship between CB1R availability and PTSD diagnosis and symptoms. Using positron emission tomography (PET) with the CB1R-specific radiotracer [¹¹C]OMAR, scans from 62 individuals, including 46 trauma-exposed participants (19 with current PTSD) and 16 healthy controls, were analyzed. Our findings revealed no differences in CB1R availability between groups in either the whole brain or regions of interest. However, emotional numbing symptoms of PTSD were significantly linked to CB1R availability. These results suggest that the ECS role in the maintenance of PTSD is more nuanced than previously suggested. The ECS was linked to specific PTSD symptom expression, highlighting the potential for treatments targeting the ECS in mitigating these specific symptoms of this multi-faceted disorder.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"310"},"PeriodicalIF":6.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970635","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}