Translational Psychiatry最新文献

{"title":"The involvement of 5-HT was necessary for EA-mediated improvement of post-stroke depression.","authors":"Bing Deng, Wenhui Di, Haoxi Long, Qian He, Zhiyuan Jiang, Taiyu Nan, Jun Gu, Keni Huang, Hongtao Li, Shaoyang Cui, Nenggui Xu, Lulu Yao","doi":"10.1038/s41398-025-03621-y","DOIUrl":"10.1038/s41398-025-03621-y","url":null,"abstract":"<p><p>The prevalence of depression is as high as about 30% within five years after stroke, while there is still no breakthrough in the Western medical treatments for post-stroke depression (PSD) in clinical practice. The traditional acupuncture treatment has been practiced to be effective for the therapy of PSD, but its mechanism still needs to be elucidated. With a combination of methods, including behavioral testing, immunofluorescence, in vivo electrophysiological recording, mRNA sequencing, genetic modulation, and in vivo fiber recording techniques, this study showed that electroacupuncture (EA) at Baihui (GV20) and Shenting (GV24) acupoints improved the depressive-like behaviors and neuronal electrophysiological activities in PSD model mice, which was established by bilateral injection of collagenase IV into the medial prefrontal cortex (mPFC). Moreover, it was found that the EA-mediated improvement was comparable to that of fluoxetine. The mRNA sequence analysis indicated that the 5-hydroxytryptamine (5-HT) system was involved in the pathogenesis of PSD. Meanwhile, the number of 5-HT positive neurons in the dorsal raphe nucleus (DRN) and 5-HT in the mPFC was significantly decreased, and ablation of neurons in the DRN could prevent the efficacy of EA. The neuronal activity of excitatory and inhibitory neurons in mPFC can be modulated by chemogenetic activation or inhibition of the TPH2-positive neurons in the DRN projecting to the mPFC. Together, our results have provided the insight of the biological mechanism underlying acupuncture in the treatment of PSD and revealed the scientific connotation of acupuncture in both clinical and scientific value.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"382"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239929","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":"Prenatal depression-associated gut microbiota induces depressive-like behaviors and hippocampal neuroinflammation in germ-free mice.","authors":"Yanan Cao, Xiaoxiao Fan, Tianzi Zang, Tianlai Qiu, Qingbo Fang, Jinbing Bai, Yanqun Liu","doi":"10.1038/s41398-025-03606-x","DOIUrl":"10.1038/s41398-025-03606-x","url":null,"abstract":"<p><p>Numerous studies have described the role of the microbiome-gut-brain axis in depression. However, the molecular mechanisms underlying the involvement of gut microbiota in the development of prenatal depression are limited. In this study, fecal microbiota from women with prenatal depression was transplanted into germ-free mice to investigate the potential causal relationships between the gut microbiota and depressive phenotypes. Shotgun metagenomic sequencing and untargeted metabolomics approaches were used to investigate the characteristics of gut microbiota and microbial metabolites. The levels of neuroinflammation in the brain were detected using immunofluorescence and real-time quantitative PCR. We found significant changes in gut microbiota composition and metabolites in mice with fecal microbiota transplantation (FMT) from women with prenatal depression, including decreased Ligilactobacillus, increased Akkermansia, and abnormal glycerophospholipid metabolism. Besides, significant increase in plasma lipopolysaccharide (LPS) levels and significant proliferation of microglia in the hippocampus were observed in mice receiving FMT from women with prenatal depression, accompanied by a significant increase in the expression of nuclear factor-κB (NF-κB) p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA. The gut microbiota and its metabolites were strongly associated with depressive-like behaviors, plasma LPS and neuroinflammation. Our study collectively demonstrates that dysbiosis of the gut microbiota may play a causal relationship in the development of prenatal depression. This process potentially involves the activation of neuroinflammation through the LPS-NF-κB signaling pathway.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"383"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239727","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":"Metabolic syndrome increases the risk of suicide attempt: evidence from a population-based cohort and genomic analysis.","authors":"Zhengyang Zhao, Min Xie, Shiwan Tao, Qiuyue Lv, Jiashuo Zhang, Jia Cai, Yunjia Liu, Yunqi Huang, Siyi Liu, Yulu Wu, Qiang Wang","doi":"10.1038/s41398-025-03575-1","DOIUrl":"10.1038/s41398-025-03575-1","url":null,"abstract":"<p><p>Suicide is a critical global public health issue, where traditional risk assessment tools have limited predictive value, warranting the identification of novel risk assessment factors. Metabolic syndrome (MetS) has been linked to poor cognition and brain volumes, which may lead to abnormal behaviors. The relationship between MetS and suicide risk has been less studied. This study aims to explore the association of MetS on suicide attempt leveraging data from the UK Biobank and genomic analyses. We first explored the cross-sectional and longitudinal relationships between MetS and suicide attempt, while also exploring the mediating role of cognitive performance. Second, using summary data from the largest genome-wide association studies, the genetic associations between MetS, suicide attempt, and cognitive performance were examined. Of 380,557 participants tracked over 13 years, we identified 1847 new cases of suicide attempt. The presence of MetS was found to significantly increase the risk of suicide attempt (HR = 1.250, 95% CI = 1.134-1.379). In participants lacking traditional suicide risk factors, such as being female, younger, and having higher educational attainment, MetS still presented a greater risk in predicting future suicide attempts. Additionally, MetS and suicide attempt exhibited significant genetic correlation (rg = 0.080 ± 0.026), and Mendelian randomization analysis suggested MetS had a significant negative effect on suicide attempt (β = 0.156, 95% CI = 0.077-0.235). These findings highlight a significant association between MetS and increased suicide risk. Addressing MetS may offer an avenue for improved suicide management.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"365"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239729","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":"TGR5 dysfunction underlies chronic social defeat stress via cAMP/PKA signaling pathway in the hippocampus.","authors":"Xiangyu Chen, Qinji Zhou, Yong He, Yue Wang, Yanyi Jiang, Yi Ren, Yikun Ren, Junchao Cai, Heming Yu, Chong Chen, Ke Cheng, Peng Xie","doi":"10.1038/s41398-025-03599-7","DOIUrl":"10.1038/s41398-025-03599-7","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a debilitating mental health disorder that has a wide impact on many patients and has imposed a heavy burden on society in recent years. However, the specific pathogenesis of depression remains to be elucidated. Numerous studies have shown that metabolic disorders and molecules play important roles in MDD. Here, we demonstrate a preliminary mechanism through which TGR5 functions in the hippocampus during bile acid synthesis dysfunction in mice subjected to chronic social defeat stress (CSDS). According to the enzyme-linked immunosorbent assay (ELISA), susceptible mice subjected to CSDS presented reduced expression of key bile acid enzymes in the serum and total bile acids (TBAs) in the hippocampus. The expression of the bile acid-related receptor TGR5 in the hippocampus was lower in CSDS-exposed susceptible mice than in control mice. By analyzing the potential downstream signaling pathways of TGR5, we found that specific TGR5/cAMP/PKA regulation effectively increased the plasticity of Schaffer collateral (SC)-CA1 synapses in the hippocampus and further alleviated anxiety- and depression-like behavior in susceptible mice. These findings suggest that CSDS susceptibility is accompanied by dysfunction of TGR5 in the hippocampus and the downstream cAMP/PKA signaling pathway. Activating cAMP/PKA signaling can ameliorate behavioral deficits in susceptible mice. This study may support the development of potential effective pharmacotherapies for the treatment of MDD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"366"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239896","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 role of dorsomedial striatum and parvalbumin interneurons in schizophrenia-related cognitive deficits: insights from disrupted strategic decision-making in Akt1 heterozygous mice.","authors":"Chia-Yuan Chang, Ching Chen, Ya-Wen Liu, Shiang-Shin Gau, Yu-Ling Pan, Wen-Sung Lai","doi":"10.1038/s41398-025-03541-x","DOIUrl":"10.1038/s41398-025-03541-x","url":null,"abstract":"<p><p>Schizophrenia, a debilitating disorder with genetic and neurobiological underpinnings, often manifests cognitive deficits, including impaired decision-making. Utilizing Akt1 heterozygous mutant (HET) mice as a model, which mimic schizophrenia due to AKT1's implication as a susceptibility gene, we investigated the involvement of Akt1 and its neural mechanisms influencing strategic decision-making to identify potential therapeutic targets for schizophrenia-associated cognitive impairments. In six experiments, we first revealed that lesions targeting the dorsomedial striatum (DMS) significantly impacted performance in a mouse version of the two-choice probabilistic decision-making task, surpassing effects observed in other striatal subregions. Behavioral assessments in HET mice unveiled notable disturbances, including reduced accumulated trials to reach criteria, diminished ratio of lose-stay behavior, elevated learning rates, and decreased choice consistency in reinforcement learning models. Moreover, we found a strong correlation between DMS local field potential power and choice outcome, particularly evident in no-reward condition. The behavioral abnormalities observed in HET mice were restored when the DMS was chemogenetically inhibited, while their locomotor activity remained unaffected. Furthermore, RNA-seq analysis and immunohistochemistry uncovered a decrease in the number of striatal parvalbumin (PV) interneurons in HET mice. Targeted lesioning of PV interneurons in the DMS of wild-type mice resulted in behavioral alterations mirroring those in HET mice. In summary, our findings suggest that Akt1 deficiency-induced downregulation of PV expression alters neural oscillations in the DMS, influencing choice strategies, especially in no-reward condition during probabilistic decision-making. These results underscore the crucial involvement of AKT1 and PV interneurons in modulating strategic decision-making, with particular relevance to the understanding of schizophrenia.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"362"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239945","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":"Reconfiguration of functional brain hierarchy in schizophrenia.","authors":"Irene Acero-Pousa, Anira Escrichs, Paulina Clara Dagnino, Yonatan Sanz Perl, Morten L Kringelbach, Peter J Uhlhass, Gustavo Deco","doi":"10.1038/s41398-025-03584-0","DOIUrl":"10.1038/s41398-025-03584-0","url":null,"abstract":"<p><p>The multidimensional nature of schizophrenia requires a comprehensive exploration of the functional and structural brain networks. While prior research has provided valuable insights into these aspects, our study goes a step further to investigate the reconfiguration of the hierarchy of brain dynamics, which can help understand how brain regions interact and coordinate in schizophrenia. We applied an innovative thermodynamic framework, which allows for a quantification of the degree of functional hierarchical organisation by analysing resting state fMRI-data. Our findings reveal increased hierarchical organisation at the whole-brain level and within specific resting-state networks in individuals with schizophrenia, which correlated with negative symptoms, positive formal thought disorder and apathy. Moreover, using a machine learning approach, we showed that hierarchy measures allow a robust diagnostic separation between healthy controls and schizophrenia patients. Thus, our findings provide new insights into the nature of functional connectivity anomalies in schizophrenia, suggesting that they could be caused by the breakdown of the functional orchestration of brain dynamics.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"356"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239774","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":"Integrating genetic regulation and schizophrenia-specific splicing quantitative expression with GWAS prioritizes novel risk genes for schizophrenia.","authors":"Xiaoyan Li, Lingli Fan, Yiran Zhao, Yuanyuan Li, Junyang Wang, Shengmin Xu, Junfeng Xia","doi":"10.1038/s41398-025-03633-8","DOIUrl":"10.1038/s41398-025-03633-8","url":null,"abstract":"<p><p>Alternative splicing (AS) plays a vital role in the pathogenesis of schizophrenia (SCZ). Previous studies have linked the genetic signals from genome-wide association studies (GWAS) with expression quantitative trait loci (eQTL), but the interplay with other genetic regulatory mechanisms, particularly splicing QTL (sQTL), remains unclear. Here, we constructed a comprehensive disease-specific sQTL map to provide genetic variants that could alter gene activity through RNA splicing in SCZ. We analyzed data from 539 SCZ patients, identifying a total of 24,810 significant sQTLs (FDR < 0.05) involving in AS events of 7083 unique genes. By combining this with a large-scale SCZ GWAS, we employed Mendelian randomization (MR) and colocalization analyses to pinpoint 27 significant risk genes with genetic AS regulation that may play a causal role in SCZ. Additional differential splicing analysis of these genes in 539 cases and 754 controls revealed 12 significant genes that may increase SCZ risk due to their AS dysregulation. Notably, five genes (DPYD, LACC1, CCDC122, ANAPC7, and DGKZ) showed consistent splicing regulation effects in both MR analysis and differential splicing analysis. Pathway enrichment analysis of differentially spliced genes revealed potential biologically pathways relevant to SCZ, particularly in synaptic transmission and microtubule movement. Furthermore, single-cell RNA-seq analysis revealed that several genes were preferentially expressed in specific brain cell types, including oligodendrocytes, microglia, and excitatory neurons. Overall, our findings highlight several susceptibility genes that may contribute to SCZ risk by AS regulation. Further characterization of these genes could advance mechanistic understanding and therapeutic discovery for SCZ.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"379"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239724","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":"Early treatment-related changes in dorsolateral prefrontal cortex activity and functional connectivity as potential biomarkers for antidepressant response in major depressive disorder.","authors":"Han Zhang, Cun Li, Ke Shi, Ye Xia, Yanhui Song, Jie Feng, Ziwei Wang, Kai Wang, Yuan Yang","doi":"10.1038/s41398-025-03576-0","DOIUrl":"10.1038/s41398-025-03576-0","url":null,"abstract":"<p><p>Cognitive deficits are prevalent in major depressive disorder (MDD). Given that the dorsolateral prefrontal cortex (DLPFC) is a crucial region within the executive control network, its activity and functional connectivity (FC) may serve as potential indicators of antidepressant response. This prospective cohort study recruited 115 MDD patients and 43 healthy controls. Psychological assessments, electroencephalogram and event-related potential recordings were performed at baseline and 1 week after venlafaxine treatment, with a 12-week follow-up. Independent sample t-tests and Mann-Whitney U tests analyzed group differences, while linear mixed-effects models and logistic regression evaluated associations between DLPFC activity/FC changes and clinical outcomes. The MDD group showed significantly reduced right DLPFC current density during the N2 time window evoked by oddball stimuli (p = 0.028). Higher right DLPFC current density during the N2 time window was correlated with lower HAMD-21 scores one week after treatment (p = 0.041, n = 46). Furthermore, an early increase predicted remission at week 12 (p = 0.005). Decreased beta-band FC between the left DLPFC and both side of posterior cingulate cortex (PCC) (left: p = 0.003; right: p = 0.004) were correlated with lower HAMD-21 scores (n = 71). Moreover, an early reduction in these connectivity measures (left: odds ratio (OR) = 0.534, 95% confidence interval (CI): 0.297-0.972, p = 0.036; right: OR = 0.533, 95% CI: 0.299-0.950, p = 0.033) predicted remission at week 12. Early changes in DLPFC activity and FC may serve as biomarkers for monitoring treatment efficacy and predicting clinical outcomes, informing personalized treatment approaches.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"350"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239749","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":"Inflammatory and MRI perfusion biomarkers in predicting persistence of depression: a 6-month Longitudinal Study.","authors":"Jean-Marie Batail, Isabelle Corouge, Tristan Blanchard, Jean-Charles Roy, Gabriel Robert, Dominique Drapier","doi":"10.1038/s41398-025-03587-x","DOIUrl":"10.1038/s41398-025-03587-x","url":null,"abstract":"<p><p>Systemic inflammation has been linked with major depressive episode (MDE) severity and treatment-resistant depression (TRD), but not for all patients. Brain mechanisms underlying these processes are still under investigation. Objectives: based on an integrative approach, we aimed at identifying clinical, inflammatory and perfusion markers predictive of depression outcome at 6 months. We conducted a longitudinal study including 60 patients diagnosed with MDE, focusing on anxiety and anhedonia as main clinical candidates, inflammation (C-Reactive Protein - CRP) and cerebral blood flow (CBF) using pseudo-continuous arterial spin labeling (pcASL) MRI. A bootstrapped elastic net regression analysis was conducted including clinical, CBF and inflammation as predictors with depressive severity at 6 months as the dependent variable. Our findings exhibited positive association of depression outcome with baseline depression intensity, duration of current episode, CRP, right accumbens, as well as left and right orbito-frontal CBF. Negative predictors were age, disease duration, right and left caudate nuclei, left amygdala, left mid frontal gyrus, and right ventromedial prefrontal cortex CBF. Neither anxiety nor anhedonia were significant predictors. Combining clinical, inflammation and brain imaging outperformed other models in diagnosing depression severity change over time, highlighting the interest of integrative approaches. These results suggested that systemic inflammation and cerebral perfusion abnormalities in key regions involved in emotion, reward processing and decision making, may serve as biomarkers for identifying patients at risk for persistence of depression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"370"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239763","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":"Sex-specific disruptions in the developmental trajectory of anxiety-like behaviors due to prenatal cannabidiol exposure.","authors":"Daniela Iezzi, Alba Cáceres-Rodríguez, Pascale Chavis, Olivier J Manzoni","doi":"10.1038/s41398-025-03517-x","DOIUrl":"10.1038/s41398-025-03517-x","url":null,"abstract":"<p><p>Many pregnant women use cannabidiol (CBD) as a natural remedy to alleviate symptoms such as nausea, insomnia, anxiety, and chronic pain. As much as 20% of pregnancies in the USA and Canada may involve the use of CBD-only products. CBD crosses the placenta and may affect fetal development, potentially leading to neuropsychiatric conditions later in life. Given the limited understanding of the effects of CBD during pregnancy, we adopted a longitudinal approach to investigate the neurodevelopmental trajectory associated with prenatal CBD exposure. Pregnant mice were administered 3 mg/kg CBD from gestational days 5 to 18. At early adolescence, offspring displayed sex-specific behavioral changes. Females, but not males, exhibited a complex anxiety-like phenotype during the elevated plus maze task. This phenotype persisted into adulthood in the open field test and was accompanied by altered reward responsiveness. Throughout post-natal life, female offspring demonstrated heightened stretch-attend postures, a risk-assessment behavior reflecting approach-avoidance tendencies and anxiety-like behavior. Finally, prenatal CBD exposure increased repetitive behaviors in adult animals of both sexes, as evidenced by the marble burying task. These results provide strong evidence of sex-specific disruptions in the developmental trajectories of anxiety-like behaviors associated with prenatal CBD exposure. They challenge the perception that CBD is universally safe and highlight vulnerabilities linked to gestational CBD exposure.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"354"},"PeriodicalIF":6.2,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12500939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239915","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}