Translational Psychiatry最新文献

{"title":"Randomization and placebo effects in clinical trials of major depressive disorder.","authors":"James A Rogers, Stephen Senn","doi":"10.1038/s41398-025-03263-0","DOIUrl":"10.1038/s41398-025-03263-0","url":null,"abstract":"","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"43"},"PeriodicalIF":5.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256842","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":"Autism spectrum disorder common variants associated with regional lobe volume variations at birth: cross-sectional study in 273 European term neonates in developing human connectome project.","authors":"Hai Le, Daphna Fenchel, Konstantina Dimitrakopoulou, Hamel Patel, Charles Curtis, Lucilio Cordero-Grande, A David Edwards, Joseph Hajnal, Jacques-Donald Tournier, Maria Deprez, Harriet Cullen","doi":"10.1038/s41398-025-03253-2","DOIUrl":"10.1038/s41398-025-03253-2","url":null,"abstract":"<p><p>Increasing lines of evidence suggest cerebral overgrowth in autism spectrum disorder (ASD) children in early life, but few studies have examined the effect of ASD common genetic variants on brain volumes in a general paediatric population. This study examined the association between ASD polygenic risk score (PRS) and volumes of the frontal, temporal, parietal, occipital, fronto-temporal and parieto-occipital lobes in 273 term-born infants of European ancestry in the developing Human Connectome Project. ASD PRS was positively associated with frontal (β = 0.027, p_FDR = 0.04) and fronto-temporal (β = 0.024, p_FDR = 0.01) volumes, but negatively with parietal (β = -0.037, p_FDR = 0.04) and parieto-occipital (β = -0.033, p_FDR = 0.01) volumes. This preliminary result suggests the potential involvement of ASD common genetic variants in early structural variations linked to ASD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"41"},"PeriodicalIF":5.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256768","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":"Examining the epigenetic transmission of risk for chronic pain associated with paternal post-traumatic stress disorder: a focus on veteran populations.","authors":"James Freeman, Sabrina Salberg, Melanie Noel, Richelle Mychasiuk","doi":"10.1038/s41398-025-03267-w","DOIUrl":"10.1038/s41398-025-03267-w","url":null,"abstract":"<p><p>Chronic pain is a public health problem that significantly reduces quality of life. Although the aetiology is often unknown, recent evidence suggests that susceptibility can be transmitted intergenerationally, from parent to child. Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder, often associated with chronic pain, that has high prevalence rates in military personnel and Veterans. Therefore, we aimed to characterise the epigenetic mechanisms by which paternal trauma, such as PTSD, is transmitted across generations to confer risk in the next generation, specifically focusing on Veterans where possible. Numerous overlapping neurological pathways are implicated in both PTSD and chronic pain; many of which are susceptible to epigenetic modification, such as DNA methylation, histone modifications, and RNA regulation. Hence, epigenetic changes related to pain perception, inflammation, and neurotransmission may influence an individual's predisposition to chronic pain conditions. We also examine the effects of PTSD on parenting behaviours and discuss how these variations could impact the development of chronic pain in children. We highlight the need for further research regarding the interactions between paternal trauma and epigenetic processes to ultimately generate effective prevention and therapeutic strategies for Veterans who have been affected by PTSD and chronic pain.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"42"},"PeriodicalIF":5.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256771","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":"Autism common variants associated with white matter alterations at birth: cross-sectional fixel-based analyses of 221 European term-born neonates from the developing human connectome project.","authors":"Hai Le, Alexandra F Bonthrone, Alena Uus, Daphna Fenchel, Alexandra Lautarescu, Konstantina Dimitrakopoulou, A David Edwards, Joseph V Hajnal, Serena J Counsell, Lucilio Cordero-Grande, Daan Christiaens, Dafnis Batalle, Maximilian Pietsch, Anthony N Price, Hamel Patel, Charles Curtis, Harriet Cullen, Maria Deprez, Jacques-Donald Tournier","doi":"10.1038/s41398-025-03252-3","DOIUrl":"10.1038/s41398-025-03252-3","url":null,"abstract":"<p><p>Increasing lines of evidence suggest white matter (WM) structural changes associated with autism can be detected in the first year of life. Despite the condition having high heritability, the relationship between autism common genetic variants and WM changes during this period remains unclear. By employing advanced regional and whole-brain fixel-based analysis, the current study investigated the association between autism polygenic scores (PS) and WM microscopic fibre density and macrostructural morphology in 221 term-born infants of European ancestry from the developing Human Connectome Project. The results suggest greater tract mean fibre-bundle cross-section of the left superior corona radiata is associated with higher autism PS. Subsequent exploratory enrichment analysis revealed that the autism risk single nucleotide polymorphisms most associated with the imaging phenotype may have roles in neuronal cellular components. Together, these findings suggest a possible link between autism common variants and early WM development.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"40"},"PeriodicalIF":5.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190601","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":"Association of active commuting with incidence of depression and anxiety: prospective cohort study.","authors":"Jingwen Fan, Xuesong Zhang, Xiaocan Jia, Zhixing Fan, Chaojun Yang, Yuping Wang, Chenyu Zhao, Nana Wang, Xuezhong Shi, Yongli Yang","doi":"10.1038/s41398-024-03219-w","DOIUrl":"10.1038/s41398-024-03219-w","url":null,"abstract":"<p><p>Evidence is limited on the incidence of depression and anxiety in relation to active commuting. Our study aimed to explore their association and examine the mediating role of inflammatory. This study included 240,547 workers in the UK Biobank. The exposure variable was the mode of transport used to get to and from work including active (walking, cycling, mixed mode) and non-active commuting (car or public transport). The incidence of depression and anxiety was defined using ICD-10 codes. Cox proportional hazard regression models were used to explore the hazard ratios (HRs) of active commuting with depression and anxiety, and mediation analyses were used to test the mediating role of inflammatory in this association. There were 10,862 depression and 9407 anxiety events. Active commuting was associated with lower risk of depression [cycling: HR 0.775, 95% confidence interval (0.674-0.890); mixed mode walking: 0.858 (0.800-0.919); mixed mode cycling: 0.821 (0.744-0.907)] and anxiety [cycling: 0.781 (0.675-0.904); mixed mode walking: 0.867 (0.805-0.934); mixed mode cycling 0.810 (0.728-0.902)], and there were distinct dose-response trends between commuting distance and incidence of depression or anxiety. Inflammatory explained 19.75% of the association between cycling with depression, and 18.05% with anxiety. There were interactions between commuting and occupation type. Cycle and mix mode commuting were associated with lower risk of depression and anxiety, and inflammation partially mediated these association. Implementing initiatives that facilitate active commuting may help alleviate the poor mental health.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"39"},"PeriodicalIF":5.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075547","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":"SIV infection induces alterations in gene expression and loss of interneurons in Rhesus Macaque frontal cortex during early systemic infection.","authors":"Richard C Crist, Samar N Chehimi, Saurabh S Divakaran, Michael J Montague, Sébastien Tremblay, Noah Snyder-Mackler, Martin O Bohlen, Kenneth L Chiou, Trish M Zintel, Michael L Platt, Halvor Juul, Guido Silvestri, Matthew R Hayes, Dennis L Kolson, Benjamin C Reiner","doi":"10.1038/s41398-025-03261-2","DOIUrl":"10.1038/s41398-025-03261-2","url":null,"abstract":"<p><p>Understanding the neurobiological mechanisms underlying HIV-associated neurocognitive decline in people living with HIV is frequently complicated by an inability to analyze changes across the course of the infection and frequent presence of comorbid psychiatric and substance use disorders. Preclinical non-human primate simian immunodeficiency virus (SIV) models help address these shortcomings. However, SIV studies frequently target protracted endpoints, limiting our understanding of the neuromolecular alterations during the early post-infection window. To begin to address this knowledge gap, we utilized single nuclei transcriptomics to examine frontal cortex samples of rhesus macaques 10- and 20-days post-SIV infection, compared to non-infected controls. We identify and validated a decrease in inhibitory neurons during the early post infection window, representing a potential substrate of longer-term injury and neurocognitive impairment in people living with HIV. Differential expression identified alterations in cellular subtype gene expression that persisted over the 20-day time course and short-lived differences only detected at 10-days post-SIV infection. In silico predicted regulatory mechanisms and dysregulated neural signaling pathways are presented. Analysis of cell-cell interaction networks identify altered signal pathways in the frontal cortex that may represent regional alterations in cell-cell communications. In total, these results identify cell type-specific molecular mechanisms putatively capable of underlying long-term neurocognitive alterations in persons living with HIV.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"38"},"PeriodicalIF":5.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075523","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":"Double-blind, randomized, placebo-controlled pilot clinical trial with gamma-band transcranial alternating current stimulation for the treatment of schizophrenia refractory auditory hallucinations.","authors":"Xiaojuan Wang, Xiaochen Zhang, Yuan Chang, Jingmeng Liao, Shuang Liu, Dong Ming","doi":"10.1038/s41398-025-03256-z","DOIUrl":"10.1038/s41398-025-03256-z","url":null,"abstract":"<p><p>Gamma oscillations are essential for brain communication. The 40 Hz neural oscillation deficits in schizophrenia impair left frontotemporal connectivity and information communication, causing auditory hallucinations. Transcranial alternating current stimulation is thought to enhance connectivity between different brain regions by modulating brain oscillations. In this work, we applied a frontal-temporal-parietal 40 Hz-tACS stimulation strategy for treating auditory hallucinations and further explored the effect of tACS on functional connectivity of brain networks. 32 schizophrenia patients with refractory auditory hallucinations received 20daily 20-min, 40 Hz, 1 mA sessions of active or sham tACS on weekdays for 4 consecutive weeks, followed by a 2-week follow-up period without stimulation. Auditory hallucination symptom scores and 64-channel electroencephalograms were measured at baseline, week2, week4 and follow-up. For clinical symptom score, we observed a significant interaction between group and time for auditory hallucinations symptoms (F(3,90) = 26.964, p < 0.001), and subsequent analysis showed that the 40Hz-tACS group had a higher symptom reduction rate than the sham group at week4 (p = 0.036) and follow-up (p = 0.047). Multiple comparisons of corrected EEG results showed that the 40Hz-tACS group had higher functional connectivity in the right frontal to parietal (F (1,30) = 7.24, p = 0.012) and right frontal to occipital (F (1,30) = 7.98, p = 0.008) than the sham group at week4. Further, functional brain network controllability outcomes showed that the 40Hz-tACS group had increased average controllability (F (1,30) = 6.26, p = 0.018) and decreased modality controllability (F (1,30) = 6.50, p = 0.016) in the right frontal lobe compared to the sham group. Our polit study indicates that 40Hz-tACS combined with medicine may be an effective treatment for targeting symptoms specific to auditory hallucinations and altering functional connectivity and controllability at the network level.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"36"},"PeriodicalIF":5.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068157","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":"Improving explainability of post-separation suicide attempt prediction models for transitioning service members: insights from the Army Study to Assess Risk and Resilience in Servicemembers - Longitudinal Study.","authors":"Emily R Edwards, Joseph C Geraci, Sarah M Gildea, Claire Houtsma, Jacob A Holdcraft, Chris J Kennedy, Andrew J King, Alex Luedtke, Brian P Marx, James A Naifeh, Nancy A Sampson, Murray B Stein, Robert J Ursano, Ronald C Kessler","doi":"10.1038/s41398-025-03248-z","DOIUrl":"10.1038/s41398-025-03248-z","url":null,"abstract":"<p><p>Risk of U.S. Army soldier suicide-related behaviors increases substantially after separation from service. As universal prevention programs have been unable to resolve this problem, a previously reported machine learning model was developed using pre-separation predictors to target high-risk transitioning service members (TSMs) for more intensive interventions. This model is currently being used in a demonstration project. The model is limited, though, in two ways. First, the model was developed and trained in a relatively small cross-validation sample (n = 4044) and would likely be improved if a larger sample was available. Second, the model provides no guidance on subtyping high-risk TSMs. This report presents results of an attempt to refine the model to address these limitations by re-estimating the model in a larger sample (n = 5909) and attempting to develop embedded models for differential risk of post-separation stressful life events (SLEs) known to mediate the association of model predictions with post-separation nonfatal suicide attempts (SAs; n = 4957). Analysis used data from the Army STARRS Longitudinal Surveys. The revised model improved prediction of post-separation SAs in the first year (AUC = 0.85) and second-third years (AUC = 0.77) after separation, but embedded models could not predict post-separation SLEs with enough accuracy to support intervention targeting.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"37"},"PeriodicalIF":5.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068183","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":"Nitrous oxide exerts rewarding effect via regulating D1 receptor and BDNF pathway in ventral tegmental area-nucleus accumbens dopamine circuit.","authors":"Wen-Qi Li, Sheng-Nan Liu, Si-Chang Yang, Xiang Lin, Zhang-Jin Zhang","doi":"10.1038/s41398-025-03257-y","DOIUrl":"10.1038/s41398-025-03257-y","url":null,"abstract":"<p><p>Recreational use of nitrous oxide (N₂O) has risen dramatically over the past decades. This study aimed to examine its rewarding effect and the underlying mechanisms. The exposure of mice to a subanesthetic concentration (20%) of N₂O for 30 min for 4 consecutive days paired with N₂O in the morning and paired with the air in the afternoon produced apparent rewarding behavior in the conditioned place preference (CPP) paradigm. This was abrogated by microinjection into the nucleus accumbens (NAc) of the dopamine (DA) D1 receptor antagonist SCH23390, but not the D2 antagonist haloperidol. N₂O robustly enhanced DAergic neuronal activity of the ventral tegmental area (VTA) and the concentration of DA in the NAc. The repeated N₂O exposure also upregulated the expression of brain-derived neurotrophic factor (BDNF) in the VTA and its multiple downstream mediators in the NAc. Conversely, VTA focal knockdown of BDNF and the inhibition of the downstream mediators suppressed the N₂O-induced rewarding effect and the DAergic neuronal activity of the VTA. Further, the combined intervention of BDNF knockdown and D1 antagonist significantly inhibited the N₂O-induced rewarding effect in mice, which was greater than that of BDNF knockdown alone, but was not significantly different from that of D1 antagonist alone. These results indicate that the rewarding properties of N₂O at subanesthetic concentration are associated with its upregulation of the VTA-NAc DA reward pathway probably via mediation of D1 receptor and BDNF/TrkB signaling. Among them, the modulation of BDNF may be the upstream of D1 receptor involved in N₂O rewarding effect.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"34"},"PeriodicalIF":5.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11775255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060724","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 fecal bacteriome virome interplay and microbiota-derived dysfunction in patients with schizophrenia.","authors":"Shiwan Tao, Yulu Wu, Liling Xiao, Yunqi Huang, Han Wang, Yiguo Tang, Siyi Liu, Yunjia Liu, Qianshu Ma, Yubing Yin, Minhan Dai, Min Xie, Jia Cai, Zhengyang Zhao, Qiuyue Lv, Jiashuo Zhang, Mengting Zhang, Menghan Wei, Yang Chen, Mingli Li, Qiang Wang","doi":"10.1038/s41398-025-03239-0","DOIUrl":"10.1038/s41398-025-03239-0","url":null,"abstract":"<p><p>Rising studies have consistently reported gut bacteriome alterations in schizophrenia (SCZ). However, little is known about the role of the gut virome on shaping the gut bacteriome in SCZ. Here in, we sequenced the fecal virome, bacteriome, and host peripheral metabolome in 49 SCZ patients and 49 health controls (HCs). We compared the gut bacterial community composition and specific abundant bacteria in SCZ patients and HCs. Specific gut viruses and host peripheral metabolites co-occurring with differential bacteria were identified using Multiple Co-inertia Analysis (MCIA). Additionally, we construct a latent serial mediation model (SMM) to investigate the effect of the gut virome on SCZ through the bacteriome and host metabolic profile. SCZ patients exhibited a decreased gut bacterial β-diversity compared to HCs, with seven differentially abundant bacteria, including Coprobacillaceae, Enterococcaceae etc. Gut viruses including Suoliviridae and Rountreeviridae, co-occur with these SCZ-related bacteria. We found that the viral-bacterial transkingdom correlations observed in HCs were dramatically lost in SCZ. The altered correlations profile observed in SCZ may impact microbiota-derived peripheral metabolites enriched in the bile acids pathway, eicosanoids pathway, and others, contributing to host immune dysfunction and inflammation. The SMM model suggested potential causal chains between gut viruses and SCZ, indicating that the effect of gut virome on SCZ is significantly mediated by bacteriome and metabolites. In conclusion, these findings provide a comprehensive perspective on the role of gut microbiota in the pathogenesis of SCZ. They reveal that patients with schizophrenia harbor an abnormal virome-bacteriome ecology, shedding light on the potential development of microbial therapeutics.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"35"},"PeriodicalIF":5.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11779829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068138","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}