Translational Psychiatry最新文献

{"title":"Suicidal risk is associated with hyper-connections in the frontal-parietal network in patients with depression.","authors":"Yanping Ren, Meiling Li, Chunlin Yang, Wei Jiang, Han Wu, Ruiqi Pan, Zekun Yang, Xue Wang, Wei Wang, Wen Wang, Wenqing Jin, Xin Ma, Hesheng Liu, Rena Li","doi":"10.1038/s41398-025-03249-y","DOIUrl":"https://doi.org/10.1038/s41398-025-03249-y","url":null,"abstract":"<p><p>Suicide is a complex behavior strongly associated with depression. Despite extensive research, an objective biomarker for evaluating suicide risk precisely and timely is still lacking. Using the precision resting-state fMRI method, we studied 61 depressive patients with suicide ideation (SI) or suicide attempt (SA), and 35 patients without SI to explore functional biomarkers of suicide risk. Among them, 21 participants also completed electroconvulsive therapy (ECT) treatment, allowing the examination of functional changes across different risk states within the same individual. Functional networks were localized in each subject using resting-state fMRI and then an individualized connectome was constructed to represent the subject's functional brain organization. We identified a set of connections that track suicide risk (r = 0.41, p = 0.001) and found that these risk-associated connections were hyper-connected in the frontoparietal network (FPN, p = 0.008, Cohen's d = 0.58) in patients with suicide risk compared to those without. Moreover, ECT treatment significantly reduced (p = 0.001, Cohen's d = 0.56) and normalized these FPN hyper-connections. These findings suggest that connections involving FPN may constitute an important biomarker for evaluating suicide risk and may provide potential targets for interventions such as non-invasive brain stimulation.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"49"},"PeriodicalIF":5.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profiles link corticostriatal microarchitecture to genetics of neurodevelopment and neuropsychiatric risks.","authors":"Sheng Hu, Yanming Wang, Xiaoxiao Wang, Yang Ji, Chuanfu Li, Bensheng Qiu","doi":"10.1038/s41398-025-03260-3","DOIUrl":"10.1038/s41398-025-03260-3","url":null,"abstract":"<p><p>Many studies on macroscale organization have focused on only the cerebral cortex or striatum, leaving a large gap in the microstructural gradient of corticostriatal covariance. Here, we partitioned the striatum into seven distinct parcels and computed the microstructural covariance between each parcel and the cerebral cortex using T1-weighted/T2-weighted mapping. We found that corticostriatal microstructural covariance exhibited a microstructural gradient along the anterior-posterior axis of the striatum. The patterns of corticostriatal microstructural covariance are linked to geodesic distance and cell type-specific gene expression profiles, revealing a gradually attenuated relationship along the anterior-posterior axis of the striatum. Linking gene expression profile to corticostriatal microstructural patterns showed that the transcriptional variations in cell type-specific genes are different between the anterior and posterior striatum and suggested that anterior striatum are more enriched in psychiatric disorders. Moreover, at the genetic level, the corticostriatal microarchitecture showed a spatiotemporal trait during neurodevelopment. Finally, we identified the neural circuits from limbic and medial frontal cortex to striatum that contributes to the common neuropsychiatric disorders. Collectively, our findings reveal spatially covarying of transcriptional specializations with microarchitecture of corticostriatal covariance, highlighting the mechanisms underlying that neurodevelopmental corticostriatal circuits may be involved in neuropsychiatric disorders.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"48"},"PeriodicalIF":5.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methods to address functional unblinding of raters in CNS trials.","authors":"Steven D Targum, William P Horan, Vicki G Davis, Alan Breier, Stephen K Brannan","doi":"10.1038/s41398-025-03262-1","DOIUrl":"10.1038/s41398-025-03262-1","url":null,"abstract":"<p><p>Treatment-emergent adverse events (TEAEs) associated with the unique properties of a pharmaceutical product may functionally unblind clinician ratings, obscure true medication effects, and affect confidence about clinical trial results. Central nervous system studies are particularly susceptible to functional unblinding because they rely on relatively subjective symptom assessments. Two different methods were used to examine possible functional unblinding in pooled data from three recent five-week, double-blind, placebo-controlled trials of xanomeline and trospium chloride (formerly known as KarXT) in participants with schizophrenia experiencing acute psychosis. Xanomeline/trospium is an M₁/M₄ muscarinic receptor agonist that may produce cholinergic side effects. First, we compared the scores of remote (site-independent) raters, blinded to TEAEs, who listened to audio recorded, site-based Positive and Negative Syndrome Scale (PANSS) interviews. Second, we conducted a post hoc analysis of participant subgroups with or without reported cholinergic-related TEAEs to ascertain whether cholinergic TEAEs influenced trial outcome. Remote ratings closely replicated 575 available \"paired\" site-based PANSS total scores at baseline and endpoint (intraclass correlation coefficient = 0.88 and 0.93, respectively). Both site-based and remote PANSS scores yielded significant improvement favouring xanomeline/trospium over placebo (both p < 0.0001) and yielded significantly greater treatment response (≥30% improvement from baseline) than placebo (both p < 0.0001). The significant improvement of PANSS scores favouring xanomeline/trospium over placebo was comparable in magnitude for all subgroups regardless of whether participants reported cholinergic-related TEAEs, or any TEAEs at all (all p < 0.001). In sum, the two different methods used to assess functional unblinding in these studies found no impact of cholinergic TEAEs, or any TEAEs, on the trial results. These methods may have utility across all clinical trials.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"47"},"PeriodicalIF":5.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11805955/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371256","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":"Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder.","authors":"Yilu Zhao, Zhao Fu, Eric J Barnett, Ning Wang, Kangfuxi Zhang, Xuping Gao, Xiangyu Zheng, Junbin Tian, Hui Zhang, XueTong Ding, Shaoxian Li, Shuyu Li, Qingjiu Cao, Suhua Chang, Yufeng Wang, Stephen V Faraone, Li Yang","doi":"10.1038/s41398-025-03250-5","DOIUrl":"10.1038/s41398-025-03250-5","url":null,"abstract":"<p><p>Although the efficacy of pharmacy in the treatment of attention deficit/hyperactivity disorder (ADHD) has been well established, the lack of predictors of treatment response poses great challenges for personalized treatment. The current study employed a comprehensive approach, combining genome-wide association analyses (GWAS) and deep learning (DL) methods, to elucidate the genetic underpinnings of pharmacological treatment response in ADHD. Based on genotype data of medication-naïve patients with ADHD who received pharmacological treatments for 12 weeks, the current study performed GWAS using the percentage changes in ADHD-RS score as phenotype. Then, DL models were constructed to predict percentage changes in symptom scores using genetic variants selected based on four different genome-wide P thresholds (E-02, E-03, E-04, E-05) as inputs. The current GWAS results identified two significant loci (rs10880574, P = 2.39E-09; rs2000900, P = 3.31E-09) which implicated two genes, TMEM117 and MYO5B, that were primarily associated with both brain- and gut-related disorders. The convolutional neural network (CNN) model, using variants with genome-wide P values less than E-02 (5516 SNPs), demonstrated the best performance with mean squared error (MSE) equals 0.012 (Accuracy = 0.83; Sensitivity = 0.90; Specificity = 0.75) in the validation dataset, 0.081 in an independent test dataset (Acc = 0.61, Sensitivity = 0.81; Specificity = 0.26). Notably, the variant that contributed most to the CNN model was NKAIN2, an ADHD-related gene, which is also associated with metabolic processes. To conclude, the integration of GWAS and DL methods revealed new genes contribute to ADHD pharmacological treatment responses, and underscored the interplay between neural systems and metabolic processes, potentially providing critical insights into precision treatment. Furthermore, our CNN model exhibited good performance in an independent dataset, encouraged future studies and implied potential clinical applications.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"46"},"PeriodicalIF":5.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371225","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":"Individualized resting-state functional connectivity abnormalities unveil two major depressive disorder subtypes with contrasting abnormal patterns of abnormality.","authors":"Keke Fang, Lianjie Niu, Baohong Wen, Liang Liu, Ya Tian, Huiting Yang, Ying Hou, Shaoqiang Han, Xianfu Sun, Wenzhou Zhang","doi":"10.1038/s41398-025-03268-9","DOIUrl":"10.1038/s41398-025-03268-9","url":null,"abstract":"<p><p>Modern neuroimaging research has recognized that major depressive disorder (MDD) is a connectome disorder, characterized by altered functional connectivity across large-scale brain networks. However, the clinical heterogeneity, likely stemming from diverse neurobiological disturbances, complicates findings from standard group comparison methods. This variability has driven the search for MDD subtypes using objective neuroimaging markers. In this study, we sought to identify potential MDD subtypes from subject-level abnormalities in functional connectivity, leveraging a large multi-site dataset of resting-state MRI from 1276 MDD patients and 1104 matched healthy controls. Subject-level extreme functional connections, determined by comparing against normative ranges derived from healthy controls using tolerance intervals, were used to identify biological subtypes of MDD. We identified a set of extreme functional connections that were predominantly between the visual network and the frontoparietal network, the default mode network and the ventral attention network, with the key regions in the anterior cingulate cortex, bilateral orbitofrontal cortex, and supramarginal gyrus. In MDD patients, these extreme functional connections were linked to age of onset and reward-related processes. Using these features, we identified two subtypes with distinct patterns of functional connectivity abnormalities compared to healthy controls (p < 0.05, Bonferroni correction). When considering all patients together, no significant differences were found. These subtypes significantly enhanced case-control discriminability and showed strong internal discriminability between subtypes. Furthermore, the subtypes were reproducible across varying parameters, study sites, and in untreated patients. Our findings provide new insights into the taxonomy and have potential implications for both diagnosis and treatment of MDD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"45"},"PeriodicalIF":5.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366067","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":"Clinical trials since 2020 of rapid anti-suicidal ideation effects of ketamine and its enantiomers: a systematic review.","authors":"Sumra Sajid, J John Mann, Michael F Grunebaum","doi":"10.1038/s41398-025-03255-0","DOIUrl":"10.1038/s41398-025-03255-0","url":null,"abstract":"<p><strong>Background: </strong>Suicide is a global public health problem with few empirically supported treatments.</p><p><strong>Methods: </strong>We conducted a systematic review of clinical trials (CT) since 2020 of racemic ketamine or one of its enantiomers' (R/S) potential to reduce suicidal ideation or behavior (SIB). An initial PubMed search on April 15th, 2024 yielded 2483 results. 104 relevant CTs were identified. An additional search using other search engines on March 19th, 2024 yielded 52 sources. After screening, 14 RCTs met the inclusion criteria which required clinically significant SIB among participants, ketamine or one of its enantiomers as an anti-SIB treatment, and SIB as an outcome. We excluded neuroimaging studies, meta-analyses, reviews, and case reports. Open-label studies were also excluded except in the case of R-ketamine where we included 2 open trials due to limited published data for this enantiomer, yielding a total of 16 CTs. We used the Revised Cochrane risk-of-bias tool for the RCTs. CTs reviewed had suicidal ideation (SI) but none had suicidal behavior as an outcome.</p><p><strong>Results: </strong>The studies include ketamine augmentation of other treatments such as electroconvulsive therapy (ECT), various routes of administration - intravenous (IV), intramuscular (IM), and intranasal (IN) - and single versus multiple dose designs. Multiple doses of IV ketamine/S-ketamine produced reductions in SI for periods of several days to weeks, while single doses showed shorter, more variable effects. Multiple and single doses of IN ketamine/S-ketamine and single doses of IV ketamine produced less consistent anti-SI results. IN and IV ketamine/S-ketamine administration appears to be well tolerated. R-ketamine appears to produce fewer side effects, but additional clinical research is needed to clarify its antidepressant and anti-SI effects in humans.</p><p><strong>Conclusion: </strong>This review affirms the time-limited, anti-SI effects of ketamine and the need for personalized treatment. Limitations include study heterogeneity, small samples, and paucity of data for suicidal behavior or R-ketamine.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"44"},"PeriodicalIF":5.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143366065","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":"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}