Translational Psychiatry最新文献

{"title":"Alterations in cerebral resting state functional connectivity associated with social anxiety disorder and early life adversities.","authors":"Melina Leypoldt, Ariane Wiegand, Matthias Munk, Sanja Drohm, Andreas J Fallgatter, Vanessa Nieratschker, Benjamin Kreifelts","doi":"10.1038/s41398-025-03301-x","DOIUrl":"10.1038/s41398-025-03301-x","url":null,"abstract":"<p><p>Social Anxiety Disorder (SAD) involves fear of negative evaluation and social avoidance, impacting quality of life. Early life adversities (ELA) are recognized as risk factors for SAD. Previous research indicated inconsistent alterations in resting state functional connectivity (RSFC) in SAD, particularly in the prefrontal cortex and precuneus. This study investigated the interaction between SAD and ELA at the RSFC level. Functional magnetic resonance imaging (fMRI) was conducted on 120 participants (aged 19-48). Four groups were formed: low/ high ELA controls (n = 49, n = 22) and low/ high ELA SAD participants (n = 30, n = 19). Seed-based correlation analyses (SCA) and multi-voxel pattern analysis (MVPA) were applied. A network in which ELA moderates the neural correlates of SAD during the resting state was identified, involving key nodes like the subgenual anterior cingulate cortex, left middle frontal gyrus, and an area in the calcarine fissure/precuneus. Five distinct interaction patterns of SAD and ELA were observed, showcasing opposite RSFC patterns in individuals with SAD based on ELA experience. Results remained significant when controlled for general anxiety and depression measures. Emotional aspects of ELA played a significant role in these interactions. These findings stress the necessity of considering primarily emotional ELA as covariate in neuroimaging studies investigating SAD and potentially also other psychiatric disorders, addressing inconsistencies in prior research. The left middle frontal gyrus emerges as a link in the SAD-ELA interaction during resting state and anxiety-relevant stimulation. Longitudinal studies, starting from childhood, are needed to understand ELA's impact on brain function and to identify potential neuromarkers for SAD predisposition post-ELA exposure.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"80"},"PeriodicalIF":5.8,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625963","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 therapy guided by single-cell sequencing in anti-GABA_AR encephalitis.","authors":"Yaqing Shu, Yu Huang, Qihui Li, Huilu Li, Zhibin Li, Jinlong Ye, Jianning Chen, Jianfang Li, Ling Fang, Jing Li, Yi Lu, Libao Liu, Yongjian Luo, Zhanhang Wang, Zhengqi Lu, Zhongxi Huang, Fuhua Peng, Wei Qiu","doi":"10.1038/s41398-025-03300-y","DOIUrl":"10.1038/s41398-025-03300-y","url":null,"abstract":"<p><p>We presented a patient with refractory anti-GABA_A-R encephalitis, and constructed libraries for single-cell sequencing from the patient's peripheral blood mononuclear cells (PBMCs), cerebrospinal fluid cells, as well as four healthy volunteer's PBMCs. A distinct group of monoclonal CD8⁺ T cells and an abnormal JAK-STAT signaling pathway was implicated in the disease. The cross-reactive protein LIM-domain-only protein 5 (LMO5) identified in the patient's thymoma, prompted the activation of the specific CD8⁺ T cells. Furthermore, in vitro analysis revealed the involvement of the JAK-STAT pathway in LMO5-induced CD8⁺T cell activation, a process effectively suppressed by tofacitinib, which improved the patient's clinical outcome.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"78"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586920","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":"Fine-tuning of dopamine receptor signaling with aripiprazole counteracts ketamine's dissociative action, but not its antidepressant effect.","authors":"Daiki Nakatsuka, Taro Suwa, Yuichi Deguchi, Yoshihisa Fujita, Ryoichi Tashima, Soichiro Ohnami, Hirotsugu Kawashima, Naoya Oishi, Koichi Ogawa, Hidekuni Yamakawa, Toshiya Murai","doi":"10.1038/s41398-025-03284-9","DOIUrl":"10.1038/s41398-025-03284-9","url":null,"abstract":"<p><p>Ketamine, a rapid-acting antidepressant, has undesirable psychotomimetic effects, including a dissociative effect. There is currently no effective strategy to suppress these side effects while preserving its antidepressant effect. Here, we investigated the effects of a D2/D3 receptor antagonist and partial agonists on the psychotomimetic and antidepressant effects of ketamine in mice and humans. Aripiprazole, a partial agonist, attenuated the psychotomimetic effect, but maintaining and even enhancing the antidepressant-like effect of ketamine in the forced swim test, whereas raclopride, an antagonist, suppressed both effects in mice. Brain-wide Fos mapping and its network analysis suggested the ventral tegmental area (VTA) as a critical region for distinguishing the effects of aripiprazole and raclopride. In the chronic stress model, local infusion of raclopride into the VTA inhibited ketamine's antidepressant-like effect, accompanied by activation of dopaminergic neurons, suggesting the inhibitory effect of VTA activation on the antidepressant-like effect of ketamine. Consistently, systemic injections of raclopride and brexpiprazole, a partial agonist similar to aripiprazole but closer to an antagonist (lower E_max), activated dopaminergic neurons in the VTA and suppressed ketamine's antidepressant-like effect in the model when co-administered with ketamine, whereas aripiprazole didn't. In line with these results, in a single-arm, double-blinded clinical study of sequential treatments in depressed patients (N = 9), co-administration of 12 mg of aripiprazole suppressed the dissociative symptoms induced by ketamine while maintaining its antidepressant effects. Together, these findings suggest that fine-tuning dopamine receptor signaling with aripiprazole allows selective suppression of ketamine-induced dissociation preserving its antidepressant effects, and that the combined use of aripiprazole and ketamine may be a preferred therapy for treatment-resistant depression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"77"},"PeriodicalIF":5.8,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586911","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":"Oxytocin improves maternal licking behavior deficits in autism-associated Shank3 mutant dogs.","authors":"Wen Lyu, Yuan Li, Aiyu Yao, Qing-Quan Tan, Rong Zhang, Jian-Ping Zhao, Kun Guo, Yong-Hui Jiang, Rui Tian, Yong Q Zhang","doi":"10.1038/s41398-025-03296-5","DOIUrl":"10.1038/s41398-025-03296-5","url":null,"abstract":"<p><p>Impaired social interaction and repetitive behavior are key features observed in individuals with autism spectrum disorder (ASD). SHANK3 is a high-confidence ASD risk gene that encodes an abundant scaffolding protein in the postsynaptic density. In wild-type (WT) domestic dogs, maternal behaviors such as licking and nursing (largely milk feeding) of puppies are most commonly observed. To address whether SHANK3 plays a role in social behaviors especially maternal behaviors, we analyzed Shank3 mutant dogs generated by CRISPR/Cas9 methodology. We found that Shank3 mutant dams exhibited a fewer and shorter licking behavior, as well as reduced nursing frequency when compared with WT dams. Additionally, a significant decrease in blood oxytocin (OXT) concentration was detected in Shank3 mutant dams. We thus conducted a vehicle-controlled experiment to examine whether a two-week intranasal OXT treatment, initiated on the 8^th postpartum day, could rescue the maternal licking deficits in Shank3 mutant dams. We found that the decreased licking behavior in Shank3 mutant dams was significantly attenuated both acutely and chronically by OXT treatment. The rescue effect of OXT implicates an oxytocinergic contribution to the maternal defects in Shank3 mutant dams, suggesting a potential therapeutic strategy for SHANK3-associated ASD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"76"},"PeriodicalIF":5.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574150","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":"Alexithymia may explain the genetic relationship between autism and sensory sensitivity.","authors":"Isabel Yorke, Jennifer Murphy, Fruhling Rijsdijk, Emma Colvert, Stephanie Lietz, Francesca Happé, Geoffrey Bird","doi":"10.1038/s41398-025-03254-1","DOIUrl":"10.1038/s41398-025-03254-1","url":null,"abstract":"<p><p>Sensory symptoms are highly prevalent amongst autistic individuals and are now considered in the diagnostic criteria. Whilst evidence suggests a genetic relationship between autism and sensory symptoms, sensory symptoms are neither universal within autism nor unique to autism. One explanation for the heterogeneity within autism and commonality across conditions with respect to sensory symptoms, is that it is alexithymia (a condition associated with difficulties identifying and describing one's own emotions) that has a genetic relationship with sensory symptoms, and that alexithymia commonly co-occurs with autism and with several other conditions. Using parent-reports of symptoms in a sample of adolescent twins, we sought to examine the genetic association between autism, alexithymia and sensory symptoms. Results showed that the genetic correlation between autism and sensory symptoms was not significant after controlling for alexithymia. In contrast, after controlling for variance in alexithymia explained by autism, the genetic correlation between alexithymia and sensory symptoms was significant (and the proportion of variance explained by genetic factors remained consistent after controlling for autism). These results suggest that 1) alexithymia and sensory symptoms share aetiology that is not accounted for by their association with autism and 2) that the genetic association between sensory symptoms and autism may be, in part or wholly, a product of alexithymia. Future research should seek to examine the contribution of alexithymia to sensory symptoms across other conditions.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"75"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568313","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":"Interventions for suicidal and self-injurious related behaviors in adolescents with psychiatric disorders: a systematic review and meta-analysis.","authors":"Junjie Lu, Jun Huang, Wanting Gao, Zexin Wang, Nan Yang, Yingbin Luo, Junxin Guo, Weng Ian Phoenix Pang, Grace Ka In Lok, Wenwang Rao","doi":"10.1038/s41398-025-03278-7","DOIUrl":"10.1038/s41398-025-03278-7","url":null,"abstract":"<p><p>As a leading cause of adolescent death, suicidal and self-injurious related behaviors (SSIRBs) is a devastating global health problem, particularly among patients with psychiatric disorders (PDs). Previous studies have shown that multiple interventions can alleviate symptoms and reduce risks. This review aimed to provide a systematic summary of interventions (i.e., medication, physical therapy, psychosocial therapy) for the treatment of SSIRBs among Chinese adolescents with PDs. From inception to September 17, 2023, twelve databases (PubMed, CINAHL, ScienceDirect, PsycINFO, EMBASE, Cochrane Library, Clinical Trial, Web of Science, CEPS, SinoMed, Wanfang and CNKI) were searched. We qualitatively and quantitatively synthesized the included studies. Standardized mean differences (SMDs), risk ratios and their 95% confidence intervals (CIs) used the Der Simonian and Laird random-effects model. Fifty-two studies covering 3709 eligible participants were included. Overall, the commonly used interventions targeting SSIRBs and negative feelings in PDs adolescents with SSIRBs included psychosocial therapy (e.g., cognitive behavioral therapy), medication (e.g., antidepressants), and physiotherapy (e.g., repetitive transcranial magnetic stimulation). Importantly, quetiapine fumarate in combination with sodium valproate (SV) had positive effects on reducing self-injury behaviors score [SMD: -2.466 (95% CI: -3.305, -1.628), I² = 88.36%], depression [SMD: -1.587 (95% CI: -2.505, -0.670), I² = 90.45%], anxiety [SMD: -1.925 (95% CI: -2.700, -1.150), I² = 85.23%], impulsivity [SMD: -2.439 (95% CI: -2.748, -2.094), I² = 0%], as well as its safety in comparison with SV alone. No significant difference of adverse reactions was found by low-dose QF (P > 0.05). This review systematically outlined the primary characteristics, safety and effectiveness of interventions for Chinese PDs adolescents with SSIRBs, which could serve as valuable evidence for guidelines aiming to formulate recommendations.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"73"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568319","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 and shared biological bases between birth weight and cortical structure.","authors":"Lu Zhang, Qiaoyue Ge, Zeyuan Sun, Rui Zhang, Xinxi Li, Xiaoli Luo, Run Tian, Yuheng Cao, Chunyan Pu, Lin Li, Dongsheng Wu, Ping Jiang, Chuan Yu, Chiara Nosarti, Chenghan Xiao, Zhenmi Liu","doi":"10.1038/s41398-025-03294-7","DOIUrl":"10.1038/s41398-025-03294-7","url":null,"abstract":"<p><p>Associations between birth weight and cortical structural phenotypes have been detected; however, the understanding is incomprehensive, and the potential biological bases are not well defined. Leveraging data from genome-wide association studies, we investigated the associations and the shared transcriptomic, proteomic and cellular bases of birth weight and 13 cortical structural phenotypes. Mendelian randomization analyses were performed to examine associations between birth weight and cortical structure. Downstream transcriptome-wide association study (TWAS), proteome-wide association study (PWAS) and summary-based Mendelian randomization (SMR) analyses were utilized to identify the shared cis-regulated gene expressions and proteins. Finally, cell-type expression-specific integration for complex traits (CELLECT) analyses were conducted to explore the enriched cell types. The Mendelian randomization analyses found positive associations between birth weight and global cortical folding index, intrinsic curvature index, local gyrification index, surface area and volume. Downstream transcriptomic-level TWAS and SMR identified three gene expressions both linked to birth weight and at least one cortical structural phenotype (CNNM2, RABGAP1 and CENPW). Parallel PWAS and SMR analyses at the proteomic level identified four proteins linked to both phenotypes (CNNM2, RAB7L1, RAB5B and PPA2), of which CNNM2 was replicated. CELLECT analyses revealed brain cell types enriched in birth weight, including pericytes, inhibitory GABAergic neurons and cerebrovascular cells. These findings support the importance of early life growth to cortical structure, and suggest underlying transcriptomic, proteomic and cellular bases. These results provide intriguing targets for further research into the mechanisms of cortical development.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"74"},"PeriodicalIF":5.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568316","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":"Dissecting biological heterogeneity in major depressive disorder based on neuroimaging subtypes with multi-omics data.","authors":"Lili Tang, Rui Tang, Junjie Zheng, Pengfei Zhao, Rongxin Zhu, Yanqing Tang, Xizhe Zhang, Xiaohong Gong, Fei Wang","doi":"10.1038/s41398-025-03286-7","DOIUrl":"10.1038/s41398-025-03286-7","url":null,"abstract":"<p><p>The heterogeneity of Major Depressive Disorder (MDD) has been increasingly recognized, challenging traditional symptom-based diagnostics and the development of mechanism-targeted therapies. This study aims to identify neuroimaging-based MDD subtypes and dissect their predominant biological characteristics using multi-omics data. A total of 807 participants were included in this study, comprising 327 individuals with MDD and 480 healthy controls (HC). The amplitude of low-frequency fluctuations (ALFF), a functional neuroimaging feature, was extracted for each participant and used to identify MDD subtypes through machine learning clustering. Multi-omics data, including profiles of genetic, epigenetics, metabolomics, and pro-inflammatory cytokines, were obtained. Comparative analyses of multi-omics data were conducted between each MDD subtype and HC to explore the molecular underpinnings involved in each subtype. We identified three neuroimaging-based MDD subtypes, each characterized by unique ALFF pattern alterations compared to HC. Multi-omics analysis showed a strong genetic predisposition for Subtype 1, primarily enriched in neuronal development and synaptic regulation pathways. This subtype also exhibited the most severe depressive symptoms and cognitive decline compared to the other subtypes. Subtype 2 is characterized by immuno-inflammation dysregulation, supported by elevated IL-1 beta levels, altered epigenetic inflammatory measures, and differential metabolites correlated with IL-1 beta levels. No significant biological markers were identified for Subtype 3. Our results identify neuroimaging-based MDD subtypes and delineate the distinct biological features of each subtype. This provides a proof of concept for mechanism-targeted therapy in MDD, highlighting the importance of personalized treatment approaches based on neurobiological and molecular profiles.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"72"},"PeriodicalIF":5.8,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543428","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":"Lack of association between pretreatment glutamate/GABA and major depressive disorder treatment response.","authors":"Feiyang Dai, Kenneth Wengler, Xiang He, Junying Wang, Jie Yang, Ramin V Parsey, Christine DeLorenzo","doi":"10.1038/s41398-025-03292-9","DOIUrl":"10.1038/s41398-025-03292-9","url":null,"abstract":"<p><p>Studies have shown gamma-amino-butyric acid (GABA) and Glx (a combination of glutamate and glutamine) to be altered in major depressive disorder (MDD). Using proton Magnetic Resonance Spectroscopy (¹H-MRS), this study aimed to determine whether lower pretreatment GABA and Glx levels in the medial frontal cortex, a region implicated in MDD pathophysiology, are associated with better antidepressant treatment response. Participants with MDD (N = 74) were antidepressant naïve or medication-free for at least three weeks before imaging. Two MEGA-PRESS ¹H-MRS acquisitions were collected, interleaved with a water unsuppressed reference scan. GABA and Glx concentrations were quantified from an average difference spectrum, with preprocessing using Gannet and spectral fitting using TARQUIN. Following imaging, participants were randomized to escitalopram or placebo for 8 weeks in a double-blind design. Multivariable logistic regression models were applied with treatment type and age as covariates. Bayes Factor hypothesis testing was used to interpret the strength of the evidence. No significant association was found between pretreatment Glx, GABA, or Glx/GABA and depression remission status or the continuous outcome, percent change in symptom severity. In an exploratory analysis, no significant correlation was found between pretreatment Glx, GABA or Glx/GABA and days to response. Bayes factor analysis showed strong evidence towards the null hypotheses in all cases. To date, there are no replicated biomarkers in psychiatry. To address this, well-powered, placebo-controlled trials need to be undertaken and reported. The present analysis suggests pretreatment GABA, Glx, or their ratio cannot predict antidepressant treatment response. Future direction including examining glutamate and glutamine separately or examining biological subtypes of MDD separately.Trial Name: Advancing Personalized Antidepressant Treatment Using PET/MRI.Registration Number: NCT02623205 URL: https://clinicaltrials.gov/ct2/show/NCT02623205.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"71"},"PeriodicalIF":5.8,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The relationship between cortical synaptic terminal density marker SV2A and glutamate early in the course of schizophrenia: a multimodal PET and MRS imaging study.","authors":"Ellis Chika Onwordi, Thomas Whitehurst, Ekaterina Shatalina, Richard Carr, Ayla Mansur, Atheeshaan Arumuham, Martin Osugo, Tiago Reis Marques, Sameer Jauhar, Susham Gupta, Sofia Pappa, Ravi Mehrotra, Maja Ranger, Nikola Rahaman, Eugenii A Rabiner, Roger N Gunn, Sridhar Natesan, Oliver D Howes","doi":"10.1038/s41398-025-03269-8","DOIUrl":"10.1038/s41398-025-03269-8","url":null,"abstract":"<p><p>Loss of glutamatergic terminals is hypothesised to contribute to excitation-inhibition imbalance in schizophrenia, supported by evidence that the normal positive association between glutamate concentrations and synaptic terminal density is not found in patients with chronic schizophrenia. However, it is unknown whether the relationship between synaptic terminal density and glutamate levels is altered early in the course of illness. To address this, we investigated [¹¹C]UCB-J distribution volume ratio (DVR) and glutamatergic markers in healthy volunteers (HV) and in antipsychotic-naïve/free patients with schizophrenia (SCZ) recruited from first-episode psychosis services. Forty volunteers (HV n = 19, SCZ n = 21) underwent [¹¹C]UCB-J positron emission tomography and proton magnetic resonance spectroscopy (¹H-MRS) imaging in the anterior cingulate cortex (ACC) and left hippocampus to index [¹¹C]UCB-J DVR and creatine-scaled glutamate (Glu/Cr) and glutamate in combination with glutamine (Glx/Cr). In the HV but not SCZ group, [¹¹C]UCB-J DVR was significantly positively associated with Glu/Cr (Spearman's rho = 0.55, p = 0.02) and Glx/Cr (Spearman's rho = 0.73, p = 0.0004) in the ACC, and with Glu/Cr in the left hippocampus (Spearman's rho = 0.77, p = 0.0001). DVR was significantly lower in the ACC in the SCZ group compared to the HV group (Kolmogorov-Smirnov Z = 1.44, p = 0.03). Together, these findings indicate that the normal relationship between levels of a synaptic terminal density marker and levels of glutamate is disrupted early in the course of schizophrenia. This is consistent with the hypothesis that there is loss of glutamatergic terminals at illness onset.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"70"},"PeriodicalIF":5.8,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537618","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}