Journal of Psychiatry & Neuroscience最新文献

{"title":"Structural-informed functional MRI analysis of patients with empathy impairment following stroke.","authors":"Jian-Feng Qu, Xiao-Wen Liu, Ming-Zi Wang, Yi-Shan Luo, Ting Gao, Lin Shi, Yang-Kun Chen","doi":"10.1503/jpn.240084","DOIUrl":"10.1503/jpn.240084","url":null,"abstract":"<p><strong>Background: </strong>The underlying functional alterations of brain structural changes among patients with empathy impairment following stroke remain unclear. We sought to investigate functional connectivity changes informed by brain structural abnormalities in multimodal magnetic resonance imaging (MRI) among patients with empathy impairment following stroke.</p><p><strong>Methods: </strong>We enrolled people who had experienced their first ischemic stroke, along with healthy controls. We assessed empathy 3 months after stroke using the Chinese version of the Empathy Quotient (EQ). During the acute phase, all patients underwent basic magnetic resonance imaging (MRI), followed by multimodal MRI during follow-up. Our MRI analyses encompassed acute infarction segmentation, volumetric brain measurements, regional quantification of diffusion parameters, and both region-of-interest-based and seed-based functional connectivity assessments. We grouped patients based on the severity of their empathy impairment for comparative analysis.</p><p><strong>Results: </strong>We included 84 patients who had stroke and 22 healthy controls. Patients had lower EQ scores than controls. Patients with low empathy had larger left cortical infarcts (odds ratio [OR] 4.082, 95% confidence interval [CI] 1.183-14.088), more pronounced atrophy in the right cingulate cortex (OR 1.248, 95% CI 1.038-1.502), and lower scores on the Montreal Cognitive Assessment (OR 0.873, 95% CI 0.74-0.947). In addition, the cingulate cortex served as the seed in the seed-based analysis, which showed heightened functional connectivity between the anterior cingulate gyrus and the right superior parietal lobule, specifically in the low-empathy group.</p><p><strong>Limitations: </strong>We did not evaluate the relationship between specific network involvement and empathy impairment among patients following stroke.</p><p><strong>Conclusion: </strong>Among patients with subacute ischemic stroke, reduced empathy was strongly associated with a more severe cognitive profile and atrophy of the right cingulate cortex. Our subsequent structural-informed functional MRI analysis suggests that the enhanced connectivity between the anterior cingulate gyrus and the superior parietal lobule may function as a compensatory mechanism for this atrophy.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 5","pages":"E345-E356"},"PeriodicalIF":4.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial transcriptomic analysis of adult hippocampal neurogenesis in the human brain.","authors":"Sophie Simard, Reza Rahimian, Maria Antonietta Davoli, Stéphanie Théberge, Natalie Matosin, Gustavo Turecki, Corina Nagy, Naguib Mechawar","doi":"10.1503/jpn.240026","DOIUrl":"10.1503/jpn.240026","url":null,"abstract":"<p><strong>Background: </strong>Adult hippocampal neurogenesis has been extensively characterized in rodent models, but its existence in humans remains controversial. We sought to assess the phenomenon in postmortem human hippocampal samples by combining spatial transcriptomics and multiplexed fluorescent in situ hybridization.</p><p><strong>Methods: </strong>We computationally examined the spatial expression of various canonical neurogenesis markers in postmortem dentate gyrus (DG) sections from young and middle-aged sudden-death males. We conducted in situ assessment of markers expressed in neural stem cells, proliferative cells, and immature granule neurons in postmortem DG sections from infant, adolescent, and middle-aged males.</p><p><strong>Results: </strong>We examined frozen DG tissue from infant (<i>n</i> = 1, age 2 yr), adolescent (<i>n</i> = 1, age 16 yr), young adult (<i>n</i> = 2, mean age 23.5 yr), and middle-aged (<i>n</i> = 2, mean age 42.5 yr) males, and frozen-fixed DG tissue from middle-aged males (<i>n</i> = 6, mean age 43.5 yr). We detected very few cells expressing neural stem cell and proliferative markers in the human DG from childhood to middle age. However, at all ages, we observed a substantial number of DG cells expressing the immature neuronal marker <i>DCX</i>. Most <i>DCX</i> ⁺ cells displayed an inhibitory phenotype, while the remainder were non-committed or excitatory in nature.</p><p><strong>Limitations: </strong>The study was limited by small sample sizes and included samples only from males.</p><p><strong>Conclusion: </strong>Our findings indicate very low levels of hippocampal neurogenesis throughout life and the existence of a local reserve of plasticity in the adult human hippocampus. Overall, our study provides important insight into the distribution and phenotype of cells expressing neurogenesis markers in the adult human hippocampus.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 5","pages":"E319-E333"},"PeriodicalIF":4.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of the gut microbiota and brain functional connectivity in late-life depression.","authors":"Chia-Fen Tsai, Chia-Hsien Chuang, Pei-Chi Tu, Wan-Chen Chang, Yen-Po Wang, Pei-Yi Liu, Po-Shan Wu, Chung-Yen Lin, Ching-Liang Lu","doi":"10.1503/jpn.240050","DOIUrl":"10.1503/jpn.240050","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD).</p><p><strong>Methods: </strong>We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms.</p><p><strong>Results: </strong>We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of <i>Enterobacter</i>, <i>Akkermansiaceae</i>, <i>Hemophilus</i>, <i>Burkholderia</i>, and <i>Rothia</i> was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of <i>Enterobacter</i> (dominant genus among patients with LLD) was positively correlated with both HAMD scores (<i>r</i> = 0.49, <i>p</i> = 0.0004) and group-characterized FC (<i>r</i> = -0.37, <i>p</i> < 0.05), while <i>Odoribacter</i> (dominant genus among controls) was negatively correlated with both HAMD scores (<i>r</i> = -0.30, <i>p</i> = 0.04) and group-characterized FC.</p><p><strong>Limitations: </strong>The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses.</p><p><strong>Conclusion: </strong>We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 5","pages":"E289-E300"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CCNP Innovations in Neuropsychopharmacology Award: The psychopharmacology of psychedelics: where the brain meets spirituality.","authors":"Gabriella Gobbi","doi":"10.1503/jpn.240037","DOIUrl":"10.1503/jpn.240037","url":null,"abstract":"<p><p>For 3000 years, psychedelics have been used in religious contexts to enhance spiritual thinking, well-being, and a sense of community. In the last few years, a renaissance in the use of psychedelic drugs for mental disorders has occurred in Western society; consequently, a pressing scientific need to elucidate the intricate mechanisms underlying their actions has arisen. Psychedelics mainly bind to serotonin (5-HT) receptors, particularly 5-HT_2A receptors, but may also bind to other receptors. Unlike conventional psychotropic drugs used in psychiatry, psychedelics introduce a distinctive complexity. They not only engage in receptor activation, but also exert influence over specific neural circuits, thereby facilitating transformative cognitive experiences and fostering what many have identified as a spiritual contemplation or mystical experience. This comprehensive review describes clinical studies that have examined the propensity of psychedelics to enhance spiritual, mystical, and transcendent cognitive states. This multifaceted nature, encompassing diverse components and paradigms, necessitates careful consideration during the investigation of psychedelic mechanisms of action to avoid oversimplification. The present review endeavours to elucidate the mechanisms underlying the actions of 2 principal psychedelic substances, psilocybin and lysergic acid diethylamide (LSD), with a focus on monoamine and glutamate receptor mechanisms; molecular aspects, such as neuroplasticity and epigenetics; as well as the impact of psychedelics on brain circuits, including the default mode network and the cortico-striato-thalamo-cortical network. Given their distinctive and intricate mechanisms of action, psychedelics necessitate a novel conceptual framework in psychiatry, offering insight into the treatment of mental health disorders and facilitating the integration of the realms of brain, mind, and spirituality.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 5","pages":"E301-E318"},"PeriodicalIF":4.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11426389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142299781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspective on adolescent psychiatric illness and emerging role of microRNAs as biomarkers of risk.","authors":"Alice Morgunova, Maxime Teixeira, Cecilia Flores","doi":"10.1503/jpn.240072","DOIUrl":"10.1503/jpn.240072","url":null,"abstract":"","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 4","pages":"E282-E288"},"PeriodicalIF":4.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine-induced priapism in a man with schizoaffective disorder.","authors":"Jennifer Woo, Mohamed Eisa","doi":"10.1503/jpn.240048","DOIUrl":"10.1503/jpn.240048","url":null,"abstract":"","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 4","pages":"E263-E264"},"PeriodicalIF":4.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma exosomes carrying mmu-miR-146a-5p and Notch signalling pathway-mediated synaptic activity in schizophrenia.","authors":"Zhichao Wang, Tong Wu, Houjia Hu, Alabed Ali A Alabed, Guangcheng Cui, Lei Sun, Zhenghai Sun, Yuchen Wang, Ping Li","doi":"10.1503/jpn.230118","DOIUrl":"10.1503/jpn.230118","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is characterized by a complex interplay of genetic and environmental factors, leading to alterations in various molecular pathways that may contribute to its pathogenesis. Recent studies have shown that exosomal microRNAs could play essential roles in various brain disorders; thus, we sought to explore the potential molecular mechanisms through which microRNAs in plasma exosomes are involved in schizophrenia.</p><p><strong>Methods: </strong>We obtained sequencing data sets (SUB12404730, SUB12422862, and SUB12421357) and transcriptome sequencing data sets (GSE111708, GSE108925, and GSE18981) from mouse models of schizophrenia using the Sequence Read Archive and the Gene Expression Omnibus databases, respectively. We performed differential expression analysis on mRNA to identify differentially expressed genes. We conducted Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine differentially expressed genes. Subsequently, we determined the intersection of differentially expressed microRNAs in plasma exosomes and in prefrontal cortex tissue. We retrieved downstream target genes of mmu-miR-146a-5p from TargetScan and used Cytoscape to visualize and map the microRNA-target gene regulatory network. We conducted in vivo experiments using MK-801-induced mouse schizophrenia models and in vitro experiments using cultured mouse neurons. The role of plasma exosomal miR-146a-5p in schizophrenia was validated using a cell counting kit, detection of lactate dehydrogenase, dual-luciferase assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis.</p><p><strong>Results: </strong>Differential genes were mainly enriched in synaptic regulation-related functions and pathways and were associated with neuronal degeneration. We found that mmu-miR-146a-5p was highly expressed in both prefrontal cortical tissue and plasma exosomes, which may be transferred to lobe cortical vertebral neurons, leading to the synergistic dysregulation of gene network functions and, therefore, promoting schizophrenia development. We found that mmu-miR-146a-5p may inhibit the Notch signalling pathway-mediated synaptic activity of mouse pyramidal neurons in the lobe cortex by targeting <i>NOTCH1</i>, which in turn could promote the onset and development of schizophrenia in mice.</p><p><strong>Limitations: </strong>The study's findings are based on animal models and in vitro experiments, which may not fully replicate the complexity of human schizophrenia.</p><p><strong>Conclusion: </strong>Our findings suggest that mmu-miR-146a-5p in plasma-derived exosomes may play an important role in the pathogenesis of schizophrenia. Our results provide new insights into the underlying molecular mechanisms of the disease.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 4","pages":"E265-E281"},"PeriodicalIF":4.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emotional dysregulation and stimulant medication in adult ADHD.","authors":"Myrto Sklivanioti Greenfield, Yanlu Wang, J Paul Hamilton, Per Thunberg, Mussie Msghina","doi":"10.1503/jpn.240009","DOIUrl":"10.1503/jpn.240009","url":null,"abstract":"<p><strong>Background: </strong>Emotional dysregulation affects up to two-thirds of adult patients with attention-deficit/hyperactivity disorder (ADHD) and is increasingly seen as a core ADHD symptom that is clinically associated with greater functional impairment and psychiatric comorbidity. We sought to investigate emotional dysregulation in ADHD and explored its neural underpinnings.</p><p><strong>Methods: </strong>We studied emotion induction and regulation in a clinical cohort of adult patients with ADHD before and after a stimulant challenge. We compared patients with age- and gender-matched healthy controls using behavioural, structural, and functional measures. We hypothesized that patients would demonstrate aberrant emotion processing compared with healthy controls, and sought to find whether this could be normalized by stimulant medication.</p><p><strong>Results: </strong>Behaviourally, the ADHD group showed reduced emotion induction and regulation capacity. Brain imaging revealed abberant activation and deactivation patterns during emotion regulation, lower grey-matter volume in limbic and paralimbic areas, and greater grey-matter volume in visual and cerebellar areas, compared with healthy controls. The behavioural and functional deficits seen in emotion induction and regulation in the ADHD group were not normalized by stimulant medication.</p><p><strong>Conclusion: </strong>Patients with ADHD may have impaired emotion induction and emotion regulation capacity, but these deficits are not reversed by stimulant medication. These results have important clinical implications when assessing which aspects of emotional dysregulation are relevant for patients and if and how traditional ADHD pharmacotherapy affects emotion induction and emotion regulation.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 4","pages":"E242-E251"},"PeriodicalIF":4.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perplexity of utterances in untreated first-episode psychosis: an ultra-high field MRI dynamic causal modelling study of the semantic network.","authors":"Maria Francisca Alonso-Sánchez, Wolfram Hinzen, Rui He, Joseph Gati, Lena Palaniyappan","doi":"10.1503/jpn.240031","DOIUrl":"10.1503/jpn.240031","url":null,"abstract":"<p><strong>Background: </strong>Psychosis involves a distortion of thought content, which is partly reflected in anomalous ways in which words are semantically connected into utterances in speech. We sought to explore how these linguistic anomalies are realized through putative circuit-level abnormalities in the brain's semantic network.</p><p><strong>Methods: </strong>Using a computational large-language model, Bidirectional Encoder Representations from Transformers (BERT), we quantified the contextual expectedness of a given word sequence (perplexity) across 180 samples obtained from descriptions of 3 pictures by patients with first-episode schizophrenia (FES) and controls matched for age, parental social status, and sex, scanned with 7 T ultra-high field functional magnetic resonance imaging (fMRI). Subsequently, perplexity was used to parametrize a spectral dynamic causal model (DCM) of the effective connectivity within (intrinsic) and between (extrinsic) 4 key regions of the semantic network at rest, namely the anterior temporal lobe, the inferior frontal gyrus (IFG), the posterior middle temporal gyrus (MTG), and the angular gyrus.</p><p><strong>Results: </strong>We included 60 participants, including 30 patients with FES and 30 controls. We observed higher perplexity in the FES group, indicating that speech was less predictable by the preceding context among patients. Results of Bayesian model comparisons showed that a DCM including the group by perplexity interaction best explained the underlying patterns of neural activity. We observed an increase of self-inhibitory effective connectivity within the IFG, as well as reduced self-inhibitory tone within the pMTG, in the FES group. An increase in self-inhibitory tone in the IFG correlated strongly and positively with inter-regional excitation between the IFG and posterior MTG, while self-inhibition of the posterior MTG was negatively correlated with this interregional excitation.</p><p><strong>Limitation: </strong>Our design did not address connectivity in the semantic network during tasks that selectively activated the semantic network, which could corroborate findings from this resting-state fMRI study. Furthermore, we do not present a replication study, which would ideally use speech in a different language.</p><p><strong>Conclusion: </strong>As an explanation for peculiar speech in psychosis, these results index a shift in the excitatory-inhibitory balance regulating information flow across the semantic network, confined to 2 regions that were previously linked specifically to the executive control of meaning. Based on our approach of combining a large language model with causal connectivity estimates, we propose loss in semantic control as a potential neurocognitive mechanism contributing to disorganization in psychosis.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 4","pages":"E252-E262"},"PeriodicalIF":4.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aberrant functional connectivity of the globus pallidus in the modulation of the relationship between childhood trauma and major depressive disorder.","authors":"Jinrou Xia, Xiaohui Lin, Tong Yu, Huiwen Yu, Yurong Zou, Qianyi Luo, Hongjun Peng","doi":"10.1503/jpn.240019","DOIUrl":"10.1503/jpn.240019","url":null,"abstract":"<p><strong>Background: </strong>Childhood trauma plays a crucial role in the dysfunctional reward circuitry in major depressive disorder (MDD). We sought to explore the effect of abnormalities in the globus pallidus (GP)-centric reward circuitry on the relationship between childhood trauma and MDD.</p><p><strong>Methods: </strong>We conducted seed-based dynamic functional connectivity (dFC) analysis among people with or without MDD and with or without childhood trauma. We explored the relationship between abnormal reward circuitry, childhood trauma, and MDD.</p><p><strong>Results: </strong>We included 48 people with MDD and childhood trauma, 30 people with MDD without childhood trauma, 57 controls with childhood trauma, and 46 controls without childhood trauma. We found that GP subregions exhibited abnormal dFC with several regions, including the inferior parietal lobe, thalamus, superior frontal gyrus (SFG), and precuneus. Abnormal dFC in these GP subregions showed a significant correlation with childhood trauma. Moderation analysis revealed that the dFC between the anterior GP and SFG, as well as between the anterior GP and the precentral gyrus, modulated the relationship between childhood abuse and MDD severity. We observed a negative correlation between childhood trauma and MDD severity among patients with lower dFC between the anterior GP and SFG, as well as higher dFC between the anterior GP and precentral gyrus. This suggests that reduced dFC between the anterior GP and SFG, along with increased dFC between the anterior GP and precentral gyrus, may attenuate the effect of childhood trauma on MDD severity.</p><p><strong>Limitations: </strong>Cross-sectional designs cannot be used to infer causality.</p><p><strong>Conclusion: </strong>Our findings underscore the pivotal role of reward circuitry abnormalities in MDD with childhood trauma. These abnormalities involve various brain regions, including the postcentral gyrus, precentral gyrus, inferior parietal lobe, precuneus, superior frontal gyrus, thalamus, and middle frontal gyrus.</p><p><strong>Clinical trial registration: </strong>ChiCTR2300078193.</p>","PeriodicalId":50073,"journal":{"name":"Journal of Psychiatry & Neuroscience","volume":"49 4","pages":"E218-E232"},"PeriodicalIF":4.1,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11230669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}