Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Exploring the potential of psychedelic-assisted psychotherapy for moral injury: A scoping review.","authors":"Viktoriia Kurkova, Olga Winkler, Andrew Greenshaw, Rakesh Jetly, Jennifer Swainson, Kalee Lodewyk, Parisa Saghafi, Elizabeth Dennett, Lisa Burback","doi":"10.1016/j.pnpbp.2025.111333","DOIUrl":"10.1016/j.pnpbp.2025.111333","url":null,"abstract":"<p><p>This scoping review addresses the need to comprehensively explore the potential of psychedelic-assisted psychotherapy (PAP) to facilitate recovery from moral injury. Moral injury (MI), characterized by profound psychological distress arising from morally challenging experiences, has garnered increased attention as a complex mental health concern with significant functional sequelae, especially in the context of post-traumatic stress disorder (PTSD). There is growing interest in exploring alternative therapeutic approaches, with psychedelics emerging as an exciting potential intervention, as moral injury impacts treatment resistance, suicidality, social isolation, and overall functioning. Ten studies were included from 11,734 publications. Studies utilized psilocybin, MDMA, or LSD. None focused specifically on moral injury. Diagnoses included PTSD, alcohol use disorder, insomnia, human Immunodeficiency virus-related demoralized men, barbiturate dependence, anxiety associated with life-threatening illness, major depression, and PTSD comorbid with generalized anxiety disorder, panic disorder, and borderline personality disorder. Studies reported rapid, increasing, and sustained self-compassion over time, alongside increases in self-forgiveness and self-acceptance, reduction in demoralization, and decreased drinking scores. Though in other diagnostic contexts, PAP has shown efficacy in addressing symptoms commonly associated with moral injury, particularly within the context of PTSD. It holds promise as an intervention for MI and requires further exploration.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111333"},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurological soft signs and thyroid hormones in schizophrenia spectrum disorders","authors":"Michael Carl Treiber ,&nbsp;Eva-Maria Tsapakis ,&nbsp;Sophia Athanasiou ,&nbsp;Kostas Chovardas ,&nbsp;Theocharis Kyziridis ,&nbsp;Konstantinos N. Fountoulakis","doi":"10.1016/j.pnpbp.2025.111338","DOIUrl":"10.1016/j.pnpbp.2025.111338","url":null,"abstract":"<div><h3>Background</h3><div>Neurological soft signs (NSS) are minor sensory and motor deviations linked to neurodevelopmental disorders and schizophrenia spectrum disorders (SSD). Thyroid hormones (TH) are essential for neurodevelopment and are suggested to be altered in SSD. Yet, the relationship between NSS and TH is unclear.</div></div><div><h3>Objectives</h3><div>We evaluated the relationship between NSS and TH in individuals with SSD.</div></div><div><h3>Methods</h3><div>We examined a total of 72 individuals with SSD. We assessed NSS using the Neurological Evaluation Scale (NES) and clinical symptoms using the Positive and Negative Syndrome Scale (PANSS). We collected fasting blood samples to measure serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3). We used the <em>t</em>-test to compare differences between sex and the Pearson correlation to test for correlations between NSS, TH and psychopathology separately for males and females.</div></div><div><h3>Results</h3><div>We observed a negative correlation between fT4 and NES total score (<em>r</em> = −0.374, <em>p</em> = .032), and NES subdomain “sensory integration” (<em>r</em> = −0.372, <em>p</em> = .033). The correlation between fT4 and “sensory integration” remained largely unchanged when controlling for age, DOI, and antipsychotic dose in OLZ equivalents by performing partial correlation analyses (<em>r</em> = −0.424, <em>p</em> = .049). Serum fT3 and TSH levels exhibited no significant correlation with NES scores but the PANSS negative symptoms score was negatively associated with fT3 (<em>r</em> = −0.472, <em>p</em> &lt; .001).</div></div><div><h3>Conclusions</h3><div>Lower fT4 levels were associated with NSS severity and specific NSS subdomains only in male individuals. In the overall sample, we detected a significant negative correlation between fT3 and negative symptoms. Future studies should examine a larger sample of drug-naïve individuals with SSDs, followed-up longitudinally in time to infer causality.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111338"},"PeriodicalIF":5.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671739","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":"Impact of sex and complex PTSD comorbidity on pharmacological treatment response in bipolar disorder patients","authors":"Luca Steardo Jr. ,&nbsp;Michele Fornaro ,&nbsp;Martina D'Angelo ,&nbsp;Valeria Di Stefano ,&nbsp;Francesco Monaco ,&nbsp;Caterina Scuderi ,&nbsp;Luca Steardo ,&nbsp;Marta Valenza","doi":"10.1016/j.pnpbp.2025.111337","DOIUrl":"10.1016/j.pnpbp.2025.111337","url":null,"abstract":"<div><h3>Background</h3><div>The prevalence of bipolar disorder (BD) is similar in men and women. However, factors such as sex and comorbid psychiatric conditions can influence its clinical presentation and treatment outcomes, including complex PTSD (cPTSD), a newly categorized trauma-related condition. Little is known about how sex and cPTSD comorbidity affect the response to mood stabilizers, a cornerstone treatment for BD. This observational, cross-sectional study examines the impact of sex and cPTSD comorbidity on clinical and behavioral BD features as well as their interplay in influencing pharmacological treatment response.</div></div><div><h3>Methods</h3><div>A cohort of BD patients (females = 177, males = 166, age range: 19–76; BD-I = 253, BD-II = 90) was recruited over three years. Clinical assessments were conducted, and patients were administered the International Trauma Questionnaire to evaluate cPTSD comorbidity and the Alda Scale to assess response to mood stabilizers.</div></div><div><h3>Results</h3><div>Our results show distinct clinical profiles based on sex and cPTSD. Female BD patients exhibit more hypomanic episodes, antidepressant-induced mania, and longer periods of untreated illness than males. Comorbid cPTSD was diagnosed in 154 patients (44.8 %), among which 69 were females. Patients with cPTSD display more severe BD symptoms, including earlier onset, more frequent episodes, and a higher prevalence of psychosis and suicidality. Importantly, comorbid cPTSD was associated with poorer mood stabilizer response, particularly in males, who otherwise responded better to treatment than females.</div></div><div><h3>Conclusions</h3><div>These findings underscore the importance of addressing trauma symptoms in BD treatment and highlight the need for individualized approaches considering both sex and comorbid trauma, as standard mood stabilizers may be insufficient for certain subgroups.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111337"},"PeriodicalIF":5.3,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143651841","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 patterns of individual morphological deformation in schizophrenia: Putative cortical compensatory of unaffected sibling","authors":"Pan Yunzhi ,&nbsp;Zhong Mingjun ,&nbsp;Chen Yuqing ,&nbsp;Han Lin ,&nbsp;Huang Weiqing ,&nbsp;Tan Wenjian ,&nbsp;Huang Danqing ,&nbsp;Yang Jun ,&nbsp;Cheng Yixing ,&nbsp;Chen Xudong","doi":"10.1016/j.pnpbp.2025.111329","DOIUrl":"10.1016/j.pnpbp.2025.111329","url":null,"abstract":"<div><h3>Background</h3><div>Neuroimaging advancements have revealed morphological deformation across various indicators, illuminating the neuropathological origins of schizophrenia. However, consolidating the findings across indicators and assessing regional global deformation at individual-level poses a significant challenge.</div></div><div><h3>Methods</h3><div>We propose individual morphological deformation index (IMDI) as potential biomarker for schizophrenia leveraging a distance algorithm that incorporates three key indicators (cortical thickness, gyrification, and volume), and applied it for 199 schizophrenia patients, 218 healthy controls, and 47 unaffected siblings. Additionally, we studied the relationships between polygenic risks, symptomology, cognition, social functioning and regional IMDI.</div></div><div><h3>Results</h3><div>Our findings reveal significantly higher IMDI in specific brain regions (bilateral pars opercularis, lateral orbitofrontal, left superior parietal, right pars orbitalis, and superior temporal) in patients, demonstrating two distinct spatial patterns linked to either isolated indicator reduction or concurrent declines across multiple indicators. Notably, unaffected siblings exhibited higher IMDI than controls, primarily due to cortical volume expansion in the right pars opercularis and superior temporal regions. Patients with higher IMDI had more severe positive symptoms, impaired cognition, reduced social functioning and selfcare ability. Participants with higher polygenic scores showed higher IMDI specifically in left caudal middle frontal regions.</div></div><div><h3>Conclusions</h3><div>The proposed IMDI biomarker offers an objective, interpretable way to quantify global regional deformation and integrate disparate neuroimaging indicators. Our results indicate that schizophrenia-related cortical deformations encompass sensorimotor, attention, default mode, and frontoparietal networks, exhibiting at least two spatial patterns. Moreover, siblings may exhibit compensation in cortical volume. These insights offer a novel perspective on the neuroanatomical underpinnings of schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111329"},"PeriodicalIF":5.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The underlying neurobiological basis of gray matter volume alterations in schizophrenia with auditory verbal hallucinations: A meta-analytic investigation","authors":"Yuanjun Xie ,&nbsp;Tian Zhang ,&nbsp;Chaozong Ma ,&nbsp;Muzhen Guan ,&nbsp;Chenxi Li ,&nbsp;Lingling Wang ,&nbsp;Xinxin Lin ,&nbsp;Yijun Li ,&nbsp;Zhongheng Wang ,&nbsp;Huaning Wang ,&nbsp;Peng Fang","doi":"10.1016/j.pnpbp.2025.111331","DOIUrl":"10.1016/j.pnpbp.2025.111331","url":null,"abstract":"<div><div>Schizophrenia patients with auditory verbal hallucinations (AVH) frequently exhibit brain structural alterations, particularly reductions in gray matter volume (GMV).Understanding the neurobiological mechanisms underlying the changes is essential for advancing treatment strategies. To address this, a meta-analysis was conducted to identify GMV changes in schizophrenia patients with AVH and their associations with gene expression and neurotransmitter receptor profiles. The results indicated significant GMV reductions in the left and the right insula, as well as the left anterior cingulate cortex. Ontology analysis of genes associated with GMV alternations revealed enrichment in biological processes related to ion transport and synaptic transmission. Hub genes from the KCN, SCN, GN, and PRK families, along with neurotransmitter receptors such as D2, VAChT, and mGluR5, showed significant correlations with GMV changes. Furthermore, multivariate linear regression analysis demonstrated that GNB2, GNB4, PRKCG, D2, and mGluR5 significantly predicted GMV alternations. These findings suggest that GMV reductions in schizophrenia with AVH are linked to disruptions in neurobiological processes involving specific genes and neurotransmitter systems, highlighting the potential targets for therapeutic intervention.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111331"},"PeriodicalIF":5.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Common neural correlates of chronic pain – A systematic review and meta-analysis of resting-state fMRI studies","authors":"Juliana Fiúza-Fernandes ,&nbsp;Joana Pereira-Mendes ,&nbsp;Madalena Esteves ,&nbsp;Joaquim Radua ,&nbsp;Maria Picó-Pérez ,&nbsp;Hugo Leite-Almeida","doi":"10.1016/j.pnpbp.2025.111326","DOIUrl":"10.1016/j.pnpbp.2025.111326","url":null,"abstract":"<div><div>Maladaptive brain plasticity has been reported in chronic pain (CP) conditions, though it remains unclear if there are common alterations across pathologies. Therefore, we systematically synthesized literature comparing resting-state functional magnetic resonance imaging (rs-fMRI) in CP patients and healthy controls (HC), and meta-analyzed data whenever applicable. Separate meta-analyses were performed for each method – (fractional) amplitude of low-frequency fluctuations (fALFF, ALFF), regional homogeneity (ReHo), seed-based connectivity (according to the seed) and independent component analysis (according to the network). In qualitative synthesis, sensory-discriminative pain processing – thalamus, insula, temporal and sensory cortices – and cognitive and emotional processing – cingulate, prefrontal and parietal cortices and precuneus – regions concentrated CP/HC differences. Meta-analyses revealed decreased ALFF and increased ReHo in the precuneus, increased fALFF in the left posterior insula and disrupted within- and cross-network connectivity of default mode network (DMN) nodes, as well as altered connectivity in top-down pain modulation pathways. Specifically, it showed decreased anterior and increased posterior components' representation within DMN, enhanced connectivity between the medial prefrontal cortex (mPFC, part of the DMN) and anterior insula (part of the salience network), and decreased mPFC connectivity with the periaqueductal gray matter (PAG). Collectively, results suggest that CP disrupts the natural functional organization of the brain, particularly impacting DMN nodes (mPFC and precuneus), insula and top-town pain modulation circuits.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111326"},"PeriodicalIF":5.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631054","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":"Pyroptosis; igniting neuropsychiatric disorders from mild depression to aging-related neurodegeneration","authors":"Kiavash Hushmandi ,&nbsp;Russel J. Reiter ,&nbsp;Najma Farahani ,&nbsp;William C. Cho ,&nbsp;Mina Alimohammadi ,&nbsp;Seyedeh Mahdieh Khoshnazar","doi":"10.1016/j.pnpbp.2025.111325","DOIUrl":"10.1016/j.pnpbp.2025.111325","url":null,"abstract":"<div><div>Neuropsychiatric disorders significantly impact global health and socioeconomic well-being, highlighting the urgent need for effective treatments. Chronic inflammation, often driven by the innate immune system, is a key feature of many neuropsychiatric conditions. NOD-like receptors (NLRs), which are intracellular sensors, detect danger signals and trigger inflammation. Among these, NLR protein (NLRP) inflammasomes play a crucial role by releasing pro-inflammatory cytokines and inducing a particular cell death process known as pyroptosis. Pyroptosis is defined as a proinflammatory form of programmed cell death executed by cysteine-aspartic proteases, also known as caspases. Currently, the role of pyroptotic flux has emerged as a critical factor in innate immunity and the pathogenesis of multiple diseases. Emerging evidence suggests that the induction of pyroptosis, primarily due to NLRP inflammasome activation, is involved in the pathophysiology of various neuropsychiatric disorders, including depression, stress-related issues, schizophrenia, autism spectrum disorders, and neurodegenerative diseases. Within this framework, the current review explores the complex relationship between pyroptosis and neuropsychiatric diseases, aiming to identify potential therapeutic targets for these challenging conditions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111325"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the causal relationship between delirium and sarcopenia using bidirectional two-sample Mendelian randomization study","authors":"Rui Zhou ,&nbsp;Yumeng Fu ,&nbsp;Peiling Wan,&nbsp;Baoli Cheng","doi":"10.1016/j.pnpbp.2025.111327","DOIUrl":"10.1016/j.pnpbp.2025.111327","url":null,"abstract":"<div><h3>Background</h3><div>Population-based studies have validated the significant associations between delirium and sarcopenia. Nonetheless, the causality remains ambiguous. This study aims to elucidate the causal associations between delirium and sarcopenia, as well as the causal effects of medication use on both conditions.</div></div><div><h3>Methods</h3><div>A bidirectional two-sample Mendelian randomization (MR) analysis was performed based on public genome-wide association studies (GWAS) data. Causal effects were evaluated through the inverse-variance weighted (IVW) method as the principal analysis, supplemented by the weighted median, weighted mode. Cochran's Q test, MR-Egger regression, MR-PRESSO test and leave-one-out were applied for sensitivity analyses.</div></div><div><h3>Results</h3><div>The IVW method indicated a causal relationship between genetically predicted low hand-grip strength and delirium (OR = 1.31, 95 % CI: 1.02–1.67, <em>P</em> = 0.032). Additionally, diuretics (OR = 1.05, 95 % CI: 1.03–1.07, <em>P</em> &lt; 0.001) and glucocorticoids (OR = 1.06, 95 % CI: 1.01–1.12, <em>P</em> = 0.012) were causally associated with appendicular lean mass, and diabetes medications (OR = 1.04, 95 % CI: 1.02–1.06, <em>P</em> = 0.001) and immunosuppressants (OR = 1.05, 95 % CI: 1.02–1.09, <em>P</em> = 0.005) causally associated with low hand-grip strength. Alternative analytic methods yielded consistent results. Heterogeneity and horizontal pleiotropy were evident in associations between medication use and both delirium and sarcopenia, but the results remained consistent after excluding outliers.</div></div><div><h3>Conclusion</h3><div>This study provided evidence of a causal relationship between genetically predicted low hand-grip strength and delirium. However, the analysis revealed that medication use did not appear to act as a mediating factor between these two conditions. Larger population-based studies are needed to validate these findings.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111327"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related abnormalities in brain functional and molecular neuroimaging signatures in first-episode depression","authors":"Yu Jiang ,&nbsp;Yuan Chen ,&nbsp;Ruiping Zheng ,&nbsp;Bingqian Zhou ,&nbsp;Ying Wei ,&nbsp;Shuying Li ,&nbsp;Shaoqiang Han ,&nbsp;Yong Zhang ,&nbsp;Jingliang Cheng","doi":"10.1016/j.pnpbp.2025.111330","DOIUrl":"10.1016/j.pnpbp.2025.111330","url":null,"abstract":"<div><div>Abnormalities in resting-state brain activity have been demonstrated in depression patients with different ages, yet the age-related changes in dynamics of brain activity in depression are still limited. Here, we investigated the impacts of age on dynamics of brain activity and the molecular architecture. Resting-state functional magnetic resonance images were obtained from 138 first-episode depression patients and 120 healthy volunteers. All the participants were classified into two age cohorts, including adolescents and adults. Two-way analysis of variance was performed to examine the effect of age on dynamic amplitude of low-frequency fluctuations (ALFF) in depression. Then, cross-modal correlation analyses between dynamic ALFF and neurotransmitter maps were established. Significant diagnosis-by-age interaction of dynamic ALFF was located in medial frontal gyrus, supplementary motor area, postcentral gyrus, paracentral lobule and rolandic operculum. Dynamic ALFF alterations in the diagnosis-by-age interaction effect were associated with serotonergic, dopaminergic, noradrenergic, and GABAergic systems. These findings highlight the interaction between depression and age in brain functional and molecular neuroimaging signatures, which may be useful for future treatment strategies of different ages of depression.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111330"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated genetic analysis and single cell-RNA sequencing for brain image-derived phenotypes and Parkinson's disease","authors":"Lin Pan ,&nbsp;Laiyu Yang ,&nbsp;Weijie Ding ,&nbsp;Yongfei Hu ,&nbsp;Wenzhuo Yang ,&nbsp;Jingning Wang ,&nbsp;Zhiyun Zhang ,&nbsp;Kangli Fan ,&nbsp;Zhihui Sun ,&nbsp;Yue Liang ,&nbsp;Xiaoyue Lin ,&nbsp;Jun Chen ,&nbsp;Ying Zhang","doi":"10.1016/j.pnpbp.2025.111317","DOIUrl":"10.1016/j.pnpbp.2025.111317","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have reported Parkinson's disease (PD) patients usually have changes in brain image-derived phenotypes (IDPs). However, the role of genetic factors in their association and biological mechanism remains unclear. We aimed to unveil genetic and biological links between brain IDPs and PD.</div></div><div><h3>Methods</h3><div>Using genome-wide association study (GWAS) summary statistics and single-cell RNA sequencing (scRNA-seq) data, we performed a comprehensive analysis between 624 brain IDPs and PD. The genetic correlations and causality were examined by linkage disequilibrium score regression (LDSC), two-sample bidirectional Mendelian randomization (MR) and meta-analysis. Potential shared genes were identified using MAGMA and PLACO. Finally, pathway enrichment using FUMA and Metascape, and scRNA-seq analysis were performed to determine biological mechanisms and gene expression atlas across various cell types in brain tissue.</div></div><div><h3>Results</h3><div>LDSC revealed that 50 brain IDPs were genetically correlated with PD (<em>P</em> &lt; 0.05), in which 5 IDPs, exhibited putative causality on PD through MR (<em>P</em> &lt; 0.05). For instance, we identified that the increased volume of the right thalamus (IVW: OR = 2.08, 95 % CI: 1.33 to 3.25, <em>PFDR</em> = 0.03) was positively correlated with the risk of PD, which was also supported by replicated MR (IVW: OR = 1.63, 95 % CI: 1.17–2.26, <em>PFDR</em> = 0.02) in FinnGen and meta-analysis (OR = 1.78, 95 % CI: 1.36–2.31, <em>PFDR</em> = 5.00 × 10⁻⁴). Additionally, we identified 56 unique pleiotropic genes, such as FAM13A, with notable enrichment in neuronal cells. Biological mechanism analysis revealed these genes were enriched in brain tissues and a variety of pathways such as negative regulation of neuron apoptotic processes.</div></div><div><h3>Conclusion</h3><div>We indicated the shared genetic architecture and biological mechanisms between brain IDPs and PD. These findings might provide insights on the therapeutic intervention and early prediction of PD at the brain imaging level.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111317"},"PeriodicalIF":5.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620288","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}