Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Comparative analysis of inflammatory biomarkers in methamphetamine-associated psychosis and schizophrenia","authors":"Ali Baran Tanrıkulu ,&nbsp;Hilal Kaya ,&nbsp;Zekiye Çatak","doi":"10.1016/j.pnpbp.2025.111404","DOIUrl":"10.1016/j.pnpbp.2025.111404","url":null,"abstract":"<div><h3>Introduction</h3><div>Methamphetamine-associated psychosis (MAP) can present a spectrum of clinical manifestations, ranging from transient psychotic symptoms to a full-blown primary psychotic disorder. Differentiating between acute exacerbations of MAP and primary psychotic disorders remains challenging due to the overlapping clinical symptoms. In this study, we aimed to investigate whether CBC-derived inflammatory markers, C-reactive protein/albumin ratio (CAR), and neutrophil/albumin ratio (NAR) levels can be used as inflammatory markers in the differential diagnosis of MAP and schizophrenia.</div></div><div><h3>Method</h3><div>The study sample included 206 patients hospitalized with acute exacerbation of psychosis (103 diagnosed with MAP, 103 diagnosed with schizophrenia) and 103 matched healthy controls. Logistic regression models were developed to determine the predictive value of group membership: Model 1 compared schizophrenia and MAP; Model 2 compared MAP and the control group; Model 3 compared the schizophrenia and the control group.</div></div><div><h3>Results</h3><div>NLR, MLR, PLR, and NAR levels were significantly higher in patients with schizophrenia and MAP when compared with healthy controls. The NLR level was found to be a significant predictor of group membership in regression analysis for schizophrenia (Model 1, Model 3; <em>p</em> &lt; 0.001). As a result of the regression model created with the MAP patients and control group, NAR was found to be a predictive variable for the MAP patients (Model 2, <em>p</em> = 0.011).</div></div><div><h3>Discussion</h3><div>The results showed that NLR may be a potential biomarker for distinguishing patients with schizophrenia from patients with MAP and healthy controls. NAR level may be a potential biomarker for distinguishing MAP patients from healthy controls.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111404"},"PeriodicalIF":5.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144114948","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":"Longitudinal DNA methylation and cell-type proportions alterations in risperidone treatment response in first-episode psychosis","authors":"Vanessa Kiyomi Ota ,&nbsp;Leticia Maria Spindola ,&nbsp;Anne-Kristin Stavrum ,&nbsp;Giovany Oliveira Costa ,&nbsp;Amanda Victória Gomes Bugiga ,&nbsp;Mariane Nunes Noto ,&nbsp;Carolina Muniz Carvalho ,&nbsp;Sang-Hyuck Lee ,&nbsp;Ana Lokmer ,&nbsp;Charanraj Goud Alladi ,&nbsp;Deepak Gopal Shewade ,&nbsp;Ravi Philip Rajkumar ,&nbsp;Frank Bellivier ,&nbsp;Rodrigo Affonseca Bressan ,&nbsp;Ary Gadelha ,&nbsp;Stéphane Jamain ,&nbsp;Cynthia Marie-Claire ,&nbsp;Cristiano Noto ,&nbsp;Gerome Breen ,&nbsp;Marcos Leite Santoro ,&nbsp;Sintia Iole Belangero","doi":"10.1016/j.pnpbp.2025.111402","DOIUrl":"10.1016/j.pnpbp.2025.111402","url":null,"abstract":"<div><div>Identifying biological markers to guide treatment decisions in first-episode psychosis (FEP) is essential for improving patient outcomes. This longitudinal study investigated DNA methylation (DNAm) patterns and DNAm-derived cell-type proportions (CTP) in blood and associated them with response to risperidone treatment, a second-generation antipsychotic drug, in antipsychotic-naïve FEP patients. We also explored longitudinal changes in DNAm associated with risperidone treatment. We profiled DNAm in 114 individuals before (anFEP) and after two months of risperidone treatment using microarrays. The main results were compared with 115 healthy controls and validated in an independent cohort of subjects with schizophrenia (<em>n</em> = 26) with one-month follow-up data. We identified 302 differentially methylated positions (DMPs) associated with treatment response, measured by changes in the Positive and Negative Syndrome Scale score, of which 16 were validated in the independent cohort. Sixteen differentially methylated regions (DMRs) were associated with response, with one (in <em>SIPA1L3</em>) being validated. A decrease in B-cell proportions was correlated with symptom improvement in both cohorts. Additionally, four DMPs associated with risperidone treatment were identified: two related to the psychotic state and two specifically to risperidone treatment. DNAm-derived CTP showed alterations in anFEP compared with controls, particularly in the neutrophil-to-lymphocyte ratio, which normalized after treatment. These findings suggest that DNAm, particularly in B-cells, may be a promising marker for monitoring response to risperidone treatment in schizophrenia. Our longitudinal study revealed novel and known genes that may be regulated by risperidone and could be used as response markers to improve prognosis in schizophrenia and FEP.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111402"},"PeriodicalIF":5.3,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112878","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":"Mangiferin: A natural neuroprotective polyphenol with anti-inflammatory and anti-oxidant properties for depression","authors":"Lan Lei,&nbsp;Cong-Ya Chen,&nbsp;Yu-Fei Wang,&nbsp;Zhen-Yu Guo,&nbsp;Yi Zhang","doi":"10.1016/j.pnpbp.2025.111401","DOIUrl":"10.1016/j.pnpbp.2025.111401","url":null,"abstract":"<div><div>Depression is a severe global health problem accompanied by persistent low mood that harms the physical and mental health of people and places a substantial economic burden on society. Mangiferin (MGF), a natural polyphenol in the traditional Chinese herb <em>Anemarrhena asphodeloides</em> Bge., can improve neuronal damage, memory, and cognitive deficits, implicating the therapeutic potential of MGF for depression. MGF has a unique C-glycosyl and phenolic structure that endows it with multiple biological properties, e.g., anti-oxidant, anti-inflammatory, and anti-mitochondrial dysfunction. However, the pharmacological role of MGF in depression remains unclear. Therefore, this review describes the neuroprotective effects and the antidepressant mechanisms of MGF in preclinical depression studies. MGF ameliorates cognitive deficits in depression and neurodegenerative diseases animal models by reducing amyloid-beta deposition, ameliorating cholinergic dysfunction, and increasing neurotrophic factors. Also, MGF regulates molecular mechanisms in depressed animals mainly through anti-inflammation (by inhibiting NLRP3 inflammasome activation, mitogen-activated protein kinase phosphorylation and its downstream nuclear factor-кB signaling pathway, and indoleamine 2,3-dioxygenase activity), anti-oxidant (by increasing levels of anti-oxidant enzymes and inhibiting lipid peroxidation). Notably, the potential mechanisms of MGF in treating depression by modulating neurotransmission (e.g., glutamate, dopamine, norepinephrine, and serotonin) need to be further explored. It is hoped to explore further the potential molecular mechanisms of MGF's biological activity in depression and provide directions for further clinical applications.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111401"},"PeriodicalIF":5.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071327","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":"Sirtuin 1 underlies depression-related behaviors by modulating the serotonin system in the dorsal raphe nucleus in female mice","authors":"Lihong Xu ,&nbsp;Yifan Cao ,&nbsp;Shasha Zhang ,&nbsp;Lin Du ,&nbsp;Wentao Wang ,&nbsp;Jing Liu ,&nbsp;Dan Wang ,&nbsp;Di Zhao ,&nbsp;Minghu Cui ,&nbsp;Shujun Jiang ,&nbsp;Gaofeng Qin ,&nbsp;Fantao Meng ,&nbsp;Mengdi Zhang ,&nbsp;Chen Li","doi":"10.1016/j.pnpbp.2025.111400","DOIUrl":"10.1016/j.pnpbp.2025.111400","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a primary driver of disability and greatly escalates the worldwide disease burden. Sirtuin 1 (Sirt1), a key regulator of cellular metabolism, is associated with genetic variations in MDD. We investigated how Sirt1 in serotonin (5-HT) neurons within the dorsal raphe nucleus (DRN) in mice affected behaviors associated with depression and susceptibility to stress. Our findings revealed that Sirt1 expression in the DRN was decreased when chronic unpredictable stress was induced in depressed female mice. Additionally, Sirt1 was co-localized with 5-HT neurons within the DRN, and its selective ablation in these neurons have induced depressive phenotypes in female mice but not in males. Adeno-associated virus-mediated knockdown of Sirt1 in adult female mice induced depressive behaviors, whereas Sirt1 overexpression eliminated these behaviors. Moreover, fiber-optic recordings showed a decrease in the neural excitability of 5-HT neurons and 5-HT levels in the DRN after Sirt1 knockdown. Furthermore, we observed that Sirt1 knockdown reduced the expression of tryptophan hydroxylase-2 (Tph2) and phosphorylation levels of extracellular signal-regulated kinase (ERK) and CAMP response element binding protein (CREB). Finally, variable molecular targets regarding immune responses and cytokine productions after Sirt1 knockdown were analyzed via high-throughput RNA-seq analysis of specimens from the DRN. The findings of this study emphasize the importance of Sirt1 for regulating depression-related behaviors in female mice by influencing the activity of 5-HT neurons in the DRN.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111400"},"PeriodicalIF":5.3,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144082037","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":"Effects of different methods of cannabis use on cognition and blood THC: A systematic review","authors":"Danial Behzad ,&nbsp;Siddhi Patel ,&nbsp;Reena Besa ,&nbsp;Arthur W.H. Chan ,&nbsp;Sheng Chen ,&nbsp;Sergio Rueda ,&nbsp;Anthony C. Ruocco ,&nbsp;Patricia Di Ciano","doi":"10.1016/j.pnpbp.2025.111399","DOIUrl":"10.1016/j.pnpbp.2025.111399","url":null,"abstract":"<div><div>Novel methods of cannabis use are becoming popular, but the differential impact of these new methods on cognition have not been widely studied. Further, the impact of cannabis on cognition is mediated by delta-9-tetrahydrocannabinol (THC), but few studies have directly compared the pharmacokinetics of different methods. This systematic review (PROSPERO, CRD42023442731) was conducted to determine whether the different forms of cannabis and routes of administration have differential acute effects on cognition or blood THC. In total, six studies were found that directly compared the effects of at least two different methods of cannabis administration on cognition and eight studies compared the impact of different methods on blood THC. In general, few differences between methods were found on cognitive performance but two studies found some evidence for worse performance on attention tasks after vaping cannabis versus edibles or smoked cannabis. One study found worse performance on a memory task in participants who smoked high potency flower with cannabidiol compared to a group of concentrates users. Despite this, the clear consensus is that inhaled routes of administration result in higher peak levels of THC, while edible cannabis has a longer duration of action. Additionally, one study found an inverse correlation between blood THC and cognition. Given that THC levels are used to detect impairment, this suggests that the ability to detect impairment may vary by method, with edibles presenting more of a challenge. More studies are needed to understand the effects of these newer methods of cannabis administration on performance and blood THC.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111399"},"PeriodicalIF":5.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071887","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":"Swimming into the future: Machine learning in zebrafish behavioral research","authors":"Barbara D. Fontana ,&nbsp;Julia Canzian ,&nbsp;Denis B. Rosemberg","doi":"10.1016/j.pnpbp.2025.111398","DOIUrl":"10.1016/j.pnpbp.2025.111398","url":null,"abstract":"<div><div>The zebrafish (<em>Danio rerio</em>) has emerged as a powerful organism in behavioral neuroscience, offering invaluable insights into the neural circuits and molecular pathways underlying complex behaviors. Although the knowledge of zebrafish behavioral repertoire is expanding rapidly, fundamental questions regarding complex behaviors remain poorly explored. Recent advances in machine learning offer potential for enhancing zebrafish behavioral analysis, enabling more precise, scalable, and unbiased assessments when compared to the traditional method. Thus, machine learning automates tracking and pattern recognition, uncovering new behavioral phenotypes and streamlining analysis typically manually assessed. Here, we highlight the potential use of machine learning tools in zebrafish-based models uncovering nuanced behavioral phenotypes to accelerate discoveries in translational neurobehavioral research, addressing the challenges and ethical considerations in the field. We emphasize that associating machine learning with zebrafish behavioral research, significant advances to elucidate neural and molecular mechanisms driving complex behaviors are expected. Collectively, the progressive refinement of these methods by enabling more detailed and efficient analysis will not only enhance the utility of zebrafish in translational neuroscience, but also contribute to develop more effective models of human disorders and in the search of potential neuroprotective strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111398"},"PeriodicalIF":5.3,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941117","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":"Improved classification of alcohol intake groups in the Intermittent-Access Two-Bottle choice rat model using a latent class linear mixed model","authors":"Diego Angeles-Valdez ,&nbsp;Alejandra López-Castro ,&nbsp;Jalil Rasgado-Toledo ,&nbsp;Lizbeth Naranjo-Albarrán ,&nbsp;Eduardo A. Garza-Villarreal","doi":"10.1016/j.pnpbp.2025.111397","DOIUrl":"10.1016/j.pnpbp.2025.111397","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) is a major public health problem in which preclinical models allow the study of AUD development, phenotypes, and the exploration of potential new treatments. The intermittent access two-bottle choice (IA2BC) model is a validated preclinical model for studying alcohol intake patterns similar to human AUD clinical studies. Typically, the mean/median of overall alcohol intake or the last drinking sessions is used as a threshold to divide groups of animals into high or low alcohol consumers. Nevertheless, this approach has the potential for introducing bias due to the a priori selection of a threshold, as opposed to measuring the consumption drinking pattern along the protocol and subgrouping accordingly. This study aimed to assess the efficacy of utilizing longitudinal data of all drinking sessions to classify the population into high or low alcohol intake groups, employing a latent class linear mixed model (LCLMM). We compared LCLMM with traditional classification methods: (i) percentiles, (ii) K-means clustering, and (iii) hierarchical clustering. In addition, we used simulations to compare the accuracy, specificity, and sensitivity of these methods. By considering the entire trajectory of alcohol intake, LCLMM provides a more robust classification based on accuracy (0.94) between high and low alcohol classes. We recommend the use of longitudinal statistical models in research on substance use disorders in preclinical studies, since they could improve the classification of subpopulations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111397"},"PeriodicalIF":5.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992427","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":"Microbiota-based therapies as novel targets for autism spectrum disorder: A systematic review and meta-analysis","authors":"Lucas Hassib ,&nbsp;Alexandre Kanashiro ,&nbsp;João Francisco Cordeiro Pedrazzi ,&nbsp;Bárbara Ferreira Vercesi ,&nbsp;Sayuri Higa ,&nbsp;Íris Arruda ,&nbsp;Yago Soares ,&nbsp;Adriana de Jesus de Souza ,&nbsp;Tatiana Barichello ,&nbsp;Francisco Silveira Guimarães ,&nbsp;Frederico Rogério Ferreira","doi":"10.1016/j.pnpbp.2025.111385","DOIUrl":"10.1016/j.pnpbp.2025.111385","url":null,"abstract":"<div><h3>Background</h3><div>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by persistent deficits in social interaction and communication. Emerging evidence suggests that alterations in the gut–brain axis play a key role in the pathophysiology of ASD, and that microbiota-targeted interventions may offer therapeutic benefits. However, no clear consensus has been reached regarding the effectiveness of these strategies in ameliorating behavioral characteristics. This systematic review and meta-analysis (PROSPERO registration ID: CRD42023494067) aimed to evaluate the impact of microbiota-based interventions—including synbiotics, prebiotics, single-strain probiotics, probiotic blends, and fecal microbiota transplantation (FMT)—on behavioral outcomes in individuals with ASD, with particular emphasis on social functioning.</div></div><div><h3>Results</h3><div>Of the 373 records initially identified, 20 studies met the inclusion criteria, comprising 16 randomized controlled trials and 4 open-label studies. The overall effect size indicated a statistically significant improvement in ASD-related behavioral symptoms following microbiota manipulation (Hedges' g = 0.47; 95 % CI: 0.30–0.64; <em>p</em> &lt; 0.001; I² = 33.01 %), representing a small but clinically relevant effect. Heterogeneity was classified as moderate. Among the interventions, FMT and probiotic blends yielded the most substantial effects. All major limitations of the current studies were thoroughly addressed and discussed to guide future experimental designs. Additionally, we examined preclinical evidence supporting the involvement of neural, immune, and metabolic pathways in mediating the observed behavioral improvements.</div></div><div><h3>Conclusions</h3><div>Our findings support the potential of microbiota-based therapies as a promising and well-tolerated strategy for improving behavioral symptoms in individuals with ASD. FMT and multi-strain probiotic formulations appear particularly effective. Nevertheless, further high-quality randomized controlled trials—especially involving FMT—are urgently needed to validate these results and guide clinical implementation. Thus, these findings provide a critical foundation for future investigations seeking to refine microbiota-based interventions and uncover the underlying mechanisms through which they influence ASD-related behaviors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111385"},"PeriodicalIF":5.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942515","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":"Extracellular vesicles as a promising tool in neuropsychiatric pharmacotherapy application and monitoring","authors":"Nikola Balic ,&nbsp;Matea Nikolac Perkovic ,&nbsp;Tina Milos ,&nbsp;Barbara Vuic ,&nbsp;Matea Kurtovic Kodzoman ,&nbsp;Dubravka Svob Strac ,&nbsp;Gordana Nedic Erjavec","doi":"10.1016/j.pnpbp.2025.111393","DOIUrl":"10.1016/j.pnpbp.2025.111393","url":null,"abstract":"<div><div>This review deals with the application of extracellular vesicles (EVs) in the treatment of various neuropsychiatric disorders, including mood disorders, neurodegeneration, psychosis, neurological insults and injuries, epilepsy and substance use disorders. The main challenges of most neuropsychiatric pharmaceuticals nowadays are how to reach the central nervous system at therapeutic concentration and maintain it long enough and how to avoid undesirable side effects caused by unsatisfying toxicity. Extracellular vesicles, as very important mediators of intercellular communication, can have a variety of therapeutic qualities. They can act neuroprotective, regenerative and anti-inflammatory, but they also have characteristics of a good drug delivery system, including their nano- scale size, biological safety and abilities to cross BBB, to pack drugs within the lipid bilayer, and not to trigger an immunological response. Besides, due to their presence in readily accessible biofluids, they are good candidates for biomarkers of the disease, its progression and therapy response monitoring. Alternations in EVs' cargo profiles can reflect the pathogenesis of neuropsychiatric disorders, but they could also affect the disease outcomes. In the future, EVs could help physicians to tailor treatment strategies for individual patients, however, more extensive studies are needed to standardize isolation, purification and production procedures, increase efficacy of drug loading and limit unwanted effects of innate EVs' content.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111393"},"PeriodicalIF":5.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921977","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 role of the brain-bone axis in skeletal degenerative diseases and psychiatric disorders, A genome-wide pleiotropic analysis","authors":"Shang Gao ,&nbsp;Lijie Qi ,&nbsp;Nianhu Li ,&nbsp;Xin Li ,&nbsp;Jie Zhang ,&nbsp;Zhaoqi Zhang ,&nbsp;Wei Liu","doi":"10.1016/j.pnpbp.2025.111388","DOIUrl":"10.1016/j.pnpbp.2025.111388","url":null,"abstract":"<div><h3>Introduction</h3><div>Skeletal degenerative diseases and psychiatric disorders often coexist clinically. However, the genetic correlations and underlying biological mechanisms between these two types of diseases remain unclear.</div></div><div><h3>Objectives</h3><div>To investigate the genetic correlations between skeletal degenerative diseases and psychiatric disorders and to identify shared genomic loci, genes, and pathways.</div></div><div><h3>Methods</h3><div>This comprehensive genome-wide pleiotropic association study utilized summary statistics from publicly available genome-wide association data. Various statistical genetic correlation methods were employed, including LDSC, HDL, PLACO, Coloc, Hyprcoloc, and Mendelian randomization (MR) analysis, along with immune cell colocalization analysis. The study aimed to identify potential shared genetic factors among three skeletal degenerative diseases (osteoarthritis, intervertebral disc degeneration, and osteoporosis) and three psychiatric disorders (schizophrenia, anxiety disorder, and major depressive disorder).</div></div><div><h3>Results</h3><div>Analyses using LDSC, HDL, and Bonferroni corrections revealed significant genetic correlations between intervertebral disc degeneration (IVDD) and anxiety disorder (ANX); fractures, IVDD, and arthritis with major depressive disorder (MDD); and arthritis with schizophrenia (SCZ). Significant genetic correlations were also observed between VDD and ANX, fractures, IVDD, hip osteoarthritis (HipOA), knee osteoarthritis (KneeOA) and MDD, and KneeOA and SCZ. Pleiotropy analysis using PLACO, MAGMA, and multitrait colocalization Hyprcoloc identified 65 pleiotropic loci, 27 shared causal loci, and 9 shared risk loci involving immune cells related to both psychiatric and bone-related diseases. Additionally, tissue-specific enrichment analysis showed that genes mapped to these loci were enriched in brain, cardiovascular, pancreatic, and other tissues. The IVW method demonstrated that MDD increased the risk of IVDD and KneeOA, while IVDD increased the risk of ANX and MDD. Conversely, SCZ was associated with a reduced risk of KneeOA. Multiple sensitivity analyses further supported a positive causal effect of IVDD on MDD.</div></div><div><h3>Conclusion</h3><div>These findings suggest significant genetic correlations between skeletal degenerative diseases and psychiatric disorders, highlighting multiple shared comorbid genes and key immune cell types. Importantly, the study supports the role of the brain-bone axis in the regulation of skeletal degenerative diseases and psychiatric disorders, which could provide valuable insights for potential therapeutic targets and interventions for these conditions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111388"},"PeriodicalIF":5.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055503","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}