Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"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}

{"title":"Initial exposure to addictive drugs activates polysialylated NCAM-mediated hippocampal memory-associated synaptic plasticity in the rat prior to the emergence of dependence behaviour","authors":"Nanette Rombach,&nbsp;Rocio Fedriani,&nbsp;Darren Scully,&nbsp;Josiah O'Sullivan,&nbsp;Sean K. Mulvany,&nbsp;Keith J. Murphy","doi":"10.1016/j.pnpbp.2025.111395","DOIUrl":"10.1016/j.pnpbp.2025.111395","url":null,"abstract":"<div><div>The early neural adaptations to addictive substances are crucial to understanding how drug-associated memories form and contribute to later compulsive drug-seeking behaviour. This study investigated whether initial exposures to drugs of abuse engage hippocampal memory mechanisms, specifically through the activation of polysialylated neural cell adhesion molecule (NCAM PSA), a well-established marker of neuroplasticity.</div><div>Using a rodent model, we assessed hippocampal NCAM PSA expression and synaptic remodelling in response to acute and repeated administration of heroin, cocaine, and amphetamine. We compared these neuroplastic responses with those observed during normal spatial learning. Additionally, we examined changes in hippocampal NCAM PSA levels during heroin self-administration to evaluate the relationship between memory-related hippocampal activation and the emergence of drug-seeking behaviour.</div><div>Our findings reveal that addictive drugs acutely induce hippocampal neuroplasticity in a manner that parallels normal memory consolidation, including increased NCAM PSA expression and synaptic reorganisation. Following sufficient daily drug exposure, the memory-associated neuroplastic response is lost. Specifically in a setting of drug self-administration, we show that heroin continues to activate molecular memory mechanisms within the hippocampal dentate until the emergence of drug seeking behaviour based on recall of an association between drug reward and lever press. This pattern of hippocampal activity is shown to mirror precisely the molecular events associated with learning a normal explicit memory task, the water maze. Importantly, following chronic exposure to either heroin or cocaine, non-drug-related hippocampal-dependent learning events are no longer processed effectively for long-term storage in the absence of the addictive drug suggesting dependence on the drug for normal memory function.</div><div>These results identify hippocampal memory machinery as a key early target of addictive drugs and suggest that drug-associated memories may co-opt normal learning processes, contributing to the persistent and intrusive nature of drug cravings. The study provides novel insights into the mechanisms by which early drug experiences shape enduring behavioural vulnerability to addiction.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111395"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143937033","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":"Identifying novel protein biomarkers with cross-psychiatric disorders effects and potential intervention targets: Evidence from proteomic-Mendelian randomization","authors":"Ronghui Zhang ,&nbsp;Jia Luo ,&nbsp;Tong Wang ,&nbsp;Weijing Wang ,&nbsp;Jing Sun ,&nbsp;Dongfeng Zhang","doi":"10.1016/j.pnpbp.2025.111396","DOIUrl":"10.1016/j.pnpbp.2025.111396","url":null,"abstract":"<div><div>Plasma proteins are the potential therapeutic targets for psychiatric disorders due to their important roles in signal transduction. We aimed to explore the plasma protein biomarkers with cross-psychiatric disorders effects. Proteome-wide Mendelian randomization (MR) and colocalization analyses were performed to investigate the potential causal relationship between plasma protein biomarkers and 12 psychiatric disorders and further identify the potential proteins with cross-effects. To assess the directionality and exclude potential reverse causation, Steiger directionality tests and reverse MR analyses were additionally conducted. Then, validation analysis was performed by employing summary data from cross-psychiatric disorder GWAS to validate the cross-psychiatric effects of proteins. Protein-protein interactions were conducted to evaluate the interaction between candidate proteins and druggability assessment was used to prioritize potential drug targets for psychiatric disorders. We identified novel plasma proteins that possessed cross-psychiatric disorder effects, especially BTN2A1 and BTN3A2 associated with major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BIP); ITIH1, ITIH3, ITIH4 and FES associated with SCZ and BIP, and the cross-effects of these proteins on SCZ and BIP were confirmed by validation analyses. Steiger tests and reverse MR supported causal directionality. Besides, the protein-protein interactions (PPI) analysis indicated cross-effects proteins had significant interaction, especially ITIH1-ITIH3. The druggability assessment prioritized eight proteins, two of which (ITIH3 and NCAM1) has been targeted by antipsychotic drugs. Our findings provided insights into shared biological mechanisms underlying these conditions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111396"},"PeriodicalIF":5.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918272","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":"Dysfunction and recovery of the cortical connectome gradient and its association with gene expression profiles in methamphetamine and heroin use disorders","authors":"Zhe Du ,&nbsp;Wenhan Yang ,&nbsp;Xinwen Wen ,&nbsp;Suping Cai ,&nbsp;Jun Liu ,&nbsp;Kai Yuan","doi":"10.1016/j.pnpbp.2025.111391","DOIUrl":"10.1016/j.pnpbp.2025.111391","url":null,"abstract":"<div><h3>Background</h3><div>The hierarchy and segregation of community-based brain networks can be characterized by functional connectome gradient (FCG). Whether the cortical FCG was disrupted and could even be reversed after prolonged abstinence in substance use disorders (SUDs) remained unclear. Less is known about the underlying genetic basis.</div></div><div><h3>Methods</h3><div>We utilized three independent datasets (<em>n</em> = 247) to investigate cortical FCG dysfunction and recovery after prolonged abstinence in methamphetamine use disorder (MUD) (<em>n</em> = 131), and validated in heroin use disorder (HUD) (<em>n</em> = 36). Furthermore, magnetic resonance spectroscopy (MRS) was employed to test the relationship between the glutamate in the ventral tegmental area (VTA) and cortical FCG. Postmortem gene expression was utilized to assess the transcriptional profiles related to cortical FCG alterations. Support vector regression (SVR) model based on the baseline cortical FCG was built to predict craving changes after long-term abstinence. <strong>Results:</strong> MUD and HUD individuals exhibited similar cortical FCG dysfunction and recovery at global and network levels, mainly in dorsal and ventral attentions network (DAN and VAN), frontoparietal network (FPN) and default mode network (DMN). The glutamate levels in VTA were correlated with the gradient distance between FPN and limbic network (LIM). The transcriptional profiles explained variance of the altered gradient pattern, with the most related genes enriched in synaptic signaling. Baseline cortical FCG significantly predicted craving changes after long-term abstinence.</div></div><div><h3>Conclusions</h3><div>We provided novel insights into the understanding of SUD as treatable health conditions from cortical FCG changes, which could be considered as the potential biomarkers of craving changes after prolonged abstinence for SUDs.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111391"},"PeriodicalIF":5.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918270","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":"Dopamine D3 receptor in the nucleus accumbens modulates opioid taking and seeking in mice","authors":"Meng-die Yang ,&nbsp;Xing-fang Cun ,&nbsp;Ning Wu,&nbsp;Jin Li,&nbsp;Rui Song","doi":"10.1016/j.pnpbp.2025.111389","DOIUrl":"10.1016/j.pnpbp.2025.111389","url":null,"abstract":"<div><div>Accumulating preclinical evidence suggests that selective antagonists of dopamine receptor D3 (Drd3) affects opioid-induced addictive behaviors across various animal models, highlighting Drd3 as a potential therapeutic target for opioid use disorders. However, the cellular type and neural circuit mechanisms by which Drd3 mediates these effects remains unclear. We employed YQA14, a selective antagonist and knock-out to selectively block or delete Drd3 in the nucleus accumbens (NAc) or ventral tegmental area (VTA). We utilized a battery of morphine-induced self-administration assays, fiber photometry, RNAscope in situ hybridization and RT-PCR to functionally characterize the roles of antagonists of Drd3s in the morphine actions. Our results revealed Drd3 mRNA expression in approximately 80 % of vesicular GABA transporter 1 (VGAT1)-positive GABA neurons in the NAc and approximately 50 % of tyrosine hydroxylase (TH)-positive dopamine neurons in the VTA. Strikingly, microinjections of YQA14 into the NAc, rather than the VTA, inhibited morphine taking and cue-induced drug-seeking. Transgenic down-regulation of Drd3 gene expression in the NAc yielded similar results. To explore the dopamine-dependent mechanism underlying Drd3's action, we found that intra-NAc microinjections of YQA14 significantly reduced morphine- or cue-induced activation of dopamine neurons in the VTA during morphine self-administration or cue-induced drug-seeking tests. These results suggest that YQA14 effectively reduces opioid taking and seeking, mainly by blocking Drd3 in the NAc, which subsequently inhibits VTA dopamine neuron activity and opioid action in dopamine transmission.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111389"},"PeriodicalIF":5.3,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918271","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 clinical outcomes based on cognitive and hippocampal clusters of first episode psychosis","authors":"Lucas A. Ronat ,&nbsp;Delphine Raucher-Chéné ,&nbsp;Katie M. Lavigne ,&nbsp;Mallar Chakravarty ,&nbsp;Ridha Joober ,&nbsp;Ashok Malla ,&nbsp;Jai Shah ,&nbsp;Martin Lepage","doi":"10.1016/j.pnpbp.2025.111392","DOIUrl":"10.1016/j.pnpbp.2025.111392","url":null,"abstract":"<div><h3>Background</h3><div>In first episode psychosis (FEP), cognitive impairments are core features contributing to clinical and functional heterogeneity. Significant impairment indicates greater clinical severity throughout the course of the illness, particularly for negative symptoms. Hippocampal volume is smaller in FEP than in healthy controls (notably subfields like Cornu Ammonis 1–3 and subiculum), and is related to cognitive impairments and negative symptoms. The aim of this study was to compare the clinical and functional trajectories of FEP subgroups as a function of cognitive performance and hippocampal volumes.</div></div><div><h3>Methods</h3><div>One hundred FEP patients and sixty healthy controls initially assessed using the CogState research battery, underwent 3 T MRI to extract hippocampal subfields and adjacent structures using the MAGeT brain algorithm. Clinical assessments were carried out for negative (Motivational and Pleasure – MAP, and diminished expression – EXP) and depressive symptoms, and global functioning. Measurements were taken at 4 time points (3, 9, 15, 21 months following program entry). Based on available first timepoint standardized cognitive and hippocampal features, using healthy controls as reference, clusters were determined by a hierarchical ascending classification. Their clinical and functional longitudinal trajectories were analyzed using linear mixed-effects models.</div></div><div><h3>Results</h3><div>Three baseline clusters were revealed: normal-range hippocampal volume with low attention, working and verbal memory (FEP 0), small hippocampus with low verbal memory and social cognition (FEP 1), and large hippocampus with low verbal memory (FEP 2). At baseline, the clusters did not differ on symptoms severity and global functioning. Longitudinally, MAP, EXP and depressive symptoms decreased over time in FEP 0. Global functioning improved in FEP 0 and FEP 1, while FEP 2 was clinically and functionally stable over time. Longitudinal inter-group comparisons did not yield any significant differences.</div></div><div><h3>Conclusion</h3><div>The clusters were dissociated between hippocampus and cognition, but their trajectories suggest the importance of hippocampal integrity in the clinical and/or functional outcome. Future studies are needed to understand intervention efficiency depending on hippocampal integrity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111392"},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143903669","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":"Neuroimaging pattern interactions for suicide risk in depression captured by ensemble learning over transcriptome-defined parcellation","authors":"Ting Wang ,&nbsp;Junneng Shao ,&nbsp;Rui Yan ,&nbsp;Zhongpeng Dai ,&nbsp;Cong Pei ,&nbsp;Wei Zhang ,&nbsp;Zhijian Yao ,&nbsp;Qing Lu","doi":"10.1016/j.pnpbp.2025.111390","DOIUrl":"10.1016/j.pnpbp.2025.111390","url":null,"abstract":"<div><h3>Background</h3><div>For suicide in major depression disorder, it is urgent to seek for a reliable neuroimaging biomarker with interpretable links to molecular tissue signatures. Accordingly, we developed an ensemble learning scheme over transcriptome-defined parcellations (TDP) to explore homogeneously parcellated brain patterns and their interactions.</div></div><div><h3>Methods</h3><div>96 depressed patients without suicide attempt (SA), 86 with SA and 102 healthy controls were recruited for resting state fMRI scanning. Six genetic dimensions were created by homogenous transcriptomic delineations from Allen Human Brain Atlas. Spatially-continuous TDPs were generated according to expression-levels of each brain region along diverse dimensions. Subsequently, TDPs were integrated with a three-layer ensemble learning scheme, where brain dysfunction of each TDP related to suicide was quantified with a resting-state functional abnormality (RSFA) score. Then, personalized index of brain dysfunction was produced according to the interactive pattern across TDPs.</div></div><div><h3>Results</h3><div>Ensemble learning over TDPs displayed higher suicide predictive performance, relative to that over the regions level, and over null model (95 % CI of accuracy: 73.23 ± 1.07 %; 64.59 ± 3.00 %; 65.41 ± 3.97 %, respectively). Empowered by specific parieto-occipital TDP (PO-TDP) pattern quantified with RSFA score in suicide risk prediction, its alternations of SA effects were spatially associated with transcriptional profiles of <em>GRIN2A</em> and <em>GABRG2</em>. Moreover, glutamatergic and GABAergic synapse were overrepresented in enrichment analysis.</div></div><div><h3>Conclusion</h3><div>Glutamatergic and GABAergic dysfunction in the visual cortex was suggested via the PO-TDP specific interaction pattern. The inherent excitatory/inhibitory imbalance could contribute to aberrant emotional processing and neurocognitive impairment, ultimately leading to suicide.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"139 ","pages":"Article 111390"},"PeriodicalIF":5.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907743","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}