Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Inter-subject functional variability of gray and white matter in autism spectrum disorder","authors":"Hairong Xiao ,&nbsp;Lina Yang ,&nbsp;Yingzhuo Wan ,&nbsp;Wei Zhao ,&nbsp;Shuixia Guo","doi":"10.1016/j.pnpbp.2025.111500","DOIUrl":"10.1016/j.pnpbp.2025.111500","url":null,"abstract":"<div><h3>Background</h3><div>Autism spectrum disorder (ASD) is biologically highly heterogeneous; however, most studies focused on group-level analyses, overlooking inter-subject variability in functional connectivity (IVFC), particularly in white matter IVFC (WM-IVFC) where mechanisms and genetic influences remain unclear.</div></div><div><h3>Methods</h3><div>Resting-state functional magnetic resonance imaging data from 272 patients with ASD and 368 typical controls (TC) were obtained from the Autism Brain Imaging Data Exchange Project (ABIDE II) database. Gray matter IVFC (GM-IVFC) and WM-IVFC were compared between groups and correlated with symptom severity. A support vector machine (SVM) model was constructed to assess the diagnostic potential of GM-IVFC, WM-IVFC, and their combination. Transcriptome neuroimaging analyses were conducted by correlating IVFC alterations with regional gene expression data from the Allen Human Brain Atlas.</div></div><div><h3>Results</h3><div>Both GM-IVFC and WM-IVFC showed regionally uneven distributions across the brain. Compared to TC, patients with ASD exhibited increased GM-IVFC mainly in the default mode and attention networks, and altered WM-IVFC mainly in the genu of the corpus callosum and superior fronto-occipital fasciculus, which were significantly associated with symptom severity. The SVM model utilizing both the GM-IVFC and WM-IVFC features yielded the best diagnostic performance (accuracy = 0.77). Transcriptome-neuroimaging associations revealed that GM-IVFC alterations were enriched in genes involved in sensory organ morphogenesis, whereas WM-IVFC alterations were linked to astrocyte-related pathways.</div></div><div><h3>Conclusions</h3><div>Our findings highlight the complementary roles of GM-IVFC and WM-IVFC, supporting their potential as biomarkers and offering novel insights into the genetic and neurobiological underpinnings of ASD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111500"},"PeriodicalIF":3.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088147","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":"Disentangling the role of tau pathology in autism spectrum disorders","authors":"Francisca Villavicencio-Tejo,&nbsp;Margrethe A. Olesen,&nbsp;M. Leonardo Moya,&nbsp;Rodrigo A. Quintanilla","doi":"10.1016/j.pnpbp.2025.111496","DOIUrl":"10.1016/j.pnpbp.2025.111496","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficient social interaction, altered communication, and repetitive, stereotyped behaviors. Pathologically, ASD is characterized by abnormal brain development, including dendritic spine and axonal alterations, which are both associated with synaptic plasticity disturbances. Microtubules (MT) and microtubule-associated proteins (MAPs) are critical in regulating brain development by the neuronal cytoskeleton and synaptic formation. Tau is a neuronal MAP protein in which pathological posttranslational modifications (PTMs) are involved in the pathogenesis of neurodegenerative diseases (NDs), including Alzheimer's disease (AD). In this context, accumulative evidence suggests that tau is altered in mouse models and human patients of ASD. Toxic tau modifications like hyperphosphorylation, a disruptor of MTs dynamics, produced alterations in ASD, suggesting that the imbalance of this protein may contribute to neurodevelopmental deficiencies produced during ASD.</div><div>In this systematic review, we revised essential evidence suggesting that the dysregulation of cytoskeletal components produced by tau pathology could play a crucial role in the pathological and behavioral changes produced in ASD.</div><div>Finally, we will focus on discussing how the presence of tau pathology in ASD contributes to brain development impairment and whether pathological forms of tau could be suggested as a novel biomedical strategy to support the diagnosis of this disorder.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111496"},"PeriodicalIF":3.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082109","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":"Comparative proteome analysis of dried blood spots for high-risk group screening in children with autism spectrum disorder","authors":"Taeyeop Lee ,&nbsp;Jiyoung Yu ,&nbsp;Hee Sung Ahn ,&nbsp;Jeonghun Yeom ,&nbsp;Yerin Hyun ,&nbsp;Ju Yeon Kim ,&nbsp;Jeongyeon Hong ,&nbsp;Jung-Yoon Yoo ,&nbsp;Kyunggon Kim ,&nbsp;Hyo-Won Kim","doi":"10.1016/j.pnpbp.2025.111499","DOIUrl":"10.1016/j.pnpbp.2025.111499","url":null,"abstract":"<div><h3>Objective</h3><div>Reliable biomarkers that assist in the diagnosis of autism spectrum disorder (ASD) are limited. This study aimed to identify proteins that can differentiate children with ASD from controls.</div></div><div><h3>Methods</h3><div>A total of 30 children with ASD and 30 control children participated in the study. Psychological tests and questionnaires to assess cognitive function, adaptive function, autism symptoms, and behavioral problems were administered. Dried blood spots collected from the participants were analyzed using the SWATH LC-MS platform. Core proteins were identified to build a classifying model to predict ASD and control group status.</div></div><div><h3>Results</h3><div>Among the 849 proteins quantified, 33 candidate proteins were identified by combining two different algorithms. Candidate proteins were involved in biological pathways related to the skin, muscle functioning, immune system, and cytoskeleton organization. Of the candidate proteins, we selected 7 core proteins that overlapped between different algorithms. The core proteins, PSME1, two isoforms of TPM1, two isoforms of TPM3, S100A6, and TBCA, were negatively correlated with the Childhood Autism Rating Scale, Aberrant Behavior Checklist, and Social Responsiveness Scale, and positively correlated with the Full-scale Intellectual Quotient. Furthermore, a logistic regression model with the core proteins predicted the ASD group with an area under the curve (AUC) of 0.956, sensitivity of 0.967, and specificity of 0.867.</div></div><div><h3>Conclusion</h3><div>We performed a proteomic analysis of dried blood spot (DBS) from ASD and control group children to explore candidate biomarkers. Our data supports the possibility of using proteins as potential biomarkers for ASD, although further verification is warranted in an independent cohort.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111499"},"PeriodicalIF":3.9,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145071275","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":"Neurodevelopmental deviations in schizophrenia: Evidences from multimodal connectome-based brain ages","authors":"Yun-Shuang Fan ,&nbsp;Pengfei Yang ,&nbsp;Yucheng Zhu ,&nbsp;Wenfeng Jing ,&nbsp;Yuting Xu ,&nbsp;Yong Xu ,&nbsp;Jing Guo ,&nbsp;Fengmei Lu ,&nbsp;Mi Yang ,&nbsp;Wei Huang ,&nbsp;Huafu Chen","doi":"10.1016/j.pnpbp.2025.111498","DOIUrl":"10.1016/j.pnpbp.2025.111498","url":null,"abstract":"<div><h3>Background</h3><div>Pathologic schizophrenia processes originate early in brain development, leading to detectable brain alterations via structural and functional magnetic resonance imaging (MRI). Recent MRI studies have sought to characterize disease effects from a brain age perspective, but developmental deviations from the typical brain age trajectory in youths with schizophrenia remain unestablished. This study investigated brain development deviations in early-onset schizophrenia (EOS) patients by applying machine learning algorithms to structural and functional MRI data.</div></div><div><h3>Methods</h3><div>Multimodal MRI data, including T1-weighted MRI (T1w-MRI), diffusion MRI, and resting-state functional MRI (rs-fMRI) data, were collected from 80 antipsychotic-naive first-episode EOS patients and 91 typically developing (TD) controls. The morphometric similarity connectome (MSC), structural connectome (SC), and functional connectome (FC) were separately constructed by using these three modalities. According to these connectivity features, eight brain age estimation models were first trained with the TD group, the best of which was then used to predict brain ages in patients. Individual brain age gaps were assessed as brain ages minus chronological ages.</div></div><div><h3>Results</h3><div>Both the SC and MSC features performed well in brain age estimation, whereas the FC features did not. Compared with the TD controls, the EOS patients showed increased absolute brain age gaps when using the SC or MSC features, with opposite trends between childhood and adolescence. These increased brain age gaps for EOS patients were positively correlated with the severity of their clinical symptoms.</div></div><div><h3>Conclusion</h3><div>These findings from a multimodal brain age perspective suggest that advanced brain age gaps exist early in youths with schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111498"},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058731","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-based subtypes of major depressive disorder in different sex and age groups: a potential link to sex hormone dynamics","authors":"Yuqun Zhang ,&nbsp;Jian Ouyang ,&nbsp;Xianhua Zhang ,&nbsp;Ju Gao ,&nbsp;Jialin Zhang ,&nbsp;Yonggui Yuan","doi":"10.1016/j.pnpbp.2025.111497","DOIUrl":"10.1016/j.pnpbp.2025.111497","url":null,"abstract":"<div><h3>Background</h3><div>Functional connectivity (FC) features serve as effective biomarkers to enhance the diagnostic and treatment of major depressive disorder (MDD). While sex hormones play a crucial role in MDD pathogenesis, neuroimaging signatures specifically linked to sex hormone fluctuations remain critically underexplored for MDD identification.</div></div><div><h3>Methods</h3><div>A dataset including 7316 participants with sex hormones and depression assessment was used to analyzed the relationships between depression and sex hormones across age and sex groups. Additionally, employing REST-meta-MDD dataset including 753 MDD patients, we established a novel graph classification framework based on multi-convolution network and attention pooling to identify MDD subtypes related to sex hormone dynamics</div></div><div><h3>Results</h3><div>MDD individuals of both sexes showed elevated estrogen levels than healthy controls (HC). Female MDD individuals also had higher testosterone levels than HC. Depressive symptoms differences between young and middle-aged MDD individuals were predominantly observed in females, whereas no significant age-related variations were detected in males. Our novel method achieved over 75 % accuracy in classifying young and middle-aged MDD patients. Discriminative features were mainly in the sensorimotor network for males and the cingulo-opercular network for females</div></div><div><h3>Conclusion</h3><div>These findings revealed that sex- and age-specific FCs were critically in identifying MDD subtypes, especially for female patients. The indirect association with lifelong sex hormone fluctuation suggests that future research should investigate sex hormone effects across age-sex dimensions rather than merely comparing imaging differences. Thus, this approach could advance personalized MDD diagnosis and clinical interventions</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111497"},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050225","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":"Augmentation with glutamatergic modulators for schizophrenia: A network meta-analysis","authors":"Chun-Wei Liang ,&nbsp;Hsiao-Yi Cheng ,&nbsp;Mei-Chih Meg Tseng","doi":"10.1016/j.pnpbp.2025.111495","DOIUrl":"10.1016/j.pnpbp.2025.111495","url":null,"abstract":"<div><div>This network meta-analysis evaluated the effects of glutamatergic modulators as augmentation treatments on schizophrenia. A systematic search of PubMed, Embase, Cochrane Library, and PsycInfo for randomized controlled trials was conducted until January 2025. A random-effects network meta-analysis was performed within a frequentist framework, and the certainty of evidence was evaluated using the GRADE approach. A total of 148 randomized controlled trials and 12,339 patients were included. Among add-on glutamatergic modulators with moderate to high certainty of benefit over placebo, piracetam 2400–4800 mg/day showed the greatest improvement in total psychopathology (standardized mean differences [SMD] −0.94, 95 % confidence interval [CI] −1.47 to −0.41), benzoate 1000–2000 mg/day was most effective for positive symptoms (SMD −0.43, 95 % CI −0.71 to −0.16), memantine 5–20 mg/day ranked highest for negative symptom reduction (SMD −0.64, 95 % CI −0.85 to −0.43), and the combination of sarcosine 2000 mg/day and benzoate 1000 mg/day showed the greatest enhancement in global cognitive function (SMD 1.08, 95 % CI 0.45 to 1.71). Other agents, including <span>d</span>-serine 2000–4000 mg/day, evenamide 30–60 mg/day, iclepertine 10–25 mg/day, lamotrigine, luvadaxistat 50 mg/day, minocycline 100–300 mg/day, <em>N</em>-acetylcysteine 2000 mg/day, sarcosine 2000 mg/day, and topiramate demonstrated benefits with moderate to high certainty in one or more domains. Notably, memantine, <em>N</em>-acetylcysteine, and sarcosine exhibited efficacy across multiple outcome domains. The effects of some novel agents within specific dose ranges on cognitive function improvement were also observed.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111495"},"PeriodicalIF":3.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058743","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":"Investigating ghrelin and its isoforms in eating disorders: a network meta-analysis","authors":"Cristiano Dani ,&nbsp;Sara Giachetti ,&nbsp;Matteo Mura ,&nbsp;Sara Tedesco ,&nbsp;Eleonora Rossi ,&nbsp;Emanuele Cassioli ,&nbsp;Livio Tarchi ,&nbsp;Nadia Micali ,&nbsp;Valdo Ricca ,&nbsp;Giovanni Castellini","doi":"10.1016/j.pnpbp.2025.111489","DOIUrl":"10.1016/j.pnpbp.2025.111489","url":null,"abstract":"<div><h3>Background</h3><div>Eating disorders (EDs) are serious psychiatric conditions disorders characterized by impairments in appetite regulation and energy balance. Among the biological factors implicated in their pathophysiology, the orexigenic hormone ghrelin and its isoforms (acyl-ghrelin [AG] and desacyl-ghrelin [DAG]) have been shown to play a key role in appetite regulation and may contribute to the maintenance of disordered eating behaviors.</div></div><div><h3>Methods</h3><div>A systematic review of existing literature and meta-analysis were conducted, including 80 studies examining fasting blood levels of ghrelin, AG, and DAG across various ED diagnostic categories and healthy controls (HC), including also individuals with recovered AN (AN-rec). A network meta-analysis (NMA) approach through a multilevel linear mixed-effects meta-regression model was employed to estimate hormone levels, while accounting for covariates such as body mass index (BMI), sex, blood composition and assay type.</div></div><div><h3>Results</h3><div>Ghrelin levels were significantly elevated in individuals with anorexia nervosa (AN) and bulimia nervosa (BN) when compared to HC, while binge eating disorder (BED) was associated with lower ghrelin levels than individuals with BN and HC. AG and DAG levels were significantly elevated in individuals with AN compared to HC, and confirmed higher in AN-rec if compared to HC. No significant differences in ghrelin, AG and DAG levels were observed for avoidant/restrictive food intake disorder (ARFID).</div></div><div><h3>Conclusions</h3><div>This meta-analysis highlighted significant differences in the levels of ghrelin and its isoforms across various ED subgroups and HC, emphasizing their potential roles in the pathophysiology of these disorders, in a perspective of potential targeted therapeutic implications.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111489"},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145050625","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":"Targeting mitochondrial dysfunction in Alzheimer's disease: New findings and perspectives","authors":"Authors: Jana Hroudová ,&nbsp;Zdeněk Fišar","doi":"10.1016/j.pnpbp.2025.111491","DOIUrl":"10.1016/j.pnpbp.2025.111491","url":null,"abstract":"<div><div>Alterations in mitochondrial energy metabolism, impaired processes of mitochondrial dynamics and mitophagy have recently been identified as important contributors to the pathophysiology of Alzheimer's disease (AD). Genetic predispositions and defects in mitochondrial metabolism, particularly within the electron transport chain of the oxidative phosphorylation system, have been linked to the pathology of intracellular and extracellular amyloid-beta (Aβ) and tau protein. This review summarizes the current molecular background of AD and explains the relationships between genetic factors, impaired energy metabolism, and the formation of pathological proteins. It highlights altered mitochondrial dynamics, impaired mitochondrial signaling, mitophagy, neuroinflammation, and apoptosis. Based on these findings, the review discusses mitochondrial biomarkers and novel molecules targeting mitochondrial dysfunction in the pathophysiology of AD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111491"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042451","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":"Childhood maltreatment-related cortical structural differences between treatment-naïve early adults with major depressive disorder and healthy controls","authors":"Azi Shen ,&nbsp;Yinghong Huang ,&nbsp;Haowen Zou ,&nbsp;Qinghua Zhai ,&nbsp;Wenyue Gong ,&nbsp;Yiwen Wang ,&nbsp;Kaiyu Shi ,&nbsp;Moxuan Song ,&nbsp;Qiudong Xia ,&nbsp;Zhijian Yao ,&nbsp;Qing Lu ,&nbsp;Rui Yan","doi":"10.1016/j.pnpbp.2025.111488","DOIUrl":"10.1016/j.pnpbp.2025.111488","url":null,"abstract":"<div><h3>Objectives</h3><div>Childhood maltreatment (CM) is a known risk factor for major depressive disorder (MDD) and significantly impacts brain structure, although it is noteworthy that some trauma-exposed individuals do not subsequently develop clinical depression. This study investigates the interaction effects of CM and MDD on morphology of cerebral cortex in early adults.</div></div><div><h3>Methods</h3><div>This study employed a 2 (MDD vs. Healthy controls) × 2 (CM: Yes vs. No) with vertex-wise general linear models to investigate differential neuroanatomical effects of CM on cortical morphology across diagnostic groups. Complementary region-of-interest (ROI) analyses focused on the medial prefrontal cortex given its established role in emotional stress processing and regulation.</div></div><div><h3>Results</h3><div>Whole-brain vertex-wise analysis revealed that in the MDD group, individuals with a history of CM exhibited significantly reduced bilateral precuneus volume and left cuneus thickness compared to those without CM. Conversely, in the HC group, individuals with CM showed increased bilateral precuneus cortical volume and left cuneus thickness. ROI analysis showed CM-exposed HC had greater cACC thickness, whereas MDD patients exhibited reduced trends. In the HC group, significant positive correlations emerged between left cuneus thickness and physical neglect, left precuneus volume and emotional neglect, and right precuneus volume and sexual abuse. In the MDD group, a significant negative correlation was found between right precuneus volume and disease course.</div></div><div><h3>Conclusion</h3><div>These findings suggest that CM induces cortical abnormalities in individuals with MDD, whereas HC may demonstrate neuroadaptive responses to early adversity, identifying potential neurobiological markers of vulnerability or resilience to MDD following CM.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111488"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042383","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":"Apomorphine susceptibility and prenatal infection alter neurodevelopment, synaptic density and anticipatory behavior in rats","authors":"Kate Witt ,&nbsp;Meyrick Kidwell ,&nbsp;Janine Doorduin ,&nbsp;Erik.F.J. de Vries ,&nbsp;Iris E. Sommer ,&nbsp;Darren J. Day ,&nbsp;Bart A. Ellenbroek ,&nbsp;Cyprien G.J. Guerrin","doi":"10.1016/j.pnpbp.2025.111490","DOIUrl":"10.1016/j.pnpbp.2025.111490","url":null,"abstract":"<div><div>Schizophrenia is a complex psychiatric disorder, driven by genetic and environmental factors. While individual risk genes have limited impact, polygenic susceptibility increases the likelihood of schizophrenia and heightens sensitivity to environmental stressors, such as prenatal immune activation. Yet, preclinical studies often focused on single-gene mutations, leaving polygenic influences largely unexplored. Using the apomorphine-susceptible (APO-SUS) rat model, which exhibits schizophrenia-like features, we investigated how polygenic susceptibility influences early neurodevelopment, synaptic density, and behavior, and how these effects are modulated by prenatal immune activation. APO-SUS rats demonstrated early neurodevelopmental abnormalities, including a reduced number and duration of separation-induced ultrasonic vocalizations (USVs), increased principal frequency of USVs, and reduced heart rate variability (HRV), indicative of heightened sympathetic dominance commonly seen in psychiatric disorders. These effects were particularly pronounced in females. Male APO-SUS rats exhibited elevated synaptophysin levels, a presynaptic marker for synaptic density, in the frontal cortex during adolescence and in the hippocampus during adulthood. Interestingly, prenatal immune activation counteracted some of these changes, preventing HRV reduction and normalizing synaptophysin levels. Male and female APO-SUS rats, as well as Wistar male rats exposed to prenatal immune activation, showed anticipatory behavior during adolescence, but not in adulthood. Our results suggest that polygenic susceptibility induces early neurodevelopmental changes and that genetic and environmental risk factors do not always act synergistically; sometimes counterbalancing each other. Future studies should explore how early neurodevelopmental changes, such as alterations in USVs and HRV, influence later behavioral outcomes in polygenic models of schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111490"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145027713","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}