Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Astrocyte alterations and dysfunction in alcohol use disorder: A comprehensive scoping review of clinical postmortem and preclinical evidence","authors":"Emma Nadler ,&nbsp;Stephen J Kish ,&nbsp;Junchao Tong ,&nbsp;Anh Dzung Lê ,&nbsp;Isabelle Boileau","doi":"10.1016/j.pnpbp.2025.111509","DOIUrl":"10.1016/j.pnpbp.2025.111509","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) is a prevalent mental health condition associated with numerous comorbidities and health complications. Astrocytes are vital glial cells that are essential in maintaining homeostasis and responding to injury. Dysregulation of astrocytic function has been implicated in various disorders, including AUD, but the specific effects of alcohol and AUD on astrocytes remain unclear. This scoping review synthesizes evidence on alterations in astrocyte morphology and astrocytic protein expression in AUD and preclinical models. Post-mortem investigations are limited to a few brain regions and report no overall changes in the astrocyte protein, glial fibrillary acidic protein (GFAP) in AUD. In preclinical models, GFAP levels are elevated, particularly following periods of alcohol abstinence. In contrast, morphological changes in astrocytes are minimal following periods of alcohol abstinence and most notable with continuous ethanol exposure. Overall, convincing evidence of classically reactive astrocytes is lacking across paradigms. This review also highlights the lack of clinical research and sex-based analyses in the field. Future work should focus on in vivo PET imaging and employ more comprehensive measures of astrocyte function in multiple brain regions. A better understanding of astrocytic involvement in AUD could inform future research and therapeutic interventions, ultimately alleviating the disorder's burden.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111509"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234086","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":"Psilocybin-assisted psychotherapy in adults with depression – A literature review","authors":"Marie Celine Dorczok ,&nbsp;Gloria Mittmann ,&nbsp;Thomas Ettl ,&nbsp;Verena Steiner-Hofbauer","doi":"10.1016/j.pnpbp.2025.111508","DOIUrl":"10.1016/j.pnpbp.2025.111508","url":null,"abstract":"<div><h3>Background</h3><div>Psilocybin-Assisted Psychotherapy (PAP) has gained increasing attention in recent years as a potential treatment for depression, particularly in cases resistant to conventional therapies. This article aims to assess the efficacy of PAP in adults with various forms of depression by conducting a comprehensive review of the available literature.</div></div><div><h3>Method</h3><div>A systematic search was conducted across several major databases (PubMed and Ebsco Host (incl. MEDLINE Ultimate, eBook Clinical Collection, DynaMed, APA PsycARTICLES, APA PsycINFO, Psychology &amp; Behavioral Sciences Collection), focusing on studies that investigated the effects of psilocybin in a therapeutic setting.</div></div><div><h3>Results</h3><div>The overall systematic literature search identified 139 items, of which seven were selected for detailed analysis. The studies employed different dosing regimens and varied in their methodologies of psychological support before, during, and after psilocybin administration. Most studies found significant improvements in depression symptoms after administration of Psilocybin and sustained antidepressant effects up to twelve months post-treatment. Response and remission rates were consistently high across studies.</div></div><div><h3>Conclusions</h3><div>PAP combined with structured psychological support shows sustained reductions in depressive symptoms for treatment-resistant depression and major depressive disorder. Higher doses generally yield stronger benefits. While PAP holds significant potential as a holistic treatment, methodological limitations, such as heterogeneity in study designs, inconsistent levels of psychological support and difficulties in blinding due to the nature of the drug's effect, highlight the need for more standardized protocols in future studies to ensure reliable outcomes. More research is needed to better understand the mechanisms underlying its therapeutic effects.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111508"},"PeriodicalIF":3.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151987","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":"New frontier for epilepsy treatment through targeting cellular senescence","authors":"Stephen Temitayo Bello ,&nbsp;Md. Rajdoula Rafe ,&nbsp;Fengwen Huang","doi":"10.1016/j.pnpbp.2025.111506","DOIUrl":"10.1016/j.pnpbp.2025.111506","url":null,"abstract":"<div><div>Epilepsy is a life-threatening brain disorder that affects about 1–2 % of the world's population. Various mechanisms facilitating epilepsy development and seizure propagation have been identified. Nevertheless, an improved understanding of the cellular mechanisms that underlie epilepsy development is necessary for designing better therapeutic strategies for epilepsy treatment. Cellular senescence, a cellular mechanism wherein cell growth is permanently halted and causes cells to exit the proliferative pool, has been associated with neurological disorders such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and epilepsy. How the various mechanisms that drive a cell towards senescence and the phenotypes that characterize senescent cells are associated with the development and progression of epilepsy might be necessary in improving our understanding of epilepsy. Therefore, this review discusses the mechanisms and pathways associated with cellular senescence and how senescence-associated secretory phenotype (SASP) promotes inflammation and tissue dysfunction. We then explained how different types of cells, including brain cells, become senescent, the inter-relationship between cellular senescence and epilepsy, and potential biomarkers common to epilepsy and cellular senescence. Finally, we reviewed the use of senolytics and senomorphics for epilepsy treatment. Further research can, therefore, be directed towards a thorough understanding of cellular senescence in epilepsy development, and this can open new frontiers for epilepsy treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111506"},"PeriodicalIF":3.9,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139389","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":"Behavioural effects of shoaling on nicotine place preference in zebrafish","authors":"L. Rocco,&nbsp;R. Bernabeu","doi":"10.1016/j.pnpbp.2025.111502","DOIUrl":"10.1016/j.pnpbp.2025.111502","url":null,"abstract":"<div><div>Nicotine activates the brain's reward systems leading to addiction. Zebrafish exhibit social behaviours, such as shoaling, making them an attractive model for investigating how social interactions influence behaviour. Here, we assessed the rewarding effects of nicotine on zebrafish shoaling behaviour, examined whether the shoal influences the rewarding properties of nicotine. To study shoaling behaviour under drug exposure, we compared nicotine at 15 and 50 mg/L as a reinforcer and a social stimulus through Pavlovian conditioning. Visual interaction of individual zebrafish with a shoal during conditioning or the CPP test was sufficient to decrease nicotine-CPP, spending more time closer to the shoal. We then examined the effect of the shoal during conditioning. When fish were conditioned as a group, 15 mg/L of nicotine induced a positive CPP, but 50 mg/L did not. No evidence of anxiety or stress was found. At 50 mg/L, the distance between zebrafish in the shoal increased, indicating a relaxed behaviour. To better characterize this effect, we exposed the fish to phenylbutyrate (PhB) (an HDAC inhibitor) known to reduce nicotine-CPP. In zebrafish conditioned in a shoal, 15 mg/L of nicotine inhibited CPP, but 50 mg/L did not, with reduced interfish distances. Our results indicate that the social environment, such as the presence of a shoal, can influence nicotine preference in zebrafish, which is significant for understanding social influences on addiction in vertebrates, including humans.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111502"},"PeriodicalIF":3.9,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092942","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":"Sex differences in endocannabinoid and inflammatory markers associated with posttraumatic stress disorder","authors":"Therese A. Rajasekera ,&nbsp;Anna Joseph ,&nbsp;Hui Pan ,&nbsp;Jonathan M. Dreyfuss ,&nbsp;Doruntina Fida ,&nbsp;Julia C. Wilson ,&nbsp;Madeline Behee ,&nbsp;Raina N. Fichorova ,&nbsp;Resat Cinar ,&nbsp;Primavera A. Spagnolo","doi":"10.1016/j.pnpbp.2025.111501","DOIUrl":"10.1016/j.pnpbp.2025.111501","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD), a severe psychiatric disorder that predominantly affect women, is characterized by heightened inflammation and perturbations of the stress-buffering endocannabinoid system. However, whether these alterations contribute to PTSD pathophysiology in both men and women is largely unknown. This case-control study examined sex-differences in circulating levels of endocannabinoids (eCBs) and pro-inflammatory markers in a cohort of individuals with PTSD and non-psychiatric controls.</div><div>Eighty-eight patients with PTSD and 85 sex- and age- matched healthy controls (HCs) were retrospectively selected from the Mass General Brigham Biobank. Serum samples were assayed to measure circulating levels of eCBs [<em>N</em>-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), and arachidonic acid (AA)] and pro-inflammatory markers [interleukin-1β (IL-1β), IL-6, IL-8, IL-18, tumor necrosis factor-alpha (TNF-α), and C-reactive Protein (CRP)].</div><div>Our results showed distinct molecular profiles based on sex and PTSD diagnosis. Male PTSD patients exhibited decreased levels of AEA, AA and OEA compared to both male controls (<em>p's &lt; 0.001 to 0.05</em>) and to the female subgroups (PTSD and HCs) (<em>p &lt; 0.01</em>). In contrast, female PTSD patients showed elevated levels of IL-6 and IL-8 compared to the other subgroups (<em>p's</em> &lt; 0<em>.010</em>), although only a trend-level effect in IL-6 levels persisted when examining the magnitude of group differences (PTSD <em>vs</em> HCs) across sexes. Similar results were obtained after controlling for the <em>FAAH</em> 385 A genotype and in the subgroup of individuals with comorbid MDD.</div><div>These findings suggest that distinct neurobiological mechanisms may underlie PTSD in men and women and highlight the need for sex-based therapeutic approaches.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111501"},"PeriodicalIF":3.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088167","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":"Cognitive and psychotic effects of ketamine \"short- vs. long-term\" therapy in a rat model of depression: Hippocampal TrkB/Akt/GSK-3β/mTOR/autophagy trajectories.","authors":"Safaa K Aref, Mohamed Z Habib, Dalia M Eid, Eman H Eltantawy, Mohamed Taeimah, Fatma E Hassan, Dina Aly El-Gabry, Heba Hamed Elshahawi, Magda I Mohamad, Ahmed M Abdel-Tawab, Sawsan Aboul-Fotouh","doi":"10.1016/j.pnpbp.2025.111503","DOIUrl":"10.1016/j.pnpbp.2025.111503","url":null,"abstract":"<p><p>Accumulating evidence indicates the role of ketamine as a rapid-onset antidepressant, with a rising controversy regarding its cognitive and psychotic effects, especially with long-term use. However, no previous experimental study has directly compared short-term and long-term ketamine effects using a time schedule that simulates infusion protocols in major depressive disorder patients. This study investigated the short- versus long-term antidepressant, cognitive, and psychotic effects of ketamine (10 mg/kg), with an emphasis on hippocampal mechanistic cascades in a chronic unpredictable stress (CUS) rat model of depression. Both short- and long-term ketamine administration improved CUS-induced depressive-like behaviors and HPA axis activity markers. Short-term ketamine did not elicit significant cognitive changes, whereas in the long-term study, ketamine impaired rats' performance in the novel object recognition test, suggesting a potential exacerbation of the CUS-induced cognitive deficits. However, in the Morris water maze's probe trial, CUS-exposed animals exhibited a trend of cognitive improvement, which was dampened by chronic administration of ketamine. Furthermore, ketamine significantly increased stereotypic behaviors, an important phenotype of psychotic behavior. Interestingly, ketamine enhanced hippocampal expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), phosphorylated protein kinase B (p-Akt), phosphorylated glycogen synthase kinase-3β (p-GSK-3β), phosphorylated mechanistic target of rapamycin (p-mTOR), deactivated Unc-51-like autophagy activating kinase 1 (ULK1), and synapsin I, while decreasing phosphorylated eukaryotic elongation factor 2 (p-eEF2), autophagy markers (Beclin-1 and LC3), caspase-3, p-tau, and oxidative/nitrosative stress markers, reflecting the amendment of the CUS-induced disturbed synaptogenesis, autophagy, and tauopathy. This is the first study to highlight the potential cognitive impairments and psychotic behaviors associated with long-term ketamine administration despite its favorable effect on depressive-like symptoms and the implication of the BDNF/TrkB/Akt/GSK-3β/mTOR/autophagy mechanistic cascade in ketamine-induced enhancement of neuronal survival and synaptogenesis.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111503"},"PeriodicalIF":3.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088139","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 preconceptional social isolation on risk-taking behaviour and levels of neurochemical, neuroendocrine and neuroinflammatory markers in male offspring","authors":"Maria Bove ,&nbsp;Vladyslav Sikora ,&nbsp;Stefania Dimonte ,&nbsp;Lisa Pia Agosti ,&nbsp;Martina Santoro ,&nbsp;Maria Adelaide Palmieri ,&nbsp;Paolo Tucci ,&nbsp;Maria Grazia Morgese ,&nbsp;Luigia Trabace ,&nbsp;Stefania Schiavone","doi":"10.1016/j.pnpbp.2025.111504","DOIUrl":"10.1016/j.pnpbp.2025.111504","url":null,"abstract":"<div><div>The impact of chronic stress during the preconceptional period on the adolescent progeny has been poorly investigated. Although impulsivity and risk-taking behaviour are physiological during adolescence, they may represent key symptoms of psychiatric conditions of this life period.</div><div>Here, we evaluated the possible development of risk-taking behaviour and cognitive dysfunctions in the male offspring of socially isolated female rats, housed in control or isolation conditions (as second stressful hit) from weaning to adolescence. Underlying neurochemical, neuroendocrine and neuroinflammatory alterations were also assessed.</div><div>Increased distance travelled, time spent in the centre of an open field arena and in the open arms of an elevated plus maze were detected in the adolescent offspring of socially isolated females, together with reduced time spent in the wall, decreased latency time in the passive avoidance task and reduced discrimination index in the novel object recognition test. Elevations in glutamate levels, reduction of GABA concentrations, enhanced GLU/GABA ratio and expression of GFAP and CD11beta, as well as reduced NGF amount, were found in the prefrontal cortex of adolescent rats born from females exposed to social isolation before pregnancy. This same group showed a significant decrease of plasmatic oxytocin levels and enhanced vasopressin and prolactin concentrations, compared to controls.</div><div>In conclusion, our results point toward a detrimental effect of female exposure to chronic social stress during preconception in inducing risk-taking behaviour in the adolescent male offspring, possibly via alterations of neurochemical, neuroinflammatory and neuroendocrine pathways, thus identifying adolescence as a specific window for preventive and therapeutic approaches.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111504"},"PeriodicalIF":3.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088099","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":"Fluoxetine ameliorates affective- and pain-related responses in adult zebrafish","authors":"Julia Canzian ,&nbsp;Rossano M. Silva ,&nbsp;Khadija A. Mohammed ,&nbsp;Cássio M. Resmim ,&nbsp;Falco L. Gonçalves ,&nbsp;Kimberly Fontoura ,&nbsp;Camilla W. Pretzel ,&nbsp;Mariana L. Muller ,&nbsp;Hevelyn S. Moraes ,&nbsp;Barbara D. Fontana ,&nbsp;Fabiano V. Costa ,&nbsp;Carla D. Bonan ,&nbsp;Denis B. Rosemberg","doi":"10.1016/j.pnpbp.2025.111505","DOIUrl":"10.1016/j.pnpbp.2025.111505","url":null,"abstract":"<div><div>Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), increases serotonin levels in the brain and modulates affective behaviors and pain. Developing reliable animal models to investigate the effects of fluoxetine across these domains is critical. The zebrafish (<em>Danio rerio</em>) represents a valuable vertebrate model in the field due to the well-characterized behavioral responses and conserved serotonergic system, making suitable for investigating the role of serotonin in emotion and nociception. Here, we investigated whether fluoxetine modulates behavioral phenotypes closely resembling those found in affective disorders and pain in adult zebrafish. To modulate affective domains, para-chlorophenylalanine (pCPA) was administrated for 2 consecutive days to induce increase in anxiety and depressive-like behaviors, followed by an acute fluoxetine exposure. Secondly, the protective effects of fluoxetine were tested in the acetic acid model. We found that fluoxetine reduced anxiety- and depressive-like phenotypes, as well as prevented pain-related behaviors in zebrafish. Importantly, correlations between anxiety- and despair-related phenotypes were observed, supporting the existence of distinct behavioral associations across groups. Overall, our results highlight the novelty of testing fluoxetine across multiple behavioral domains in zebrafish, reinforcing beneficial effects on affective disorders and pain response. We also reinforce the practical advantages of this aquatic species to explore the relieving properties of fluoxetine, as well as to understand the neurobiological bases involved in different behavioral phenotypes and associated therapeutic targets.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111505"},"PeriodicalIF":3.9,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088085","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":"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}