Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"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":"2025-10-02","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":"Oral guanfacine treatment ameliorates the ADHD-like symptoms caused by developmental manganese exposure","authors":"Ellie Fisher ,&nbsp;Stephane A. Beaudin ,&nbsp;Barbara J. Strupp ,&nbsp;Donald R. Smith","doi":"10.1016/j.pnpbp.2025.111517","DOIUrl":"10.1016/j.pnpbp.2025.111517","url":null,"abstract":"<div><div>Epidemiological studies have linked developmental manganese (Mn) exposure to increased risk of ADHD and related symptoms in children and adolescents. Rodent model studies have 1) confirmed causality by demonstrating that developmental Mn exposure can cause lasting ADHD-like symptoms, 2) revealed that these symptoms (in Mn-exposed animals) are accompanied by a hypofunctioning catecholaminergic system in fronto-cortical-striatal brain areas, and 3) demonstrated that methylphenidate is efficacious in ameliorating these ADHD-like symptoms in Mn-exposed animals. However, stimulant medications such as methylphenidate do not lessen symptoms in 25–30 % of children and adolescents diagnosed with ADHD, indicating the need for alternative ADHD medications. Guanfacine, a specific noradrenergic α_2A receptor agonist, has proven to be an effective non-stimulant ADHD medication, although it is unknown whether this drug is effective in treating the ADHD-like symptoms produced by developmental Mn exposure. The present study was designed to test this hypothesis. Additionally, due to the pharmacological specificity of guanfacine, its use may provide mechanistic insight into the role of noradrenergic dysfunction as a contributor to the Mn-induced impairments. Male Long-Evans neonatal rats were orally dosed with vehicle or Mn (50 mg Mn/kg/d) from postnatal day 1–21, and orally treated with guanfacine (0, 0.1, or 0.3 mg/kg/d) during behavioral testing as adults. The results revealed that developmental Mn exposure produced lasting impairments in impulse control, attention, and sensorimotor function, and that oral guanfacine was efficacious in ameliorating the Mn-induced impairments in all three functional domains, although the treatment duration needed for efficacy varied by functional domain. In addition, in control (unexposed) animals, there was little or no effect of guanfacine on any functional domain. There was also little effect of the drug in the Mn-exposed animals under trial conditions where Mn deficits did not emerge. These findings 1) demonstrate the efficacy of oral guanfacine to ameliorate the lasting ADHD-like symptoms caused by developmental Mn exposure, and 2) provide additional support for the hypothesis that hypofunctioning of the noradrenergic system contributes to these lasting Mn deficits. Collectively, these findings suggest that individuals with environmentally-induced ADHD, such as that induced by developmental Mn exposure, may benefit from oral guanfacine treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111517"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245277","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":"Changing your mind: neuroplastic mechanisms underlying the therapeutic effect of psychedelics in depression, PTSD, and addiction","authors":"Marta Palhas,&nbsp;Rémi Corne,&nbsp;Raymond Mongeau","doi":"10.1016/j.pnpbp.2025.111533","DOIUrl":"10.1016/j.pnpbp.2025.111533","url":null,"abstract":"<div><div>After years of restrictions due to concerns about their potentially harmful effects, research on psychedelics has entered a new era. Increasing attention has been directed toward their immense therapeutic potential, particularly for psychiatric disorders. Pre-clinical and clinical studies have consistently demonstrated that psychedelic treatments produce therapeutic effects within hours of administration, with these effects persisting well beyond their elimination by the organism, hinting at the involvement of neuroplasticity-related mechanisms. This review explores these putative mechanisms, from receptor activation to neuronal and behavioral changes. Among the most studied psychedelics, serotonergic psychedelics and ketamine appear to share common cellular mechanisms. They both recruit glutamatergic neurons to stimulate BDNF-trKB signaling, which promotes synaptogenesis via the mTOR pathway. These changes may explain their efficacy in diseases such as depression, anxiety, PTSD, and addiction. On the other hand, ibogaine exerts its effects primarily through GDF-mediated mechanisms which may underly its beneficial effect in addiction. Finally, MDMA, a therapeutic agent for PTSD, presents a paradox: while it influences synaptogenesis via 5-HT2A-dependant effects on BDNF, it appears to have deleterious effects on neurotrophic signaling in the hippocampus, impacting plasticity differently. Although the modulation of the neurotrophic system by psychedelics clearly contributes to the reduction of depressive symptoms, its role in PTSD and addiction remains less well understood. A better understanding of the downstream pathways activated by neurotrophins may help refine therapeutic approaches and enhance outcomes for individuals with these conditions. Future research should elucidate the precise mechanisms by which psychedelics exert their effects on psychiatric and substance use disorders to fully utilize their therapeutic potential while ensuring safe and effective integration into clinical practice.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111533"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356801","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":"2025-10-02","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":"Neural correlates of abnormal regional functional efficiency in major depressive disorder: a large, multi-scale study","authors":"Keke Fang ,&nbsp;Baohong Wen ,&nbsp;Liang Liu ,&nbsp;Ya Tian ,&nbsp;Huiting Yang ,&nbsp;Shaoqiang Han ,&nbsp;Xianfu Sun ,&nbsp;Lianjie Niu","doi":"10.1016/j.pnpbp.2025.111537","DOIUrl":"10.1016/j.pnpbp.2025.111537","url":null,"abstract":"<div><div>Whether patients with major depressive disorder (MDD) are associated with abnormal regional functional efficiency (RFE) remain unknown. This study aimed to investigate the abnormal RFE pattern and its neural correlates in MDD using a large, multi-site cohort. We calculated voxel-wise RFE from resting-state functional magnetic resonance imaging data of 1265 MDD patients and 1094 matched healthy controls (HCs). Raw RFE values were transformed into W-scores using a normative model and then compared between MDD and HC groups. We validated the reproducibility of the group differences through leave-one-site-out and subsample validation approaches. Additionally, we examined the associations between the abnormal RFE pattern and clinical features, as well as neurotransmitter receptor/transporter profiles derived from a public positron emission tomography-based atlas. Our results showed that MDD was associated with increased RFE in the cerebellum, thalamus, bilateral dorsolateral prefrontal cortex, and the middle and inferior frontal gyrus, while decreased RFE was observed in the posterior cingulate, precuneus, postcentral gyrus, and fusiform gyrus. This abnormal pattern demonstrated high spatial similarity with validation results, indicating reproducibility. Early-onset MDD patients exhibited reduced RFE in the bilateral ventromedial prefrontal cortex, bilateral insula, left putamen, right caudate, and angular gyrus, alongside increased RFE in the cerebellum anterior lobe, cuneus, and precuneus compared to middle-to-late onset patients. Furthermore, the abnormal RFE pattern in MDD showed significant associations with neurotransmitter receptor/transporter profiles, particularly GABA_a and mGluR₅, suggesting a molecular basis for these findings. These results highlight abnormal regional functional efficiency and its neural correlates in MDD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111537"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363616","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 involvement of the endogenous opioid system in binge eating, food devaluation and food reward in mice","authors":"Iffat Hasnin Era,&nbsp;Abdul Hamid,&nbsp;Kabirullah Lutfy","doi":"10.1016/j.pnpbp.2025.111539","DOIUrl":"10.1016/j.pnpbp.2025.111539","url":null,"abstract":"<div><div>The endogenous opioid system is known to regulate both homeostatic and hedonic aspects of feeding behavior. In particular, the mu-opioid receptor (MOR) plays a central role in modulating palatable food intake and reward processing. This study investigated the contributions of MORs, and the two potential peptides, i.e., beta-endorphin (β-END), and enkephalin (ENK), acting on MORs in binge eating, food reward, and food devaluation using genetically modified mice. First, male mice lacking MORs and their wildtype littermates were tested for regular chow diet (RCD) and high fat diet (HFD) intake for 24 h each and tested for binge eating 4 weeks later. We found no change in RCD or HFD intake during the first exposure between mice of the two genotypes but mice lacking MORs showed reduced binge eating on a subsequent HFD exposure. Additionally, these mice showed diminished RCD devaluation after a 7-day HFD exposure to HFD. Furthermore, MORs knockout mice failed to exhibit any reward after conditioning with HFD. To explore which opioid peptide mediates these behaviors, mice lacking β-END or ENK and their wildtype controls were tested for binge eating, food devaluation and food reward. Mice lacking β-END displayed reduced binge eating and diminished food reward, but food devaluation remained unchanged. In contrast, mice lacking ENK exhibited no significant alterations in any of these responses. These findings demonstrate that MORs play a critical role in binge eating, food reward, and food devaluation, while β-END specifically contributes to binge eating and food reward. Enkephalins, however, appear to have minimal influence on these behaviors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111539"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363614","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":"Psychostimulants and the cerebellum: Does the cerebellum get involved in the abuse of methamphetamine and cocaine?","authors":"Fatemeh Darvishzadeh-Mahani ,&nbsp;Soodeh Rajabi ,&nbsp;Maryam Alehashem ,&nbsp;Hojjatallah Alaei ,&nbsp;Effat Ramshini","doi":"10.1016/j.pnpbp.2025.111479","DOIUrl":"10.1016/j.pnpbp.2025.111479","url":null,"abstract":"<div><div>Clinical evidence suggests that the cerebellum is one of the brain areas most vulnerable to the effects of psychostimulants. Functional neuroimaging studies support the idea that the cerebellum is involved in the neural circuits affected by these drugs. The cerebellum plays a vital role in the brain's reward mechanisms, working in conjunction with the striatum, ventral tegmental area (VTA), and prefrontal cortex (PFC). The cerebellum plays a crucial role in processing rewards and associated emotions. Research indicates that the cerebellum serves as a central hub for regional disconnection during different mood states. This suggests that mental disorders, including mood disorders and substance use disorders, are linked to the circuitry of the cerebellum. This review provides a comprehensive overview of the brain regions affected by methamphetamine (METH) and cocaine, compiling both clinical and animal evidence regarding the involvement of the cerebellum in the abuse of these drugs. We analyze the effects of METH and cocaine on the cerebellum, detailing the resulting changes in various areas, including imaging, molecular, structural, and functional alterations. By exploring the cerebellum's role in the abuse of METH and cocaine, we can improve our understanding of the underlying mechanisms associated with these substances.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111479"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979087","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":"2025-10-02","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":"The effect of sertraline and voluntary exercise during pregnancy on litter characteristics and postpartum affective behaviour in rat dams","authors":"Noor S. Jarbou ,&nbsp;Olivia Mairinger ,&nbsp;Elise Kulen ,&nbsp;Lucas Mushahwar ,&nbsp;Samara Walpole ,&nbsp;Jasmine Matthews ,&nbsp;Simon Maksour ,&nbsp;Katrina Weston-Green ,&nbsp;Mirella Dottori ,&nbsp;Kelly A. Newell","doi":"10.1016/j.pnpbp.2025.111520","DOIUrl":"10.1016/j.pnpbp.2025.111520","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Sertraline is the frontline pharmacotherapy for the treatment of depression and anxiety during pregnancy. However, there is little evidence regarding the effects of sertraline on maternal behaviour or the maternal brain. Furthermore, the efficacy of non-pharmacological approaches to treatment in pregnancy, such as exercise, are unclear. Therefore, the aim of this study was to examine the effects of sertraline and exercise during pregnancy on maternal postpartum depressive-like, anxiety-like and associated behaviours, as well as litter characteristics, in a rat model of depression. We also investigated the effects of these treatments on the maternal brain, focusing initially on DNA methylation and glutamatergic markers, which have been implicated in depression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;Twenty-four female Wistar-Kyoto (WKY; strain that models depression and anxiety) rats were divided into three groups: 1. WKY-Sertraline; 2. WKY-Exercise, 3. WKY-Vehicle; Six female Wistar (WIS) rats were included as controls. Rats were treated with sertraline (10 mg/kg) or vehicle (33 % propylene glycol) twice/day, from gestational day (GD) 1 to postpartum day 14. The WKY-Exercise group were provided access to a running wheel during pregnancy for 3 h/day from GD1–18. Dam and litter characteristics, as well as pup ultrasonic vocalisations (USVs), were measured. Dams underwent behavioural testing at 5-weeks postpartum to assess depressive-, anxiety- and cognitive-like behaviours. Gene expression of DNA methylation markers (&lt;em&gt;Dnmt1, Dnmt3a&lt;/em&gt;) and glutamate receptors (&lt;em&gt;Grin1, Grin2a, Grin2b&lt;/em&gt;) were measured in the prefrontal cortex (PFC), using RT-qPCR.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Result&lt;/h3&gt;&lt;div&gt;The WKY-Sertraline group gained 39 % less weight in their first pregnancy week compared to all other groups (&lt;em&gt;p&lt;/em&gt; &lt; 0.05) and produced smaller litters compared to WIS controls (−43 %; &lt;em&gt;p&lt;/em&gt; = 0.003) and WKY-Exercise (−38 %; &lt;em&gt;p&lt;/em&gt; = 0.012); WKY-Sertraline pups had slightly smaller brain weights compared to WKY-Vehicle (&lt;em&gt;p&lt;/em&gt; = 0.031). WKY-Vehicle pups showed reduced number of USV calls, call amplitude and call duration compared to WIS control (&lt;em&gt;p&lt;/em&gt; &lt; 0.001). The WKY-Exercise pups produced increased number of USVs, with increased call amplitude of USVs, at postnatal day (PN)7 compared to WKY-Vehicle (&lt;em&gt;p&lt;/em&gt; &lt; 0.01). Maternal sertraline treatment did not significantly affect dam postpartum behavioural measures, or maternal cortical gene expression. The WKY-Exercise group however showed reduced anxiety-like behaviours, spending more time in the open arms (620 %; &lt;em&gt;p&lt;/em&gt; = 0.027) and less time in the closed arms (−22 %; &lt;em&gt;p&lt;/em&gt; = 0.047) of the elevated plus maze (EPM) compared to WKY-Vehicle, and more time in the centre of the open field test (OFT) compared to WKY-Vehicle (132 %; &lt;em&gt;p&lt;/em&gt; = 0.057). Furthermore, WKY-Exercise dams showed a 64 % increase in &lt;em&gt;Dnmt3a&lt;/em&gt; mRNA levels in the PF","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111520"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276648","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":"Impaired deviance detection as the core psychopathological mechanism of schizophrenia","authors":"Yi Fan Zhang ,&nbsp;Michiel Spape ,&nbsp;Yu-Tao Xiang ,&nbsp;Kuzma Strelnikov","doi":"10.1016/j.pnpbp.2025.111516","DOIUrl":"10.1016/j.pnpbp.2025.111516","url":null,"abstract":"<div><div>Understanding the core psychopathological mechanism of schizophrenia is crucial for its diagnosis and treatment. In this article, we update the evidence for our previous proposal that the core of neurocognitive dysfunctions in schizophrenia is the impairment of deviance detection. We discuss the dysfunction of the <em>N</em>-methyl-<span>d</span>-aspartate (NMDA) receptors in schizophrenia, which resembles that induced by ketamine and leads to a reduced mismatch negativity in electroencephalography (EEG), and we demonstrate that the genetic findings and structural changes in the brain associated with schizophrenia correspond to impaired deviance detection as the core cognitive impairment. In a broader psychopathological perspective, this impairment disrupts the interaction between predictive and evidence-based mechanisms of speech processing in the brain, which may help elucidate the emergence of core symptoms such as delusions and hallucinations. Furthermore, we discuss how disruptions in deviance detection contribute to negative symptoms and significantly hinder everyday functioning and autonomy in individuals with schizophrenia.</div><div>Integration of numerous findings into this model provides compelling evidence that impaired deviance detection is a prominent contributor to the manifestation of symptoms and the pathological progression of this psychiatric condition. We suggest that targeting the core cognitive deficiency, that of deviance detection may enhance psychological and pharmacological approaches to diagnose and rehabilitate schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111516"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145240263","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}