Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Targeting neurochemical and immune dysregulation in schizophrenia: From molecular mechanisms to emerging therapeutic strategies","authors":"Aastha Datta ,&nbsp;Himani Rana,&nbsp;Shareen Singh ,&nbsp;Thakur Gurjeet Singh","doi":"10.1016/j.pnpbp.2025.111535","DOIUrl":"10.1016/j.pnpbp.2025.111535","url":null,"abstract":"<div><div>Schizophrenia is a multifaceted neuropsychiatric condition marked by a diverse array of symptoms, which can be categorized into positive, negative, and cognitive deficits. The underlying pathophysiology of this disorder is complex, involving a variety of mechanisms such as the dysregulation of neurotransmitter systems, neuroinflammatory responses, and neuronal dysfunction induced by oxidative stress. These interrelated processes lead to synaptic and neuronal impairments, which ultimately result in the clinical manifestations observed in patients with schizophrenia. The challenge of elucidating the molecular mechanisms that contribute to schizophrenia is significant, given the disorder's intricate and multifactorial characteristics. Neuroinflammatory pathways, such as those involving NF-κB, MAPK/ERK, kynurenine pathway and the activation of the NLRP3 inflammasome, play a significant role in promoting oxidative stress, synaptic dysfunction, and neuronal injury, which in turn aggravate cognitive and negative symptoms associated with schizophrenia. Although current pharmacological treatments primarily focus on dopamine and glutamate systems, their limited effectiveness in alleviating cognitive and negative symptoms highlights the necessity for a deeper mechanistic understanding of the disorder at the molecular level. Progress in neurobiological research, particularly concerning inflammatory pathways, mitochondrial dysfunction, and synaptic plasticity, is essential for the development of more targeted and effective therapeutic strategies for schizophrenia. This review underscores the critical need for a deeper understanding of molecular insights and treatment methodologies in the context of schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111535"},"PeriodicalIF":3.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370590","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 electroencephalographic potentials evoked by words as markers of the severity of the pathology and resistance to treatment in obsessive-compulsive disorder.","authors":"Issa Wassouf ,&nbsp;Nicolas Vibert ,&nbsp;Julien Dampuré ,&nbsp;Damien Doolub ,&nbsp;Ghina Harika-Germaneau ,&nbsp;Nicolas Langbour ,&nbsp;Nematollah Jaafari","doi":"10.1016/j.pnpbp.2025.111530","DOIUrl":"10.1016/j.pnpbp.2025.111530","url":null,"abstract":"<div><div>Patients suffering from obsessive-compulsive disorder (OCD) show an attentional bias towards pathology-related words. Electroencephalographic cognitive potentials were used to investigate how patients responded to words related to their obsessions and compulsions. Forty OCD patients with various levels of severity and treatment-resistance were included to assess links between word-evoked potentials and patients' clinical variables, and compared with 40 control participants. The P200 component evoked by both neutral and pathology-related words was greater in patients than in controls, suggesting that patients were more attentive overall. In the N400 time window, pathology-related words evoked less negative potentials than neutral words in OCD patients, suggesting that pathology-related words were particularly familiar to them and permanently pre-activated in their mental lexicon. Finally, correlations were detected between pathology severity and the profile of word-evoked potentials in the N400 time window, and between the patients' treatment resistance and the amplitude of late word-evoked positive potentials (P600).</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111530"},"PeriodicalIF":3.9,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370484","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":"Adverse event reporting and management in psilocybin therapy clinical trials: A systematic review to guide clinical and research protocol development","authors":"Danielle Bukovsky ,&nbsp;Aron Amaev ,&nbsp;Jianmeng Song ,&nbsp;Shannen Kyte ,&nbsp;Edgardo Carmona-Torres ,&nbsp;Fumihiko Ueno ,&nbsp;Vincenzo Deluca ,&nbsp;Antonio P. Strafella ,&nbsp;Muhammad I. Husain ,&nbsp;Ariel Graff-Guerrero ,&nbsp;Philip Gerretsen","doi":"10.1016/j.pnpbp.2025.111541","DOIUrl":"10.1016/j.pnpbp.2025.111541","url":null,"abstract":"<div><div>Psilocybin, a psychedelic prodrug, has gained renewed interest for its potential to treat various psychiatric disorders, including depression, anxiety, and substance use disorders. While promising, concerns remain regarding its safety profile and the management of potential adverse events (AEs). This systematic review aimed to evaluate the incidence, nature, and severity of adverse events and serious adverse events (SAEs) associated with psilocybin use across diverse clinical populations.</div><div>A comprehensive search was conducted across MEDLINE, Embase, and APA PsycInfo via the OVID platform, from database inception to June 5, 2024. A total of 42 clinical studies (<em>N</em> = 1068 participants) met inclusion criteria, all of which reported on AEs and/or SAEs following psilocybin administration. All studies were deemed to have a high risk of bias due to concerns regarding blinding. We synthesized information on common, uncommon, and SAEs, instances of suicidal ideation, methods of measuring AEs, and AEs requiring medical intervention. Reported AEs included headache, transient increases in blood pressure, and nausea, which typically resolved on their own. In rare instances, medical intervention was required. SAEs were reported infrequently in 2 of 42 studies and were limited to participants with underlying depressive disorders (e.g., suicidal behaviour, hospitalization).</div><div>Overall, psilocybin appears to have a favourable safety profile when administered in controlled settings. Based on our findings, we provide an outline of commonly reported AEs, uncommon AEs, SAEs, and considerations for future clinical and research protocols.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111541"},"PeriodicalIF":3.9,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370534","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 disruption and autism phenotypes in slc6a3−/− zebrafish: Behavioural and molecular insights","authors":"Wen Li ,&nbsp;Xiaocong Zhang ,&nbsp;Xiaoyu Niu ,&nbsp;Nan Qin ,&nbsp;Lulu Kang ,&nbsp;Kai Wang ,&nbsp;Mingyong Wang","doi":"10.1016/j.pnpbp.2025.111528","DOIUrl":"10.1016/j.pnpbp.2025.111528","url":null,"abstract":"<div><div>Dopamine plays a crucial role in regulating movement, motivation, attention, and emotions. Disruptions in dopamine metabolism have been linked to various psychiatric disorders, including autism spectrum disorder (ASD). In this study, we generated an <em>slc6a3</em> knockout zebrafish model using the CRISPR-Cas9 system to investigate the relationship between dopamine dysfunction and autism. Our results revealed that <em>slc6a3</em> knockout significantly reduced dopamine levels, leading to impaired dopamine synthesis, transport, and metabolism. Behavioural analysis demonstrated that <em>slc6a3</em>−/− zebrafish exhibited decreased motor activity, increased anxiety-like behaviour, and autism-related symptoms, such as impaired social ability and “digging” behaviour. Pharmacological intervention with risperidone and clozapine improved motor function, social interaction, and anxiety levels, with risperidone showing superior effects. Transcriptomic analysis identified significant changes in several nervous system-related genes in <em>slc6a3</em>−/− zebrafish, suggesting that these gene alterations may contribute to the observed behavioural abnormalities. Our study highlights the crucial role of dopamine dysfunction in autism and establishes <em>slc6a3</em>−/− zebrafish as a valuable model for studying autism and screening potential therapeutic drugs.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"143 ","pages":"Article 111528"},"PeriodicalIF":3.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310021","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 possible effect of fentanyl on PTSD","authors":"Yehudit O. Weiss Schonberg ,&nbsp;Leehe Peled-Avron","doi":"10.1016/j.pnpbp.2025.111519","DOIUrl":"10.1016/j.pnpbp.2025.111519","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a severe mental health disorder that appears as a result of trauma exposure and adversely affects the daily life and well-being of those who suffer from it. Major risk factors for PTSD include serving as a combat soldier and having traumatic and painful injuries. This review aims to investigate the possible beneficial effects of fentanyl on PTSD, and the possible theoretical mechanisms at the base of these effects. Fentanyl is a powerful analgesic from the opioid family that is often administered in cases of painful injuries, both as a prehospital battlefield treatment and at the hospital. Morphine, another opioid used for analgesia in similar situations, was shown to help both with the prevention and treatment of PTSD. Only a few studies examine the direct influence of fentanyl on PTSD, but there is evidence that indirectly suggests that fentanyl can treat or prevent PTSD via three mediating factors. In this review we suggest three possible hypotheses. In one possible route, the influence of fentanyl on PTSD is mediated by pain relief. Fentanyl was found to effectively reduce pain, and a positive correlation between pain level and PTSD severity was also found. The second route suggests that fentanyl's influence on PTSD is mediated by the activity of the vagus nerve. There is evidence that fentanyl administration results in vagal activity and that the activation of the vagus nerve reduces PTSD levels. A third possible route may be through fentanyl's activation of opioid receptors in limbic region which were found to have protective effects against PTSD. Future research of fentanyl's role in PTSD prevention and treatment is essential, and should account for pre-existing mental health struggles, TBI, delirium, and injury severity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111519"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276605","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":"Differential effects of psilocybin and lisuride on serotonin and dopamine neuronal activity and behavior","authors":"Brandon Richardson ,&nbsp;Antonio Inserra ,&nbsp;Michael Pileggi ,&nbsp;Thomas Prud’Homme ,&nbsp;Vitor Bruno ,&nbsp;Derek Wan-Yan-Chan ,&nbsp;Ilia Shareghi-Ghahreman ,&nbsp;Sofia Nasini ,&nbsp;Tadhg Strand ,&nbsp;Marco Leyton ,&nbsp;Nahum Sonenberg ,&nbsp;Danilo De Gregorio ,&nbsp;Jeffrey Sprouse ,&nbsp;Francis R. Bambico ,&nbsp;Gabriella Gobbi","doi":"10.1016/j.pnpbp.2025.111522","DOIUrl":"10.1016/j.pnpbp.2025.111522","url":null,"abstract":"<div><div>Psilocybin and lisuride are 5-HT_2A receptor agonists, but only psilocybin elicits the head twitch response (HTR) in rodents, a behavior commonly used as a proxy for hallucinogenic activity. This study aimed to compare their effects on serotonin (5-HT) and dopamine (DA) neuronal activity, as well as related behavioral outcomes, to elucidate the mechanisms underlying their divergent effects. Adult male C57BL/6N mice were administered intraperitoneal injections of psilocybin (0.3–3 mg/kg), lisuride (0.1–0.5 mg/kg), or vehicle. <em>In vivo</em> electrophysiological recordings were performed in the dorsal raphe nucleus (DRN) and substantia nigra (SN) to monitor 5-HT and DA neuronal firing. MDL 100907 (0.2 mg/kg) pretreatment was used to determine 5-HT_2A receptor specificity. Behavioral assessments included HTR testing 10 min post-injection, followed by either the forced swim test (FST), open field test (OFT), or elevated plus maze (EPM) at 20 min post-injection. Psilocybin-induced inhibition, but not lisuride-induced inhibition, of 5-HT neuron firing was blocked by MDL 100907. Both drugs reduced DA neuron firing, however, lisuride's effect was more sensitive to 5-HT_2A receptor antagonism. Psilocybin elicited HTR, while lisuride did not. In the FST, only high-dose lisuride reduced immobility time. Both drugs reduced locomotor activity in the OFT and EPM. Principal Component Analysis (PCA) sufficiently separated the effects of each drug from each other, indicating distinct effect profiles. Although both drugs target 5-HT_2A receptors, they engage distinct neurobiological pathways. Psilocybin produces psychedelic-like, 5-HT–dominant effects, whereas lisuride displays DA-linked improvements in coping behavior, informing future development of serotonergic therapeutics.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111522"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281804","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":"Neurogliovascular unit adaptations following chronic distress predict motivational deficits in mice","authors":"Lidia Cabeza ,&nbsp;Damien Mor ,&nbsp;Bahrie Ramadan ,&nbsp;Guillaume Benhora-Chabeaux ,&nbsp;Christophe Houdayer ,&nbsp;Emmanuel Haffen ,&nbsp;Yvan Peterschmitt ,&nbsp;Adeline Etievant ,&nbsp;Fanchon Bourasset","doi":"10.1016/j.pnpbp.2025.111510","DOIUrl":"10.1016/j.pnpbp.2025.111510","url":null,"abstract":"<div><div>The neurogliovascular unit (NGVU) reflects the complex interplay between neural tissue and blood flow. Dysfunction in this NGVU system is involved in neuropsychiatric disorders, however, whether the alterations are a cause or consequence of these conditions remains unclear. This study investigates the role of NGVU adaptations in motivational deficits associated with depressive episodes, focusing on blood vessel structural changes and blood-brain barrier (BBB) permeability. We used brain samples from adult male C57BL/6jRj mice that were chronically treated with corticosterone (CORT), and which presented severe motivational deficits in an operant progressive ratio task, along with altered neural activation in brain regions involved in motivational processing (anterior insular cortex, basolateral amygdala, bed nucleus of the stria terminalis and ventral tegmental area), as assessed by FosB expression. NGVU modifications were first evaluated through immunofluorescence staining for microglia (IBA-1), endothelial tight junctions (ZO-1), and astrocytes (GFAP). BBB permeability was assessed using intravenous perfusion of fluorescent 40 kDa Dextran. Principal component analysis revealed that NGVU alterations in the ventral tegmental area and basolateral amygdala predicted motivational deficits in CORT-treated mice. Specifically, ZO-1 expression was downregulated, and Dextran extravasation was increased in these regions. These findings suggest that NGVU adaptations induced by chronic CORT exposure impact BBB integrity and are integral to understanding behavioural performance. In conclusion, NGVU modifications may play a key role in the cognitive and behavioural dysfunction seen in neuropsychiatric disorders, highlighting their relevance in the biological substrate of these conditions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111510"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180064","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":"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":"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}