Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Investigating the disconnection between cytokine and symptom clusters in clinical high risk populations: Towards a comprehensive cross-dimensional analysis","authors":"TianHong Zhang ,&nbsp;LiHua Xu ,&nbsp;YanYan Wei ,&nbsp;XiaoChen Tang ,&nbsp;MingLiang Ju ,&nbsp;XiaoHua Liu ,&nbsp;Dan Zhang ,&nbsp;HaiChun Liu ,&nbsp;ZiXuan Wang ,&nbsp;Tao Chen ,&nbsp;Jin Gao ,&nbsp;Qiang Hu ,&nbsp;LingYun Zeng ,&nbsp;ZhengHui Yi ,&nbsp;ChunBo Li ,&nbsp;JiJun Wang","doi":"10.1016/j.pnpbp.2025.111356","DOIUrl":"10.1016/j.pnpbp.2025.111356","url":null,"abstract":"<div><h3>Objective</h3><div>Clustering individuals at the Clinical High-Risk(CHR) stage of psychosis often relies on single dimensions, and the independence or overlap of clustering results across different dimensions lacks sufficient evidence. Additionally, it remains unclear whether combining different dimensions—such as biological markers(e.g., cytokines) and symptomatic dimensions—can enhance predictive efficacy.</div></div><div><h3>Methods</h3><div>This study included 370 individuals with CHR and conducted a three-year follow-up, 50 CHR individuals transitioned to psychosis. The participants underwent thorough symptom assessments, encompassing both clinical symptoms and cognitive impairments. Baseline measurements of eight cytokines were obtained. Latent Class Analysis(LCA) was employed to construct clusters based on both symptom profiles and cytokine levels separately. Survival analysis was utilized to explore differences in conversion rates among different clusters.</div></div><div><h3>Results</h3><div>The LCA determined the selection of the four-cluster solution for symptoms, cytokines, and the integrated clusters. Symptom-Cluster-2 exhibited the most severe clinical symptoms and cognitive impairments, while Symptom-Cluster-4 displayed the mildest clinical symptoms and cognitive impairments. Cytokine-Cluster-1 was characterized by the highest levels of inflammatory cytokines, excluding vascular endothelial growth factor, whereas Symptom-Cluster-4 exhibited the lowest levels of cytokines. The clusters identified based on symptoms and cytokines showed substantial inconsistency. Survival analysis comparing conversion rates across four clusters revealed no significant difference in symptom(<em>χ</em>^<em>2</em> = 6.731, <em>p</em> = 0.081) and cytokine(<em>χ</em>^<em>2</em> = 7.139, <em>p</em> = 0.068) clusters but was significant in integrated clusters(<em>χ</em>^<em>2</em> = 9.234, <em>p</em> = 0.026).</div></div><div><h3>Conclusion</h3><div>The study emphasizes the distinct perspectives on psychosis risk offered by symptom and cytokine dimensions, advocating for the integration of these dimensions in a cross-modal approach to enhance predictive accuracy.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111356"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747327","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":"Abnormal intrinsic functional network connectivity in adolescent major depressive disorder related to severity of insomnia","authors":"Weijie Bao ,&nbsp;Yingxue Gao ,&nbsp;Ruohan Feng ,&nbsp;Xue Li ,&nbsp;Hailong Li ,&nbsp;Lingxiao Cao ,&nbsp;Zilin Zhou ,&nbsp;Mengyue Tang ,&nbsp;Yingying Wang ,&nbsp;Lihua Zhuo ,&nbsp;Hongwei Li ,&nbsp;Xinqin Ouyang ,&nbsp;Xinyue Hu ,&nbsp;Guoping Huang ,&nbsp;Xiaoqi Huang","doi":"10.1016/j.pnpbp.2025.111357","DOIUrl":"10.1016/j.pnpbp.2025.111357","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Insomnia is closely associated with depression and plays a critical role in its development. Investigating insomnia-related neuroimaging changes in depression could enhance understanding of the neural mechanisms underlying depression insomnia. However, the brain network mechanism underlying the bidirectional relationship between depression and insomnia in adolescents remains unknown.</div></div><div><h3>Methods</h3><div>We recruited 83 drug-naïve adolescents with MDD and classified them into high- (HI-aMDD) and low-insomnia (LI-aMDD) groups based on the Hamilton Depression Rating Scale sleep subscale. Static and dynamic functional network connectivity (FNC) were analyzed in 34 HI-aMDD, 49 LI-aMDD patients, and 59 gender-matched healthy controls (HCs) using independent component analysis. Partial correlation analysis examined the links between FNC differences and clinical variables.</div></div><div><h3>Results</h3><div>The HI-aMDD patients showed decreased static FNC between the cerebellum network (CeN) and both the dorsal attention (DAN) and frontoparietal networks (FPN) and decreased dynamic CeN-DAN/limbic FNC, compared to both HCs and LI-aMDD. The LI-aMDD patients exhibited decreased static CeN-DAN/FPN connectivity and decreased dynamic CeN-DAN connectivity compared to HCs. These network connectivity alterations were negatively related to insomnia symptoms in the aMDD group.</div></div><div><h3>Conclusion</h3><div>Our study revealed graded static and dynamic CeN-DAN functional connectivity associated with insomnia severity in aMDD patients. High-insomnia aMDD patients showed unique dynamic interactions between CeN and limbic network, highlighting critical neural pathways involved in depression-related insomnia. These findings suggest that cerebellum, dorsal attention and limbic networks may be specifically involved in the pathophysiology of insomnia in adolescent depression and provide new potential treatment targets.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111357"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796933","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":"Evidence for independent actions of the CRF and ghrelin systems in binge-like alcohol drinking in mice","authors":"Rani S. Richardson ,&nbsp;Lindsay A. Kryszak ,&nbsp;Janaina C.M. Vendruscolo ,&nbsp;George F. Koob ,&nbsp;Lorenzo Leggio ,&nbsp;Leandro F. Vendruscolo","doi":"10.1016/j.pnpbp.2025.111341","DOIUrl":"10.1016/j.pnpbp.2025.111341","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) and binge drinking are highly prevalent public health issues. Both ghrelin and corticotrophin-releasing factor (CRF) drive stress responses and alcohol drinking. Despite evidence of a relationship between the ghrelin and CRF systems, their potential interaction in modulating alcohol drinking is unclear. We tested the effect of a brain-penetrant CRF₁ receptor antagonist (R121919) and a peripherally restricted nonselective CRF receptor antagonist (astressin) on plasma ghrelin levels. We also tested effects of R121919 and astressin alone and combined with the growth hormone secretagogue receptor (GHSR; the ghrelin receptor) antagonist JMV2959 and GHSR antagonist/inverse agonist PF-5190457 in a model of binge-like alcohol drinking in male and female C57BL/6 J mice. The intraperitoneal administration of R121919 but not astressin increased plasma ghrelin levels. R121919 but not astressin reduced binge-like alcohol drinking. CRF receptor antagonism had no effect on the ability of GHSR blockers to reduce alcohol drinking. No sex × drug treatment interactions were observed. These findings suggest that while both CRF receptor antagonism and GHSR antagonism reduce alcohol drinking, these two pharmacological approaches may not interact to mediate binge-like alcohol drinking in mice. Additionally, these results provide evidence that GHSR but not peripheral endogenous ghrelin may be key in driving binge-like alcohol drinking.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111341"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732878","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":"Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis","authors":"María Flores-López ,&nbsp;Jesús Herrera-Imbroda ,&nbsp;Nerea Requena-Ocaña ,&nbsp;Nuria García-Marchena ,&nbsp;Pedro Araos ,&nbsp;Julia Verheul-Campos ,&nbsp;Juan Jesús Ruiz ,&nbsp;Antoni Pastor ,&nbsp;Rafael de la Torre ,&nbsp;Antonio Bordallo ,&nbsp;Francisco Javier Pavón-Morón ,&nbsp;Fernando Rodríguez de Fonseca ,&nbsp;Antonia Serrano","doi":"10.1016/j.pnpbp.2025.111350","DOIUrl":"10.1016/j.pnpbp.2025.111350","url":null,"abstract":"<div><div>Substance use disorder (SUD) is a major global public health challenge, frequently co-occurring with psychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD). Endocannabinoid system (ECS) dysregulation has been implicated in both SUD and ADHD, but the interplay between these conditions remains poorly understood. This study investigates plasma concentrations of endocannabinoid-congeners in individuals with SUD, with and without comorbid ADHD, to identify potential biomarkers.</div><div>This exploratory study included 469 participants divided into three groups: (1) healthy controls (<em>n</em> = 136), (2) patients with SUD without ADHD (<em>n</em> = 267), and (3) patients with SUD and comorbid ADHD (<em>n</em> = 66). Plasma concentrations of 12 endocannabinoid-related molecules, including acylglycerols (2-AG, 2-LG, 2-OG) and acylethanolamides (AEA, DEA, DHEA, DGLEA, LEA, OEA, PEA, POEA, and SEA), were quantified using high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). A multinomial Elastic Net regression model was applied to assess their biomarker potential.</div><div>Patients with SUD exhibited significantly lower plasma concentrations of 2-AG and 2-LG compared to controls, while most acylethanolamides were elevated, except for POEA and SEA. ADHD comorbidity was associated with lower concentrations of 2-AG, 2-LG, AEA, DGLEA, DHEA, and SEA, while PEA was elevated. Machine learning analysis identified AEA, OEA, PEA, and SEA as key biomarkers, achieving an accuracy of 72.1 % and an ROC-AUC of 0.77.</div><div>This study suggests distinct ECS alterations in SUD and comorbid ADHD, highlighting endocannabinoid-congeners as potential biomarkers. Future research should validate these findings in larger cohorts and explore ECS-targeted therapeutic interventions for dual-diagnosis populations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111350"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oleoylethanolamide effects on stress-induced ethanol consumption: A lipid at the crossroads between stress, reward and neuroinflammation","authors":"Sandra Montagud-Romero ,&nbsp;Macarena González-Portilla ,&nbsp;Susana Mellado ,&nbsp;Pedro Grandes ,&nbsp;Fernando Rodríguez de Fonseca ,&nbsp;María Pascual ,&nbsp;Marta Rodríguez-Arias","doi":"10.1016/j.pnpbp.2025.111365","DOIUrl":"10.1016/j.pnpbp.2025.111365","url":null,"abstract":"<div><div>The endocannabinoid system is involved in multiple drug-related behaviors and the transient increase in endogenous cannabinoids and endocannabinoid-like molecules contributes to healthy adaptation to stress exposure. Oleoylethanolamide (OEA) belongs to the N-acylethanolamines and interacts with the endocannabinoid system. In this study, we investigated the effect of systemic OEA treatment (10 mg/kg), before or after social defeat (SD), on ethanol self-administration (SA). Mice were divided into non-stressed (EXP) and stressed (SD) groups and randomly assigned to a treatment condition (control-CTRL, OEA or 10OEA). The EXP/SD-OEA group of mice received four doses of OEA before each SD encounter, while mice in the EXP/SD-10OEA group received a daily dose for 10 consecutive days following stress exposure. Three weeks after SD, mice were trained to self-administer a 20 % (vol/vol) ethanol solution. Upon extinction, a cue-induced reinstatement test was performed. Our results showed that both OEA treatments effectively prevented the stress-induced increase in ethanol consumption observed in defeated mice. No significant effects of OEA on relapse-like behavior were observed. Additionally, we found that animals exposed to OEA during SD encounters showed reduced nuclear factor kappa B (NF-κB) levels, suggesting an anti-inflammatory effect of OEA, while tumor necrosis factor (TNFα) gene expression decreased in defeated animals. In summary, these findings suggest that exogenously increasing OEA levels counteracts the adverse effects of stress on ethanol drinking while having some impact on inflammatory patterns.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111365"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843824","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 and age effects on prevalence of CYP2C19 and CYP2D6 Phenoconversion risk over time in patients with psychosis","authors":"Emma Y. De Brabander ,&nbsp;Nicole K. Leibold ,&nbsp;Thérèse van Amelsvoort ,&nbsp;Roos van Westrhenen","doi":"10.1016/j.pnpbp.2025.111363","DOIUrl":"10.1016/j.pnpbp.2025.111363","url":null,"abstract":"<div><div>Pharmacogenetics in psychiatry may have benefits for medication treatment success. However, medication regimes leading to drug-drug interactions and potential phenoconversion of actionable pharmacogenetic phenotypes challenge the application of pharmacogenetics. Although polypharmacy is common, its impact in patients with psychosis is understudied, even though these patients might benefit from pharmacogenetics-guided medication adjustment. Here, we investigated the impact of two pharmacogenes relevant in psychiatric practice, CYP2C19 and CYP2D6, and the effect of sex and age. Medication use and predicted occurrence of phenoconversion was examined in a sample of patients with psychosis over a period of approximately six years. Bayesian statistics were applied to examine longitudinal effects. Our results show that women used more medications, including CYP2C19 and CYP2D6 inhibitors and (actionable) substrates. No significant sex or age differences were found for phenoconversion of either enzyme. A sex-effect on CYP2C19 inhibitor use was found but appeared to be driven by weakly inhibiting oral contraceptives, which were reported only in women. The phenoconversion rate for both enzymes appeared to change over time, suggesting that phenoconversion is a dynamic state that may affect patients differently over their lifetime. To further improve treatment in this patient population, long-term and regular updated medication monitoring in (pharmacogenetic) research as well as application in practice are recommended.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111363"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829241","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":"Exploring the potential of psychedelic-assisted psychotherapy for moral injury: A scoping review","authors":"Viktoriia Kurkova (Виктория Куркова) ,&nbsp;Olga Winkler ,&nbsp;Andrew Greenshaw ,&nbsp;Rakesh Jetly ,&nbsp;Jennifer Swainson ,&nbsp;Kalee Lodewyk ,&nbsp;Parisa Saghafi ,&nbsp;Elizabeth Dennett ,&nbsp;Lisa Burback","doi":"10.1016/j.pnpbp.2025.111333","DOIUrl":"10.1016/j.pnpbp.2025.111333","url":null,"abstract":"<div><div>This scoping review addresses the need to comprehensively explore the potential of psychedelic-assisted psychotherapy (PAP) to facilitate recovery from moral injury. Moral injury (MI), characterized by profound psychological distress arising from morally challenging experiences, has garnered increased attention as a complex mental health concern with significant functional sequelae, especially in the context of post-traumatic stress disorder (PTSD). There is growing interest in exploring alternative therapeutic approaches, with psychedelics emerging as an exciting potential intervention, as moral injury impacts treatment resistance, suicidality, social isolation, and overall functioning. Ten studies were included from 11,734 publications. Studies utilized psilocybin, MDMA, or LSD. None focused specifically on moral injury. Diagnoses included PTSD, alcohol use disorder, insomnia, human Immunodeficiency virus-related demoralized men, barbiturate dependence, anxiety associated with life-threatening illness, major depression, and PTSD comorbid with generalized anxiety disorder, panic disorder, and borderline personality disorder. Studies reported rapid, increasing, and sustained self-compassion over time, alongside increases in self-forgiveness and self-acceptance, reduction in demoralization, and decreased drinking scores. Though in other diagnostic contexts, PAP has shown efficacy in addressing symptoms commonly associated with moral injury, particularly within the context of PTSD. It holds promise as an intervention for MI and requires further exploration.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111333"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671733","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 low-dose psilocybin on brain neurotransmission and rat behavior","authors":"Agnieszka Bysiek ,&nbsp;Adam Wojtas ,&nbsp;Izabela Szpręgiel ,&nbsp;Agnieszka Wawrzczak-Bargieła ,&nbsp;Marzena Maćkowiak ,&nbsp;Krystyna Gołembiowska","doi":"10.1016/j.pnpbp.2025.111347","DOIUrl":"10.1016/j.pnpbp.2025.111347","url":null,"abstract":"<div><div>Psilocybin has various therapeutic effects in mental and psychological disorders, including depression and mood disorders, obsessive-compulsive disorders, substance addiction and anxiety. Pharmacodynamic properties of psilocybin depend on doses used and time after administration. The psilocybin dose range varies depending on whether it is used therapeutically or for recreational purposes in humans, but most animal studies require larger doses to induce an effect on brain neurotransmission and animal behavior. The aim of this study was to investigate the effect of psilocybin on the release of cortical neurotransmitters and rat behavior when it was administered subcutaneously at doses of 0.1, 0.3 and 0.6 mg/kg. Psilocybin affected the release of dopamine, noradrenaline, serotonin and acetylcholine in the frontal cortex as measured by microdialysis in freely moving rats. Psilocybin increased the release of aminergic transmitters in a non-linear manner with the dose of 0.3 mg/kg being the weakest. Psilocybin also increased the release of γ-aminobutyric acid, but glutamate release was enhanced only for the first 2 h after drug injection and was followed by a decrease for the rest of the experimental period. In contrast to 25I-NBOMe, an agonist of 5-HT2A receptors, psilocybin did not produce hallucinogenic activity expressed as wet dog shakes and did not disrupt sensorimotor gating in the acoustic startle response test. Furthermore, psilocybin showed anxiolytic effect in the light dark box test 1 h after administration. It also modulated the hypothalamic-pituitary-adrenal axis activity as it transiently increased serum corticosterone level, decreased serotonin, but increased dopamine turnover rates in the hypothalamus and inhibited the content of noradrenaline and adrenaline in the adrenal glands. The changes in the neurotransmitter release seem to play a role in psilocybin behavioral effects. The lack of hallucinogenic activity and disruptive effect on sensorimotor gating by psilocybin lower doses indicates that psychotomimetic effects did not occur. Psilocybin in contrast to 25I-NBOMe, ketamine and MDMA did not produce oxidative damage of DNA in the frontal cortex and hippocampus. Thus, the single low doses of psilocybin may have some beneficial properties and fewer harmful effects.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111347"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744565","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 has a narrow therapeutic window as an antidepressant treatment","authors":"Lenka Seillier ,&nbsp;Barbora Čechová ,&nbsp;Alexandre Seillier ,&nbsp;Romana Šlamberová","doi":"10.1016/j.pnpbp.2025.111368","DOIUrl":"10.1016/j.pnpbp.2025.111368","url":null,"abstract":"<div><div>Psilocybin, a naturally occurring psychedelic compound in magic mushrooms, shows promise as a novel intervention with a single administration inducing rapid and long-lasting antidepressant effects. However, there are limited studies on the optimal dosing required for the beneficial effects of psilocybin given its side effects. To address this gap, we investigated in Wistar rats whether a single psilocybin administration (0.1, 0.32, 1.0, and 3.2 mg/kg) had antidepressant-like effects in the forced swim test (FST), a pro-social effect in the social interaction test (SIT), and the ability to alter pleasure using the sucrose preference test (SPT). We also examined the dose-response relationships of psilocybin on the head-twitch response (HTR), locomotor activity, body temperature, and weight gain. Furthermore, we explored whether the brain-derived neurotrophic factor (BDNF) levels in the hippocampus and prefrontal cortex (PFC) paralleled the behavioral changes observed after psilocybin. In the FST, psilocybin induced dose-dependent inverted-U-shaped responses with only the intermediate dose of 0.32 mg/kg producing short and long-term antidepressant-like effects. A similar pattern was observed for the SIT, the SPT, and the HTR. In contrast, the high doses of psilocybin (1.0 and 3.2 mg/kg), while deprived of anti-depressant-like activity, significantly reduced body temperature, locomotor activity, and body weight gain. BDNF levels in the hippocampus and PFC increased dose-dependently after psilocybin, but linearly suggesting a dissociation between high BDNF levels and the observed antidepressant-like behaviors. Our results indicated that there is a narrow window for the therapeutic potential of psilocybin, with 0.32 mg/kg effectively producing antidepressant-like effects without the accompanying adverse effects observed only at higher doses.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111368"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143879281","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":"Chemogenetic attenuation of PFC pyramidal neurons restores recognition memory deficits following adolescent NMDA receptor blockade","authors":"Hagar Bauminger ,&nbsp;Sailendrakumar Kolatt Chandran ,&nbsp;Hiba Zaidan ,&nbsp;Irit Akirav ,&nbsp;Inna Gaisler-Salomon","doi":"10.1016/j.pnpbp.2025.111359","DOIUrl":"10.1016/j.pnpbp.2025.111359","url":null,"abstract":"<div><div>During adolescence, the prefrontal cortex (PFC) undergoes significant developmental changes, affecting the balance between excitatory glutamate and inhibitory GABA transmission (i.e., the E/I balance). This process is critical for intact cognitive function and social behavior in adulthood and is disrupted in schizophrenia (SZ). While acute NMDA receptor (NMDAr) blockade leads to excess glutamate transmission in the PFC, less is known about the long-term impacts of NMDAr blockade in adolescence on the E/I balance and adult cognitive function and social behavior. Here we show that early-adolescence chronic MK-801 administration leads to deficits in recognition memory and social function as well as increased E/I balance in the medial prefrontal cortex (mPFC) of adult male rats, stemming from reduced inhibitory synaptic transmission rather than changes in excitatory transmission or intrinsic excitability. Interestingly, chemogenetic attenuation of prelimbic mPFC pyramidal neurons reverses adolescent MK-801-induced deficits in recognition memory, but not social behavior. These findings emphasize the critical role of intact NMDAr function during adolescence on behavior in adulthood and on the E/I balance, and imply that reduced mPFC pyramidal neuron activity may hold therapeutic potential in treating recognition memory deficits in SZ.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111359"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803950","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}