Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Sexual dimorphism of white-matter functional connectome in healthy young adults","authors":"Zhuo-Yan Cai ,&nbsp;Kang Hu ,&nbsp;Ze-Qiang Linli","doi":"10.1016/j.pnpbp.2025.111486","DOIUrl":"10.1016/j.pnpbp.2025.111486","url":null,"abstract":"<div><h3>Background</h3><div>Sexual dimorphism in human brain has garnered significant attention in neuroscience research. Although multiple investigations have examined sexual dimorphism in gray matter (GM) functional connectivity (FC), the research of white matter (WM) FC remains relatively limited.</div></div><div><h3>Methods</h3><div>Utilizing resting-state fMRI data from 569 healthy young adults, we investigated sexual dimorphism in the WM functional connectome. We constructed both WM-WM and GM-WM FC networks and subsequently analyzed their FC strength, functional connectivity density, and network topological properties. Based on identified dimorphic features, a radial basis function support vector machine model was employed for sex prediction and classification. Validation analyses confirmed the reproducibility of our findings.</div></div><div><h3>Results</h3><div>Our analyses revealed significant sexual dimorphism in FC within both the WM-WM and GM-WM networks. Notably, females generally exhibited stronger connection strengths across numerous pathways compared to males. Topologically, females displayed greater global system aggregation (higher clustering coefficient) in the WM-WM network. Similarly, within the GM-WM connectome, females showed enhanced network integration, specifically higher global and local efficiency in the frontoparietal network and increased clustering coefficient in the attention network. Critically, these dimorphic WM features proved effective for sex classification using machine learning; an integrated model combining WM-WM and GM-WM FCs achieved superior predictive performance over models using individual feature sets, highlighting the unique information encoded in WM functional dynamics.</div></div><div><h3>Conclusion</h3><div>This finding extends our understanding of brain sex differences beyond gray matter and provides novel insights into the neurological mechanisms potentially underlying sex-specific patterns in cognition, behavior, and susceptibility to brain disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111486"},"PeriodicalIF":3.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034645","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":"Genetic variation of the estrogen receptor and its association with depression and anxiety symptoms in young females","authors":"Mirac Nur Musaoglu ,&nbsp;Susanne Olofsdotter ,&nbsp;Sofia Vadlin ,&nbsp;Cecilia Åslund ,&nbsp;Ann-Christin S. Kimmig ,&nbsp;Catherine Tuvblad ,&nbsp;Kent W. Nilsson ,&nbsp;Vanessa Nieratschker ,&nbsp;Erika Comasco","doi":"10.1016/j.pnpbp.2025.111485","DOIUrl":"10.1016/j.pnpbp.2025.111485","url":null,"abstract":"<div><div>Estrogens are suggested to affect mood by binding to widespread estrogen receptors in the brain and therewith modulating a variety of neurosignaling pathways. Single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptors might influence these actions and thereby play a role in the genetic foundation of mood disorders. Several SNPs in the estrogen receptor 1 (<em>ESR1</em>) gene have been studied in relation to anxiety and depression, while confounders and interaction with psychosocial factors have largely been overlooked. The present study investigated the effect of the functional polymorphisms rs2234693 <em>(PvuII)</em> and rs9340799 <em>(XbaI)</em> in the <em>ESR1</em> gene on depression and anxiety symptoms as well as their interaction with early life adversities and parenting in two independent female cohorts, considering relevant confounding factors. In adolescent females (<em>n</em> = 1036), the rs9340799 minor allele (G) was found to protect against increasing anxiety symptoms from age 14 to 17, whereas, in young adult females (<em>n</em> = 1314, mean age: 22.2 years), it was associated with a greater risk of experiencing above-threshold anxiety symptoms. No genetic effect was found for rs2234693 and depressive symptoms in either cohort. A significant three-way gene-environment interaction was observed between rs9340799, stressful early life events, and supportive parenting on anxiety symptoms in female adolescents. These findings suggest a potential differential plasticity of the G allele in relation to anxiety symptoms in female youth. By incorporating longitudinal assessments and gene-environment analyses, this study contributes to the literature on internalizing symptoms in females in the context of estrogen-related constitutive vulnerability.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111485"},"PeriodicalIF":3.9,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014494","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":"Activation of Kv7.2/3 channels in the PL-NAcc circuit attenuates methamphetamine-associated contextual memory","authors":"E Liu ,&nbsp;Zhaofang Hang ,&nbsp;Min Liu ,&nbsp;Shouhong Mu ,&nbsp;Weikai Han ,&nbsp;Siqi Fan ,&nbsp;Ziyu Shiney Shi ,&nbsp;Qingwei Yue ,&nbsp;Jinhao Sun","doi":"10.1016/j.pnpbp.2025.111483","DOIUrl":"10.1016/j.pnpbp.2025.111483","url":null,"abstract":"<div><div>Methamphetamine (METH), a powerful psychoactive substance, promotes the formation of the persistent drug-associated memories that have a significant contribution to relapse in drug addiction. The reward circuit of prelimbic cortical (PL) to the nucleus accumbens core (NAcc) is closely related to METH-associated contextual memory. To evaluate METH-associated contextual memory, we employed the conditioned place preference (CPP) paradigm. Inhibition of the PL-NAcc circuit by using chemogenetic strategies could significantly suppressed METH-induced CPP. The expression of Kv7.2 and Kv7.3 in the PL projecting to NAcc was reduced in METH-administered mice compared to control mice. In METH-administered mice, METH-induced CPP, neuronal excitability and synaptic plasticity in the PL-NAcc circuit could be attenuated by injecting the Kv7.2/3 agonist retigabine in PL. Furthermore, overexpression of Kv7.3 channels' in the PL-NAcc circuit attenuated METH-induced CPP. Our findings identify hat the PL-NAcc circuit could be the main reason in METH-associated contextual memory and provide evidence that Kv7.2/3′ activation in the PL may emerge as a novel therapeutic strategy for METH abuse.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111483"},"PeriodicalIF":3.9,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001975","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":"An overview of psilocybin, LSD, MDMA, and ketamine in revitalizing psychedelic-assisted therapy: Insights, limitations and future directions","authors":"Kiana Askariyan ,&nbsp;Mohammad Taghi Joghataei ,&nbsp;Samaneh Dehghan ,&nbsp;Shabnam Nohesara ,&nbsp;Leila Riahi pour ,&nbsp;Mohammad Hossein Mohammadi ,&nbsp;Nooshin Ahmadirad","doi":"10.1016/j.pnpbp.2025.111461","DOIUrl":"10.1016/j.pnpbp.2025.111461","url":null,"abstract":"<div><div>The resurgence of psychedelic-assisted psychotherapy marks a pivotal evolution in mental health treatment, challenging traditional paradigms by integrating compounds such as psilocybin, LSD, MDMA, and ketamine into clinical practice. Historically marginalized due to regulatory and societal concerns, these agents are now gaining recognition for their unique neurobiological mechanisms and therapeutic potential in addressing complex conditions like depression, PTSD, and addiction. Unlike conventional treatments, psychedelics exert their effects primarily through modulation of serotonin receptors and brain network connectivity, with each substance demonstrating distinct pharmacological profiles and clinical applications. Notably, psilocybin and LSD share serotonergic pathways but differ in receptor specificity and subjective effects, while MDMA's empathogenic properties and ketamine's rapid antidepressant action offer alternative therapeutic avenues. Recent FDA breakthrough therapy designations for psilocybin and MDMA underscore a shift toward evidence-based acceptance, yet the field remains challenged by methodological limitations, regulatory barriers, and ethical considerations. This narrative review synthesizes historical developments, mechanistic insights, and clinical outcomes, emphasizing the need for rigorous research, diverse patient cohorts, and thoughtful integration of psychedelics with psychotherapeutic modalities to realize their full therapeutic promise.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111461"},"PeriodicalIF":3.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735482","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":"Delineating lifetime multimorbidity associated with 16p13.11 duplication: A literature review, meta-analysis, and case study.","authors":"Rose Mary Xavier, Wenxin Bian, Fadhah Alshammari, Matthew K Harner, Tyler E Dietterich, Maya Lichtenstein, Robert Stowe, Martilias Farrell, Jin P Szatkiewicz, Rita A Shaughnessy, Jonathan S Berg, Patrick F Sullivan, Richard C Josiassen","doi":"10.1016/j.pnpbp.2025.111462","DOIUrl":"10.1016/j.pnpbp.2025.111462","url":null,"abstract":"<p><p>The 16p13.11 duplication is a rare copy number variation (CNV) that appears to increase risk for multimorbidity across the life span. Initial reports implicated the duplication in autism spectrum disorder, intellectual disability, and various congenital anomalies; however, it was also observed in \"phenotypically normal\" individuals suggesting incomplete penetrance or non-pathogenicity. Recent studies suggest that duplication carriers often present with multimorbidity, but more data are needed to elucidate the full range of associated phenotypes. Lifetime multimorbidity remains unclear, and no reviews summarizing this literature currently exist. We report a systematic literature review and meta-analysis of published phenotypic characteristics. Speech delays, developmental delays, intellectual disability, learning disability, and autistic symptoms were reported in >30 % of cases. Musculoskeletal abnormalities and cardiovascular disorders were commonly reported. Included is a lifespan case report of a 71-year-old female with a history of behavioral disturbance and treatment-resistant schizophrenia, identified as being a 16p13.11 duplication carrier.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111462"},"PeriodicalIF":3.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765794","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":"5-HT2A receptors shape whole-brain monoaminergic coherence in male mice","authors":"Jasmine Jade Butler ,&nbsp;Margherita Virgili ,&nbsp;Giuseppe Di Giovanni ,&nbsp;Abdeslam Chagraoui ,&nbsp;Anna Beyeler ,&nbsp;Philippe De Deurwaerdère","doi":"10.1016/j.pnpbp.2025.111437","DOIUrl":"10.1016/j.pnpbp.2025.111437","url":null,"abstract":"<div><div>The mechanism of action of serotonergic psychedelics is increasingly explored worldwide due to their clinical benefits in various psychiatric conditions. Beyond the stimulation of serotonin 2A (5-HT_2A) receptors, psychedelics may desynchronize activity between brain regions, however the involvement of the corresponding neurotransmission systems has been largely overlooked. Given that monoaminergic systems target virtually all brain regions and play a role in exploratory behavior, we hypothesized that psychedelics disrupt the coherence of monoamine systems across brain regions during forced exploratory behavior in mice. Using post-mortem tissue quantification of serotonin (5-HT), dopamine (DA), noradrenaline (NA), and their metabolites in 28 distinct brain regions, we observed a dense and highly organized pattern of correlations within and between monoamines in vehicle-treated mice. This organization was disrupted by both the psychedelic 5-HT_2A receptor agonist TCB-2 (0.3, 3 and 10 mg/kg) and the antagonist MDL-100,907 (0.2 mg/kg), both of which decreased correlations between regional neurochemical concentrations. Interestingly, the combination of MDL-100,907 and TCB-2 partially restored correlations. Quantitatively, TCB-2 dose-dependently decreased 5-HT turnover (metabolite/5-HT) across all brain regions, and DA turnover (3-methoxytyramine/DA) in the striatum. TCB-2 also enhanced markers of the DA and NA systems in certain brain regions, notably including the anterior cingulate cortex. MDL-100,907, which had minimal impact on monoamine levels when administered alone, reduced TCB-2 (3 mg/kg)-induced head twitches and increased monoamine concentrations in the anterior cingulate cortex, but did not affect the TCB-2-induced decrease 5-HT turnover across the brain. These data suggest that the functional connectivity of monoaminergic systems during exploration is highly sensitive to modulation through either activation or blockade of 5-HT_2A receptors.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111437"},"PeriodicalIF":3.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644157","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":"A plasma protein profile of antidepressant response to omega-3 fatty acids","authors":"Jesper Lindahl ,&nbsp;Miranda Stiernborg ,&nbsp;Filip Ventorp ,&nbsp;Klara Suneson ,&nbsp;Gustav Söderberg Veibäck ,&nbsp;Johanna Tjernberg ,&nbsp;Darya Ståhl ,&nbsp;Marie Hjärn ,&nbsp;Catharina Lavebratt ,&nbsp;Daniel Lindqvist","doi":"10.1016/j.pnpbp.2025.111481","DOIUrl":"10.1016/j.pnpbp.2025.111481","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies suggest an antidepressant effect of omega-3 fatty acids (n-3 PUFAs). This effect may be larger in patients with low-grade inflammation, defined as mild elevations of high sensitivity C-reactive protein or other commonly used inflammatory markers. The antidepressant mechanisms of n-3 PUFAs are not fully understood but may involve modulation of immunometabolic processes and neurotrophic effects. Here we investigated inflammatory and cardiometabolic biomarkers in patients with major depressive disorder (MDD) and controls, how these biomarkers change with n-3 PUFA treatment, and their association with antidepressant response.</div></div><div><h3>Methods</h3><div>Ninety-four MDD patients were treated with 2.2 g eicosapentaenoic acid, 400 mg docosahexaenoic acid, and 800 mg other omega-3 fatty acids per day, added to stable antidepressant treatment for 8 weeks. Inflammatory and cardiometabolic plasma markers were assayed in MDD patients, before and after n-3 PUFA treatment, and in healthy controls (<em>n</em> = 76) using proximity extension assay technology. Treatment response was defined as ≥50 % reduction on the 17-item Hamilton Depression Rating Scale. Partial least squares discriminant analysis identified plasma proteins with differential levels between patients, controls, responders, and non-responders.</div></div><div><h3>Results</h3><div>After adjusting for relevant covariates and multiple comparisons, baseline levels of several biomarkers associated with immunometabolic functions and neurotrophic processes differed significantly between MDD patients and controls and between n-3 PUFA responders and non-responders. Some of these biomarkers, related to cell-cell communication and neurotrophy, increased significantly with treatment.</div></div><div><h3>Conclusion</h3><div>These findings provide new insights into the antidepressant mechanisms of n-3 PUFAs. Consistent with previous reports, we found evidence of pre-treatment immune activation in responders compared to non-responders, which could be used to personalize antidepressant n-3 PUFA treatment.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111481"},"PeriodicalIF":3.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912896","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-specific dysregulation of the CX3CL1/CX3CR1 Axis following cocaine exposure: Translational evidence for a potential biomarker of abstinence","authors":"Oscar Porras-Perales ,&nbsp;Laura Sánchez-Marín ,&nbsp;Dina Medina-Vera ,&nbsp;María Flores-López ,&nbsp;Laura Martín-Chaves ,&nbsp;Milena Boccalon ,&nbsp;Nerea Requena-Ocaña ,&nbsp;Nuria García-Marchena ,&nbsp;Raquel Reviriego ,&nbsp;Luis J. Santín ,&nbsp;Remi Martin-Fardon ,&nbsp;Manuel Jiménez-Navarro ,&nbsp;Fernando Rodríguez de Fonseca ,&nbsp;Antonia Serrano ,&nbsp;Francisco Javier Pavón-Morón","doi":"10.1016/j.pnpbp.2025.111482","DOIUrl":"10.1016/j.pnpbp.2025.111482","url":null,"abstract":"<div><div>Cocaine disrupts neurotransmitter systems and promotes neuroinflammation by activating microglia and altering cytokine signaling. The CX₃CL1/CX₃CR1 axis is an essential signaling pathway for microglial regulation, may exhibit sex-specific responses to cocaine. In this study, male and female Wistar rats were exposed to acute (5, 15, or 30 mg/kg) or repeated (15 mg/kg/day for two weeks) cocaine. Gene expression of <em>Cx3cl1</em> and <em>Cx3cr1</em> was assessed in the amygdala and hippocampus, alongside plasma CX₃CL1 concentrations. Additionally, plasma CX₃CL1 concentrations were assessed in 88 abstinent patients with cocaine use disorder (CUD) and 30 matched healthy controls. Female rats exhibited significantly lower baseline mRNA expression of <em>Cx3cl1</em> and <em>Cx3cr1</em> in both brain regions compared with male rats. Acute cocaine induced dose- and time-dependent transcriptional changes, with female rats exhibiting more pronounced and sustained <em>Cx3cl1</em> and <em>Cx3cr1</em> expression changes compared with males. Repeated exposure produced sex-, region-, and abstinence-dependent regulations of <em>Cx3cl1</em> and <em>Cx3cr1</em>, with persistent downregulation of <em>Cx3cl1</em> and compensatory <em>Cx3cr1</em> upregulation in female rats. In plasma, only male rats exhibited elevated CX₃CL1 concentrations following cocaine exposure, particularly during early abstinence (<em>i.e.</em>, 2 h–72 h). In humans, overall CX₃CL1 concentrations did not differ between CUD patients and controls. However, CX₃CL1 concentrations increased with abstinence duration, particularly in males (<em>r</em> = +0.34, <em>p</em> &lt; 0.01), but not in females. These findings highlight sex-specific regulation of the CX₃CL1/CX₃CR1 axis in cocaine-induced neuroinflammation and suggest that plasma CX₃CL1 concentrations may serve as a potential biomarker or contribute to a composite biosignature, together with other biomolecules, of CUD progression and abstinence. Considering sex differences, may enhance our understanding of addiction pathophysiology and inform targeted therapeutic strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111482"},"PeriodicalIF":3.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932162","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 impact of prior exposure to severe stressors on fear learning: The critical contribution of the type of stressor and the rat strain","authors":"Sara Serrano ,&nbsp;Xavier Belda ,&nbsp;Antonio Armario","doi":"10.1016/j.pnpbp.2025.111484","DOIUrl":"10.1016/j.pnpbp.2025.111484","url":null,"abstract":"<div><div>The appearance of long-lasting behavioral alterations is considered critical for the characterization of acute stressors as putative animal models of PTSD. However, the traumatic nature of the different stressors used is objectively difficult to demonstrate and literature is plagued by inconsistent results. In the present study we wanted to demonstrate the relevance of qualitative aspects of stressors not linked to their severity (as evaluated by classical biological markers) and how the use of different mouse or rat strains can contribute to the inconsistencies. We then exposed Sprague-Dawley (SD) and Long-Evans (LE) rats to two different severe stressors of roughly similar intensity, immobilization on boards (IMO) and inescapable foot-shocks (IS), and studied their impact on contextual fear conditioning, generalization, extinction and extinction recall. The results confirmed that the two stressors are of similar severity (IMO a little bit more severe) in terms of biological markers of stress, but their impact of fear conditioning was strongly dependent on the stressor and the strain, with a strong impact of IS in LE rats, a modest impact of IMO in the latter strain and almost null impact of the two stressors in SD rats. We thus confirm the relevance of both qualitative aspects of stressors and the strain used in order to characterize appropriate models of PTSD. Deciphering the processes underlying the contribution of the two factors is fundamental and requires comparison of stressors and strains at different neurobiological levels.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111484"},"PeriodicalIF":3.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001960","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":"Examining the potential of psilocybin and 5-MeO-DMT as therapeutics for traumatic brain injury","authors":"Zoe Plummer ,&nbsp;Josh Allen ,&nbsp;Justin Brand ,&nbsp;Leah M. Mayo ,&nbsp;Sandy R. Shultz ,&nbsp;Brian R. Christie","doi":"10.1016/j.pnpbp.2025.111448","DOIUrl":"10.1016/j.pnpbp.2025.111448","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death - factors that contribute to the development of neurological and psychiatric disorders. Emerging evidence suggests that serotonergic psychedelics psilocybin and 5-methoxy-<em>N</em>,<em>N</em>-dimethyltryptamine (5-MeO-DMT) may hold promise as treatments for TBI. These compounds promote neuroplasticity, exert anti-inflammatory and neuroprotective effects, and have shown efficacy in treating psychiatric conditions that share pathophysiological features with TBI. 5-HT1A and 5-HT2A receptors are implicated in their effects, but psilocybin also targets neurotrophic TrkB receptors, whereas 5-MeO-DMT targets sigma-1 receptors, known to have neuroprotective properties. This review integrates current preclinical and clinical research, highlighting both the shared and distinct mechanistic pathways through which psilocybin and 5-MeO-DMT may alleviate TBI-related impairments, such as cognitive and affective dysfunction and neuroinflammation. Additionally, the safety profiles, dosing paradigms, and clinical challenges of these psychedelics are critically examined. By bridging insights from psychedelic science and neurotrauma research, this review underscores the innovative potential of psilocybin and 5-MeO-DMT as adjunctive treatments for TBI, paving the way for novel interventions in neurorehabilitation.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"141 ","pages":"Article 111448"},"PeriodicalIF":3.9,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651254","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}