Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Maternal separation and post-weaning feeding behavior in rodents: A critical review and meta-analysis","authors":"Elin Kachuki Dory ,&nbsp;Reut Hazani ,&nbsp;Yoni Loterstein ,&nbsp;Gil Zalsman ,&nbsp;Michal Lavidor ,&nbsp;Aron Weller","doi":"10.1016/j.pnpbp.2025.111511","DOIUrl":"10.1016/j.pnpbp.2025.111511","url":null,"abstract":"<div><div>Child neglect is a worldwide phenomenon that is associated with an increased risk of suffering from eating disorders. We aimed to examine the impact of child neglect on eating behaviors using two animal models of developmental disruption, maternal separation and maternal deprivation (MS and MD). The search resulted in 38 relevant studies, and datasets were divided into two meta-analytical analyses – for regular and palatable food intake (RFI and PFI). Procedure, sex and developmental stage were investigated as potential moderators in the RFI analysis and procedure, sex and main macronutrient in palatable food were investigated as potential moderators in the PFI analysis. MS increased RFI in males regardless of developmental stage, and reduced RFI in adult females. MS also increased PFI in both sexes but the main component in the palatable diet moderated the effect of MS on PFI only in males, whose consumption of palatable foods increased when the food was rich in carbohydrates and decreased when the food was rich in carbohydrates and lipids/fats. Thus, MS may influence feeding behaviors that resemble aspects of anorexia nervosa and binge-eating like behavior in adult females (depending on the diet) and alter males' hunger and satiety signalling. Additionally, MD reduced RFI and PFI in both sexes, indicating that MD is a useful model for altered behavioral eating pattens that relate to depression. Further research is needed given the existence of publication biases, and the high, unresolved heterogeneity between effect sizes.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111511"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193815","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":"Behavioral assessments and differential excitability, oscillatory dynamics in dorsal and ventral hippocampal CA1 neurons in male rats of a prenatal VPA-exposed autism model","authors":"Mona Rahdar ,&nbsp;Morteza Salimi ,&nbsp;Kiarash Eskandari ,&nbsp;Milad Nazari ,&nbsp;Shima Davoudi ,&nbsp;Mohammad Reza Raoufy ,&nbsp;Javad Mirnajafi-Zadeh ,&nbsp;Narges Hosseinmardi ,&nbsp;Gila Behzadi ,&nbsp;Mahyar Janahmadi","doi":"10.1016/j.pnpbp.2025.111507","DOIUrl":"10.1016/j.pnpbp.2025.111507","url":null,"abstract":"<div><div>The distinct electrophysiological properties of the dorsal (dHPC) and ventral (vHPC) hippocampus play crucial roles in cognitive and emotional processing. This study investigates the variations in firing activities between these hippocampal regions to develop targeted therapies for conditions such as autism. We conducted behavioral assessments and explored the properties of CA1 pyramidal neurons in the dHPC and vHPC using whole-cell patch-clamp recordings in a prenatal Valproic Acid (VPA)-exposed autistic-like model. Additionally, oscillatory activities in the dHPC and vHPC were analyzed through local field potential recordings across specific frequency bands during immobility in awake rats.</div><div>Our evaluation confirmed ASD-like phenotypes, including social deficits, repetitive behaviors, cognitive impairments, and emotional dysregulation. Significant differences in membrane properties and firing activities were revealed between the dHPC and vHPC regions, examining network alterations and intrinsic neuronal properties. Notably, autism induction increased excitability in dorsal CA1 neurons compared to ventral neurons in the autism-like group. Analysis of delta, theta, and gamma frequency bands showed distinct spectral power differences between control and autism-like groups exposed to VPA. Autistic-like rats exhibited higher delta and theta power, with a significant impact on gamma activity, specifically in the dHPC.</div><div>These findings provide novel insights into the behavioral and electrophysiological alterations in a prenatal VPA-exposed autistic-like model, emphasizing hippocampal hyperexcitability's role in ASD. The results underscore the complexity of anatomical and functional distinctions between the dHPC and vHPC, highlighting spectral dynamics and potential pathological alterations in oscillatory patterns under neuropsychiatric conditions.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111507"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139302","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":"Leveraging language and cognitive data for PPA subtyping: A systematic review of AI-based approaches","authors":"Joël Macoir ,&nbsp;Fenise Selin Karalı ,&nbsp;Samet Tosun","doi":"10.1016/j.pnpbp.2025.111514","DOIUrl":"10.1016/j.pnpbp.2025.111514","url":null,"abstract":"<div><div>Primary Progressive Aphasia (PPA) is a neurodegenerative disorder marked by a gradual and selective decline in language. Accurate classification into its three clinical variants—nonfluent/agrammatic (nfvPPA), semantic (svPPA), and logopenic (lvPPA)—is essential but often limited by the time demands and expertise required for traditional assessments. This systematic review evaluates the application of artificial intelligence (AI) in the detection and classification of PPA variants using language and cognitive data. Following PRISMA 2020 guidelines, 14 peer-reviewed studies published between 2014 and 2024 were included. Studies were grouped by input modality: transcribed speech, acoustic features, multimodal data, and language-focused neuropsychological or task-based inputs (excluding studies based solely on general cognitive screening tools). Each was analyzed for methodological approach, AI technique, classification performance, and clinical relevance. AI-based approaches demonstrated high accuracy in distinguishing PPA variants. Transcribed linguistic features provided a practical and effective input source, while acoustic features were particularly sensitive to motor speech deficits in nfvPPA. Multimodal methods achieved the highest classification performance, and task-based models relying on language-oriented standardized assessments yielded interpretable and clinically applicable results. AI-driven analysis of language and cognitive data shows strong potential for improving PPA diagnosis and subtype classification. Future work should address limitations such as methodological variability, and lack of pathological validation. Advancements in cross-linguistic datasets, model transparency, and clinical integration will be essential for broader adoption.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111514"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145260057","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":"Biological motion stimuli reveals the severity of the social deficits of ASD: an EEG study","authors":"Baodan Chen ,&nbsp;Jiaxin Zhao ,&nbsp;Yuqin Li ,&nbsp;Chunli Chen ,&nbsp;Runyang He ,&nbsp;Guangyin Wang ,&nbsp;Peng Xu ,&nbsp;Fali Li ,&nbsp;Dezhong Yao","doi":"10.1016/j.pnpbp.2025.111513","DOIUrl":"10.1016/j.pnpbp.2025.111513","url":null,"abstract":"<div><div>The integration of individuals with autism spectrum disorder (ASD) into society and their capacity to lead fulfilling lives are significantly hindered by challenges in social communication. Consequently, it is crucial to explore the underlying neural mechanisms and establish early diagnostic approaches to accurately assess the severity of social interaction impairments in ASD. To investigate the social deficits in ASD, particularly in identifying reliable biomarkers for predicting the severity of social impairments, the current study focused on the sample entropy, functional connectivity, and network properties under biological motion tasks (biological motion (BM) and scramble motion (Scr) in both ASD and typically developing (TD) children. The findings suggest that, compared to TD, those with ASD exhibit higher sample entropy in localized brain regions, specifically the frontal and occipital lobes, regardless of whether they are under BM or Scr conditions. Moreover, ASD is characterized by enhanced long-range connectivity involving the frontal, parietal, and occipital lobes. These results collectively highlight the abnormal neural mechanisms of ASD when engaging with BM tasks, which further found a significant correlation between the network properties and the ADOS social score. Notably, by utilizing network properties and sample entropy as features, the severity of social impairments in autism can be effectively predicted through multiple stepwise regression analyses. These findings illuminate the pathophysiological mechanisms of ASD's social deficits from both local and global perspectives, offering potential biomarkers for quantifying social dysfunction in autism.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111513"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208422","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 salutogenic signature of the placebo effect in brain oscillations: A systematic review and meta-analysis","authors":"Jorge Ortega-Márquez ,&nbsp;Luis Fernando Gonzalez-Gonzalez ,&nbsp;William Sosa ,&nbsp;Kevin Pacheco-Barrios ,&nbsp;Felipe Fregni","doi":"10.1016/j.pnpbp.2025.111518","DOIUrl":"10.1016/j.pnpbp.2025.111518","url":null,"abstract":"<div><h3>Background</h3><div>The placebo effect is increasingly recognized in rehabilitation, yet its mechanisms remain poorly understood. Brain oscillations offer a non-invasive, time-sensitive and dynamic measure of neural activity, making them ideal for capturing the dynamic changes linked to placebo responses. This study explores oscillatory activity as a biomarker of the placebo effect's neural basis.</div></div><div><h3>Methodology</h3><div>A systematic literature review up to September 2024 searched PubMed, Embase, and Cochrane databases for randomized controlled and cross-over trials reporting brain oscillations in resting state from placebo-controlled neurorehabilitation trials in healthy and subjects with neurological disorders. The analysis included a semi-quantitative (albatross plots), and quantitative meta-analysis (Hedge's g), focusing on the effect sizes of power differences between placebo and active groups.</div></div><div><h3>Results</h3><div>We included 63 studies with 180 healthy subjects and 1758 neurological disorder patients. In healthy subjects, placebo showed an increase in alpha power compared to no intervention (g = 0.45, 95 % CI [0.09; 0.8]). In patients, sham interventions elevated alpha power in frontal (g = 0.08, 95 % CI [0.07; 0.08]), central (g = 0.55, 95 % CI [0.47; 0.65]), and parietal areas (g = 0.28, 95 % CI [0.18; 0.44]), as well as beta (g = 1.31, 95 % CI [1.06; 1.63]) and theta central (g = 0.58, 95 % CI [0.46; 0.72]). These effects were non-significant when compared to active interventions.</div></div><div><h3>Conclusion</h3><div>Alpha oscillations in fronto-central regions are the primary biomarkers of the placebo effect, with beta and theta oscillations also indicative, especially in patients with neurological disorders. These effects were reversed when compared to active interventions, suggesting that active rehabilitation also encompass the placebo effect. Intriguingly, these placebo effects vary based on baseline brain activity, highlighting a tendency towards more stable, salutogenic rhythms in different populations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111518"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in ketamine treatment for depressive disorders: A systematic review","authors":"Ziqin Feng ,&nbsp;Hengjin Wu ,&nbsp;Fengquan Xu,&nbsp;Yu Zheng,&nbsp;Huazhao Xu","doi":"10.1016/j.pnpbp.2025.111521","DOIUrl":"10.1016/j.pnpbp.2025.111521","url":null,"abstract":"<div><div>In recent years, ketamine has gained attention for its rapid onset and significant antidepressant effects, but research on its differential treatment effects between sexes is limited. This study systematically reviews 22 studies (<em>n</em>=1,155; 485 males, 670 females) to explore the sex differences in the effects of ketamine treatment for depression. The findings indicate that while some studies reported sex differences, such as variations in metabolite levels, side effects, and efficacy, the overall evidence is limited, with small sample sizes and inadequate study designs being major contributing factors. Additionally, sex differences may be influenced by hormone levels, drug dosage, and baseline characteristics, which have not been adequately considered. Accordingly, the current lack of consistent sex-specific findings should be interpreted as inconclusive, reflecting limited sample sizes, non-prespecified sex analyses, and heterogeneity of study designs, rather than as evidence of no sex differences. Future research should conduct in-depth analyses of the sex-specific mechanisms of ketamine treatment in larger, sex-balanced studies to advance the development of personalized medicine.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111521"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268987","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":"Personality and repeated social defeat affect health condition and gene expression in the skin and intestines in zebrafish","authors":"Lisa Benrejdal ,&nbsp;Pavla Hubená ,&nbsp;David Brodin ,&nbsp;Rodrigo A. Morales Castro ,&nbsp;Rokeya Sultana Rekha ,&nbsp;Svante Winberg ,&nbsp;Peter Bergman","doi":"10.1016/j.pnpbp.2025.111487","DOIUrl":"10.1016/j.pnpbp.2025.111487","url":null,"abstract":"<div><div>Personality traits and acquired experience affect the capacity of an individual to cope with environmental and social changes. Behavioural adaptation and physiological alterations are important to prepare the body for these potential challenges. Whether inherited traits or acquired social rank (reflecting stress levels) are more important and how different personality-social rank combinations affect an individual's health is not well understood. One important aspect of health status is the function of biological barriers, as they represent the first line of defence of an organism. In the current study, we used a model of social defeat stress applied to a bold and a shy line of zebrafish. The Fulton's condition factor was determined, and gene expression analysis was performed on skin and intestines. The differences between lines explained a major part of the transcriptional changes observed as compared to differences in social rank. Additionally, shy fish that experienced repeated social defeat presented a poor body condition, accompanied by changes in gene expression suggesting inflammation in the gut. In the skin, shy fish showed a transcriptional enrichment of pathways related to cell division as well as increased expression of the stress response-associated gene <em>crh2r</em>. Together, these results complement our previous work and show that shy loser fish experience important changes not only in behaviour but also in their biological barriers, potentially putting their overall health at higher risk.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111487"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042481","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":"Unravelling gender differences in cannabis cue-reactivity in individuals who use cannabis","authors":"A.M. Kaag ,&nbsp;J. Cousijn ,&nbsp;E. Kroon","doi":"10.1016/j.pnpbp.2025.111515","DOIUrl":"10.1016/j.pnpbp.2025.111515","url":null,"abstract":"<div><div>The development of cannabis use disorder (CUD) shows notable gender differences. While men have a higher overall prevalence of CUD, women transition more rapidly from initial use to CUD and often present with more severe psychiatric symptoms when seeking treatment. Despite these clinical observations, research into the neural mechanisms underlying these gender differences remains limited. This study aimed to investigate gender-dependent differences in neural cue-reactivity and session-induced craving (change in craving from the beginning to end of the experimental session) among regular cannabis users and non-using controls, as well as gender-specific associations between neural cue-reactivity, craving, and cannabis use characteristics.</div><div>A total of 66 regular cannabis users (27 women), who used cannabis 2 to 7 days per week, and 71 controls (31 women) completed a functional MRI cannabis cue-reactivity task involving exposure to cannabis-related and neutral images. Craving was measured twice using the Marijuana Craving Questionnaire, which measures craving related to the loss of control, relief from negative affect, anticipated positive outcomes, and intention to use. To assess session-induced craving, craving at the end of the experimental session was subtracted from craving at the beginning of the experimental session.</div></div><div><h3>Results revealed that women who use cannabis displayed blunted neural cue-reactivity in the right insula and putamen compared to men, a pattern opposite to that seen in controls. Among women, but not men, session-induced relief and reward craving correlated positively with cue-reactivity in the right superior frontal gyrus, cerebellum, and precentral gyrus. Additionally, cannabis use severity was linked to cue-reactivity in the precentral gyrus in women only</h3><div>These findings underscore complex, gender-related interactions between neural responses, craving, and cannabis use severity, emphasizing the need for gender-tailored research to address critical gaps in understanding the development and treatment of CUD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111515"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226381","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":"Astrocyte alterations and dysfunction in alcohol use disorder: A comprehensive scoping review of clinical postmortem and preclinical evidence","authors":"Emma Nadler ,&nbsp;Stephen J Kish ,&nbsp;Junchao Tong ,&nbsp;Anh Dzung Lê ,&nbsp;Isabelle Boileau","doi":"10.1016/j.pnpbp.2025.111509","DOIUrl":"10.1016/j.pnpbp.2025.111509","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) is a prevalent mental health condition associated with numerous comorbidities and health complications. Astrocytes are vital glial cells that are essential in maintaining homeostasis and responding to injury. Dysregulation of astrocytic function has been implicated in various disorders, including AUD, but the specific effects of alcohol and AUD on astrocytes remain unclear. This scoping review synthesizes evidence on alterations in astrocyte morphology and astrocytic protein expression in AUD and preclinical models. Post-mortem investigations are limited to a few brain regions and report no overall changes in the astrocyte protein, glial fibrillary acidic protein (GFAP) in AUD. In preclinical models, GFAP levels are elevated, particularly following periods of alcohol abstinence. In contrast, morphological changes in astrocytes are minimal following periods of alcohol abstinence and most notable with continuous ethanol exposure. Overall, convincing evidence of classically reactive astrocytes is lacking across paradigms. This review also highlights the lack of clinical research and sex-based analyses in the field. Future work should focus on in vivo PET imaging and employ more comprehensive measures of astrocyte function in multiple brain regions. A better understanding of astrocytic involvement in AUD could inform future research and therapeutic interventions, ultimately alleviating the disorder's burden.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111509"},"PeriodicalIF":3.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145234086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psilocybin-assisted psychotherapy in adults with depression – A literature review","authors":"Marie Celine Dorczok ,&nbsp;Gloria Mittmann ,&nbsp;Thomas Ettl ,&nbsp;Verena Steiner-Hofbauer","doi":"10.1016/j.pnpbp.2025.111508","DOIUrl":"10.1016/j.pnpbp.2025.111508","url":null,"abstract":"<div><h3>Background</h3><div>Psilocybin-Assisted Psychotherapy (PAP) has gained increasing attention in recent years as a potential treatment for depression, particularly in cases resistant to conventional therapies. This article aims to assess the efficacy of PAP in adults with various forms of depression by conducting a comprehensive review of the available literature.</div></div><div><h3>Method</h3><div>A systematic search was conducted across several major databases (PubMed and Ebsco Host (incl. MEDLINE Ultimate, eBook Clinical Collection, DynaMed, APA PsycARTICLES, APA PsycINFO, Psychology &amp; Behavioral Sciences Collection), focusing on studies that investigated the effects of psilocybin in a therapeutic setting.</div></div><div><h3>Results</h3><div>The overall systematic literature search identified 139 items, of which seven were selected for detailed analysis. The studies employed different dosing regimens and varied in their methodologies of psychological support before, during, and after psilocybin administration. Most studies found significant improvements in depression symptoms after administration of Psilocybin and sustained antidepressant effects up to twelve months post-treatment. Response and remission rates were consistently high across studies.</div></div><div><h3>Conclusions</h3><div>PAP combined with structured psychological support shows sustained reductions in depressive symptoms for treatment-resistant depression and major depressive disorder. Higher doses generally yield stronger benefits. While PAP holds significant potential as a holistic treatment, methodological limitations, such as heterogeneity in study designs, inconsistent levels of psychological support and difficulties in blinding due to the nature of the drug's effect, highlight the need for more standardized protocols in future studies to ensure reliable outcomes. More research is needed to better understand the mechanisms underlying its therapeutic effects.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"142 ","pages":"Article 111508"},"PeriodicalIF":3.9,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}