Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"The entorhinal cortex and cognitive impairment in schizophrenia: A comprehensive review","authors":"Kun Li ,&nbsp;Liju Qian ,&nbsp;Chenchen Zhang ,&nbsp;Jiajia Zhang ,&nbsp;Chuang Xue ,&nbsp;Yuebing Zhang ,&nbsp;Wei Deng","doi":"10.1016/j.pnpbp.2024.111218","DOIUrl":"10.1016/j.pnpbp.2024.111218","url":null,"abstract":"<div><div>Schizophrenia, a severe mental illness characterized by cognitive impairment and olfactory dysfunction, remains an enigma with its pathological mechanism yet to be fully elucidated. The entorhinal cortex, a pivotal structure involved in numerous neural loop circuits related to olfaction, cognition, and emotion, has garnered significant attention due to its structural and functional abnormalities, which have been implicated in the pathogenesis of schizophrenia. This review focuses on the abnormal structural and functional changes in the entorhinal cortex in schizophrenia patients, as evidenced by neuroimaging, cellular biology, and genetic studies. These changes are posited to play a crucial role in the pathogenesis of cognitive impairment in schizophrenia. Furthermore, this review explores the various intervention strategies targeting the entorhinal cortex in current treatment modalities and proposes potential directions for future research endeavors, thereby providing a novel perspective on unraveling the complexity of neural mechanisms underlying schizophrenia and developing innovative therapeutic approaches for schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111218"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822896","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":"Adiponectin, resistin, interleukin-4 and TGF-β2 levels in treatment resistant schizophrenia patients","authors":"Andreas Karampas ,&nbsp;George Leontaritis ,&nbsp;Georgios Markozannes ,&nbsp;Alexandros Asimakopoulos ,&nbsp;Dimitra T. Archimandriti ,&nbsp;Polyxeni Spyrou ,&nbsp;Georgios Georgiou ,&nbsp;Marios Plakoutsis ,&nbsp;Konstantinos Kotsis ,&nbsp;Paraskevi V. Voulgari ,&nbsp;Petros Petrikis","doi":"10.1016/j.pnpbp.2024.111221","DOIUrl":"10.1016/j.pnpbp.2024.111221","url":null,"abstract":"<div><h3>Background</h3><div>The aim of the present study was to measure adiponectin, resistin, interleukin-4 and TGF-β levels in first episode, treatment resistant patients with schizophrenia.</div></div><div><h3>Methods</h3><div>In total, fifty-three treatment-resistant patients were included in the study. In subgroups of these patients, we measured Interleukin-4 (IL-4), Tumor Growth Factor-β2 (TGF-β2), adiponectin and resistin levels at three different timepoints: in the drug-naïve state, after two rounds of treatment with different antipsychotic drugs for a total of 16 weeks and, after clozapine treatment for 12 weeks.</div></div><div><h3>Results</h3><div>TGF-β2 and adiponectin levels decreased after treatment with olanzapine and risperidone, while resistin and IL-4 levels did not differ significantly.Comparing the levels of the aforementioned cytokines before the initiation and after clozapine treatment, we found an even greater decrease in adiponectin levels while resistin and IL-4 levels significantly increased and TGF-β2 levels did not differ significantly.</div></div><div><h3>Conclusions</h3><div>We report elevated resistin and IL-4 levels and decreased adiponectin levels in first-episode, treatment resistant schizophrenia patients after clozapine treatment. These findings may be at least partly due to the anti-inflammatory action of clozapine, although sub-clinical metabolic disturbances may also have played a role as far as resistin and adiponectin are concerned. In a subgroup of these patients we report reduced TGF-β2 and adiponectin levels after two unsuccessful trials with risperidone and olanzapine comparing them with the ones of the same subgroup in the drug-naïve phase.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111221"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866364","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":"Systemic heterogeneity in autism spectrum disorder revealed by individualized structural covariance network analysis","authors":"Qiuyue Zhang ,&nbsp;Xi Yang ,&nbsp;Jianfeng Qiu ,&nbsp;Weizhao Lu","doi":"10.1016/j.pnpbp.2024.111224","DOIUrl":"10.1016/j.pnpbp.2024.111224","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Autism spectrum disorder (ASD) is clinically heterogeneous, and resent neuroimaging studies have shown the presence of brain structural heterogeneity in ASD. However, there is currently a lack of evidence for systemic level brain structural heterogeneity. This study aimed to reveal the heterogeneity of brain structural changes at the systemic level in ASD patients through individual differential structural covariance network (IDSCN) analysis.</div></div><div><h3>Materials and methods</h3><div>We included 803 neurotypical controls (NCs) and 650 ASD patients from 24 sites and the corresponding structural magnetic resonance and clinical data. 516 ASD patients were used as training group, and 134 ASD patients were selected as an independent validation group. In the training group, we constructed IDSCN for each ASD patient, identified differentiated structural covariance edges, and resolved systemic heterogeneity using K-means clustering algorithm. We then conducted statistical analyses on the demographical and clinical data of the ASD subgroups, and performed correlation analyses between structural covariance edges and clinical profiles within each ASD subgroup. We also tested the reliability of the IDSCN in the validation group.</div></div><div><h3>Results</h3><div>The results of the training and validation groups were similar, revealing two subtypes of ASD, with 17 brain connections showing differences between the two subtypes. There were differences in clinical profiles between the two subgroups in restricted repetitive behavior score from autism diagnostic interview-revised (ADI_RRB_TOTAL), total score of autism diagnostic observation schedule (ADOS), social interaction score from ADOS and stereotyped behaviors score from ADOS. In both datasets, we also found a significant correlation between ADI_RRB_TOTAL scale and the <em>Z</em>-score for edges between the bilateral ventral tegmental area (VTA) and between the left VTA and right substantia nigra pars compacta.</div></div><div><h3>Conclusion</h3><div>ASD exhibited brain structural heterogeneity at the systemic level, mainly involving nucleus in the subcortical regions and brainstem, which can affect RRB in ASD patients. The two subtypes discovered in this study have the potential to be applied in precise diagnosis and treatment of the disorder.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111224"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873524","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":"Natural polyphenols as therapeutic candidates for mitigating neuropsychiatric symptoms in post-traumatic stress disorder: Evidence from preclinical studies","authors":"Payman Raise-Abdullahi ,&nbsp;Mehrnaz Rezvani ,&nbsp;Fatemeh Yousefi ,&nbsp;Sadaf Rahmani ,&nbsp;Morvarid Meamar ,&nbsp;Ehsan Raeis-Abdollahi ,&nbsp;Abbas Ali Vafaei ,&nbsp;Hamed Rashidipour ,&nbsp;Ali Rashidy-Pour","doi":"10.1016/j.pnpbp.2024.111230","DOIUrl":"10.1016/j.pnpbp.2024.111230","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a challenging mental health condition that affects millions of people worldwide after they experience traumatic events. The current medications often do not fully address the wide range of PTSD symptoms or the underlying brain mechanisms, prompting the need to explore new treatments. Polyphenols, which are natural compounds found in many plant-based foods, have gained interest due to their brain-protective, anti-inflammatory, and antioxidant benefits. This review looks at how polyphenols might help treat PTSD by influencing important brain pathways related to the disorder. We explored how polyphenols affect the stress-response system, fear-related memories, brain chemicals, and inflammation. Specifically, we discuss how compounds like resveratrol, curcumin, green tea extract, and quercetin can balance stress hormones, help reduce fear memories, regulate brain chemicals, and decrease brain inflammation. Studies with animals have provided insights into how these compounds might work to ease PTSD symptoms. Based on the preclinical studies, the present review suggests that polyphenols could be a valuable addition or alternative to current PTSD treatments. However, more research is needed to confirm these findings and to determine the best ways to use polyphenols in treating PTSD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111230"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900471","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 ReHo and ALFF values in drug-naïve depressed patients with suicidal ideation or attempts: Evidence from the REST-meta-MDD consortium","authors":"Guowei Luo ,&nbsp;Jian Zhou ,&nbsp;Luyu Liu ,&nbsp;Xinran Song ,&nbsp;Min Peng ,&nbsp;Xiangyang Zhang ,&nbsp;the REST-meta-MDD Consortium","doi":"10.1016/j.pnpbp.2024.111210","DOIUrl":"10.1016/j.pnpbp.2024.111210","url":null,"abstract":"<div><h3>Background</h3><div>The assessment of suicide risk in patients with major depressive disorder (MDD) is somewhat subjective in clinical diagnosis and may lead to diagnostic bias and serious consequences. Therefore, the aim of this study was to determine whether MDD patients with suicidal ideation or suicide attempts exhibited local brain functional synchrony and spontaneous activity intensity, thus providing certain imaging basis for suicide assessment.</div></div><div><h3>Methods</h3><div>This study was conducted using ReHo and ALFF analyses on 213 first episode drug-naïve MDD patients from the REST-meta-MDD consortium. All patients were categorized into MDD with SI or SA group and MDD without SI and SA. A voxel-based two-sample <em>t</em>-test was then used to identify brain regions with significant differences in ReHo or ALFF values. Finally, Reho or ALFF values of those brain regions in MDD with SI or SA group were extracted for correlation analysis with suicide severity.</div></div><div><h3>Results</h3><div>Compared with MDD patients without SI or SA, MDD patients with SI or SA had increased ReHo in the triangular part of left inferior frontal gyrus, orbital part of right inferior frontal gyrus and right precuneus gyrus, and increased ALFF in the middle occipital gyrus. All of these brain region characteristics were positively correlated with suicide severity on the HAMD 3th item score and HAMD 9th item score.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that abnormalities of regional spontaneous brain activity were found in IFG, precuneus gyrus, and MOG among MDD patients with suicidal thoughts or attempts, which provides a reliable imaging basis for identifying and preventing suicide.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111210"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781676","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":"Alterations in white matter microstructure in bipolar disorder patients with and without psychosis","authors":"Xiuli Wang ,&nbsp;Xipeng Long ,&nbsp;Bochao Cheng ,&nbsp;Yuan Cao ,&nbsp;Di Kong ,&nbsp;Baolin Wu ,&nbsp;Hongsheng Xie ,&nbsp;Ziru Zhao ,&nbsp;Neil Roberts ,&nbsp;Nenghan Zhang ,&nbsp;Zhiyun Jia","doi":"10.1016/j.pnpbp.2024.111229","DOIUrl":"10.1016/j.pnpbp.2024.111229","url":null,"abstract":"<div><h3>Objective</h3><div>The overlap of affective disturbance and psychosis considerably makes it complex to determine the etiology of bipolar disorder (BD) and develop targeted interventions. The present study aimed to determine the white matter microstructural alterations that distinguish between BD with psychosis (BDP) and BD with no psychosis (BDNP) to identify patients who may specifically benefit from appropriately effective treatments.</div></div><div><h3>Methods</h3><div>Diffusion-weighted magnetic resonance images were acquired from 38 participants with BDP, 52 participants with BDNP and 70 healthy controls (HCs). The indices of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were computed and compared among the three groups via tract-based spatial statistics (TBSS).</div></div><div><h3>Results</h3><div>Analysis of covariance (ANCOVA) revealed the main effects of group on the FA, MD and RD values of the forceps minor (FMI) of the corpus callosum, right anterior thalamic radiation (ATR), and left corticospinal tract (CST). Post hoc analysis revealed that BDP patients had lower FA value in the FMI than HCs did, as well as lower FA and higher RD values in the FMI than BDNP patients did, whereas BDNP patients had lower FA and MD values in the right ATR, as well as higher FA and lower RD values in the left CST than HCs did.</div></div><div><h3>Conclusion</h3><div>These findings provide further insights into the specific neurobiological mechanisms that underlie the presence of psychosis in BD patients and represent potential objective biomarkers for differentiating between BDP and BDNP.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111229"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883652","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":"Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy.","authors":"Randall D Ordovich-Clarkson, Maurice Jabbour, Daniel Arteaga Pelayo, Daniel Lara, Sebastian La Croix, Macie Mumman, Shoshanah Stukas, Reagan Anderson, David Meraz, Anthony Bangura, Brooklyn Anderson, Luke Bamrud, Caleb Blake","doi":"10.1016/j.pnpbp.2024.111155","DOIUrl":"10.1016/j.pnpbp.2024.111155","url":null,"abstract":"<p><strong>Background & aim: </strong>Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD.</p><p><strong>Methods: </strong>The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects.</p><p><strong>Results: </strong>The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT_2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation.</p><p><strong>Conclusion: </strong>Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111155"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367380","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":"Volumetric MRI correlates of persistent auditory verbal hallucinations and olfactory identification impairment in chronic schizophrenia: A cross-sectional study","authors":"Qianjin Wang ,&nbsp;Zongchang Li ,&nbsp;Jinguang Li ,&nbsp;Ying He ,&nbsp;Jun Zhou ,&nbsp;Chunwang Li ,&nbsp;Xiaogang Chen ,&nbsp;Jinsong Tang ,&nbsp;Honghong Ren","doi":"10.1016/j.pnpbp.2024.111204","DOIUrl":"10.1016/j.pnpbp.2024.111204","url":null,"abstract":"<div><h3>Background</h3><div>Olfactory impairments are often observed in schizophrenia (SCZ) patients experiencing persistent auditory verbal hallucinations (pAVHs), yet it remains unclear whether these symptoms share a common neural mechanism with specific brain regions' gray matter volume (GMV) abnormalities. This study aimed to preliminarily elucidate olfactory impairment differences between SCZ patients with and without pAVHs and their correlation with GMV abnormalities in relevant brain regions.</div></div><div><h3>Methods</h3><div>A total of 75 SCZ patients with pAVHs (pAVH group), 56 SCZ patients without AVHs (non-AVH group), and 83 healthy controls (HC group) were examined. Voxel-based morphometry is useful for comparing and analyzing the differences in GMV among three groups. The Odor Stick Identification Test for Japanese (OSIT-J) was harnessed to gauge olfactory abilities.</div></div><div><h3>Results</h3><div>Olfactory impairments are notably significant across entire SCZ patients compared to HC, with no significant differences in olfactory performance among SCZ subgroups. Notably, the pAVH group demonstrated a significant GMV diminution in the frontal-temporal cortex, starkly contrasting with the non-pAVH and HC groups. Intriguingly, stepwise regression analysis confirmed a strong positive relation between OSIT-J scores and a GMV reduction in the right medial orbitofrontal cortex (mOFC), although this correlation was only observed in the overall SCZ patient group (<em>P</em> &lt; 0.0036, Bonferroni correction).</div></div><div><h3>Conclusions</h3><div>The GMV perturbations within the mOFC, distinctive to SCZ, may underpin the neuroimaging substrates linked to heightened vulnerability to olfactory impairments in this population. This exploration underscores the imperative of delving into the neural underpinnings of sensory impairments within SCZ, propelling a nuanced understanding of its heterogeneity.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111204"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717839","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":"Progressive structural alterations associated with negative symptoms in schizophrenia: A causal structural covariance network analysis","authors":"Chao Zhou ,&nbsp;Rongrong Zhang ,&nbsp;Mubing Ding ,&nbsp;Wenhuan Duan ,&nbsp;Jin Fang ,&nbsp;Xiaowei Tang ,&nbsp;Qiushuang Qu ,&nbsp;Xiangrong Zhang","doi":"10.1016/j.pnpbp.2024.111236","DOIUrl":"10.1016/j.pnpbp.2024.111236","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Aberrant brain structures in schizophrenia have been widely explored. However, the causal effects of negative symptoms on brain structural alterations are still unclear. This study aims to explore the synchronous and progressive alterations in gray matter volume (GMV) associated with negative symptoms.</div></div><div><h3>Methods</h3><div>81 Deficit schizophrenia (DS) patients, 101 non-deficit schizophrenia (NDS) patients, and 177 healthy controls (HCs) were enrolled in this study. T1-weighted images were collected, and the severity of clinical symptoms in patients was evaluated. Then voxel-based morphometry and source-based morphometry were used for gray matter segmentation and structural covariance network construction. Finally, DS patients were ranked based on the severity of negative symptoms, and a causal structural covariance network (CaSCN) was constructed using Granger causality analysis.</div></div><div><h3>Results</h3><div>Twenty-four independent components were identified. Among them, 20 components showed smaller GMV in patients with schizophrenia compared to HCs. Furthermore, DS exhibited decreased GMV in right inferior frontal gyrus triangular part, bilateral para-hippocampal gyrus, and bilateral anterior cerebellum compared to NDS. Both patient groups showed increased structural covariance across various brain regions compared to HCs. Additionally, DS exhibited decreased structural covariance in left middle frontal gyrus, bilateral inferior frontal gyrus and right superior frontal gyrus compared to NDS. In CaSCN, as negative symptoms worsened, the volume of bilateral caudate decreased along with the atrophy of bilateral para-hippocampal gyrus, the volume of bilateral thalamus increased along with the decline in multiple brain regions, and the decreased volume of bilateral posterior cingulate cortex resulted in increased volume of bilateral lingual gyrus and other brain regions.</div></div><div><h3>Conclusions</h3><div>The present study demonstrated the specific brain structural covariance patterns in DS, providing new evidence for the causal effects of negative symptoms on progressive structural abnormalities in schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111236"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900465","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":"Role of peroxisome proliferator-activated receptors α and γ in mediating the beneficial effects of β-caryophyllene in a rat model of fragile X syndrome","authors":"Alessandro Rava ,&nbsp;Valeria Buzzelli ,&nbsp;Alessandro Feo ,&nbsp;Fabrizio Ascone ,&nbsp;Melania Di Trapano ,&nbsp;Sara Schiavi ,&nbsp;Emilia Carbone ,&nbsp;Andrea Pasquadibisceglie ,&nbsp;Fabio Polticelli ,&nbsp;Antonia Manduca ,&nbsp;Viviana Trezza","doi":"10.1016/j.pnpbp.2024.111234","DOIUrl":"10.1016/j.pnpbp.2024.111234","url":null,"abstract":"<div><div>β-Caryophyllene (BCP) is a naturally occurring sesquiterpene found in numerous plant species, including <em>Cannabis sativa</em>. BCP has shown a high safety profile and a wide range of biological functions, including beneficial effects in neurodegenerative and inflammatory diseases. Here, we used behavioral, pharmacological, and <em>in-silico</em> docking analyses to investigate the effects and mechanism of action of BCP in Fragile X Syndrome (FXS), the most common inherited cause of Autism Spectrum Disorder (ASD) and intellectual disability. To this aim, we used the recently validated <em>Fmr1-</em>^<em>Δ</em><em>exon 8</em> rat model of FXS, that is also a genetic rat model of ASD.</div><div>Acute and repeated oral administration of BCP rescued the cognitive deficits displayed by <em>Fmr1-</em>^<em>Δ</em><em>exon 8</em> rats, without inducing tolerance after repeated administration. These beneficial effects were mediated by activation of hippocampal peroxisome proliferator-activated receptors (PPARs) α and γ, and were mimicked by the PPARα agonist Fenofibrate and the PPARγ agonist Pioglitazone. Conversely, CB2 cannabinoid receptors were not involved. Docking analyses further confirmed the ability of BCP to bind rat PPARs. Together, our findings demonstrate that hippocampal PPARs α and γ play a role in the cognitive deficits observed in a rat model of FXS, and provide first preclinical evidence about the efficacy and mechanism of action of BCP in neurodevelopmental disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111234"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900467","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}