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Natural polyphenols as therapeutic candidates for mitigating neuropsychiatric symptoms in post-traumatic stress disorder: Evidence from preclinical studies 天然多酚作为减轻创伤后应激障碍神经精神症状的治疗候选者：来自临床前研究的证据

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111230

Payman Raise-Abdullahi , Mehrnaz Rezvani , Fatemeh Yousefi , Sadaf Rahmani , Morvarid Meamar , Ehsan Raeis-Abdollahi , Abbas Ali Vafaei , Hamed Rashidipour , Ali Rashidy-Pour

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.

创伤后应激障碍（PTSD）是一种具有挑战性的精神健康状况，在经历创伤性事件后影响着全世界数百万人。目前的药物往往不能完全解决创伤后应激障碍的广泛症状或潜在的大脑机制，这促使人们需要探索新的治疗方法。多酚是一种存在于许多植物性食物中的天然化合物，由于其对大脑的保护、抗炎和抗氧化作用而引起了人们的兴趣。这篇综述着眼于多酚如何通过影响与PTSD相关的重要脑通路来帮助治疗PTSD。我们探索了多酚如何影响压力反应系统、与恐惧相关的记忆、大脑化学物质和炎症。具体来说，我们讨论了像白藜芦醇、姜黄素、绿茶提取物和槲皮素这样的化合物如何平衡压力激素，帮助减少恐惧记忆，调节大脑化学物质，减少大脑炎症。对动物的研究为这些化合物如何缓解创伤后应激障碍症状提供了见解。基于临床前研究，目前的综述表明，多酚可能是目前PTSD治疗的一种有价值的补充或替代方法。然而，需要更多的研究来证实这些发现，并确定使用多酚治疗创伤后应激障碍的最佳方法。

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引用次数: 0

Abnormal ReHo and ALFF values in drug-naïve depressed patients with suicidal ideation or attempts: Evidence from the REST-meta-MDD consortium drug-naïve有自杀意念或企图的抑郁症患者ReHo和ALFF值异常：来自REST-meta-MDD联盟的证据

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111210

Guowei Luo , Jian Zhou , Luyu Liu , Xinran Song , Min Peng , Xiangyang Zhang , the REST-meta-MDD Consortium

Background

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.

Methods

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 t-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.

Results

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.

Conclusion

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.

背景：重度抑郁障碍（MDD）患者自杀风险评估在临床诊断中存在一定的主观性，可能导致诊断偏差和严重后果。因此，本研究的目的是确定有自杀意念或自杀企图的MDD患者是否表现出局部脑功能同步性和自发活动强度，从而为自杀评估提供一定的影像学依据。方法：本研究对来自REST-meta-MDD联盟的213例首发drug-naïve MDD患者进行ReHo和ALFF分析。将所有患者分为伴有SI或SA的MDD组和不伴有SI和SA的MDD组。然后使用基于体素的双样本t检验来识别ReHo或ALFF值存在显著差异的大脑区域。最后提取MDD合并SI或SA组脑区Reho或ALFF值与自杀严重程度的相关性分析。结果：与未伴SI或SA的MDD患者相比，伴SI或SA的MDD患者左侧额下回三角区、右侧额下回眶区和右侧楔前回的ReHo升高，枕中回ALFF升高。这些脑区特征与自杀严重程度在HAMD第3项和第9项得分上呈显著正相关。结论：我们的研究结果提示MDD患者有自杀念头或企图时，IFG、楔前回、MOG等区域自发性脑活动出现异常，为识别和预防自杀提供了可靠的影像学依据。

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引用次数: 0

Alterations in white matter microstructure in bipolar disorder patients with and without psychosis 双相情感障碍伴和不伴精神病患者白质微结构的改变。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111229

Xiuli Wang , Xipeng Long , Bochao Cheng , Yuan Cao , Di Kong , Baolin Wu , Hongsheng Xie , Ziru Zhao , Neil Roberts , Nenghan Zhang , Zhiyun Jia

Objective

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.

Methods

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).

Results

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.

Conclusion

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.

目的：情感障碍与精神疾病的重叠使得确定双相情感障碍（BD）的病因和制定有针对性的干预措施变得非常复杂。本研究旨在确定区分双相障碍合并精神病（BDP）和双相障碍合并非精神病（BDNP）的白质微结构改变，以确定可能从适当有效治疗中获益的患者。方法：对38例BDP患者、52例BDNP患者和70例健康对照（hc）进行弥散加权磁共振成像。采用基于束的空间统计方法（TBSS）计算并比较各组的分数各向异性（FA）、平均扩散系数（MD）、径向扩散系数（RD）和轴向扩散系数（AD）。结果：协方差分析（ANCOVA）揭示了各组对胼胝体小腹（FMI） FA、MD和RD值、右侧丘脑前辐射（ATR）和左侧皮质脊髓束（CST）的主要影响。事后分析显示，BDP患者在FMI的FA值低于hcc患者，FMI的FA值低于BDNP患者，FMI的RD值高于BDNP患者，而BDNP患者在右侧ATR的FA和MD值低于hcc患者，左侧CST的FA和RD值高于hcc患者。结论：这些发现进一步揭示了BD患者精神病存在的特定神经生物学机制，并为区分BDP和BDNP提供了潜在的客观生物标志物。

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引用次数: 0

Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy. 比较迷幻药和二甲双胍作为帕金森痴呆症的神经保护剂：对证据和疗效的系统回顾。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 Epub Date: 2024-09-30 DOI: 10.1016/j.pnpbp.2024.111155

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

Background & aim: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

背景和目的：帕金森病（PD）的治疗方法基本未变，主要侧重于通过激活多巴胺能通路来缓解症状。目前，还没有经证实的预防帕金森病的方法。本系统综述旨在比较两种不同的化合物--二甲双胍（MTF）和迷幻药--作为预防帕金森氏症的潜在疗法：作者进行了一项系统性综述，重点关注在细胞和动物模型上测试这两种化合物的主要研究，以确定它们是否具有任何神经保护或神经可塑性作用：综述结果发现，MTF 可通过多种机制阻止帕金森病等疾病的发展，包括减少线粒体水平的氧化应激，从而减少与 α-突触核蛋白相关的损伤。另一方面，迷幻药可能会通过激活血清素能通路，特别是激活 5-HT2A 受体，增加受损神经元的修复，最终增加脑源性神经营养因子（BDNF）的释放，减少α-突触核蛋白的积累：本研究的意义包括需要进一步研究MTF的标签外使用，以及进一步研究5-羟色胺能化合物，如治疗和预防神经退行性疾病的迷幻药。

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引用次数: 0

Volumetric MRI correlates of persistent auditory verbal hallucinations and olfactory identification impairment in chronic schizophrenia: A cross-sectional study 慢性精神分裂症患者持续性听觉言语幻觉和嗅觉识别障碍的容积磁共振成像相关性：横断面研究

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111204

Qianjin Wang , Zongchang Li , Jinguang Li , Ying He , Jun Zhou , Chunwang Li , Xiaogang Chen , Jinsong Tang , Honghong Ren

Background

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.

Methods

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.

Results

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 (P < 0.0036, Bonferroni correction).

Conclusions

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.

背景：精神分裂症（SCZ）患者在出现持续性听觉言语幻觉（pAVH）时常会出现嗅觉障碍，但这些症状是否与特定脑区灰质体积（GMV）异常有共同的神经机制，目前仍不清楚。本研究旨在初步阐明伴有和不伴有持续性听觉言语幻觉的SCZ患者的嗅觉障碍差异及其与相关脑区灰质体积异常的相关性：共研究了75名患有pAVHs的SCZ患者（pAVH组）、56名不患有AVHs的SCZ患者（非AVH组）和83名健康对照组（HC组）。基于体素的形态计量学有助于比较和分析三组之间 GMV 的差异。日语气味棒识别测试（OSIT-J）被用来衡量嗅觉能力：结果：与HC相比，所有SCZ患者的嗅觉障碍都非常明显，而SCZ亚组之间的嗅觉表现没有显著差异。值得注意的是，pAVH 组的额颞叶皮层 GMV 明显减少，与非 pAVH 组和 HC 组形成鲜明对比。耐人寻味的是，逐步回归分析证实，OSIT-J评分与右侧内侧眶额皮层（mOFC）的GMV减少之间存在很强的正相关关系，但这种相关性仅在整个SCZ患者组中观察到（P 结论：OSIT-J评分与右侧内侧眶额皮层（mOFC）的GMV减少之间存在很强的正相关关系：内侧眶额皮层 GMV 的扰动是 SCZ 独有的特征，它可能是与该人群嗅觉障碍易感性增加有关的神经影像学基质的基础。这一探索强调了深入研究 SCZ 感觉障碍的神经基础的必要性，从而推动了对其异质性的深入理解。

{"title":"Volumetric MRI correlates of persistent auditory verbal hallucinations and olfactory identification impairment in chronic schizophrenia: A cross-sectional study","authors":"Qianjin Wang , Zongchang Li , Jinguang Li , Ying He , Jun Zhou , Chunwang Li , Xiaogang Chen , Jinsong Tang , 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> < 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}

引用次数: 0

Progressive structural alterations associated with negative symptoms in schizophrenia: A causal structural covariance network analysis 精神分裂症中与阴性症状相关的进行性结构改变：因果结构协方差网络分析

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111236

Chao Zhou , Rongrong Zhang , Mubing Ding , Wenhuan Duan , Jin Fang , Xiaowei Tang , Qiushuang Qu , Xiangrong Zhang

Backgrounds

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.

Methods

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.

Results

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.

Conclusions

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.

背景：精神分裂症患者的异常脑结构已被广泛探讨。然而，阴性症状对大脑结构改变的因果影响尚不清楚。本研究旨在探讨与阴性症状相关的灰质体积（GMV）的同步和进行性改变。方法：81例缺乏性精神分裂症（DS）患者、101例非缺乏性精神分裂症（NDS）患者和177例健康对照（hc）进行研究。收集t1加权图像，评估患者临床症状的严重程度。然后分别采用基于体素的形态学和基于源的形态学进行脑灰质分割和结构协方差网络构建。最后，根据阴性症状的严重程度对DS患者进行排序，并采用格兰杰因果分析构建因果结构协方差网络（CaSCN）。结果：鉴定出24种独立成分。其中，精神分裂症患者有20个组分的GMV小于hc。与NDS相比，DS表现出右侧额下回三角区、双侧海马旁回和双侧小脑前部的GMV下降。与hc相比，两组患者在不同脑区的结构协方差均有所增加。此外，与NDS相比，DS在左侧额中回、双侧额下回和右侧额上回的结构协方差降低。CaSCN中，随着阴性症状加重，双侧尾状核体积减小，双侧海马旁回萎缩，双侧丘脑体积增大，多脑区萎缩，双侧后扣带皮质体积减小，双侧舌回等脑区体积增大。结论：本研究揭示了退行性痴呆的特定脑结构协方差模式，为阴性症状与精神分裂症进行性结构异常的因果关系提供了新的证据。

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引用次数: 0

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 过氧化物酶体增殖物激活受体α和γ在脆性X综合征大鼠模型中介导β-石竹烯有益作用的作用。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111234

Alessandro Rava , Valeria Buzzelli , Alessandro Feo , Fabrizio Ascone , Melania Di Trapano , Sara Schiavi , Emilia Carbone , Andrea Pasquadibisceglie , Fabio Polticelli , Antonia Manduca , Viviana Trezza

β-Caryophyllene (BCP) is a naturally occurring sesquiterpene found in numerous plant species, including Cannabis sativa. 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 in-silico 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 Fmr1-^Δexon 8 rat model of FXS, that is also a genetic rat model of ASD.

Acute and repeated oral administration of BCP rescued the cognitive deficits displayed by Fmr1-^Δexon 8 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.

β-石竹烯（BCP）是一种天然存在的倍半萜，存在于许多植物物种中，包括大麻。BCP已显示出高安全性和广泛的生物学功能，包括对神经退行性疾病和炎症性疾病的有益作用。本研究采用行为学、药理学和计算机对接分析的方法，研究了BCP在脆性X综合征（FXS）中的作用及其机制。脆性X综合征是自闭症谱系障碍（ASD）和智力残疾最常见的遗传原因。为此，我们使用了最近验证的Fmr1-Δexon 8大鼠FXS模型，该模型也是ASD的遗传大鼠模型。急性和反复口服BCP可恢复Fmr1-Δexon 8大鼠的认知缺陷，但反复给药后未产生耐受。这些有益作用是通过激活海马过氧化物酶体增殖物激活受体(ppar) α和γ介导的，并被PPARα激动剂非诺贝特和PPARγ激动剂吡格列酮模拟。相反，CB2大麻素受体不参与。对接分析进一步证实了BCP结合大鼠PPARs的能力。总之，我们的研究结果表明，海马ppar α和γ在FXS大鼠模型中观察到的认知缺陷中起作用，并为BCP在神经发育障碍中的疗效和作用机制提供了第一个临床前证据。

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引用次数: 0

The gut-brain axis: Unveiling the impact of xenobiotics on neurological health and disorders 肠脑轴：揭示外源性药物对神经系统健康和疾病的影响。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111237

Sushruta Koppula , Nitu Wankhede , Ashishkumar Kyada , Suhas Ballal , Renu Arya , Anurag Kumar Singh , Monica Gulati , Astha Sute , Sanskruti Sarode , Shruti Polshettiwar , Vaibhav Marde , Brijesh Taksande , Aman Upaganlawar , Mohammad Fareed , Milind Umekar , Spandana Rajendra Kopalli , Mayur Kale

The Gut-Brain Axis (GBA) is a crucial link between the gut microbiota and the central nervous system. Xenobiotics, originating from diverse sources, play a significant role in shaping this interaction. This review examines how these compounds influence neurotransmitter dynamics within the GBA. Environmental pollutants can disrupt microbial populations, impacting neurotransmitter synthesis—especially serotonin, gamma-aminobutyric acid (GABA), and dopamine pathways. Such disruptions affect mood regulation, cognition, and overall neurological function. Xenobiotics also contribute to the pathophysiology of neurological disorders, with changes in serotonin levels linked to mood disorders and imbalances in GABA and dopamine associated with anxiety, stress, and reward pathway disorders. These alterations extend beyond the GBA, leading to complications in neurological health, including increased risk of neurodegenerative diseases due to neuroinflammation triggered by neurotransmitter imbalances. This review provides a comprehensive overview of how xenobiotics influence the GBA and their implications for neurological well-being.

肠脑轴（GBA）是肠道微生物群和中枢神经系统之间的关键联系。来自不同来源的异种生物在形成这种相互作用中起着重要作用。这篇综述探讨了这些化合物如何影响大湾区内的神经递质动力学。环境污染物可以破坏微生物种群，影响神经递质合成——尤其是血清素、γ -氨基丁酸（GABA）和多巴胺途径。这种干扰会影响情绪调节、认知和整体神经功能。异种生物制剂也有助于神经系统疾病的病理生理学，血清素水平的变化与情绪障碍有关，GABA和多巴胺的失衡与焦虑、压力和奖励通路障碍有关。这些改变延伸到大湾区以外，导致神经系统健康并发症，包括神经递质失衡引发的神经炎症导致神经退行性疾病风险增加。本文综述了外源药物如何影响大湾区及其对神经系统健康的影响。

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引用次数: 0

Understanding the role of environment in associative learning of nicotine-induced place preference conditioning in zebrafish 了解环境在尼古丁诱导的斑马鱼位置偏好条件反射的联想学习中的作用。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111242

M.P. Faillace, L. Rocco, J. Ortiz, R. Bernabeu

Environmental enrichment (EE) is a well-known strategy in animal behavior to improve the welfare and health of animals in captivity. EE provides animals with stimulating and engaging environments that promote natural behaviors, cognitive stimulation and stress reduction. EE turns out to be an important strategy to increase the validity and reproducibility of behavioral data. Zebrafish is a useful experimental model for pharmaceutical and toxicological screening to study mechanisms involved in behavioral flexibility. The present work examined for the first time whether exposure to an EE during conditioning in the conditioned place preference (EE-CPP) task modulates the rewarding properties of nicotine in zebrafish. Various combinations of preferred and avoided environments (via positive and aversive cues introduced in each compartment of the CPP tank) were tested in the EE-CPP task. Positive nicotine-CPP scores were obtained in all conditions tested, except when the aversive and preferred stimuli were placed in the same compartment. When two highly preferred stimuli (brown walls and plants) were associated with dots drawn on the floor of the nicotine-matched compartment, nicotine-CPP score was lower. These findings suggest that threatening stimuli in the environment where the drug is administered or consumed could disrupt conditioning and reduce drug rewarding effects. A series of other behavioral parameters corroborated EE-CPP scores. Our findings underscore the need for further research to better understand how these factors interact and influence an individual's vulnerability to nicotine addiction. The present study contributes to expand our understanding of the dynamics involved in the behavioral flexibility underlying nicotine addiction.

环境富集（EE）是一种众所周知的动物行为策略，旨在改善圈养动物的福利和健康。情感表达为动物提供了刺激和参与的环境，促进了自然行为、认知刺激和压力减轻。结果表明，情感表达是提高行为数据有效性和可重复性的重要策略。斑马鱼是一种有用的实验模型，用于药物和毒理学筛选，以研究行为灵活性的机制。本研究首次研究了斑马鱼在条件性位置偏好（EE- cpp）任务中暴露于情感表达是否会调节尼古丁的奖励特性。在EE-CPP任务中测试了偏好和避免环境的各种组合（通过在CPP水箱的每个隔间中引入积极和厌恶的线索）。在所有测试条件下，除了将厌恶刺激和偏好刺激放在同一隔间中，尼古丁- cpp得分均为正。当两种高度偏好的刺激（棕色墙壁和植物）与尼古丁匹配的隔间地板上画的点相关联时，尼古丁- cpp得分较低。这些发现表明，在给药或服用药物的环境中，威胁性刺激可能会破坏条件反射，降低药物奖励效应。一系列其他行为参数证实了EE-CPP评分。我们的发现强调了进一步研究的必要性，以更好地了解这些因素如何相互作用并影响个人对尼古丁成瘾的脆弱性。本研究有助于扩大我们对尼古丁成瘾行为灵活性动力学的理解。

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引用次数: 0

Neuroanatomical subtypes of tobacco use disorder and relationship with clinical and molecular features 烟草使用障碍的神经解剖学亚型及其与临床和分子特征的关系。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111235

Mengzhe Zhang, Xiaoyu Niu, Jinghan Dang, Jieping Sun, Qiuying Tao, Weijian Wang, Shaoqiang Han, Jingliang Cheng, Yong Zhang

Background

Individual neurobiological heterogeneity among patients with tobacco use disorder (TUD) hampers the identification of neuroimaging phenotypes.

Methods

The current study recruited 122 TUD individuals and 57 healthy controls, and obtained their 3D-T1 images. Heterogeneity through discriminative analysis (HYDRA) was applied to uncover the potential subtype of TUD where regional gray matter volume (GMV) was treated as the feature. Then we examined the clinical, neuroimaging and molecular characteristics of subtypes.

Results

Two distinct neuroanatomical subtypes were found. In subtype 1, TUD individuals showed decreased GMV in right orbitofrontal cortex (OFC), while subtype 2 exhibited distributed pattern of widely GMV increase. Moreover, subtype 1 showed older initial smoking age, longer duration of smoking than Subtype 2. Persistent smoking behavior in subtype 1 is more likely caused by substance dependence/addiction rather than psychosocial factors. GMV correlated negatively with cumulative tobacco exposure in Subtype 1 but not in Subtype 2. Besides, neuroanatomical aberrance in subtype 1 was mainly associated with dopamine system, while neuroanatomical abnormalities in subtype 2 were primarily associated with GABAa.

Conclusions

Overall, our results revealed two opposite neuroanatomical subtypes of TUD, which largely overlapped with their clinical and molecular features respectively. TUD subtypes taxonomy based on objective anatomy could help to facilitate the development of individualized treatment for TUD.

背景：烟草使用障碍（TUD）患者的个体神经生物学异质性阻碍了神经影像学表型的识别。方法：本研究招募了122名TUD患者和57名健康对照者，获取他们的3D-T1图像。以区域灰质体积（GMV）为特征，应用异质性判别分析（HYDRA）揭示TUD的潜在亚型。然后我们检查了亚型的临床、神经影像学和分子特征。结果：发现两种不同的神经解剖学亚型。在亚型1中，TUD个体表现为右侧眶额皮质（OFC） GMV下降，而亚型2表现为GMV广泛升高的分布模式。亚型1比亚型2的初吸烟年龄大，吸烟持续时间长。1型患者的持续吸烟行为更可能是由物质依赖/成瘾引起的，而不是社会心理因素。GMV与累积烟草暴露在亚型1中呈负相关，而在亚型2中无相关。此外，亚型1的神经解剖学异常主要与多巴胺系统有关，亚型2的神经解剖学异常主要与GABAa有关。结论：总的来说，我们的结果揭示了两种相反的神经解剖学亚型，它们的临床和分子特征在很大程度上重叠。基于客观解剖的TUD亚型分类有助于促进TUD个体化治疗的发展。

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引用次数: 0