Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献_第3页

High-fat diet-induced obesity enhances stress vulnerability and promotes a PTSD-like phenotype in rats 高脂肪饮食引起的肥胖增加应激易感性，促进大鼠ptsd样表型。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2025.111596

Carmit Cohen , Joseph Zohar , Doron Todder , Hagit Cohen

The association between post-traumatic stress disorder (PTSD) and subsequent obesity is well-established in humans, however, whether obesity exacerbates vulnerability to PTSD remains underexplored. To investigate this, we employed a rat model fed either a high-fat diet (HFD; 60 % kcal from fat) or a control diet (CD). After confirming significant body mass index differences between HFD and CD groups, rats were exposed to predator scent stress (PSS) or a sham-PSS control. Behavioral phenotyping was conducted using the elevated plus maze (EPM) and acoustic startle response (ASR) to classify stress response profiles, supplemented by the forced swim test to assess depressive-like behavior and the Morris water maze to evaluate spatial learning and memory. Neural cytoarchitecture and molecular mechanisms were examined via Golgi-Cox staining and immunohistochemistry, targeting shared modulators of the orexigenic and anxiolytic systems in the hippocampus and hypothalamus. Our findings reveal that HFD-induced obesity promotes a PTSD-like phenotype, exacerbates depressive-like behavior, and impairs spatial learning and memory acquisition. Morphological alterations in the hippocampus and amygdala of HFD-fed rats resembled those in PSS-exposed CD-fed rats, regardless of stress exposure, suggesting common neurostructural changes. Furthermore, HFD-induced obesity modulated region-specific expression of neuropeptide Y (NPY), NPY-Y1 receptor, and glucocorticoid receptor immunoreactivity in hippocampal and hypothalamic nuclei. These results underscore a bidirectional interplay between diet-induced obesity and stress-related disorders, highlighting the critical role of the orexigenic and anxiolytic systems and their neurobiological underpinnings in mediating these effects.

创伤后应激障碍（PTSD）和随后的肥胖之间的联系在人类中是公认的，然而，肥胖是否会加剧创伤后应激障碍的易感性仍未得到充分研究。为了研究这一点，我们采用了高脂肪饮食（HFD； 60% %卡路里来自脂肪）或对照饮食（CD）的大鼠模型。在确认HFD组和CD组之间的显著体重指数差异后，将大鼠暴露于捕食者气味应激（PSS）或假PSS对照组。行为表型研究采用升高+迷宫（EPM）和声惊反应（ASR）对应激反应进行分类，辅以强迫游泳测试评估抑郁样行为，Morris水迷宫评估空间学习和记忆。通过高尔基-考克斯染色和免疫组织化学检测神经细胞结构和分子机制，以海马和下丘脑的促氧和抗焦虑系统的共同调节剂为目标。我们的研究结果表明，hfd诱导的肥胖促进了ptsd样表型，加剧了抑郁样行为，并损害了空间学习和记忆的获得。hfd喂养的大鼠海马和杏仁核的形态学改变与pss喂养的cd喂养的大鼠相似，无论应激暴露如何，都表明了共同的神经结构变化。此外，hfd诱导的肥胖调节了海马和下丘脑核中神经肽Y （NPY）、NPY- y1受体和糖皮质激素受体免疫反应性的区域特异性表达。这些结果强调了饮食引起的肥胖和压力相关疾病之间的双向相互作用，强调了产氧和抗焦虑系统及其神经生物学基础在介导这些影响中的关键作用。

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引用次数: 0

Effects of intermittent theta- burst stimulation on emotion anticipation and processing in depression- investigating behavioral, electrodermal and neural activity 间歇性波爆发刺激对抑郁症情绪预期和加工的影响——行为、皮肤电和神经活动的研究。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2026.111606

Wiebke Struckmann , Magdalena Wlad , Jörgen Rosén , David Fällmar , Robert Bodén , Jonas Persson , Malin Gingnell

Background

Depression is characterized by disturbed emotion processing. Repetitive transcranial magnetic stimulation, and its development intermittent theta- burst stimulation (iTBS), induces brain network changes and is an emerging treatment alternative for depression. In this sham- controlled study, we aimed at studying the effects of iTBS on emotion anticipation and processing in depression.

Methods

42 patients with depression were allocated to receive active or sham iTBS treatment. Before treatment (baseline) and four weeks after baseline (follow- up), participants underwent functional magnetic resonance imaging (fMRI) scanning with simultaneous recordings of skin conductance responses (SCR). During scanning, participants were presented to an emotion anticipation and processing paradigm. Behavioral data (symptom ratings and ratings of emotional stimuli) were also collected.

Results

There were no differences in behavioral, skin conductance or neural activity after active, compared with sham, treatment. However, across groups, SCRs to positive anticipation increased and SCRs to negative processing decreased at follow- up. Additionally, amygdala and right insula reactivity to negative processing, and right amygdala reactivity to positive processing, decreased at follow- up. Increased ACC activity after active treatment to positive anticipation and processing was correlated with decreased anhedonia symptoms.

Conclusions

Active, compared with sham, iTBS treatment does not affect behavioral, skin conductance or neural activity to emotion anticipation and processing in depression. However, across treatment groups, changes occur with time, perhaps reflecting normalization processes or partial treatment effect of sham iTBS. The ACC seems to be involved in the treatment mechanism of iTBS.

背景：抑郁症以情绪加工障碍为特征。反复经颅磁刺激及其发展为间歇性θ波爆发刺激（iTBS），可诱导脑网络变化，是一种新兴的抑郁症治疗方法。在本实验中，我们旨在研究iTBS对抑郁症患者情绪预期和加工的影响。方法：将42例抑郁症患者分为主动iTBS和假iTBS两组。在治疗前（基线）和基线后4周（随访），参与者接受功能性磁共振成像（fMRI）扫描，同时记录皮肤电导反应（SCR）。在扫描过程中，参与者被呈现在情绪预期和处理范式中。行为数据（症状评分和情绪刺激评分）也被收集。结果：与假治疗相比，治疗后大鼠的行为、皮肤电导及神经活动均无明显差异。然而，在随访中，各组对积极预期的scr增加，对消极加工的scr减少。此外，杏仁核和右脑岛对消极加工的反应性，以及右杏仁核对积极加工的反应性在随访中有所下降。积极的预期和加工治疗后ACC活性的增加与快感缺乏症状的减少相关。结论：与假治疗相比，主动iTBS治疗不影响抑郁症患者的行为、皮肤电导或情绪预期和加工的神经活动。然而，在整个治疗组中，随着时间的推移会发生变化，这可能反映了假性iTBS的正常化过程或部分治疗效果。ACC似乎参与了iTBS的治疗机制。

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引用次数: 0

Complex relationship between endocannabinoids, fatty acid amide hydrolase, and stress reactivity in human intrusive memories of analogue trauma 内源性大麻素、脂肪酸酰胺水解酶和应激反应在人类模拟创伤侵入性记忆中的复杂关系

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2026.111610

Madeline A. Jarvis , Allison Matthews , Ken Chia Min Hsu , Emma Nicholson , Khalisa Amir Hamzah , Natalie Turner , Daniel V. Zuj , David Nichols , Kim Felmingham , Luke J. Ney

The endocannabinoid system has been shown to be involved in posttraumatic stress disorder-like behaviours in animal and human subjects. However, to date no studies have tested the relationship between blood markers of endocannabinoid signalling and intrusive memory development in humans. Across two studies, we tested the relationship between endocannabinoid genotypes, blood markers of endocannabinoids AEA and 2-AG, and intrusive memories of violent imagery and film clips. In study 1, we found a significant effect of rs324420 genotype on explicit memory recall, with A allele carriers (indicative of higher AEA) recalling fewer negative memories. Post-task AEA was negatively associated with explicit recall but not intrusive memories, though post-task AEA and 2-AG did interact with rs324420 to predict intrusive memory frequency. In study 2, stress induced changes in AEA but not 2-AG were negatively associated with intrusive memory frequency. In summary, we found evidence that AEA is involved in explicit and intrusive memories of negative stimuli. Evidence from both studies suggests that lower AEA is associated with higher explicit and intrusive memories. These findings support animal literature and have implications for targeted treatments for negative memory symptomology in posttraumatic stress disorder.

内源性大麻素系统已被证明与动物和人类的创伤后应激障碍行为有关。然而，到目前为止，还没有研究测试内源性大麻素信号的血液标记物与人类侵入性记忆发展之间的关系。在两项研究中，我们测试了内源性大麻素基因型、内源性大麻素AEA和2-AG的血液标记物与暴力图像和电影片段的侵入性记忆之间的关系。在研究1中，我们发现rs324420基因型对外显记忆回忆有显著影响，a等位基因携带者（表明AEA较高）回忆的负面记忆较少。任务后AEA与外显记忆呈负相关，但与侵入性记忆无关，但任务后AEA和2-AG与rs324420确实相互作用，预测侵入性记忆频率。在研究2中，应激引起的AEA变化与侵入记忆频率呈负相关，但与2- ag无关。总之，我们发现的证据表明，AEA与负面刺激的外显记忆和侵入性记忆有关。两项研究的证据都表明，较低的AEA与较高的外显记忆和侵入性记忆有关。这些发现支持动物文献，并对创伤后应激障碍负记忆症状的靶向治疗具有启示意义。

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引用次数: 0

Cross-trial prediction of treatment response to transcranial direct current stimulation in patients with major depressive disorder 重度抑郁症患者经颅直流电刺激治疗反应的交叉试验预测。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2025.111600

Gerrit Burkhardt , Stephan Goerigk , Lucia Bulubas , Esther Dechantsreiter , Daniel Keeser , Ulrike Vogelmann , Katharina von Wartensleben , Johannes Wolf , Christian Plewnia , Andreas Fallgatter , Berthold Langguth , Claus Normann , Lukas Frase , Peter Zwanzger , Thomas Kammer , Carlos Schönfeldt-Lecuona , Daniel Kamp , Malek Bajbouj , Nikolaos Koutsouleris , Andre R. Brunoni , Frank Padberg

Machine-learning (ML) classification may offer a promising approach for treatment response prediction in patients with major depressive disorder (MDD) undergoing non-invasive brain stimulation. This analysis aims to develop and validate such classification models based on easily attainable sociodemographic and clinical information across two randomized controlled trials on transcranial direct-current stimulation (tDCS) in MDD. Using data from 246 patients with MDD from the randomized-controlled DepressionDC and ELECT-TDCS trials, we employed an ensemble machine learning strategy to predict treatment response to either active tDCS or sham tDCS/placebo, defined as ≥50 % reduction in the Montgomery-Åsberg Depression Rating Scale at 6 weeks. Separate models for active tDCS and sham/placebo were developed in each trial and evaluated for external validity across trials and for treatment specificity across modalities. In the DepressionDC trial, models achieved a balanced accuracy of 63.5 % for active tDCS and 62.5 % for sham tDCS in predicting treatment responders. Baseline self-rated depression was consistently ranked as the most informative feature. However, response prediction in the ELECT-TDCS trial and across trials was not successful. Our findings suggest that ML models based on easily attainable sociodemographic and clinical variables can yield modest improvements in predicting individual tDCS response, but performance remains insufficient for clinical application and will require refinement and external validation in larger, more comprehensively phenotyped cohorts.

机器学习（ML）分类可能为重度抑郁症（MDD）患者接受非侵入性脑刺激的治疗反应预测提供了一种有希望的方法。本分析旨在通过两项经颅直流电刺激（tDCS）治疗重度抑郁症的随机对照试验，基于易于获得的社会人口学和临床信息，开发和验证这种分类模型。使用来自随机对照Depression dc和ELECT-TDCS试验的246例重度抑郁症患者的数据，我们采用集成机器学习策略来预测对活性tDCS或假tDCS/安慰剂的治疗反应，定义为6 周时Montgomery-Åsberg抑郁评定量表降低≥50% %。在每个试验中分别开发了活动性tDCS和假药/安慰剂模型，并评估了不同试验的外部有效性和不同模式的治疗特异性。在DepressionDC试验中，模型在预测治疗反应方面达到了63.5 %活跃tDCS和62.5 %假tDCS的平衡准确性。基线自评抑郁一直被列为最具信息性的特征。然而，在ELECT-TDCS试验和跨试验中的反应预测并不成功。我们的研究结果表明，基于易于获得的社会人口学和临床变量的ML模型可以在预测个体tDCS反应方面产生适度的改进，但对于临床应用来说，性能仍然不足，需要在更大、更全面的表型队列中进行改进和外部验证。

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引用次数: 0

The association between long-term opioid use and dementia risk: A systematic review and meta-analysis 长期阿片类药物使用与痴呆风险之间的关系：一项系统综述和荟萃分析。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2025.111595

Diana Marisol Abrego-Guandique , Saverio Nucera , Sara Ilari , Lucia Carmela Passacatini , Rosamaria Caminiti , Valeria Mazza , Jessica Maiuolo , Erika Cione , Vincenzo Mollace , Maria Cristina Caroleo , Carolina Muscoli

Introduction

In recent years, the increasing use of opioids has raised significant concerns about their potential long-term effects on cognitive health, particularly in elderly and vulnerable populations. While opioids are widely prescribed for chronic pain management, evidence suggests that prolonged use may accelerate cognitive decline.

Objective

This systematic review and meta-analysis aimed to investigate the association between opioid use and the risk of dementia.

Methods

To identify relevant studies published, a comprehensive search was conducted across multiple databases, including PubMed, Scopus, and the Web of Science. Studies examining opioid exposure and subsequent dementia diagnosis were included. Two independent reviewers performed data extraction and quality assessment. Meta-analyses were conducted to assess pooled risk estimates.

Results

Nine observational cohort studies were included. The random-effects model was applied. The pooled analysis showed a significant association between opioid use and an increased risk of dementia (HR = 1.35, 95 % CI = 1.21–1.50, P = ≤0.0001). Subgroup analyses by geographical region showed consistent associations, with no significant differences between regions (P = 0.70). The P-value for Egger's test was 0.11, indicating no publication bias.

Conclusion

These findings suggest that regular opioid use may be associated with a higher risk of dementia across the included studies; however, this finding should not be interpreted as evidence of causality. Clinicians should be aware of these potential risks when prescribing opioids, especially for older adults or those at higher risk of cognitive decline. Further research is needed to clarify underlying mechanisms and establish safe prescribing guidelines.

近年来，阿片类药物使用的增加引起了人们对其对认知健康，特别是老年人和弱势群体的潜在长期影响的严重关切。虽然阿片类药物被广泛用于慢性疼痛治疗，但有证据表明，长期使用阿片类药物可能会加速认知能力下降。目的：本系统综述和荟萃分析旨在调查阿片类药物使用与痴呆风险之间的关系。方法：在PubMed、Scopus和Web of Science等多个数据库中进行综合检索，以确定已发表的相关研究。研究包括阿片类药物暴露和随后的痴呆诊断。两名独立审稿人进行数据提取和质量评估。进行荟萃分析以评估综合风险估计。结果：纳入9项观察性队列研究。采用随机效应模型。合并分析显示阿片类药物使用与痴呆风险增加之间存在显著关联（HR = 1.35,95% % CI = 1.21-1.50,P ≤0.0001）。按地理区域进行的亚组分析显示出一致的相关性，区域间无显著差异（P = 0.70）。Egger检验的p值为0.11，无发表偏倚。结论：这些发现表明，在纳入的研究中，经常使用阿片类药物可能与痴呆的高风险相关；然而，这一发现不应被解释为因果关系的证据。临床医生在开阿片类药物处方时应该意识到这些潜在的风险，尤其是对老年人或认知能力下降风险较高的人。需要进一步的研究来阐明潜在的机制并建立安全的处方指南。

{"title":"The association between long-term opioid use and dementia risk: A systematic review and meta-analysis","authors":"Diana Marisol Abrego-Guandique , Saverio Nucera , Sara Ilari , Lucia Carmela Passacatini , Rosamaria Caminiti , Valeria Mazza , Jessica Maiuolo , Erika Cione , Vincenzo Mollace , Maria Cristina Caroleo , Carolina Muscoli","doi":"10.1016/j.pnpbp.2025.111595","DOIUrl":"10.1016/j.pnpbp.2025.111595","url":null,"abstract":"<div><h3>Introduction</h3><div>In recent years, the increasing use of opioids has raised significant concerns about their potential long-term effects on cognitive health, particularly in elderly and vulnerable populations. While opioids are widely prescribed for chronic pain management, evidence suggests that prolonged use may accelerate cognitive decline.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis aimed to investigate the association between opioid use and the risk of dementia.</div></div><div><h3>Methods</h3><div>To identify relevant studies published, a comprehensive search was conducted across multiple databases, including PubMed, Scopus, and the Web of Science. Studies examining opioid exposure and subsequent dementia diagnosis were included. Two independent reviewers performed data extraction and quality assessment. Meta-analyses were conducted to assess pooled risk estimates.</div></div><div><h3>Results</h3><div>Nine observational cohort studies were included. The random-effects model was applied. The pooled analysis showed a significant association between opioid use and an increased risk of dementia (HR = 1.35, 95 % CI = 1.21–1.50, <em>P</em> = ≤0.0001). Subgroup analyses by geographical region showed consistent associations, with no significant differences between regions (<em>P</em> = 0.70). The <em>P</em>-value for Egger's test was 0.11, indicating no publication bias.</div></div><div><h3>Conclusion</h3><div>These findings suggest that regular opioid use may be associated with a higher risk of dementia across the included studies; however, this finding should not be interpreted as evidence of causality. Clinicians should be aware of these potential risks when prescribing opioids, especially for older adults or those at higher risk of cognitive decline. Further research is needed to clarify underlying mechanisms and establish safe prescribing guidelines.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111595"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844288","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

Orbitofrontal rTMS modulates inferior parietal lobule functional reorganization to alleviate negative symptoms in first-episode, drug-naïve patients with schizophrenia 眼窝额部rTMS调节下顶叶功能重组以减轻首发drug-naïve精神分裂症患者的阴性症状。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2025.111602

Kexu Zhang , Xiong Jiao , Yanli Zhang , Ningning Zeng , Min Wang , Kun Li , Ziliang Wang , Junfeng Sun , Jijun Wang , Qiang Hu

Background

Recent studies have identified the orbitofrontal cortex (OFC) as a potential target for alleviating negative symptoms in schizophrenia. However, the neurobiological mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) delivered to the OFC remain unclear.

Methods

In this randomized controlled trial, seventy first-episode, drug-naïve patients with schizophrenia were assigned to receive either 20 sessions of active 1 Hz rTMS over the right lateral OFC (N = 36) or sham stimulation (N = 34). Clinical outcomes were measured using the Positive and Negative Syndrome Scale (PANSS). Resting-state functional MRI data were collected before and after treatment to assess changes in regional brain activity and functional connectivity, using fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and seed-based connectivity analyses.

Results

Compared to sham stimulation, active OFC-rTMS led to significantly greater reductions in PANSS scores (total: 22.7 vs. 14.3, p = 0.003, Cohen's d = 0.733; negative: 6.2 vs. 4.0, p = 0.037, Cohen's d = 0.510). Neuroimaging analyses revealed increased spontaneous activity (fALFF and ReHo) in the right OFC and bilateral inferior parietal lobule (IPL), along with enhanced functional connectivity between the OFC and IPL in the active rTMS group. Importantly, IPL-related functional reorganization was significantly associated with symptom improvement, particularly in negative and general domains.

Conclusions

These findings suggest that rTMS targeting the OFC exerts therapeutic effects in schizophrenia by modulating IPL function and OFC–IPL connectivity. The IPL may serve as a critical downstream node mediating the clinical benefits of OFC-rTMS, offering novel insights into network-based neuromodulation strategies for negative symptoms.

背景：最近的研究已经确定眶额皮质（OFC）是缓解精神分裂症阴性症状的潜在靶点。然而，OFC重复性经颅磁刺激（rTMS）的神经生物学机制尚不清楚。方法：在这项随机对照试验中，70名首发drug-naïve精神分裂症患者被分配到接受20次活动1 Hz rTMS的右侧OFC （N = 36）或假刺激（N = 34）。临床结果采用阳性和阴性综合征量表（PANSS）进行测量。在治疗前后收集静息状态功能MRI数据，使用低频波动分数幅值（fALFF）、区域均匀性（ReHo）和基于种子的连通性分析来评估区域大脑活动和功能连通性的变化。结果：与假性刺激相比，活跃OFC-rTMS导致PANSS评分显著降低（total: 22.7 vs. 14.3, p = 0.003,Cohen's d = 0.733；阴性：6.2 vs. 4.0, p = 0.037,Cohen's d = 0.510）。神经影像学分析显示，在活跃的rTMS组中，右侧OFC和双侧下顶叶（IPL）的自发活动（fALFF和ReHo）增加，同时OFC和IPL之间的功能连接增强。重要的是，ipl相关的功能重组与症状改善显著相关，特别是在阴性和一般领域。结论：这些研究结果表明，针对OFC的rTMS通过调节IPL功能和OFC-IPL连通性来治疗精神分裂症。IPL可能是介导OFC-rTMS临床益处的关键下游节点，为阴性症状的基于网络的神经调节策略提供了新的见解。

{"title":"Orbitofrontal rTMS modulates inferior parietal lobule functional reorganization to alleviate negative symptoms in first-episode, drug-naïve patients with schizophrenia","authors":"Kexu Zhang , Xiong Jiao , Yanli Zhang , Ningning Zeng , Min Wang , Kun Li , Ziliang Wang , Junfeng Sun , Jijun Wang , Qiang Hu","doi":"10.1016/j.pnpbp.2025.111602","DOIUrl":"10.1016/j.pnpbp.2025.111602","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies have identified the orbitofrontal cortex (OFC) as a potential target for alleviating negative symptoms in schizophrenia. However, the neurobiological mechanisms underlying repetitive transcranial magnetic stimulation (rTMS) delivered to the OFC remain unclear.</div></div><div><h3>Methods</h3><div>In this randomized controlled trial, seventy first-episode, drug-naïve patients with schizophrenia were assigned to receive either 20 sessions of active 1 Hz rTMS over the right lateral OFC (<em>N</em> = 36) or sham stimulation (<em>N</em> = 34). Clinical outcomes were measured using the Positive and Negative Syndrome Scale (PANSS). Resting-state functional MRI data were collected before and after treatment to assess changes in regional brain activity and functional connectivity, using fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and seed-based connectivity analyses.</div></div><div><h3>Results</h3><div>Compared to sham stimulation, active OFC-rTMS led to significantly greater reductions in PANSS scores (total: 22.7 vs. 14.3, <em>p</em> = 0.003, Cohen's d = 0.733; negative: 6.2 vs. 4.0, <em>p</em> = 0.037, Cohen's d = 0.510). Neuroimaging analyses revealed increased spontaneous activity (fALFF and ReHo) in the right OFC and bilateral inferior parietal lobule (IPL), along with enhanced functional connectivity between the OFC and IPL in the active rTMS group. Importantly, IPL-related functional reorganization was significantly associated with symptom improvement, particularly in negative and general domains.</div></div><div><h3>Conclusions</h3><div>These findings suggest that rTMS targeting the OFC exerts therapeutic effects in schizophrenia by modulating IPL function and OFC–IPL connectivity. The IPL may serve as a critical downstream node mediating the clinical benefits of OFC-rTMS, offering novel insights into network-based neuromodulation strategies for negative symptoms.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"144 ","pages":"Article 111602"},"PeriodicalIF":3.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145879434","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

Topologic but not volumetric differences diversify sex effects on thalamic nuclei in drug-naive patients with major depressive disorder 未用药的重性抑郁症患者丘脑核的拓扑而非体积差异使性别效应多样化。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2025.111594

Yidan Wang , Xinyue Hu , Lianqing Zhang , Hailong Li , Yingxue Gao , Mengyue Tang , Zilin Zhou , Shuangwei Chai , Liqiong Liu , Weihong Kuang , Qiyong Gong , Xiaoqi Huang

Background

The thalamus is a crucial subcortical structure in etiological models of major depressive disorder (MDD). Given the well-documented sex differences in MDD prevalence and clinical manifestations, it remains unclear whether these differences are linked to structural characteristics of thalamus. This study aimed to investigate the divergent sex effects on thalamus nuclei in drug-naive patients with MDD.

Methods

High-resolution 3D T1-weighted and diffusion tensor imaging images were obtained for 174 drug-naive patients with MDD and 118 age-, sex-, education years- and handedness-matched healthy controls (HCs). The thalamus was segmented into 22 nuclei using FreeSurfer. A general linear model (GLM) was used to test sex-by-diagnosis interactions for volumes of whole thalamus and individual nuclei between groups. We also performed a graph theory analysis of the structural covariance network (SCN) of thalamic nuclei in females and males with MDD, compared to their sex-matched HCs, respectively.

Results

There were no significant sex-by-diagnosis interactions in whole thalamus or nuclei volumes. The disruptions of SCN were observed in females with MDD, including lower nodal degree in left lateral posterior (LP) nucleus, lower betweenness centrality across several nuclei in the left intralaminar and bilateral antero-lateral nuclei group, and higher betweenness and closeness centrality in right pulvinar lateral nucleus, compared to female HCs. Males with MDD displayed lower nodal degree in left ventral anterior magnocellular and right medial ventral reuniens nuclei and higher betweenness centrality in left mediodorsal lateral parvocellular nucleus relative to male HCs. Moreover, male HCs exhibited higher closeness centrality in the right LP nucleus than female HCs.

Conclusion

These findings represent the first evidence of sex-specific alterations in the topological properties rather than the volumes of thalamic nuclei in early untreated patients with MDD, indicating the structural reorganization of SCN of thalamic nuclei may represent a potential neuro-mechanism underlying sex differences in MDD.

背景：在重度抑郁症（MDD）的病因模型中，丘脑是一个至关重要的皮质下结构。鉴于重度抑郁症患病率和临床表现的性别差异，这些差异是否与丘脑的结构特征有关尚不清楚。本研究旨在探讨不同性别对MDD患者丘脑核的影响。方法：对174例初治MDD患者和118例年龄、性别、受教育程度和手性匹配的健康对照（hc）进行高分辨率3D t1加权和弥散张量成像。使用FreeSurfer将丘脑分割成22个核。使用一般线性模型（GLM）来测试各组间整个丘脑和单个核体积的性别诊断相互作用。我们还对女性和男性重度抑郁症患者丘脑核的结构协方差网络（SCN）进行了图论分析，并分别与性别匹配的hc进行了比较。结果：在整个丘脑或核体积中没有明显的性别诊断相互作用。在MDD女性患者中观察到SCN的破坏，包括与女性hcc相比，左侧外侧后核（LP）的结度较低，左侧板内核组和双侧前外侧核组几个核的中间中心性较低，右侧枕侧外侧核的中间中心性和紧密中心性较高。与男性hcc相比，男性MDD表现为左侧腹侧前大细胞核和右侧内侧腹侧团聚核结度较低，左侧中背侧旁细胞核间性中心性较高。此外，男性hcc在右侧LP核中表现出比女性hcc更高的紧密中心性。结论：这些发现首次证明了早期未经治疗的MDD患者丘脑核的拓扑特性而非体积发生了性别特异性改变，表明丘脑核SCN的结构重组可能是MDD性别差异背后的潜在神经机制。

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引用次数: 0

Lower plasma DHEAS and BDNF levels as indicators of cognitive decline 较低的血浆DHEAS和BDNF水平作为认知能力下降的指标。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2026.111605

Marcela Konjevod , Nikola Balic , Lucija Tudor , Suzana Uzun , Matea Nikolac Perkovic , Barbara Vuic , Tina Milos , Gordana Nedic Erjavec , Ninoslav Mimica , Nela Pivac , Dubravka Svob Strac

Gradual loss of cognitive abilities is common during ageing but might also result in mild cognitive impairment and dementia. Research suggests that neurotrophins, such as brain derived neurotrophic factor (BDNF), and neurosteroids, such as dehydroepiandrosterone (DHEA) and its sulphate (DHEAS), play crucial role in cognitive functions and are often dysregulated in neurocognitive disorders. This study aimed to investigate variations in the genes for BDNF and sulfotransferase 2A1 (SULT2A1), the enzyme converting DHEA into DHEAS, as well as plasma BDNF and DHEAS levels, in individuals with normal cognition, and mild, moderate, and severe cognitive impairment. Cognitive functions of 453 participants were evaluated using Mini-Mental State Examination (MMSE) and Clock Drawing test (CDT). Genotyping of BDNF (rs6265) and SULT2A1 (rs2637125) polymorphisms was conducted, and plasma BDNF and DHEAS concentrations were determined by enzyme-linked immunosorbent assays (ELISA). Obtained results demonstrated that participants with moderate to severe cognitive impairment had significantly lower plasma BDNF and DHEAS levels, compared to individuals with normal cognition. In contrast to DHEAS, BDNF changes were more pronounced in men than in women. However, no significant associations of BDNF rs6265 and SULT2A1 rs2637125 polymorphisms with cognitive decline, or with plasma BDNF and DHEAS levels, respectively, were observed. Compared to CDT, MMSE was superior in distinguishing plasma BDNF and DHEAS variations, especially between individuals with mild and moderate to severe cognitive impairment. Further studies should investigate the potential of BDNF and DHEAS as peripheral biomarkers of cognitive decline and possible benefits of their replacement therapy in neurocognitive disorders.

认知能力的逐渐丧失在衰老过程中很常见，但也可能导致轻度认知障碍和痴呆。研究表明，神经营养因子，如脑源性神经营养因子（BDNF）和神经类固醇，如脱氢表雄酮（DHEA）及其硫酸盐（DHEAS），在认知功能中起着至关重要的作用，并且经常在神经认知障碍中失调。本研究旨在研究认知正常、轻度、中度和重度认知障碍个体中BDNF和亚砜转移酶2A1 （SULT2A1，将DHEA转化为DHEAS的酶）基因的变化以及血浆BDNF和DHEAS水平。采用简易精神状态测验（MMSE）和时钟绘制测验（CDT）对453名参与者的认知功能进行评估。对BDNF （rs6265）和SULT2A1 （rs2637125）多态性进行基因分型，并采用酶联免疫吸附试验（ELISA）检测血浆BDNF和DHEAS浓度。获得的结果表明，与认知正常的个体相比，中度至重度认知障碍的参与者血浆BDNF和DHEAS水平显著降低。与DHEAS相比，BDNF在男性中的变化比女性更明显。然而，BDNF rs6265和SULT2A1 rs2637125多态性分别与认知能力下降或血浆BDNF和DHEAS水平没有显著关联。与CDT相比，MMSE在区分血浆BDNF和DHEAS变化方面具有优势，特别是在轻度和中度至重度认知障碍患者之间。进一步的研究应该调查BDNF和DHEAS作为认知能力下降的外周生物标志物的潜力，以及它们在神经认知障碍替代疗法中的可能益处。

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引用次数: 0

Hypersensitization of peripheral immune cells from major depressive disorder patients is mildly attenuated by fluoxetine in vitro 氟西汀可轻度减轻重度抑郁症患者外周免疫细胞的超敏反应。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2026.111608

Yingqian Zhang , Qi Lai , Tangcong Chen , Yueyang Luo , Mengdie Li , Mengqi Niu , Jing Li , Michael Maes

Major depressive disorder (MDD) is accompanied by activation of the immune-inflammatory response system (IRS) and the compensatory immunoregulatory system (CIRS). Fluoxetine, the most commonly used selective serotonin reuptake inhibitor (SSRI), shows anti-inflammatory effects in both MDD patients and depressive-like behaviors in rodents. The present study examines the effects of fluoxetine on immune profiles, such as M1 and M2 macrophages, T helper (Th)1, Th2, Th17, IRS, and CIRS in MDD and healthy controls (HC). Culture supernatant of immunogen-stimulated whole blood of 18 MDD and 18 HC was measured for 48 cytokines using a multiplex assay. The effects of three fluoxetine concentrations (0.1 mM, 0.01 mM, and 0.001 mM) were examined. MDD was characterized by significantly increased M1, M2, Th1, Th2, Th17, IRS, and CIRS profiles under the stimulation of phytohemagglutinin (PHA) and lipopolysaccharide (LPS). Fluoxetine exhibited different effects on immune functions when comparing culture supernatant from MDD to HC. In HC samples, the administration of fluoxetine did not impact the immune system. In MDD samples, fluoxetine administration significantly reduces the stimulated production of Th1, Th17, M2, IRS, Th2, as well as IL-1 and TNF signaling pathways. Fluoxetine significantly attenuated the production of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, tumor necrosis factor-α, IL-12, interferon-γ, chemokines (CCL27, CXCL10), growth factors, and colony-stimulating factors. However, this suppressant effect is merely partial, insufficient to normalize the immune sensitization in the culture supernatant from MDD patients. In summary, fluoxetine has highly significant immunoregulatory effects in patients with MDD and not in controls. Unfortunately, these effects only partly attenuate the immune sensitization in MDD.

重度抑郁障碍（MDD）伴随着免疫炎症反应系统（IRS）和代偿性免疫调节系统（CIRS）的激活。氟西汀是最常用的选择性血清素再摄取抑制剂（SSRI），对重度抑郁症患者和啮齿动物的抑郁样行为都有抗炎作用。本研究探讨了氟西汀对MDD和健康对照（HC）免疫谱的影响，如M1和M2巨噬细胞、T辅助（th1）、Th2、Th17、IRS和CIRS。采用多重法测定18例MDD和18例HC免疫原刺激全血培养上清中48种细胞因子的含量。考察了三种氟西汀浓度（0.1 mM、0.01 mM和0.001 mM）的影响。MDD的特征是在植物血凝素（PHA）和脂多糖（LPS）的刺激下，M1、M2、Th1、Th2、Th17、IRS和CIRS谱显著升高。对比MDD和HC培养上清液，氟西汀对免疫功能的影响不同。在HC样本中，氟西汀对免疫系统没有影响。在MDD样本中，氟西汀显著降低了Th1、Th17、M2、IRS、Th2以及IL-1和TNF信号通路的刺激产生。氟西汀显著降低促炎细胞因子的产生，包括白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α、IL-12、干扰素-γ、趋化因子（CCL27、CXCL10）、生长因子和集落刺激因子。然而，这种抑制作用仅仅是部分的，不足以使MDD患者培养上清中的免疫致敏正常化。综上所述，氟西汀在重度抑郁症患者中具有高度显著的免疫调节作用，而在对照组中没有。不幸的是，这些作用只能部分减弱MDD的免疫致敏性。

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引用次数: 0

The striatal heterogeneous nuclear ribonucleoprotein H1 mRNA targetome associated with methamphetamine administration and behavior 纹状体异质核核糖核蛋白H1 mRNA靶组与甲基苯丙胺给药和行为相关。

IF 3.9 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2026-01-02 DOI: 10.1016/j.pnpbp.2025.111598

Qiu T. Ruan , William B. Lynch , Rebecca H. Cole , Michael A. Rieger , Britahny M. Baskin , Sophia A. Miracle , Jacob A. Beierle , Emily J. Yao , Jiayi W. Cox , Amarpreet Kandola , Kayla T. Richardson , Melanie M. Chen , Julia C. Billups , R. Keith Babbs , Peter E.A. Ash , Benjamin Wolozin , Karen K. Szumlinski , W. Evan Johnson , Joseph D. Dougherty , Camron D. Bryant

Methamphetamine addiction remains a major public health concern in the United States that has paralleled the opioid epidemic. Psychostimulant use disorders have a heritable genetic component that remains unexplained. Methamphetamine targets membrane and vesicular transporters to increase synaptic dopamine, norepinephrine, and serotonin. We previously identified Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) as a quantitative trait gene underlying methamphetamine behavioral sensitivity. Hnrnph1 encodes the RNA-binding protein hnRNP H1 that is ubiquitously expressed in neurons throughout the adult brain. Gene-edited mice with a heterozygous frameshift deletion in Hnrnph1's first coding exon showed reduced methamphetamine-induced dopamine release and behaviors. To potentially inform the mechanism linking hnRNP H with methamphetamine behavior, we surveyed the mRNA targetome of hnRNP H via cross-linking immunoprecipitation coupled with RNA-sequencing in striatum at baseline and at 30 min post-methamphetamine in wild-type female and male C57BL/6 J mice. Methamphetamine induced changes in RNA-binding targets of hnRNP H in mice, including 3’UTRs of enriched mRNAs involved in synaptic plasticity. Targetome, transcriptome, and spliceome analyses triangulated on Cacna2d2 which showed methamphetamine-induced changes in hnRNP H binding, gene expression and splicing. Pre-treatment with pregabalin, an inhibitor of CACNA2D2 and CACNA2D1 voltage-gated calcium channel subunits, attenuated methamphetamine-induced locomotor activity, suggesting CACNA2D2 could contribute to methamphetamine locomotor stimulant sensitivity. Our study identifies a dynamic hnRNP H RNA targetome that can respond rapidly to methamphetamine and could potentially contribute to synaptic plasticity and behavior. Given our discovery-based findings, future studies will require directly validating the link between methamphetamine-induced changes in hnRNP H binding, gene regulation, synaptic plasticity, and behavior.

在美国，甲基苯丙胺成瘾仍然是一个与阿片类药物流行相当的重大公共卫生问题。精神兴奋剂使用障碍具有遗传成分，目前仍无法解释。甲基苯丙胺靶向膜和囊泡转运蛋白，增加突触多巴胺、去甲肾上腺素和血清素。我们之前发现Hnrnph1（异质核核糖核蛋白H1）是甲基苯丙胺行为敏感性的数量性状基因。Hnrnph1编码rna结合蛋白hnRNP H1，该蛋白在整个成人大脑的神经元中普遍表达。Hnrnph1第一个编码外显子杂合移码缺失的基因编辑小鼠显示甲基苯丙胺诱导的多巴胺释放和行为减少。为了潜在地了解hnRNP H与甲基苯丙胺行为之间的联系机制，我们在野生型雌性和雄性C57BL/6 J小鼠的纹状体中，通过交联免疫沉淀结合rna测序，在基线和30 min后，研究了hnRNP H的mRNA靶组。甲基苯丙胺诱导小鼠hnRNP H的rna结合靶点发生变化，包括参与突触可塑性的富集mrna的3' utr。靶组、转录组和剪接组对Cacna2d2进行了三角分析，结果显示甲基苯丙胺诱导hnRNP H结合、基因表达和剪接发生变化。预处理普瑞巴林（CACNA2D2和CACNA2D1电压门控钙通道亚基抑制剂）可减弱甲基苯丙胺诱导的运动活性，提示CACNA2D2可能有助于甲基苯丙胺运动兴奋剂的敏感性。我们的研究确定了一个动态hnRNP H RNA靶组，它可以对甲基苯丙胺快速反应，并可能有助于突触的可塑性和行为。鉴于我们基于发现的发现，未来的研究将需要直接验证甲基苯丙胺诱导的hnRNP H结合变化、基因调控、突触可塑性和行为之间的联系。

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引用次数: 0