Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献_第4页

Combined cognitive assessment and automated MRI volumetry improves the diagnostic accuracy of detecting MCI due to Alzheimer's disease 认知评估与自动磁共振成像容积测量相结合，提高了检测阿尔茨海默病导致的 MCI 的诊断准确性。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-29 DOI: 10.1016/j.pnpbp.2024.111157

Background

Mild cognitive impairment (MCI) confers a high annual risk of 10–15 % of conversion to Alzheimer's disease (AD) dementia. MRI atrophy patterns derived from automated ROI analysis, particularly hippocampal subfield volumes, were reported to be useful in diagnosing early clinical stages of Alzheimer's disease.

Objective

The aim of the present study was to combine automated ROI MRI morphometry of hippocampal subfield volumes and cortical thickness estimates using FreeSurfer 6.0 with cognitive measures to predict disease progression and time to conversion from MCI to AD dementia.

Methods

Baseline (Neuropsychology, MRI) and clinical follow-up data from 62 MCI patients were analysed retrospectively. Individual cortical thickness and volumetric measures were obtained from T1-weighted MRI. Linear discriminant analysis (LDA) of both, cognitive measures and MRI measures (hippocampal subfields, temporal and parietal lobe volumes), were performed to differentiate MCI converters from stable MCI patients.

Results

Out of 62 MCI patients 21 (34 %) converted to AD dementia within a mean follow-up time of 74.7 ± 36.8 months (mean ± SD, range 12 to 130 months). LDA identified temporal lobe atrophy and hippocampal subfield volumes in combination with cognitive measures of verbal memory, verbal fluency and executive functions to correctly classify 71.4.% of MCI subjects converting to AD dementia and 92.7 % with stable MCI. Lower baseline GM volume of the subiculum and the superior temporal gyrus was associated with faster disease progression of MCI converters.

Conclusion

Combining cognitive assessment with automated ROI MRI morphometry is superior to using a single test in order to distinguish MCI due to AD from non converting MCI patients.

背景：轻度认知障碍（MCI）每年有 10-15% 的高风险转化为阿尔茨海默病（AD）痴呆。据报道，通过自动 ROI 分析得出的 MRI 萎缩模式，尤其是海马亚区体积，有助于诊断阿尔茨海默病的早期临床阶段：本研究旨在将使用 FreeSurfer 6.0 进行的海马子野体积和皮质厚度估算的自动 ROI MRI 形态测量与认知测量相结合，以预测疾病进展和从 MCI 向 AD 痴呆症转化的时间：对62名MCI患者的基线（神经心理学、核磁共振成像）和临床随访数据进行了回顾性分析。从 T1 加权核磁共振成像中获得了单个皮层厚度和容积测量值。对认知测量和 MRI 测量（海马亚区、颞叶和顶叶容积）进行线性判别分析（LDA），以区分 MCI 转换者和稳定型 MCI 患者：62 名 MCI 患者中有 21 人（34%）在平均 74.7 ± 36.8 个月（平均 ± SD，范围为 12 至 130 个月）的随访时间内转为 AD 痴呆。LDA结合言语记忆、言语流畅性和执行功能的认知测量，确定了颞叶萎缩和海马亚区体积，从而正确地将71.4%的MCI受试者和92.7%的稳定型MCI受试者归类为AD痴呆症患者。脑下凹和颞上回基线GM体积较低与MCI转换者疾病进展较快有关联：结论：将认知评估与自动ROI核磁共振成像形态测量相结合，比使用单一测试方法更能区分AD导致的MCI和非转换型MCI患者。

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引用次数: 0

Abnormal developmental of hippocampal subfields and amygdalar subnuclei volumes in young adults with heavy cannabis use: A three-year longitudinal study 大量吸食大麻的年轻人海马亚区和杏仁核体积的异常发育：一项为期三年的纵向研究

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-29 DOI: 10.1016/j.pnpbp.2024.111156

Background

Differences in the volumes of the hippocampus and amygdala have consistently been observed between young adults with heavy cannabis use relative to their non-using counterparts. However, it remains unclear whether the subfields of these functionally and structurally heterogenous regions exhibit similar patterns of change in young adults with long-term heavy cannabis use disorder (CUD).

Objectives

This study aims to investigate the effects of long-term heavy cannabis use in young adults on the subregional structures of the hippocampus and amygdala, as well as their longitudinal alterations.

Methods

The study sample comprised 20 young adults with heavy cannabis use and 22 matched non-cannabis using healthy volunteers. All participants completed the Cannabis Use Disorder Identification Test (CUDIT) and underwent two T1-structural magnetic resonance imaging (MRI) scans, one at baseline and another at follow-up 3 years later. The amygdala, hippocampus, and their subregions were segmented on T1-weighted anatomical MRI scans, using a previously validated procedure.

Results

At baseline, young adults with heavy CUD exhibited significantly larger volumes in several hippocampal (bilateral presubiculum, subiculum, Cornu Ammonis (CA) regions CA1, CA2-CA3, and right CA4-Dentate Gyrus (DG)) and amygdala (bilateral paralaminar nuclei, right medial nucleus, and right lateral nucleus) subregions compared to healthy controls, but these differences were attenuated at follow-up. Longitudinal analysis revealed an accelerated volumetric decrease in these subregions in young adults with heavy CUD relative to controls. Particularly, compared to healthy controls, significant accelerated volume decreases were observed in the right hippocampal subfields of the parasubiculum, subiculum, and CA4-DG. In the amygdala, similar trends of accelerated volumetric decreases were observed in the left central nucleus, right paralaminar nucleus, right basal nucleus, and right accessory basal nucleus.

Conclusions

The current findings suggest that long-term heavy cannabis use impacts maturational process of the amygdala and hippocampus, especially in subregions with high concentrations of cannabinoid type 1 receptors (CB1Rs) and involvement in adult neurogenesis.

背景：在大量吸食大麻的年轻人与未吸食大麻的年轻人之间，海马体和杏仁核的体积一直存在差异。然而，这些在功能和结构上具有异质性的区域的亚领域是否在长期大量使用大麻障碍（CUD）的年轻人身上表现出类似的变化模式，目前仍不清楚：本研究旨在探讨长期大量吸食大麻对青壮年海马和杏仁核亚区结构的影响及其纵向改变：研究样本包括 20 名大量吸食大麻的年轻人和 22 名匹配的不吸食大麻的健康志愿者。所有参与者都完成了大麻使用障碍鉴定测试（CUDIT），并接受了两次 T1 结构磁共振成像（MRI）扫描，一次是基线扫描，另一次是 3 年后的随访扫描。采用先前验证过的程序，在T1加权解剖磁共振成像扫描中对杏仁核、海马及其亚区进行了分割：与健康对照组相比，重度 CUD 患者的海马（双侧管前区、管下区、Cornu Ammonis (CA) 区 CA1、CA2-CA3 和右侧 CA4-齿状回 (DG)）和杏仁核（双侧副核、右侧内侧核和右侧外侧核）亚区的体积在基线时明显增大，但这些差异在随访时有所减弱。纵向分析表明，与对照组相比，重度 CUD 青壮年患者这些亚区的体积加速缩小。特别是，与健康对照组相比，右侧海马亚区的副钟面、亚钟面和CA4-DG的体积明显加速缩小。在杏仁核中，左侧中央核、右侧旁核、右侧基底核和右侧附属基底核也观察到类似的体积加速缩小趋势：目前的研究结果表明，长期大量吸食大麻会影响杏仁核和海马的成熟过程，尤其是在大麻素 1 型受体（CB1R）浓度较高且参与成年神经发生的亚区域。

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引用次数: 0

Augmentation of psychiatric symptom onset vulnerability in male mice due to mild traumatic brain injury 轻度脑外伤导致雄性小鼠精神症状发病易感性增强

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-25 DOI: 10.1016/j.pnpbp.2024.111153

Mild traumatic brain injury (mTBI) can induce psychiatric symptoms, including anxiety, depression, and diminished interest. These symptoms can manifest shortly after injury or exhibit delayed onset months or years later, often worsening in severity. Therefore, early intervention and effective treatment are crucial. However, mTBI lacks clear diagnostic markers, making the underlying pathophysiological mechanisms elusive. Additionally, there is a dearth of suitable animal models and a limited understanding of the biochemical changes in the brain that contribute to post-mTBI psychological symptoms. In this study, we hypothesized that mTBI can trigger brain vulnerability mechanisms, which eventually lead to symptom manifestation in response to subsequent stressors. Using a mouse model, we induced very mild blast-induced mTBI without overt trauma or behavioral changes and subsequently subjected the mice to psychological stress. We analyzed the behavioral alterations and gene expression changes in the brain, focusing on microglial and astrocytic markers involved in the immune system and immune responses. The mice exposed to both blast and defeat stress exhibited significantly lower preference scores in the social interaction test than the mice subjected to blast exposure alone, defeat stress alone, or the control condition. Gene expression analysis revealed a distinct set of genes associated with blast exposure during the development of psychiatric symptoms and genes associated with social defeat stress. The results revealed that neither blast exposure nor defeat stress alone significantly affected mouse social behavior; however, their combined influence resulted in noticeable aberrations in social interactions and/or interest. The findings of the present study provide critical insights into the complex interplay between mTBI and psychological stress. Additionally, they provide a novel mouse model for future research aimed at elucidating the pathophysiological mechanisms underlying the psychiatric symptoms associated with mTBI. Ultimately, this knowledge may enhance early intervention and therapeutic strategies for individuals with mTBI-related psychiatric disorders.

轻度脑外伤（mTBI）可诱发精神症状，包括焦虑、抑郁和兴趣减退。这些症状可能在受伤后不久表现出来，也可能在数月或数年后延迟出现，而且往往会越来越严重。因此，早期干预和有效治疗至关重要。然而，mTBI 缺乏明确的诊断标志物，使其潜在的病理生理机制难以捉摸。此外，目前还缺乏合适的动物模型，对导致创伤后心理症状的大脑生化变化的了解也很有限。在本研究中，我们假设 mTBI 可触发大脑脆弱机制，最终导致在应对后续压力时出现症状。我们利用小鼠模型，在没有明显创伤或行为变化的情况下诱导了非常轻微的爆炸诱导性 mTBI，随后让小鼠承受心理压力。我们分析了小鼠的行为改变和大脑中基因表达的变化，重点研究了涉及免疫系统和免疫反应的小胶质细胞和星形胶质细胞标记物。同时受到爆炸和挫败应激的小鼠在社会交往测试中的偏好得分明显低于只受到爆炸应激、只受到挫败应激或对照组的小鼠。基因表达分析表明，在精神症状的发展过程中，与爆炸暴露相关的基因和与社会挫败应激相关的基因各不相同。结果表明，单独的爆炸暴露或失败应激都不会对小鼠的社会行为产生显著影响；但是，它们的共同影响会导致小鼠在社会交往和/或兴趣方面出现明显的畸变。本研究的结果为了解创伤性脑损伤与心理压力之间复杂的相互作用提供了重要的见解。此外，它们还为今后旨在阐明与 mTBI 相关的精神症状的病理生理机制的研究提供了一种新型小鼠模型。最终，这些知识可能会加强对 mTBI 相关精神障碍患者的早期干预和治疗策略。

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引用次数: 0

Efficacy of single and repeated ketamine administration for suicidal ideation in adults with psychiatric disorders: A meta-analysis 单次和多次使用氯胺酮对患有精神障碍的成人自杀意念的疗效：荟萃分析

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-25 DOI: 10.1016/j.pnpbp.2024.111152

Background

Previous studies have demonstrated rapid-onset anti-suicidal ideation effects of ketamine. This study aimed to compare the efficacy and duration of anti-suicidal thoughts following single- and repeated-dose ketamine administration.

Methods

We retrieved published studies on ketamine for suicidal ideation (SI) from PubMed, OVID (MEDLINE), Web of Science, and Embase, spanning from inception to May 1, 2024. Standardized mean differences (SMD) in the SI scores were calculated for continuous outcomes.

Results

This study included 49 independent clinical trials involving 3982 participants. After a single ketamine administration, a significant reduction in SI was observed at 4 h (SMD = −0.607, 95 % confidence interval (CI) = [−0.797, −0.418], I² = 40.69 %), with peak effects observed at 24 h (SMD = −0.955, 95 % CI = [−1.229, −0.682], I² = 63.66 %) and effects persisted for one month (SMD = −0.948, 95 % CI = [−1.611, −0.285], I² = 74.32 %). Similar anti-suicidal effects were observed at the treatment endpoint (SMD = −1.228, 95 % CI = [−1.506, −0.950], I² = 94.56 %) and during a follow-up period of greater than or equal to 1 month (SMD = −1.012, 95 % CI = [−1.695, −0.330], I² = 80.44 %) with multiple doses of ketamine administration.

Conclusions

Single ketamine treatment may have a significant and lasting (up to 1 month) beneficial effect on SI. There was no statistical difference in the efficacy and duration of anti-suicidal thoughts between single and serial ketamine administration.

背景：先前的研究表明氯胺酮具有快速起效的抗自杀意念作用。本研究旨在比较单剂量和重复剂量氯胺酮给药后抗自杀意念的疗效和持续时间：我们从PubMed、OVID (MEDLINE)、Web of Science和Embase检索了从开始到2024年5月1日发表的关于氯胺酮治疗自杀意念（SI）的研究。对连续结果计算了SI评分的标准化平均差（SMD）：本研究包括49项独立临床试验，涉及3982名参与者。单次氯胺酮给药后，4 小时内观察到 SI 显著降低（SMD = -0.607，95 % 置信区间 (CI) = [-0.797, -0.418]，I2 = 40.69 %），24 小时后观察到峰值效应（SMD = -0.955，95 % 置信区间 = [-1.229, -0.682]，I2 = 63.66 %），效应持续一个月（SMD = -0.948，95 % 置信区间 = [-1.611, -0.285]，I2 = 74.32 %）。在治疗终点（SMD = -1.228, 95 % CI = [-1.506, -0.950]，I2 = 94.56%）和大于或等于1周的随访期间（SMD = -1.012, 95 % CI = [-1.695, -0.330]，I2 = 80.44%），多剂量氯胺酮也能观察到类似的抗自杀效果：单次氯胺酮治疗可对 SI 产生显著而持久（长达 1 个月）的疗效。单次氯胺酮治疗和连续氯胺酮治疗在疗效上没有统计学差异，但连续氯胺酮治疗的持久性较差。

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引用次数: 0

The brain, rapid eye movement sleep, and major depressive disorder: A multimodal neuroimaging study 大脑、快速眼动睡眠和重度抑郁症：多模态神经成像研究。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-24 DOI: 10.1016/j.pnpbp.2024.111151

Background

Evidence has established the prominent involvement of rapid eye movement (REM) sleep disturbance in major depressive disorder (MDD). However, the neural correlates of REM sleep in MDD and their clinical significance are less clear.

Methods

Cross-sectional and longitudinal polysomnography and resting-state functional MRI data were collected from 131 MDD patients and 71 healthy controls to measure REM sleep and voxel-mirrored homotopic connectivity (VMHC). Correlation and mediation analyses were performed to examine the associations between REM sleep, VMHC, and clinical variables. Moreover, we conducted spatial correlations between the neural correlates of REM sleep and a multimodal collection of reference brain maps to facilitate genetic, structural and functional annotations.

Results

MDD patients exhibited REM sleep abnormalities manifesting as higher REM sleep latency and lower REM sleep duration, which were correlated with decreased VMHC of the precentral gyrus and inferior parietal lobe and mediated their associations with more severe anxiety symptoms. Longitudinal data showed that VMHC increase of the inferior parietal lobe was related to improvement of depression symptoms in MDD patients. Spatial correlation analyses revealed that the neural correlates of REM sleep in MDD were linked to gene categories primarily involving cellular metabolic process, signal pathway, and ion channel activity as well as linked to cortical microstructure, metabolism, electrophysiology, and cannabinoid receptor.

Conclusion

These findings may add important context to the growing literature on the complex interplay between sleep and MDD, and more broadly may inform future treatment for depression via regulating sleep.

背景：有证据表明，快速眼动（REM）睡眠障碍与重度抑郁障碍（MDD）密切相关。然而，快速眼动睡眠在重度抑郁症中的神经相关性及其临床意义尚不明确：收集了131名MDD患者和71名健康对照者的横向和纵向多导睡眠图和静息态功能磁共振成像数据，以测量REM睡眠和体素映射同位连接（VMHC）。我们进行了相关分析和中介分析，以研究快速动眼期睡眠、VMHC 和临床变量之间的关联。此外，我们还对快速动眼期睡眠的神经相关性与参考脑图的多模态集合进行了空间相关性分析，以便于进行遗传、结构和功能注释：结果：MDD患者表现出快速眼动睡眠异常，表现为快速眼动睡眠潜伏期较高和快速眼动睡眠持续时间较短，这与前中央回和顶叶下部的VMHC减少有关，并与更严重的焦虑症状相关。纵向数据显示，顶叶下部VMHC的增加与MDD患者抑郁症状的改善有关。空间相关性分析表明，MDD患者快速眼动睡眠的神经相关性与主要涉及细胞代谢过程、信号通路和离子通道活动的基因类别有关，也与皮质微结构、代谢、电生理学和大麻素受体有关：这些发现可能会为越来越多关于睡眠与多发性抑郁症之间复杂相互作用的文献增添重要的背景，更广泛地说，可能会为未来通过调节睡眠来治疗抑郁症提供依据。

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引用次数: 0

Associations between human blood metabolome and vascular dementia 人类血液代谢组与血管性痴呆之间的关系

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-19 DOI: 10.1016/j.pnpbp.2024.111150

Background

Effective and specific biomarkers are warranted for the management of vascular dementia. We aimed to systematically screen the human blood metabolome to identify potential mediators of vascular dementia via a two-sample Mendelian randomization (MR) design.

Methods

We selected 93 unique blood metabolites from 3 metabolome genome-wide association studies (GWASs) with a total of 147,827 participants of European ancestry. Summary statistics for vascular dementia originated from a European-descent GWAS dataset released by the FinnGen Study, involving 859 cases and 211,300 controls. We applied the inverse-variance weighted MR method in the main analysis to examine the causal roles of blood metabolites in vascular dementia, followed by several sensitivity analyses for robustness validation.

Results

Genetically determined glycoproteins (OR per 1-SD increase, 0.75; 95 % CI, 0.68–0.83, P = 1.08 × 10⁻⁸) and O-methylascorbate (OR per 1-SD increase, 0.08; 95 % CI, 0.02–0.32; P = 3.74 × 10⁻⁴) levels had negative associations with the risk of vascular dementia, whereas genetically determined total cholesterol (OR per 1-SD increase, 1.77; 95 % CI, 1.32–2.38; P = 1.39 × 10⁻⁴) and low-density lipoprotein (LDL) cholesterol (OR per 1-SD increase, 1.94; 95 % CI, 1.48–2.55; P = 1.61 × 10⁻⁶) levels had positive associations with the risk of vascular dementia. MR-Egger regression suggested no directional pleiotropy for the identified associations, and sensitivity analyses with different MR models further confirmed these findings.

Conclusion

Glycoproteins, O-methylascorbate, total cholesterol, and LDL cholesterol might be promising blood markers of vascular dementia, which may provide novel insights into the prevention of vascular dementia. Further studies are warranted to replicate our findings and elucidate the potential mechanistic pathways.

背景：血管性痴呆症的治疗需要有效而特异的生物标志物。我们旨在通过双样本孟德尔随机化（MR）设计系统地筛选人类血液代谢组，以确定血管性痴呆的潜在介导因素：我们从3项代谢组全基因组关联研究（GWAS）中选取了93种独特的血液代谢物，共有147827名欧洲血统的参与者参与了研究。血管性痴呆的汇总统计数据来自芬兰基因研究（FinnGen Study）发布的欧洲血统 GWAS 数据集，其中包括 859 例病例和 211,300 例对照。我们在主要分析中采用了逆方差加权MR方法来研究血液代谢物在血管性痴呆中的因果作用，随后又进行了几项敏感性分析以验证其稳健性：基因决定的糖蛋白（每增加 1-SD OR，0.75；95 % CI，0.68-0.83，P = 1.08 × 10-8）和 O-甲基抗坏血酸（每增加 1-SD OR，0.08；95 % CI，0.02-0.32；P = 3.74 × 10-4）水平与血管性痴呆风险呈负相关，而基因决定的总胆固醇（每增加 1-SD OR，1.77；95 % CI，1.32-2.38；P = 1.39 × 10-4）和低密度脂蛋白（LDL）胆固醇（OR 每增加 1-SD，1.94；95 % CI，1.48-2.55；P = 1.61 × 10-6）水平与血管性痴呆风险呈正相关。MR-Egger回归表明，已确定的关联不存在方向性多重效应，使用不同MR模型进行的敏感性分析进一步证实了这些发现：结论：糖蛋白、O-甲基抗坏血酸、总胆固醇和低密度脂蛋白胆固醇可能是血管性痴呆有希望的血液标志物，可为预防血管性痴呆提供新的见解。我们有必要开展进一步研究，以复制我们的发现并阐明潜在的机理途径。

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引用次数: 0

Stable construction and analysis of MDD modular networks based on multi-center EEG data 基于多中心脑电图数据的 MDD 模块化网络的稳定构建与分析。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-19 DOI: 10.1016/j.pnpbp.2024.111149

Background

The modular structure can reflect the activity pattern of the brain, and exploring it may help us understand the pathogenesis of major depressive disorder (MDD). However, little is known about how to build a stable modular structure in MDD patients and how modules are separated and integrated.

Method

We used four independent resting state Electroencephalography (EEG) datasets. Different coupling methods, window lengths, and optimized community detection algorithms were used to find a reliable and robust modular structure, and the module differences of MDD were analyzed from the perspectives of global module attributes and local topology in multiple frequency bands.

Results

The combination of the Phase Lag Index (PLI) and the Louvain algorithm can achieve better results and can achieve stability at smaller window lengths. Compared with Healthy Controls (HC), MDD had higher Modularity (Q) values and the number of modules in low-frequency bands. In addition, MDD showed significant structural changes in the frontal and parietal-occipital lobes, which were confirmed by further correlation analysis.

Conclusion

Our results provided a reliable validation of the modular structure construction method in MDD patients and contributed strong evidence for the changes in emotional cognition and visual system function in MDD patients from a new perspective. These results would afford valuable insights for further exploration of the pathogenesis of MDD.

背景：模块化结构可以反映大脑的活动模式，探索模块化结构有助于我们了解重度抑郁障碍（MDD）的发病机制。然而，我们对重度抑郁症患者如何建立稳定的模块化结构以及模块是如何分离和整合的知之甚少：我们使用了四个独立的静息状态脑电图（EEG）数据集。方法：我们使用了四个独立的静息状态脑电图（EEG）数据集，采用不同的耦合方法、窗口长度和优化的群落检测算法来寻找可靠、稳健的模块结构，并从多个频段的全局模块属性和局部拓扑结构的角度分析了 MDD 的模块差异：结果：相位滞后指数（PLI）和卢万算法的组合能取得更好的效果，并能在较小的窗口长度下实现稳定性。与健康对照组（HC）相比，MDD 的模块化（Q）值和低频段的模块数量更高。此外，MDD 的额叶和顶叶-枕叶结构也发生了显著变化，这一点在进一步的相关分析中得到了证实：我们的研究结果为模块结构构建方法在 MDD 患者中的应用提供了可靠的验证，并从一个新的角度为 MDD 患者情绪认知和视觉系统功能的变化提供了有力的证据。这些结果将为进一步探索 MDD 的发病机制提供有价值的见解。

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引用次数: 0

Transcranial magnetic stimulation for obsessive-compulsive disorder and post-traumatic stress disorder: A comprehensive systematic review and analysis of therapeutic benefits, cortical targets, and psychopathophysiological mechanisms 经颅磁刺激治疗强迫症和创伤后应激障碍：对治疗效果、皮层目标和精神病理生理机制的全面系统回顾和分析。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-16 DOI: 10.1016/j.pnpbp.2024.111147

Transcranial magnetic stimulation (TMS) is a safe non-invasive treatment technique. We systematically reviewed randomised controlled trials (RCTs) applying TMS in obsessive compulsive disorder (OCD) and post-traumatic stress disorder (PTSD) to analyse its therapeutic benefits and explore the relationship between cortical target and psychopathophysiology.

We included 47 randomised controlled trials (35 for OCD) and found a 22.7 % symptom improvement for OCD and 29.4 % for PTSD. Eight cortical targets were investigated for OCD and four for PTSD, yielding similar results. Bilateral dlPFC-TMS exhibited the greatest symptom change (32.3 % for OCD, N = 4 studies; 35.7 % for PTSD, N = 1 studies), followed by right dlPFC-TMS (24.4 % for OCD, N = 8; 26.7 % for PTSD, N = 10), and left dlPFC-TMS (22.9 % for OCD, N = 6; 23.1 % for PTSD, N = 1). mPFC-TMS showed promising results, although evidence is limited (N = 2 studies each for OCD and PTSD) and findings for PTSD were conflicting.

Despite clinical improvement, reviewed reports lacked a consistent and solid rationale for cortical target selection, revealing a gap in TMS research that complicates the interpretation of findings and hinders TMS development and optimisation.

Future research should adopt a hypothesis-driven approach rather than relying solely on correlations from imaging studies, integrating neurobiological processes with affective, behavioural, and cognitive states, thereby doing justice to the complexity of human experience and mental illness.

经颅磁刺激（TMS）是一种安全的非侵入性治疗技术。我们系统回顾了将经颅磁刺激应用于强迫症和创伤后应激障碍的随机对照试验（RCT），以分析其治疗效果，并探讨皮质靶点与精神病理生理学之间的关系。我们纳入了 47 项随机对照试验（35 项针对强迫症），发现强迫症的症状改善率为 22.7%，创伤后应激障碍的症状改善率为 29.4%。对强迫症和创伤后应激障碍分别进行了八项和四项皮质靶点研究，结果相似。双侧 dlPFC-TMS 的症状变化最大（强迫症 32.3%，4 项研究；创伤后应激障碍 35.7%，1 项研究），其次是右侧 dlPFC-TMS（强迫症 24.4%，8 项研究；创伤后应激障碍 26.7%，10 项研究）和左侧 dlPFC-TMS（强迫症 22.9%，1 项研究）。mPFC-TMS显示出令人鼓舞的结果，尽管证据有限（强迫症和创伤后应激障碍各有2项研究），而且创伤后应激障碍的研究结果也相互矛盾。尽管临床效果有所改善，但综述报告在皮层目标选择方面缺乏一致且可靠的理论依据，这揭示了 TMS 研究中的一个空白点，它使研究结果的解释变得复杂，并阻碍了 TMS 的发展和优化。未来的研究应采用假设驱动的方法，而不是仅仅依赖于成像研究的相关性，将神经生物学过程与情感、行为和认知状态结合起来，从而公正地对待人类经历和精神疾病的复杂性。

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引用次数: 0

Sequential physical and cognitive training disrupts cocaine-context associations via multi-level stimulation of adult hippocampal neurogenesis 通过对成人海马神经发生的多层次刺激，循序渐进的体能和认知训练可破坏可卡因与情境的关联

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-14 DOI: 10.1016/j.pnpbp.2024.111148

Cocaine-related contextual cues are a recurrent source of craving and relapse. Extinction of cue-driven cocaine seeking remains a clinical challenge, and the search for adjuvants is ongoing. In this regard, combining physical and cognitive training is emerging as a promising strategy that has shown synergistic benefits on brain structure and function, including enhancement of adult hippocampal neurogenesis (AHN), which has been recently linked to reduced maintenance of maladaptive drug seeking. Here, we examined whether this behavioral approach disrupts cocaine-context associations via improved AHN. To this aim, C57BL/6J mice (N = 37) developed a cocaine-induced conditioned place preference (CPP) and underwent interventions consisting of exercise and/or spatial working memory training. Bromodeoxyuridine (BrdU) was administered during early running sessions to tag a subset of new dentate granule cells (DGCs) reaching a critical window of survival during spatial learning. Once these DGCs became functionally mature (∼ 6 weeks-old), mice received extinction training before testing CPP extinction and reinstatement. We found that single and combined treatments accelerated CPP extinction and prevented reinstatement induced by a low cocaine priming (2 mg/kg). Remarkably, the dual-intervention mice showed a significant decrease of CPP after extinction relative to untreated animals. Moreover, combining the two strategies led to increased number and functional integration of BrdU⁺ DGCs, which in turn maximized the effect of spatial training (but not exercise) to reduce CPP persistence. Together, our findings suggests that sequencing physical and cognitive training may redound to decreased maintenance of cocaine-context associations, with multi-level stimulation of AHN as a potential underlying mechanism.

与可卡因相关的情境线索是导致渴求和复吸的一个经常性来源。抑制线索驱动的可卡因渴求仍是一项临床挑战，目前仍在寻找辅助疗法。在这方面，将体能训练和认知训练相结合是一种很有前景的策略，它对大脑结构和功能具有协同作用，包括增强成人海马神经发生（AHN），而最近的研究表明，AHN与减少不良药物寻求的维持有关。在这里，我们研究了这种行为方法是否会通过改善海马神经发生来破坏可卡因与情境的关联。为此，C57BL/6J小鼠（N = 37）产生了可卡因诱导的条件性位置偏好（CPP），并接受了由运动和/或空间工作记忆训练组成的干预。在小鼠早期跑步过程中注射溴脱氧尿苷（BrdU），以标记在空间学习过程中达到存活关键窗口期的新齿状颗粒细胞（DGCs）。一旦这些 DGCs 功能成熟（∼ 6 周龄），小鼠将接受消退训练，然后再测试 CPP 消退和恢复。我们发现，在低可卡因引物（2 毫克/千克）的诱导下，单药和联合用药都能加速CPP的消退并阻止其恢复。值得注意的是，与未接受治疗的小鼠相比，接受双重干预的小鼠在熄灭后CPP显著下降。此外，将这两种策略结合在一起会增加BrdU+ DGCs的数量和功能整合，这反过来又会最大限度地提高空间训练（而非运动）减少CPP持续性的效果。总之，我们的研究结果表明，将体能训练和认知训练进行排序可能会减少可卡因-情境关联的维持，而多层次的AHN刺激是潜在的内在机制。

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引用次数: 0

Emotional processing in binge drinking, tobacco use disorder and their comorbidity in youth: A preregistered PRISMA scoping review 青少年暴饮、烟草使用障碍及其合并症中的情绪处理：预先注册的 PRISMA 范围综述。

IF 5.3 2区医学 Q1 CLINICAL NEUROLOGY

Progress in Neuro-Psychopharmacology & Biological Psychiatry

Pub Date : 2024-09-11 DOI: 10.1016/j.pnpbp.2024.111138

Background

Binge drinking (BD) and tobacco use disorder (TUD) are prevalent among youth, with significant social and health implications. However, research into the emotional impairments associated with BD and TUD during adolescence is sparse and lacks integration within a comprehensive model of emotional processes. Moreover, the impact of comorbid BD and TUD on emotional deficits remains largely unexplored. We propose the first review focused on the variation of emotional deficits in BD, TUD, or their comorbidity among adolescents and we systematically explore differences across various emotional abilities.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines (PRISMA-ScR), we conducted a preregistered review of existing literature on emotional processing impairments in BD and/or TUD among adolescents. From 481 papers initially identified, 7 were included in this review. Additionally, we proposed experimental avenues for future research based on identified shortcomings in current literature.

Results

Our scoping review indicates that emotional deficits are likely prevalent in both BD and TUD populations, affecting emotional appraisal/identification, response, and regulation. However, further investigation is necessary to ascertain the magnitude and scope of these deficits in adolescents and adults, as well as to delineate the distinct or combined influence of BD and TUD on emotional disturbances.

Conclusion

While some emotional deficits are apparent, we contend that examining emotional deficits in BD and TUD separately, as well as together, would offer a more comprehensive understanding of their nature and inform the development of novel treatment strategies.

背景暴饮暴食（BD）和烟草使用障碍（TUD）在青少年中十分普遍，对社会和健康产生了重大影响。然而，对青春期暴饮暴食和烟草使用障碍相关的情感障碍的研究却很少，而且缺乏情感过程综合模型的整合。此外，合并 BD 和 TUD 对情绪缺陷的影响在很大程度上仍未得到探讨。我们提出了第一份综述，重点研究 BD、TUD 或它们在青少年中的合并症所导致的情绪缺陷的变化，并系统地探讨了各种情绪能力之间的差异。方法按照《系统性综述和元分析扩展报告指南》（PRISMA-ScR），我们对有关 BD 和/或 TUD 在青少年中的情绪处理障碍的现有文献进行了预先登记的综述。在初步确定的 481 篇文献中，只有 7 篇被纳入本综述。此外，我们还根据目前文献中发现的不足之处，提出了未来研究的实验途径。结果我们的范围性综述表明，情绪缺陷可能在 BD 和 TUD 群体中普遍存在，影响了情绪评估/识别、反应和调节。结论虽然某些情绪缺陷是显而易见的，但我们认为，对 BD 和 TUD 的情绪缺陷进行单独或合并研究，将有助于更全面地了解其性质，并为制定新的治疗策略提供依据。

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引用次数: 0