European Neuropsychopharmacology最新文献

英文中文

Placental epigenetic signatures of maternal distress in glucocorticoid-related genes and newborn outcomes: A study of Spanish primiparous women 糖皮质激素相关基因中孕产妇痛苦的胎盘表观遗传学特征与新生儿结局：对西班牙初产妇的研究。

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-11-06 DOI: 10.1016/j.euroneuro.2024.10.001

Maternal stress during pregnancy can impact offspring health, increasing the risk of neuropsychiatric disorders. The human placenta plays a crucial role in understanding this effect, influencing fetal programming as it connects maternal and fetal circulation. Our hypothesis centers on maternal stress influencing children's outcomes through placental DNA methylation, targeting three cortisol-regulating genes: NR3C1, FKBP5, and HSD11B2.

In this pilot study, chorionic villi and maternal decidua placental layers from 45 mother-infant dyads (divided into two groups based on high/low maternal stress exposure) were analyzed for DNA methylation at the genes of interest via targeted bisulfite sequencing. Pregnant women provided four saliva samples throughout a day for cortisol determinations and were assessed for the presence of depressive symptoms at each of the three trimesters of pregnancy. Newborns underwent neurodevelopmental assessments and salivary cortisol evaluations at 7 weeks.

Increased maternal diurnal cortisol levels in the first trimester of pregnancy was significantly associated with elevated DNA methylation at exon 1D of the NR3C1 gene and lower DNA methylation at intron 7 of the FKBP5 gene, both in chorionic villi samples. Elevated DNA methylation at introns 1 and 7 of FKBP5 in the maternal decidua were strongly linked to an anticipated delivery. DNA methylation at the HSD11B2 promoter region was uniformly low across all placental samples. No associations with newborn neurodevelopment were found.

These results emphasize the importance of exploring layer-specific methylation differences at distinct pregnancy stages, highlighting the complex interplay between maternal stress, placental epigenetic modifications, and fetal development throughout the prenatal period.

孕期母体的压力会影响后代的健康，增加患神经精神疾病的风险。人类胎盘在了解这种影响方面起着至关重要的作用，它连接着母体和胎儿的血液循环，影响着胎儿的发育。我们的假说集中于母体压力通过胎盘 DNA 甲基化影响儿童的结果，目标是三个皮质醇调节基因：NR3C1、FKBP5 和 HSD11B2。在这项试验性研究中，通过靶向亚硫酸氢盐测序分析了45对母婴（根据母婴压力暴露程度分为高/低两组）的绒毛和母体蜕膜胎盘层中相关基因的DNA甲基化情况。孕妇每天提供四份唾液样本用于皮质醇测定，并在怀孕三个月的每个阶段对是否存在抑郁症状进行评估。新生儿在 7 周时接受神经发育评估和唾液皮质醇评估。在绒毛样本中，妊娠头三个月母体昼夜皮质醇水平的升高与NR3C1基因外显子1D的DNA甲基化升高和FKBP5基因内含子7的DNA甲基化降低有显著关联。母体蜕膜中 FKBP5 基因内含子 1 和 7 的 DNA 甲基化升高与预产期密切相关。在所有胎盘样本中，HSD11B2 启动子区域的 DNA 甲基化程度都很低。没有发现与新生儿神经发育有关的关联。这些结果强调了在不同妊娠阶段探索特定层甲基化差异的重要性，突出了整个产前期间母体压力、胎盘表观遗传修饰和胎儿发育之间复杂的相互作用。

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引用次数: 0

The microRNA profile of brain-derived extracellular vesicles: A promising step forward in developing pharmacodynamic biomarkers for psychiatric disorders 脑源性细胞外囊泡的 microRNA 图谱：在开发精神疾病药效学生物标记物方面迈出充满希望的一步

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-11-06 DOI: 10.1016/j.euroneuro.2024.10.002

MicroRNAs (miRNAs) have the potential to affect drug metabolism, and some drugs affect cellular miRNA expression. miRNAs are found inside extracellular vesicles (EVs), and the profile of these EV-miRNAs can change across different diseases and disease states. Consequently, in recent years EV-miRNAs have attracted increasing attention as possible non-invasive biomarkers. For example, analyzing the miRNA expression profile of brain-derived EVs in blood may allow us to non-invasively assess miRNA dysregulation and thus to gain knowledge about the pathophysiology of psychiatric disorders and identify potential new predictive targets. We searched PubMed for all studies related to the effects of psychiatric medications on EV-miRNAs and identified 14 relevant articles. Taken together, findings indicate that certain EV-miRNAs may be targets for psychiatric medications and that antipsychotics such as olanzapine and antidepressants such as fluoxetine may alter the expression levels of particular EV-miRNAs. If confirmed and replicated, these findings may lead to the suggested miRNA profiles being used as pharmacodynamic biomarkers. However, heterogeneities and uncertainties remain regarding the role of EV-miRNAs in psychiatric disorders and their interaction with neuronal gene expression and drugs. This minireview summarizes some of the findings on the effects of psychiatric medications on EV-miRNAs and describes the potential role of EV-miRNAs as pharmacodynamic biomarkers for psychiatric disorders.

微小RNA（miRNA）可能会影响药物代谢，有些药物会影响细胞中miRNA的表达。miRNA存在于细胞外囊泡（EV）中，这些EV-miRNA的特征在不同疾病和疾病状态下会发生变化。因此，近年来，EV-miRNA 作为可能的非侵入性生物标记物引起了越来越多的关注。例如，分析血液中脑源EVs的miRNA表达谱可让我们非侵入性地评估miRNA失调，从而了解精神疾病的病理生理学并确定潜在的新预测靶点。我们在PubMed上搜索了所有与精神科药物对EV-miRNA影响相关的研究，并确定了14篇相关文章。综上所述，研究结果表明，某些EV-miRNA可能是精神科药物的靶点，奥氮平等抗精神病药物和氟西汀等抗抑郁药物可能会改变特定EV-miRNA的表达水平。如果这些发现得到证实和复制，可能会将建议的 miRNA 图谱用作药效学生物标志物。然而，关于 EV-miRNA 在精神疾病中的作用及其与神经元基因表达和药物之间的相互作用，仍然存在异质性和不确定性。本微综述总结了精神科药物对 EV-miRNAs 影响的一些研究结果，并阐述了 EV-miRNAs 作为精神疾病药效学生物标记物的潜在作用。

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引用次数: 0

A meta-analysis of data-driven cognitive subgroups in bipolar disorder 双相情感障碍认知分组数据荟萃分析

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-11-06 DOI: 10.1016/j.euroneuro.2024.10.008

The delineation of cognitive subgroups of bipolar disorder (BD) might be helpful for identifying biologically valid subtypes of this disorder. This meta-analysis identified peer-reviewed literature on studies investigating cognitive subgroups of BD with data-driven clustering methods. Relevant studies were searched in PubMed, Scopus, and Web of Science. Random-effects meta-analysis was performed using R software. A total of 14 cross-sectional studies including euthymic or mildly symptomatic patients with BD were included in the current meta-analysis. The available studies have consistently supported a 3-cluster solution. The pooled prevalence of the severe-impairment, moderate-impairment, and major good-functioning groups were 23.1 % (95%CI, 18.5 %–27.7 %), 42.5 % (95%CI, 36.3 %–48.8 %), and 33.5 % (95%CI, 25.9 %–41.1 %) respectively. Compared to healthy controls, both the severe-impairment (g=−1.40 to −1.73) and moderate-impairment groups (g=−0.59 to −0.96) had significant deficits in all six cognitive domains (verbal memory, visual memory, executive functions, working memory, attention and processing speed). The good-performance subgroup had a small increase in the performance of executive functions (g=0.23) and normal functioning in all other domains. Compared to the good-performance subgroup, the severe-impairment subgroup was characterized by more severe functional impairment, more hospital admissions, a higher percentage of type I BD and antipsychotic use. The characteristics of the moderate-impairment subgroup were lying between the other two subgroups for most of the measures. The current findings support the existence of 3 cognitive subgroups in BD including severe-impairment and moderate-impairment groups which are associated with a more severe course of illness.

双相情感障碍（BD）认知亚组的划分可能有助于确定该障碍在生物学上有效的亚型。这项荟萃分析采用数据驱动的聚类方法，对调查双相情感障碍认知亚组的研究进行了同行评议，并确定了相关文献。相关研究在 PubMed、Scopus 和 Web of Science 中进行了检索。使用 R 软件进行随机效应荟萃分析。目前的荟萃分析共纳入了 14 项横断面研究，其中包括无症状或症状轻微的 BD 患者。现有研究一致支持 3 簇解决方案。重度受损组、中度受损组和主要功能良好组的汇总患病率分别为 23.1%（95%CI，18.5%-27.7%）、42.5%（95%CI，36.3%-48.8%）和 33.5%（95%CI，25.9%-41.1%）。与健康对照组相比，重度受损组（g=-1.40 至-1.73）和中度受损组（g=-0.59 至-0.96）在所有六个认知领域（言语记忆、视觉记忆、执行功能、工作记忆、注意力和处理速度）均存在显著缺陷。表现良好的亚组在执行功能方面的表现略有提高（g=0.23），而在所有其他领域的表现正常。与表现良好亚组相比，重度受损亚组的特点是功能受损更严重、入院次数更多，I 型 BD 的比例更高，并使用抗精神病药物。中度受损亚组在大多数测量指标上的特征介于其他两个亚组之间。目前的研究结果支持在 BD 中存在 3 个认知亚组，包括重度损伤组和中度损伤组，它们与更严重的病程有关。

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引用次数: 0

“The role of gut microbiota in adult attention deficit hyperactivity disorder: Insights and implications” "肠道微生物群在成人注意缺陷多动障碍中的作用：见解和影响"

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-11-06 DOI: 10.1016/j.euroneuro.2024.09.008

引用次数: 0

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-11-06 DOI: 10.1016/j.euroneuro.2024.10.010

引用次数: 0

Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area 口服一水肌酸对抑郁症认知行为疗法的疗效和安全性：在资源匮乏地区进行的为期 8 周的双盲、随机、安慰剂对照可行性和探索性试验。

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-11-01 DOI: 10.1016/j.euroneuro.2024.10.004

Pre-clinical and clinical evidence proposes that creatine monohydrate, an affordable nutraceutical, could be a useful adjunct to conventional antidepressant treatments. In this pilot feasibility and exploratory study, we investigate the 8-week effects of creatine in addition to cognitive-behavioural therapy (CBT) versus placebo plus CBT in depression. For the primary efficacy outcome of change in Patient Health Questionnaire-9 depression score at study endpoint, we used mixed-model repeated measures analysis of covariance. Logistic regressions were employed to assess acceptability (any-cause dropouts), tolerability (dropouts for adverse events), and safety (patients experiencing one or more adverse events). We calculated effect sizes adjusted for age, sex, and baseline depression score. One-hundred participants (50 females, mean age= 30.4 ± 7.4 years) with depression (mean PHQ-9 = 17.6 ± 6.3) were randomised to either creatine+CBT (N = 50) or placebo+CBT (N = 50). At 8 weeks, PHQ-9 scores were lower in both study arms, but significantly more so in participants taking creatine (mean difference= -5.12). Treatment discontinuations due to any cause and to adverse events, and proportion of participants with at least one adverse event were comparable between study arms. This hypothesis-generating trial suggests that creatine could be a useful and safe supplement to CBT for depression. Longer and larger clinical trials are warranted.

临床前和临床证据表明，一水肌酸这种经济实惠的营养保健品可以作为传统抗抑郁治疗的有效辅助药物。在这项试验性可行性和探索性研究中，我们调查了肌酸在认知行为疗法（CBT）基础上与安慰剂加 CBT 相比对抑郁症患者的 8 周疗效。对于研究终点时患者健康问卷-9 抑郁症评分变化这一主要疗效结果，我们采用了混合模型重复测量协方差分析法。逻辑回归用于评估可接受性（任何原因的退出）、耐受性（因不良事件退出）和安全性（出现一次或多次不良事件的患者）。我们计算了根据年龄、性别和基线抑郁评分调整后的效应大小。100 名抑郁症患者（50 名女性，平均年龄= 30.4 ± 7.4 岁）（平均 PHQ-9 = 17.6 ± 6.3）被随机分配到肌酸+CBT（50 人）或安慰剂+CBT（50 人）治疗方案中。8周时，两个研究组的PHQ-9评分均有所下降，但服用肌酸的参与者的PHQ-9评分明显更高（平均差异=-5.12）。因任何原因和不良事件导致的治疗中断，以及出现至少一种不良事件的参与者比例，在各研究组之间不相上下。这项提出假设的试验表明，肌酸可以作为抑郁症 CBT 的一种有用且安全的补充。有必要进行更长时间和更大规模的临床试验。

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引用次数: 0

Does 18 Hz deep TMS benefit a different subgroup of depressed patients relative to 10 Hz rTMS? The role of the individual alpha frequency 与 10 赫兹经颅磁刺激相比，18 赫兹深部经颅磁刺激是否能使不同亚组的抑郁症患者受益？个体阿尔法频率的作用

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-10-12 DOI: 10.1016/j.euroneuro.2024.09.007

Both 10 Hz repetitive transcranial magnetic stimulation (rTMS) as well as 18 Hz deep TMS (dTMS) constitute effective, FDA-approved TMS treatment protocols for depression. However, not all patients experience sufficient symptom relief after either of these protocols. Biomarker-guided treatment stratification could aid in personalizing treatment and thereby enhancing improvement. An individual alpha frequency (iAF)-based EEG-biomarker, Brainmarker-I, can differentially stratify patients to depression treatments. For instance, an iAF close to 10 Hz was associated with better improvement to 10 Hz rTMS, possibly reflecting entrainment of endogenous oscillations to the stimulation frequency.

Accordingly, we examined whether 18 Hz dTMS would result in better improvement in individuals whose iAF lies around 9 Hz, a harmonic frequency of 18 Hz.

Curve fitting and regression analyses were conducted to assess the relation between iAF and improvement. For treatment stratification purposes, correlations with iAF-distance to 10 Hz compared 18 Hz dTMS (N = 114) to 10 Hz rTMS (N = 72).

We found a robust quadratic effect, indicating that patients with an iAF around 9 Hz exhibited least symptom improvement (r²=0.126, p<.001). Improvement correlated positively with iAF-distance to 10 Hz (p=.003). A secondary analysis in 20 Hz figure-of-eight data confirmed this direction. A significant interaction of iAF-distance and stimulation frequency between 10 and 18 Hz datasets emerged (p=.026).

These results question entrainment of endogenous oscillations by their harmonic frequency for 18 Hz, and suggest that 10 Hz and 18 Hz TMS target different subgroups of depression patients. This study adds to iAF stratification, augmenting Brainmarker-I with alternative TMS protocols (18 Hz/20 Hz) for patients with a slower iAF, thereby broadening clinical applicability and relevance of the biomarker.

10 赫兹重复经颅磁刺激（rTMS）和 18 赫兹深部经颅磁刺激（dTMS）都是经美国食品及药物管理局批准的有效抑郁症经颅磁刺激治疗方案。然而，并非所有患者在接受这两种治疗方案后症状都能得到充分缓解。以生物标志物为指导的治疗分层有助于个性化治疗，从而改善病情。基于个体α频率（iAF）的脑电图生物标志物--Brainmarker-I，可以对抑郁症患者进行分层治疗。例如，iAF接近10赫兹与10赫兹经颅磁刺激的改善效果更佳相关，这可能反映了内源性振荡对刺激频率的诱导作用。因此，我们研究了iAF位于9赫兹（18赫兹的谐波频率）附近的个体，18赫兹经颅磁刺激是否会带来更好的改善效果。出于治疗分层的目的，将 18 赫兹经颅磁刺激（N = 114）与 10 赫兹经颅磁刺激（N = 72）进行了比较。我们发现了一个强有力的二次效应，表明 iAF 在 9 赫兹左右的患者症状改善最少（r2=0.126，p<.001）。改善程度与 iAF 与 10 赫兹的距离呈正相关（p=.003）。对 20 赫兹八位数数据的二次分析证实了这一方向。在10赫兹和18赫兹数据集之间，iAF-距离与刺激频率之间出现了明显的交互作用（p=.026）。这些结果质疑了18赫兹谐波频率对内源性振荡的诱导作用，并表明10赫兹和18赫兹TMS针对的是不同的抑郁症患者亚群。这项研究为iAF分层增添了新的内容，为iAF较慢的患者提供了可供选择的TMS方案（18赫兹/20赫兹）来增强Brainmarker-I，从而扩大了生物标记的临床适用性和相关性。

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引用次数: 0

UPDATE FROM THE “PEDIGREE-BASED WHOLE GENOME SEQUENCING OF AFFECTIVE AND PSYCHOTIC DISORDERS" CONSORTIUM 基于谱系的情感障碍和精神障碍全基因组测序 "的最新进展联合会

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-10-01 DOI: 10.1016/j.euroneuro.2024.08.082

引用次数: 0

TRACKING THE LONGITUDINAL COURSE IN YOUNG PEOPLE AT HIGH RISK OF BIPOLAR DISORDER 追踪躁郁症高危青少年的纵向病程

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-10-01 DOI: 10.1016/j.euroneuro.2024.08.019

Young people with a first-degree relative with bipolar disorder (BD) have a 10-15% risk of developing this illness, but currently we have little understanding of the specific clinical and/or biological features which predict such an outcome. Our group in Sydney established the Bipolar Disorder Kids and Sibs high-risk cohort over a decade ago (with 170 high risk young people, 130 controls and 65 who had already developed BD) and have collaborated closely with the US multi-site consortium led by John Nurnberger. We have followed this Australian sample regularly over time, with particular interest in neuroimaging, genetic (including epigenetic), neuropsychological and clinical findings. We have scanned subjects on 3 occasions (baseline, 2 and 10 years), having already published on changes over the first two years. We reported significant weakening in the high-risk subjects of structural connectivity in a network encompassing the left inferior and middle frontal areas, left striatal and thalamic structures, the left fusiform, and right parietal and occipital regions. These findings were more pronounced in those who had developed a first episode of hypo(mania) over those two years. We have also explored for clinical predictors of hypo(mania) onset, finding particular depressive features to be a strong predictor of this outcome. We will present clinical and biological findings of our 10-year follow-up. More studies of long-term biological and clinical changes over time, and predictors of the onset of hypo(mania) are needed to enable rational development of early intervention studies in those at increased familial risk of BD.

有一级亲属患有躁郁症（BD）的年轻人有 10-15% 的患病风险，但目前我们对预测这种结果的具体临床和/或生物学特征知之甚少。我们在悉尼的研究小组十多年前建立了双相情感障碍儿童和兄弟姐妹高风险队列（包括170名高风险青少年、130名对照组和65名已经患上双相情感障碍的青少年），并与约翰-努恩伯格（John Nurnberger）领导的美国多站点研究小组密切合作。我们一直定期跟踪这一澳大利亚样本，尤其关注神经影像学、遗传学（包括表观遗传学）、神经心理学和临床研究结果。我们对受试者进行了 3 次扫描（基线、2 年和 10 年），并已发表了前两年的变化情况。我们发现，在高危人群中，包括左侧额叶下部和中部区域、左侧纹状体和丘脑结构、左侧纺锤体以及右侧顶叶和枕叶区域在内的网络结构连通性明显减弱。这些发现在两年内首次出现低（躁）狂症的患者中更为明显。我们还探索了低躁狂症发病的临床预测因素，发现特定的抑郁特征是预测这一结果的有力因素。我们将介绍 10 年随访的临床和生物学研究结果。我们需要对长期的生物学和临床变化以及低（躁）狂发病的预测因素进行更多的研究，以便对那些BD家族风险增加的人群进行合理的早期干预研究。

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引用次数: 0

DRUG REPOSITIONING ANALYSIS IDENTIFIED HUNDREDS OF NOVEL COMPOUNDS ASSOCIATED WITH TOBACCO USE DISORDER 药物重新定位分析发现了数百种与烟草使用障碍有关的新型化合物

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology

Pub Date : 2024-10-01 DOI: 10.1016/j.euroneuro.2024.08.097

引用次数: 0

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