Biological psychiatry global open science最新文献_第7页

Borderline Personality Disorder Symptoms and Stressful Life Events: An Evaluation of Gene-Environment Interplay 边缘型人格障碍症状与生活压力事件：基因与环境相互作用的评估

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-30 DOI: 10.1016/j.bpsgos.2024.100390

Vilde Sofie Arneberg , Vilde Sundsvold , Ludvig Daae Bjørndal , Eivind Ystrom

Background

Borderline personality disorder (BPD) is associated with high rates of stressful life events (SLEs). It is unclear whether people who experience SLEs have more BPD symptoms after accounting for the effects of familial risk factors. Our aims in the current study were to 1) create a predictive model of BPD using stressors across age and contexts and 2) examine whether SLEs resulted in higher levels of BPD symptoms beyond the effects of genetic and environmental risk factors.

Methods

The sample comprised 2801 twins from the Norwegian Institute of Public Health Twin Panel. Poisson regression was used to explore which SLEs predicted BPD symptoms. Elastic net penalized regression was conducted to develop a predictive model for SLEs and BPD symptoms. Co-twin control analyses were performed to differentiate between environmental and genetic factors.

Results

SLEs experienced during childhood and adulthood were associated with BPD symptoms. A weighted polyevent risk score explained 22% of the total variation in symptoms. Shared environmental and heritable factors explained 31% and 47% of individual differences in BPD symptomatology, respectively. Measured SLEs explained 42% of the shared environmental risk for BPD. The predictive risk of SLEs for BPD was reduced when shared environmental and genetic factors were accounted for. However, SLEs increased risk of BPD symptoms beyond the effects of shared genetic and environmental factors.

Conclusions

BPD symptomatology following SLEs cannot fully be explained by genetic and shared environmental factors. The SLE-BPD symptoms associations were primarily due to selection by family environments. It is important to identify familial factors that lead to both SLEs and BPD symptoms. SLEs remained associated with BPD symptoms beyond genetic and environmental confounding.

背景边缘型人格障碍（BPD）与高比率的生活压力事件（SLEs）有关。目前还不清楚在考虑了家族风险因素的影响后，经历过 SLE 的人是否会有更多的 BPD 症状。本研究的目的是：1）利用跨年龄和跨环境的压力源建立一个BPD预测模型；2）研究SLE是否会导致遗传和环境风险因素影响之外的更高水平的BPD症状。采用泊松回归法探讨哪些SLE可预测BPD症状。弹性净惩罚回归用于建立SLE和BPD症状的预测模型。为了区分环境因素和遗传因素，还进行了同卵双生子对照分析。加权多事件风险评分解释了症状总变化的 22%。共同的环境因素和遗传因素分别解释了 31% 和 47% 的 BPD 症状个体差异。测得的 SLE 可解释 42% 的 BPD 共同环境风险。在考虑了共同环境因素和遗传因素后，SLEs 对 BPD 的预测风险降低了。然而，SLE 增加的 BPD 症状风险超出了共同遗传和环境因素的影响。系统性红斑狼疮与 BPD 症状的关联主要是由于家庭环境的选择。确定导致系统性红斑狼疮和 BPD 症状的家族因素非常重要。系统性红斑狼疮与 BPD 症状的相关性仍然超出了遗传和环境因素的影响。

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引用次数: 0

A Systematic Review and Meta-Analysis of Anxiety- and Depressive-Like Behaviors in Rodent Models of Neuropathic Pain 神经性疼痛啮齿动物模型中焦虑和抑郁样行为的系统回顾和元分析

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-26 DOI: 10.1016/j.bpsgos.2024.100388

Tomás de la Rosa , Meritxell Llorca-Torralba , Adrián Martínez-Cortés , Cristina Romero-López-Alberca , Esther Berrocoso

Background

Epidemiological studies have frequently shown the concurrence of chronic pain with symptoms of anxiety and depression, particularly in women. Animal models are useful to understand the complex mechanisms underlying comorbidities, but the wide range of methods employed and the wealth of evidence sometimes impedes effective translation and reproducibility. In this systematic review and meta-analysis, we aimed to synthesize the evidence regarding the influence of variables such as sex and species on anxiety- and depressive-like behaviors in rodent models of neuropathic pain.

Methods

Following PROSPERO registration, we searched EMBASE, Scopus, and the Web of Science from their inception to November 24, 2023, identifying 126 studies that met the inclusion criteria. The Hedges’ g value for each experiment and study was calculated, and further subgroup and meta-regression analyses were performed.

Results

Neuropathic pain significantly reduced the time that rats and mice spent in the open arms of the elevated plus and zero mazes (g = −1.14), time spent in the center of the open field (g = −1.12), sucrose consumption in the sucrose preference test (g = −1.43), and grooming time in the splash test (g = −1.37) while increasing latency to feed in the novelty-suppressed feeding test (g = 1.59) and immobility in the forced swimming (g = 1.85) and tail suspension (g = 1.91) tests. Sex differences were observed, with weaker effects in female than in male rodents for several behavioral paradigms, and funnel plots identified positive publication bias in the literature.

Conclusions

This meta-analysis emphasizes the effect of neuropathic pain on anxiety- and depressive-like behaviors in rodents, highlighting the importance of investigating sex differences in future experimental studies.

背景流行病学研究经常显示慢性疼痛与焦虑和抑郁症状同时存在，尤其是在女性中。动物模型有助于了解并发症的复杂机制，但所采用的方法种类繁多，证据数量巨大，有时会妨碍有效的转化和可重复性。在这篇系统综述和荟萃分析中，我们旨在综合性别和物种等变量对神经病理性疼痛啮齿类动物模型中焦虑和抑郁样行为影响的证据。结果神经病理性疼痛显著减少了大鼠和小鼠在高架正迷宫和零迷宫开放臂中的停留时间（g = -1.14）、在开放场地中心的停留时间（g = -1.12 ）、蔗糖偏好试验中的蔗糖消耗量（g = -1.43 ）和飞溅试验中的梳理时间（g = -1.37 ），同时增加了新奇感抑制摄食试验中的摄食潜伏期（g = 1.59 ）以及强迫游泳（g = 1.85 ）和尾悬吊（g = 1.91 ）试验中的不动性。结论这项荟萃分析强调了神经性疼痛对啮齿类动物焦虑和抑郁样行为的影响，突出了在未来实验研究中调查性别差异的重要性。

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引用次数: 0

Associations Between Mental Disorders in Donors and Matched Recipients of Hematopoietic Stem Cell Transplants: A Population-Based Cohort Study 造血干细胞移植供体和配型受体精神障碍之间的关系：基于人群的队列研究

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-26 DOI: 10.1016/j.bpsgos.2024.100389

Troels Boldt Rømer , Henrik Sengeløv , Rune Haubo Bojesen Christensen , Michael Eriksen Benros

Background

Immunological mechanisms have been implicated in the development of mental disorders, and interestingly, case reports have suggested that hematopoietic stem cell transplantation (HSCT) can both transmit and cure psychotic disorders by replacing immune progenitor cells.

Methods

Using Danish registers, we followed patients who received HSCT from donors with a psychiatric diagnosis or psychotropic medication use. We assessed risk of incident mental disorders or psychotropic medication use compared with recipients with unaffected donors. We identified 464 donor-recipient pairs (51.3% male recipients). All donor-recipient pairs were related.

Results

Receiving HSCT from a donor with a psychiatric history was not significantly associated with incident psychiatric diagnoses (hazard rate ratio [HRR] 2.79, 95% CI, 0.83–9.39; p = .098) or incident use of psychotropics (HRR 1.43, 95% CI, 0.91–2.24; p = .118). Subgroup analysis showed an increased risk of antipsychotic use, which remained significant after adjusting for confounders (HRR 4.73, 95% CI, 1.26–17.78; p = .021); however, this was based on a small number of cases. For depression and antidepressant use, data were available to perform a meta-analysis of our and one additional study, which showed no significant difference (HRR 1.24, 95%, CI 0.66–2.35).

Conclusions

Receiving HSCT from a donor with a psychiatric history did not affect risk of mental disorders. An increased risk of antipsychotic use was observed only in subgroup analyses; however, the exploratory nature of the study, the limited sample size, and family relationship between donors and recipients do not allow for causal conclusions, and external replication studies are warranted.

背景免疫学机制被认为与精神障碍的发生有关，有趣的是，有病例报告表明，造血干细胞移植（HSCT）通过替代免疫祖细胞，既可传播精神障碍，也可治愈精神障碍。与未受影响的供体受者相比，我们评估了发生精神障碍或使用精神药物的风险。我们确定了 464 对供体-受体（51.3% 为男性受体）。结果接受有精神病史捐献者的造血干细胞移植与精神病诊断（危险率比 [HRR] 2.79，95% CI，0.83-9.39；p = .098）或精神药物使用（危险率比 1.43，95% CI，0.91-2.24；p = .118）无显著相关性。亚组分析表明，使用抗精神病药物的风险增加，在调整了混杂因素后仍然显著（HRR 4.73，95% CI，1.26-17.78；p = .021）；然而，这只是基于少数病例。对于抑郁症和抗抑郁药的使用，我们有数据对我们的研究和另外一项研究进行了荟萃分析，结果显示两者无显著差异（HRR 1.24，95%，CI 0.66-2.35）。仅在亚组分析中观察到使用抗精神病药物的风险增加；然而，由于该研究的探索性、样本量有限以及供体和受体之间的家庭关系，因此无法得出因果关系的结论，需要进行外部重复研究。

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引用次数: 0

Sex-Specific Effects of Birth Weight on Longitudinal Behavioral Outcomes: A Mendelian Randomization Approach Using Polygenic Scores 出生体重对纵向行为结果的性别特异性影响：使用多基因评分的孟德尔随机化方法

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-26 DOI: 10.1016/j.bpsgos.2024.100387

Lars Meinertz Byg , Carol Wang , John Attia , Andrew Whitehouse , Craig Pennell

Background

It is unclear whether sex differences in behavior arising from birth weight (BW) are genuine because of the cross-sectional nature and potential confounding in previous studies. We aimed to test whether sex differences associated with BW phenotype were reproducible using a Mendelian randomization approach, i.e., association between polygenic score (PGS) for BW and behavior outcomes across childhood and adolescence.

Methods

Using data from the Raine Study, we had 1484 genotyped participants with a total of 6446 Child Behavior Checklist assessments from ages 5 to 17 years. We used BW-PGSs in linear mixed-effect models to predict parentally assessed attention, aggression, and social problems scales; we also derived estimates and significance for a sex-by-genotype interaction. We used a Bonferroni-corrected significance threshold and tested robustness of the results with teacher assessments of behavior and a second PGS.

Results

We found a sex-by-genotype interaction with lower BW-PGSs associated with increased aggression in males compared with females. These findings were consistent across various analyses, including teacher assessments. Surprisingly, a lower BW-PGS showed protective effects in females, while a lower BW phenotype had detrimental effects in males with evidence of a genotype-phenotype mismatch increasing aggression problems in males only.

Conclusions

This study underscores the genuine nature of behavioral sex differences arising from low BW and highlights the sex-dependent and diverging effects of environmental and genetic BW determinants.

背景由于以往研究的横断面性质和潜在混杂因素，出生体重（BW）引起的行为性别差异是否真实尚不清楚。我们的目的是采用孟德尔随机化方法检验与出生体重表型相关的性别差异是否具有可重复性，即出生体重的多基因评分（PGS）与儿童和青少年时期行为结果之间的关联。方法利用雷恩研究（Raine Study）的数据，我们对 1484 名参与者进行了基因分型，并对其 5 至 17 岁期间的 6446 项儿童行为检查表进行了评估。我们在线性混合效应模型中使用 BW-PGS 来预测父母评估的注意力、攻击性和社会问题量表；我们还得出了性别-基因型交互作用的估计值和显著性。我们使用了 Bonferroni 校正的显著性阈值，并通过教师对行为的评估和第二个 PGS 检验了结果的稳健性。结果我们发现了性别-基因型交互作用，与女性相比，较低的 BW-PGS 与男性的攻击性增加有关。这些结果在包括教师评估在内的各种分析中都是一致的。令人惊讶的是，较低的体重-PGS 对女性有保护作用，而较低的体重表型则对男性有不利影响，有证据表明基因型-表型不匹配只会增加男性的攻击性问题。

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引用次数: 0

Modulation of Posterior Default Mode Network Activity During Interoceptive Attention and Relation to Mindfulness 互感注意期间后部默认模式网络活动的调节及其与正念的关系

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-23 DOI: 10.1016/j.bpsgos.2024.100384

Dhakshin Ramanathan , Jason Nan , Gillian Grennan , Satish Jaiswal , Suzanna Purpura , James Manchanda , Vojislav Maric , Pragathi Priyadharsini Balasubramani , Jyoti Mishra

Background

Interoceptive attention to internal sensory signals, such as the breath, is fundamental to mindfulness. However, interoceptive attention can be difficult to study, with many studies relying on subjective and retrospective measures. Response consistency is an established method for evaluating variability of attention on exteroceptive attention tasks, but it has rarely been applied to interoceptive attention tasks.

Methods

In this study, we measured consistency of response times on a breath-monitoring task with simultaneous electroencephalography in individuals across the life span (15–91 years of age, N = 324).

Results

We found that consistency on the breath-monitoring task was positively correlated with attentive performance on an exteroceptive inhibitory control task. Electroencephalography source reconstruction showed that on-task alpha band (8–12 Hz) activity was greater than that measured at rest. Low-consistency/longer breath responses were associated with elevated brain activity compared with high-consistency responses, particularly in posterior default mode network (pDMN) brain regions. pDMN activity was inversely linked with functional connectivity to the frontoparietal network and the cingulo-opercular network on task but not at rest, suggesting a role for these frontal networks in on-task regulation of pDMN activity. pDMN activity within the precuneus region was greater in participants who reported low subjective mindfulness and was adaptively modulated by task difficulty in an independent experiment.

Conclusions

Elevated pDMN alpha activity serves as an objective neural marker for low-consistency responding during interoceptive breath attention, scales with task difficulty, and is associated with low subjective mindfulness.

背景对呼吸等内部感觉信号的感知间注意是正念的基础。然而，感知间注意力很难研究，许多研究都依赖于主观和回顾性测量。在这项研究中，我们用同步脑电图测量了不同年龄段（15-91 岁，N = 324）的人在呼吸监测任务上的反应时间一致性。结果我们发现，呼吸监测任务上的一致性与外感知抑制控制任务上的注意力表现呈正相关。脑电图源重构显示，任务中的α波段（8-12赫兹）活动比休息时测得的活动要强。与高一致性反应相比，低一致性/较长的呼吸反应与大脑活动的升高有关，尤其是在后默认模式网络（pDMN）脑区。pDMN活动与任务中的额顶叶网络和丘脑-小脑网络的功能连通性成反比，但与休息时的功能连通性无关，这表明这些额叶网络在任务中调节pDMN活动的作用。楔前区的pDMN活动在报告主观正念较低的参与者中更大，并且在一项独立实验中受任务难度的调节。

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引用次数: 0

Resilience to Chronic Stress Is Characterized by Circadian Brain-Liver Coordination 对慢性压力的复原力以昼夜节律脑肝协调为特征

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-23 DOI: 10.1016/j.bpsgos.2024.100385

Christina Savva , Ivan Vlassakev , Blynn G. Bunney , William E. Bunney , Lucas Massier , Marcus Seldin , Paolo Sassone-Corsi , Paul Petrus , Shogo Sato

Background

Chronic stress has a profound impact on circadian regulation of physiology. In turn, disruption of circadian rhythms increases the risk of developing both psychiatric and metabolic disorders. To explore the role of chronic stress in modulating the links between neural and metabolic rhythms, we characterized the circadian transcriptional regulation across different brain regions and the liver as well as serum metabolomics in mice exposed to chronic social defeat stress, a validated model for studying depressive-like behaviors.

Methods

Male C57BL/6J mice underwent chronic social defeat stress, and subsequent social interaction screening identified distinct behavioral phenotypes associated with stress resilience and susceptibility. Stressed mice and their control littermates were sacrificed every 4 hours over the circadian cycle for comprehensive analyses of the circadian transcriptome in the hypothalamus, hippocampus, prefrontal cortex, and liver together with assessments of the circadian circulatory metabolome.

Results

Our data demonstrate that stress adaptation was characterized by reprogramming of the brain as well as the hepatic circadian transcriptome. Stress resiliency was associated with an increase in cyclic transcription in the hypothalamus, hippocampus, and liver. Furthermore, cross-tissue analyses revealed that resilient mice had enhanced transcriptional coordination of circadian pathways between the brain and liver. Conversely, susceptibility to social stress resulted in a loss of cross-tissue coordination. Circadian serum metabolomic profiles corroborated the transcriptome data, highlighting that stress-resilient mice gained circadian rhythmicity of circulating metabolites, including bile acids and sphingomyelins.

Conclusions

This study reveals that resilience to stress is characterized by enhanced metabolic rhythms and circadian brain-liver transcriptional coordination.

背景慢性压力对生理的昼夜节律调节有着深远的影响。反过来，昼夜节律紊乱也会增加患精神疾病和代谢紊乱的风险。为了探索慢性应激在调节神经节律和代谢节律之间的联系中的作用，我们对暴露于慢性社交失败应激（一种研究抑郁样行为的有效模型）的小鼠的不同脑区和肝脏的昼夜节律转录调控以及血清代谢组学进行了表征。结果我们的数据表明，应激适应的特点是大脑和肝脏昼夜节律转录组的重编程。应激恢复能力与下丘脑、海马和肝脏中循环转录的增加有关。此外，跨组织分析显示，抗压能力强的小鼠大脑和肝脏之间昼夜节律通路的转录协调性增强。相反，易受社会压力影响的小鼠则丧失了跨组织协调能力。昼夜节律血清代谢组图谱证实了转录组数据，突出表明具有应激复原力的小鼠获得了包括胆汁酸和鞘磷脂在内的循环代谢物的昼夜节律性。

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引用次数: 0

Predicting Prenatal Depression and Assessing Model Bias Using Machine Learning Models 利用机器学习模型预测产前抑郁症并评估模型偏差

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-14 DOI: 10.1016/j.bpsgos.2024.100376

Yongchao Huang , Suzanne Alvernaz , Sage J. Kim , Pauline Maki , Yang Dai , Beatriz Peñalver Bernabé

Background

Perinatal depression is one of the most common medical complications during pregnancy and postpartum period, affecting 10% to 20% of pregnant individuals, with higher rates among Black and Latina women who are also less likely to be diagnosed and treated. Machine learning (ML) models based on electronic medical records (EMRs) have effectively predicted postpartum depression in middle-class White women but have rarely included sufficient proportions of racial/ethnic minorities, which has contributed to biases in ML models. Our goal is to determine whether ML models could predict depression in early pregnancy in racial/ethnic minority women by leveraging EMR data.

Methods

We extracted EMRs from a large U.S. urban hospital serving mostly low-income Black and Hispanic women (n = 5875). Depressive symptom severity was assessed using the Patient Health Questionnaire-9 self-report questionnaire. We investigated multiple ML classifiers using Shapley additive explanations for model interpretation and determined prediction bias with 4 metrics: disparate impact, equal opportunity difference, and equalized odds (standard deviations of true positives and false positives).

Results

Although the best-performing ML model's (elastic net) performance was low (area under the receiver operating characteristic curve = 0.61), we identified known perinatal depression risk factors such as unplanned pregnancy and being single and underexplored factors such as self-reported pain, lower prenatal vitamin intake, asthma, carrying a male fetus, and lower platelet levels. Despite the sample comprising mostly low-income minority women (54% Black, 27% Latina), the model performed worse for these communities (area under the receiver operating characteristic curve: 57% Black, 59% Latina women vs. 64% White women).

Conclusions

EMR-based ML models could moderately predict early pregnancy depression but exhibited biased performance against low-income minority women.

背景产后抑郁症是孕期和产后最常见的医疗并发症之一，影响 10%-20%的孕妇，其中黑人和拉丁裔妇女的发病率较高，而她们也较少得到诊断和治疗。基于电子病历（EMR）的机器学习（ML）模型可以有效预测中产阶级白人妇女的产后抑郁症，但很少包含足够比例的少数种族/族裔，这导致了 ML 模型的偏差。我们的目标是通过利用 EMR 数据来确定 ML 模型是否能预测少数种族/族裔妇女的孕早期抑郁症。方法我们从美国一家大型城市医院提取了 EMR，该医院主要服务于低收入的黑人和西班牙裔妇女（n = 5875）。抑郁症状严重程度通过患者健康问卷-9 自我报告问卷进行评估。我们使用沙普利加法解释对多个 ML 分类器进行了研究，并用 4 个指标确定了预测偏差：差异影响、机会均等差异和均等化几率（真阳性和假阳性的标准偏差）。结果虽然表现最好的 ML 模型（弹性网）性能较低（接收者操作特征曲线下面积 = 0.61），但我们发现了已知的围产期抑郁风险因素，如计划外怀孕和单身，以及未被充分探索的因素，如自我报告的疼痛、产前维生素摄入量较低、哮喘、怀有男胎和血小板水平较低。尽管样本中大多数是低收入的少数民族妇女（54% 黑人，27% 拉丁裔），但该模型在这些群体中的表现较差（接收者操作特征曲线下的面积：57% 黑人，59% 拉丁裔）：结论基于 EMR 的 ML 模型可适度预测孕早期抑郁症，但对低收入少数民族妇女的预测表现出偏差。

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引用次数: 0

Alcohol Use Disorder–Associated DNA Methylation in the Nucleus Accumbens and Dorsolateral Prefrontal Cortex 与酒精使用障碍相关的凹凸核和背外侧前额叶皮层 DNA 甲基化

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-13 DOI: 10.1016/j.bpsgos.2024.100375

Julie D. White , Melyssa S. Minto , Caryn Willis , Bryan C. Quach , Shizhong Han , Ran Tao , Amy Deep-Soboslay , Lea Zillich , Stephanie H. Witt , Rainer Spanagel , Anita C. Hansson , Shaunna L. Clark , Edwin J.C.G. van den Oord , Thomas M. Hyde , R. Dayne Mayfield , Bradley T. Webb , Eric O. Johnson , Joel E. Kleinman , Laura J. Bierut , Dana B. Hancock

Background

Alcohol use disorder (AUD) has a profound public health impact. However, understanding of the molecular mechanisms that underlie the development and progression of AUD remains limited. Here, we investigated AUD-associated DNA methylation changes within and across 2 addiction-relevant brain regions, the nucleus accumbens and dorsolateral prefrontal cortex.

Methods

Illumina HumanMethylation EPIC array data from 119 decedents (61 cases, 58 controls) were analyzed using robust linear regression with adjustment for technical and biological variables. Associations were characterized using integrative analyses of public annotation data and published genetic and epigenetic studies. We also tested for brain region–shared and brain region–specific associations using mixed-effects modeling and assessed implications of these results using public gene expression data from human brain.

Results

At a false discovery rate of ≤.05, we identified 105 unique AUD-associated CpGs (annotated to 120 genes) within and across brain regions. AUD-associated CpGs were enriched in histone marks that tag active promoters, and our strongest signals were specific to a single brain region. Some concordance was found between our results and those of earlier published alcohol use or dependence methylation studies. Of the 120 genes, 23 overlapped with previous genetic associations for substance use behaviors, some of which also overlapped with previous addiction-related methylation studies.

Conclusions

Our findings identify AUD-associated methylation signals and provide evidence of overlap with previous genetic and methylation studies. These signals may constitute predisposing genetic differences or robust methylation changes associated with AUD, although more work is needed to further disentangle the mechanisms that underlie these associations and their implications for AUD.

背景酒精使用障碍（AUD）对公共健康有着深远的影响。然而，人们对 AUD 发生和发展的分子机制的了解仍然有限。在这里，我们研究了成瘾相关的两个脑区（伏隔核和背外侧前额叶皮层）内部和之间与 AUD 相关的 DNA 甲基化变化。方法使用稳健线性回归分析了来自 119 名死者（61 例病例，58 例对照）的 Allumina 人类甲基化 EPIC 阵列数据，并对技术和生物变量进行了调整。通过对公共注释数据以及已发表的遗传学和表观遗传学研究进行综合分析，确定了关联的特征。我们还使用混合效应模型检验了脑区共享和脑区特异性关联，并使用人脑的公共基因表达数据评估了这些结果的意义。结果在错误发现率≤.05的条件下，我们在脑区内部和跨脑区鉴定出了105个独特的AUD相关CpGs（注释到120个基因）。AUD相关的CpGs富集于标记活性启动子的组蛋白标记中，而且最强的信号是单个脑区特有的。我们的研究结果与早期发表的酒精使用或依赖甲基化研究结果有一定的一致性。在这 120 个基因中，有 23 个与以前的药物使用行为遗传相关性研究重叠，其中一些还与以前的成瘾相关甲基化研究重叠。这些信号可能构成与 AUD 相关的易感基因差异或稳健的甲基化变化，尽管还需要做更多的工作来进一步阐明这些关联的机制及其对 AUD 的影响。

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引用次数: 0

Sex Differences in the Development of an Opioid Addiction–Like Phenotype: A Focus on the Telescoping Effect 类阿片成瘾表型发展过程中的性别差异：聚焦伸缩效应

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-13 DOI: 10.1016/j.bpsgos.2024.100373

Eleanor Blair Towers , Kyle A. Hsu , Emaan I. Qillawala , Shaniece D. Fraser , Wendy J. Lynch

Background

Women develop addiction and drug-related health consequences after fewer years of drug use than men; this accelerated time course, or telescoping effect, has been observed clinically for multiple drugs, including opioids. Preclinical studies indicate that this is a biologically based phenomenon; however, these studies have focused exclusively on cocaine, and none have considered health effects.

Methods

In this study, we used a rat (Sprague Dawley) model to determine sex differences in the time course for the development of an opioid addiction–like phenotype, as defined by the development of physical dependence (withdrawal-induced weight loss) and an increase in motivation for fentanyl (under a progressive-ratio schedule). Effects were determined following either 10 days (optimized, experiment 1) or 3 days (threshold, experiment 2) of extended-access fentanyl self-administration (24 hours/day, fixed ratio 1, 2- to 5-minute trials/hour) or following short-access fentanyl self-administration (subthreshold, experiment 3; fixed ratio 1, up to 40 infusions/day). Opioid-related adverse health effects were also determined (experiment 4).

Results

Motivation for fentanyl was similarly increased in males and females following 10 days of extended-access self-administration (experiment 1), was transiently increased in females, but not males, following 3 days of extended-access self-administration (experiment 2) and was not increased in either sex following short-access self-administration (experiment 3). Females developed fentanyl-associated adverse health effects more readily than males (experiment 4), with particularly robust differences during extended-access self-administration and withdrawal.

Conclusions

As with findings in humans, female rats developed opioid addiction–like features and adverse health consequences more readily than male rats. These data provide support for a biologically based telescoping effect in females for opioids, particularly for opioid-related adverse health consequences.

背景与男性相比，女性吸食毒品的年数较少，但却会成瘾并产生与毒品相关的健康后果；临床上已经观察到包括阿片类药物在内的多种药物会出现这种加速的时间过程或伸缩效应。在这项研究中，我们使用大鼠（Sprague Dawley）模型来确定阿片类药物成瘾样表型发展时间过程中的性别差异，该表型的定义是生理依赖性的发展（戒断引起的体重减轻）和芬太尼动机的增加（在渐进比率时间表下）。实验结果是在 10 天（优化，实验 1）或 3 天（阈值，实验 2）延长芬太尼自我给药（24 小时/天，固定比率 1，2 到 5 分钟/小时）或短期芬太尼自我给药（阈值以下，实验 3；固定比率 1，最多 40 次/天）后得出的。结果男性和女性在延长自我给药时间 10 天后对芬太尼的渴求度同样增加（实验 1），女性在延长自我给药时间 3 天后对芬太尼的渴求度短暂增加，而男性则没有（实验 2），男性和女性在短时间自我给药后对芬太尼的渴求度都没有增加（实验 3）。结论与人类的研究结果一样，雌性大鼠比雄性大鼠更容易出现类似阿片类药物成瘾的特征和不良健康后果（实验 4）。这些数据支持雌性大鼠对阿片类药物产生基于生物学的伸缩效应，尤其是与阿片类药物相关的不良健康后果。

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引用次数: 0

Exploring the Embodied Mind: Functional Connectome Fingerprinting of Meditation Expertise 探索具身心灵：冥想专长的功能连接组指纹图谱

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-08-09 DOI: 10.1016/j.bpsgos.2024.100372

Sébastien Czajko , Jelle Zorn , Loïc Daumail , Gael Chetelat , Daniel S. Margulies , Antoine Lutz

Background

Short mindfulness-based interventions have gained traction in research due to their positive impact on well-being, cognition, and clinical symptoms across various settings. However, these short-term trainings are viewed as preliminary steps within a more extensive transformative path, presumably leading to long-lasting trait changes. Despite this, little is still known about the brain correlates of these meditation traits.

Methods

To address this gap, we investigated the neural correlates of meditation expertise in long-term Buddhist practitioners, comparing the large-scale brain functional connectivity of 28 expert meditators with 47 matched novices. Our hypothesis posited that meditation expertise would be associated with specific and enduring patterns of functional connectivity present during both meditative (open monitoring/open presence and loving-kindness and compassion meditations) and nonmeditative resting states, as measured by connectivity gradients.

Results

Applying a support vector classifier to states not included in training, we successfully decoded expertise as a trait, demonstrating its non–state-dependent nature. The signature of expertise was further characterized by an increased integration of large-scale brain networks, including the dorsal and ventral attention, limbic, frontoparietal, and somatomotor networks. The latter correlated with a higher ability to create psychological distance from thoughts and emotions.

Conclusions

Such heightened integration of bodily maps with affective and attentional networks in meditation experts could point toward a signature of the embodied cognition cultivated in these contemplative practices.

背景基于正念的短期干预对各种环境下的幸福感、认知和临床症状产生了积极影响，因此在研究中备受关注。然而，这些短期培训被视为更广泛的转化途径中的初步步骤，可能会导致长期的特质变化。为了填补这一空白，我们研究了长期佛教修行者禅修专长的神经相关性，比较了 28 名禅修专家和 47 名匹配新手的大规模大脑功能连接。我们的假设是，冥想专长将与冥想（开放式监控/开放式存在以及慈爱和慈悲冥想）和非冥想静息状态下存在的特定且持久的功能连接模式相关联，并通过连接梯度进行测量。结果将支持向量分类器应用于未纳入训练的状态，我们成功地将专长解码为一种特质，证明了其不依赖于状态的性质。专业知识的特征进一步表现为大规模大脑网络整合的增强，包括背侧和腹侧注意力网络、边缘网络、额顶网络和躯体运动网络。结论冥想专家身体图谱与情感和注意力网络的高度整合可能是这些沉思练习中培养的具身认知的特征。

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引用次数: 0