Biological psychiatry global open science最新文献_第2页

Group Social Dynamics in a Seminatural Setup Reflect the Adaptive Value of Aggression in Male Mice 半自然环境中的群体社会动态反映了雄性小鼠攻击行为的适应价值

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-10-01 DOI: 10.1016/j.bpsgos.2024.100399

Sergey Anpilov , Yair Shemesh , Asaf Benjamin , Tommaso Biagini , Daniil Umanski , Yehonatan Zur , Yehezkel Sztainberg , Alon Richter-Levin , Oren Forkosh , Alon Chen

Background

Maladaptive aggression in humans is associated with several psychiatric conditions and lacks effective treatment. Nevertheless, tightly regulated aggression is essential for survival throughout the animal kingdom. Studying how social dominance hierarchies regulate aggression and access to resources in an enriched environment (EE) can narrow the translational gap between aggression in animal models and normal and pathological human behavior.

Methods

The social box is a seminatural setup for automatic and prolonged monitoring of mouse group dynamics. We utilized the social box to decipher tradeoffs between aggression, social avoidance, resource allocation, and dominance in 2 mouse models of increased aggression: 1) a model of early exposure to an EE and 2) a model of oxytocin receptor deficiency (Oxtr^−/−). While environmental enrichment increases aggression as an adaptive response to external stimuli, hyperaggression in Oxtr^−/− mice is accompanied by marked abnormalities in social behavior.

Results

EE groups exhibited significant social avoidance, and an increased proportion of their encounters developed into aggressive interactions, resulting in lower levels of exploratory activity and overall aggression. The hierarchy in EE groups was more stable than in control groups, and dominance was correlated with access to resources. In Oxtr^−/− groups, mice engaged in excessive social encounters and aggressive chasing, accompanied by increased overall activity. In Oxtr^−/− groups, dominance hierarchies existed but were not correlated with access to resources.

Conclusions

Measuring aggression and social dominance hierarchies in a seminatural setup reveals the adaptive value of aggression in EE and Oxtr^−/− mice. This approach can enhance translational research on pathological aggression.

背景人类的适应性攻击行为与多种精神疾病有关，而且缺乏有效的治疗方法。然而，在整个动物界，受到严格调控的攻击行为对于生存至关重要。研究丰富环境（EE）中社会支配等级如何调节攻击行为和资源获取，可以缩小动物模型中的攻击行为与正常和病态人类行为之间的转化差距。我们利用 "社交箱 "在两种攻击性增加的小鼠模型中解读了攻击性、社会回避、资源分配和支配地位之间的权衡：1）早期暴露于 EE 的模型；2）催产素受体缺乏（Oxtr-/-）的模型。结果EE组小鼠表现出明显的社会回避，而且它们相遇时发展成攻击性互动的比例增加，导致探索活动和整体攻击性水平降低。与对照组相比，EE 组的等级制度更加稳定，支配地位与获得资源的机会相关。在Oxtr-/-组中，小鼠进行了过度的社交接触和攻击性追逐，同时总体活动增加。结论在半自然设置中测量攻击性和社会支配等级揭示了EE和Oxtr-/-小鼠攻击性的适应价值。这种方法可以促进病理性攻击行为的转化研究。

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引用次数: 0

Effect of an 18-Month Meditation Training on Telomeres in Older Adults: A Secondary Analysis of the Age-Well Randomized Controlled Trial 为期 18 个月的冥想训练对老年人端粒的影响：年龄-健康随机对照试验的二次分析

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-10-01 DOI: 10.1016/j.bpsgos.2024.100398

Perla Kaliman , María Jesús Álvarez-López , Asrar Lehodey , Daniel Fernández , Anne Chocat , Marco Schlosser , Vincent de La Sayette , Denis Vivien , Natalie L. Marchant , Gael Chételat , Antoine Lutz , Géraldine Poisnel

Background

Shorter telomeres are associated with increased risk of cognitive decline and age-related diseases. Developing interventions to promote healthy aging by preserving telomere integrity is of paramount importance. Here, we investigated the effect of an 18-month meditation intervention on telomere length (TL) measures in older people without cognitive impairment.

Methods

A total of 137 adults age ≥65 years were randomized to one of the 3 groups (meditation training, non-native language training, or passive control). We evaluated the 50th and 20th percentile TL and the percentage of critically short telomeres (<3 kbp) in peripheral blood mononuclear cells.

Results

Mixed model analysis showed a time effect indicating a general decrease on the 50th percentile TL (F = 80.72, p_adjusted < .001), without a significant group effect or time × group interaction. No significant effect was detected in the 20th percentile TL or the percentage of critically short telomeres. Secondary analysis showed that only in the meditation training group 1) the 50th percentile TL positively correlated with class attendance time (r = 0.45, p_adjusted < .011), 2) the 50th and 20th percentile TL positively correlated with responsiveness to the intervention, evaluated through a composite score (r = 0.46, p_adjusted < .010 and r = 0.41, p_adjusted = .029, respectively), and 3) lower scores on a measure of the personality trait “openness to experience” correlated with a lower percentage of critically short telomeres after the intervention (r = 0.44, p_adjusted = .015).

Conclusions

In older adults, we found no evidence for a main effect of an 18-month meditation training program on TL compared with the control groups. Our findings highlight the importance of considering the impact of moderating factors when measuring the effectiveness of meditation-based trainings.

背景端粒变短与认知能力下降和老年相关疾病的风险增加有关。制定干预措施，通过保护端粒完整性来促进健康老龄化至关重要。在此，我们研究了为期18个月的冥想干预对无认知障碍老年人端粒长度（TL）测量的影响。方法：137名年龄≥65岁的成年人被随机分配到3个组（冥想训练组、非母语训练组或被动对照组）中的一组。我们评估了外周血单核细胞中第50和第20百分位数端粒长度和极短端粒（3 kbp）的百分比。结果混合模型分析表明，时间效应表明第50百分位数端粒长度普遍下降（F = 80.72，padjusted <.001），而没有显著的组效应或时间×组交互作用。在第20百分位数端粒长度或极短端粒的百分比方面没有发现明显的影响。二次分析表明，只有在冥想训练组中，1）第 50 位百分位数端粒长度与上课时间呈正相关（r = 0.45，经垫底调整后为 0.011）；2）第 50 位和第 20 位百分位数端粒长度与通过综合评分评估的干预响应度呈正相关（r = 0.46，经垫底调整后为 0.010 和 r = 0.41，经垫底调整后为 0.029）；3）第 50 位和第 20 位百分位数端粒长度与通过综合评分评估的干预响应度呈正相关（r = 0.46，经垫底调整后为 0.010 和 r = 0.41，经垫底调整后为 0.029）。结论在老年人中，与对照组相比，我们没有发现证据表明为期 18 个月的冥想训练计划对端粒寿命有主要影响。我们的研究结果凸显了在衡量冥想训练的有效性时考虑调节因素影响的重要性。

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引用次数: 0

The Transition From Homogeneous to Heterogeneous Machine Learning in Neuropsychiatric Research 神经精神研究中从同构机器学习到异构机器学习的转变

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-26 DOI: 10.1016/j.bpsgos.2024.100397

Qingyu Zhao , Kate B. Nooner , Susan F. Tapert , Ehsan Adeli , Kilian M. Pohl , Amy Kuceyeski , Mert R. Sabuncu

Despite the advantage of neuroimaging-based machine learning (ML) models as pivotal tools for investigating brain-behavior relationships in neuropsychiatric studies, these data-driven predictive approaches have yet to yield substantial, clinically actionable insights for mental health care. A notable impediment lies in the inadequate accommodation of most ML research to the natural heterogeneity within large samples. Although commonly thought of as individual-level analyses, many ML algorithms are unimodal and homogeneous and thus incapable of capturing the potentially heterogeneous relationships between biology and psychopathology. We review the current landscape of computational research targeting population heterogeneity and argue that there is a need to expand from brain subtyping and behavioral phenotyping to analyses that focus on heterogeneity at the relational level. To this end, we review and suggest several existing ML models with the capacity to discern how external environmental and sociodemographic factors moderate the brain-behavior mapping function in a data-driven fashion. These heterogeneous ML models hold promise for enhancing the discovery of individualized brain-behavior associations and advancing precision psychiatry.

尽管基于神经成像的机器学习（ML）模型作为神经精神研究中调查大脑与行为关系的关键工具具有优势，但这些数据驱动的预测方法尚未为精神健康护理带来实质性的、临床上可操作的见解。一个显著的障碍在于，大多数 ML 研究无法充分适应大型样本中的自然异质性。尽管通常被认为是个体层面的分析，但许多 ML 算法都是单模态和同质的，因此无法捕捉生物学与精神病理学之间潜在的异质性关系。我们回顾了当前针对群体异质性的计算研究，认为有必要从大脑亚型和行为表型扩展到关注关系层面异质性的分析。为此，我们回顾并提出了几种现有的 ML 模型，这些模型有能力以数据驱动的方式辨别外部环境和社会人口因素是如何调节大脑-行为映射功能的。这些异质性 ML 模型有望促进个性化大脑行为关联的发现，并推动精准精神病学的发展。

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引用次数: 0

Intraindividual Variability of Event-Related Potentials in Psychosis: A Registered Report 精神病患者事件相关电位的个体内差异性：注册报告

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-21 DOI: 10.1016/j.bpsgos.2024.100396

Amanda Holbrook , Bohyun Park , Philippe Rast , Gregory A. Light , Peter E. Clayson

Background

Neurophysiological tools have yielded valuable insights into the pathophysiology and treatment of psychosis. However, studies using event-related potentials (ERPs) have primarily focused on mean scores and neglected the within-person variability of ERP scores. The neglect of within-person variability of ERPs in the search for biomarkers might have resulted in crucial differences related to psychosis being missed. In this registered report, we aimed to determine whether distinct patterns of intraindividual variability in ERP biomarkers would be observed in people with a lifetime psychosis diagnosis.

Methods

Publicly available data posted to the National Institute of Mental Health Data Archive for 1R01MH110434-01 was obtained for 162 patients with a lifetime history of psychosis and 178 never-psychotic (NP) participants. Participants completed tasks that measured the auditory mismatch negativity (MMN), P300, error-related negativity, and reward positivity. Multilevel location-scale models were used to determine whether patients showed greater intraindividual variability of ERP scores than NP participants.

Results

Contrary to predictions, the groups did not differ in within-person variability of MMN frequency, P300, or error-related negativity; patients showed less variability in MMN duration than NP participants. Exploratory analyses of a subset of patients with schizophrenia showed greater variability of MMN in this group than in the NP group. Greater severity of thought disorder and activation symptoms were associated with higher intraindividual MMN variability.

Conclusions

Distinct patterns of intraindividual variability in the measured ERPs were not observed for the broad group of people with lifetime psychotic disorders. Exploratory analyses suggest that intraindividual differences in ERPs are more relevant to schizophrenia and certain symptom dimensions than to psychotic disorders broadly, but research is needed to confirm these exploratory findings.

背景神经生理学工具为精神病的病理生理学和治疗提供了宝贵的见解。然而，使用事件相关电位（ERPs）进行的研究主要集中在平均得分上，而忽视了ERP得分的人内变异性。在寻找生物标志物的过程中忽视ERP的人内变异性可能会导致与精神病有关的关键差异被遗漏。在这份注册报告中，我们旨在确定在终生被诊断为精神病的人群中是否会观察到ERP生物标志物的个体内变异性的独特模式。方法我们获得了美国国家精神卫生研究所数据档案1R01MH110434-01的公开数据，其中包括162名终生有精神病史的患者和178名从未患过精神病（NP）的参与者。参与者完成了测量听觉错配负性（MMN）、P300、错误相关负性和奖赏正性的任务。结果与预测相反，两组在 MMN 频率、P300 或错误相关负性的人内变异性方面没有差异；患者在 MMN 持续时间方面的变异性低于 NP 参与者。对精神分裂症患者子集的探索性分析表明，该组患者的 MMN 变异性高于 NP 组。更严重的思维障碍和激活症状与更高的个体内部 MMN 变异性相关。探索性分析表明，ERPs的个体内差异与精神分裂症和某些症状维度的关系比与广泛的精神病性障碍的关系更为密切，但这些探索性发现还需要研究来证实。

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引用次数: 0

Oxytocin Reduces Noradrenergic-Induced Opioid-Like Withdrawal Symptoms in Individuals on Opioid Agonist Therapy 催产素能减轻接受阿片类激动剂治疗者的去甲肾上腺素能诱发的阿片类戒断症状

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-18 DOI: 10.1016/j.bpsgos.2024.100395

Brian J. Gully , Zoe E. Brown , Rivkah Hornbacher , Joshua C. Brown , Sudie E. Back , Elinore F. McCance-Katz , Robert M. Swift , Carolina L. Haass-Koffler

Background

Intranasal administration of the neuropeptide oxytocin has been explored as a potential therapeutic agent for substance use disorder including opioid use disorder (OUD).

Methods

This phase 1, crossover, randomized, double-blind, placebo-controlled trial tested the safety, tolerability, and efficacy of intranasal oxytocin (80 IU) twice a day for 7 days in participants (N = 20) with OUD who were taking an opioid agonist therapy. In the laboratory, participants underwent opioid cue exposure paired with noradrenergic activation produced by yohimbine (32.4 mg) or placebo. Assessments included, 1) subjective response: craving, withdrawal, anxiety, and stress; 2) biomedical markers: hypothalamic-pituitary-adrenal axis response (cortisol) and noradrenergic activation (α-amylase); and 3) safety measures: hemodynamics and adverse event evaluation. Generalized linear model with model-based estimator in the covariance matrix was used, with medication (oxytocin/placebo) and noradrenergic activation (yohimbine/placebo) as within-subject factors.

Results

Oxytocin significantly reduced opioid-like withdrawal, anxiety symptoms, and cortisol levels elicited by cue exposure under noradrenergic activation produced by yohimbine. This effect was specific because oxytocin did not reduce craving, hemodynamics, or α-amylase levels increased by yohimbine administration. A single dose of yohimbine elicited the noradrenergic stimulation, and 7-day oxytocin administration was safe and well tolerated among individuals diagnosed with OUD and taking opioid agonist therapy.

Conclusions

The findings of this study suggest that oxytocin alleviates opioid-like withdrawal symptoms and anxiety by modulating the hypothalamic-pituitary-adrenal axis.

方法这项一期交叉、随机、双盲、安慰剂对照试验测试了鼻内注射催产素（80 IU）的安全性、耐受性和疗效，对正在接受阿片类激动剂治疗的 OUD 患者（20 人）进行了为期 7 天、每天两次的测试。在实验室中，参与者在接触阿片类物质线索的同时，还接受育亨宾（32.4 毫克）或安慰剂产生的去甲肾上腺素能激活。评估包括：1）主观反应：渴求、戒断、焦虑和压力；2）生物医学指标：下丘脑-垂体-肾上腺轴反应（皮质醇）和去甲肾上腺素能激活（α-淀粉酶）；3）安全性测量：血液动力学和不良事件评估。结果催产素能显著降低阿片类戒断、焦虑症状和皮质醇水平，在育亨宾产生的去肾上腺素能激活作用下，暴露于诱因引起的皮质醇水平显著降低。这种效应是特异性的，因为催产素并不能降低因服用育亨宾而增加的渴求、血液动力学或α-淀粉酶水平。本研究结果表明，催产素可通过调节下丘脑-垂体-肾上腺轴来缓解阿片类戒断症状和焦虑。

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引用次数: 0

Differing Pattern of Mismatch Negativity Responses in Clinical and Nonclinical Voice Hearers Challenge Predictive Coding Accounts of Psychosis 临床和非临床听声辩位者的错配负性反应模式不同，这对精神病的预测编码描述提出了挑战

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-17 DOI: 10.1016/j.bpsgos.2024.100394

Molly A. Erickson , Sonia Bansal , Charlotte Li , James Waltz , Philip Corlett , James Gold

Background

Among people with schizophrenia (PSZ), reduced mismatch negativity (MMN) is conceptualized as evidence of disrupted prediction error signaling that underlies positive symptoms. However, this conceptualization has been challenged by observations that MMN and positive symptoms are often uncorrelated. In the current study, we tested the hypothesis that reduced MMN is associated with the presence of hallucinations and delusions specifically rather than the presence of a psychiatric illness. A second aim was to determine whether the strength of the association with positive symptoms increases for indices that reflect predictions at higher levels of abstraction.

Methods

Fifty-six PSZ, 34 nonclinical voice hearers, and 48 healthy comparison subjects (HCs) completed 2 MMN paradigms: one with a simple duration deviant type, and one with a higher-level, pattern-violation deviant type. We also measured the repetition positivity, which reflects the formation of auditory memory traces.

Results

We observed that although PSZ exhibited the expected pattern of significantly reduced duration MMN and reduced pattern-violation MMN at the trend level compared with HCs, nonclinical voice hearers exhibited a pattern of duration MMN and pattern-violation MMN amplitude that was statistically similar to that of HCs (ps > .64). Similarly, PSZ exhibited a significantly reduced repetition positivity slope compared with HCs in the duration condition and a trend-level reduction compared with HCs in the pattern-violation condition. Nonclinical voice hearers did not differ from either group in repetition positivity slope in either condition.

Conclusions

These results indicate that the MMN as a prediction error signal does not reflect processes relevant for the manifestation of hallucinations and delusions.

背景在精神分裂症（PSZ）患者中，错配负性（MMN）的降低被认为是预测错误信号传递中断的证据，而预测错误信号传递中断是阳性症状的基础。然而，MMN与阳性症状往往不相关的观察结果却对这一概念提出了质疑。在本研究中，我们检验了这样一个假设，即 MMN 的降低与幻觉和妄想的出现相关，而不是与精神疾病的出现相关。研究方法：56 名 PSZ、34 名非临床语音倾听者和 48 名健康对比受试者（HCs）完成了 2 个 MMN 范例：一个是简单的持续时间偏差类型，另一个是更高层次的模式违反偏差类型。我们还测量了反映听觉记忆痕迹形成的重复积极性。结果我们观察到，虽然 PSZ 与 HCs 相比，在趋势水平上表现出预期的持续时间 MMN 显著减少和模式违反 MMN 减少的模式，但非临床语音听者表现出的持续时间 MMN 和模式违反 MMN 振幅模式在统计学上与 HCs 相似（ps >.64）。同样，在持续时间条件下，PSZ 的重复阳性斜率与 HC 相比明显降低；在模式违反条件下，PSZ 的重复阳性斜率与 HC 相比呈下降趋势。这些结果表明，MMN 作为一种预测错误信号，并不能反映与幻觉和妄想表现相关的过程。

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引用次数: 0

The Balance N1 Is Larger in Children With Anxiety and Associated With the Error-Related Negativity 焦虑症儿童的平衡 N1 较大，与错误相关的负性有关

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-16 DOI: 10.1016/j.bpsgos.2024.100393

Aiden M. Payne , Norman B. Schmidt , Alex Meyer , Greg Hajcak

Background

The error-related negativity (ERN) is a brain response evoked by mistakes in cognitive tasks that is enhanced with anxiety and can predict the subsequent onset or exacerbation of anxiety in children and adolescents. A physical disturbance to standing balance evokes a brain response called the balance N1 that resembles the ERN in scalp topography and in response to a variety of moderating factors. We recently found that the balance N1 and ERN correlate in amplitude across small samples of adults.

Methods

In the current study, we tested the effect of anxiety on the balance N1 in children (ages 9–12 years) with and without diagnosed anxiety disorders (38 children with generalized anxiety, social anxiety, and/or obsessive-compulsive disorder and 50 children without these disorders). We measured the balance N1 in response to sudden release of support from a forward leaning posture, the ERN in response to mistakes on a Go/NoGo task, and anxiety symptoms using child- and parent-report forms of the Screen for Child Anxiety and Related Emotional Disorders.

Results

Both the balance N1 and the ERN were larger in the anxious group. The balance N1 was also associated with both the ERN and parent report of child anxiety symptom severity across individuals.

Conclusions

The higher measurement reliability of the balance N1 than the ERN and greater experimental control over errors suggest that balance paradigms may provide a more powerful method for investigating individual differences in error-related brain activity related to anxiety.

背景错误相关负性（error-related negativity，ERN）是由认知任务中的错误所诱发的一种大脑反应，这种反应会随着焦虑而增强，并能预测儿童和青少年随后焦虑的发生或加重。对站立平衡的物理干扰会诱发一种称为平衡 N1 的大脑反应，这种反应在头皮地形图和对各种调节因素的反应方面与 ERN 相似。在本研究中，我们测试了焦虑对患有和未患有焦虑症的儿童（9-12 岁）平衡 N1 的影响（38 名患有广泛性焦虑症、社交焦虑症和/或强迫症的儿童和 50 名未患有这些疾病的儿童）。我们测量了从前倾姿势突然松开支撑时的平衡N1、在 "去/不去 "任务中出现错误时的ERN，以及使用儿童焦虑和相关情绪障碍筛查的儿童和家长报告表测量的焦虑症状。结论与 ERN 相比，平衡 N1 的测量可靠性更高，而且对错误的实验控制更强，这表明平衡范式可能为研究与焦虑有关的错误相关大脑活动的个体差异提供了一种更有效的方法。

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引用次数: 0

Investigating the Shared Genetic Architecture Between Psychiatric Disorders and Executive Function 研究精神疾病与执行功能之间的共同遗传结构

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-10 DOI: 10.1016/j.bpsgos.2024.100392

Sijie Zhang , Linlin Zhao , Aijun Liao , David Li , Hong Li , Lijun Ouyang , Xiaogang Chen , Zongchang Li

Background

Evidence for widespread comorbidity of executive dysfunctions with psychiatric disorders suggests common mechanisms underlying their pathophysiology. However, the shared genetic architectures between psychiatric disorders and executive function (EF) remain poorly understood.

Methods

Leveraging large genome-wide association study datasets of European ancestry on bipolar disorder (N = 353,899), major depressive disorder (N = 674,452), and schizophrenia (N = 130,644) from the Psychiatric Genomics Consortium and iPSYCH and a common factor of EF (N = 427,037) from UK Biobank, we systematically investigated the shared genomic architectures between psychiatric disorders and EF with a set of statistical genetic, functional genomic, and gene-level analyses.

Results

Our study demonstrated substantial genetic overlaps and significant genetic correlations between psychiatric disorders and EF. EF showed an estimated 95.9%, 98.1%, and 99.2% of phenotype-influencing variants, as well as 50, 23, and 130 genomic loci shared with bipolar disorder, major depressive disorder, and schizophrenia, respectively. Single nucleotide polymorphism heritability enrichment suggests that the genetic architecture of psychiatric disorders and EF involves the brain’s frontal cortex and prefrontal glutamatergic neurons 1 and 2. Functional genomic analysis of shared variants identified 12 functional regulatory variants that regulate gene expression by affecting the binding affinities of 5 transcription factors. In addition, functional characterization analyses of shared genes revealed potential common biological mechanisms related to synaptic processes and fetal brain development.

Conclusions

Our findings provide evidence for extensive shared genetic architectures between psychiatric disorders and EF and have valuable implications for future mechanistic investigations and drug development efforts.

背景执行功能障碍与精神障碍广泛共存的证据表明，它们的病理生理学有着共同的机制。然而，人们对精神疾病与执行功能（EF）之间的共同遗传结构仍然知之甚少。方法利用精神病基因组学联合会和 iPSYCH 的大型欧洲血统双相情感障碍（N = 353,899 ）、重度抑郁障碍（N = 674,452 ）和精神分裂症（N = 130,644 ）全基因组关联研究数据集，以及英国生物库的 EF 共同因子（N = 427、037），我们通过一系列遗传统计、功能基因组和基因水平分析，系统地研究了精神疾病和 EF 之间的共享基因组结构。结果我们的研究表明，精神疾病与心房颤动之间存在大量的遗传重叠和显著的遗传相关性。估计 95.9%、98.1% 和 99.2% 的表型影响变异以及 50、23 和 130 个基因组位点分别与双相情感障碍、重度抑郁障碍和精神分裂症共享。单核苷酸多态性遗传富集表明，精神障碍和EF的遗传结构涉及大脑额叶皮层和前额叶谷氨酸能神经元1和2。对共有变异的功能基因组分析发现了 12 个功能调控变异，它们通过影响 5 个转录因子的结合亲和力来调控基因表达。此外，共享基因的功能特征分析揭示了与突触过程和胎儿大脑发育有关的潜在共同生物机制。结论我们的研究结果为精神疾病和 EF 之间广泛的共享遗传结构提供了证据，对未来的机理研究和药物开发工作具有重要意义。

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引用次数: 0

Size and Topography of the Brain’s Functional Networks with Psychotic Experiences, Schizophrenia, and Bipolar Disorder 精神错乱体验、精神分裂症和躁郁症患者大脑功能网络的规模和拓扑图

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-07 DOI: 10.1016/j.bpsgos.2024.100386

Daniel Mamah , Shing Shiun Chen , Evan Gordon , Sridhar Kandala , Deanna M. Barch , Michael P. Harms

Background

Existing functional connectivity studies of psychosis use population-averaged functional network maps, despite highly variable topographies of these networks across the brain surface. We aimed to define the functional network areas and topographies in the general population and the changes associated with psychotic experiences (PEs) and disorders.

Methods

Maps of 8 functional networks were generated using an individual-specific template-matching procedure for each participant from the Human Connectome Project Young Adult cohort (n = 1003) and from a matched case cohort (schizophrenia [SCZ], n = 27; bipolar disorder, n = 35) scanned identically with the same Connectom scanner. In the Human Connectome Project Young Adult cohort, PEs were estimated based on scores from the Achenbach Self-Report Scale. The relationship of symptoms to the probability of network representation at each cortical vertex was assessed using logistic regression.

Results

In Human Connectome Project Young Adult participants, PE severity on the Achenbach thought problems scale was predicted by increased language network (LAN) and dorsal attention network (DAN) areas and decreased cingulo-opercular network area (r < 0.12). Significant effects were found in SCZ, with a larger DAN and LAN and a smaller frontoparietal network. Network pattern analysis in SCZ showed an increased probability of LAN in the posterior region of the left superior temporal gyrus and of the visual network in the left insula. Regression analyses in SCZ found that mood dysregulation was related to increased DAN surface area.

Conclusions

Those with PEs and SCZ showed abnormal functional network cortical topographies, particularly involving DAN and LAN. Network findings may predict psychosis progression and guide earlier intervention.

背景现有的精神病功能连接研究使用的是人群平均功能网络图，尽管这些网络在整个大脑表面的拓扑结构变化很大。我们的目的是确定普通人群的功能网络区域和拓扑图，以及与精神病性体验（PEs）和障碍相关的变化。方法使用特定于个体的模板匹配程序，为人类连接组项目青年成人队列（n = 1003）和匹配病例队列（精神分裂症 [SCZ]，n = 27；双相情感障碍，n = 35）中的每位参与者生成 8 个功能网络图。在人类连接组计划年轻成人队列中，PE 是根据 Achenbach 自我报告量表的得分估算的。结果在人类连接组计划的年轻成人参与者中，语言网络（LAN）和背侧注意力网络（DAN）区域的增加以及丘脑-小脑网络区域的减少（r <0.12）可预测Achenbach思想问题量表中PE的严重程度。在 SCZ 中发现了显著的影响，DAN 和 LAN 变大，额顶网络变小。SCZ 的网络模式分析显示，左侧颞上回后部区域和左侧岛叶视觉网络出现 LAN 的概率增加。SCZ患者的回归分析发现，情绪失调与DAN表面积的增加有关。网络发现可预测精神病的发展并指导早期干预。

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引用次数: 0

Deep Screening for X Chromosome Parent-of-Origin Effects on Neurobehavioral and Neuroanatomical Phenotypes in 47,XXY Klinefelter Syndrome 深度筛查 X 染色体原生父母对 47,XXY 克莱恩费尔特综合征神经行为和神经解剖表型的影响

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science

Pub Date : 2024-09-04 DOI: 10.1016/j.bpsgos.2024.100391

Isabella G. Larsen , Rachel Gore Moses , Bryce A. Seifert , Siyuan Liu , Samuel Li , Andrew J. Oler , Elizabeth Levitis , Lukas Schaffer , Rylee Duncan , Colleen Jodarski , Michael Kamen , Jia Yan , François M. Lalonde , Rajarshi Ghosh , Erin Torres , Liv S. Clasen , Jonathan Blumenthal , Morgan Similuk , Armin Raznahan , Magdalena A. Walkiewicz

Background

X chromosome parent of origin (POX) has been proposed as a source of phenotypic variation within sex chromosome aneuploidies such as Klinefelter syndrome (XXY/KS) and between XX and XY individuals. However, previous studies have yielded conflicting results regarding the presence and nature of POX effects, which we sought to clarify in an expanded sample with deeper neurobehavioral phenotyping.

Methods

A cohort of 58 individuals with XXY/KS underwent duo or trio genome sequencing with parents (n = 151), measurement of 66 neurobehavioral phenotypes by standardized research assessments, and measurement of over 1000 anatomical phenotypes by structural magnetic resonance imaging. We developed a novel algorithm, the uniparental disomy visualization for variant call format files, to determine proband POX and then systematically tested for POX associations with all neurobehavioral and neuroanatomical outcomes.

Results

The uniparental disomy visualization for variant call format files algorithm showed maternal POX in 35 of 58 cases (60.3%). There were no statistically significant POX effects on any of the 66 subscale measures of cognition, psychopathology, or behavior. Neuroimaging analysis identified 2 regions in the right hemisphere with significantly higher surface area (mean effect size = 1.20) among individuals with paternal versus maternal POX (q = .021).

Conclusions

Using deeper phenotyping in an expanded sample, we did not find evidence for substantial POX effects on neurobehavioral variability, except for localized unilateral modulations of surface area in the absence of co-occurring behavioral associations. These findings help to clarify previous inconsistencies in POX research and direct attention toward other sources of clinical variability in sex chromosome aneuploidies.

背景X染色体原父（POX）被认为是性染色体非整倍体（如Klinefelter综合征（XXY/KS））内部以及XX和XY个体之间表型变异的来源。方法：58 名 XXY/KS 患者与父母（n = 151）一起接受了双基因组或三基因组测序，通过标准化研究评估测量了 66 种神经行为表型，并通过结构磁共振成像测量了 1000 多种解剖表型。我们开发了一种新型算法--变异调用格式文件的单亲断裂可视化算法，用于确定原告的POX，然后系统检测了POX与所有神经行为和神经解剖结果的关联。在认知、精神病理学或行为的 66 个分量表测量中，POX 对任何一项都没有统计学意义上的影响。结论通过对扩大样本进行更深入的表型分析，我们没有发现POX对神经行为变异性有实质性影响的证据，除了在没有并发行为关联的情况下，局部单侧表面积的改变。这些发现有助于澄清以前在 POX 研究中存在的不一致之处，并引导人们关注性染色体非整倍体临床变异的其他来源。

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引用次数: 0