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Neurotyping depression using multiple event-related potentials (ERPs): Leveraging task-based variation to predict remission in depression 使用多事件相关电位(ERPs)对抑郁症进行神经分型:利用基于任务的变异来预测抑郁症的缓解。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111233
Greg Hajcak , Nicholas Santopetro , Kazutaka Okuda

Aims

Depression is a prevalent, burdensome, and difficult mental health disorder to treat. Significant heterogeneity in clinical characteristics and course of depression hinders treatment success. Efforts to identify more homogeneous subgroups of depression could reduce heterogeneity of depression and therefore improve treatment development and randomized clinical trial outcomes. Event-related potentials (ERPs) derived from continuous electroencephalogram (EEG) can be used to identify depression and predict course (i.e., advance precision psychiatry).

Methods

In the current study, we demonstrate how multiple ERPs collected from the same individual across different experimental paradigms can provide insight into brain function and individual differences in depression using factor analysis. This approach for neurotyping depression exploits the high within-task and low between-task associations between ERPs to better understand brain function and depression.

Results

We observed three neurotypes, two of which differentiated depressed from non-depressed individuals. Only one neurotype – related to affective processing – prospectively predicted full remission. This neurotype predicted remission even when accounting for other clinical and demographic variables related to subsequent remission. The AUC of this neurotype was acceptable (i.e., 0.72) in predicting remission, exceeding previous study's measures within a single task.

Conclusion

Leveraging multiple ERPs derived from many tasks is an important yet underutilized approach in precision psychiatry.
目的:抑郁症是一种普遍的、繁重的、难以治疗的精神健康障碍。临床特征和病程的显著异质性阻碍了治疗的成功。努力确定更均匀的抑郁症亚组可以减少抑郁症的异质性,从而改善治疗开发和随机临床试验结果。从连续脑电图(EEG)中获得的事件相关电位(ERPs)可用于识别抑郁症和预测病程(即先进的精确精神病学)。方法:在本研究中,我们展示了从不同实验范式中收集的同一个体的多个erp如何利用因子分析来深入了解抑郁症的脑功能和个体差异。这种神经型抑郁症的方法利用erp在任务内高和任务间低的关联来更好地理解大脑功能和抑郁症。结果:我们观察到三种神经类型,其中两种可以区分抑郁和非抑郁个体。只有一种与情感处理相关的神经类型预测完全缓解。即使考虑到与随后的缓解相关的其他临床和人口统计学变量,这种神经类型也能预测缓解。该神经类型的AUC在预测缓解方面是可接受的(即0.72),超过了先前研究在单一任务中的测量。结论:利用来自多个任务的多个erp是精确精神病学中重要但未充分利用的方法。
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引用次数: 0
A computational and multi-brain signature for aberrant social coordination in schizophrenia 精神分裂症异常社会协调的计算和多脑特征。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111225
Ya-Jie Wang , Yalan Wen , Leilei Zheng , Ji Chen , Zheng Lin , Yafeng Pan
Social functioning impairment is a core symptom of schizophrenia (SCZ). Yet, the computational and neural mechanisms of social coordination in SCZ under real-time and naturalistic settings are poorly understood. Here, we instructed patients with SCZ to coordinate with a healthy control (HC) in a joint finger-tapping task, during which their brain activity was measured by functional near-infrared spectroscopy simultaneously. The results showed that patients with SCZ exhibited poor rhythm control ability and unstable tapping behaviour, which weakened their interpersonal synchronization when coordinating with HCs. Moreover, the dynamical systems modeling revealed disrupted between-participant coupling when SCZ patients coordinated with HCs. Importantly, increased inter-brain synchronization was identified within SCZ-HC dyads, which positively correlated with behavioural synchronization and successfully predicted dimensions of psychopathology. Our study suggests that SCZ individuals may require stronger interpersonal neural alignment to support their deficient coordination performance. This hyperalignment may be relevant for developing inter-personalized treatment strategies.
社会功能障碍是精神分裂症的核心症状之一。然而,在实时和自然环境下,SCZ社会协调的计算和神经机制尚不清楚。在这里,我们指导SCZ患者与健康对照(HC)配合进行关节手指敲击任务,在此过程中,他们的大脑活动同时被功能近红外光谱测量。结果表明,SCZ患者节律控制能力差,轻敲行为不稳定,与hc协调时人际同步减弱。此外,动力学系统模型显示,当SCZ患者与hc协调时,参与者之间的耦合被破坏。重要的是,在SCZ-HC双体中发现了增加的脑间同步,这与行为同步呈正相关,并成功预测了精神病理的维度。我们的研究表明,SCZ个体可能需要更强的人际神经对齐来支持他们缺乏协调的表现。这种高度一致可能与开发个性化治疗策略有关。
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引用次数: 0
Early auditory impairments as a candidate marker of attenuated sensory symptoms of psychosis 早期听觉障碍作为精神病感觉症状减弱的候选标志。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111214
Clément Dondé , Emma Palmer-Cooper , Christophe Gauld , Mircea Polosan , Ben Alderson-Day

Background and hypothesis

Deficits in early auditory processing (EAP), as indexed by tone-matching performance, have been consistently demonstrated in individuals with schizophrenia spectrum disorders. However, the ontogeny of tone-matching deficits in schizophrenia remains relatively unknown. The current study aims to determine the relationship between clinical high risk for psychosis and EAP.

Study design

We employed a web-based screening approach to identify CHR individuals. A sample of 892 community dwelling participants completed the 16-tem version of the prodromal questionnaire (PQ16) for the assessment of attenuated psychotic symptoms, a 9-item questionnaire of perceptual and cognitive aberrations (PCA) for the assessment of basic symptoms and a tone-matching task.

Study results

505 (43.4 %) participants met cut-off criteria for attenuated psychotic symptoms (PQ16 ≥ 6 endorsed items), 614 (68.3 %) for basic symptoms (PCA ≥ 3 endorsed items), 647 (72.0 %) for either and 358 (40.1 %) for both of them. No significant differences in tone-matching performance were observed between CHR and non-CHR subjects, using either attenuated psychotic symptoms, basic symptoms, either or both cutoffs. In the CHR group screened with attenuated psychotic symptoms, auditory and tactile sensory symptoms were significantly associated with tone-matching deficits.

Conclusion

Tone-matching may not serve as a reliable biomarker for CHR status but rather a risk marker for the emergence of early sensory manifestations.
背景与假设:早期听觉加工(EAP)缺陷,作为音调匹配表现的指标,已经在精神分裂症谱系障碍患者中得到了一致的证明。然而,精神分裂症中音调匹配缺陷的个体发生机制仍然相对未知。本研究旨在确定临床精神病高风险与EAP之间的关系。研究设计:我们采用基于网络的筛选方法来识别CHR个体。892名社区居民完成了16项精神病症状评估前驱问卷(PQ16)、9项基本症状评估知觉与认知偏差问卷(PCA)和声调匹配任务。研究结果:505名(43.4% %)受试者符合精神病症状减轻的截止标准(PQ16 ≥ 6项认可项目),614名(68.3% %)受试者符合基本症状(PCA ≥ 3项认可项目),647名(72.0 %)受试者符合一项标准,358名(40.1 %)受试者符合两项标准。在使用减轻的精神病症状、基本症状、其中一种或两种截断值时,CHR和非CHR受试者在音调匹配表现上没有观察到显著差异。在精神病症状减轻的CHR组中,听觉和触觉症状与音调匹配缺陷显著相关。结论:音调匹配可能不是CHR状态的可靠生物标志物,而是早期感觉表现出现的风险标志物。
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引用次数: 0
Assessment of factors associated with antipsychotic-induced weight gain: A nationwide cohort study 抗精神病药物引起体重增加的相关因素评估:一项全国性队列研究。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111231
Shuhei Ishikawa , Naoki Hashimoto , Ryo Okubo , Ryo Sawagashira , Ryodai Yamamura , Yoichi M. Ito , Norihiro Sato , Ichiro Kusumi

Background

The incidence of antipsychotic-induced weight gain (AIWG) is difficult to predict in real-world practice because various factors influence it. This study aimed to explore background and medication-related factors associated with weight gain in patients newly prescribed with antipsychotic medication.

Methods

This nationwide, multicenter, prospective cohort study was conducted in Japan. The primary endpoint was the incidence of AIWG (≥7 % weight gain) over 12 months after initiation of antipsychotic treatment. Factors influencing AIWG incidence were assessed using Cox proportional hazards regression analysis stratified by facility characteristics.

Results

Of the 865 enrolled participants, 262 developed AIWG. Compared with aripiprazole, clozapine and olanzapine were related to a higher AIWG incidence (hazard ratio [HR] = 2.17, 95 % confidence interval [CI] = 1.05–4.51; HR = 2.01, 95 % CI = 1.36–2.96, respectively), whereas blonanserin was related to a lower AIWG incidence (HR = 0.49, 95 % CI = 0.24–0.98). Furthermore, co-administration of antidepressants and mood stabilizers increased the AIWG incidence (HR = 1.94, 95 % CI = 1.35–2.77; HR = 1.47, 95 % CI = 1.07–2.01, respectively). The impact of concomitant medications on AIWG incidence varied by the pharmacological characteristics of the newly initiated antipsychotic, in addition to the type and duration of concomitant medications.

Conclusions

The findings of this study suggest that the risk of AIWG incidence may be estimated by assessing the type of concomitant medication and its duration of use, type of newly initiated antipsychotic, and background factors prior to initiation of antipsychotic treatment.
背景:在现实生活中,由于各种因素的影响,抗精神病药致体重增加(AIWG)的发生率难以预测。本研究旨在探讨新开抗精神病药物患者体重增加的背景和药物相关因素。方法:这项在日本进行的全国性、多中心、前瞻性队列研究。主要终点是开始抗精神病药物治疗后12 个月内AIWG(体重增加≥7 %)的发生率。采用按设施特征分层的Cox比例风险回归分析对影响AIWG发病率的因素进行评估。结果:在865名入组参与者中,262人发展为AIWG。与阿立哌唑相比,氯氮平和奥氮平与较高的AIWG发生率相关(风险比[HR] = 2.17,95 %可信区间[CI] = 1.05-4.51;人力资源 = 2.01,95 % CI = 1.36 - -2.96,分别),而blonanserin有关AIWG发病率较低(HR = 0.49,95 CI  % = 0.24 - -0.98)。此外,抗抑郁药和情绪稳定剂的联合使用增加了AIWG的发生率(HR = 1.94,95 % CI = 1.35-2.77;HR = 1.47,95 % CI = 1.07-2.01)。除了联合用药的类型和持续时间外,联合用药对AIWG发病率的影响因新开始的抗精神病药物的药理学特征而异。结论:本研究的结果表明,可以通过评估伴随药物的类型及其使用时间、新开始的抗精神病药物的类型以及开始抗精神病药物治疗前的背景因素来估计AIWG发生的风险。
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引用次数: 0
Advances in transcranial focused ultrasound neuromodulation for mental disorders 经颅聚焦超声神经调节治疗精神障碍的研究进展。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111244
Yu Shi, Wen Wu
Mental disorders are a major public health concern, affecting millions worldwide. Current treatments have limitations, highlighting the need for novel, effective, and safe interventions. Transcranial focused ultrasound (tFUS), a non-invasive neuromodulation technology, has emerged as a promising tool for treating mental disorders due to its high controllability, precision, and safety. This review summarizes the research progress of tFUS in several major mental disorders, including depression, anxiety, schizophrenia, and substance use disorders (SUDs). Animal studies have demonstrated the efficacy of tFUS in improving psychiatric symptoms and modulating neural circuits through various mechanisms, such as enhancing neuronal activity, synaptic plasticity, and neurotransmitter release. Preliminary clinical trials have also shown the potential of tFUS in alleviating symptoms in patients with treatment-resistant mental disorders. Safety evaluation studies across in vitro, animal, and human levels have supported the overall safety of tFUS under commonly used parameters. tFUS has shown broad application prospects in treating mental disorders, supported by its efficacy in animal models and preliminary clinical trials. By modulating neuronal activity, synaptic plasticity, neurotransmitters, and brain networks, tFUS could improve psychiatric symptoms and regulate neural circuits. However, current research on tFUS in mental disorders is still in its early stages, and further studies are needed to elucidate its mechanisms of action, expand its applications, and conduct large-sample, long-term clinical trials to systematically evaluate its efficacy, protocol optimization, and safety. As an innovative neuromodulation technology, tFUS has the potential to complement conventional therapies and provide new hope for addressing the global challenge of mental disorders.
精神障碍是一个重大的公共卫生问题,影响着全世界数百万人。目前的治疗方法有局限性,因此需要新的、有效的和安全的干预措施。经颅聚焦超声(tFUS)是一种非侵入性神经调节技术,由于其高可控性、精度和安全性,已成为治疗精神障碍的一种很有前途的工具。本文综述了tFUS在抑郁症、焦虑症、精神分裂症和物质使用障碍(SUDs)等主要精神障碍中的研究进展。动物研究已经证明tFUS在改善精神症状和通过多种机制调节神经回路方面的功效,如增强神经元活动、突触可塑性和神经递质释放。初步临床试验也显示了tFUS在缓解难治性精神障碍患者症状方面的潜力。体外、动物和人体水平的安全性评估研究支持在常用参数下tFUS的总体安全性。tFUS在治疗精神障碍方面具有广阔的应用前景,动物模型和初步临床试验的有效性为其提供了支持。通过调节神经元活动、突触可塑性、神经递质和脑网络,tFUS可以改善精神症状并调节神经回路。然而,目前tFUS治疗精神障碍的研究仍处于早期阶段,需要进一步研究阐明其作用机制,扩大其应用范围,并开展大样本、长期临床试验,系统评价其疗效、方案优化和安全性。作为一种创新的神经调节技术,tFUS具有补充传统疗法的潜力,为解决精神障碍的全球挑战提供了新的希望。
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引用次数: 0
Role of depression, suicide attempt history and childhood trauma in neutrophil-to-lymphocyte ratio dynamics: A 30-week prospective study 抑郁症、自杀企图史和童年创伤在中性粒细胞与淋巴细胞比率动力学中的作用:一项为期30周的前瞻性研究。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111227
M. Lion , M. Muller , E.C. Ibrahim , W. El-Hage , A. Lengvenyte , P. Courtet , A. Lefrere , R. Belzeaux
Studying the biology of suicidal behaviour and developing blood-based biomarkers may help stratify individuals with suicidal behaviors into clinically relevant categories. Literature suggests that people diagnosed with mood disorders and suicidal behaviour show an increased neutrophil to lymphocyte ratio (NLR). For the first time, we investigated NLR variability in mood disorders, a critical aspect of biomarker development. Our study provides a result on the influence of our variables on the NLR and also on the intrinsic properties of the ratio. Consequently, our objective was to analyse the differences in NLR between healthy subjects and patients diagnosed with mood disorder with suicidal behaviour or mood disorder without suicidal attempt. A prospective study was conducted on 97 healthy subjects, 63 patients with mood disorder without suicidal behaviour and 61 patients with mood disorder with suicidal behaviour (mean age [SD] = 44.2 [14.31]; 66.1 % female). Participants were assessed four times over 30 weeks, where blood samples and clinical data were collected. After controlling for confounding factors such as smoking and medical history, we found that NLR stability was low but NLR was significantly associated with a history of suicide attempt (mixed linear model, F = 4.044; p = 0.018). We also observed a significant interaction between NLR values and childhood trauma (p = 0.002). Furthermore, our results demonstrate that NLR is influenced by childhood trauma, including in controls (p = 0.014). Finally, NLR expression differs between patients with and without suicidal behaviour, but only in those without a history of childhood trauma (p = 0.026). Despite its variability over time, our data suggest that NLR may be a promising biomarker for identifying individuals at high risk of suicidal behaviour among patients with mood disorders.
研究自杀行为的生物学和开发基于血液的生物标志物可能有助于将有自杀行为的个体划分为临床相关的类别。文献表明,被诊断为情绪障碍和自杀行为的人表现出中性粒细胞与淋巴细胞比率(NLR)的增加。我们首次研究了情绪障碍中NLR的变异性,这是生物标志物发展的一个关键方面。我们的研究提供了我们的变量对NLR的影响的结果,以及对该比率的内在性质的影响。因此,我们的目的是分析健康受试者与诊断为有自杀行为的情绪障碍患者或无自杀企图的情绪障碍患者之间NLR的差异。前瞻性研究纳入97名健康受试者、63名无自杀行为的情绪障碍患者和61名有自杀行为的情绪障碍患者(平均年龄[SD] = 44.2 [14.31];66.1 %女)。参与者在30 周内接受了四次评估,收集了血液样本和临床数据。在控制吸烟和病史等混杂因素后,我们发现NLR的稳定性较低,但NLR与自杀企图史显著相关(混合线性模型,F = 4.044; = 0.018页)。我们还观察到NLR值与儿童创伤之间存在显著的相互作用(p = 0.002)。此外,我们的研究结果表明,NLR受到童年创伤的影响,包括对照组(p = 0.014)。最后,NLR表达在有和没有自杀行为的患者之间存在差异,但仅在没有童年创伤史的患者中存在差异(p = 0.026)。尽管其随时间变化,我们的数据表明,NLR可能是一种有希望的生物标志物,用于识别情绪障碍患者中自杀行为高风险的个体。
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引用次数: 0
Putative epicenters identified by transcriptome-neuromorphic interactions in attention-deficit/hyperactivity disorder biotypes 注意缺陷/多动障碍生物型中转录组-神经形态相互作用确定的假定中心。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2025.111247
Qin Tang , Jinzhong Peng , Yilu Li , Lin Liu , Pan Wang , Huafu Chen , Bharat B. Biswal
Attention-deficit hyperactivity disorder (ADHD) is a heterogenous behavioral disorder with inattention, hyperactivity and impulsivity symptoms, indicating the important implication of identifying biotypes and its epicenters in understanding disease's pathogenesis. The study investigated the neuromorphic heterogeneity relating to transcriptional similarity architecture in ADHD, and further analyzed the epicenters of network-spreading in each ADHD biotype and their correlations with clinical characteristics. Individuals with ADHD could be identified into two discriminative biotypes that exhibited distinct neuromorphic aberrances. As increased regional cortical thickness deviation in ADHD, the first component of partial least squares (PLS1) positively weighted genes were over-expressed, whereas PLS1 negatively weighted genes were under-expressed as its reduction. Both ADHD biotypes exhibited distinct disease epicenters that distributed in cognitive control and attention networks with significantly heterogeneous characteristics, holding promise for advancing our understanding, and ultimately the treatment, of ADHD. Overall, our findings identified two discriminative biotypes and its epicenters in ADHD, promoting the understanding of underlying transcriptome-neuroimaging relationships.
注意缺陷多动障碍(Attention-deficit hyperactivity disorder, ADHD)是一种具有注意力不集中、多动和冲动症状的异质性行为障碍,这表明识别生物型及其中心对了解疾病的发病机制具有重要意义。该研究调查了ADHD中与转录相似性结构相关的神经形态异质性,并进一步分析了每种ADHD生物型中网络传播的中心及其与临床特征的相关性。ADHD个体可以被识别为两种具有区别性的生物型,表现出不同的神经形态异常。随着ADHD区域皮质厚度偏差的增加,偏最小二乘(PLS1)第一分量正加权基因过表达,而PLS1负加权基因过表达。两种ADHD生物型都表现出不同的疾病中心,分布在认知控制和注意力网络中,具有显著的异质特征,有望促进我们对ADHD的理解,并最终治疗ADHD。总的来说,我们的研究结果确定了ADHD的两种区别性生物型及其中心,促进了对潜在转录组-神经影像学关系的理解。
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引用次数: 0
Differential effects of gestational Cannabis smoke and phytocannabinoid injections on male and female rat offspring behavior 妊娠期大麻烟雾和植物大麻素注射对雄性和雌性大鼠后代行为的不同影响。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111241
Tallan Black , Ilne L. Barnard , Sarah L. Baccetto , Quentin Greba , Spencer N. Orvold , Faith V.L. Austin-Scott , Genre B. Sanfuego , Timothy J. Onofrychuk , Aiden E. Glass , Rachel M. Andres , Leah M. Macfarlane , Jesse C. Adrian , Ashton L. Heidt , Dan L. McElroy , Robert B. Laprairie , John G. Howland
Our understanding of the implications of gestational Cannabis exposure (GCE) remains unclear as Cannabis use increases worldwide. Much of the existing knowledge of the effects of GCE has been gained from preclinical experiments using injections of isolated Δ9-tetrahydrocannabinol (THC) at relatively high doses. Few investigations of the effects of GCE to smoke from the whole Cannabis flower have been conducted, despite this being the most common mode of human consumption. Here, we compared the effects of repeated gestational exposure to high-THC or high-cannabidiol (CBD) Cannabis smoke to i.p. THC or i.p. CBD to those of GCE to high-THC or high-CBD Cannabis smoke on litter health and the offspring. We found that injecting phytocannabinoids generally had a more severe impact on measures of maternal and litter health and produced distinct behavioral phenotypes when compared to offspring from dams treated with high-THC and high-CBD smoke during gestation. GCE to high-THC smoke decreased prepulse inhibition (PPI) and MK-801-induced locomotor activity in female adolescent offspring, which normalized in adulthood. GCE to i.p. THC increased exploratory behavior in the open field test in adolescent offspring of both sexes. GCE had a negative impact on offspring performance in the Identical Stimuli Test and Different Stimuli Test with odors regardless of gestational treatment, sex, or age. CBD (i.p) impaired PPI in both male and female offspring in adulthood and increased time spent in proximity during social interaction for male offspring. There were no effects of GCE in the 5 Choice Serial Reaction Time Task. These data establish distinct behavioral phenotypes in the offspring between smoked and injected GCE, further demonstrating that route and specific phytocannabinoid dose produce differential outcomes across offspring lifespan. Smoked Cannabis is still the most common means of consumption, and more preclinical investigation is needed to determine the effects of smoked Cannabis on developmental trajectories.
随着全球大麻使用量的增加,我们对妊娠期大麻暴露(GCE)的影响的理解仍不清楚。大部分关于GCE作用的现有知识都是通过注射相对高剂量的分离的Δ9-tetrahydrocannabinol (THC)的临床前实验获得的。尽管吸食大麻是人类最常见的方式,但很少有人调查GCE对吸食整个大麻花的影响。在这里,我们比较了妊娠期反复暴露于高四氢大麻酚或高大麻二酚(CBD)大麻烟雾到吸食四氢大麻酚或吸食CBD与妊娠期暴露于高四氢大麻酚或高CBD大麻烟雾对产仔健康和后代的影响。我们发现,与怀孕期间使用高thc和高cbd烟雾处理的母鼠后代相比,注射植物大麻素通常对母鼠和窝鼠健康的影响更严重,并且产生了不同的行为表型。GCE对高thc烟雾的影响降低了青春期雌性后代的脉冲前抑制(PPI)和mk -801诱导的运动活动,并在成年后恢复正常。GCE与四氢大麻酚的结合增加了青少年后代在野外试验中的探索性行为。不论妊娠治疗、性别或年龄,GCE均对子代气味相同刺激测验和气味不同刺激测验的表现有负向影响。CBD (i.p)损害了成年后雄性和雌性后代的PPI,并增加了雄性后代在社交互动中接近的时间。GCE对5项选择连续反应时间任务没有影响。这些数据在吸烟和注射GCE的后代中建立了不同的行为表型,进一步证明了途径和特定的植物大麻素剂量在后代一生中产生不同的结果。吸食大麻仍然是最常见的消费方式,需要更多的临床前调查来确定吸食大麻对发育轨迹的影响。
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引用次数: 0
Implications of prenatal exposure to hyperandrogen for hippocampal neurodevelopment and autism-like behavior in offspring 产前暴露于高雄激素对后代海马神经发育和自闭症样行为的影响。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-10 DOI: 10.1016/j.pnpbp.2024.111219
Dan Qiao , Chenyu Mu , Huan Chen , Di Wen , Zhao Wang , Bohan Zhang , Fangzhen Guo , Chang Wang , Rong Zhang , Chongying Wang , Huixian Cui , Sha Li
Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder that significantly jeopardizes the physical and mental well-being of children. Autism spectrum disorder results from a combination of environmental and genetic factors. Hyperandrogenic exposure during pregnancy increases their risk of developing autism. Nevertheless, the prenatal exposure to androgens affects offspring neurodevelopment and the underlying mechanisms have not been fully elucidated. In the present study, administration of excessive dihydrotestosterone (DHT) to pregnant mice was found to impair neuronal development and dendritic spine formation in offspring, inducing autism-like behaviors. Furthermore, through mRNA transcriptome sequencing technology, the key molecule Nr4a2 was identified during this process of change. Overexpression of Nr4a2 and treatment with amodiaquine (AQ) significantly improved the abnormal phenotypes in offspring caused by prenatal exposure to androgens. Overall, Nr4a2 emerges as a crucial molecule involved in the impairment of offspring neurodevelopment due to prenatal androgen exposure, which provides a new perspective for the in-depth study of the influencing factors and underlying mechanisms.
自闭症谱系障碍(ASD)是一种高度异质性的神经发育障碍,严重危害儿童的身心健康。自闭症谱系障碍是环境和遗传因素共同作用的结果。怀孕期间暴露于高雄激素会增加患自闭症的风险。然而,产前暴露于雄激素影响后代神经发育和潜在的机制尚未完全阐明。在本研究中,发现给怀孕小鼠过量的双氢睾酮(DHT)会损害后代的神经元发育和树突棘形成,诱发自闭症样行为。进一步,通过mRNA转录组测序技术,确定了这一变化过程中的关键分子Nr4a2。Nr4a2过表达和阿莫地喹(amodiaquine, AQ)治疗可显著改善产前暴露于雄激素所致子代的异常表型。综上所述,Nr4a2作为产前雄激素暴露导致子代神经发育障碍的关键分子,为深入研究其影响因素和机制提供了新的视角。
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引用次数: 0
The associations between paternal postpartum depressive symptoms and testosterone and cortisol levels in hair over the first two years postpartum 产后头两年父亲产后抑郁症状与头发中睾酮和皮质醇水平之间的关系。
IF 5.3 2区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-09 DOI: 10.1016/j.pnpbp.2024.111245
Lydia Richter , Luisa Bergunde , Marlene Karl , Isabel Jaramillo , Victoria Weise , Judith T. Mack , Kerstin Weidner , Wei Gao , Tilmann von Soest , Susan Garthus-Niegel , Susann Steudte-Schmiedgen

Background

After the birth of a child, also fathers may develop postpartum depression. Altered steroid hormone concentrations are discussed as a possible underlying mechanism, as these have been associated with depressive symptoms in previous studies outside the postpartum period. While higher paternal testosterone levels have been found to protect against paternal postpartum depressive symptoms (PPDS), an association between higher cortisol levels and PPDS has been seen in postpartum mothers, with no comparable studies available on fathers.

Objective

This study aimed to investigate cross-sectional and longitudinal associations between testosterone and cortisol levels in hair and PPDS over a period of 2 years postpartum.

Methods

Data from N = 226 fathers, who took part in the endocrine sub-study DREAMHAIR of the longitudinal prospective cohort study DREAM, were used. PPDS were assessed 8 weeks, 14 months, and 24 months after birth using the Edinburgh Postnatal Depression Scale. At the same time, fathers provided 2 cm scalp-near hair samples in which testosterone (HairT) and cortisol (HairF) levels were determined. Cross-sectional and longitudinal associations between HairT, HairF and paternal PPDS were investigated.

Results

Correlation analyses showed a negative cross-sectional association between HairF levels and paternal PPDS 14 months after birth. A random intercept cross-lagged panel model revealed prospective relationships between paternal PPDS 8 weeks postpartum and HairF 14 months postpartum, and additionally between 14 months and 2 years postpartum in an exploratory model with similarly good model fit. No further significant associations of HairF with paternal PPDS emerged, and none of the analyses with HairT became significant. The overall pattern of results was confirmed when controlling for the influence of batch and storage time on HairT and HairF levels.

Conclusion

No consistent relationships between HairT or HairF and paternal PPDS emerged in this relatively healthy cohort. In HairF analyses with significant results, lower HairF was associated with more severe PPDS. Longitudinal results imply that altered cortisol secretion may rather follow than precede changes in paternal PPDS. Further research on hormonal changes in PPDS in fathers should consider possible covariates and examine fathers with higher depressive burden, which may help to identify fathers at risk and inform future preventive and interventive approaches.
背景:孩子出生后,父亲也可能患上产后抑郁症。类固醇激素浓度的改变作为一种可能的潜在机制进行了讨论,因为在之前的研究中,它们与产后以外的抑郁症状有关。虽然研究发现父亲较高的睾丸激素水平可以预防父亲产后抑郁症状(PPDS),但在产后母亲中发现了较高的皮质醇水平与产后抑郁症状之间的联系,但在父亲中没有类似的研究。目的:本研究旨在调查产后2 年头发和产后抑郁症中睾酮和皮质醇水平的横断面和纵向关联。方法:采用参与纵向前瞻性队列研究DREAM的内分泌亚研究DREAMHAIR的N = 226名父亲的数据。PPDS分别在出生后8 周、14 个月和24 个月使用爱丁堡产后抑郁量表进行评估。与此同时,父亲们提供了2 厘米头皮附近的头发样本,其中睾酮(HairT)和皮质醇(HairF)水平被测定。研究了HairT、HairF与父亲PPDS的横断面和纵向关联。结果:相关分析显示,出生后14 个月,HairF水平与父亲PPDS呈负相关。随机截距交叉滞后面板模型显示父亲产后8 周和产后14 个月的PPDS之间的前瞻性关系,以及产后14 个月和产后2 年的探索性模型具有同样良好的模型拟合。HairF与父亲PPDS之间没有进一步的显著关联,与HairT相关的分析也都不显著。在控制批次和储存时间对HairT和HairF水平的影响时,结果的总体模式得到了证实。结论:在这个相对健康的队列中,HairT或HairF与父亲PPDS之间没有一致的关系。在有显著结果的HairF分析中,较低的HairF与更严重的PPDS相关。纵向结果表明,皮质醇分泌的改变可能是在父亲PPDS变化之后而不是之前。对父亲产后抑郁症激素变化的进一步研究应考虑可能的协变量,并检查抑郁负担较高的父亲,这可能有助于识别有风险的父亲,并为未来的预防和干预方法提供信息。
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引用次数: 0
期刊
Progress in Neuro-Psychopharmacology & Biological Psychiatry
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