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Sex-Dependent Effects of Angiotensin Type 2 Receptor–Expressing Medial Prefrontal Cortex Interneurons in Fear Extinction Learning 表达血管紧张素 2 型受体的内侧前额叶皮层中间神经元在恐惧消退学习中的性别依赖效应
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-06-05 DOI: 10.1016/j.bpsgos.2024.100340
Hannah C. Smith , Zhe Yu , Laxmi Iyer , Paul J. Marvar

Background

The renin-angiotensin system has been identified as a potential therapeutic target for posttraumatic stress disorder, although its mechanisms are not well understood. Brain angiotensin type 2 receptors (AT2Rs) are a subtype of angiotensin II receptors located in stress and anxiety-related regions, including the medial prefrontal cortex (mPFC), but their function and mechanism in the mPFC remain unexplored. Therefore, we used a combination of imaging, cre/lox, and behavioral methods to investigate mPFC-AT2R–expressing neurons in fear and stess related behavior.

Methods

To characterize mPFC-AT2R–expressing neurons in the mPFC, AT2R-Cre/tdTomato male and female mice were used for immunohistochemistry. mPFC brain sections were stained with glutamatergic or interneuron markers, and density of AT2R+ cells and colocalization with each marker were quantified. To assess fear-related behaviors in AT2R-flox mice, we selectively deleted AT2R from mPFC neurons using a Cre-expressing adeno-associated virus. Mice then underwent Pavlovian auditory fear conditioning, elevated plus maze, and open field testing.

Results

Immunohistochemistry results revealed that AT2R was densely expressed throughout the mPFC and primarily expressed in somatostatin interneurons in a sex-dependent manner. Following fear conditioning, mPFC-AT2R Cre-lox deletion impaired extinction and increased exploratory behavior in female but not male mice, while locomotion was unaltered by mPFC-AT2R deletion in both sexes.

Conclusions

These results identify mPFC-AT2R+ neurons as a novel subgroup of somatostatin interneurons and reveal their role in regulating fear learning in a sex-dependent manner, potentially offering insights into novel therapeutic targets for posttraumatic stress disorder.

背景肾素-血管紧张素系统已被确定为创伤后应激障碍的潜在治疗靶点,但其作用机制尚不十分清楚。脑血管紧张素 2 型受体(AT2Rs)是血管紧张素 II 受体的一种亚型,位于包括内侧前额叶皮层(mPFC)在内的应激和焦虑相关区域,但其在 mPFC 中的功能和机制仍有待探索。因此,我们综合使用成像、cre/lox和行为学方法研究了mPFC-AT2R表达神经元在恐惧和焦虑相关行为中的作用。用谷氨酸能或中间神经元标记物染色mPFC脑切片,量化AT2R+细胞的密度以及与每种标记物的共定位。为了评估AT2R-flox小鼠的恐惧相关行为,我们使用Cre表达的腺相关病毒选择性地从mPFC神经元中删除了AT2R。结果免疫组化结果显示,AT2R在整个mPFC中密集表达,并且主要以性别依赖的方式在体司他丁中间神经元中表达。结论这些结果确定了mPFC-AT2R+神经元是体生长激素中间神经元的一个新亚群,并揭示了它们以性别依赖的方式在调节恐惧学习中的作用,有可能为创伤后应激障碍的新治疗靶点提供启示。
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引用次数: 0
Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults 以杏仁核为靶点的经颅聚焦超声可提高健康老年人的心理生理和主观负性情绪反应能力
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-06-05 DOI: 10.1016/j.bpsgos.2024.100342

Background

The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively.

Methods

We studied healthy older adult participants (N = 21, ages 48–79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task.

Results

Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation.

Conclusions

The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

背景杏仁核与一系列精神疾病密切相关,但目前可用的非侵入性神经调节技术无法触及杏仁核。低强度经颅聚焦超声(TFUS)是一种神经调节技术,能够无创到达皮层下区域。方法我们研究了健康的老年参与者(N = 21,年龄 48-79 岁),他们接受了针对右侧杏仁核和左侧内侧皮层(活动控制区)的 TFUS,采用了 2 次参与者内交叉设计。在进行 TFUS 治疗前后,通过国家-特质焦虑量表和利用国际情感图像系统中的中性和负性图像进行的情绪反应和调节任务收集了行为测量数据。结果当TFUS以杏仁核为目标时,自我报告的对负面图像的唤醒程度以及在情绪反应和调节任务的试验间歇期间的心率均显著增加;而以内侧皮层为目标时,这些变化并不明显。结论:本研究的结果提供了初步证据,表明针对杏仁核的单次 TFUS 治疗可能会改变心理生理和主观情绪反应,这表明 TFUS 在未来的神经精神应用中具有一定的潜力。然而,还需要对 TFUS 参数和靶向进行更多的优化,以确定如何以更有利于临床的方式引起变化。
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引用次数: 0
Using Organoids to Model Sex Differences in the Human Brain 利用器官组织模拟人脑的性别差异
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-06-04 DOI: 10.1016/j.bpsgos.2024.100343
Adam Pavlinek , Dwaipayan Adhya , Alex Tsompanidis , Varun Warrier

Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages. Animal models have played a crucial role in understanding sex differences, but the study of human sex differences requires an experimental model that can recapitulate complex genetic traits. To fill this gap, human induced pluripotent stem cell–derived brain organoids are now being used to study how complex genetic traits influence prenatal brain development. For example, brain organoids from individuals with autism and individuals with X chromosome–linked Rett syndrome and fragile X syndrome have revealed prenatal differences in cell proliferation, a measure of brain volume differences, and excitatory-inhibitory imbalances. Brain organoids have also revealed increased neurogenesis of excitatory neurons due to androgens. However, despite growing interest in using brain organoids, several key challenges remain that affect its validity as a model system. In this review, we discuss how sex steroids and the sex chromosomes each contribute to sex differences in brain development. Then, we examine the role of X chromosome inactivation as a factor that drives sex differences. Finally, we discuss the combined challenges of modeling X chromosome inactivation and limitations of brain organoids that need to be taken into consideration when studying sex differences.

性别差异广泛存在于神经发育过程中,并在自闭症等神经精神疾病中发挥作用,而自闭症在男性中的发病率高于女性。在人类中,男性的脑容量比女性大,海马体和杏仁核的发育显示出显著的性别差异。从机理上讲,性类固醇和性染色体推动了大脑发育的这些差异,这些差异似乎在产前和青春期阶段达到高峰。动物模型在理解性别差异方面发挥了至关重要的作用,但人类性别差异的研究需要一个能再现复杂遗传特征的实验模型。为了填补这一空白,人类诱导多能干细胞衍生的脑器官现在被用来研究复杂的遗传特征如何影响产前大脑发育。例如,来自自闭症患者和与X染色体相关的雷特综合征和脆性X综合征患者的脑器官组织显示了产前细胞增殖差异、脑容量差异和兴奋抑制失衡。脑器官组织也显示,由于雄激素的作用,兴奋性神经元的神经发生增加。然而,尽管人们对使用脑器官组织的兴趣与日俱增,但仍有几个关键挑战影响着其作为模型系统的有效性。在这篇综述中,我们将讨论性类固醇和性染色体如何各自导致大脑发育的性别差异。然后,我们将探讨 X 染色体失活作为性别差异驱动因素的作用。最后,我们讨论了在研究性别差异时需要考虑的 X 染色体失活建模的综合挑战和脑器官模型的局限性。
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引用次数: 0
Childhood Maltreatment and Biological Aging in Middle Adulthood: The Role of Psychiatric Symptoms 童年虐待与中年期的生理衰老:精神症状的作用
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-06-03 DOI: 10.1016/j.bpsgos.2024.100341
Cathy Spatz Widom , Hang (Heather) Do , Quincy C. Miller , Magda Javakhishvili , Claire Eckstein Indik , Daniel W. Belsky

Background

Childhood maltreatment and psychiatric morbidity have each been associated with accelerated biological aging primarily through cross-sectional studies. Using data from a prospective longitudinal study of individuals with histories of childhood maltreatment and control participants followed into midlife, we tested 2 hypotheses examining whether 1) psychiatric symptoms mediate the relationship between childhood maltreatment and biological aging and 2) psychiatric symptoms of anxiety, depression, or posttraumatic stress disorder (PTSD) act in conjunction with childhood maltreatment to exacerbate the association of child maltreatment to aging.

Methods

Children (ages 0–11 years) with documented histories of maltreatment and demographically matched control children were followed into adulthood (N = 607) and interviewed over several waves of the study. Depression, anxiety, and PTSD symptoms were assessed at mean ages of 29 (interview 1) and 40 (interview 2) years. Biological age was measured from blood chemistries collected later (mean age = 41 years) using the Klemera-Doubal method. Hypotheses were tested using linear regressions and path analyses.

Results

Adults with documented histories of childhood maltreatment showed more symptoms of depression, PTSD, and anxiety at both interviews and more advanced biological aging, compared with control participants. PTSD symptoms at both interviews and depression and anxiety symptoms only at interview 2 predicted accelerated biological aging. There was no evidence of mediation; however, anxiety and depression moderated the relationship between childhood maltreatment and biological aging.

Conclusions

These new findings reveal the shorter- and longer-term longitudinal impact of PTSD on biological aging and the amplifying effect of anxiety and depression on the relationship between child maltreatment and biological aging.

背景童年虐待和精神病发病率均与生物衰老加速有关,这主要是通过横断面研究得出的结论。我们利用一项前瞻性纵向研究的数据,对有童年虐待史的人和进入中年后的对照组参与者进行了追踪调查,并检验了两个假设:1)精神症状是否会介导童年虐待与生物衰老之间的关系;2)焦虑、抑郁或创伤后应激障碍(PTSD)等精神症状是否会与童年虐待一起加剧童年虐待与衰老之间的关系。方法对有虐待史记录的儿童(0-11 岁)和人口统计学上相匹配的对照组儿童进行成年跟踪调查(N = 607),并在研究的几个波次中进行访谈。抑郁、焦虑和创伤后应激障碍症状分别在平均 29 岁(访谈 1)和 40 岁(访谈 2)时进行评估。生物年龄是通过后来收集的血液化学成分(平均年龄 = 41 岁),使用 Klemera-Doubal 方法测量得出的。使用线性回归和路径分析对假设进行了检验。结果与对照组受试者相比,有童年虐待史记录的成年人在两次面谈中都表现出更多的抑郁症状、创伤后应激障碍和焦虑症状,生物年龄也更大。两次面谈中的创伤后应激障碍症状以及仅在第二次面谈中出现的抑郁和焦虑症状都预示着生物衰老的加速。这些新发现揭示了创伤后应激障碍对生物衰老的短期和长期纵向影响,以及焦虑和抑郁对儿童虐待与生物衰老之间关系的放大效应。
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引用次数: 0
Unraveling the Molecular Mechanisms of the Neurodevelopmental Consequences of Fetal Protein Deficiency: Insights From Rodent Models and Public Health Implications 揭示胎儿蛋白质缺乏症对神经发育影响的分子机制:啮齿动物模型的启示和对公共卫生的影响。
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-06-03 DOI: 10.1016/j.bpsgos.2024.100339
Pieter Vancamp , Morgane Frapin , Patricia Parnet , Valérie Amarger

Fetal brain development requires increased maternal protein intake to ensure that offspring reach their optimal cognitive potential in infancy and adulthood. While protein deficiency remains a prevalent issue in developing countries, it is also reemerging in Western societies due to the growing adoption of plant-based diets, some of which are monotonous and may fail to provide sufficient amino acids crucial for the brain’s critical developmental phase. Confounding variables in human nutritional research have impeded our understanding of the precise impact of protein deficiency on fetal neurodevelopment, as well as its implications for childhood neurocognitive performance. Moreover, it remains unclear whether such deficiency could predispose to mental health problems in adulthood, mirroring observations in individuals exposed to prenatal famine. In this review, we sought to evaluate mechanistic data derived from rodent models, placing special emphasis on the involvement of neuroendocrine axes, the influence of sex and timing, epigenetic modifications, and cellular metabolism. Despite notable progress, critical knowledge gaps remain, including understanding the long-term reversibility of effects due to fetal protein restriction and the interplay between genetic predisposition and environmental factors. Enhancing our understanding of the precise mechanisms that connect prenatal nutrition to brain development in future research endeavors can be significantly advanced by integrating multiomics approaches and utilizing additional alternative models such as nonhuman primates. Furthermore, it is crucial to investigate potential interventions aimed at alleviating adverse outcomes. Ultimately, this research has profound implications for guiding public health strategies aimed at raising awareness about the crucial role of optimal maternal nutrition in supporting fetal neurodevelopment.

胎儿的大脑发育需要母体摄入更多的蛋白质,以确保后代在婴儿期和成年期达到最佳认知潜能。虽然蛋白质缺乏症在发展中国家仍是一个普遍问题,但由于西方社会越来越多地采用植物性饮食,蛋白质缺乏症在西方社会也再次出现,因为有些植物性饮食比较单调,可能无法提供足够的对大脑关键发育阶段至关重要的氨基酸。人类营养研究中的干扰变量阻碍了我们了解蛋白质缺乏对胎儿神经发育的确切影响及其对儿童神经认知表现的影响。此外,这种蛋白质缺乏是否会导致成年后出现心理健康问题,这与在产前遭受饥荒的个体身上观察到的情况如出一辙,目前仍不清楚。在这篇综述中,我们试图评估从啮齿动物模型中获得的机理数据,特别强调神经内分泌轴的参与、性别和时间的影响、表观遗传修饰和细胞代谢。尽管取得了显著进展,但仍存在关键的知识差距,包括了解胎儿蛋白质限制所造成影响的长期可逆性,以及遗传易感性和环境因素之间的相互作用。在未来的研究工作中,通过整合多组学方法和利用更多的替代模型(如非人灵长类动物),可以极大地促进我们对产前营养与大脑发育之间确切联系机制的理解。此外,研究旨在减轻不良后果的潜在干预措施也至关重要。最终,这项研究对指导公共卫生策略具有深远的意义,旨在提高人们对最佳母体营养在支持胎儿神经发育中的关键作用的认识。
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引用次数: 0
Degradation of Perineuronal Nets in the Ventral Hippocampus of Adult Rats Recreates an Adolescent-Like Phenotype of Stress Susceptibility 成年大鼠海马腹侧神经元网的退化再现了类似青少年的压力易感性表型
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-05-31 DOI: 10.1016/j.bpsgos.2024.100338
Débora A.E. Colodete , Anthony A. Grace , Francisco S. Guimarães , Felipe V. Gomes

Background

Psychiatric disorders often emerge during late adolescence/early adulthood, a period with increased susceptibility to socioenvironmental factors that coincides with incomplete parvalbumin interneuron (PVI) development. Stress during this period causes functional loss of PVIs in the ventral hippocampus (vHip), which has been associated with dopamine system overdrive. This vulnerability persists until the appearance of perineuronal nets (PNNs) around PVIs. We assessed the long-lasting effects of adolescent or adult stress on behavior, ventral tegmental area dopamine neuron activity, and the number of PVIs and their associated PNNs in the vHip. Additionally, we tested whether PNN removal in the vHip of adult rats, proposed to reset PVIs to a juvenile-like state, would recreate an adolescent-like phenotype of stress susceptibility.

Methods

Male rats underwent a 10-day stress protocol during adolescence or adulthood. Three to 4 weeks poststress, we evaluated behaviors related to anxiety, sociability, and cognition, ventral tegmental area dopamine neuron activity, and the number of PV+ and PNN+ cells in the vHip. Furthermore, adult animals received intra-vHip infusion of ChABC (chondroitinase ABC) to degrade PNNs before undergoing stress.

Results

Unlike adult stress, adolescent stress induced anxiety responses, reduced sociability, cognitive deficits, ventral tegmental area dopamine system overdrive, and decreased PV+ and PNN+ cells in the vHip. However, intra-vHip ChABC infusion caused the adult stress to produce changes similar to the ones observed after adolescent stress.

Conclusions

Our findings underscore adolescence as a period of heightened vulnerability to the long-lasting impact of stress and highlight the protective role of PNNs against stress-induced damage in PVIs.

背景精神障碍通常出现在青春期晚期/成年早期,这一时期对社会环境因素的易感性增加,恰逢副发光体中间神经元(PVI)发育不全。这一时期的压力会导致腹侧海马(vHip)的副发光体功能丧失,这与多巴胺系统的过度驱动有关。这种脆弱性一直持续到 PVI 周围出现神经元周围网(PNN)为止。我们评估了青春期或成年期压力对行为、腹侧被盖区多巴胺神经元活动以及 vHip 中 PVIs 及其相关 PNNs 数量的长期影响。此外,我们还测试了将成年大鼠vHip中的PNN移除是否会重置PVIs至类似于青少年的状态,从而重现类似于青少年的应激易感性表型。应激后三到四周,我们评估了与焦虑、社交能力和认知相关的行为、腹侧被盖区多巴胺神经元的活性以及vHip中PV+和PNN+细胞的数量。结果与成人应激不同,青少年应激会诱发焦虑反应、社交能力下降、认知障碍、腹侧被盖区多巴胺系统过度活跃以及vHip中PV+和PNN+细胞数量减少。结论我们的研究结果表明,青少年时期更容易受到应激的长期影响,并强调了PNNs在PVIs中对应激引起的损伤所起的保护作用。
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引用次数: 0
Comorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome 创伤后应激障碍在整个医学表型组中的共病特征
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-05-29 DOI: 10.1016/j.bpsgos.2024.100337
Emily M. Hicks , Maria Niarchou , Slavina Goleva , Dia Kabir , Jessica Johnson , Keira J.A. Johnston , Julia Ciarcia , Gita A. Pathak , Jordan W. Smoller , Lea K. Davis , Caroline M. Nievergelt , Karestan C. Koenen , Laura M. Huckins , Karmel W. Choi , PGC/PsycheMERGE PTSD & Trauma EHR Working Group

Background

Previous epidemiological research has linked posttraumatic stress disorder (PTSD) with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records provide an opportunity to overcome clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex.

Methods

PTSD was defined among biobank participants (N = 145,959) in 3 major healthcare systems using 2 ICD code-based definitions: broad (≥1 PTSD or acute stress codes vs. 0; ncases = 16,706) and narrow (≥2 PTSD codes vs. 0; ncases = 3325). Using a phenome-wide association study design, we tested associations between each PTSD definition and all prevalent disease umbrella categories, i.e., phecodes. We also conducted sex-stratified phenome-wide association study analyses including a sex × diagnosis interaction term in each logistic regression.

Results

A substantial number of phecodes were significantly associated with PTSDNarrow (61%) and PTSDBroad (83%). While the strongest associations were shared between the 2 definitions, PTSDBroad captured 334 additional phecodes not significantly associated with PTSDNarrow and exhibited a wider range of significantly associated phecodes across various categories, including respiratory, genitourinary, and circulatory conditions. Sex differences were observed in that PTSDBroad was more strongly associated with osteoporosis, respiratory failure, hemorrhage, and pulmonary heart disease among male patients and with urinary tract infection, acute pharyngitis, respiratory infections, and overweight among female patients.

Conclusions

This study provides valuable insights into a diverse range of comorbidities associated with PTSD, including both known and novel associations, while highlighting the influence of sex differences and the impact of defining PTSD using electronic health records.

背景以前的流行病学研究已将创伤后应激障碍(PTSD)与特定的身体健康问题联系起来,但与创伤后应激障碍相关的医疗条件的综合情况仍未定性。电子健康记录提供了一个机会来克服临床知识差距,并发现可能因性别而异的生物学相关性。方法在 3 个主要医疗保健系统的生物库参与者(N = 145959)中使用 2 种基于 ICD 代码的定义来定义创伤后应激障碍:广义(≥1 个创伤后应激障碍或急性应激代码 vs. 0;ncases = 16706)和狭义(≥2 个创伤后应激障碍代码 vs. 0;ncases = 3325)。我们采用全表型关联研究设计,检验了每种创伤后应激障碍定义与所有流行疾病总类(即Phecodes)之间的关联。我们还进行了性别分层的全表型关联研究分析,在每个逻辑回归中都加入了性别 × 诊断交互项。结果 大量的嗜铬细胞编码与 PTSDNarrow(61%)和 PTSDBroad(83%)显著相关。虽然这两种定义之间的关联性最强,但 PTSDBroad 还捕获了 334 个与 PTSDNarrow 无关的额外症状代码,并在包括呼吸系统、泌尿生殖系统和循环系统疾病在内的各种类别中显示出更广泛的显著相关症状代码。在男性患者中,PTSDBroad 与骨质疏松症、呼吸衰竭、出血和肺心病的相关性更强;在女性患者中,PTSDBroad 与尿路感染、急性咽炎、呼吸道感染和超重的相关性更强。
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引用次数: 0
Age Trajectories of the Structural Connectome in Child and Adolescent Offspring of Individuals With Bipolar Disorder or Schizophrenia 双相情感障碍或精神分裂症患者的儿童和青少年后代结构连接组的年龄轨迹
IF 4 Q2 NEUROSCIENCES Pub Date : 2024-05-28 DOI: 10.1016/j.bpsgos.2024.100336
Simon R. Poortman , Marjolein E.A. Barendse , Nikita Setiaman , Martijn P. van den Heuvel , Siemon C. de Lange , Manon H.J. Hillegers , Neeltje E.M. van Haren

Background

Offspring of parents with severe mental illness (e.g., bipolar disorder or schizophrenia) are at elevated risk of developing psychiatric illness owing to both genetic predisposition and increased burden of environmental stress. Emerging evidence indicates a disruption of brain network connectivity in young offspring of patients with bipolar disorder and schizophrenia, but the age trajectories of these brain networks in this high-familial-risk population remain to be elucidated.

Methods

A total of 271 T1-weighted and diffusion-weighted scans were obtained from 174 offspring of at least 1 parent diagnosed with bipolar disorder (n = 74) or schizophrenia (n = 51) and offspring of parents without severe mental illness (n = 49). The age range was 8 to 23 years; 97 offspring underwent 2 scans. Anatomical brain networks were reconstructed into structural connectivity matrices. Network analysis was performed to investigate anatomical brain connectivity.

Results

Offspring of parents with schizophrenia had differential trajectories of connectivity strength and clustering compared with offspring of parents with bipolar disorder and parents without severe mental illness, of global efficiency compared with offspring of parents without severe mental illness, and of local connectivity compared with offspring of parents with bipolar disorder.

Conclusions

The findings of this study suggest that familial high risk of schizophrenia is related to deviations in age trajectories of global structural connectome properties and local connectivity strength.

背景父母患有严重精神疾病(如躁郁症或精神分裂症)的后代罹患精神疾病的风险很高,这既有遗传易感性的原因,也有环境压力负担加重的原因。新近的证据表明,双相情感障碍和精神分裂症患者的年轻后代的大脑网络连接出现了中断,但这些大脑网络在这一高危家庭人群中的年龄轨迹仍有待阐明。研究方法从174名父母至少一方被诊断患有双相情感障碍(74人)或精神分裂症(51人)的后代和父母未患有严重精神疾病(49人)的后代中获得了271张T1加权和弥散加权扫描图像。年龄范围为 8 至 23 岁;97 名后代接受了 2 次扫描。大脑解剖网络被重建为结构连接矩阵。结果与患有双相情感障碍的父母的后代和未患有严重精神疾病的父母的后代相比,患有精神分裂症的父母的后代在连通性强度和聚类方面存在差异;与未患有严重精神疾病的父母的后代相比,患有精神分裂症的父母的后代在整体效率方面存在差异;与患有双相情感障碍的父母的后代相比,患有精神分裂症的父母的后代在局部连通性方面存在差异。结论本研究结果表明,家族性精神分裂症高风险与全局结构连接组特性和局部连接强度的年龄轨迹偏差有关。
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引用次数: 0
Multiple Stressors Induce Amygdalohippocampal Volume Reduction in Adult Male Rats as Detected by Longitudinal Structural Magnetic Resonance Imaging 纵向结构磁共振成像检测到多重压力诱导成年雄性大鼠杏仁核海马体积缩小
Q2 NEUROSCIENCES Pub Date : 2024-05-15 DOI: 10.1016/j.bpsgos.2024.100334
Rie Ryoke, Teruo Hashimoto, Ryuta Kawashima

Background

Traumatic events can cause long-lasting and uncontrollable fear and anxiety. Posttraumatic stress disorder is an intractable mental disorder, and neurobiological mechanisms using animal models are expected to help development of posttraumatic stress disorder treatment. In this study, we combined multiple stress (MS) and longitudinal in vivo magnetic resonance imaging to reveal the effects of long-lasting anxiety-like behaviors on adult male rat brains.

Methods

Twelve male Wistar rats (8 weeks old) were exposed to the MS of 1-mA footshocks and forced swimming, while 12 control rats were placed in a plastic cage. Contextual fear conditioning with 0.1-mA footshocks in a context different from the MS was conducted 15 days after the MS for both groups. Three retention tests were administered after 24 hours and 9 and 16 days. Two magnetic resonance imaging scans were conducted, one on the day before MS induction and one the day after the third retention test, with a 32-day interval.

Results

The MS group showed greater freezing responses than the control group in all retention tests. Whole-brain voxel-based morphometry analyses revealed reduced gray matter volume in the anterior amygdalohippocampal area in MS group rats compared with control rats. These volume changes were negatively associated with freezing time in the third retention test in the MS group.

Conclusions

These results suggest that individual variability in the amygdalohippocampal area may be related to long-lasting fear responses after severe stress.

背景创伤事件会导致长期无法控制的恐惧和焦虑。创伤后应激障碍是一种难治性精神障碍,利用动物模型研究神经生物学机制有望有助于创伤后应激障碍治疗的发展。在这项研究中,我们将多重应激(MS)和纵向体内磁共振成像相结合,揭示了长期焦虑样行为对成年雄性大鼠大脑的影响。方法将12只雄性Wistar大鼠(8周大)置于1毫安脚震和强迫游泳的MS中,同时将12只对照组大鼠置于塑料笼中。两组大鼠均在接触 MS 15 天后,在不同于 MS 的情境中进行 0.1 毫安脚震的情境恐惧条件反射。分别在 24 小时、9 天和 16 天后进行了三次保持测试。进行了两次磁共振成像扫描,一次是在诱导 MS 的前一天,另一次是在第三次保持测试的第二天,间隔时间为 32 天。基于体素的全脑形态计量分析显示,与对照组大鼠相比,MS 组大鼠杏仁核海马前区灰质体积减少。这些结果表明,杏仁海马区的个体差异可能与严重应激后的持久恐惧反应有关。
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引用次数: 0
Understanding Cognitive Behavioral Therapy for Psychosis Through the Predictive Coding Framework 通过预测编码框架了解精神病认知行为疗法 (CBTp)
Q2 NEUROSCIENCES Pub Date : 2024-05-13 DOI: 10.1016/j.bpsgos.2024.100333
Julia M. Sheffield , Aaron P. Brinen , Brandee Feola , Stephan Heckers , Philip R. Corlett

Psychological treatments for persecutory delusions, particularly cognitive behavioral therapy for psychosis, are efficacious; however, mechanistic theories explaining why they work rarely bridge to the level of cognitive neuroscience. Predictive coding, a general brain processing theory rooted in cognitive and computational neuroscience, has increasing experimental support for explaining symptoms of psychosis, including the formation and maintenance of delusions. Here, we describe recent advances in cognitive behavioral therapy for psychosis–based psychotherapy for persecutory delusions, which targets specific psychological processes at the computational level of information processing. We outline how Bayesian learning models employed in predictive coding are superior to simple associative learning models for understanding the impact of cognitive behavioral interventions at the algorithmic level. We review hierarchical predictive coding as an account of belief updating rooted in prediction error signaling. We examine how this process is abnormal in psychotic disorders, garnering noisy sensory data that is made sense of through the development of overly strong delusional priors. We argue that effective cognitive behavioral therapy for psychosis systematically targets the way sensory data are selected, experienced, and interpreted, thus allowing for the strengthening of alternative beliefs. Finally, future directions based on these arguments are discussed.

针对迫害妄想症的心理疗法,尤其是针对精神病的认知行为疗法,疗效显著;然而,解释这些疗法为何有效的机理理论却很少达到认知神经科学的水平。预测编码是一种植根于认知和计算神经科学的通用大脑处理理论,在解释精神病症状(包括妄想的形成和维持)方面得到了越来越多的实验支持。在此,我们将介绍基于认知行为疗法的精神病心理疗法的最新进展,该疗法针对的是信息处理计算层面的特定心理过程。我们概述了在预测编码中采用的贝叶斯学习模型如何优于简单的联想学习模型,从而在算法层面上理解认知行为干预的影响。我们回顾了分层预测编码,它是对植根于预测错误信号的信念更新的一种解释。我们研究了这一过程如何在精神障碍中出现异常,如何通过发展过于强烈的妄想先验来获取嘈杂的感官数据。我们认为,治疗精神病的有效认知行为疗法可以系统地针对感官数据的选择、体验和解释方式,从而强化替代性信念。最后,我们基于这些论点讨论了未来的发展方向。
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引用次数: 0
期刊
Biological psychiatry global open science
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