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Impact of Childhood Trauma Exposure, Genetic Variation in Endocannabinoid Signaling, and Anxiety on Frontolimbic Pathways in Children

焦虑 心理学 扣带回(脑) 脂肪酸酰胺水解酶 穹窿 白质 5-羟色胺能 部分各向异性 5-HTTLPR型 内大麻素系统 内科学 医学 神经科学 血清素转运体 精神科 血清素 海马体 放射科 磁共振成像 大麻素受体 受体 兴奋剂
作者
Hilary A. Marusak,Julia Evanski,Shreya Desai,Christine A. Rabinak
标识
DOI:10.1089/can.2022.0144
摘要

Introduction: The endocannabinoid (eCB) system plays a key role in modulating brain development, including myelination processes. Recent studies link a common variant (C385A, rs324420) in the fatty acid amide hydrolase (FAAH) gene to higher circulating eCB levels, lower anxiety, and altered frontolimbic development. Frontolimbic pathways, which demonstrate a protracted maturational course across childhood and adolescence, are associated with anxiety, and are vulnerable to environmental stressors such as trauma exposure. Here, we examined the impact of trauma exposure, FAAH genotype, and anxiety on frontolimbic white matter microstructure in children. Materials and Methods: We leveraged baseline data from the Adolescent Brain Cognitive Development (ABCD) study (n=9969; mean±standard deviation age=9.92±0.62 years; 47.1% female). Saliva samples were used for genotyping, and caregivers reported on their child's anxiety symptoms and trauma exposure. Fractional anisotropy (FA), a nonspecific measure of white matter integrity, was estimated for frontolimbic tracts. Results: Thirty-six percent of youth experienced one or more potentially traumatic events according to DSM-5 Criterion A (64% controls), and 45% were FAAH A-allele carriers (55% noncarriers). Relative to controls, trauma-exposed youth demonstrated higher anxiety and higher FA of the left uncinate. The FAAH A-allele (vs. CC) was associated with lower FA in the left fornix and left parahippocampal cingulum, and there was an indirect effect of FAAH genotype on anxiety through FA of the left fornix. Moreover, genotype moderated the association between FA of the left cingulum and anxiety. Conclusions: Our findings demonstrate distinct effects of trauma exposure and the FAAH C385A variant on frontolimbic pathways and subsequent anxiety risk in preadolescent children. This line of work may provide important insights into neurodevelopmental mechanisms leading to anxiety risk, and potential targets for intervention.
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