鳥塚 通弘

Individuals with autism spectrum disorder (ASD) are more likely to experience adverse childhood experiences (ACEs) compared with typically developing (TD) individuals, which predisposes them to an elevated risk of mental health issues. This review elucidates the profound impact of ACEs on individuals with ASD by synthesizing findings from a plethora of epidemiologic and biological studies, encompassing genetics, epigenetics, and neuroimaging. Despite the limited number of studies explicitly focusing on this intersection, the extant literature consistently demonstrates that ASD individuals are disproportionately affected by ACEs, leading to significant deterioration in mental health and brain function. Furthermore, the nature and extent of the effects of ACEs appear to diverge between ASD and TD populations, underscoring the necessity for tailored clinical and research approaches. Understanding these complex and intertwined interactions is imperative for advancing both clinical practice and research, with the goal of mitigating the adverse outcomes associated with ACEs in ASD individuals.

AIM: Adverse childhood experiences are potentially traumatic events with long-lasting effects on the health and well-being of patients with autism spectrum disorder (ASD). It is important to clarify which types of long-lasting autism-related symptoms are influenced by childhood experiences to design future intervention studies. However, few studies have examined the association between childhood experiences and autistic symptoms in large samples of adults with ASD and individuals with typical development (TD). In this study, we evaluate the effects of adverse childhood experiences on multiple ASD phenotypes among both individuals with ASD and those with TD. METHOD: We combined questionnaire evaluations; Childhood Abuse and Trauma Scale, the Japanese version of the Autism-Spectrum Quotient, Conners' Adult ADHD Rating Scale, the Japanese version of the Impact of Event Scale-Revised, and the Japanese version of the Adolescent/Adult Sensory Profile. RESULTS: Individuals with ASD and those with TD (n = 205 and 104, respectively) were included. There were significant correlations between the extent of adverse childhood experiences and severity of attention-deficit/hyperactivity disorder symptoms, posttraumatic stress disorder symptoms, and hypersensitivity in both participants with ASD and those with TD. By contrast, ASD core symptoms showed no significant correlation with adverse childhood experiences in either group. These results remained consistent after adjusting for age, sex, and the estimated intelligence quotient. CONCLUSION: These findings suggest the need for a detailed disentanglement of ASD-related core and peripheral symptoms of adverse childhood experiences, which may help to appropriately set outcomes for future early interventions for the childhood experiences of individuals with ASD.

Background Social isolation during critical periods of development is associated with alterations in behavior and neuronal circuitry. This study aimed to investigate the immediate and developmental effects of social isolation on firing properties, neuronal activity-regulated pentraxin (NARP) and parvalbumin (PV) expression in the prefrontal cortex (PFC), social behavior in juvenile socially isolated mice, and the biological relevance of NARP expression in autism spectrum disorder (ASD). Methods Mice were subjected to social isolation during postnatal days 21–35 (P21–P35) and were compared with group-housed control mice. Firing properties in the PFC pyramidal neurons were altered in P35 socially isolated mice, which might be associated with alterations in NARP and PV expression. Results In adulthood, mice that underwent juvenile social isolation exhibited difficulty distinguishing between novel and familiar mice during a social memory task, while maintaining similar levels of social interaction as the control mice. Furthermore, a marked decrease in NARP expression in lymphoblastoid cell lines derived from adolescent humans with ASD as compared to typically developing (TD) humans was found. Conclusion Our study highlights the role of electrophysiological properties, as well as NARP and PV expression in the PFC in mediating the developmental consequences of social isolation on behavior.

がん研究領域において顕著な進展を遂げた細胞外小胞の研究が,精神医学の分野でも注目を集めている。特に,エクソソームと称される細胞間コミュニケーションに不可欠な細胞外小胞は,多様な生物学的物質を内包しており,それらの生体における役割が明らかにされている。脳由来のエクソソームは末梢血からの抽出が可能であり,これを「脳リキッドバイオプシー」とよび,精神医学領域における診断的価値について広く議論されている。自閉スペクトラム症においては,脳内外の免疫細胞の活性化が報告されているが,その背景病理は依然として不明である。本稿では,エクソソームが示す血液脳関門の高い透過性を踏まえ,これらの粒子が脳内外の免疫細胞に働きかけ,脳内外において同様の免疫応答を引き起こす可能性について考察する。さらに,脳実質よりも血液脳関門が脆弱な領域に位置する脳境界マクロファージが,脳内外の免疫応答にどのように関与しうるのかについても説明する。(著者抄録)