Lower Availability of Mitochondrial Complex I in Anterior Cingulate Cortex in Autism: A Positron Emission Tomography Study
Lower Availability of Mitochondrial Complex I in Anterior Cingulate Cortex in Autism: A Positron Emission Tomography Study
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DOI：
10.1176/appi.ajp.22010014
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发表时间：
2023-04-01
影响因子：
17.7
通讯作者：
Yamasue，Hidenori
中科院分区：
文献类型：
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作者：
Kato，Yasuhiko;Yokokura，Masamichi;Yamasue，Hidenori
线粒体功能障碍已被牵连在自闭症谱系障碍（ASD）的病理生理学在以前的研究死后的大脑或外周样本。作者调查了ASD患者的活体脑中是否以及在何处发生线粒体功能障碍，并确定检测到的线粒体功能障碍的临床相关性。（2-[18F]氟乙氧基）-乙氧基]-吡啶-3-基甲氧基}-2H-哒嗪-3-酮（[18 F]BCPP-EF），一种与线粒体电子传递链复合物I结合的放射性配体，研究ASD患者活体脑中线粒体功能障碍的地形分布。23名患有高功能ASD的成年男性，无精神病合并症，无精神药物治疗，24名典型的发展男性，无精神病诊断，与ASD组的年龄，父母的社会经济背景和智商相匹配，进行[18 F]BCPP-EF PET测量。与线粒体疾病的个人被排除在乳酸和丙酮酸level.ResultsAmong线粒体功能障碍已被报道在自闭症大脑的尸检研究的大脑区域的临床评价和血液检测异常，与ASD的参与者显着降低[18 F]BCPP-EF的可用性，特别是在前扣带皮层与典型发达的参与者相比。诊断与脑区之间存在显著的相互作用，揭示了区域特异性。此外，较低的[18 F]BCPP-EF在前扣带皮层的可用性显着相关的更严重的ASD的核心症状的社会communication deficits.ConclusionsThis study provides direct evidence to link in vivo brain mitochondrial dysfunction with ASD pathophysiology and its communicational deficits.这些发现支持线粒体电子传递链复合物I是ASD核心症状的新治疗靶点的可能性。
ObjectiveMitochondrial dysfunction has been implicated in the pathophysiology of autism spectrum disorder (ASD) in previous studies of postmortem brain or peripheral samples. The authors investigated whether and where mitochondrial dysfunction occurs in the living brains of individuals with ASD and to identify the clinical correlates of detected mitochondrial dysfunction.MethodsThis case-control study used positron emission tomography (PET) with 2-tert-butyl-4-chloro-5-{6-[2-(2-[18F]fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one ([18F]BCPP-EF), a radioligand that binds to the mitochondrial electron transport chain complex I, to examine the topographical distribution of mitochondrial dysfunction in living brains of individuals with ASD. Twenty-three adult males with high-functioning ASD, with no psychiatric comorbidities and free of psychotropic medication, and 24 typically developed males with no psychiatric diagnoses, matched with the ASD group on age, parental socioeconomic background, and IQ, underwent [18F]BCPP-EF PET measurements. Individuals with mitochondrial disease were excluded by clinical evaluation and blood tests for abnormalities in lactate and pyruvate levels.ResultsAmong the brain regions in which mitochondrial dysfunction has been reported in postmortem studies of autistic brains, participants with ASD had significantly decreased [18F]BCPP-EF availability specifically in the anterior cingulate cortex compared with typically developed participants. The regional specificity was revealed by a significant interaction between diagnosis and brain regions. Moreover, the lower [18F]BCPP-EF availability in the anterior cingulate cortex was significantly correlated with the more severe ASD core symptom of social communication deficits.ConclusionsThis study provides direct evidence to link in vivo brain mitochondrial dysfunction with ASD pathophysiology and its communicational deficits. The findings support the possibility that mitochondrial electron transport chain complex I is a novel therapeutic target for ASD core symptoms.