Neurodevelopmental risk and adaptation as a model for comorbidity among internalizing and externalizing disorders: genomics and cell-specific expression enriched morphometric study

作者：Nanyu Kuang, Zhaowen Liu, Gechang Yu, Xinran Wu, Benjamin Becker, Huaxin Fan, Songjun Peng, Kai Zhang, Jiajia Zhao, Jujiao Kang, Guiying Dong, Xing‐Ming Zhao, Barbara J. Sahakian, Trevor W. Robbins, Wei Cheng, Jianfeng Feng, Günter Schumann, Lena Palaniyappan, Jie Zhang · 发表于：BMC Medicine · 年份：2023 · DOI：10.1186/s12916-023-02920-9 · 被引用次数：68 · 研究领域：Tryptophan and brain disorders、Stress Responses and Cortisol、Bipolar Disorder and Treatment

BACKGROUND: Comorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregate of the effects on each disorder and if these comorbidity-associated cortical surface differences relate to a distinct genetic underpinning. METHODS: We studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (dysthymia, major depressive disorder, disruptive mood dysregulation disorder, agoraphobia, panic disorder, specific phobia, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder), externalizing (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) diagnostic groups, a group with comorbidity of the two and a healthy control group. Genome-wide association analysis (GWAS) and cell type specificity analysis were performed on 4468 unrelated European participants from this cohort. RESULTS: Smaller cortical surface area but higher thickness was noted across patient groups when compared to controls. Children with comorbid internalizing and ext...