Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable neuroanatomical heterogeneity. Thus, how and to what extent the brains of individuals with ASD differ from each other is still unclear. In this study, brain structural MRI data from 356 right‐handed, male subjects with ASD and 403 right‐handed male healthy controls were selected from the Autism Brain Image Data Exchange database (age range 5–35 years old). Voxel‐based morphometry preprocessing steps were conducted to compute the gray matter volume maps for each subject. Individual neuroanatomical difference patterns for each ASD individual were calculated. A data‐driven clustering method was next utilized to stratify individuals with ASD into several subtypes. Whole‐brain functional connectivity and clinical severity were compared among individuals within the ASD subtypes identified. A searchlight analysis was applied to determine whether subtyping ASD could improve the classification accuracy between ASD and healthy controls. Three ASD subtypes with distinct neuroanatomical difference patterns were revealed. Different degrees of clinical severity and atypical brain functional connectivity patterns were observed among these three subtypes. By dividing ASD into three subtypes, the classification accuracy between subjects of two out of the three subtypes and healthy controls was improved. The current study confirms that ASD is not a disorder with a uniform neuroanatomical signature. Understanding neuroanatomical heterogeneity in ASD could help to explain divergent patterns of clinical severity and outcomes.
Accumulating neuroimaging evidence has shown remarkable volume reductions in the hippocampi of patients with schizophrenia. However, the relationship among hippocampal morphometry, clinical symptoms, and cognitive impairments in schizophrenia is still unclear. In this study, high-resolution structural magnetic resonance imaging data were acquired in 36 patients with adolescent-onset schizophrenia (AOS, age range: 13–18 years) and 30 age-, gender-, and education-matched typically developing controls (TDCs). Hippocampal volume was assessed automatically through volumetric segmentation and measurement. After adjusting for total intracranial volume, we found reduced hippocampal volume in individuals with AOS compared with TDCs, and the hippocampal volume was positively correlated with verbal memory and negatively correlated with negative symptoms in AOS. In addition, mediation analysis revealed the indirect effect of hippocampal volume on negative symptoms via verbal memory impairment. When the negative symptoms were represented by 2 dimensions of deficits in emotional expression (EXP) and deficits in motivation and pleasure (MAP), the indirect effect was significant for EXP but not for MAP. Our findings provide further evidence of hippocampal volume reduction in AOS and highlight verbal memory impairment as a mediator to influence the relationship between hippocampal morphometry and negative symptoms, especially the EXP dimension of negative symptoms, in individuals with AOS.
Autism spectrum disorder is an early-onset neurodevelopmental condition. This study aimed to investigate the progressive structural alterations in the autistic brain during early childhood. Structural magnetic resonance imaging scans were examined in a cross-sectional sample of 67 autistic children and 63 demographically matched typically developing (TD) children, aged 2–7 years. Voxel-based morphometry and a general linear model were used to ascertain the effects of diagnosis, age, and a diagnosis-by-age interaction on the gray matter volume. Causal structural covariance network analysis was performed to map the interregional influences of brain structural alterations with increasing age. The autism group showed spatially distributed increases in gray matter volume when controlling for age-related effects, compared with TD children. A significant diagnosis-by-age interaction effect was observed in the fusiform face area (FFA, Fpeak = 13.57) and cerebellum/vermis (Fpeak = 12.73). Compared with TD children, the gray matter development of the FFA in autism displayed altered influences on that of the social brain network regions (false discovery rate corrected, P < 0.05). Our findings indicate the atypical neurodevelopment of the FFA in the autistic brain during early childhood and highlight altered developmental effects of this region on the social brain network.
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