Subcortical structural covariance predicts symptoms in children with different subtypes of ADHD

Abstract Attention-deficit/hyperactivity disorder has increasingly been conceptualized as a disorder of abnormal brain connectivity. However, far less is known about the structural covariance in different subtypes of this disorder and how those differences may contribute to the symptomology of these subtypes. In this study, we used a combined volumetric-based methodology and structural covariance approach to investigate structural covariance of subcortical brain volume in attention-deficit/hyperactivity disorder-combined and attention-deficit/hyperactivity disorder-inattentive patients. In addition, a linear support vector machine was used to predict patient’s attention-deficit/hyperactivity disorder symptoms. Results showed that compared with TD children, those with attention-deficit/hyperactivity disorder-combined exhibited decreased volume of both the left and right pallidum. Moreover, we found increased right hippocampal volume in attention-deficit/hyperactivity disorder-inattentive children. Furthermore and when compared with the TD group, both attention-deficit/hyperactivity disorder-combined and attention-deficit/hyperactivity disorder-inattentive groups showed greater nonhomologous inter-regional correlations. The abnormal structural covariance network in the attention-deficit/hyperactivity disorder-combined group was located in the left amygdala–left putamen/left pallidum/right pallidum and right pallidum–left pallidum; in the attention-deficit/hyperactivity disorder-inattentive group, this difference was noted in the left hippocampus–left amygdala/left putamen/right putamen and right hippocampus–left amygdala. Additionally, different combinations of abnormalities in subcortical structural covariance were predictive of symptom severity in different attention-deficit/hyperactivity disorder subtypes. Collectively, our findings demonstrated that structural covariance provided valuable diagnostic markers for attention-deficit/hyperactivity disorder subtypes.