Cortical and Subcortical Structural Differences in Psychostimulant-Free ADHD Youth With and Without a Family History of Bipolar I Disorder: A Cross-Sectional Morphometric Comparison

Abstract

Abstract Although attention-deficit/hyperactivity disorder (ADHD) and a family history of bipolar I disorder (BD) both increase the risk for developing BD, associated neuroanatomical substrates remain poorly understood. This study compared cortical and subcortical gray matter morphology in psychostimulant-free ADHD youth with and without a first-degree relative with BD and typically developing healthy controls. ADHD youth (ages 10–18 years) with (‘high-risk’, HR) or without (‘low-risk’, LR) a first-degree relative with BD and healthy comparison youth (HC) were enrolled. High-resolution 3D T1-weighted images were acquired using a Philips 3.0 T MR scanner. The FreeSurfer image analysis suite was used to measure cortical thickness, surface area, and subcortical volumes. A general linear model evaluated group differences with age and sex as covariates, and exploratory correlational analyses investigated associations with different symptom ratings. A total of n = 142 youth (mean age: 14.16 ± 2.54 years, 35.9% female) were included in the analysis (HC, n = 48; LR, n = 49; HR, n = 45). The HR group exhibited a more severe symptom profile, including higher mania and dysregulation scores, compared to the LR group. For subcortical volumes, the HR group exhibited smaller bilateral thalamic, hippocampal, and left caudate nucleus volumes compared to both LR and HC, and smaller right caudate nucleus compared with LR. No differences were found between LR and HC groups. For cortical surface area, HR exhibited lower parietal and temporal surface area compared with HC and LR, and lower orbitofrontal and superior frontal surface area compared to LR. LR exhibited greater right pars opercularis surface area compared with the HC group. A subset of these cortical regions correlated with relevant symptom ratings. These findings suggest that ADHD in conjunction with BD family history is associated with a more a severe symptom profile and a neuroanatomical phenotype that distinguishes it from ADHD without a BD family history.