ADHD-inattentive versus ADHD-Combined subtypes: A severity continuum or two distinct entities? A comprehensive analysis of clinical, cognitive and neuroimaging data

The current study aimed to explore the multimodal differences between the inattentive ADHD (ADHD-I) subtype and the combined ADHD (ADHD-C) subtype. A large sample of medication-naïve children with pure ADHD (i.e., without any comorbidity) (145 with ADHD-I, 132 with ADHD-C) and healthy controls (n = 98) were recruited. A battery of multiple scales and cognitive tests were utilized to assess the clinical and cognitive profiles of each individual. In addition, structural and diffusion magnetic resonance imaging (MRI) were acquired for 120 subjects with ADHD and 85 controls. Regional gray matter volume, white matter volume, and diffusion tensors, e.g., axial diffusivity (AD), were compared among the three groups in a whole-brain voxel-wise manner. Compared with healthy controls, both ADHD groups exhibited elevated levels of behavioral and emotional problems. The ADHD-C group had more behavioral problems and emotional liability, as well as less anxiety, than the ADHD-I group. The two ADHD groups were equally impaired in most cognitive domains, with the exception of sustained attention. Compared with healthy controls, the ADHD-C group showed a high gray matter volume (GMV) in the bilateral thalamus and a high white matter volume in the body of the corpus callosum, while the ADHD-I group presented an elevated GMV mainly in the left precentral gyrus and posterior cingulate cortex. Compared with participants with ADHD-C and healthy controls, subjects with ADHD-I showed increased AD in widespread brain regions. Our study has revealed a distinct, interconnected pattern of behavioral, cognitive, and brain structural characteristics in children with different ADHD subtypes.