Classification of familial and non-familial ADHD using auto-encoding network and binary hypothesis testing

Family history is one the most powerful risk factor for attention-deficit/hyperactivity disorder (ADHD), yet no study has tested whether multimodal Magnetic Resonance Imaging (MRI) combined with deep learning can separate familial ADHD (ADHD-F) and non-familial ADHD (ADHD-NF). T1-weighted and diffusion-weighted MRI data from 438 children (129 ADHD-F, 159 ADHD-NF, and 150 controls) were parcellated into 425 cortical and white-matter metrics. Our pipeline combined three feature-selection steps (t-test filtering, mutual-information ranking, and Lasso) with an auto-encoder and applied the binary-hypothesis strategy throughout; each held-out subject was assigned both possible labels in turn and evaluated under leave-one-out testing nested within five-fold cross-validation. Accuracy, sensitivity, specificity, and area under the curve (AUC) quantified performance. The model achieved accuracies/AUCs of 0.66 / 0.67 for ADHD-F vs controls, 0.67 / 0.70 for ADHD-NF vs controls, and 0.62 / 0.67 for ADHD-F vs ADHD-NF. In classification between ADHD-F and controls, the most informative metrics were the mean diffusivity (MD) of the right fornix, the MD of the left parahippocampal cingulum, and the cortical thickness of the right inferior parietal cortex. In classification between ADHD-NF and controls, the key contributors were the fractional anisotropy (FA) of the left inferior fronto-occipital fasciculus, the MD of the right fornix, and the cortical thickness of the right medial orbitofrontal cortex. In classification between ADHD-F and ADHD-NF, the highlighted features were the volume of the left cingulate cingulum tract, the volume of the right parietal segment of the superior longitudinal fasciculus, and the cortical thickness of the right fusiform cortex. Our binary hypothesis semi-supervised deep learning framework reliably separates familial and non-familial ADHD and shows that advanced semi-supervised deep learning techniques can deliver robust, generalizable neurobiological markers for neurodevelopmental disorders.