Machine Learning Classification of Attention-Deficit/Hyperactivity Disorder Using Structural MRI Data

Abstract

Background: Clinical symptoms-based ADHD diagnosis is considered "subjective". Machine learning (ML) classifiers have been explored to develop objective diagnosis of ADHD using magnetic resonance imaging (MRI) biomarkers. Methods: We reviewed previous literature and developed ensemble classifiers using the ENIGMA-ADHD dataset, with the implementation of data balancing to control for age, sex, diagnostic groups, and sample sites and a held-out test set for independent evaluation. Results: Our review showed that classification accuracies reported previously using cross-validation (CV) samples were inflated and did not generalize well to independent test samples. Our results showed a significant discrimination between ADHD and control samples for both adult and children, but the accuracies were modest (the area under the receiver operating characteristic curve (AUC): 66% and 67% respectively). We found that child samples were informative for predicting adult ADHD, and vice versa. The most important brain MRI structures for prediction were intracranial volume (ICV), followed by surface area and some subcortical volumes. The cortical thickness measurements were the least useful. Conclusions: Although previous ML classification studies reported overly optimistic accuracies and suffered methodological limitations, our results suggest that clinically useful classification of ADHD may be possible with larger samples. In contrast to prior reports of ENIGMA-ADHD studies, our work finds ADHD-related sMRI differences in adults and shows that the brain differences between cases and controls seen in youth can be useful in discriminating adults with and without ADHD. This provides additional evidence for the continuity of ADHD's pathophysiology from childhood to adulthood.