Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

Context: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. Objective: To study the morphology of the hippocampus and amygdala in children with ADHD. Design: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. Settings: University research institute. Patients: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. Main Outcome Measures: Volumes and measures of surface morphology for the hippocampus and amygdala. Results: The hippocampus was larger bilaterally in the ADHD group than in the control group (t=3.35; P<.002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. Conclusions: The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD.