A multimodal MRI study of the hippocampus in medication-naive children with ADHD: What connects ADHD and depression?

• We used MRI to examine hippocampal volumes and connectivity in children with ADHD.
• Hippocampal volumes were reduced in ADHD.
• Hippocampal–orbitofrontal cortex connectivity was also reduced in ADHD.
• Hippocampal effects were associated with depressive, but not ADHD, symptoms.
• Hippocampal anomalies in ADHD may confer risk for mood disorders.

Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for developing depression. The neurobiological substrates that convey this risk remain poorly understood. On the basis of considerable data implicating hippocampal abnormalities in depressive disorders, we aimed to explore the relationship between the hippocampus and levels of depressive symptomatology in ADHD. We used magnetic resonance imaging (MRI) to examine the volumes and resting-state functional connectivity of the hippocampus in a sample of 32 medication naive children with ADHD (ages 6 – 13) and 33 age- and sex-matched healthy control (HC) participants. Compared with the HC participants, the participants with ADHD had (i) reduced volumes of the left hippocampus and (ii) reduced functional connectivity between the left hippocampus and the left orbitofrontal cortex (OFC); these hippocampal effects were associated with more severe depressive symptoms, even after controlling for the severity of inattentive and hyperactive/impulsive symptoms. Altered hippocampal structure and connectivity were not associated with anxiety or more general internalizing symptoms. Though preliminary, these findings suggest that the relationship between hippocampal anomalies and ADHD youth׳s susceptibility to developing depression and other mood disorders may merit further investigation with follow-up longitudinal research.