Familial risk and ADHD-specific neural activity revealed by case-control, discordant twin pair design

•This study demonstrates both familial and ADHD-specific patterns in two distinct prefrontal networks involved in executive function.•Familial effects were found such that ADHD twins and their discordant control co-twins showed deactivation in the medial and orbital frontal regions compared to the unrelated controls.•ADHD-specific effects were found such that ADHD twins showed less activation of superior frontoparietal regions compared to both their control co-twins and unrelated controls.

Individuals with ADHD, as well as their family members who do not meet clinical criteria, have shown deficits in executive function. However, it remains unclear whether underlying neural alterations are familial or ADHD-specific. To investigate this issue, neural activation underlying executive function was assessed using functional magnetic resonance imaging during performance of a Stroop task in three groups of individuals: 20 young adults who were diagnosed with ADHD in childhood, their 20 dizygotic co-twins without ADHD in childhood, and 20 unrelated controls selected from dizygotic twin pairs in which neither twin had ADHD in childhood (total n=60). Implicating the frontoparietal network as a location of effects specific to ADHD, activation in the superior frontal (Brodmann’s Area — BA 6) and parietal regions (BA 40) was significantly reduced in twins with childhood ADHD compared to both their control co-twins and unrelated control twins. Consistent with familial influences, activity in the anterior cingulate and insula was significantly reduced in both the twins with ADHD and their co-twins compared to the unrelated controls. These results show that both ADHD-specific and familial influences related to an ADHD diagnosis impact neural systems underlying executive function.