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

Abstract

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.

A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD)

“…Clinical studies suggest that heritability significantly contributes to impaired EF in ADHD (Bidwell et al, 2007; Friedman et al, 2008). Neuroimaging and neuropsychological studies in siblings found that compared to controls, patients with ADHD and their unaffected siblings had smaller inferior, medial and orbitofrontal GM volume (Pironti et al, 2014; Bralten et al, 2016), reduced superior frontal activations and fronto-striatal functional connectivity during performance of go/nogo tasks, correlated with lower WM integrity in prefrontal lobe (Rapoport and Shaw, 2008; Godinez et al, 2015), as well as significant cognitive deficits in EF (Friedman et al, 2008; Godinez et al, 2015). All these studies suggest that some frequently observed brain and behavioral abnormalities associated with frontal lobe and EF in ADHD may have heritable patterns.…”

The Stroop Effect Occurs at Multiple Points Along a Cascade of Control: Evidence From Cognitive Neuroscience Approaches

“…A study utilizing a case-control discordant twin pair design revealed that co-twins of individuals with ADHD, like their affected ADHD twin, show reduced activity in the anterior cingulate and insula compared to the unrelated controls, suggesting familial influences. In contrast, portions of the frontoparietal network appear to be the location of effects specific to ADHD, with twins with childhood ADHD showing reduced superior frontal (Brodmann’s Area – BA 6) and parietal region (BA 40) activity compared to both their control co-twins and unrelated control twins (Godinez et al, 2015).…”

Association of Epigenetic Differences Screened in a Few Cases of Monozygotic Twins Discordant for Attention-Deficit Hyperactivity Disorder With Brain Structures

“…Although the function of the orbital gyri appears related to emotional information and calculations, emotional information may play an important role in decision-making and executive function ( Bechara et al, 2000 ; Rolls and Grabenhorst, 2008 ). Numerous imaging studies using emotional and executive function tasks have reported reduced functional activation in the right orbital gyrus ( Epstein et al, 2007 ; Rubia et al, 2009 ; Cubillo et al, 2012 ; Godinez et al, 2015 ). Taken together, these findings suggest that SorCS2 gene methylation may induce both reduced GMV in the orbital gyrus and emotional behavioral problems, although the direct association between the two could not be confirmed in this study.…”