The Architecture of ADHD

ADHD is a childhood-onset neurodevelopmental disorder that can persist into the adult years. However, according to the ICD-10 and DSM-5 diagnostic criteria, although behavioral symptoms must have been present before six or 12 years of age, the condition can be diagnosed later in life (late-diagnosed ADHD). Affecting around 6 percent of school-age children and about 3 percent of adults, risk factors for ADHD are a complex issue, with both environmental and genetic factors playing a role.

Given the condition’s complex nature, might childhood, persistent, and late-diagnosed ADHD stem from different etiologies? To find out, an international team of researchers conducted a genome-wide association study for each subgroup to understand whether there are genetic differences between them (1).

For childhood ADHD, the study revealed four genome-wide significant loci on chromosomes 1, 5, 18, and 20. The risk loci on chromosomes 1 and 5 were already known, but those on chromosomes 18 and 20 were new. Analysis of late-diagnosed ADHD revealed one significant locus on chromosome 7, but none were found for persistent ADHD – an expected outcome given the low number of cases in this group. When measuring genetic overlap with ADHD symptoms in the general population, the team found that measures of hyperactivity and inattention were highly correlated with childhood and persistent ADHD, but less so with late-diagnosed ADHD.

People with ADHD sometimes have comorbid psychiatric disorders; to understand whether this might be linked with differences in genetic architecture, the team performed genetic correlation and polygenic score analyses for major psychiatric disorders. They found positive genetic correlations between ADHD subgroups and schizophrenia, bipolar disorder, autism, major depressive disorder, cannabis use disorder, and alcohol use disorder, as well as negative correlations with anorexia and obsessive-compulsive disorder. Childhood ADHD had greater genetic overlap with autism than late-diagnosed ADHD; the latter had a higher overlap with depression.

Overall, the findings demonstrate the impact of genetic heterogeneity of ADHD on age at first diagnosis, persistence, and comorbidity patterns across subgroups.