ADHD Polygenic Risk Scores May Benefit Pediatric Bipolar, Mood Disorder Understanding

Joseph Biederman, MD (MGH)

ADHD polygenic risk scores may be the most beneficial of all related mood disorder risk scores in the assessment of disorder development.

In research presented at The American Professional Society of ADHD and Related Disorders (APSARD) 2021 Annual Conference this weekend, a team of Massachusetts General Hospital investigators reported that such risk scores may even provide explanation into the significant comorbidity rate of ADHD and other youth mood and emotional dysregulation issues.

Presented by author Joseph Biederman, MD, the study sought to assess the available body of information available on associations between polygenic risk scores for bipolar disorder (BP-PRS) and pediatric bipolar spectrum and related disorders.

As Biederman and colleagues noted, the strong genetic basis of mood disorders could potentially provide clinicians with diagnostic insights when few avenues of care are clear.

“Because the genetic basis of complex disorders such as mood disorders is polygenic, clinically relevant information could emerge from genetic markers in aggregate in the form of polygenic risk scores,” they wrote.

Their research included an online literature search for the following grouped terms:

• PRS and Bipolar Disorder, Bipolar, or Bipolar Depression
• PRS and Depression, MD, or MDD
• PRS and Attention, ADHD, Conduct Disorder symptoms, emotional dysregulation, aggression

The investigators additionally screened for predetermined inclusion and exclusion criteria.A litany of variables were extracted from relevant studies, including population age, study size, source of PRSs, source of clinical and genetic data, primary study outcome, assessments used, and main findings.

In their findings, Biederman and colleagues observed bipolar PRSs were significantly associated with deficits in executive functioning, ADHD diagnoses, and associated executive function deficits.

In the lone study to compare depression PRSs to bipolar PRSs directly in youths, investigators noted that, among the 40,000 children aged 6-17 years old, only depression PRSs were associated with ADHD symptoms, internalizing problems, and social problems.

ADHD PRSs, the team reported, were associated with conduct problems, depressive symptomatology, and externalizing disorders symptoms.

“Findings revealed that while higher BP-PRSs were correlated with increased hypomania scores, ADHD-PRSs were more clearly associated with emotional reactivity, emotional dysregulation, and irritability—frequent correlates of pediatric bipolar spectrum disorder,” investigators wrote.

Though depression PRSs were predictive of more severe pediatric trajectories toward major depressive disorder, their contribution toward pediatric bipolar spectrum and related disorders is still unknown; available studies did not examine such risk in observed patients.

Taken together, one form of polygenic risk scores seems to best inform interpretation of pediatric mood disorder risks and progression.

“These finding suggest that ADHD-PRSs may have the most important contribution to the development of mood related problems in youth and may begin to explain the high comorbidity between ADHD with mood and emotional dysregulation problems in the young,” Biederman and colleagues wrote.

The study, “Can Polygenic Risk Scores Help Identify Pediatric Bipolar Spectrum and Related Disorders?” was presented at APSARD 2021.