ADHD’s Genetic Links Come Into Focus with Study of Cognitive Deficits in Families

April 18, 2025

Deficits in working memory, response inhibition, and processing speed are present not only in individuals with ADHD but also in their family members without the condition, according to a new study published in the Journal of Psychopathology and Clinical Science that suggests these shared cognitive deficits may be “endophenotypes,” or measurable genetic traits that essentially act as biomarkers for ADHD. 1

The multilevel meta-analysis found that “unaffected first-degree relatives” (parents, siblings, or children) of individuals with ADHD performed significantly worse than non-ADHD controls in working memory, processing speed, response time variability, temporal processing, and cognitive flexibility. However, unaffected first-degree relatives did not display significant differences in inhibition, arousal, motor functioning, planning, or delay aversion compared to the control group.

“This is an incredibly important study,” Russell A. Barkley, Ph.D., said recently on his YouTube channel. “This study suggests that there is a larger endophenotype within families of people with ADHD, such that first-degree relatives show some symptoms and signs of the disorder. Think of it as an iceberg; underneath the surface lies the variability in the genetic endophenotype within these families. Then above the surface is a smaller peak, that’s the diagnosed people with ADHD.”

The researchers said that more studies focusing on basic cognitive functions, like working memory and cognitive flexibility, are needed to better understand how genes predispose someone to ADHD and how these genetic factors interact with other influences to cause ADHD symptoms.

Subthreshold ADHD

Identifying and studying potential ADHD endophenotypes may help researchers better understand subthreshold ADHD, which may be experienced by individuals who display ADHD symptoms but not to the severity or frequency required for a formal ADHD diagnosis.

“People with subthreshold ADHD may not exhibit impairing symptoms before age 12, as required in the current DSM-5 for a diagnosis. However, these undiagnosed, untreated adults may experience significant distress later in life and face an elevated risk for substance abuse, burnout, and professional and personal problems as a result,” said Maggie Sibley, Ph.D., a professor of psychiatry and behavioral sciences at the University of Washington School of Medicine, during the 2024 American Professional Society of ADHD and Related Disorders (APSARD) conference.

Sibley cited research from the 2022 Multimodal Treatment of Attention Deficit Hyperactivity Disorder (MTA) study showing that 63.8% of people with ADHD experienced symptom fluctuations throughout their lives. “We need to recognize that ADHD symptoms are not stable; they wax and wane over the lifespan,” she said. “Even individuals with mild, non-clinical symptoms can experience fluctuations that temporarily send their symptoms or impairment severity into the clinical range.”2

Sibley expanded on the MTA data in “ADHD’s Vanishing (and Reappearing) Act,” an article in the Spring 2025 issue of ADDitude magazine. “Most adults today with new diagnoses of ADHD probably did not develop their symptoms in adulthood,” she wrote. “Instead, they were likely missed, or they had mild, non-clinical symptoms in childhood that became more impairing as life’s demands multiplied. The study suggested that ADHD is more likely to be missed in childhood in females and minorities. People with intellectual gifts or supportive environments are more likely to compensate for their ADHD in childhood, so symptoms appear milder.”

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