A new study led by Stanford University School of Medicine has found that three distinct brain biotypes exist in children with attention-deficit/hyperactivity disorder (ADHD), anxiety disorders, or both conditions. According to the study, published in the journal Nature Mental Health, each biotype is characterized by dysfunction in specific brain circuits. The findings could help specialists better understand the neurobiological underpinnings of two of the most common and frequently overlapping mental health conditions in childhood.
The biotypes were identified through an analysis of thousands of functional magnetic resonance imaging (fMRI) brain scans of children. According to study co-author Dr. Yu Zhang, an assistant professor of psychiatry and behavioral sciences, the high rate of overlap between ADHD and anxiety makes it difficult to understand the underlying neurobiological picture using traditional, symptom-based diagnostic approaches. Children diagnosed with one condition often also exhibit symptoms characteristic of the other.
The researchers used data from the Adolescent Brain Cognitive Development (ABCD) study, which includes more than 11,000 American children. The analysis included 3,508 children who had already been diagnosed with ADHD, anxiety, or both conditions at the time of enrollment; 693 children who had no initial diagnosis but received one later; and 1,947 control participants without either diagnosis. To validate the findings, the researchers also used brain scans from an additional 224 children enrolled in the Healthy Brain Network study.
Using an artificial intelligence (AI)-based model, the scientists analyzed functional connectivity between different brain regions. The model identified two major dimensions of brain dysfunction: cognitive-behavioral and emotional-attentional dysfunction. Different combinations of these mechanisms give rise to three newly identified biotypes:
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Externalizing-disinhibited biotype: Characterized by hostility, defiance, impulsivity, aggression, and rule-breaking. This biotype is more frequently associated with an ADHD diagnosis.
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Internalizing-distressed biotype: Characterized by feelings of guilt, tension, perfectionism, and anxiety- and depression-related symptoms. It is more commonly observed in children diagnosed with anxiety disorders.
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Mixed biotype: Associated with attention problems, irritability, and a tendency toward self-harm.
One of the study’s most significant findings is that all three biotypes could also be identified through baseline brain scans in children who had no diagnosis at the time of enrollment but were subsequently diagnosed with ADHD or anxiety. According to Dr. Zhang, this suggests that the biotypes could serve as early indicators of these conditions, potentially enabling timely intervention and helping slow their progression.
The researchers emphasize that brain biotypes are not intended to replace traditional, symptom-based diagnostic approaches but rather to complement them. Currently, selecting the optimal treatment for ADHD and anxiety disorders often involves a trial-and-error approach. As Dr. Zhang explains, this means that a physician prescribes a new medication and waits weeks or months to assess whether it works. If it proves ineffective, the physician switches to another drug, making the process lengthy, costly, and exhausting. In the future, these new biomarkers could help physicians match specific treatments to individual biotypes, ensuring that patients receive the “right treatment at the right time.”
