A Stanford Medicine-led study published Oct. 16 in *Nature Mental Health* identified three brain biotypes among children with ADHD, anxiety, or both, based on brain-circuit activity and related symptoms.

Researchers analyzed functional MRI scans and behavioral data from thousands of children in the Adolescent Brain Cognitive Development study and tested their findings against scans from 224 children in a separate study.

An artificial intelligence model identified two dimensions of dysfunction—cognitive-behavioral and emotion-attention—that combine in different ways to form the externalizing-disinhibited, internalizing-distressed, and mixed biotypes.

The externalizing-disinhibited pattern was associated with hostility, defiance, impulsivity, aggression, and rule-breaking, and was more common among children diagnosed with ADHD; the internalizing-distressed pattern involved guilt, tension, perfectionism, and anxious-depressed symptoms, and was more common among children diagnosed with anxiety.

The mixed biotype was linked to attention problems, irritability, and self-injury, and was more common among children with ADHD, although all three biotypes appeared across the ADHD, anxiety, and combined-diagnosis groups.

Researchers also found the biotypes in baseline scans of some children who were diagnosed with ADHD, anxiety, or both only later, suggesting the patterns could eventually help identify risk earlier and support timely intervention.

The researchers do not expect biotypes to replace symptom-based diagnoses; instead, they hope future research and clinical trials will show whether the patterns can help clinicians match children with effective treatments and reduce trial and error.

The study was led by Yong Jiao, with Yu Zhang and Jing Jiang as co-senior authors, and included researchers from Stanford, the University of Iowa, the University of Texas at Austin, and the University of Pennsylvania Perelman School of Medicine.