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Mapping ADHD Heterogeneity and Biotypes by Topological Deviations in Morphometric Similarity Networks.

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Summary
This summary is machine-generated.

This study identified three distinct subtypes of attention-deficit/hyperactivity disorder (ADHD) using brain imaging and normative modeling. These ADHD biotypes have unique clinical and neural profiles, paving the way for personalized treatments.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Developmental Psychology

Background:

  • Attention-deficit/hyperactivity disorder (ADHD) presents significant clinical heterogeneity, challenging current classification systems.
  • Existing frameworks limit the development of neurobiologically informed subtyping approaches for ADHD.

Purpose of the Study:

  • To investigate if normative modeling of brain morphometry similarity networks can identify robust stratification markers for ADHD in children.
  • To explore novel subtyping approaches for ADHD based on neurobiological characteristics.

Main Methods:

  • Utilized multisite, cross-sectional neuroimaging data with longitudinal cognitive assessments.
  • Constructed morphometric similarity networks and applied normative modeling to topological metrics (degree centrality, nodal efficiency, participation coefficient).
  • Employed semisupervised clustering to delineate ADHD biotypes and examined their clinical and neural profiles, including neurochemical and functional correlates, with external validation.

Main Results:

  • ADHD cases showed atypical brain network organization compared to controls, particularly in the orbitofrontal cortex.
  • Identified three distinct ADHD biotypes: severe-combined with emotional dysregulation, predominantly hyperactive/impulsive, and predominantly inattentive.
  • Each biotype exhibited unique clinical features, longitudinal trajectories, and distinct neurobiological underpinnings, with findings replicated in an independent cohort.

Conclusions:

  • Normative modeling combined with semisupervised clustering offers valuable insights into ADHD heterogeneity.
  • The identified ADHD biotypes possess distinct clinical-neural profiles, advancing the understanding of ADHD's neurobiological complexity.
  • These findings provide a foundation for developing personalized management strategies for ADHD.