Individual differences v. the average patient: mapping the heterogeneity in ADHD using normative models.

Area of Science:

• Neuroscience
• Psychiatry
• Computational Biology

Background:

• Traditional case-control studies oversimplify biologically heterogeneous mental disorders like attention-deficit/hyperactivity disorder (ADHD).
• These methods create an 'average patient' concept, obscuring individual biological variations within the ADHD population.
• A novel approach is needed to model individual differences in persistent ADHD.

Purpose of the Study:

• To present a novel approach for modeling individual differences in persistent ADHD.
• To investigate how normative modeling reveals inter-individual variations masked by case-control analyses.
• To demonstrate the limited informative value of the 'average ADHD patient' concept.

Main Methods:

• Utilized a normative modeling approach to map inter-individual differences in brain structure.
• Compared structural brain changes across the lifespan against normative data.
• Examined the extent to which case-control analyses obscure individual differences.

Main Results:

• Deviations from the normative model were common in individuals with persistent ADHD.
• Significant overlap in brain loci affected by ADHD was minimal (less than 2%).
• Individuals with ADHD showed reduced gray matter in the cerebellum and hippocampus, but group differences poorly represented individual variations.

Conclusions:

• Case-control comparisons obscure crucial inter-individual differences in ADHD brain biology.
• The 'average ADHD patient' provides limited biological insight.
• This study provides evidence for analyzing ADHD's biological facets at the individual level.