ADHD Biotypes and Personalized Medicine
According to JAMA Psychiatry 2026 research, 3 new ADHD biotypes based on deviations in brain networks and their clinical reflections.
Methodology: MSN and Normative Modeling
Instead of traditional statistical methods, 'Morphometric Similarity Networks' (MSN) and 'Normative Modeling' approaches were used to categorize ADHD—a heterogeneous phenotype—into subgroups. This approach, rather than focusing on a single brain region, measures topological deviations in the brain's overall neuro-architectural organization.
Normative modeling treats the brain like a 'growth chart.' Using thousands of data points obtained from typically developing brains, this chart allows for determining the magnitude (Z-score) and direction of deviations in the brain connectivity of individuals with ADHD. MSN models the 'communication quality' of neural networks by examining the correlation of parameters such as gray matter volume, cortical thickness, and surface area between brain regions.
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Biotype 1: Delayed Neural Maturation (D-Type)
Biotype 1 is a profile closest to typically developing control groups but falls behind the chronological age on the maturation curve (developmental delay). Deviations in this type are usually concentrated in the connectivity between the Prefrontal Cortex and the Anterior Cingulate Cortex (ACC). These regions are the main centers for executive functions and cognitive control.
Clinically, this group is the type closest to classic ADHD symptoms (inattention, hyperactivity). The most significant finding is that this biotype is the group that benefits most (85%+) from stimulant medications (e.g., Methylphenidate). This shows that biologically, the 'braking mechanism' is just weak and can normalize with stimulation.
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Biotype 2: Atypical/Deviated Connectivity (A-Type)
Biotype 2 exhibits an entirely different network organization path (atypical developmental trajectory) rather than just a delay. Deviations are concentrated more in Sensorimotor Networks, the Limbic System, and Thalamic connections. There is an atypical interaction between the processing of sensory inputs and emotional regulation centers.
While this group usually responds average or lower to stimulants, they may respond better to neuromodulation (e.g., tDCS, Neurofeedback) or specific non-stimulant therapies. The clinical picture is generally characterized by intense sensory sensitivity (Sensory Overload) and impulsivity.
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Biotype 3: Global/Complex Deviation (C-Type)
Biotype 3 is the most heterogeneous group showing widespread and complex (global) deviations in the brain's gray and white matter organization. In this type, deviations are not limited to a single network but affect the integrated communication capacity of the brain. Significant structural differences are usually observed from the early developmental period onwards.
Clinically, this group has the highest risk of comorbidity (secondary diagnoses). Overlap with Autism (AuDHD), Learning Disabilities, and major mood disorders is more frequent in these types. The treatment process requires a multimodal (multifaceted) approach; medication alone may generally not be sufficient for symptom management.
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The 'Tailor-Made' Era in Psychiatry
The discovery of these biotypes indicates that we are approaching the end of the 'trial-and-error' era in ADHD management. By looking at the deviations in an individual's brain map (MSN profile), it will be possible to predict which biotype they fall into, whether they will respond to stimulants, or what side effect risks they carry at the moment of diagnosis.
Personalized medicine aims to choose the treatment protocol most suitable for the individual's nervous system architecture (tailor-made treatment) by combining biological data with clinical observation. This approach both increases treatment success and minimizes years lost due to incorrect medication use.