Individualized gray matter morphological abnormalities uncover two robust transdiagnostic biotypes.

Area of Science:

• Neuroscience
• Psychiatry
• Medical Imaging

Background:

• Psychiatric disorders share underlying neuropathology but present diversely.
• Identifying transdiagnostic subtypes is crucial for improved diagnosis and treatment.
• Personalized analysis of brain structure can reveal these subtypes.

Purpose of the Study:

• To uncover transdiagnostic subtypes of psychiatric disorders using personalized gray matter morphology.
• To validate the identified subtypes across multiple datasets and disorders.

Main Methods:

• Utilized normative modeling on gray matter morphology data from 496 patients and 255 healthy controls (HCs) across three datasets.
• Identified transdiagnostic subtypes based on individualized structural abnormalities.
• Performed reproducibility and generalizability analyses on validation datasets.

Main Results:

• Discovered two distinct transdiagnostic subtypes with contrasting gray matter abnormality patterns compared to HCs.
• Subtypes showed reproducible and generalizable patterns across new patients and disorders.
• Subtype 1 abnormalities linked to excitatory receptors; Subtype 2 linked to inhibitory receptors and inflammation-related gene expression.

Conclusions:

• Identified two robust transdiagnostic biotypes in psychiatric disorders.
• Findings provide novel insights into psychiatric nosology and potential therapeutic targets.
• Personalized brain morphology analysis is a promising approach for psychiatric research.