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Exposotypes in psychotic disorders.

Walid Yassin1,2, Bryan Kromenacker3, James B Green4,5

  • 1Beth Israel Deaconess Medical Center, Boston, MA, U.S.. walid.yassin00@gmail.com.

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|August 8, 2025
PubMed
Summary
This summary is machine-generated.

Psychiatry can improve diagnosis by identifying etiological factors. This study found distinct exposotypes linked to childhood trauma and substance use, impacting psychotic disorder symptoms, cognition, and brain structure.

Keywords:
Childhood traumaCognitive functionMachine learningPsychotic disordersSocioeconomic statusSubstance use

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Area of Science:

  • Psychiatry
  • Neuroscience
  • Genetics

Background:

  • Psychiatry diagnosis, prognosis, and outcome prediction lag behind other medical fields in adopting etiological approaches.
  • Childhood trauma (CHT), substance use (SU), and socioeconomic status (SES) significantly influence psychotic disorder symptoms.
  • Understanding the interplay of these expository factors is crucial for advancing psychiatric care.

Purpose of the Study:

  • To apply an agnostic clustering approach to identify exposome clusters, termed "Exposotypes (ETs)".
  • To examine the relationship between identified exposotypes and clinical, cognitive, and functional outcomes in individuals with psychotic disorders.
  • To elucidate the complex etiological interplay between trauma, substance use, and their effects on various outcomes.

Main Methods:

  • Utilized data from 1,350 individuals with psychotic disorders and 623 controls.
  • Employed an agnostic clustering approach to define exposotypes based on CHT, SU, and SES.
  • Assessed relationships between exposotypes and clinical symptoms, cognitive function, functional outcomes, intracranial volume, and schizophrenia polygenic risk scores.

Main Results:

  • Identified four exposotypes: ET1 (high CHT & SU), ET2 (high CHT), ET3 (high SU), and ET4 (low exposure).
  • ET1 showed increased positive/general symptoms, anxiety, depression, impulsivity, and mania; ET2 showed higher anxiety, depression, and impulsivity.
  • ET3 exhibited better cognitive/functional outcomes and lower negative symptoms; ET3 had the largest intracranial volume, ET2 the smallest. Age of onset was 5 years earlier in ET1 vs. ET4.

Conclusions:

  • Exposotypes provide a framework for understanding the etiological heterogeneity in psychotic disorders.
  • Specific combinations of childhood trauma and substance use uniquely influence clinical presentation, cognitive function, neurobiology, and age of onset.
  • Findings highlight the need for personalized approaches in psychiatry based on etiological profiles.