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Multivariate Resting-State Functional Connectivity Features Linked to Transdiagnostic Psychopathology in Early

Haley R Wang1, Zhen-Qi Liu2, Jason S Nomi3

  • 1Department of Psychology, University of California, Los Angeles, Los Angeles, California; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, California.

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|October 31, 2025
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Summary
This summary is machine-generated.

Early psychosis (EP) involves altered brain connectivity, particularly in sensory and subcortical networks. This study links these neural changes to cognitive inflexibility and arousal dysregulation, offering new insights into transdiagnostic symptoms in EP.

Keywords:
Clinical heterogeneityEarly psychosisNeuroimagingPsychopathologyResting-state functional connectivity

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Brain Imaging

Background:

  • Early psychosis (EP) exhibits neurobiological changes, including altered resting-state functional connectivity (RSFC).
  • Symptom and neural changes can overlap across EP diagnostic categories.
  • The link between RSFC patterns and transdiagnostic symptom dimensions in EP is not well understood.

Purpose of the Study:

  • To investigate the multivariate relationships between whole-brain RSFC and clinical symptoms in early psychosis patients.
  • To identify specific patterns of brain connectivity associated with transdiagnostic symptom dimensions.

Main Methods:

  • Partial Least Squares correlation analysis was used.
  • Examined whole-brain RSFC in 124 early psychosis patients (schizophrenia, schizoaffective disorder, psychotic mood disorder).
  • Assessed 41 clinical symptoms across positive, negative, general psychopathology, and manic dimensions.

Main Results:

  • A significant latent component explained 41.6% of the RSFC-symptom covariance.
  • Increased connectivity in sensory-motor, default mode, and subcortical networks (amygdala, thalamus) was observed.
  • Associated symptoms included cognitive rigidity and arousal dysregulation, not traditional positive/negative symptoms.

Conclusions:

  • Identified a transdiagnostic phenotype in EP characterized by cognitive inflexibility and arousal dysregulation.
  • This phenotype is linked to altered integration between sensory, default mode, and subcortical networks.
  • Suggests network-level functional connectivity patterns may inform targeted therapeutic approaches for EP.