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Neural variability in three major psychiatric disorders.

Wei Wei1,2,3, Lihong Deng4, Chunxia Qiao4

  • 1Affiliated Mental Health Center & Hangzhou Seventh People's Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310013, China.

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Neural variability at rest shows shared disruptions across major psychiatric disorders (MPDs). These patterns link to gene expression and neurotransmitter profiles, suggesting a transdiagnostic biomarker for MPDs.

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Genetics

Background:

  • Major psychiatric disorders (MPDs) are suspected to share disruptions in brain physiology.
  • Neural variability, a marker of brain function, is a potential transdiagnostic indicator.

Purpose of the Study:

  • To investigate neural variability at rest across MPDs.
  • To explore the genetic and neurochemical underpinnings of disrupted neural variability.

Main Methods:

  • Resting-state fMRI was used to measure standard deviation of the BOLD signal (SDBOLD) in 219 controls and 279 patients (schizophrenia, major depressive disorder, bipolar disorder).
  • Partial least-squares correlation analyzed transdiagnostic SDBOLD patterns, clinical symptoms, and cognitive functions.
  • Spatial correlations were computed between SDBOLD patterns and postmortem gene expression, cognitive functions, and neurotransmitter receptor profiles.

Main Results:

  • Two transdiagnostic patterns of disrupted SDBOLD were identified.
  • Pattern 1, present in all groups (most in schizophrenia), showed higher SDBOLD in language/auditory networks and lower in default mode/sensorimotor networks, correlating with clinical and cognitive deficits.
  • Pattern 2, specific to depression, showed higher SDBOLD in default mode/salience networks and lower in sensorimotor networks.
  • Both patterns exhibited distinct spatial correlations with gene expression, cognitive functions, and neurotransmitter receptor profiles.

Conclusions:

  • Neural variability at rest is a potential transdiagnostic biomarker for MPDs.
  • Gene expression and neurotransmitter receptor profiles significantly explain the spatial distribution of neural variability disruptions.
  • Aberrant neural variability patterns contribute to the diverse pathophysiology and clinical-cognitive profiles observed in MPDs.