GABA levels and TSPO expression in people at clinical high risk for psychosis and healthy volunteers: a PET-MRS study

J Psychiatry Neurosci. 2019 Mar 1;44(2):111-119. doi: 10.1503/jpn.170201.

Abstract

Background: γ-Aminobutyric acidergic (GABAergic) dysfunction and immune activation have been implicated in the pathophysiology of schizophrenia. Preclinical evidence suggests that inflammation-related abnormalities may contribute to GABAergic alterations in the brain, but this has never been investigated in vivo in humans. In this multimodal imaging study, we quantified cerebral GABA plus macromolecule (GABA+) levels in antipsychotic-naive people at clinical high risk for psychosis and in healthy volunteers. We investigated for the first time the association between GABA+ levels and expression of translocator protein 18 kDa (TSPO; a marker of microglial activation) using positron emission tomography (PET).

Methods: Thirty-five people at clinical high risk for psychosis and 18 healthy volunteers underwent 3 T proton magnetic resonance spectroscopy to obtain GABA+ levels in the medial prefrontal cortex (mPFC). A subset (29 people at clinical high risk for psychosis and 15 healthy volunteers) also underwent a high-resolution [18F]FEPPA PET scan to quantify TSPO expression. Each participant was genotyped for the TSPO rs6971 polymorphism.

Results: We found that GABA+ levels were significantly associated with TSPO expression in the mPFC (F1,40 = 10.45, p = 0.002). We found no significant differences in GABA+ levels in the mPFC (F1,51 = 0.00, p > 0.99) between people at clinical high risk for psychosis and healthy volunteers. We found no significant correlations between GABA+ levels or residuals of the association with TSPO expression and the severity of prodromal symptoms or cognition.

Limitations: Given the cross-sectional nature of this study, we could determine no cause-and-effect relationships for GABA alterations and TSPO expression.

Conclusion: Our findings suggest that TSPO expression is negatively associated with GABA+ levels in the prefrontal cortex, independent of disease status.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anilides
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Multimodal Imaging
  • Positron-Emission Tomography / methods*
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / metabolism*
  • Prodromal Symptoms*
  • Proton Magnetic Resonance Spectroscopy / methods*
  • Psychotic Disorders / metabolism*
  • Pyridines
  • Receptors, GABA / genetics
  • Receptors, GABA / metabolism*
  • Risk
  • Young Adult
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Anilides
  • N-(2-((N-(4-phenoxypyridin-3-yl)acetamido)methyl)phenoxy)ethyl fluoride
  • Pyridines
  • Receptors, GABA
  • TSPO protein, human
  • gamma-Aminobutyric Acid