Neurometabolic abnormalities in the associative striatum in antipsychotic-naïve first episode psychosis patients

Psychiatry Res Neuroimaging. 2018 Nov 30;281:101-106. doi: 10.1016/j.pscychresns.2018.06.003. Epub 2018 Jun 9.

Abstract

Schizophrenia is a chronic, often progressive, disorder. Understanding the underlying neurobiology present in the early stages of the illness is as a pivotal step in designing targeted interventions aimed at arresting disease progression. The aim of our study was to examine neurometabolic changes in the dopamine rich associative striatum in medication-naïve first episode psychosis (FEP). We quantified neurometabolites in 14 FEP and 18 healthy controls (HC) matched on key demographic characteristics. Spectra from the voxel in the left associative striatum were acquired using a PRESS sequence (TR/TE = 2000/80 ms; 512 averages). MRS data were quantified in the time domain with AMARES in jMRUI. Choline was significantly elevated in FEP compared to HC. No significant alterations in other metabolites were observed. We did not observe correlations between metabolite levels and clinical characteristics in FEP. Here, we demonstrated elevated choline and a disruption of the relationship between N-acetyl-aspartate and Glx (glutamate + glutamine) in medication-naïve FEP patients in the left striatum indicating possible mitochondrial, membrane and glial dysfunction as an underlying pathological phenomenon. In addition, striatal choline shows promise as a biomarker for FEP that may have utility in clinical trials investigating target engagement in experimental regimens.

Trial registration: ClinicalTrials.gov NCT02034253.

Keywords: Antipsychotic; Choline; Glutamate; Magnetic resonance spectroscopy; Striatum.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Biomarkers / metabolism
  • Case-Control Studies
  • Choline / metabolism*
  • Corpus Striatum / metabolism*
  • Disease Progression
  • Dopamine / metabolism
  • Female
  • Glutamic Acid / metabolism
  • Humans
  • Male
  • Middle Aged
  • Proton Magnetic Resonance Spectroscopy
  • Psychotic Disorders / metabolism*
  • Schizophrenia / metabolism*
  • Young Adult

Substances

  • Biomarkers
  • Aspartic Acid
  • Glutamic Acid
  • N-acetylaspartate
  • Choline
  • Dopamine

Associated data

  • ClinicalTrials.gov/NCT02034253