Altered phospholipid metabolism in schizophrenia: a phosphorus 31 nuclear magnetic resonance spectroscopy study

Psychiatry Res. 2013 Dec 30;214(3):365-73. doi: 10.1016/j.pscychresns.2013.06.011. Epub 2013 Sep 14.

Abstract

Phospholipid (PL) metabolism is investigated by in vivo 31P magnetic resonance spectroscopy (MRS). Inconsistent alterations of phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) have been described in schizophrenia, which might be overcome by specific editing techniques. The selective refocused insensitive nuclei-enhanced polarization transfer (RINEPT) technique was applied in a cross-sectional study involving 11 schizophrenia spectrum disorder patients (SZP) on stable antipsychotic monotherapy and 15 matched control subjects. Metabolite signals were found to be modulated by cerebrospinal fluid (CSF) content and gray matter/brain matter ratio. Corrected metabolite concentrations of PC, GPC and PE differed between patients and controls in both subcortical and cortical regions, whereas antipsychotic medication exerted only small effects. Significant correlations were found between the severity of clinical symptoms and the assessed signals. In particular, psychotic symptoms correlated with PC levels in the cerebral cortex, depression with PC levels in the cerebellum and executive functioning with GPC in the insular and temporal cortices. In conclusion, after controlling for age and tissue composition, this investigation revealed alterations of metabolite levels in SZP and correlations with clinical properties. RINEPT 31P MRS should also be applied to at-risk-mental-state patients as well as drug-naïve and chronically treated schizophrenic patients in order to enhance the understanding of longitudinal alterations of PL metabolism in schizophrenia.

Keywords: 4th edition; AMARES; ARMS; ATP; BGL; BGM; BM; BPRS; BS; CB; CC; CCTCC; CDSS; CP; CPZ; CSF; CSI; Calgary depression scale for schizophrenia; Cerebellum; D-CSI; DSM-IVR; FC; FEP; GAF; GLM; GM; GPC; GPE; HC; HI; HMPT; IC; Java based magnetic resonance user interface; MWT-B; Magnetic resonance spectroscopy; Mehrfachwahl–Wortschatz–Intelligenztest, version B; PANSS; PC; PDE; PE; PL; PME; Phosphocholine; Phospholipids; Pi; Positive and Negative Syndrome Scale; RINEPT; ROI; SANS; SPM5; SPSS; SZP; Scale for the Assessment of Negative Symptoms; Schizophrenia; Statistical Package for the Social Sciences; TC; VBR; WCST; WM; Wisconsin Card Sorting Test; adenosine triphosphate; advanced method for accurate, robust and efficient signal fitting; at-risk mental state for psychosis; basal ganglia, lateral part; brain matter; brainstem; brief psychiatric rating scale; cerebellum; cerebrospinal fluid; chemical shift imaging; chlorpromazine; cingulate cortex; circular-polarized volume head coil; cortical-cerebellar-thalamic-cortical circuit; diagnostic and statistical manual; first-episode patients; frontal cortex; general linear model; global assessment of functioning; glycerophosphocholine; glycerophosphoethanolamine; gray matter; healthy control; hexamethyl-phosphorous triamide; hippocampus; inorganic phosphate; insular cortex; jMRUI AMARES; phosphocholine; phosphodiester; phosphoethanolamine; phospholipid; phosphomonoester; refocused insensitive nucleus enhancement by polarization transfer; region of interest; revised version; schizophrenia spectrum disorder patients; statistical parametrical mapping, version 5; temporal cortex; thalamus and medial part of basal ganglia; three dimensional chemical shift imaging; ventricle to brain-ratio; white matter.

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use
  • Brain / metabolism*
  • Case-Control Studies
  • Cerebellum / metabolism
  • Cerebral Cortex / metabolism
  • Cross-Sectional Studies
  • Ethanolamines / metabolism
  • Female
  • Glycerylphosphorylcholine / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Nerve Fibers, Unmyelinated / metabolism
  • Phosphatidylethanolamines / metabolism
  • Phospholipids / metabolism*
  • Phosphorus Isotopes
  • Phosphorylcholine / metabolism
  • Schizophrenia / cerebrospinal fluid
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*

Substances

  • Antipsychotic Agents
  • Ethanolamines
  • Phosphatidylethanolamines
  • Phospholipids
  • Phosphorus Isotopes
  • Phosphorylcholine
  • glycerophosphoethanolamine
  • Glycerylphosphorylcholine
  • phosphorylethanolamine