Links of platelet glutamate and glutathione metabolism with attenuated positive and negative symptoms in depressed patients at clinical high risk for psychosis

Eur Arch Psychiatry Clin Neurosci. 2023 Feb;273(1):157-168. doi: 10.1007/s00406-022-01396-7. Epub 2022 Mar 15.

Abstract

Aim of the study is to reveal clinical and biological correlations in patients with adolescent depression and attenuated psychotic symptoms. Activity of platelet enzymes involved in glutamate-, glutathione- and energy metabolism was evaluated in control group and in the patients, because these systems are suspected as related to pathogenesis of psychosis. Adolescents (78 men, 16-25 years old) hospitalized with the first acute depressive state composed two groups: with prevalence of attenuated psychotic positive or negative symptoms (Gr1 and Gr2, 48 and 30 patients, respectively). Control group comprised 20 mentally healthy men of 19-25 years old. Gr1 differed significantly from Gr2 in scores by the Scale of Prodromal Symptoms (SOPS) for positive symptoms, p < 0.001, for disorganization symptoms, p < 0.003, and for total SOPS score, p < 0.001, before the treatment started. When patients from either Gr1 or Gr2 were compared with the control group, significantly decreased baseline activities of platelet glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione S-transferase (GST) were found (p < 0.0001). Different correlations were found between baseline enzymatic activities in Gr1 and Gr2: GDH activity correlated with GR activity in Gr1 (R = 0.37), and with GST activity in Gr2 (R = 0.70). Significant correlations were found only in Gr2 between the delta of scores by SOPS negative symptoms (SOPS-N) under treatment and baseline GDH, GST, and GR activities (R = - 0.36, R = - 0.60, and R = 0.38, respectively). The found correlations of the baseline enzymatic activity levels with the value of the decrease (delta) in SOPS-N scores under the treatment represent interest for the prediction of the pharmacotherapy efficiency.

Keywords: Adolescent-onset depression; Clinical high risk for psychosis; Glutamate dehydrogenase; Glutathione S-transferase; Glutathione reductase; Platelets.

MeSH terms

  • Adolescent
  • Adult
  • Antioxidants
  • Glutamic Acid*
  • Glutathione / metabolism
  • Glutathione Reductase / metabolism
  • Glutathione Transferase / metabolism
  • Humans
  • Male
  • Psychotic Disorders*
  • Young Adult

Substances

  • Glutamic Acid
  • Glutathione
  • Antioxidants
  • Glutathione Reductase
  • Glutathione Transferase