Oxidative injury and potential use of antioxidants in schizophrenia

https://doi.org/10.1016/S0952-3278(96)90144-1Get rights and content

Abstract

There is increasing evidence that oxidative injury contributes to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and CSF, and altered levels of both enzymatic and non-enzymatic antioxidants in chronic and drug-naive first-episode schizophrenic patients. The increased plasma lipid peroxidation is also supported by concomitant lower levels of esterified polyunsaturated essential fatty acids of red blood cell plasma membrane phospholipids. Because membrane phospholipids play a critical role in neuronal signal transduction, oxidative damage of these lipids may contribute to the proposed altered neurotransmitter receptor-mediated signal transduction and thereby alter information processing in schizophrenia. Adjunctive treatment with antioxidants (e.g. vitamins E and C, β-carotene and quinones) at the initial stages of illness may prevent further oxidative injury and thereby ameliorate and prevent further possible deterioration of associated neurological and behavioral deficits in schizophrenia.

References (117)

  • J.M.C Gutteridge

    The role of superoxide and hydroxyl radicals in phospholipid peroxidation catalysed by iron salts

    FEBS Lett

    (1982)
  • R.L Levine et al.

    Determination of carbonyl content in oxidatively modified proteins

    Methods Enzymol

    (1990)
  • R.G Allen et al.

    Oxidative influence on development and differentiation: an overview of a free radical theory of development

    Free Radical Biol Med

    (1989)
  • U Rafalowska et al.

    Peroxidation induced changes in synaptosomal transport of dopamine and - aminobutyric acid

    Free Radical Biol Medicine

    (1989)
  • H.S Pall et al.

    Evidence of enhanced lipid peroxidation in cerebrospinal fluid of patients taking phenothiazines

    Lancet

    (1987)
  • J.B Lohr et al.

    Increased indices of free radical activity in the cerebrospinal fluid of patients with tardive dyskinesia

    Biol Psychiatr

    (1990)
  • S.P Mahadik et al.

    Elevated levels of lipid peroxidation products in plasma from drug-naive patient at the onset of psychosis

    Schizophr Res

    (1995)
  • M.S Keshavan et al.

    Erythrocyte membrane phospholipids in psychotic patients

    Psychiatr Res

    (1993)
  • S.P Mahadik et al.

    Distribution of plasma membrane phospholipids and cholesterol in skin fibroblasts from drug-naive patients at the onset of psychosis

    Schizophr Res

    (1994)
  • K.S Vaddadi et al.

    A double-blind trial of essential fatty acid supplementation in patients with tardive dyskinesia

    Psychiatr

    (1989)
  • A.I.M Glen et al.

    A red cell membrane abnormality in a subgroup of schizophrenic patients: Evidence for two diseases

    Schizophr Res

    (1994)
  • S Mukherjee et al.

    Membrane fatty acid composition of fibroblasts from schizophrenic patients

    Biol Psychiatr

    (1994)
  • J.K Yao et al.

    Red blood cell membrane dynamics in schizophrenia. II. Fatty acid composition

    Schizophr Res

    (1994)
  • D.F Horrobin et al.

    Fatty acid levels in brains of schizophrenics and normal controls

    Biol Psychiatr

    (1991)
  • J.B Lohr et al.

    Alpha-tocopherol in tardive dyskinesia

    Lancet

    (1987)
  • R Reddy et al.

    Enzymes of the antioxidant defense system in chronic schizophrenic patients

    Biol Psychiatr

    (1991)
  • T.D Buckman et al.

    Glutathione peroxidase and CT scan abnormalities in schizophrenia

    Biol Psychiatr

    (1987)
  • T.D Buckman et al.

    Platelet glutathione peroxidase and monoamine oxidase activity in schizophrenics with CT scan abnormalities: relation to psychosocial variables

    Psych Res

    (1990)
  • L Szabo et al.

    Effects of neuroleptics on lipid peroxidation and peroxide metabolism enzyme activities in various discrete areas of the brain

    Chem Pharmacol

    (1983)
  • R.A Shepherd et al.

    Cell cycle characteristics after ionising radiation induced DNA damage in schizophrenia

    Biol Psychiatr

    (1993)
  • S.P Mahadik et al.

    Abnormal growth and morphology of fibroblasts from schizophrenic patients

    Psychiatr Res

    (1991)
  • S Mukherjee et al.

    Abnormal growth of cultured skin fibroblasts associated with poor premorbid history in schizophrenic patients

    Schizophr Res

    (1994)
  • R Freedman et al.

    Initial studies of embryonic transplants of human hippocampus and cerebral cortex derived from schizophrenic women

    Biol Psychiatr

    (1992)
  • H Kaiya et al.

    Accumulation of diacylglycerol in platelet phosphoinositide turnover in schizophrenia: A biological marker of good prognosis?

    Biol Psychiatr

    (1989)
  • M.A Essali et al.

    The platelet polyphopshoinositide system in schizophrenia: The effects of neuroleptic treatment

    Biol Psychiatr

    (1990)
  • J.K Yao et al.

    Increased turnover of of platelet phosphatidylinositol in schizophrenia

    Prostaglandins Leukot Essent Fatty Acids

    (1992)
  • J Chang et al.

    Phospholipase A2: function and pharmacological regulation

    Biochem Pharmacol

    (1987)
  • G.W Burton et al.

    Mechanisms of antioxidant action: preventive and chain-breaking antioxidants

  • I Fridovich

    Superoxide dismutase

    Annu Rev Biochem

    (1975)
  • I Fridovich

    Superoxide radical: an endogenous toxicant

    Annu Rev Pharmacol

    (1983)
  • B Halliwell

    Reactive oxygen species and the central nervous system

    J Neurochem

    (1992)
  • B Halliwell et al.

    Oxygen toxicity, oxygen radicals, transition metals and disease

    Biochem J

    (1984)
  • S.P Wolff et al.

    Fragmentation of proteins by free radicals and its effect on their susceptibility to enzymic hydrolysis

    Biochem J

    (1986)
  • E.R Stadtman

    Protein oxidation and aging

    Science

    (1992)
  • J.M.C Gutteridge

    Lipid peroxidation: some problems and concepts

  • A.C Mellow-Filho et al.

    In vivo formation of single strand breaks in DNA by hydrogen peroxide is mediated by the Haber-Weiss reaction

    Biochim Biophys Acta

    (1984)
  • J.L Cadet et al.

    Free radicals and the developmental pathobiology of schizophrenic burnout

    Integr Psychiatr

    (1987)
  • H Nohl et al.

    Influence of mitochondrial radical formation of energy-linked respiration

    Eur J Biochem

    (1978)
  • R Fried et al.

    Superoxide dismutase of mammalian nervous system

    J Neurochem

    (1975)
  • D.C Borg et al.

    Iron and iron-derived radicals

  • Cited by (0)

    View full text