Oxidative Stress and the Pathophysiology and Symptom Profile of Schizophrenia Spectrum Disorders

Abstract

Schizophrenia is associated with increased levels of oxidative stress, as reflected by an increase in the concentrations of damaging reactive species and a reduction in anti-oxidant defences to combat them. Evidence has suggested that whilst not the likely primary cause of schizophrenia, increased oxidative stress may contribute to declining course and poor outcomes associated with schizophrenia. Here we discuss how oxidative stress may be implicated in the aetiology of schizophrenia and examine how current understanding relates associations with symptoms, potentially via lipid peroxidation induced neuronal damage. We argue that oxidative stress may be a good target for future pharmacotherapy in schizophrenia and suggest a multi-step model of illness progression with oxidative stress involved at each stage.

Keywords: antio×idants; dopamine; glutamate; inflammation; oxidative stress; psychosis symptoms; schizophrenia.

Figure 1

Interactions between GABAergic disinhibition of glutamatergic neurons and subsequent stimulation of midbrain dopaminergic neurons. NMDAR, N-methyl-D-aspartate receptor; GABA, Gamma-Aminobutyric acid; Glu, Glutamate; DA, Dopamine.

Figure 2

The cyclical nature of schizophrenia progression from maternal pro-inflammatory state to behavioural phenotype.