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.

Evaluation of mRNA expression level of the ATP synthase membrane subunit c locus 1 (ATP5G1) gene in patients with schizophrenia

“…The oxidative stress due to elevated ROS has been associated with schizophrenia and was related to deteriorating disease course and negative progression [ 31 ]. Additionally, amplified oxidative stress in patients with schizophrenia was related to the increased aggressiveness of the negative symptoms [ 32 ].…”

HSPB1 Gene Variants and Schizophrenia: A Case-Control Study in a Polish Population

“…The oxidative stress was reported to be higher in the SCZ patients, and the disruption in the oxidative balance was associated with the increased severity of negative symptoms [ 48 ]. Additionally, patients with the subtypes of SCZ who had predominantly negative symptoms exhibited a greater decrease in their glutathione levels compared to those with the other subtypes [ 49 ]. HSPB1 protects against oxidative stress by decreasing the reactive oxygen species by upholding the levels of glutathione in its reducing form [ 50 ].…”

Advantages and Limitations of Animal Schizophrenia Models

“…As mentioned above, pharmacologically induced NMDA receptor hypofunction leads to excessive extracellular GLU release, which causes excitotoxicity, leading to neuronal dysfunction, degeneration, and even neuronal death [ 131 , 132 ]. These effects may result in an increased cellular oxidative stress response [ 133 ], which is a widely studied feature of schizophrenia [ 134 , 135 ]. MK-801 has been shown to induce oxidative stress, including elevated MDA levels and altered antioxidant enzyme activity, in several brain regions in rodents, such as the prefrontal cortex, hippocampus, retrosplenial/posterior cingulate cortex [ 119 , 136 , 137 ], and cultured neurons and glial cells [ 138 , 139 ].…”