Association of oxidative stress to the genesis of anxiety: implications for possible therapeutic interventions

Abstract

Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions (e.g., iron [Fe] and copper [Cu]), is an underlying cause of various neurodegenerative diseases. These reactive species are an inevitable by-product of cellular respiration or other metabolic processes that may cause the oxidation of lipids, nucleic acids, and proteins. Oxidative stress has recently been implicated in depression and anxiety-related disorders. Furthermore, the manifestation of anxiety in numerous psychiatric disorders, such as generalized anxiety disorder, depressive disorder, panic disorder, phobia, obsessive-compulsive disorder, and posttraumatic stress disorder, highlights the importance of studying the underlying biology of these disorders to gain a better understanding of the disease and to identify common biomarkers for these disorders. Most recently, the expression of glutathione reductase 1 and glyoxalase 1, which are genes involved in antioxidative metabolism, were reported to be correlated with anxiety-related phenotypes. This review focuses on direct and indirect evidence of the potential involvement of oxidative stress in the genesis of anxiety and discusses different opinions that exist in this field. Antioxidant therapeutic strategies are also discussed, highlighting the importance of oxidative stress in the etiology, incidence, progression, and prevention of psychiatric disorders.

Keywords: Antioxidant therapy; anxiety disorders; oxidative stress; toxicity..

Scheme. (1)

Free radical production and toxic effects. AD, anxiety disorders; Au, autism; Dep, depression; DNA Mut, DNA mutation; LPO, lipid peroxidation; Mit Dys, mitochondrial dysfunction; Neu/Glia Act, neuronal or glial activation; OCD, obsessive-compulsive disorder; Oth, other disorders; Pa.D, Parkinson’s disease; PCO, protein carbonylation; PD, panic disorder; RNS, reactive nitrogen species; ROS, reactive oxygen species; Sch, schizophrenia; SP, social phobia.

Scheme. (2)

Various aspects of MG interactions. AOT, antioxidant therapy; CAT, catalase; GABA, γ-aminobutyric acid; Glut, glutamate; GPx, glutathione peroxidase; GSR, glutathione reductase. GR = glucocorticoid receptor; GSH, glutathione; GSSG, oxidized glutathione; GST, glutathione S-transferase; MG, methylglyoxal; NADP-H, nicotinamide adenine dinucleotide phosphate; NADP+, nicotinamide adenine dinucleotide phosphate, reduced; NMDA, N-methyl-D-aspartate; OS, oxidative stress; Sero, serotonin; SOD, superoxide dismutase; Trx-R, thioredoxin reductase.

Scheme. (3)

Toxicology and pharmacology of organoselenium compounds. PPARγ, peroxisome proliferator-activated receptor γ.