Editorial Oxidative stress and therapeutic implications in psychiatric disorders Xiang Yang Zhang a, b, c, ⁎, Jeffrey K. Yao d, e, f a Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA b Michael E. DeBakey VA Medical Center, Houston, TX, USA c Psychiatry Research Center, Beijing Hui Long Guan Hospital, Peking University, Beijing, China d Medical Research Service, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA e Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA f Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA abstract article info Article history: Received 15 March 2013 Accepted 15 March 2013 Available online xxxx Keywords: Antioxidant defense system Antioxidant therapy Bipolar disorders Major depression Schizophrenia Tardive dyskinesia Increasing evidence indicates that disturbances of antioxidant defense system and presence of oxidative stress can play a part in a wide range of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and major depression, as well as antipsychotic-induced tardive dyskinesia (TD). Moreover, researchers have embarked on using antioxidant treatment as adjunct therapy for psychiatry disorders. Evidence from clinical, pre-clinical and epidemiological studies suggests that a benefit of using antioxidant compounds should be considered as an adjunctive therapy in these patients. These are some of the main perspectives that are reviewed by four articles in this special section. Overall, there has been growing recognition of the impor- tance of oxidative stress in the pathophysiology of psychiatric disorders and the development of TD. The collection of articles in this special section will contribute to providing more efficacious treatments arising from a better appreciation of the roles of oxidative stress in these psychiatric disorders. © 2013 Elsevier Inc. All rights reserved. Because of etiopathogenetic heterogeneity, extensive findings from biological, neurochemical, and neuroimaging studies have not provided conclusive evidence for any specific etiologic theory of neuropsychiatric disorders such as schizophrenia, bipolar disorder, and major depression. The vast majority of research on this area has thus far focused on the monoamine neurotransmitter system. How- ever, increasing evidence indicates that disturbances of antioxidant defense system and presence of oxidative stress may play a role in the biochemical mechanisms underlying these disorders (Maes et al., 2011; Marazziti et al., 2012; Yao and Keshavan, 2011) as well as antipsychotic-induced tardive dyskinesia (Elkashef and Wyatt, 1999; Lohr et al., 2003). It is likely that there exists a point of convergence for many of these theoretical models, one that occurs at the level of the neuronal membrane, which is the site of neurotransmitter recep- tors, ion channels, signal transduction, and drug effects (Mahadik and Yao, 2006; Skosnik and Yao, 2003). The membrane is a complex structure, composed primarily of phospholipids and their constituent fatty acids, that provides scaffolding for many key functions in mem- brane, which is also a point of a natural intersection between genetic and environmental factors (Horrobin et al., 1995). Membrane defects, such as those induced by decreased arachidonic acid in phospholipids (Skosnik and Yao, 2003), can significantly alter a broad range of membrane functions, and ipso facto behavior through multiple “down- stream” effects. Therefore, alterations in key neurotransmitters can both be modified by and contribute to oxidative stress and membrane dysfunction. Moreover, evidence from clinical, pre-clinical and epide- miological studies suggests that novel therapeutic strategies such as supplementation with antioxidants, ω-3 fatty acids or combination of both might improve the neuroplasticity and can be effective for long-term treatment management of neuropsychiatric disorders (Pillai and Yao, in press; Yao et al., in press). The collection of review articles in this special section provides updates in a link among oxidative stress, membrane dysfunction, and multi-neurotransmitter pathologies, as well as therapeutic implications in schizophrenia (papers by Wu et al., this issue and Pandya et al., this issue), bipolar disorders (paper by Pandya et al., this issue), depression (papers by Pae, et al. and by Pandya et al., this issue), and tardive dyskinesia (paper by Cho and Lee, this issue). Biological systems have evolved complex protective strategies against free radical toxicity. Under physiological conditions the potential for free radical-mediated damage is kept in check by the antioxidant defense system (AODS), which is comprised of a series of enzymatic and non-enzymatic components (Yao and Keshavan, Progress in Neuro-Psychopharmacology & Biological Psychiatry xxx (2013) xxx–xxx Abbreviations: AODS, Antioxidant defense system; BPRS, Brief Psychiatric Rating Scale; CAT, Catalase; DHA, Dehydroascorbic acid; EPA, Eicosapentaenoic acid; GSH, Glutathione; GSHPx, Glutathione peroxidase; GST, glutathione S-transferases; NAC, N-acetyl-cysteine; NADPH, reduced Nicotinamide adenine dinucleotide phosphate; NO, Nitric oxide; PANSS, Positive and Negative Syndrome Scale; ROS, Reactive oxygen species; SOD, Superoxide dismutase; RNS, Reactive nitrogen species; TD, Tardive dyskinesia. ⁎ Corresponding author at: Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas, USA. Tel.: +1 7137911414x5824; fax: +1 713 794 7938. E-mail address: xyzhang@bcm.edu (X.Y. Zhang). PNP-08359; No of Pages 3 0278-5846/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pnpbp.2013.03.003 Contents lists available at SciVerse ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp Please cite this article as: Zhang XY, Yao JK, Oxidative stress and therapeutic implications in psychiatric disorders, Prog Neuro-Psychopharmacol Biol Psychiatry (2013), http://dx.doi.org/10.1016/j.pnpbp.2013.03.003