Short communication Increased oxidative stress and DNA damage in bipolar disorder: A twin-case report Benício N. Frey a,b , Ana C. Andreazza a,b , Maurício Kunz b , Fabiano A. Gomes b , João Quevedo c , Mirian Salvador d , Carlos Alberto Gonçalves a , Flávio Kapczinski b, ⁎ a Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul. Rua Ramiro Barcelos, 2600/Anexo. Zip code: 90035-003. Porto Alegre, RS, Brazil b Bipolar Disorders Program, Centro de Pesquisas, Hospital de Clínicas de Porto Alegre. Rua Ramiro Barcelos, 2350. Zip code: 90035-003. Porto Alegre, RS, Brazil c Laboratório de Neurociências, Universidade do Extremo Sul Catarinense. Av. Universitária, 1105. Zip code: 88806-000. Criciúma, SC, Brazil d Instituto de Biotecnologia, Universidade de Caxias do Sul. Rua Francisco Getúlio Vargas, 1130. Zip code: 95070-560. Caxias do Sul, RS, Brazil Received 10 May 2006; received in revised form 8 June 2006; accepted 13 June 2006 Available online 20 July 2006 Abstract Objective: There is an emerging body of data suggesting that oxidative stress may be associated with the pathophysiology of bipolar disorder (BD). In the present study we investigated the oxidative stress profile in two monozygotic twins during a manic episode. Methods: Two monozygotic twins diagnosed as currently manic by the Structured Clinical Interview for DSM-IV were studied. Serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and catalase (CAT) were measured as parameters of oxidative stress. DNA damage was assessed using the single cell gel electrophoresis technique (Comet Assay). All biochemical measures were conducted at baseline and after a 6-week treatment. Results: Bipolar twins had higher TBARS, SOD and DNA damage, and lower CAT than the healthy control. TBARS and SOD were normalized after mood stabilization, whereas CAT and DNA damage remained altered at week 6. Conclusions: These findings support that oxidative stress may play a role in the pathophysiology of BD and that pharmacological treatment may exert antioxidant effects. Studies with larger samples are warranted to further clarify this issue. © 2006 Elsevier Inc. All rights reserved. Keywords: Bipolar disorder; DNA damage; Oxidative stress; Pathophysiology 1. Introduction Studies have consistently reported increased lipid peroxidation and changes in the major antioxidant enzymes in individuals with bipolar disorder (BD) (Ozcan et al., 2004; Ranjekar et al., 2003; Kuloglu et al., 2002), suggesting that oxidative stress may play a role in the pathophysiology of BD. The excessive generation of reactive oxygen species, such as hydroxyl radicals, can lead to lipid and protein oxidation, with consequent membrane and DNA dam- age. Moreover, there is recent evidence that the mood stabilizing agents lithium and valproate exert robust antioxidant effects in vitro (Shao et al., 2005). We have recently demonstrated that BD subjects have increased DNA damage, possibly due to increased oxidative stress (Andreazza et al., in press). As an extension of this latter study, we prospectively investigated the oxidative stress profile and DNA damage in two medication-free monozygotic twins during a manic episode. Because genetic inheritance increases the risk for the development of BD, we hypothesized that the BD twins would present increased oxidative stress and DNA damage and these changes would be reversed after mood stabilization. 2. Case report Two identical female twins, 59 years old, were assessed. One subject (patient 1) was admitted in the hospital for inpatient treatment, while the other (patient 2) refused treatment. The Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 283 – 285 www.elsevier.com/locate/pnpbp Abbreviations: BD, bipolar disorder; CAT, catalase; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition; SOD, superoxide dismutase; TBARS, thiobarbituric acid reactive substances. ⁎ Corresponding author. Tel.: +55 51 32227309; fax: +55 51 21018846. E-mail address: kapcz@terra.com.br (F. Kapczinski). 0278-5846/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.06.011