Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment H. Serdar Gergerlioglu ⁎ , Haluk A. Savas, Feridun Bulbul, Salih Selek, Efkan Uz, Mehmet Yumru Department of Physiology, Meram Faculty of Medicine, Selcuk University 42080, Konya, Turkey Received 3 September 2006; received in revised form 21 December 2006; accepted 30 December 2006 Available online 12 January 2007 Abstract Oxidant nitric oxide (NO) and antioxidant superoxide dismutase (SOD) have been implicated to play a role in the pathogenesis of bipolar disorders. This is the first prospective study aimed to evaluate NO levels and SOD activity in bipolar disorder (type I manic episode) (BD-ME). 29 inpatient subjects with BD-ME and 30 healthy controls were included. Serum NO levels and SOD activity have been studied at 1st (NO [1st] and SOD [1st] respectively) and 30th days (NO [30th] and SOD [30th] respectively) after treatment. The clinical outcome was measured by Bech- Rafaelson Mania Scale (BRMS). The mean NO [1st] ( p b .001) and NO [30th] levels ( p b .001) were higher than controls, but SOD [1st] ( p b .001) and SOD [30th] ( p b .001) activities in BD-ME were lower than controls. SOD 1 activity was higher than SOD [30th] ( p b .001), while there was no significance in comparison between NO [1st] and NO [30th] ( p N .05). SOD [30th] activity is negatively correlated with the number of previous manic attacks and NO [1st] was negatively correlated with sleep item score of BRMS at first day. Also there was a significant correlation between NO [1st] levels and with the existence of a delusion. NO and SOD appear to play a role in the pathophysiological events occurring in BD, especially in BD-ME. This study for the first time showed the possible role of NO on sleep and the generation of delusions in the pathophysiology of BD. In the light of literature, induced glutamate pathway might be responsible for delusions in BD. The results of this research need further investigation to understand the oxidative vs antioxidative process in BD. © 2007 Elsevier Inc. All rights reserved. Keywords: Antimanic treatment; Antioxidant; Bipolar disorder; Delusion; Nitric oxide; Oxidant; Sleep; Superoxide dismutase 1. Introduction Bipolar disorders (BD) are common, recurrent and disabling entities in the etiopathogenesis of which psychosocial, genetic, and biochemical factors are involved. There are recent bio- logical studies focused on BD. The hot points for new re- searches are neuroimaging, genetics, and biochemistry. There is an enormous amount of convincing data indicating that free radicals are involved in the beginning and development of the disease. Predominantly nitric oxide (NO), superoxide and hydroxyl radicals are generated in physiological processes but a big portion of those radicals are inactivated by antioxidant enzyme systems (Mahadik and Mukherjee, 1996). Oxidative and antioxidative molecules have been studied in many psychiatric disorders (Moncada et al., 1991; Akyol et al. 2004). Oxidant NO, and antioxidant superoxide dismutase (SOD) have been implicated to play a role in the pathogenesis of BD (Savas et al., 2002, 2006). NO is a soluble gas produced by the activity of an enzyme and is known to be both free oxygen radical and described as an atypical neurotransmitter or a secondary messenger (Schulman, 1997) in the central and peripheral nervous system. It has been implicated in a number of physiological functions such as noradrenalin and dopamine release, memory and learning, regulation of the cerebrovascular system, modulation of wake- fulness, modulation of nociception, olfaction, food intake and drinking, and certain pathologies like Alzheimer's and Hun- tington's diseases. The involvement of NO in depression is also proposed (Papageorgiou et al., 2001). There are studies in which the role of NO was investigated in the etiology and pathophysiology of BD during acute mania Progress in Neuro-Psychopharmacology & Biological Psychiatry 31 (2007) 697 – 702 www.elsevier.com/locate/pnpbp ⁎ Corresponding author. Tel.: +90 505 6890834; fax: +1 90 332 2237124. E-mail addresses: serdar@gergerlioglu.com, gergerlioglu@gmail.com (H.S. Gergerlioglu). 0278-5846/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2006.12.020