Analysis of two polymorphisms of the manganese superoxide dismutase gene (Ile-58Thr and Ala-9Val) in patients with recurrent depressive disorder Piotr Gałecki a, ⁎, Janusz Śmigielski b , Antoni Florkowski a , Kinga Bobińska a , Tadeusz Pietras c , Janusz Szemraj d a Department of Adult Psychiatry, Medical University of Lodz, Aleksandrowska 159 st., 91-229 Lodz, Poland b Department of Informatics and Medical Statistics, Medical University of Lodz, Lodz, Poland c Department of Pneumology and Allergy, Medical University of Lodz, Lodz, Poland d Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland abstract article info Article history: Received 25 February 2009 Received in revised form 13 June 2009 Accepted 25 June 2009 Keywords: Depression Manganese superoxide dismutase Gene polymorphism Reactive oxygen species Mitochondria Antioxidant enzymes Reactive oxygen species (ROS) may contribute to the pathogenesis of depressive disorder (DD). Functional genetic polymorphisms of manganese superoxide dismutase (MnSOD) are candidates for DD susceptibility. The study examined the relationship between MnSOD gene polymorphisms (Ala-9Val, Ile-58Thr) and DD in the Polish population. The association study was conducted in a case–control design in DD patients (n = 149) and healthy controls (CG; n =149) by genotyping. Assessment of Ala-9Val genotype distribution and disease odds ratio demonstrated a statistically significant difference between the compared groups only in the female subgroup. The obtained results suggest a role of the MnSOD polymorphism in the development and course of depression. © 2009 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Reports published in the last decade indicate abnormalities of oxidative processes in patients with severe depression episodes in the course of recurrent depressive disorder (DD) (Peet et al., 1998; Harrison, 2002; Lukash et al., 2002; Michel et al., 2007; Wei et al., 2009a,b). In particular, it should be emphasized that studies of animal depression models have demonstrated increased production of re- active oxygen species (ROS) such as superoxide anion radical (O 2 .- ) in cellular mitochondria of such cerebral structures as the hippocam- pus, prefrontal cortex, and cortex (Lucca et al., 2009a). Additionally, changes in superoxide dismutase (SOD) activity have been observed in the above-mentioned brain areas (Lucca et al., 2009b). Increased production of ROS leads to damage of lipid, protein, amino acid, and nucleic acid molecules, as well as disturbances of cellular function and integrity, and, consequently, to cell death (Valko et al., 2007). Brain cells are sensitive to oxidative stress (Halliwell, 1992) and there is evidence for ROS-mediated brain cell damage (Wei et al., 2009b). It is well known that hippocampus pyramidal neurons in CA1 (Sommer sector) and CA4 areas (Bratz sector), cells of the dorsolateral striatum, and neurons in the III and V neocortical layers belong to the vulnerable brain regions. Additionally, Campbell et al. (2004) have reported reduced hippocampus and prefrontal cortex volumes in depressive patients. Autopsy data indicate a significant reduction of glial cell number and density in these regions, as well as subtle changes in the number and density of neurons (Rajkowska et al., 1999; Bowley et al., 2002; Cotter et al., 2002; Harrison, 2002). The reason for development of these changes has not been elucidated so far. They may result from degeneration of neural cells, as well as from inhibition of neurogen- esis. Both these processes are affected negatively by ROS (Ekdahl et al., 2003; Trushina and McMurray, 2007). The enzymes involved in first-line defence against ROS include SOD, which is an enzyme catalyzing dismutation of O 2 - to hydrogen peroxide (H 2 O 2 )(Fridovich, 1974). Manganese superoxide dismutase (MnSOD/SOD2) occurring in the mitochondrial matrix is responsible for cell protection against O 2 .- , generated in mitochondrial energetic metabolism (Halliwell, 1992; Robinson, 1998). MnSOD activity is induced and regulated by the amount of ROS (Visner et al., 1990; Warner et al., 1996). MnSOD is an enzyme encoded by nuclear DNA, but its biological activity is localized in mitochondria, where it is transported after translation process (Church et al., 1992). Therefore, a change in MnSOD activity in mitochondria are likely to cause some disturbances associated with dysfunction of the mechanisms for which mitochondria are responsible. SOD plays a key role among antioxidant enzymes protecting the brain against ROS. SOD is also involved in neurodevelopment, primarily Psychiatry Research 179 (2010) 43–46 ⁎ Corresponding author. Tel.: +48 42 652 12 89; fax: +48 42 640 50 58. E-mail address: galeckipiotr@wp.pl (P. Gałecki). 0165-1781/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2009.06.016 Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres