Research report Altered expression of lipid metabolism and immune response genes in the frontal cortex of suicide completers Aleksandra Lalovic a , Tim Klempan a , Adolfo Sequeira a , Giamal Luheshi b , Gustavo Turecki a, ⁎ a McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, 6875 LaSalle Blvd., Verdun, Québec, Canada H4H 1R3 b Douglas Mental Health University Institute, McGill University, 6875 LaSalle Blvd., Verdun, Québec, Canada H4H 1R3 article info abstract Article history: Received 9 February 2009 Received in revised form 31 March 2009 Accepted 7 April 2009 Available online 13 May 2009 Background: Studies investigating the association between low cholesterol and suicidality have generated a range of ideas about how cholesterol might play a role in influencing suicide risk, extending studies to other aspects of lipid metabolism, as well as immune response, in relation to suicide. Methods: We performed large-scale microarray gene expression analysis using the Affymetrix HG-U133 chipset and focused our investigation on the expression profile of genes related to lipid metabolism and immune response in post-mortem brains from suicide completers and comparison subjects. We used tissue from three regions of the frontal cortex (Brodmann areas (BA) 8/9,11, and 47) from 22 male suicide completers,15 of whom were diagnosed with major depressive disorder, and 13 male comparison subjects. Results: Fatty acid desaturase (FADS1), leptin receptor (LEPR), phosphoinositide-3-kinase (class 2 alpha; PIK3C2A) and stearoyl-CoA desaturase (SCD) were consistently down-regulated in all three regions of the frontal cortex of depressed suicides compared to comparison subjects, and were among the genes for which significant correlations were observed between our microarray and real-time PCR data. Limitations: Given the absence of a non-suicidal depressed comparison group in this study, it cannot be ascertained whether the gene expression changes identified are associated with depression or suicide. Conclusions: Our findings suggest a role for lipid metabolism and immune response genes in depressed suicide completers and lend further support to the relationship between lipid metabolism and suicidality. © 2009 Elsevier B.V. All rights reserved. Keywords: Cholesterol Cytokines Microarray Post-mortem Depression Suicide 1. Introduction The association between low levels of serum cholesterol and suicidal behaviour has been reported in numerous studies utilizing different methodological approaches (Kunugi et al., 1997; Modai et al., 1994; Alvarez et al., 1999; Zureik et al., 1996; Ellison and Morrison, 2001; Golomb, 1998; Golomb et al., 2000; Atmaca et al., 2008). These studies have led to a range of ideas about how serum cholesterol might play a role in influencing suicide risk, and this has widened the scope of investigations to examine other aspects of lipid metabolism in relation to suicidality. Correlations have been found between other circulating lipids and suicidal behaviour, in particular fatty acids (Tanskanen et al., 2001; Huan et al., 2004; Sublette et al., 2006; Garland et al., 2007) and leptin (Atmaca et al., 2002a,b, 2003; Westling et al., 2004)—both of which are also correlated with low levels of serum total cholesterol. Low serum leptin levels have also been observed in patients with major depression (Jow et al., 2006; Kraus et al., 2001). Similarly, many studies have reported a link between fatty acids and depression (Edwards et al., 1998; Maes et al., 1996, 1999; Peet et al., 1998). Journal of Affective Disorders 120 (2010) 24–31 ⁎ Corresponding author. McGill Group for Suicide Studies, Douglas Mental Health University Institute, 6875 LaSalle Blvd., Verdun, Québec, Canada H4H 1R3. Tel.: +1 514 761 6131x2369; fax: +1 514 762 3023. E-mail address: gustavo.turecki@mcgill.ca (G. Turecki). 0165-0327/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jad.2009.04.007 Contents lists available at ScienceDirect Journal of Affective Disorders journal homepage: www.elsevier.com/locate/jad