Abstract
BackgroundThe immune system has been increasingly implicated in the development of mood and anxiety disorders. Inhibitor of kappa light polypeptide gene enhancer in B cells, kinase epsilon (IKBKE) gene encodes IKKε protein that is involved in innate immunity, predominantly antiviral response generation. It also bears pro-inflammatory properties that could affect psychiatric outcomes. In order to investigate the possible role of IKBKE gene in major depressive disorder (MDD) and panic disorder (PD), we conducted a case–control genetic association study concerning these disorders.MethodsIn all, 14 SNPs of IKBKE gene were genotyped in groups of 391 patients with MDD and 190 patients with PD together with respective 389 and 371 healthy control individuals. The given groups were further divided by gender for additional analyses.ResultsSubstantial genetic associations were revealed between IKBKE SNPs and MDD (multiple testing adjusted P < 0.05) and suggestive associations in case of PD (Padj > 0.05). In addition, two SNPs that were only associated with PD among males, also displayed significantly different allele frequencies compared to PD females. This may indicate a specific role of these SNPs in male PD, but caution should be applied here due to the small size of the studied PD males group.ConclusionsThe results of this study confirm our initial findings and indicate a possible role of IKBKE gene in mood and anxiety disorders.
Highlights
Major depressive disorder (MDD) and panic disorder (PD) are both common psychiatric disorders with a high lifetime prevalence that is generally in range 10–15% (Andrade et al 2003; Kessler et al 2005) and 3.7–5.1% (Grant et al 2006; Kessler et al 2006), respectively, and display a substantial female preponderance
The altered expression of various inflammatory mediators, for example, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha lead to changes in multiple aspects of brain functioning and behavior, and are themselves subjected to defective regulation by the hypothalamic-pituitary-adrenal (HPA) axis that begins in the central nervous system (CNS) (Capuron and Miller 2011)
14 single-nucleotide polymorphisms (SNPs) of IKBKE gene were genotyped in groups of 391 major depressive disorder (MDD) and 190 PD patients and respective 389/371 control individuals
Summary
Major depressive disorder (MDD) and panic disorder (PD) are both common psychiatric disorders with a high lifetime prevalence that is generally in range 10–15% (Andrade et al 2003; Kessler et al 2005) and 3.7–5.1% (Grant et al 2006; Kessler et al 2006), respectively, and display a substantial female preponderance. Inhibitor of kappa light polypeptide gene enhancer in B cells, kinase epsilon (IKBKE) gene encodes IKKe protein that is involved in innate immunity, predominantly antiviral response generation It bears pro-inflammatory properties that could affect psychiatric outcomes. Two SNPs that were only associated with PD among males, displayed significantly different allele frequencies compared to PD females This may indicate a specific role of these SNPs in male PD, but caution should be applied here due to the small size of the studied PD males group. Conclusions: The results of this study confirm our initial findings and indicate a possible role of IKBKE gene in mood and anxiety disorders
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