Polymorphisms in inflammation-related genes are associated with susceptibility to major depression and antidepressant response

Abstract

There are clinical parallels between the nature and course of depressive symptoms in major depressive disorder (MDD) and those of inflammatory disorders. However, the characterization of a possible immune system dysregulation in MDD has been challenging. Emerging data support the role of T-cell dysfunction. Here we report the association of MDD and antidepressant response to genes important in the modulation of the hypothalamic-pituitaryadrenal axis and immune functions in Mexican Americans with major depression. Specifically, single nucleotide polymorphisms (SNPs) in two genes critical for T-cell function are associated with susceptibility to MDD: PSMB4 (proteasome b4 subunit), important for antigen processing, and TBX21 (T bet), critical for differentiation. Our analyses revealed a significant combined allele dose-effect: individuals who had one, two and three risk alleles were 2.3, 3.2 and 9.8 times more likely to have the diagnosis of MDD, respectively. We found associations of several SNPs and antidepressant response; those genes support the role of T cell (CD3E, PRKCH, PSMD9 and STAT3) and hypothalamic-pituitary-adrenal axis (UCN3) functions in treatment response. We also describe in MDD increased levels of CXCL10/IP-10, which decreased in response to antidepressants. This further suggests predominance of type 1 T-cell activity in MDD. T-cell function variations that we describe here may account for 47.8% of the attributable risk in Mexican Americans with moderate MDD. Immune function genes are highly variable; therefore, different genes might be implicated in distinct population groups.

Potential diagnostic markers for postpartum depression point out to altered immune signaling

“…In this issue of Molecular Psychiatry, Segman et al We recently reported increased expression of the 10-kDa interferongamma-induced protein CXCL10 in depressed patients; CXCL10 levels decreased back to normal after antidepressant treatment. 2 On the basis of our genetic findings of association with T bet (TBX21) as well as the functional finding of increased CXCL10 activity, we proposed increased Th1 immune activity in depression. Of interest here, most of Segman's findings were of decreased gene expression in postpartum depression, while we reported increased levels of CXCL10.…”

Antidepressant-like effects of magnesium lithospermate B in a rat model of chronic unpredictable stress

“…MLB has also been demonstrated to inhibit lipopolysaccharide-induced expression of inflammatory molecules (Zhao et al, 2013). Inhibition of neuroinflammation may represent a novel mechanism of action for antidepressant treatment (Wong et al, 2008). Several recent studies have reported that some natural products such as omega-3 fatty acids and curcumin induced antidepressant effects through the modulation of oxidative reactions and inflammatory cytokine production in the brain (Lin et al, 2011;Su, 2009;Xu et al, 2005).…”

Pharmacogenetics of antidepressant drugs: An update

“…On the other hand, rs4792888 showed marginal evidence of association with desipramine response [160]. Other investigations showed a possible involvement of rs2270007 [158] and rs2267716-rs255105 [159] within CRHR2 in citalopram response, and of rs917195 in desipramine efficacy [161].…”