The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D)

Raison, C L; Miller, A H

An exception to the general lack of knowledge regarding GWAS-identified depression risk alleles is provided by the rs1006737 SNP in the CACNA1C gene, which codes for the a1 subunit of the L-type voltage-gated calcium channel (Cav1.2). 29 CACNA1C has been identified as a potential depression risk gene in several GWASs, 105, 141, 142 and convergent validity for its role in depression is provided by data demonstrating that carriers of the risk A allele have changes in brain function and morphology relevant to MDD. [143] [144] [145] An examination of the immune effects of CACNA1C highlights both the promise and complexities of a PATHOS-D perspective. Calcium signaling pathways play central and essential roles in multiple aspects of Table 2 Immune/host defense functions of single-nucleotide polymorphisms (SNPs) associated with major depression based on the largest meta-analysis of genome-wide association studies (GWASs) conducted to date for major depression (MDD) Abbreviations: FP, prostaglandin F; GMAP, galanin message associated peptide; HSV1, herpes simplex virus type 1; IFN-a, interferon-a; IgM, immunoglobulin M; IL, interleukin; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; MDD, major depressive disorder; NF-kB, nuclear factor-kb; PATHOS-D, Pathogen Host Defense; PKR, protein kinase R; PPAR-g, peroxisome proliferator-activated receptor-g; TLR, Toll-like receptor; TNF-a, tumor necrosis factor-a. Reference numbers in Table 2 correspond to reference numbers in paper bibliography.