Differential impact of interleukin-6 promoter gene polymorphism on hippocampal volume in antipsychotic-naïve schizophrenia patients

Background: Differential susceptibility model hypothesizes that a genotype need not be unfavorable all the time as postulated in stress-diathesis model but can be beneficial in a supportive context. Single-nucleotide polymorphism (SNP) (rs18000795) within the promoter region of interleukin-6 (IL-6) gene was earlier noted to have a differential susceptibility on hippocampal volume in schizophrenia (SCZ). Materials and Methods: We examined antipsychotic-naive/free SCZ patients (n = 35) in comparison with healthy controls (n = 68). Hippocampus volumes were assessed in 3 Tesla magnetic resonance imaging using voxel-based morphometry. Region of interest analysis was done using hippocampus mask. IL-6 SNP (rs1800795) was genotyped using TaqMan allelic discrimination assay. Results: A significantly deficient right (T = 3.03; KE= 392; PSVC-FWE= 0.04) and left (T = 3.03; KE= 47; Puncorr= 0.03) hippocampal gray matter volumes were noted in SCZ patients after controlling for the potential confounding effects of age, sex, and total brain volume. There was a significant diagnosis x rs1800795 genotype interaction involving both left (T = 2.17, KE= 95, Puncorr= 0.02) and right (T = 1.82, KE= 29, Puncorr= 0.04) hippocampal volumes. Patients with GG (left: F =5.78; P = 0.02; right: F =6.21; P = 0.01) but not GC/CC genotype (left: F =0.89; P = 0.34; right: F Conclusion: A paradoxical smaller hippocampal volume with GG genotype was noted in SCZ. Further elucidation of its mechanistic basis might have translational implications.