|Year : 2020 | Volume
| Issue : 1 | Page : 36-42
Differential impact of interleukin-6 promoter gene polymorphism on hippocampal volume in antipsychotic-naïve schizophrenia patients
Venkataram Shivakumar1, Vanteemar S Sreeraj1, Manjula Subbanna2, Sunil V Kalmady1, Anekal C Amaresha1, Janardhanan C Narayanaswamy1, Monojit Debnath2, Ganesan Venkatasubramanian1
1 Translational Psychiatry Lab, Neurobiology Research Center; InSTAR Program, Schizophrenia Clinic, Department of Psychiatry, Bengaluru, Karnataka, India
2 InSTAR Program, Schizophrenia Clinic, Department of Psychiatry; Department of Human Genetics, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
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-naïve/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 <0.01; P = 0.95) had volume depletion.
Conclusion: A paradoxical smaller hippocampal volume with GG genotype was noted in SCZ. Further elucidation of its mechanistic basis might have translational implications.
Dr. Ganesan Venkatasubramanian
InSTAR Program, Schizophrenia Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
[FULL TEXT] [PDF]*