Development of reelin biomarkers to measure psychological resilience and their interaction with 5-HTTLPR in depression

Abstract

Stress is clearly associated with the quality of life and many diseases, including mental disorders, with cortisol being a recognized biomarker for stress. Polymorphisms of the serotonin transporter gene (5-HTT), which results in long and short forms, have been reported to be associated with depression among major depressive disorder (MDD) patients. We have previously shown that 5-HTTLPR and waking cortisol do not predict depression in a general population sample, however, psychological resilience is a defence against depression. Reelin is an emerging biomarker for psychological resilience that plays an active role in neuronal migration. It is responsible for cytoarchitechtonic pattern formation in brain and modulates the migration of newly generated postmitotic neurons from the ventricular zone. In mice, overexpression of reelin in the hippocampus has anti-depressant activity by increasing neurogenesis and improving learning. A number of single nucleotide polymorphisms (SNPs), methylation of the promoter and coding region of the reelin (RELN) gene have been identified which affect the level of RELN mRNA and protein expression. Thus RELN is a potential candidate as a biomarker of psychological resilience and we have developed a rapid high-resolution melting (HRM) PCR analysis technique for the RELN SNPs and loci using gDNA isolated from buccal cells to test this hypothesis.