Abstract

The rs1006737 (A/G) single nucleotide polymorphism within the gene encoding the Cav1.2 subunit of the L-type voltage-dependent calcium channel (CACNA1C) has been strongly implicated in psychiatric disorders. In addition, calcium channels are sensitive to the effects of glucocorticoids and functional variation may contribute to altered stress responsivity. This study aimed to investigate the role of early life stress (ELS) and its interaction with CACNA1C rs1006737 in affecting the cortisol awakening response (CAR), an indicator of HPA-axis function. Salivary cortisol was measured in 103 healthy adult males (aged 21-63) on two consecutive days at awakening and 30 minutes later. The ELS measure investigated self-reported adverse life events prior to age 17. The results revealed a marginally significant main effect of CACNA1C, a significant main effect of ELS, and a significant genotype-by-ELS interaction on the CAR, whereby non-risk allele carriers (GG) who had experienced early adversity showed higher CAR compared to the other groups. Further exploratory analyses showed that this interaction may have arisen from individuals who had experienced ELS before adolescence (prior to age 13). This study is the first to provide evidence that the effect of ELS on CAR may be partially moderated via CACNA1C rs1006737 genotype, whereby the heightened CAR in the GG-ELS group may be an indicator of mental health resilience in response to ELS.