CRHR1 genotype and history of maltreatment predict cortisol reactivity to stress in adolescents

Abstract

This study examined the contributions of a polymorphism of the corticotropin-releasing hormone receptor type I (CRHR1) gene (rs110402) and a history of child maltreatment--alone and in interaction--to patterns of cortisol reactivity in adolescents. Adolescents between the age of 13 and 17 years with (n=61) and without (n=97) a history of child maltreatment were exposed to the Trier Social Stress Test (TSST). Salivary cortisol was assessed at baseline, and 15 and 30 min after the start of the speech portion of the TSST. Saliva samples for genotyping rs110402 also were collected. Adolescents with one or more G alleles of rs110402, relative to A allele homozygotes, and those exposed to maltreatment, relative to non-exposed adolescents, exhibited blunted cortisol reactivity to the TSST (although these associations approached, but did not reach, the level of statistical significance when accounting for underlying population structure in our racially and ethnically diverse sample). There was also a trend for a stronger child maltreatment association with cortisol hypo-reactivity among G allele carriers, but this association was not statistically significant. Findings suggest that CRHR1 variation may moderate the downstream effects of child maltreatment on HPA axis function, and implications for understanding mechanisms of risk associated with early adversity are discussed.

Keywords: Adolescence; CRHR1; Child maltreatment; Cortisol; Genetics; Stress reactivity; Trier Social Stress Test.

Figure 1

Cortisol response to the Trier Social Stress Test (TSST) over time as a function of rs110402 genotype. Error bars represent standard error of the mean.

Figure 2

Cortisol response to the Trier Social Stress Test (TSST) over time as a function of child maltreatment history. Error bars represent standard error of the mean.

Figure 3

Effect of child maltreatment history on cortisol response to the Trier Social Stress Test (TSST) over time for rs110402 G allele carriers (a) and A allele homozygotes (b). Error bars represent standard error of the mean.

Figure 4

Cortisol area under the curve (AUC) with respect to increase as a function of rs110402 genotype and child maltreatment history. Error bars represent standard error of the mean. Sample sizes for the subgroups are as follows: G carriers with maltreatment history (n = 48), A homozygotes with maltreatment history (n = 13), G carriers without maltreatment history (n = 67), A homozygotes without maltreatment history (n = 30).