SUN-481 Awakening Cortisol Response in Males and Females across Puberty

Abnormalities of hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of mood and anxiety disorders. Adolescence (and puberty) are associated with both an increased onset of mood/anxiety disorders, as well as the emergence of sex differences in the risk for these conditions (i.e., a 2-fold increased life-time risk in women compared with men). Finally, sex differences in HPA axis response to a range of stressors are documented in both rodents and humans. We employed the awakening cortisol response (ACR) to evaluate the HPA axis in a sample of normally-developing pre and post pubertal children. We studied 66 prepubertal children (25 girls, 41 boys) and 29 post pubertal children (14 girls,15 boys). Pubertal stage (PS) was assessed by a trained clinician: in boys based on testicular volume (TV) using the Prader orchidometer; in girls based on breast development. All children (and 1(st) degree relatives) were free of any past/current psychiatric disorder (as determined by structured diagnostic interview); all children were medically well, medication free, had a BMI within the 15(th) -85(th) percentile, normal bone age, and normal IQs. Pre and post pubertal children were selected for awakening cortisol response (ACR) analysis from a larger longitudinal study. The first visit was selected for prepubertal children. Post pubertal children were selected during their most recent visit at PS V. There was no overlap in these groups of children. ACR studies were performed on the morning of outpatient clinic visits. Salivary cortisol was measured by chemiluminescent enzyme immunoassay on Siemens Immullite1000 analyzer. The ACR area under the curve (AUC) and individual time points (0, 30, 45 and 60 minutes) were analyzed by ANOVAs. In the AUC cortisol there was a significant main effect of sex (F(1,94)=7.5; p=0.007) but no main or interactive effects of PS (p=0.3 and p=0.2, respectively). Similarly, the individual timepoints showed significant main effects of sex (ANOVA-R: F(1,91)=7.4, p=0.008) and time (F(3,89)=19, p<.001), but no main effects of PS, nor any between-subjects interactive effects. (p=ns, all comparisons). In summary, we found no effects of pubertal stage on the ACR and that sex differences in the ACR occurred independently of pubertal stage. Therefore, our preliminary findings suggest that sex differences in HPA axis appear prior to gonadarche. These findings are analogous to previous adult data from our group (Roca, et al. 2005) in which sex differences in HPA axis responsivity were observed in adult men and women during both eugonadal and GnRH agonist-induced hypogonadal conditions.