2012 › Trails



Stressphysiology outcomes: Genetically based reduced MAOA and COMT functioning is associated with the cortisol stress response - a replication study

Authors: Bouma EMC, Riese H, Doornbos B, Ormel J, Oldehinkel AJ

In 2007, Molecular Psychiatry published a unique study by Jabbi and colleagues, in which they showed that the combination of genetic variance in the MAOA and COMT gene was associated with increased responses of the HPA axis to stress. This finding was replicated in the TRAILS study and published as Letter to the Editor in Molecular Psychiatry. Our letter addresses the combined influence of the MAOA length polymorphism and the COMT val158met SNP on saliva cortisol responses towards a standardized social stress test in a large (n = 452) sample of adolescents (mean age 16.01 yrs, 38.5% girls, no oral contraceptive users). Jabbi et al. (1) showed that the COMT met/met genotype in combination with low MAOA, present in males predominantly, was associated with increased ACTH responses. We replicated this association in adolescent boys. The effect of COMT in the low MAOA group was different between boys and girls. The highest cortisol levels and most pronounced responses were observed in met/met boys while in val/val girls. This gender difference is in concordance with the hypothesized differential effects of high and low COMT functioning in the development of mental disorders in men and women. Our finding should be interpreted with caution; although our overall sample size was large, the low MAOA genotype group consisted of only 29 girls (relative to 100 boys).

Stressphysiology outcomes: Timing matters: Long term effects of adversities from prenatal period up to adolescence on adolescents’ cortisol stress response. The TRAILS study

Authors: Bosch NM, Riese H, Reijneveld SA, Bakker MP, Verhulst FC, Ormel J, Oldehinkel AJ

Objective. Altered cortisol response is a vulnerability marker for a variety of stress-related diseases and psychiatric disorders. Childhood adversity has been shown to modify this response, but evidence is inconsistent. Effects may differ depending on the timing of exposure, or due to the interplay between pre/postnatal adversity and later adversities. The present study examined the influence of adversity during different timeframes (pre/postnatal, ages 0-5, 6-11, 12-13, 14-15 years), and the interaction between pre/postnatal and later adversity on adolescents’ cortisol stress response. Method. Four salivary cortisol samples were collected before and after a social stress test in 471 16-year-old adolescents from the longitudinal study TRAILS. Data on pre/postnatal exposure to adversities were obtained from Preventive Child Healthcare records and parental reports, subsequent adversities from parental and self-reports. Results. Pre/postnatal adversity was associated with increased cortisol reactivity. Adversities during ages 0-5 were not associated with cortisol outcomes. Adversities during ages 6-11 were associated with a high cortisol level, especially in those exposed to pre/postnatal adversity, while adversities during ages 12-13 and 14-15 were associated with a low cortisol level. Conclusions. Results highlight the importance to take the timing of stress exposure into account. In addition to programming effects, pre/postnatal adversity interacts with childhood adversity in producing deviant cortisol levels. Puberty may be marked by a transition in how adversities affect the HPA-axis, with cortisol hypersecretion before age 11 and hyposecretion after age 11.

Stressphysiology outcomes: Family environment is associated with HPA-axis activity in adolescents.The TRAILS study

Authors: Marsman R, Nederhof E, Rosmalen JGM, Oldehinkel AJ, Ormel J, Buitelaar JK

The purpose of the present study was to investigate the developmental programming part of the theory of biological sensitivity to context using family environmental factors and hypothalamus-pituitary-adrenal (HPA) axis functioning. Specifically, we investigated whether perceived parenting (Rejection and Emotional Warmth) and socio-economic status (SES) predicted basal cortisol levels and the cortisol awakening response (CAR). In a population-based cohort of 1594 adolescents (mean age = 11.08, SD = 0.54) we assessed salivary cortisol, SES and perceived parenting. Perceived parental Emotional Warmth showed an inverse, linear association with basal cortisol levels. In addition, there was a curvilinear relationship between SES and both basal cortisol levels and the CAR. Our findings with regard to basal cortisol levels confirmed our hypothesis: lower basal HPA-axis activity in both high and low SES families compared to intermediate SES families.