2015 › Trails



Stressphysiology outcomes: Ghrelin-reactive immunoglobulins and anxiety, depression and stress-induced cortisol response in adolescents. The TRAILS study

Authors: François M, Schaefer JM, Bole-Feysota C, Déchelottea P, Verhulst FC, Fetissov SO

Background. Ghrelin, a hunger hormone, has been implicated in the regulation of stress-response, anxiety and depression. Ghrelin-reactive immunoglobulins (Ig) were recently identified in healthy and obese humans showing abilities to increase ghrelin's stability and orexigenic effects. Here we studied if ghrelin-reactive Ig are associated with anxiety and depression and with the stress-induced cortisol response in a general population of adolescents. Furthermore, to test the possible infectious origin of ghrelin-reactive Ig, their levels were compared with serum IgG against common viruses. Methods. We measured ghrelin-reactive IgM, IgG and IgA in serum samples of 1199 adolescents from the Dutch TRAILS study and tested their associations with 1) anxiety and depression symptoms assessed with the Youth Self-Report, 2) stress-induced salivary cortisol levels and 3) IgG against human herpesvirus 1, 2, 4 and 6 and Influenza A and B viruses. Results. Ghrelin-reactive IgM and IgG correlated positively with levels of antibodies against Influenza A virus. Ghrelin-reactive IgM correlated negatively with antibodies against Influenza B virus. Ghrelin-reactive IgM correlated positively with anxiety scores in girls and ghrelin-reactive IgG correlated with stress-induced cortisol secretion, but these associations were weak and not significant after correction for multiple testing. Conclusion. These data indicate that production of ghrelin-reactive autoantibodies could be influenced by viral infections. Serum levels of ghrelin-reactive autoantibodies probably do not play a role in regulating anxiety, depression and the stress-response in adolescents from the general population.

Copyright © 2015 Elsevier Inc. All rights reserved.

Stressphysiology outcomes: Markers of stress and inflammation as potential mediators of the relationship between exercise and depressive symptoms: Findings from the TRAILS study

Authors: Booij SH, Bos EH, De Jonge P, Oldehinkel AJ

The hypothalamic-pituitary-adrenal axis, autonomic nervous system, and immune system have been proposed to underlie the antidepressant effect of exercise. Using a population sample of 715 adolescents, we examined whether pathways from exercise to affective and somatic symptoms of depression were mediated by these putative mechanisms. Exercise (hours/week) and depressive symptoms were assessed at age 13.5 (± 0.5) and 16.1 (± 0.6). Cortisol and heart rate responses to a standardized social stress test and C-reactive protein levels were measured at age 16. Exercise was prospectively and inversely related to affective (B = -0.16, 95% CI = -0.30 to -0.03) but not somatic symptoms (B = -0.04, 95% CI = -0.21 to 0.13). Heart rate during social stress partially mediated this relationship (B = -0.03, 95% CI = -0.07 to -0.01). No other mediating effects were found. Hence, the autonomic stress system may play a role in the relationship between exercise and depressive symptoms.

© 2014 Society for Psychophysiological Research.

Stressphysiology outcomes: Glucocorticoid receptor gene methylation and HPA-axis regulation in adolescents. The TRAILS study

Authors: Van der Knaap LJ, Oldehinkel AJ, Verhulst FC, Van Oort FVA, Riese H


  • We investigated the association between HPA-axis regulation and NR3C1 methylation.
  • HPA-axis regulation was operationalized as stress response activation and recovery.
  • NR3C1 methylation was not associated with activation of the stress response.
  • NR3C1 methylation was associated with a slower recovery of the stress response.
  • NR3C1 methylation possibly impairs negative feedback of the HPA-axis.

Stressphysiology outcomes: Predicting mental disorders from hypothalamic-pituitary-adrenal axis functioning: a 3-year follow-up in the TRAILS study

Authors: Nederhof E, Van Oort FVA, Bouma E, Laceulle OM, Oldehinkel AJ, Ormel J

Background. Hypothalamic-pituitary-adrenal axis functioning, with cortisol as its major output hormone, has been presumed to play a key role in the development of psychopathology. Predicting affective disorders from diurnal cortisol levels has been inconclusive, whereas the predictive value of stress-induced cortisol concentrations has not been studied before. The aim of this study was to predict mental disorders over a 3-year follow-up from awakening and stress-induced cortisol concentrations. Method. Data were used from 561 TRAILS (TRacking Adolescents' Individual Lives Survey) participants, a prospective cohort study of Dutch adolescents. Saliva samples were collected at awakening and half an hour later and during a social stress test at age 16. Mental disorders were assessed 3 years later with the Composite International Diagnostic Interview (CIDI). Results. A lower cortisol awakening response (CAR) marginally significantly predicted new disorders [odds ratio (OR) 0.77, p = 0.06]. A flat recovery slope predicted disorders with a first onset after the experimental session (OR 1.27, p = 0.04). Recovery revealed smaller, non-significant ORs when predicting new onset affective or anxiety disorders, major depressive disorder, or dependence disorders in three separate models, corrected for all other new onsets. Conclusions. Our results suggest that delayed recovery and possibly reduced CAR are indicators of a more general risk status and may be part of a common pathway to psychopathology. Delayed recovery suggests that individuals at risk for mental disorders perceived the social stress test as less controllable and less predictable.

Stressphysiology outcomes: Adolescent Personality: Associations With Basal, Awakening, and Stress-Induced Cortisol Responses

Authors: Laceulle OM, Nederhof E, Van Aken MAG, Ormel J

The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n = 343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective cohort study of Dutch adolescents. We studied the association between facets of Neuroticism, Extraversion, and Conscientiousness and basal cortisol, the cortisol awakening response (CAR), and four measures of stress-induced HPA-axis activity. Basal cortisol levels were related to facets of all three personality traits. The CAR and stress-induced cortisol were not related to personality. Possibly due to its more trait-like nature, basal cortisol seems more informative than stress-induced cortisol when investigating trait-like characteristics such as personality facets.

© 2014 Wiley Periodicals, Inc.

Stressphysiology outcomes: Chronic Stress and Adolescents' Mental Health: Modifying Effects of Basal Cortisol and Parental Psychiatric History. The TRAILS Study

Authors: Zandstra ARE, Hartman CA, Nederhof E, Van den Heuvel ER, Dietrich A, Hoekstra PJ, Ormel J

Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to indicate high context sensitivity, would show relatively high problem levels following chronic stress, especially in the presence of parental psychiatric history. With Linear Mixed Models, we investigated the hypotheses in 1917 Dutch adolescents (53.2 % boys), assessed at ages 11, 13.5, and 16. Low basal cortisol combined with the absence of a parental psychiatric history increased the risk of externalizing but not internalizing problems following chronic stress. Conversely, low basal cortisol combined with a substantial parental psychiatric history increased the risk of internalizing but not externalizing problems following chronic stress. Thus, parental psychiatric history moderated stress- cortisol interactions in predicting psychopathology, but in a different direction than hypothesized. We conclude that the premise that basal cortisol indicates context sensitivity may be too crude. Context sensitivity may not be a general trait but may depend on the nature of the context (e.g., type or duration of stress exposure) and on the outcome of interest (e.g., internalizing vs. externalizing problems). Although consistent across informants, our findings need replication.

Stressphysiology outcomes: The role of basal cortisol in predicting change in mental health problems across the transition to middle school

Authors: Zandstra ARE, Ormel J, Nederhof E, Hoekstra PJ, Hartman CA

Purpose. The period in which the transition to middle school occurs is marked by major changes in social context, social rules, and scholastic responsibilities. Some adolescents thrive during this period whereas others are overwhelmed and fail to cope adequately with their changing environment. We investigated basal cortisol upon waking as a predictor of change in mental health problems across the transition to middle school. By taking into account the transition experience, we extend prior findings that high basal cortisol predicts deteriorated mental health after the transition. In individuals with high awakening cortisol, we expected mental health problems to increase after negative transition experiences and to decrease after positive transition experiences, reflecting differential susceptibility. Evidence for the former but not the latter would suggest diathesis-stress. Methods. Data from 1,664 subjects were obtained from two measurement waves (mean ages, 11 and 13.5 years) of the TRacking Adolescents' Individual Lives Survey. Using linear regression, we investigated effects of awakening cortisol level, school transition experience, and their hypothesized interaction on change in mental health problems. Results. We found that a negative but not a positive experience was predictive of change in mental health. Importantly, our results showed that a negative experience predicts deteriorated mental health only in adolescents with high awakening cortisol but not in adolescents with low awakening cortisol. This finding was robust across informants. The converse, high awakening cortisol predicting decreasing mental health problems after a positive transition was not found. Conclusions. These results support the diathesis-stress model but not the differential susceptibility hypothesis.

Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.