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.
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*contributed equally to this study
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.
It is well-known that childhood adversities can have long-term effects on mental health, but a lot remains to be learned about the risk they bring about for a first onset of various psychiatric disorders, and how this risk develops over time. In the present study, which was based on a Dutch longitudinal population survey of adolescents TRAILS (N = 1,584), we investigated whether and how childhood adversities, as assessed with three different measures, affected the risk of developing an incident depressive, anxiety, or disruptive behavior in childhood and adolescence. In addition, we tested gender differences in any of the effects under study. The results indicated that depressive, anxiety and disruptive behavior disorders each had their own, characteristic, pattern of associations with childhood adversities across childhood and adolescence, which was maintained after adjustment for comorbid disorders. For depressive disorders, the overall pattern suggested a high excess risk of incidence during childhood, which decreased during adolescence. Anxiety disorders were characterized by a moderately increased incident risk during childhood, which remained approximately stable over time. Disruptive behavior disorders took an intermediate position. Of the three childhood adversities tested, an overall rating of the stressfulness of the childhood appeared to predict onset of psychiatric disorders best. To conclude, the risk of developing a psychiatric disorder after exposure to adversities early in life depends on the nature of the adversities, the nature of the outcome, and the time that has passed since the adversities without disorder onset.
Background. With psychopathology rising during adolescence and evidence suggesting that adult mental health burden is often due to disorders beginning in youth, it is important to investigate the epidemiology of adolescent mental disorders. Method. We analysed data gathered at ages 11 (baseline) and 19 years from the population-based Dutch TRacking Adolescents' Individual Lives Survey (TRAILS) study. At baseline we administered the Achenbach measures (Child Behavior Checklist, Youth Self-Report) and at age 19 years the World Health Organization's Composite International Diagnostic Interview version 3.0 (CIDI 3.0) to 1584 youths. Results. Lifetime, 12-month and 30-day prevalences of any CIDI-DSM-IV disorder were 45, 31 and 15%, respectively. Half were severe. Anxiety disorders were the most common but the least severe whereas mood and behaviour disorders were less prevalent but more severe. Disorders persisted, mostly by recurrence in mood disorders and chronicity in anxiety disorders. Median onset age varied substantially across disorders. Having one disorder increased subjects' risk of developing another disorder. We found substantial homotypic and heterotypic continuity. Baseline problems predicted the development of diagnosable disorders in adolescence. Non-intact families and low maternal education predicted externalizing disorders. Most morbidity concentrated in 5-10% of the sample, experiencing 34-55% of all severe lifetime disorders. Conclusions. At late adolescence, 22% of youths have experienced a severe episode and 23% only mild episodes. This psychopathology is rather persistent, mostly due to recurrence, showing both monotypic and heterotypic continuity, with family context affecting particularly externalizing disorders. High problem levels at age 11 years are modest precursors of incident adolescent disorders. The burden of mental illness concentrates in 5-10% of the adolescent population.
Background. Some adolescents function poorly in apparently benign environments, while others thrive despite hassles and difficulties. The aim of this study was to examine if adolescents with specialized skills in the recognition of either positive or negative emotions have a context-dependent risk of developing an anxiety or depressive disorder during adolescence, depending on exposure to positive or harsh parenting. Methods. Data came from a large prospective Dutch population study (N = 1539). At age 11, perceived parental rejection and emotional warmth were measured by questionnaire, and emotion recognition skills by means of a reaction-time task. Lifetime diagnoses of anxiety and depressive disorders were assessed at about age 19, using a standardized diagnostic interview. Results. Adolescents who were specialized in the recognition of positive emotions had a relatively high probability to develop an anxiety disorder when exposed to parental rejection (Bspecialization*rejection = 0.23, P < 0.01) and a relatively low probability in response to parental emotional warmth (Bspecialization*warmth = -0.24, P = 0.01), while the opposite pattern was found for specialists in negative emotions. The effect of parental emotional warmth on depression onset was likewise modified by emotion recognition specialization (B = -0.13, P = 0.03), but the effect of parental rejection was not (B = 0.02, P = 0.72). In general, the relative advantage of specialists in negative emotions was restricted to fairly uncommon negative conditions. Conclusions. Our results suggest that there is no unequivocal relation between parenting behaviors and the probability to develop an anxiety or depressive disorder in adolescence, and that emotion recognition specialization may be a promising way to distinguish between various types of context-dependent reaction patterns.