Background. Childhood subthreshold manic symptoms may represent a state of developmental vulnerability to Bipolar Disorder (BD) and may also be associated with other adverse psychiatric outcomes. To test this hypothesis we examined the structure and predictive value of childhood subthreshold manic symptoms for common psychiatric disorders presenting by early adulthood. Methods. Subthreshold manic symptoms at age 11 years and lifetime clinical outcomes by age 19 years were ascertained in the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective Dutch community cohort. We used latent class analysis to identify subthreshold manic symptom profiles at baseline. The association between class membership and subsequent clinical diagnoses of BD (comprising BD-I, BD-II, mania and hypomania), depressive, anxiety and substance abuse disorders was determined using Cox proportional-hazard ratio (HR) models. Results. At age 11 years, we identified a normative (n=916; 47%), a mildly symptomatic (n=843; 43%) and a highly symptomatic class (n=198; 10%). Referenced to the normative class, the sex- and age-adjusted risk of new-onset BD by the age of 19 years was significantly increased in the mildly (HR=2.01, 95%CI 1.13-3.59) and highly symptomatic classes (HR=5.02, 95%CI 2.48-10.16). These estimates remained significant after further adjustments for cognitive and family function, parental socioeconomic status, parental psychiatric morbidity, and comorbid disorders at baseline (p-value for linear trend across classes<0.01). Class membership did not show significant associations with incident depressive, anxiety and substance abuse disorders in the fully adjusted regression models. Limitations. The period of risk for adult-onset BD extends beyond the observational period of the study. Conclusions. Elevated childhood subthreshold manic symptoms are associated with increased risk of BD by early adulthood and are therefore a potentially useful phenotype for the early identification of at-risk individuals.
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The experience of childhood life events is associated with higher vulnerability to develop psychiatric disorders. One of the pathways suggested to lead to this vulnerability is activation of the immune system. The aim of this study is to find out whether the association between childhood life events and the development of mood and anxiety disorders is predicted by the activation of the immune system. This study was performed in TRAILS, a large prospective population cohort, from which a subgroup was selected (N=1084, 54.3% female, mean age 19.0 (s.d., 0.6)). Childhood life events before age 16 were assessed using questionnaires at age 12, 14, 16 and 19. Immune activation was assessed at age 16 by elevated high-sensitive C-reactive protein (hsCRP) and by levels of immunoglobulin G antibodies against the herpes viruses herpes simplex virus 1, cytomegalovirus and Epstein-Barr virus. At age 19, the presence of mood and anxiety disorders was determined using the World Health Organization Composite International Diagnostic Interview Version 3.0. Regression analyses were used to study the association between life events, the inflammatory markers and mental health. We found that childhood life events score was associated with risk of mood disorders (B=0.269, P<0.001) and anxiety disorders (B=0.129, P<0.001). Childhood life events score was marginally associated with elevated hsCRP (B=0.076, P=0.006), but not with the antibody levels. This was especially due to separation trauma (P=0.015) and sexual abuse (P=0.019). Associations lost significance after correcting for lifestyle factors such as body mass index and substance abuse (P=0.042). None of the inflammatory markers were associated with development of anxiety disorders or mood disorders. In conclusion, the life event scores predicted the development of anxiety disorders and mood disorders at age 19. Life event scores were associated with elevated hsCRP, which was partly explained by lifestyle factors. Elevated hsCRP was not associated with the development of psychiatric disorders at age 19.
Background. Various sources indicate that mental disorders are the leading contributor to the burden of disease among youth. An important determinant of functioning is current mental health status. This study investigated whether psychiatric history has additional predictive power when predicting individual differences in functional outcomes.
Method. We used data from the Dutch TRAILS study in which 1778 youths were followed from pre-adolescence into young adulthood (retention 80%). Of those, 1584 youths were successfully interviewed, at age 19, using the World Health Organization Composite International Diagnostic Interview (CIDI 3.0) to assess current and past CIDI-DSM-IV mental disorders. Four outcome domains were assessed at the same time: economic (e.g. academic achievement, social benefits, financial difficulties), social (early motherhood, interpersonal conflicts, antisocial behavior), psychological (e.g. suicidality, subjective well-being, loneliness), and health behavior (e.g. smoking, problematic alcohol, cannabis use). Results. Out of the 19 outcomes, 14 were predicted by both current and past disorders, three only by past disorders (receiving social benefits, psychiatric hospitalization, adolescent motherhood), and two only by current disorder (absenteeism, obesity). Which type of disorders was most important depended on the outcome. Adjusted for current disorder, past internalizing disorders predicted in particular psychological outcomes while externalizing disorders predicted in particular health behavior outcomes. Economic and social outcomes were predicted by a history of co-morbidity of internalizing and externalizing disorder. The risk of problematic cannabis use and alcohol consumption dropped with a history of internalizing disorder. Conclusion. To understand current functioning, it is necessary to examine both current and past psychiatric status.