Persistent Childhood and Adolescent Anxiety and Risk for Psychosis: A Longitudinal Birth Cohort Study

Abstract

Background: Persistent anxiety in childhood and adolescence could represent a novel treatment target for psychosis, potentially targeting activation of stress pathways and secondary nonresolving inflammatory response. Here, we examined the association between persistent anxiety through childhood and adolescence with individuals with psychotic experiences (PEs) or who met criteria for psychotic disorder (PD) at age 24 years. We also investigated whether C-reactive protein mediated any association.

Methods: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were available in 8242 children at age 8 years, 7658 at age 10 years, 6906 at age 13 years, and 3889 at age 24 years. The Development and Well-Being Assessment was administered to capture child and adolescent anxiety. We created a composite score of generalized anxiety at ages 8, 10, and 13. PEs and PD were assessed at age 24, derived from the Psychosis-like Symptoms Interview. The mean of C-reactive protein at ages 9 and 15 years was used as a mediator.

Results: Individuals with persistent high levels of anxiety were more likely to develop PEs (odds ratio 2.02, 95% CI 1.26-3.23, p = .003) and PD at age 24 (odds ratio 4.23, 95% CI 2.27-7.88, p < .001). The mean of C-reactive protein at ages 9 and 15 mediated the associations of persistent anxiety with PEs (bias-corrected estimate -0.001, p = .013) and PD (bias-corrected estimate 0.001, p = .003).

Conclusions: Persistent high levels of anxiety through childhood and adolescence could be a risk factor for psychosis. Persistent anxiety is potentially related to subsequent psychosis via activation of stress hormones and nonresolving inflammation. These results contribute to the potential for preventive interventions in psychosis, with the novel target of early anxiety.

Keywords: ALSPAC; Anxiety; C-reactive protein; Inflammation; Psychosis; Trajectories.

Figure 1

Growth trajectories of anxiety across childhood to adolescence. The latent class growth analyses detected a best model fit for 3 classes. Class 1 (blue line on the bottom) represents individuals with persistent low levels of anxiety across time points. Class 2 (red line in the middle) represents individuals with persistent intermediate levels of anxiety. Class 3 (green line on the top) represents individuals with persistent high levels of anxiety across time points, which was the main focus of this study.

Figure 2

Path diagram showing the main direct associations. Only the direct associations of the independent variable, mediating factor, and dependent variable are shown. Persistent high levels of anxiety represent the independent variable; the mean of C-reactive protein (CRP) levels at ages 9 and 15 represent the mediating factor; and psychotic experiences (A) and meeting criteria for psychotic disorder (B) at age 24 represent the outcomes. The covariates also included in this path analysis were sex, family adversity, birth weight, and cannabis use at age 15. Significant pathways are indicated by solid arrows.