Persistent childhood and adolescent anxiety and risk for psychosis: a longitudinal birth cohort study

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

METHODS: Data from the ALSPAC were available in 8242 children at 8 years, 7658 at 10 years, 6906 at 13 years, and 3889 at 24 years. The Development and Wellbeing Assessment (DAWBA) was administered to capture child and adolescent anxiety. We created a composite score of generalized anxiety at age 8, 10 and 13. PEs and PD were assessed at age 24, derived from the Psychosis-Like Symptom Interview. The mean of CRP at 9 and 15 years was used as mediator.

RESULTS: Individuals with persistent high levels of anxiety were more likely to develop PEs (OR=2.02, 95% CI=1.26-3.23, p=0.003) and PD at age 24 ((OR)=4.23, 95%CI=2.27-7.88, p<0.001). The mean of CRP at 9 and 15 years mediated the associations of persistent anxiety with PEs (bias-corrected estimate=-0.001, p=0.013) and PD (bias-corrected estimate=0.001, p=0.003).

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 non-resolving inflammation. These results contribute to the potential for preventative interventions in psychosis, with the novel target of early anxiety.
Original languageEnglish
JournalBiological Psychiatry
Early online date12 Dec 2021
Publication statusE-pub ahead of print - 12 Dec 2021


  • Anxiety
  • C-reactive protein
  • Inflammation
  • Psychosis
  • Trajectories


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