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

  • Isabel Morales-Muñoz
    Address correspondence to Isabel Morales-Muñoz, Ph.D.
    Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom

    Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland
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  • Edward R. Palmer
    Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom

    Birmingham and Solihull Mental Health Foundation Trust, Birmingham, United Kingdom
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  • Steven Marwaha
    Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom

    Specialist Mood Disorders Clinic, Zinnia Centre, Birmingham, United Kingdom

    Barberry National Centre for Mental Health, Birmingham, United Kingdom
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  • Pavan K. Mallikarjun
    Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom

    Early Intervention Service, Birmingham Women’s and Children’s NHS Trust, Birmingham, United Kingdom
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  • Rachel Upthegrove
    Institute for Mental Health, School of Psychology, University of Birmingham, Birmingham, United Kingdom

    Early Intervention Service, Birmingham Women’s and Children’s NHS Trust, Birmingham, United Kingdom
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Open AccessPublished:December 12, 2021DOI:



      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.


      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.


      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).


      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.


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