Hanns, Laura Anne; (2018) Psychological health and inflammation in adolescents with juvenile idiopathic arthritis: describing the relationships between psychological health, laboratory measures of inflammation and disease activity for adolescents with juvenile idiopathic arthritis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Patients with inflammatory arthritis often report flares of disease during times of psychological distress. This is particularly pertinent during adolescence, a time when mental health problems often become apparent. Increasing scientific evidence supports the concept that psychological stress and depression can promote increased systemic pro-inflammatory cytokine production driven by reduced cortisol sensitivity. For patients with inflammatory arthritis, it is possible that psychological distress reduces cortisol sensitivity, increasing proinflammatory cytokine production, which leads to worsened disease activity. This association has never been explored in detail for patients with juvenile idiopathic arthritis (JIA) or in a purely adolescent population. In this thesis I profile the psychological health of 136 adolescent JIA patients and 88 healthy adolescent controls. I also investigate the associations between psychological health, disease activity and inflammatory measures. I demonstrate that depressive symptoms are highly prevalent for all adolescents (both adolescent JIA patients and healthy adolescents). There were no differences in anxiety, depression, mental wellbeing or resilience questionnaire scores between adolescent JIA patients and adolescent healthy controls. However, JIA patients reported significantly lower controllable life event scores than healthy adolescents, which is likely indicative of the lifestyle limitations that they experience. Depression and anxiety strongly associated with worsened disability and pain. When longitudinal associations between depression and disease activity were explored using data from the Childhood Arthritis Prospective Study, depression at diagnosis was found to predict future disability and pain. Disability, pain and active joint count at diagnosis were found to predict future depressive symptoms. Inflammatory mechanisms were also explored. For adolescent healthy controls, increased anxiety and depression associated with an increased pro-inflammatory profile (increased lipopolysaccharide (LPS) induced IL-6 production from peripheral blood mononuclear cells). This was consistent with previous studies. However, for JIA patients, anxiety and depression associated with an antiinflammatory profile (increased sensitivity to glucocorticoid inhibition of the LPS-induced IL-6 response). The association between anxiety, depression and increased cortisol sensitivity for JIA patients does not explain the association between anxiety, depression, disability and pain. Rather, the association between psychological health and disability and pain may be explained by subtle behavioural and cognitive changes. The increased cortisol sensitivity seen with higher anxiety and depression scores appears to be unrelated to disease activity. Overall, this thesis suggests that increased psychological support for adolescent JIA patients, especially at diagnosis, may improve their mental health and could impact on current and future pain and disability. This thesis therefore supports the notion for routine assessment of mental wellbeing and psychological distress during adolescent rheumatology appointments.

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