Variant connective tissue (joint hypermobility) and its relevance to depression and anxiety in adolescents: a cohort-based case-control study

Objective: To test whether variant connective tissue structure, as indicated by the presence of joint hypermobility, poses a developmental risk for mood disorders in adolescence. Design: Cohort-based case-control study. Setting: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were interrogated. Participants: 6105 children of the ALSPAC cohort at age 14 years old, of whom 3803 also were assessed when aged 18 years. Main outcome measures: In a risk analysis, we examined the relationship between generalised joint hypermobility (GJH) at age 14 years with psychiatric symptoms at age 18 years. In an association analysis, we examined the relationship between presence of symptomatic joint hypermobility syndrome (JHS) and International Classification of Diseases (ICD-10) indication of depression and anxiety (Clinical Interview Schedule Revised [CIS-R], Anxiety Sensitivity Index [ASI]) at age 18 years. Results: GJH was more common in females (n=856, 28%) compared to males (n=319, 11%; OR 3.20 (95% CI 2.78 to 3.68); P<0.001). In males only, GJH at age 14 years was associated with depression at 18 years (OR 2.10 (95%CI 1.17 to 3.76); P=0.013). An index of basal physiological arousal, elevated resting heart rate, mediated this effect. Across genders, the diagnosis of JHS at age 18 years was associated with the presence of depressive disorder (adjusted OR 3.53 (95%CI 1.67 to 7.40); P=0.001), anxiety disorder (adjusted OR 3.14 (95% CI 1.52 to 6.46); P=0.002), level of anxiety (B=8.08, t(3278)=3.95; P<0.001), and degree of psychiatric symptomatology (B=5.89, t(3441)=0.093; p<0.001). Conclusions: Variant collagen, indexed by joint hypermobility, is linked to the emergence of depression and anxiety in adolescence, an effect mediated by autonomic factors in males. Recognition of this association may motivate further evaluation, screening, and interventions to mitigate development of psychiatric disorders and improve health outcomes.