Dysglycaemia, inflammation and psychosis: findings from the UK ALSPAC birth cohort

Background: Psychosis is associated with both dysglycaemia and low-grade inflammation, but population-based studies investigating the interplay between these factors are scarce.

Aims: (1) To explore the direction of association between markers of dysglycaemia, inflammation and psychotic experiences (PEs); and (2) To explore whether dysglycaemia moderates and/or mediates the association between inflammation and PEs.

Method: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were modeled using logistic and linear regression to examine cross-sectional and longitudinal associations between markers of dysglycaemia (ages 9 and 18), interleukin-6 (IL-6) (age 9), and PEs (ages 12 and 18). We tested for an interaction between dysglycaemia and IL-6 on risk of PEs at age 18, and tested whether dysglycaemia mediated the relationship between IL-6 and PEs.

Results: Based on 2627 participants, at age 18, insulin resistance (IR) was associated with PEs (adjusted OR = 2.32; 95% CI, 1.37-3.97). IR was associated with IL-6 both cross-sectionally and longitudinally. Interaction analyses under a multiplicative model showed that IR moderated the association between IL-6 at age 9 and PEs at age 18 (adjusted OR for interaction term = 2.18; 95% C.I., 1.06-4.49). Mediation analysis did not support a model of IR mediating the relationship between IL-6 and PEs.

Implications: IR is associated with PEs in young people even before the onset of clinical psychosis. Metabolic alterations may interact with childhood inflammation to increase risk of PEs. The findings have implications for clinical practice and future research.