We and others have identified numerous factors that influence mental health in young adults and early adulthood. These include obstetric complications, adversity, cannabis use, population density, immigrant status (PMID: 29352556, 12091183, 31563981) and most recently exposure to COVID (PMID: 35987197). Additionally, in the ALSPAC cohort, we recently identified that suicidal ideation at age 17 is associated with 7-fold increased odds of psychotic disorder, and with depressive disorder and generalised anxiety disorder at age 24. Indeed, over 40% of those with psychotic disorder in early adulthood had experienced this symptom in late adolescence (Mongan et al, 2022, unpublished).

We and others have also identified evidence for inflammatory marker
dysregulation both preceding and in association with psychiatric disorders
including psychosis, depression and recently, long COVID (PMID: 36085284 ,
35472304). Dysregulation of acute inflammatory markers [such as Interleukin
(IL)-6 and C-Reactive Protein] and complement proteins has been reported prior to
and in association with these outcomes (PMID: 25133871, PMID: 32857162).

Using ALSPAC data we identified for the first time the cross-sectional association of suPAR (soluble urokinase plasminogen activator receptor- an established marker of chronic inflammation) and IL-6 (an established marker of primarily acute inflammation) with psychotic disorder in young adults (Mongan et al 2022, under review). We previously found an inverse association between the anti-inflammatory marker n-3 fatty acid docosahexaenoic acid (DHA) at age 17 and psychotic disorder at age 24 in the ALSPAC cohort (PMID 34059620). Using ALSPAC data we have also shown for the first time that elevated suPAR is associated cross-sectionally with cannabis exposure, itself a marker for mental illhealth (Power et al 2022 (under review)).

We now seek to expand our knowledge to mental health outcomes in early adulthood (at age 24 and also at age 30 (when available)). We wish to examine not only associations between risk factors and inflammation in relation to clinical thresholds of psychiatric disorders, but also in relation to specific symptoms and symptom severity.

We hypothesise that exposure to environmental risk factors and early-life adversity is associated with chronic inflammatory dysregulation, in line with recent evidence (PMID: 31682707, 26033244, 34990745). We also hypothesise that inflammatory dysregulation will be more common in those who go on to report mental disorders in adulthood (PMID: 25133871, PMID: 32857162). Crucially, we hypothesise that inflammatory dysregulation mediates the relationship between environmental exposures and adult mental disorders, which could provide evidence for a
biological mechanism by which environmental exposures influences the risk of adult mental disorder. Alternatively, environmental exposures and biological risk factors may operate independently, but have a cumulative effect on the risk of mental disorders.

We propose to investigate this using a combination of existing ALSPAC data, and new data derived from assays undertaken by us which assessed levels of the robust marker of chronic inflammation, suPAR, in age 24 plasma samples donated by ALSPAC participants.

Only data from B4168 will be used