The mediating role of neuro-immune markers in the long-term association between insomnia and depression: an eight-year follow-up

introduction: robust meta-analytic evidence of longitudinal epidemiological studies shows that insomnia (i.e., difficulties falling asleep or maintaining sleep, non-restorative sleep) may be associated with future onset of depressive symptoms in short- to medium-term follow-ups. however, there is still a dearth of literature on the long-term association between sleep disturbance and depression, and on the psychobiological processes underlying this association. to address these gaps, this study aimed to investigate the long-term association between insomnia and depressive symptoms in older adults and ascertain whether this association is mediated by neuro-immune markers. materials and methods: data analysis was conducted on 3998 participants aged 50 and above from the english longitudinal study of ageing (ELSA) across three waves of data collection. conditional process analysis was employed to estimate the association between insomnia symptoms assessed in 2008/9 using the Jenkins sleep scale, and self-reported depressive symptoms assessed in 2016/2017 using the centre for epidemiological studies-depression (CES-D). serum levels of high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, and insulin like growth factor-1 (IGF-1) measured in 2012/2013 were considered as mediators. participants with sh-CRP values >10 mg/L were excluded from the study since this could reflect current acute infection rather than chronic inflammation. analyses were adjusted for health-related and psychosocial confounders including cardiovascular disease, age, co-habitation status, alcohol intake, smoking, and baseline depression. results: Insomnia at baseline significantly predicted depression at eightyear follow-up. Hs-CRP and IGF-1 significantly mediated the association between insomnia and depression only in unadjusted analysis. when adjusted for health-related and psychosocial confounders, simple slopes analysis revealed that insomnia predicted higher hs-CRP only in participants with concomitant short sleep duration (#6 hours), as well as lower IGF-1 independent of sleep duration. also, hs-CRP directly predicted depressive symptoms. WBC count did not significantly correlate with insomnia in preliminary correlation analysis; thus, WBC count was not considered in the mediation model. conclusions: whilst insomnia resulted significantly associated with depressive symptoms in a long-term follow-up, present data does not provide robust evidence that increased inflammation may mediate this association. rather, present findings suggest that difficulties in sleep onset and sleep maintenance may be associated with inflammation and depressive symptoms only when coupled with short sleep duration. the mediation role of further neuro-immune markers should be explored in future longitudinal studies, including interleukin-6 (IL-6), and the brain-derived neurotrophic factor (BDNF).