Insulin-like growth factor 1 and risk of later depression in older people: prospective evidence from the English Longitudinal Study of Ageing

Abstract

BackgroundDepressive disorders are a leading cause of mortality and morbidity. Whereas the role of psychosocial and behavioural predictors has been well examined, little is known about the biological origins of depression. In mice in which insulin-like growth factor 1 (IGF-1) was knocked out with viral vectors, there was evidence of increased signs of depression. In other studies, IGF-1 infusions in rodents had antidepressant properties. We tested the association of depression with IGF-1 in a large population-based study. MethodsIGF-1 concentrations were measured from serum taken at a nurse visit in 2008 from adults participating in the English Longitudinal Study of Ageing. Symptoms of depression were assessed in 2008 and 2012 with the eight item Center for Epidemiological Studies Depression Scale (CES-D) and diagnosis was based on self-report. Cross-sectional analyses were carried out on measures collected at baseline, in 2008. Outcome measures in longitudinal analyses were new reports of depression symptoms and physician-diagnosed depression in 2012. We used logistic regression to test both the cross-sectional and longitudinal associations, adjusted in a stepwise manner for age, anthropometric measures, comorbidities, psychosocial factors, and health behaviours. FindingsSamples from 6017 adults were included (mean age 65·7 years [SD 9·3], range 50–99; mean IGF-1 15·9 nmol/L [SD 5·7]). Mean CES-D score at baseline was 1·2 (SD 1·8). In cross-sectional and longitudinal analyses, the association between IGF-1 and symptoms of depression followed a U-shaped pattern—ie, lower and higher concentrations of IGF-1 were associated with an increased risk of depression, whereas the lowest risk was seen around median concentrations. In women, with the lowest quintile of IGF-1 as the referent, the age-adjusted odds ratios for increasing quintiles of IGF-1 in longitudinal analysis were 0·88 (95% CI 0·60–1·29), 0·77 (0·51–1·16), 0·84 (0·53–1·35), and 0·95 (0·60–1·50) (p for curve=0·027). Corresponding results in men were 0·51 (0·28–0·91), 0·50 (0·27–0·92), 0·63 (0·35–1·15), and 0·63 (0·35–1·13) (p for curve=0·002). These associations were partly attributable to comorbidities, adverse socioeconomic circumstances, and psychosocial and behavioural factors. Similar results were observed for the association between IGF-1 and physician-diagnosed depression. InterpretationIn the present study, which is the first to our knowledge to use validated measures of depression, there was some evidence that low and high concentrations of IGF-1 were associated with a slightly elevated risk of diagnosed depression and symptoms of depression. Further studies are needed to examine whether the observed association is causal and whether normalising IGF-1 concentrations with drugs or IGF-1 infusions could be useful and safe in the treatment of depression in older people. FundingThis work was supported by an Economic and Social Research Council–Medical Research Council studentship (awarded to SC).