Medical Research: What are the main findings of the study?
Dr. Khandaker: The study shows low grade systemic inflammation may have a role in the pathogenesis of depression and psychotic disorders. Low grade systemic inflammation may also be a common cause for chronic physical and psychiatric illnesses.
The study shows that higher serum levels of the circulating inflammatory marker, interleukin 6 (IL-6), in childhood is associated with nearly two-fold increased risk of developing depression and psychotic disorder in young adulthood. This association persisted after taking into account effects of age, sex, social class, ethnicity, body mass index, maternal depression, and past psychological and behavioural problem in the participant.
We studied a sample of 4,500 individuals from the Avon Longitudinal Study of Parents and Children birth cohort, taking blood samples at age 9 and following up at age 18, to see if they had experienced episodes of depression or psychosis. We excluded children with an infection at the time of blood test at age 9 years.
Increased systemic inflammation, as measured by serum IL-6 and CRP, has been previously shown to be associated with risks of developing heart disease and diabetes mellitus. Depression and psychosis are also highly comorbid with heart disease and diabetes mellitus.
Thus, the results suggest that systemic inflammation may have a role in the pathogenesis of depression and psychotic disorders (which include schizophrenia). Systemic inflammation may also be a common mechanism for depression, schizophrenia, heart disease and diabetes.
Medical Research: Were any of the findings unexpected?
Dr. Khandaker: Previous studies have shown that patients with depression or psychosis have higher serum levels of IL-6, CRP and other inflammatory markers, which normalises after treatment. However, because these studies were based on people who are already unwell, they could not determine whether increase in inflammatory markers was a cause or consequence of illness. To our knowledge, we have carried out one of the first longitudinal studies of childhood inflammatory markers and subsequent mental illness; the study shows that higher levels of IL-6 at age 9 years is associated with nearly two-fold increased risk of developing depression and psychotic disorder at age 18 years. Our findings are consistent with the previous studies that showed that depression and psychosis are associated with increase in systemic inflammatory markers. Taken together, these results support a role of low grade systemic inflammation in the pathogenesis of depression and psychotic disorders.
Medical Research: What should clinicians and patients take away from your report?
Dr. Khandaker: Systemic inflammation may be a common cause for a number of chronic physical and psychiatric illnesses: heart disease, diabetes mellitus, depression, and psychosis. Thus, physical exercise and healthy diet, which are simple yet effective ways of reducing inflammation, would reduce risks of a number of illnesses.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Khandaker: In the future, studies should examine whether the association between early-life adversity, and risks of depression and psychosis in adult life could be explained by increase in systemic inflammation. We already know that early-life adversity, such as trauma, maltreatment, is associated with the risks of depression and schizophrenia. Recent studies have shown that early-life adversity is also associated with increased levels of circulating inflammatory markers, such as IL-6, in serum in childhood and adult life. Thus, it is possible that early-life adversity leads to low grade systemic inflammation, which, in turn, leads to depression, psychosis, heart disease, and diabetes.
Khandaker GM, Pearson RM, Zammit S, Lewis G, Jones PB. Association of Serum Interleukin 6 and C-Reactive Protein in Childhood With Depression and Psychosis in Young Adult Life: A Population-Based Longitudinal Study. JAMA Psychiatry. Published online August 13, 2014. doi:10.1001/jamapsychiatry.2014.1332.