Studies presented at this year’s International Early Psychosis Association (IEPA) meeting in Milan, Italy (20-22 October) suggest that increased levels of inflammatory cytokines are associated with increased rates of depression and psychosis, and that treatment to reduce cytokine levels can reduce symptoms of depression. The studies are by Dr Golam Khandaker, Department of Psychiatry, University of Cambridge, UK, and colleagues.

The authors first analysed data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort (4415 children). Their analysis found that a higher serum level of the inflammatory cytokine interleukin 6 (IL-6) at age 9 years was associated with a 55% increased risk of developing depression, an 81% increased risk of developing depression and over two-fold increased risk of psychotic disorder at age 18 years. Elevated IL-6 levels were also associated with increased risk of persistent depressive symptoms between ages 10 and 18 years.
The authors also carried out a systematic review and meta-analysis of antidepressant activity of anti-cytokine treatment (monoclonal antibodies and cytokine inhibitors) using clinical trials of chronic inflammatory conditions such as rheumatoid arthritis in which depressive symptoms were measured as a secondary outcome. Data from seven randomised controlled trials (2370 participants) showed significant antidepressant effect of anti-cytokine treatment compared with placebo. Further analysis showed that the antidepressant effect was not associated with improvement in primary physical illness. Or put another way, the anti-cytokine treatment reduced the symptoms of depression regardless of whether it improved the physical illness.
The authors say: “Inflammation may play a causal role in the pathogenesis of depression and psychosis. Anti-inflammatory drugs may be useful for some patients with depression particularly those with evidence of inflammation.”
“About a third of patients who are resistant to antidepressants show evidence of inflammation,” adds Dr Khandaker. “So, anti-inflammatory treatments could be relevant for a large number of people who suffer from depression.”
He concludes: “We need more studies, particularly randomised controlled trials of anti-inflammatory drugs in patients with depression who are inflamed but are free from major physical comorbidities, to investigate the effect of these drugs on depression. More studies are also needed to understand potential side effects of anti-cytokine drugs especially in patients with psychiatric disorders as some of these drugs can be associated with serious side effects. We and other research groups from both sides of the Atlantic are currently planning and conducting such trials.”

References:

1. 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. 2014 Oct;71(10):1121-8.
2. Kappelmann, N et al. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Molecular Psychiatry; 18 Oct 2016; DOI: doi:10.1038/mp.2016.167