Role of Inflammation in Depression: exciting therapeutic opportunity or fake news? – Dr Golam Khandaker, Lead, Inflammation and Psychiatry Research Group, Department of Psychiatry, University of Cambridge

May 14, 2020 @ 12:30 pm – 1:30 pm
Seminar Room
Herchel Smith Building
Forvie Site.
Dr Muzaffer Kaser

The immune system, particularly low-grade systemic inflammation, has been implicated in pathogenesis of depression and schizophrenia. Inflammation is thought to be a clinically relevant phenotype, as evidenced by three widely replicated findings: (1) concentrations of acute phase proteins (e.g. C-reactive protein or CRP) and inflammatory cytokines (e.g. interleukin 6 or IL-6) are elevated during acute depression; (2) these elevated levels tend to normalise after recovery; (3) patients with treatment resistant depression continue to display evidence of low-grade inflammation.
Currently, a number of RCTs are testing the efficacy of novel anti-inflammatory drugs for patients with depression. However, there are key unanswered questions both mechanistic and clinical. Is inflammation a causal risk factor for depression? Because, elevated inflammatory markers could be a result of illness/associated stress (i.e. reverse causality) or confounding by life style and other known/unknown factors. What are the features of immune-related depression? Could anti-inflammatory treatment be used to treat depressive symptoms? If so, which patients are likely to benefit? How does peripheral inflammation communicate with the brain to influence mood, cognition and behaviour?
Dr Khandaker will present current evidence on these issues. He will discuss evidence from population-based studies and Mendelian randomization genetic analysis suggesting that reverse causality and residual confounding are unlikely to fully explain previously reported associations of depression with IL-6, CRP, and that the IL-6/IL-6R pathway could be causally linked with depression. He will present data from systematic reviews and meta-analysis on the effect of anti-inflammatory drugs, including monoclonal antibodies (mAb), on depressive symptoms. These studies have informed an ongoing proof-of-concept double blind RCT of tocilizumab (anti-IL-6R mAb) for patients with depression, the Insight study (ISRCTN16942542), which will be discussed.

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