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 immune activation is associated with poor response to psychotropic medications. Currently, a number of RCTs are testing the efficacy of novel anti-inflammatory drugs for patients with depression and schizophrenia. However, there are key unanswered questions both mechanistic and clinical. Is inflammation a causal risk factor for depression and schizophrenia? Could anti-inflammatory treatment be used to treat these disorders? If so, which patients are likely to benefit?

Professor Khandaker will present evidence from population-based longitudinal studies and Mendelian randomization genetic analysis addressing the issue of causality. These studies suggest that reverse causality or residual confounding is unlikely to fully explain the associations of interleukin 6 (IL-6), a pro-inflammatory cytokine, with depression and schizophrenia. He will present data from systematic reviews and meta-analysis on the effect of anti-inflammatory drugs, including monoclonal antibodies, on depressive symptoms. These studies have led to two proof-of-concept double blind RCTs of tocilizumab (anti-IL-6R monoclonal antibody) for patients with depression and first episode of psychosis including the ongoing Insight study (ISRCTN16942542), which will be discussed.

Speaker bio: Golam Khandaker MBBS, MPhil, MRCPsych, PhD

Professor of Psychiatry, Head of Immunopsychiatry and Experimental Medicine Program, MRC Integrative Epidemiology Unit, Population Health Sciences, University of Bristol

Wellcome Trust Fellow, University of Bristol & University of Cambridge

Honorary Consultant Psychiatrist, Avon and Wiltshire Mental Health Partnership NHS Trust; Cambridgeshire and Peterborough NHS Foundation Trust

Golam’s research focuses on identifying and validating novel immunological mechanisms and potential treatment targets for depression and schizophrenia using epidemiological cohort studies, genetic analysis, and early phase clinical trials. The key impetus for this work is to move immunotherapies closer to psychiatric clinic through innovative translational research. He is also interested in the aetiology, early detection and prevention of cardiometabolic disease in people with mental illness.

Notable work includes cohort and Mendelian randomization studies suggesting that the inflammatory IL-6/IL-6R pathway could be causally linked to depression and schizophrenia. These findings have led to a proof-of-concept RCT of tocilizumab, anti-IL-6R monoclonal antibody, for patients with depression (ISRCTN16942542). Golam has received awards from the International Early Psychosis Association (2014), Schizophrenia International Research Society (2015), and was selected as a Rising Star in Psychiatry by the UK National Institute for Health Research in 2017. He was an executive committee member of the Royal College of Psychiatrists academic faculty (2014-’18). Currently, he is an elected council member for the British Association for Psychopharmacology, and editorial board member for Brain, Behavior and Immunity, and Psychoneuroendocrinology.

Seminar chair

Professor Paul Moran