Depression, schizophrenia and other mental health conditions affect 1 in 4 people in their lifetime, but mechanisms underlying these conditions are poorly understood. New research led by researchers at the University of Bristol has linked the body's immune response with schizophrenia, Alzheimer's disease, depression, and bipolar disorder. The study demonstrates mental health conditions might be affected by the whole body as well as changes in the brain. The findings could pave the way for better treatments of some mental health conditions.
Most people with depression or schizophrenia are treated with drugs that work on brain chemicals such as serotonin and dopamine. However, 1 in 3 people with these conditions do not benefit from these treatments, suggesting that other mechanisms are involved.
The study led by Dr Christina Dardani and Professor Golam Khandaker in Bristol's MRC Integrative Epidemiology Unit (IEU) used Mendelian randomisation – a computational approach that uses genetic information from large datasets – to examine whether immunological proteins are likely to be involved in 7 neuropsychiatric conditions.
The research team looked at the relationship of 735 immune response related proteins measurable in human blood with depression, anxiety, schizophrenia, bipolar disorder, Alzheimer's disease, autism, and ADHD.
The researchers found a potential causal role of 29 immune response related proteins in these 7 neuropsychiatric conditions. From the identified biomarkers, 20 showed potential as targets of drugs approved for other conditions. These biomarkers could potentially be used in the future for novel therapeutics in the area of mental health conditions.
The findings suggest a fundamental change in the understanding of causal mechanisms for neuropsychiatric conditions. To date causal explanations for depression and schizophrenia have been predicted on monoamine neurotransmitters, such as serotonin and dopamine, but this study suggests that overactivity of the immune system could also contribute to the cause of mental health conditions.
Golam Khandaker, Professor of Psychiatry and Immunology and MRC Investigator in the Bristol Medical School: Population Health Sciences (PHS), said: "Our study demonstrates that inflammation in the brain and the body might influence the risk of mental health conditions.
"The findings challenge the centuries-old Cartesian dichotomy between the body and the mind, and suggests that we should consider depression and schizophrenia as conditions affecting the whole person."
The next step is to examine biomarkers identified through genetic analysis using other methods. This includes research based on health records, animal studies, and proof-of-concept clinical trials in humans, to further evaluate causality; understand precise mechanisms from inflammation to symptoms of mental health conditions; and therapeutic potential - does modulating immune pathways improve symptoms of these conditions.
The research was funded by a Medical Research Council programme grant for immunopsychiatry to Professor Golam Khandaker. This grant forms part of the University of Bristol's MRC IEU.
Paper
'Immunological drivers and potential novel drug targets for major psychiatric, neurodevelopmental, and neurodegenerative conditions' by Christina Dardani, Golam M. Khandaker et al. in Molecular Psychiatry [open access]
