Summary: New research reveals that immune system activity may play a causal role in conditions like schizophrenia, depression, and Alzheimer’s disease. Using Mendelian randomisation, scientists linked 29 immune-related proteins to seven neuropsychiatric disorders, suggesting the brain is not the only organ involved in mental health.
About 20 of these proteins are targets of drugs used for other diseases, opening potential avenues for new treatments. These findings challenge long-standing brain-only models and point to mental health as a whole-body issue shaped by both brain and immune function.
Key Facts:
- Immune Involvement Found: 29 immune proteins linked to seven mental health conditions.
- Drug Target Potential: 20 proteins are already targeted by existing drugs for other diseases.
- Rethinking Mental Health: Findings challenge traditional brain-only views, suggesting whole-body involvement.
Source: University of Bristol
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.
Credit: Neuroscience News
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.
Funding: 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.
About this mental health research news
Author: Joanne Fryer
Source: University of Bristol
Contact: Joanne Fryer – University of Bristol
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Immunological drivers and potential novel drug targets for major psychiatric, neurodevelopmental, and neurodegenerative conditions” by Christina Dardani et al. Molecular Psychiatry
Abstract
Immunological drivers and potential novel drug targets for major psychiatric, neurodevelopmental, and neurodegenerative conditions
Immune dysfunction is implicated in the aetiology of psychiatric, neurodevelopmental, and neurodegenerative conditions, but the issue of causality remains unclear impeding attempts to develop new interventions.
Using genomic data on protein and gene expression across blood and brain, we assessed evidence of a potential causal role for 736 immune response-related biomarkers on 7 neuropsychiatric conditions by applying Mendelian randomization (MR) and genetic colocalisation analyses.
A systematic three-tier approach, grouping biomarkers based on increasingly stringent criteria, was used to appraise evidence of causality (passing MR sensitivity analyses, colocalisation, False Discovery Rate and Bonferroni thresholds).
We provide evidence for a potential causal role of 29 biomarkers for 7 conditions. The identified biomarkers suggest a role of both brain specific and systemic immune response in the aetiology of schizophrenia, Alzheimer’s disease, depression, and bipolar disorder.
Of the identified biomarkers, 20 are therapeutically tractable, including ACE, TNFRSF17, SERPING1, AGER and CD40, with drugs currently approved or in advanced clinical trials.
Based on the largest available selection of plasma immune-response related biomarkers, our study provides insight into possible influential biomarkers for the aetiology of neuropsychiatric conditions.
These genetically prioritised biomarkers now require examination to further evaluate causality, their role in the aetiological mechanisms underlying the conditions, and therapeutic potential.
