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✍️ Rachel Legg | MBiochem Biology student at the University of Bath
What is schizophrenia and what is it caused by? 🧠
Schizophrenia is a mental health condition that is caused by both genetic and environmental factors.
Schizophrenia is a mental disorder that affects approximately 1% of the worldwide population. It is characterised by a range of psychological symptoms including hallucinations, delusions, and disorganised speech- a collection of symptoms that are often referred to as psychosis.
Schizophrenia is thought to be caused by a range of both genetic and environmental factors. It has been suggested that neurotransmitter imbalances, recreational drug use, stressful life events and birth complications could all contribute to the chance of developing schizophrenia. Emerging evidence also suggests that inflammation and infections can impact the disease development in certain individuals.
What prompted research interest in this topic? 🕰
Links between schizophrenia and the immune system have been noticed for decades but have been dismissed until recent evidence.
Following large outbreaks of influenzas in the 1800s and 1900s, in particular the 1918 flu pandemic, physicians noticed an uptick in patients suffering from delusions and hallucinations. This was so common that it resulted in the term "psychoses of influenza". The link between psychosis and infections was again detected in multiple epidemiological studies which found that children born in the winter and the spring (when infectious pathogens typically circulate more) had a greater chance of developing schizophrenia. In addition, research at the University of Copenhagen revealed that the risk of developing a schizophrenia spectrum disorder increased as the individual's number of infections increased.
Many scientists have dismissed this link between infections and schizophrenia, as it was thought that the brain was protected from the body's immune response due to the blood-brain barrier. However, recent research has found that this barrier can become leaky. The brain also possesses immune cells called microglia that can promote autoimmune inflammation. Furthermore, the discovery of anti-NMDAR encephalitis, an autoimmune disease commonly presenting as acute psychosis, provided evidence that the body's own antibodies could attack the brain and manifest in schizophrenia-like symptoms.
These findings have prompted research into understanding the role of the immune system in schizophrenia, which some hope will be a "new era of schizophrenia research".
How does the immune system play a role schizophrenia? ⚙️
The immune system may be implicated in the development of schizophrenia through infections, neuroinflammation and immune proteins.
Although the precise disease mechanisms of schizophrenia are still unclear, there are many different theories about the impact of the immune system on schizophrenia.
Infections: Both viral and bacterial infections are also thought to play a role in the development of schizophrenia. Infections are known to increase the permeability of the blood-brain barrier, allowing immune cells and pro-inflammatory cytokines into the CNS. This creates an inflammatory state in the brain, which can disrupt signalling in the brain and contribute to oxidative stress. For example, pro-inflammatory cytokines are associated with raised concentrations of kyurenic acid, an NMDA receptor inhibitor. Increased concentrations of this acid disrupts certain brain signalling pathways, resulting in schizophrenia symptoms.
Inflammation: Post-mortem brain studies of schizophrenia patients have found an increase in the expression of genes related to increased inflammation, especially in the temporal cortex region. This inflammation can result in structural brain changes, such as a decrease in cortical gray matter volume. Inflammation has also been linked to a reduction in levels of neurotrophic factors, which support brain functions like generating new neurons and maintaining flexible connections between them. Treatments targeting neuroinflammation have shown some efficacy in schizophrenia, supporting this hypothesis.
Major histocompatibility complex (MHC) proteins: Genomic studies have found differences in genes linked to MHC proteins. These proteins are located on the surface of immune cells that are essential to brain development. Their disruption may contribute to the disease mechanism of schizophrenia.
How does this impact schizophrenia treatment? 💊
Further research has the potential to discover new forms of treatment for schizophrenia.
Understanding the link between schizophrenia and the immune system more clearly has the potential to provide new, personalised treatment possibilities for subgroups of individuals with schizophrenia if their immune system is implicated in the development of the disease. It has been suggested that a form of immunotherapy could dramatically improve symptoms for people experiencing psychosis.
Does everyone agree with that the immune system and schizophrenia are connected? ⚖️
Some scientists remain unconvinced that there is a strong link, but more research is needed.
Some researchers still remain sceptical that the immune system plays a significant role in schizophrenia. Although encouraging, many of the epidemiological studies on this topic highlight only an association between schizophrenia and infections, not necessarily a causative relationship. Furthermore, one study found that signs of severe inflammation are only observed in about a third of patients with schizophrenia, suggesting that the immune system may only impact schizophrenia in a subgroup of people.
Nevertheless, both proponents and sceptics would likely agree that more research is needed to understand the connection between the immune system and schizophrenia more clearly- as this has the potential to help prevention efforts and improve personalised treatment.
Edited by Zoe Davies | Associate Content Editor | BSc Pharmacology graduate, University of Leeds
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