What Is the Main Idea?

Schizophrenia is a long-term (chronic) mental health condition. In the research article “Autoantibodies against Central Nervous System Antigens and the Serum Levels of IL-32 in Patients with Schizophrenia”, published in the journal Neuroimmunomodulation, the authors investigate whether dysregulation of the immune system may play a role in the development of schizophrenia.

What Else Can You Learn?

In this blog post, schizophrenia and psychosis are discussed, as well as the immune system in general and how disorders can be caused by autoimmune responses.

What Is Schizophrenia?

Schizophrenia is associated with a state of being called “psychosis”, in which a person loses some contact with reality and may be unable to distinguish their own thoughts and ideas from what is real. Key symptoms of active schizophrenia include delusions (where someone has strong beliefs that are not shared by others, for example that someone is trying to communicate important messages to them or that there is a conspiracy against them), hallucinations (where a person experiences things that only exist inside their mind, such as seeing, hearing, smelling, or feeling things that aren’t real), and muddled thoughts as a result of them. People with active schizophrenia may also have disorganized speech; lose interest in their normal social and everyday activities and personal hygiene; difficulty remembering things, understanding information, and making decisions; difficulties focusing on things; and a lack of emotion in their face or voice. Although people with schizophrenia are sometimes portrayed as having a split personality or multiple personalities, it is not something that is associated with this condition.

How Common Is Schizophrenia?

It is estimated that schizophrenia affects around 1 in 300 people worldwide (0.32% of the global population). Although it is believed to affect men and women equally, initial symptoms tend to appear earlier in men (in their late teens and early 20s) than in women (in their 20s and early 30s). Some people with schizophrenia will have episodes throughout their lifetime while others will have minimal symptoms.

What Causes Schizophrenia?

The exact causes of schizophrenia aren’t yet known but research suggests that it is likely to be caused by a combination of factors. Possible environmental factors (external influences that can affect an individual’s health and wellbeing) include increased urbanization, cannabis use in adolescence, infections, and traumatic life experiences. It is believed that some people may be more susceptible to developing schizophrenia, which suggests that genetic factors (things that are inherited from our parents) may be involved. Some research studies have suggested that abnormal or impaired regulation (dysregulation) of the immune system may also play a part.

What Is the Immune System?

The immune system protects your body from things that could make you ill and is divided into two branches: innate (non-specific) and adaptive (specific). The innate immune system defends against harmful germs and substances that enter the body. Key components are inflammation (which traps things that might be harmful and begins to heal injured tissue) and white blood cells (which identify and eliminate things that might cause infection; they are also called “leukocytes”).The adaptive immune system makes antibodies and involves specialized immune cells, which together enable the body to fight specific germs that it has previously come into contact with, sometimes providing lifelong protection.

How Might the Immune System Be Linked to Schizophrenia?

The term “antigen” describes anything that causes a response by the immune system and can include chemicals, or molecules on the surfaces of bacteria and viruses. The cells in your body also have molecules on their surfaces, but the immune system usually recognizes them as “self-antigens”; in other words, the immune system knows that they are not “foreign” and should not be removed. However, sometimes the body’s immune system starts to recognize self-antigens as foreign ones and begins to attack them. When this happens, it is described as an “autoimmune” response and can result in the destruction of normal, healthy body tissue, or changes in the function or abnormal growth of an organ. There are more than 80 known medical conditions caused by autoimmune responses that are all very different. They include type 1 diabetes, rheumatoid arthritis, multiple sclerosis and celiac disease.

Some research studies have suggested that dysregulation of the adaptive and innate immune systems may contribute to the development of schizophrenia. Some have reported that levels of cytokines, a type of protein that has an effect on the activity of the immune system, are higher during acute (short-term or begin and worsen quickly) schizophrenic episodes and lower when people are receiving treatment. The production of autoantibodies and inflammation may also be involved. Inflammation has been shown to cause a type of cell in the central nervous system called microglia to migrate into blood vessels in the brain. If the inflammation occurs over a prolonged period of time, the microglia in the blood vessels can disrupt the blood–brain barrier. The blood–brain barrier tightly regulates which molecules and cells can move from the body’s general bloodstream into the brain, and plays an important role in preventing infections from developing in it.

What Did This Study Find?

In this study, the authors investigated whether the levels of a cytokine called interleukin-32 (IL-32) differ between people with or without schizophrenia. IL-32 plays an essential role in activating the adaptive and innate immune responses, and upregulates inflammation by causing cells in the immune system to produce cytokines that increase inflammation. They found that levels of IL-32 in blood samples from people with schizophrenia were significantly higher than from a non-schizophrenia control group, and that levels of other cytokines that promote inflammation were also increased. Increased levels of IL-32 have also been reported in people with autoimmune diseases such as Grave’s disease and rheumatoid arthritis. However, the potential role of autoantibodies attacking self-antigens in the central nervous system in the development of schizophrenia is poorly understood. The authors went on to investigate whether autoantibody levels in people with schizophrenia were higher than in the non-schizophrenia group and found that levels of autoantibodies against an enzyme called GAD were significantly increased. GAD is involved in the production of a neurotransmitter (a signaling molecule that transmits a signal from one nerve to another) called gamma-aminobutyric acid (GABA), and it is known that GABA deficiency in the central nervous system can cause motor and cognitive problems. Dysfunctional neurons that rely on GABA have been seen in the brain in several neurological disorders (which affect the brain and the nerves found throughout the body). In one study, people with psychosis were found to be more than twice as likely to have GAD autoantibodies as people in the general population.

Take-Home Message

It is possible that dysregulation of the immune system plays a role in the development of schizophrenia. However, research in this area is at an early stage and more research is needed to improve our understanding of how schizophrenia develops and can be treated most effectively.

Note: This post is based on an article that is not open-access; i.e., only the abstract is freely available.

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