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Experts have long understood that autoimmune diseases and disorders can harm a person’s physical health. Recently, though, the results of several research efforts expand on the connection between a dysfunctional immune system and mental health conditions. One new study explores the connection between autoimmune diseases and schizophrenia.

What Are Autoimmune Diseases?

The immune system is a network of organs, proteins, blood cells, and chemicals that protects the body against threats such as infections and diseases.

A properly functioning immune system identifies and fights off viruses and bacteria. Unfortunately, in some cases the immune system malfunctions and attacks healthy cells. When this occurs, a person has an autoimmune disease or an autoimmune disorder.

The Cleveland Clinic has reported that health experts have identified more than 100 autoimmune diseases. Examples include:

  • Type 1 diabetes
  • Rheumatoid arthritis
  • Celiac disease
  • Multiple sclerosis
  • Myasthenia gravis
  • Lupus
  • Autoimmune myocarditis
  • Psoriasis

Most autoimmune disorders are chronic conditions. Some responde well to proper medical care and certain behavioral changes. However, some autoimmune diseases can significantly decrease both quality of life and life expectancy.

Autoimmune Disease & Mental Health

The potential connection between autoimmune diseases and mental health concerns is not new.

As reported in an article in The Scientist magazine, healthcare workers noted an increase in patients with delusions, hallucinations, and similar symptoms in the aftermath of large-scale influenza outbreaks in the late 1800s and early 1900s.

According to the article:

“There were records of influenza pandemics whereby people acutely affected with influenza acted in ways consistent with what we now understand to be psychosis.”

According to a March 2019 article in the journal Frontiers in Psychiatry, researchers continued to note an association between autoimmune disorders, psychosis, and schizophrenia throughout the 20th century:

  • In the 1930s, German neuropsychiatrist Hermann Lehmann-Facius theorized that schizophrenia may be the result of naturally produced antibodies attacking tissue in the brain.
  • In the 1950s and 1960s, healthcare professionals observed that people who had schizophrenia also had higher-than-average rates of celiac disease.
  • Also in the 1960s, researchers found evidence of antibody interactions with antigens in the brains of people who had schizophrenia.

Through the years, “the amount of evidence supporting the notion of a link between immunological processes and psychotic disorders has increased,” wrote Rose Jeppesen and Michael Eriksen Benros, authors of the Frontiers in Psychiatry article.

“Elevated levels of inflammatory markers have been found both in the blood and [cerebral spinal fluid] of patients with psychosis, with even higher levels in patients in first episode psychosis or acute relapse,” Jeppesen and Benros added. “Moreover, it has been suggested that schizophrenia could be an autoimmune disease, based on similarities such as the remitting-relapsing phenotype of the illness, as well as the above-mentioned immunological processes.”

Autoimmune Disease & Schizophrenia

Various reputable sources estimate that schizophrenia affects 0.33%-1.0% of the global population, and that 3%-5% of people have an autoimmune disorder.

In their March 2019 Frontiers in Psychiatry article, Jeppeson and Benros reported the following statistics about an increased risk of schizophrenia and autoimmune disorders among people who already had one of the conditions:

  • Two large register-based studies from Denmark in 2011 and 2014 found that 6% of people with schizophrenia also reported hospital contact related to an autoimmune disease.
  • A 2012 study from Taiwan found that 3.4% of persons in contact with a hospital for autoimmune diseases also received care related to schizophrenia.
  • A meta-analysis published in 2018 found a diagnosis of a non-neurological autoimmune disease increased the likelihood of subsequent diagnoses with a psychotic disorder by 43%.
  • Two studies revealed risk of developing an autoimmune disorder was about 50% higher in people with symptoms of psychotic disorders than among the general public.

Jeppeson and Benros also noted that people with a first-degree relative (parent or sibling) with schizophrenia are 6 percent more likely to have an autoimmune disease. Conversely, having a family history of autoimmune disorders may increase a person’s risk of developing schizophrenia and/or psychosis by as much as 10 percent.

The Impact of Antibodies

Documenting the relationship between autoimmune diseases and schizophrenia is a significant step. But now that this connection is established, that begs a question:

Can experts use this knowledge to identify (and treat) people who may have an elevated risk of developing schizophrenia?

The answer to that question may lie in the effort to identify how some antibodies interfere with various brain functions.

Anti-NMDR Encephalitis

In Diana Kwon’s April 2022 article in The Scientist, she described research into how certain antibodies may affect mental health. Kwon’s article opens with a description of an apparently healtht\y young woman who reported rapid onset of intense hallucinations and extreme delusions:

  • The woman had a rare autoimmune disorder called anti-NMDAR encephalitis.
  • This disorder causes antibodies to interfere with the functioning of the NMDA receptor, a brain protein.
  • Abnormalities in the NMDA receptor appear in people who have autism, Alzheimer’s disease, dementia, and schizophrenia.

The presence of anti-NMDAR encephalitis demonstrates that naturally produced antibodies can disrupt brain functions. Prior to this, Kwon reported, many experts believed that the brain was protected from misdirected attacks from the body’s own immune system.

“Researchers have recognized that the blood-brain barrier can become leaky, compromising its ability to act as an impermeable shield,” Kwon wrote.

“Large-scale genomic studies in people with schizophrenia turned up genetic sequences associated with major histocompatibility complex (MHC) proteins, molecules on the surface of immune cells that present pathogen-derived peptides, as key regions implicated in the illness,” she added.

Anti-NCAM1 Antibodies

Previous research also examined the relationship between antibodies and schizophrenia.

A June 2022 Science Daily article described an antibody study conducted by researchers at Tokyo Medical and Dental University (TMDU). The TMDU team focused on an antibody that disrupts NCAM1, a protein that helps brain cells communicate.

Researchers took purified antibodies from human subjects and injected them into the brains of mice. Mice who received the antibodies demonstrated cognitive impairment, fewer synapses, and changes in startle reflex. All these signs reflect characteristics of people who have schizophrenia.

“Even though the mice only had these autoantibodies in their brains for a short time, they had changes in their behavior and synapses that were similar to what is seen in humans with schizophrenia,” the study’s lead author, Hidehiko Takahashi, said in the article.

Implications for Treatment

Research into antibodies and autoimmune diseases suggests that mental health professionals may someday have additional ways to treat schizophrenia. However, considerable work remains.

One recent effort involved the use of methotrexate, classified as an anti-metabolite. This drug is common in chemotherapy for cancer patients. It’s also effective for rheumatoid arthritis and other autoimmune diseases.

As described in a September 2021 article in the journal Translational Psychiatry, a research team in Pakistan conducted a randomized double-blind study that involved giving 10 mg of methotrexate or a placebo to 76 subjects diagnosed with schizophrenia in the previous five years.

Improvements or declines in subjects’ performance were measured via several tests, including:

  • Positive and Negative Syndrome Scale (PANSS)
  • Global Assessment of Functioning (GAF)
  • Schedule of Assessment for Insight (SAI)
  • Clinical Global Impression Scale (CGI)
  • EuroQol-5D (EQ-5D)
  • Social Functioning Scale (SFS)

After 12 weeks, the research team reported that methotrexate seemed to have a beneficial impact on the positive symptoms of schizophrenia. This category includes hallucinations, delusions, disorganized speech, and grossly disorganized behavior.

“Methotrexate appeared to exert a selective benefit on positive symptoms in early schizophrenia with no effect on negative symptoms or on cognitive performance but with an overall improvement in general and total symptoms and in general functioning,” the team reported.

Find Help for Schizophrenia in Southern California

If someone that you care about shows symptoms of schizophrenia or another complex mental health concern, please know that help is available. Crownview Psychiatric Institute, near San Diego, California, offers personalized care and comprehensive support within a dynamic community-based environment. With our help, your loved one can achieve improved functioning and a greater capacity for independent living. To learn more, please contact us.