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Evidence linking Schizophrenia to autoimmune conditions like lupus is mounting. It’s been almost 100 years since people first theorized that psychosis may be the result of the immune system attacking the brain. Up until recently, autoimmune diseases and mental illnesses have been studied as separate entities.
Now, more and more research is supporting the idea that inflammation can attack the brain and lead to mental illness symptoms. Large scale studies in multiple areas of the globe have found that people with schizophrenia have roughly a 45 to 50% increased chance of also having an autoimmune disease. For people who already have an autoimmune condition, the likelihood of developing schizophrenia or psychosis is similarly higher. Understanding this connection holds the promise of unveiling new insights into the development, diagnosis, and treatment of both autoimmune diseases and mental illnesses.
Notable stories linking autoimmune illnesses and schizophrenia
Every year, countless people suddenly begin experiencing psychotic symptoms such as visual or auditory hallucinations, delusions that people are out to get them, and general confusion, disorganization, and strange behavior. Some are even completely catatonic, unable to move, speak, or care for themselves in any way. For the vast majority of these people, their future is filled with many hospital stays and numerous medications until finding treatments that work.
A few stories stand out, though. They are of people who received drugs that treated their immune systems instead of the traditional cocktail of psychiatric medications. The Washington Post recently published the stunning story of April Burrell’s recovery from years of psychotic symptoms.
Up until her early 20s, April showed no signs of major mental illness. However, a traumatic experience triggered a sudden change, and her mind became plagued by hallucinations and delusional thoughts. She was diagnosed with Schizophrenia. She even entered a “catatonic state” – a condition of decreased movement, speech, and responsiveness to her surroundings.
April remained this way for over 20 years, until doctors discovered she also had lupus. Lupus is a chronic autoimmune disease where the immune system mistakenly attacks healthy tissues, leading to inflammation and damage in multiple systems of the body. When her team began treating the lupus, her symptoms rapidly improved. She was ultimately able to care for herself and leave the psychiatric institution she had lived in for decades.
April’s story sadly isn’t unique, either. If you’ve never read the book, “Brain on Fire”, put it on your reading list. In this autobiographical true story, the author, Susannah Cahalan, recounts how she suddenly began suffering from seizures, delusions, and paranoia at age 24. She rapidly lost the ability to communicate or think coherently. Her thoughts wandered to the bizarre. She believed people were plotting against her and that she could age people with her mind.
A series of diagnoses followed as a slew of doctors offered various psychiatric explanations and medications. But none of them worked. Finally, the last in a long line of specialists diagnosed her with anti-NMDA receptor autoimmune encephalitis – an extremely rare type of brain inflammation. With appropriate treatment, Susannah made a full recovery.
Both these stories – and many more I’ve left out – followed a similar pattern: psychotic symptoms suddenly appearing in young adults. The vast majority of people in that situation enter the medical system for answers only to meet a long series of doctors and medications. Knowing what we know now, we realize the untold number of people who needlessly suffered while searching for answers in the wrong places.
Separating schizophrenia and autoimmune conditions
That brings us to the next stumbling block. How do we separate people who actually have schizophrenia from those with autoimmune conditions causing psychotic symptoms? This is actually a fairly standard procedure in psychiatry, not just for schizophrenia but for everyone who develops psychiatric symptoms. Doctors need to make sure those symptoms are not due to any other medical conditions before looking for psychiatric explanations and treatments.
Science gives us some clues as to where to look, though. There are numerous autoimmune conditions that have suspicious correlations with schizophrenia and the appearance of psychotic symptoms. The discovery of anti-NMDA receptor autoimmune encephalitis adds one possibility to a list of existing autoimmune conditions that could cause problems.
Anti-NMDA receptor autoimmune encephalitis is just one of several types of autoimmune encephalitis. The common theme among them is that the body begins producing antibodies that target the brain’s own neurons. Antibodies are proteins that help cells in the immune system identify what they should attack and destroy. This autoimmune phenomenon is what leads to the symptoms that are so reminiscent of schizophrenia. Nearly 3 in 4 people with anti-NMDA receptor autoimmune encephalitis have psychotic symptoms. Over 1 in 8 of them initially get misdiagnosed with a psychiatric issue.
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease where the immune system attacks healthy tissues and organs. Inflammation is widespread throughout the body and usually has the most devastating effects on the kidneys, skin, joints, heart, and brain. SLE is frequenly found alongside many mental health conditions, including anxiety and depression. Studies have found up to 1 in 10 people with SLE experiencing psychotic symptoms and an increased risk of schizophrenia in people with SLE.
Multiple sclerosis (MS) is an autoimmune condition that attacks the body’s motor neurons. This results in periods of physical weakness and debility that come and go, getting progressively worse throughout a person’s life. Depression and anxiety frequently appear in people with MS, as well as psychotic symptoms. Studies connecting MS with schizophrenia have mixed results, but some show significantly increased risk of psychosis in people with this autoimmune condition.
Other potential links
Celiac disease, type 1 diabetes, and other autoimmune diseases that attack the nerves, the skin, and the thyroid gland are also possibly linked to schizophrenia. This is generally based on studies finding higher rates of these disorders among people with schizophrenia or psychotic symptoms. Research also supports links in the other direction, implying that people with these disorders are more likely to develop schizophrenia. However, that is as far as research has gotten in attempting to link these disorders.
How could this work?
This is where things get tricky. The mechanism linking autoimmune diseases and schizophrenia is a new area of research. However, there are several avenues of investigation that hold some promise.
One possible source of problems is the presence of neuronal surface antibodies, which lead the body’s immune system to attack its own tissues. They are present in multiple autoimmune conditions and have been associated with neurological problems, schizophrenia, and neuropsychiatric lupus. This is just one of many imbalances in the immune system that could be a potential culprit.
Infections, especially during pregnancy, are another common risk factor for autoimmune conditions and schizophrenia. This is because infections can increase the permeability of the blood-brain barrier. This allows the entry of immune cells and pro-inflammatory messengers into the central nervous system, where they normally would not go.
Genetic factors could also play a role in the association between autoimmune diseases and psychotic disorders. Some studies have found genetic overlaps in immune-related genes in people with schizophrenia. However, not all research shows the same promise.
The gut microbiome has been linked to both neurological, psychiatric, and autoimmune diseases. Imbalances in intestinal biology could potentially influence immune responses and mental health. Additionally, psychological stress and trauma is associated with an increased risk of autoimmune conditions and schizophrenia. Stress can potentially contribute to chronic inflammation and dysregulation of immune response.
Ultimately, this is still a very new area of investigation. These case reports provide some hope for people and families touched by schizophrenia and psychotic disorders. However, there are still many more people with schizophrenia whose symptoms cannot be attributed to autoimmune disease. Schizophrenia is still a true, independent illness. We should not expect to explain away every case of it with these new discoveries.