As researchers search for the yet to be discovered mechanism behind schizophrenia, they have traced some cases of this psychiatric condition back to an autoimmune connection- at least in mice. As with many neuropsychiatric diseases, multiple different triggers can lead to similar symptomatic pictures for the person afflicted. The search for answers and therapies requires uncovering the underlying mechanisms through which triggers cause harm while also tracking down the pathways the changes actually take. In this study, researchers built on known connections coming from genetic and other prior studies to find that nerve synapse autoantibodies in mice could result in schizophrenic behavior in the test mice.
Schizophrenia, according to the World Health Organization (Fact Sheet) affects about 24 million people worldwide, meaning about 1 in 300 have some degree of this disease (Institutes of health). With an onset usually in the late teen years or early twenties, it affects about 1 in 222 adults. The condition is associated with significant life stress and impairment along with a higher risk of early death (Laursen 2014). The symptoms may include persistent delusions, persistent hallucinations, feelings of being influenced uncontrollably by outside forces, disorganized thinking and behavior, negative symptoms such as limited speech or restricted emotional experience, and episodes of agitation. Only 1 in 3 of such people fully recover with complete remission of symptoms (Harrison 2001).
Leading into this study, researchers knew from prior studies by others that several genes related to a molecule called neurexin 1 alpha (NRXN1alpha) was linked to schizophrenia. This protein plays a role in the presynaptic end of nerve cells where they connect from the end of an axon to the next nerve receiving the signal. They also knew that autoantibodies, simply antibodies that attack our tissue instead of microbes, had been found in other neurological diseases. They were able to isolate an autoantibody against this NRXN1alpha molecule in a group of Japanese patients with schizophrenia. When tested in mice, the extracted autoantibodies “reduced the frequency of the miniature excitatory postsynaptic current in the frontal cortex of mice”. When these autoantibodies were injected into the cerebrospinal fluid of mice, they later found decreased synapses (connections between brain cells) and prior to autopsy the mice demonstrated schizophrenia like behaviors. As one more confirmation, when the autoantibodies were removed, the behaviors improved.
The researchers hope that this could lead to an effective therapy for schizophrenia patients with these autoantibodies one day. By some means of blocking or removing the antibodies, the severity of schizophrenia could be improved by such treatment in humans. Much more research is needed, but the possibilities could be life-changing for many.
In the meantime, how does this change how we approach schizophrenia or other neurological disorders today? For our patients who do not presently have the option of the forecasted yet still theoretical auto-antibody therapy, why not look for the triggers of autoimmunity which if removed could lower the pathologic process and improve symptoms now? Functional medicine already works in this way to uncouple the trigger from the mechanism. When we have a patient with autoimmunity, we look for food, toxin, and infectious triggers that could be continuing to drive an autoimmune process. While some triggers only need to be pulled once, leaving nothing to fix in the present, at times the trigger is still being pulled by continued presence of infection or toxin or even just the presence of a leaky gut. Addressing these factors sometimes brings significant relief without expensive therapies.
Helping patients restore healthier, more abundant lives means using the information we have available and the present means of relief available to help our patients as much as possible in the present. We do look forward to the potential therapies proposed by this article’s research, but that could be another 10 or 20 years. Many more could benefit from our approach until then and even afterwards as our prevention could be both more effective and cost conscious than ongoing autoantibody lowering therapies will likely end up being.
Hiroki Shiwaku, Shingo Katayama, Mengxuan Gao, Kanoh Kondo, Yuri Nakano, Yukiko Motokawa, Saori Toyoda, Fuyuko Yoshida, Hiroaki Hori, Tetsuo Kubota, Kinya Ishikawa, Hiroshi Kunugi, Yuji Ikegaya, Hitoshi Okazawa, Hidehiko Takahashi. Analyzing schizophrenia-related phenotypes in mice caused by autoantibodies against NRXN1α in schizophrenia. Brain, Behavior, and Immunity, 2023; 111: 32 DOI: 10.1016/j.bbi.2023.03.028
Thanks to Science Daily:
Tokyo Medical and Dental University. “Further link identified between autoimmunity and schizophrenia.” ScienceDaily. ScienceDaily, 31 May 2023. <www.sciencedaily.com/releases/2023/05/230531150109.htm>.
- World Health Organization. Fact Sheets: Schizophrenia. January 10, 2022. Accessed June 14, 2023. https://www.who.int/news-room/fact-sheets/detail/schizophrenia
- Harrison G, Hopper K, Craig T, Laska E, Siegel C, Wanderling J. Recovery from psychotic illness: a 15- and 25-year international follow-up study. Br J Psychiatry 2001;178:506-17.
- Institute of health Metrics and Evaluation (IHME). Global Health Data Exchange (GHDx). http://ghdx.healthdata.org/gbd-results-tool?params=gbd-api-2019-permalink/27a7644e8ad28e739382d31e77589dd7 (Accessed 25 September 2021)
- Laursen TM, Nordentoft M, Mortensen PB. Excess early mortality in schizophrenia. Annual Review of Clinical Psychology, 2014;10, 425-438.
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.