Schizophrenia is an extreme psychiatric disorder, about which doctors and scientists understand less than they do for most diseases and disorders that do not involve the brain. The brain and nervous system are incredibly complex, and there is much to learn about how the brain processes and stores information. There are many antipsychotic drugs on the market to treat schizophrenia and other mental illnesses such as bipolar disorder. Abilify®, Clozaril®, and Geodon® are only a few of the many. Through the work of multiple studies in the past decade or so, research now points to a connection between alteration of the immune system and psychosis. In a study recently published in the May issue of The Journal of Nervous and Mental Diseases by Wolters Kluwer Health, Inc., researchers investigated the potential link between prolonged inflammation and the later development of schizophrenia and bipolar disorder.
[pullquote align=”left” cite=”” link=”” color=”” class=”” size=””]Schizophrenia is an extreme psychiatric disorder, about which doctors and scientists understand less than they do for most diseases and disorders that do not involve the brain. [/pullquote]
The study, performed in Maryland, used pentraxin-3 (PTX3) as a marker of inflammation. PTX3, is a protein involved in innate immunity; the innate immune system is comprised of non-specific defenses of the body such as the physical barriers of skin and mucus, as well as fever, antimicrobial proteins, and inflammation. PTX3 is produced by some somatic and immune cells in response to inflammatory signals released by cells at sites of injury. PTX3 levels in the blood are usually low, below 2mg/mL, but can reach 200 to 800 ng/mL when there is inflammation. Using this information, researchers involved in this study tested PTX3 levels in U.S. military personnel in order to find a connection between inflammation and psychosis.
An on-going study of the U.S. military, Military New Onset Psychosis Project (MNOPP), from 1989 to 2006 collected specimens from military personnel aged 18-40. This study used the data from MNOPP, and randomly selected samples from 160 people who were later diagnosed with schizophrenia or bipolar disorder. Of the 160 people, 80 were later diagnosed with schizophrenia and 80 with bipolar disorder. In addition, to act as a control, the researchers chose the data of another 160 MNOPP participants who did not later develop schizophrenia or bipolar. These 160 people were selected to specifically match one schizophrenic or bipolar person based on age, race, military branch, age of diagnosis, years of service, and time between serum collection and diagnosis. This was done to eliminate any potential confounding variables.
After analyzing the PTX3 levels collected from all 320 military personnel, it was found that for bipolar disorder, mean and standard deviations of PTX3 levels were not significant against the matched controls. While this provides us with no solid link between bipolar disorder and inflammation, the results were different for schizophrenia. It was found that for subjects with schizophrenia, PTX3 levels were significantly lower before the onset of illness than the levels for those of the matched controls. It is possible that because PTX3 levels are low, an individual lacks certain immune functions that are present in people with normal levels. The lower level of inflammatory response could potentially contribute to the development of schizophrenia.
[pullquote align=”right” cite=”” link=”” color=”” class=”” size=””]The findings of this study may not provide any absolute conclusions, but they certainly prompt research on mental disorder in a new direction.[/pullquote]
The findings of this study may not provide any absolute conclusions, but they certainly prompt research on mental disorder in a new direction. It could be useful to study more in-depth the physiological pathway of pentraxin-3 and related blood proteins. Additionally, understanding different aspects of the neuro-inflammatory response could fill in some missing links and help shed light on biological markers for schizophrenia and bipolar disorder.
In good practice, it is important to discuss the limitations of any study as well. The PTX3 samples were collected only from physically fit U.S. military candidates, which is not representative of the U.S. or global population; therefore, the findings of this study cannot be considered 100% reliable as conclusions of a small sample can not infer parallel conclusions in a much larger population. Additionally, the study does not account for other individual genetic factors that may have attributed to either levels of PTX3 or likeliness of development of schizophrenia and bipolar disorder. Conducting a long-term, random sample study of PTX3 levels in subjects without a psychotic disorder would be a more effective study, but would also be a more costly and time-consuming study.
Weber, N., Larsen, R., Yolken, R., Cowan, D., Boivin, M., & Niebuhr, D. (2015). Predictors of the Onset of Schizophrenia in US Military Personnel. The Journal of Nervous and Mental Disease, 203, 319-324.