The Mythical Correlation of Influenza and Schizophrenia

By Mohammad Dawar Zahid


Schizophrenia is an enigmatic and debilitating psychological condition that leads to an impaired interpretation of reality and crippling paranoia. It affects well over 20 million people world-wide, with rates being higher for migrants and the homeless. Not much was understood about this mental illness. Hence, in an attempt to better understand the bizarre disorder, in-depth research of the causes and development of this disease, also known as its etiopathogenesis, was carried out. As a result, several new theories have made their way up to the chalkboard. One explanation is based around Teratogenesis.


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In a nutshell, teratogenesis is any process which leads to either apparent or hidden malformations in an infant during pregnancy (the Neonatal Period). These processes are caused by agents called Teratogens. Teratogens are classified into four types: metabolic conditions, physical agents, infections, and drugs. One teratogen you may regularly consume is alcohol. This is why consumption of alcohol by the mother during pregnancy is harmful, as it can cause a teratogenic pathway to form, leading to possible Foetal Alcohol Syndrome in the baby.


However, one particular virus caught the attention of researchers. In 1988, Dr. Saranoff A. Mednick published his Helsinki Influenza Study. Dr. Mednick’s life’s work was centered around schizophrenia, and this study sought to observe the effect of Influenza as a potential teratogen. It was noted that those who were in the womb during the 1957 Type A2 Influenza Epidemic in Helsinki had statistically increased cases of the illness. This was true for members of both genders and was seen in several psychiatric hospitals. The implication was that an infant is at an elevated chance of having schizophrenia in adult life if his/her mother contracted influenza during her pregnancy. This was informally termed as the Maternal Influenza Hypothesis by researchers. Although the explanation seemed elegant, it could produce no reason as to why an influenza infection during gestation caused schizophrenia in one’s adult life, rendering the statistical data circumstantial.


The results of the study, which were already on shaky ground, also became the basis of far-fetched conspiracy theories. These absurd claims postulated that schizophrenia was actually a man-made virus spread by the government. To what end, one may ask? The answer to that quickly became irrelevant to those afflicted with the disease as these insidious notions spread. Schizophrenic patients already possessed a symptomatic distrust of people, and with the spread of this theory, began to refuse medication, believing that it was all an attempt to ‘control their minds’.


Further studies, which were more responsible with their conclusions, have comprehensively debunked the Maternal Influenza Hypothesis. In one such example, researchers included statistical data of other countries such as the US, Europe, Australia and Japan for a diverse sample size. They also opted for a slightly different analysis approach using fixed-effect models and Relative Risks(RRs) calculations. Their findings, which were published in 2007, attempted to find an increased percentage of schizophrenia cases in patients who were in utero during the 1957 epidemic in the above mentioned countries. However no such increase was found and it concluded that there seemed to be no statistical correlation between the influenza epidemic and schizophrenia.


Furthermore, all records obtained for the Helsinki Influenza Research were only taken from hospitals, and hence scientists have argued that there is a high degree of misrepresentation in the records. Furthermore, the research assumed that all mothers had contracted influenza, when in reality only about half of them did. As mentioned previously, the Helsinki Influenza Study was also not able to provide any scientific reasoning as to why Influenza seemed to be causing Schizophrenia. And so,at its best, it was an attempt to statistically prove a correlation between Maternal Influenza and Schizophrenia, and the study itself has been declared inaccurate by many scientists.


However, while the study that originally presented the Hypothesis has been debunked, there has been ongoing work in the etiopathogenesis of Schizophrenia, which is attempting to see if there is any biochemical proof of the Maternal Influenza Hypothesis. There is some, albeit limited, evidence in favor of the theory. Mice born from mothers infected with mouse-adapted influenza exhibit a series of behavioral abnormalities that are very similar to Schizophrenia. Researchers at the Mount Sinai School of Medicine in New York, used these models to investigate the level of expression and behavioral function of 5-HT2A and mGlu2 receptors.


Still, however, even in these mouse-adapted models, scientists are unable to establish what teratogenic pathways cause these symptoms, and whether or not they are even Schizophrenic in nature, or are mere symptoms caused by maternal infection stress.


To date, the hypothesis that Maternal Influenza may contribute to the etiology of adult Schizophrenia is not fully supported by most scientists, but the possibility has not been completely eliminated yet. Previous studies were all statistical in nature, with scientists attempting to find correlation on the basis of statistics. However further research is being carried out, which may provide us with a definite etiology of Schizophrenia. In the end, we must trust in the scientific process and the experts who work on it.







Educational Content:

Q1) Does this mean that Schizophrenia cannot be caused if the mother contracted Influenza—Is the Maternal Influenza Hypothesis incorrect?


Answer: Not really. This article informs you that the chain of logical causation between Schizophrenia and Maternal Influenza being claimed by the Helsinki Research Study is flawed. The research used invalid data collecting methods, and had statistical inconsistencies present. Furthermore, it did not provide any scientific explanation as to why Maternal Influenza caused Schizophrenia. The study which disapproved of the Helsinki Research Study was also in nature a statistical study, and is thereby vulnerable to statistical anomalies. There has not been any definitive biochemical research, and thus it is too early to conclude whether or not there is a correlation between them. However, it is important to note that Maternal Influenza has been proven to cause other complications during birth. For example, it might cause high fever in the mother, which may lead to premature delivery. Thereby it is always good to take preventive measures during the flu season.


Q2) Assuming that the Maternal Influenza Hypothesis is proven correct, is there any specific period of gestation, during which if Influenza is contracted, there is an increased probability for the child to develop Schizophrenia as an adult?


Answer: In addition to the Helsinki Research Study, there has also been an additional study by Scotland. This study suggested that infants who were in the 6th month of intrauterine development during the Influenza Epidemic of 1957 seemed to be statistically more inclined towards developing schizophrenia during adult life. However, contradictions are found in the Scottish National Data, which does not reveal any increased chance. Thus, similar to the previous question, we do not have a definite answer for this one as well.


Citations:

https://embryo.asu.edu/pages/teratogens#:~:text=Teratogens%20are%20classified%20into%20four,Greek%20word%20for%20monster%2C%20teratos

https://pubmed.ncbi.nlm.nih.gov/3337616/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833128/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3037097/#:~:text=Epidemiological%20studies%20indicate%20that%20maternal,of%20action%20of%20antipsychotic%20drugs

https://www.sciencedirect.com/science/article/pii/S0920996416304996

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441883/


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