Posted on March 17, 2010 - by David

Does Flu During Pregnancy Raise Schizophrenia Risk?

The authors of a study recently published in the journal Biological Psychiatry claim that influenza infection during pregnancy may play a role in the development of schizophrenia later in life.

The study subjects were monkeys.

According to the abstract, twelve pregnant rhesus monkeys were infected with influenza early in the third trimester, and 7 healthy subjects were used as a control group. The brains of the babies were scanned using MRI after one year, and the researchers found that “exposed offspring had significantly smaller cingulate and parietal cortical gray matter and left parietal white matter than nonexposed offspring. Bilaterally, cingulate white matter was greater in exposed offspring than in controls.” (Gellner, Journal Watch Psychiatry) It is this finding that gets translated into a sentence like “The results showed ‘a significant effect’ which mirrored brain changes in schizophrenic humans” which I read in a short news clip on the Dallas-Fort Worth Fox News affiliate website, under the (only slightly misleading) title ‘Scientists Find Link Between Pregnant Women with Flu and Schizophrenia.’

The study’s main author, Sarah Short, chose her words a little more carefully:

“This was a relatively mild flu infection, but it had a significant effect on the brains of the babies,” Short said. “While these results aren’t directly applicable to humans, I do think they reinforce the idea, as recommended by the Centers for Disease Control and Prevention, that pregnant women should get flu shots, before they get sick.”

But obviously, the object of the study wasn’t merely to reinforce the idea that pregnant women should get flu shots.  The hypothesis that flu infection during pregnancy might play a role in the development in schizophrenia was first put forth over 20 years ago, in a study involving a Finnish cohort born during the 1957 influenza pandemic. They found that “those exposed to the viral epidemic during their second trimester of fetal development were at elevated risk of being admitted to a psychiatric hospital with a diagnosis of schizophrenia,” but the results of similar studies have varied considerably. To date, only about half of the 25 research papers examining this phenomenon have confirmed these findings. Those who support this hypothesis often cite one of the more recent and “scientific” studies, which looked at maternal blood tests to confirm when and if those diagnosed with schizophrenia were exposed to the flu. The 2004 investigation found that “the risk of schizophrenia was increased 7-fold for influenza exposure during the first trimester.” If this is indeed true, it’s easy to understand why the authors considered it significant, but the finding that “there was no increased risk of schizophrenia with influenza during the second or third trimester,” conflicts with the earlier studies which claimed that risk of schizophrenia was increased with second trimester exposure. Based on the available data, it’s impossible to draw any conclusions about the relationship between schizophrenia and prenatal exposure to the flu, but obviously, as the recent publication of the monkey study demonstrates, researchers are still actively pursuing this track.

A few questions/criticisms about this study from someone with an admittedly (very) limited knowledge of neurology…

Is there a difference between contracting the flu virus in the typical way and forced infection, in terms of effects on the fetus?

If the available data points to first or second trimester exposure as a risk factor, what is the comparative value of this study considering the pregnant monkeys were infected during the third trimester?

What are other health effects for children of mothers who have the flu while pregnant? Has there been any research examining the relationship between prenatal exposure to influenza and any other mental illnesses?

If this really is a significant risk factor, wouldn’t it suggest that in developing countries where the flu vaccine is less readily available, there should be higher rates of schizophrenia?

A summary of the study by Asian News International (available on many websites) says that “rhesus monkey babies born to mothers who had the flu while pregnant had smaller brains and showed other brain changes similar to those observed in human patients with schizophrenia.” To my knowledge, schizophrenics do not have “smaller brains,” and from what I’ve read, nearly every region of the brain and every neurotransmitter has been implicated by one study or another in the etiology or progression of schizophrenia.  It seems a bit misleading then to represent the changes observed in the monkey’s brains as “similar to those observed in human patients with schizophrenia.” This may be the fault of the news article and not the study authors, but I feel it’s important to point out that despite all our technology and the proliferation of research into the “biological basis” of schizophrenia, there is no test or scan, no specific brain changes that can be identified and used to diagnose schizophrenia.

Because so many potential genetic and neurological risk factors are being investigated and written about, there can be a false sense that we are approaching an understanding of what causes schizophrenia. But risk and vulnerability are merely that: factors which increase the possibility that a person exposed to the cause of schizophrenia will go on to develop the disease. In the first chapter of a 2007 book called Recovery from Schizophrenia, Norman Sartorius, former President of the World Psychiatric Association and former Director of the World Health Organization’s Division of Mental Health, writes:

“Despite advances in our knowledge about schizophrenia in the past few decades, nothing allows us to surmise that the causes of schizophrenia will soon become known, or that the prevention of the disorder will become possible in the immediate future.” (3)

Sure, I like monkeys, and I understand how biologically similar we are, but if we want to understand schizophrenia, perhaps we should be looking in the realm of what makes us human.