Your newest research looks at a particularly insidious set of chronic diseases that can result from infection in the womb. These diseases can produce lifelong psychiatric effects. How does that work?
The connection between prenatal infection and damage to the fetus has long been known. Exposure to syphilis, at its most extreme, results in stillbirth. Prenatal exposure to infections could result in
microcephaly [a neurodevelopmental disorder in which the circumference of the head is smaller than normal]. But if the damage is more subtle, subtle changes in behavior can result. The child is still breathing, the child is walking, the locomotor function is not so abnormal that it’s incompatible with life in our culture. There was a time when these children would have died in utero, but now they survive, and you see some of these abnormalities come to the fore.
Have we reached the point where we can link specific infections to specific psychiatric disorders?
No, the connection is much more complex. When I worked with LCMV, it became clear that any sort of perturbation could damage the nervous system. Nerves find their way to specific locations through signposts that are part of the immune system. And if you increase immunological molecules of certain types, a nerve may jog this way as opposed to the way it’s supposed to go. It may not make a difference what the infectious agent is—bacterial, viral, or parasitic.
If the identity of the infection isn’t critical, what is?
The important things are the genetic background of the individual and the timing of the insult. If you look at the original work on the epidemiology of
thalidomide [a morning-sickness drug that turned out to cause birth defects], there were specific time points where, if the woman was exposed, the baby had a high probability of having bona fide autism.
One of the most fascinating links between infection and mental disease concerns PANDAS, pediatric autoimmune neuropsychiatric disorders. The bottom line is that strep might cause obsessive-
compulsive disorder. How could that happen?
An infection like strep throat provokes an antibody response, but the antibody created to fight the strep also recognizes proteins that are part of your body. Antibodies don’t typically traffic much in the central nervous system. But if you have any one of a number of other infections or an insult like head trauma, the blood-brain barrier [which normally protects the brain from pathogens] opens transiently. Depending on how long and where the opening is, the antibodies get access to part of the central nervous system or brain. We are studying this process now in mice, using drugs to open up a portion of the hindbrain or the forebrain or the hippocampus and tracking the effect.
Could autism be another version of a PANDAS-like disease?
It’s possible, in some people. There is probably a group of people who have a genetic component to autism, and for them, there may not be much of a trigger or any trigger at all required. Another group is genetically predisposed, and
if they encounter some factor or factors, individually or in combination, it could result in either the onset or the aggravation of the neurodevelopmental disorder; by factors, I include everything from heavy metals to infection. And lastly, there is a group that may be relatively or entirely normal but is exposed prenatally to some factor or factors that have an effect on their nervous system and that manifests as autism. This is the hypothesis, at least.
You are trying to put all this research together through a prospective study called the Norwegian Autism Birth Cohort. What’s that about?
The idea is that you can get only so far by examining people when they’re sick, because the seeds of illness may be laid many years before. In a prospective cohort, you can follow children
from before birth in an unbiased way, collecting information and samples and maybe making associations between factors and outcomes after the fact. We’re going back as far as we can, which is the first prenatal visit at roughly 17 weeks’ gestation. And the study is being done in Norway because there’s universal health care; you don’t have to be concerned about discrimination for insurance purposes based on disease, and as people get ill, you have long-term follow-up.
What could that study tell you about the nature of autism?
We have thousands of biological samples that will be transferred back here to New York, and we’re going to analyze them using all the tools of microbiological analysis we developed to look at acute diseases in the past. Because we have blood samples that are obtained from the mother during the course of pregnancy and at the time of birth, we can examine a whole range of proteins and messenger RNA s that may be reflective of genetic defects or exposures. We may not detect an autism-causing agent specifically, but we will see that there is a marked increase in specific biomarkers. This allows us to define in a very broad sense what proteins, nucleic acids, pathogens, and toxins might be part of the milieu of the fetus.
sorry but you cant have it both ways .
