By MOISES VELASQUEZ-MANOFF
IN recent years, scientists have made extraordinary advances in understanding the causes of autism, now estimated to afflict 1 in 88 children. But remarkably little of this understanding has percolated into popular awareness, which often remains fixated on vaccines.
So here’s the short of it: At least a subset of autism — perhaps
one-third, and very likely more — looks like a type of inflammatory
disease. And it begins in the womb.
It starts with what scientists call immune dysregulation. Ideally, your
immune system should operate like an enlightened action hero, meting out
inflammation precisely, accurately and with deadly force when
necessary, but then quickly returning to a Zen-like calm. Doing so
requires an optimal balance of pro- and anti-inflammatory muscle.
In autistic individuals, the immune system fails at this balancing act. Inflammatory signals dominate. Anti-inflammatory ones are inadequate. A state of chronic activation prevails. And the more skewed toward inflammation, the more acute the autistic symptoms.
Nowhere are the consequences of this dysregulation more evident than in
the autistic brain. Spidery cells that help maintain neurons — called
astroglia and microglia — are enlarged from chronic activation. Pro-inflammatory signaling molecules abound. Genes involved in inflammation are switched on.
These findings are important for many reasons, but perhaps the most
noteworthy is that they provide evidence of an abnormal, continuing
biological process. That means that there is finally a therapeutic target
for a disorder defined by behavioral criteria like social impairments,
difficulty communicating and repetitive behaviors.
But how to address it, and where to begin? That question has led
scientists to the womb. A population-wide study from Denmark spanning
two decades of births indicates that infection during pregnancy increases the risk of autism in the child. Hospitalization for a viral infection, like the flu, during the first trimester of pregnancy triples the odds. Bacterial infection, including of the urinary tract, during the second trimester increases chances by 40 percent.
The lesson here isn’t necessarily that viruses and bacteria directly
damage the fetus. Rather, the mother’s attempt to repel invaders — her inflammatory response — seems at fault. Research by Paul Patterson,
an expert in neuroimmunity at Caltech, demonstrates this important
principle. Inflaming pregnant mice artificially — without a living
infective agent — prompts behavioral problems
in the young. In this model, autism results from collateral damage.
It’s an unintended consequence of self-defense during pregnancy.
Yet to blame infections for the autism epidemic is folly. First, in the
broadest sense, the epidemiology doesn’t jibe. Leo Kanner first described infantile autism
in 1943. Diagnoses have increased tenfold, although a careful
assessment suggests that the true increase in incidences is less than
half that. But in that same period, viral and bacterial infections have
generally declined. By many measures, we’re more infection-free than
ever before in human history.
