Feeling Too Much

How emotion shapes extraordinary sensitivity.

Prenatal Influences in Autism

Autism could result from stressors acting on a pregnant mother's immune system

If we accept the validity of the “intense world” theory of autism – and many people with ASD do – it’s fair game to ask whether the hyper-connectivity and hyper-reactivity of the autistic brain is pre-ordained by genetics or whether environmental influences may have some bearing.

In answering this question, let’s start by dismissing the outmoded assumption that it’s either/or. To assert that nature is more important than nurture or vice versa is like saying that the length of a rectangle is more important than its width. Each makes an essential contribution to the rectangle’s area, and you can’t have the whole without both of them.

That rectangle should really be a triangle, based on an increasing amount of evidence suggesting that a third leg – immune function – plays an essential role in at least some cases of ASD. Over the past eight years, research teams at the University of California-San Diego, the University of California-Davis, Johns Hopkins School of Medicine, and the Kennedy Krieger Institute in Baltimore have demonstrated, on the one hand, that immune system disorders are more common in the parents of children with ASD and, on the other hand, that the mothers of some autistic children, when pregnant, make antibodies that cross the placenta and affect proteins in the fetal brain.

Antibodies are proteins the body makes in response to viruses and bacteria. They’re also associated with autoimmune conditions such as lupus and rheumatoid arthritis – and they may also result from maternal stress, infections, and environmental exposures during pregnancy. These antibodies bind to particular proteins in the fetal brain, interfering with cell signaling and neuronal growth and otherwise disturbing brain development and organization. While this process is believed to apply to just a quarter of all cases of ASD, the documentation behind it is convincing. The implication: The “intense world” of the infant who develops ASD is, at least in some cases, less a matter of genetics and more of immune system influence and other factors (such as maternal stress) during pregnancy.

On a parallel track, neurobiologist Lisa Boulanger of Princeton University has been investigating another possible immune influence on the developing brain. Scientists now know that certain immune system molecules, instead of scouting for germs, influence the connections between neurons. One of them, known as C1q, appears to "prune" the synapses in the normal course of development (humans are born with more synapses than needed; weak and unnecessary connections are gradually eliminated during childhood).  But if C1q and other such proteins are diverted from their usual job – say, because of a virus in a mother’s body when pregnant – they wouldn’t act sufficiently in the child’s brain. Indeed, in animals it’s been found that a deficit of such proteins is linked with extraneous neural connections.  And a surfeit of neural connections is implicated in both autism and synesthesia.

The prospect raised here is that a maternal infection during pregnancy – or, for that matter, the occurrence of stress, trauma, injury, deprivation, or exposure to environmental toxins – could cause the child’s brain to be hyper-connected, setting the stage for extraordinary sensitivity.  The nature, severity, and timing of the occurrence would presumably have much to do with the condition or personality trait ultimately manifested. Population studies indicate, for example, that ASD may result if a pregnant mom develops an infection during the second trimester

There’s yet another way that the immune system exerts an influence on the developing brain.  It’s through a set of cellular players that, until recently, scientists had written off as being of no consequence – despite the fact that they outnumber neurons (which everyone knows about) by a ratio of 9-1. These players are called glial cells. Glial is Greek for glue, and historically, scientists believed they served as figurative spackle and caulk for the neurons they surround. But now glial cells are garnering lots of attention, for it seems they carry out an intricate and ongoing communication with neurons. They begin life as immune cells, migrate to the brain, and there do any number of critically important things, including surveying the entire brain for signs of injury, gobbling up invading pathogens, and clearing away cellular debris to speed repair. Glial cells also seem to trim away immature, weak or unnecessary neural connections. They are extremely dynamic, constantly on the move – and increasingly implicated in autism.

Glial cells have been found in the cerebral spinal fluid of people with autism, and at greater concentrations than control subjects.  If they’re busy pruning synaptic connections, this would be the opposite effect of the immune activity we surveyed earlier in this post. While those processes would lead to more neural connections and the likelihood of hypersensitivity, the action of glial cells in the fetal brain would cut back on synaptic connections. So the picture is not at all uniform – matching the phenomenon of ASD, which is hardly uniform either. ASD, after all, stands for Autism Spectrum Disorder, and people on one end of the spectrum (the Asperger’s side) are affected much less notably than people on the other end. Not only do scientists speculate that the combination of these various factors – genetic, environmental, immune – influence where on the autism spectrum a person will be, but that their interaction has a bearing on gender differences in autism and other conditions.  It is puzzling that synesthetes are predominantly female and persons with ASD are overwhelmingly male, and yet large numbers of both are plagued by sensory overload.

Perhaps one view that can be agreed upon, at least, is that held by pediatric neurologist Martha Herbert, of Harvard Medical School. ASD, she says, is not a disorder of the brain but a disorder that affects the brain. The entire body is presumably involved. As we’ll see in my next post, one’s entire sense of self is involved, too. 

Michael Jawer has been investigating the mind-body basis of personality and health for 15 years. He is the author of The Spiritual Anatomy of Emotion.

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