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Protein marker ties maternal inflammation to autism risk

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Laura Geggel
25 February 2013

Risk management: Preventing inflammation during the first and second trimester of a woman’s pregnancy may reduce the risk of autism in her child.

Women who have high levels of C-reactive protein (CRP), a marker of inflammation, early in their pregnancies are at increased risk of having children with autism, reports a study published 22 January in Molecular Psychiatry1.

Of 677 women in the study, those whose CRP levels are in the top ten percent of the group are 80 percent more likely to have children with autism compared with those in the bottom ten percent.

The study suggests that preventing certain causes of inflammation may help decrease autism risk, says lead investigator Alan Brown, professor of clinical psychiatry and clinical epidemiology at Columbia University in New York.

It also adds to growing evidence that the immune system plays a role in autism risk. Previous studies have shown that infections such as rubella or the flu during pregnancy increase the risk of having a child with autism.

“It’s not a huge effect, but it’s very significant,” says Paul Patterson, professor of biology at the California Institute of Technology, who was not involved with the study. “It’s another nail in the coffin on the case that inflammation — probably infection — during pregnancy is a risk factor for the offspring.”

CRP is produced in the liver in response to anti-inflammatory messengers called cytokines. The protein level rises in response to all types of inflammation, including infections, chronic inflammatory disorders such as arthritis, and injuries to any tissue in the body.

“The point of CRP is that it’s nonspecific, but it is sensitive,” says Thomas Insel, director of the National Institute of Mental Health, who was not involved in the study. “The fact that [risk of autism] has gone up tells you that you’ve got to do some digging to see what may be driving it, because there are lots of ways to get elevated CRP.” (The institute funded part of the study.)

Marking inflammation:

For the study, Brown’s team tapped the Finnish Maternity Cohort, a repository of 1.6 million blood samples collected from more than 810,000 pregnant women during the first to early-second trimester. These account for 98 percent of Finland’s pregnancies since 19832.

Since 1987, Finland has recorded childhood psychiatric diagnoses, allowing researchers to learn which women have children with autism. Of the 1.2 million births since 1987, researchers identified 1,132 children diagnosed with autism.

To confirm the accuracy of the diagnoses, Brown’s group randomly chose 80 children, evaluated them using the Autism Diagnostic Interview-Revised and found that 77 of them meet the criteria for autism.

“They actually did validate the diagnosis, which is usually not done,” Insel says. “They deserve a lot of credit for having done that very heavy-lifting kind of work.”

Brown’s team looked at 677 of the women whose children have autism, and compared them with 677 women whose children do not. They then examined a number of possible factors associated with autism, including maternal and paternal age and mental illness in either parent. None explain the relationship between CRP levels and autism risk.

When the researchers analyzed the autism group’s blood samples based on levels of CRP, they found the top 20 percent of women are 43 percent more likely to have children with autism compared with the lowest 20 percent.

“We’re getting now an emerging story about the possibility that inflammation is at least a fellow traveler with autism and may be involved even more directly in some causal mechanism,” Insel says.

Brown plans to explore the interplay between CRP and other maternal factors, including environmental influences such as an illness and genetic risk factors. 

It’s not yet clear whether elevated CRP raises autism risk specifically or developmental disorders generally. Brown says he hopes to investigate other disorders for a link with the protein.

News and Opinion articles on SFARI.org are editorially independent of the Simons Foundation.

References:

1: Brown A.S. et al. Mol. Psychiatry Epub ahead of print (2013) PubMed

2: Lampi K.M. et al. J. Autism Dev. Disord. 41, 1090-1096 (2011) PubMed

Comments

Name: Sebastian
25 February 2013 - 6:52PM

Could it be that families in which autism runs experience more stress, for example because of the social and organisational demands they face with life in society, raising the probability that they get infections due to higher levels of stress?

Name: Laura Geggel
25 February 2013 - 8:46PM

Thanks for your comment, Sebastian. In this case, because they are tracking autism risk linked to inflammation during pregnancy, the inflammation likely comes before the family has been exposed to the stress of having a child with autism.
Please let us know if you have any other questions. Thanks for reading Sfari!

Name: Sebastian
26 February 2013 - 11:47AM

Dear Laura, thank you for your response. By saying that autism runs in families, I meant that autistic traits may run in families. Therefore, one or both parents, grandparents, siblings and so forth may have a higher probability of having either clinical diagnosable levels of autistic traits or traits of the broad autism phenotype. So I was thinking about autistic traits in the parents and not the child.

Name: Sebastian Dern
26 February 2013 - 11:59AM

PS: Others speculate that being on the autistic spectrum itself may render people more sensitive, perhaps also more sensitive to stress. An account about a different sensibility threshold may be reports by psychiatrists, that the therapeutic windows of drugs used to treat comorbidities in patients on the autism spectrum may be at lower (or higher) doses of a drug. Perhaps it would help to know if parents or grandparents of an autistic child also showed autistic traist to better understand the potential role of the environment, such as that of inflammation during pregnancy.

Name: passionlessDrone
26 February 2013 - 3:22PM

Hi Laura Greggel -

Nice write up.

It seems to me that this findings is particularly problematic for the idea of a static rate of autism. If we look to conditions characterized by increased levels of inflammation, or CRP in particular, we get things like diabetes, asthma, metabolic syndrome, or obesity. Unfortunately, these conditions have been increasing in the past few decades, and we don't have the fuzzy nature of an autism diagnosis or 'greater awareness' to explain the change; we are getting fatter, more asthmatic, and more diabetic as a population.

But this would seem to have some rather profound implications for the incidence questions. As you state, the CRP findings are very robust and line up nicely with many other clinical findings; but doesn't this mean that because our lifestyles have changed in ways that are consistent with increased risk of autistic offspring, some of our observed increases in autism is *real* and not imagined?

- pD

Name: Sebastian Dern
26 February 2013 - 4:21PM

If socio-economic changes are such that the demands for social skills increased, than this might have made people with difficulties in this area stand out more. Perhaps the increase in the diagnosis of autism spectrum may partly reflect the number of people experiencing difficulties as social skills became more important for employment in the service sector economy than previously.

Name: Theresa
26 February 2013 - 9:28PM

Laura,

Do you have a link to the actual report/article for this finding?

Name: Laura Geggel
26 February 2013 - 9:34PM

Hi Theresa, thanks for asking. You can find the PubMed link to the study at the bottom of the article under references. Thanks for reading Sfari!

Name: erica
27 February 2013 - 5:09PM

This article /research supports my theory that my daughter's autism was a reaction to an MMR vaccination I got two weeks prior to her conception.....the fact that there were now Measles, Mumps and Rubella virus in my body causing inflammation and possibly damaging tissues....ehhhh, more guilt.....

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