DATE: October 02, 2024 at 12:00PM
SOURCE: PSYPOST.ORG

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TITLE: Inflammatory genes linked to autism risk in children of mothers with asthma

URL: psypost.org/inflammatory-genes…

A longitudinal study in Australia found that children of mothers with asthma who had increased expression of specific inflammatory genes were more likely to show autism-related behaviors at 12 months. The genes in question were CYSLTR2, NOX1, C1QA, CXCL10, C8A, and IL23R. The research was published in Brain, Behavior, & Immunity – Health.

Autism, or autism spectrum disorder, is a developmental condition that affects communication, social interaction, and behavior. Individuals with autism can exhibit a wide range of abilities and challenges, making it a highly variable condition. Some may have intellectual disabilities, while others may excel in specific areas, such as mathematics or the arts.

Common traits of autism include difficulties in social interaction, repetitive behaviors, and increased sensitivity to sensory inputs, such as light or sound. While the exact causes of autism are not fully understood, genetic, environmental, and immune-related factors are believed to contribute.

Recent research has pointed to the potential role of the mother’s immune system during pregnancy in influencing the likelihood of autism-related traits in infants. When a pregnant woman’s immune system becomes activated—whether due to infections, chronic conditions, or allergies—it can release immune molecules that cross the placenta and may impact fetal brain development. This phenomenon is known as maternal immune activation, and it has been implicated in neurodevelopmental conditions such as autism.

One condition known to be caused by aberrant activity of the immune system is asthma. Asthma is an inflammatory disease of the airways and it is the leading immune disease to complicate pregnancy. Studies indicate that children of mothers with asthma are more likely to develop autism.

Study author Vanessa E. Murphy and her colleagues wanted to investigate whether inflammatory gene biomarkers in blood of mothers were associated with increased likelihood of autism in their infants. Participants of their study were pregnant women recruited as part of the Breathing for Life Trial, an experimental study of novel ways to manage asthma, and their children participating in a follow-up study. All the needed data were provided by 24 mother-infant pairs.

The study was conducted as part of the Breathing for Life Trial, an Australian clinical trial investigating asthma management during pregnancy. The researchers selected 24 mother-infant pairs from this trial, all of whom provided both maternal blood samples during pregnancy and completed assessments of their infants’ early behavioral development.

The participating women were recruited between the 12th and 23rd weeks of pregnancy from John Hunter Hospital in Newcastle, Australia. The researchers collected data on each mother’s age, body mass index (BMI), gestational age, smoking status, asthma symptoms, medication use, and lung function. Importantly, they also took blood samples from the mothers during mid-pregnancy.

From these blood samples, the research team extracted RNA and measured the activity of 249 genes involved in inflammation using an advanced technique called the nCounter Human Inflammation panel (developed by Nanostring Technologies). This allowed them to profile inflammatory gene expression in each mother.

When the infants were 12 months old, the researchers used a validated parent-report tool called the First Year Inventory (FYI) to assess the likelihood of autism-related behaviors. The FYI evaluates early signs of autism in two key domains: social communication and sensory regulation. Infants with an FYI score of 19.2 or higher were classified as having an increased likelihood of autism, while those with lower scores were classified as having a low likelihood.

Of the 24 infants in the study, four were found to have an increased likelihood of autism-related behaviors, while the remaining 20 had a low likelihood. Interestingly, the mothers of infants in the high-likelihood group showed significantly higher activity of six inflammatory genes: CYSLTR2, NOX1, C1QA, CXCL10, C8A, and IL23R.

The researchers also found that two of these genes—CYSLTR2 and CXCL10—were particularly correlated with social communication difficulties in the infants, as measured by their FYI scores. This suggests that maternal expression of these genes during pregnancy may be linked to early social communication challenges in infants, a hallmark trait associated with autism.

Additionally, two other genes—ALOX5 and MAFK—were linked to sensory regulation difficulties in the infants. Sensory regulation refers to how children process and respond to sensory stimuli, such as sounds, lights, or touch. Differences in sensory regulation are also common in children on the autism spectrum. Infants whose mothers had higher levels of these genes during pregnancy tended to have more pronounced difficulties with sensory regulation.

These findings indicate that maternal immune system activity, particularly inflammation, may be linked to distinct autism-related traits in early infancy, including social communication and sensory regulation challenges.

“Six inflammatory genes were upregulated in mothers whose infants displayed a high likelihood for autism and had high scores in the social communication domain, at 12 months of age. The data also suggest that specific maternal inflammatory biomarkers may be linked to distinct autism sub-phenotypes,” the study authors concluded.

The study points to a potential novel way to predict the likelihood of autism during pregnancy. However, it should be noted that the number of participants in this study was very small, and these individuals were selected from a much larger group of 731 mothers participating in the Breathing for Life Trial. In addition, the FYI is a screening tool for autism-related behaviors, not a diagnostic test, meaning it identifies children who may be at higher risk for later autism diagnosis but does not confirm the condition itself.

The paper, “Autism likelihood in infants born to mothers with asthma is associated with blood inflammatory gene biomarkers in pregnancy,” was authored by Vanessa E. Murphy, Olivia Whalen, Evan J. Williams, Peter G. Gibson, Linda E. Campbell, Frini Karayanidis, Carly A. Mallise, Alix Woolard, Annelies L. Robijn, Joerg Mattes, Adam M. Collison, Alison E. Lane, and Katherine J. Baines.

URL: psypost.org/inflammatory-genes…

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