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Sex-specific Gene-environment Interactions Underlying ASD-like Behaviors

Science post imagehttp://www.pnas.org/content/114/6/1383

Proc Natl Acad Sci U S A. 2017 Feb 7;114(6):1383-1388. doi: 10.1073/pnas.1619312114. Epub 2017 Jan 23.

Sex-specific gene-environment interactions underlying ASD-like behaviors.

Schaafsma SM1, Gagnidze K2, Reyes A2, Norstedt N2, Månsson K2, Francis K2, Pfaff DW1.

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Abstract

The male bias in the incidence of autism spectrum disorders (ASDs) is one of the most notable characteristics of this group of neurodevelopmental disorders. The etiology of this sex bias is far from known, but pivotal for understanding the etiology of ASDs in general. Here we investigate whether a "three-hit" (genetic load × environmental factor × sex) theory of autism may help explain the male predominance. We found that LPS-induced maternal immune activation caused male-specific deficits in certain social responses in the contactin-associated protein-like 2 (Cntnap2) mouse model for ASD. The three "hits" had cumulative effects on ultrasonic vocalizations at postnatal day 3. Hits synergistically affected social recognition in adulthood: only mice exposed to all three hits showed deficits in this aspect of social behavior. In brains of the same mice we found a significant three-way interaction on corticotropin-releasing hormone receptor-1 (Crhr1) gene expression, in the left hippocampus specifically, which co-occurred with epigenetic alterations in histone H3 N-terminal lysine 4 trimethylation (H3K4me3) over the Crhr1 promoter. Although it is highly likely that multiple (synergistic) interactions may be at work, change in the expression of genes in the hypothalamic-pituitary-adrenal/stress system (e.g., Crhr1) is one of them. The data provide proof-of-principle that genetic and environmental factors interact to cause sex-specific effects that may help explain the male bias in ASD incidence.

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kws

I think Lisa is right in that it's the hormone relationship that accounts for the incidence in boys. This is what Boyd Haley looked at 10 years ago. Unfortunately, the "Proceedings for the National Academy of Science" didn't publish his data.

The genetic argument breaks down completely when you look at a strictly genetic disease, like color blindness. The rate of a genetic disease is constant, it doesn't increase or decrease. Autism has spiked in the past 20 years.

That said, genetics are involved nearly all conditions. If there's two boys in a car crash and one breaks his leg while the other doesn't, you could say one boy has genetics for a weaker leg bone. True, but why did his leg break ? It was the car crash.

Lisa

Or, simply put: Mercury-preserved vaccines, administered to male infants during their critical period of testosterone surge, cause autism. Reason: High testosterone renders mercury many times more potent. Potentiated mercury, in turn, raises testosterone levels even further. Hence, the vicious cycle is born. Add to this mix a less-than-optimal, genetically determined antioxidant system (e.g. low glutathione), and you have created the perfect storm: A highly toxic metal with no good way to eliminate it. It finds its way to the gut, where in a relatively brief period of time it wipes out entire colonies of beneficial bacteria. This creates a whole host of problems, not least of which is a weakened ability to break down certain proteins, including those found in cow's milk and wheat. Improperly digested, these proteins emit a chemical that mimics opiate, which attaches to the opiate receptors in the brain. After a brief period of euphoria, the brain becomes tolerant. Now the child is in a continuous state of protracted opiate withdrawal (i.e. autism).

Welcome to America in the 21st Century.

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