Diagnostic Disparities

George Washington University researchers have found that male and female sex hormones regulate expression of an important gene in neuronal cell culture through a mechanism that could explain not only higher levels of testosterone observed in some individuals with autism, but also why males have a higher incidence of autism than females.

The gene, RORA, encodes a protein that works as a "master switch" for gene expression, and is critical in the development of the cerebellum as well as in many other processes that are impaired in autism. Dr. Hu's earlier research found that RORA was decreased in the autistic brain. In this study, the research group demonstrates that aromatase, a protein that is regulated by RORA, is also reduced in autistic brains.

This is significant because aromatase converts testosterone to estrogen. Thus, a decrease in aromatase is expected to lead in part to build up of male hormones that, in turn, further decrease RORA expression, as demonstrated in this study using a neuronal cell model. On the other hand, female hormones were found to increase RORA in the neuronal cells. The researchers believe that females may be more protected against RORA deficiency not only because of the positive effect of estrogen on RORA expression, but also because estrogen receptors, which regulate some of the same genes as RORA, can help make up for the deficiency in RORA.

This study, performed by researchers at the University of Pennsylvania, analyzed the level of gene expression in children with autism, compared with a control group. The researchers hypothesized that the variability in the pattern of the overall of gene expression levels would be associated with variability in hippocampal-dependent behaviors, which include short-term memory and spatial navigation. Additionally, the group tested whether increased paternal age was associated with variance of gene expression. A decrease in the variability of gene expression levels was associated with the diagnosis of autism and increased paternal age. The research team believes this change to be caused by the down-regulation of gene expression pathways involved in protein synthesis regulation in the blood of children with autism and children with older fathers. Thus, the researchers concluded that alterations at the gene level of gene expression regulation are related to autism and increased paternal age.

This study examined the rates of autism according to maternal immigrant status and ethnic origins based on the vitamin D insufficiency hypothesis, which proposes that maternal vitamin D insufficiency during pregnancy could be associated with autism. The study provided further support to the association between maternal immigrant status and an increased risk of autism. In addition, although more complex, ethnic origin was shown to have an effect on the rates of autism; the study found that black ethnicity demonstrated a higher incidence of autism, particularly when considering autism associated with mental retardation. The results found in the study are consistent with the maternal vitamin D insufficiency hypothesis. To understand the effect of maternal vitamin D insufficiency during pregnancy on the development of the fetal brain, neurobiological studies are necessary.

Studies have suggested associations between immune response and idiopathic disorders (such as autism). This study explores associations between parental autoimmune disorders and children's diagnosis of autism by linking. The study found associations between parental autoimmune disorders and autism spectrum disorders, suggesting parental autoimmune disorders may represent a pathway that warrants more detailed investigation.