Investigators analyzed 25 genes in postmortem brain tissue of children with and without autism. These included genes that serve as biomarkers for brain cell types in different layers of the cortex, genes implicated in autism and several control genes.
Their findings are published in the online edition of the New England Journal of Medicine.
“Building a baby’s brain during pregnancy involves creating a cortex that contains six layers,” said Eric Courchesne, Ph.D., professor of neurosciences and director of the Autism Center of Excellence at University of California, San Diego (UC San Diego).
“We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism.”
The findings confirm the hypothesis that for some children with autism, the brain can sometimes rewire connections and the child can improve abilities — especially with early therapeutic intervention.
Rich Stoner, Ph.D., of the UC San Diego Autism Center of Excellence created a unique three-dimensional model visualizing brain locations where patches of cortex had failed to develop the normal cell-layering pattern.
“The most surprising finding was the similar early developmental pathology across nearly all of the autistic brains, especially given the diversity of symptoms in patients with autism, as well as the extremely complex genetics behind the disorder,” said Ed S. Lein, Ph.D.
During early brain development, each cortical layer develops its own specific types of brain cells, each with specific patterns of brain connectivity that perform unique and important roles in processing information.
As a brain cell develops into a specific type in a specific layer with specific connections, it acquires a distinct genetic signature or “marker” that can be observed.
The study found that in the brains of children with autism, key genetic markers were absent in brain cells in multiple layers.
“This defect,” Courchesne said, “indicates that the crucial early developmental step of creating six distinct layers with specific types of brain cells — something that begins in prenatal life — had been disrupted.”
“Equally important,” said the scientists, “these early developmental defects were present in focal patches of cortex, suggesting the defect is not uniform throughout the cortex.”
The brain regions most affected by focal patches of absent gene markers were the frontal and the temporal cortex, possibly illuminating why different functional systems are impacted across individuals with the disorder.
The frontal cortex is associated with higher-order brain function, such as complex communication and comprehension of social cues. The temporal cortex is associated with language.
The disruptions of frontal and temporal cortical layers seen in the study may underlie symptoms most often displayed in autistic spectrum disorders. The visual cortex — an area of the brain associated with perception that tends to be spared in autism — displayed no abnormalities.
“The fact that we were able to find these patches is remarkable, given that the cortex is roughly the size of the surface of a basketball, and we only examined pieces of tissue the size of a pencil eraser,” said Lein.
“This suggests that these abnormalities are quite pervasive across the surface of the cortex.”
Researching the origins of autism is challenging because it typically relies upon studying adult brains and attempting to extrapolate backwards.
“In this case,” Lein said, “we were able to study autistic and control cases at a young age, giving us a unique insight into how autism presents in the developing brain.”
“The finding that these defects occur in patches rather than across the entirety of cortex gives hope as well as insight about the nature of autism,” added Courchesne.
According to the scientists, such patchy defects, as opposed to uniform cortical pathology, may help explain why many toddlers with autism show clinical improvement with early treatment and over time.
The findings support the idea that in children with autism the brain can sometimes rewire connections to circumvent early focal defects, raising hope that understanding these patches may eventually open new avenues to explore how that improvement occurs.
Source: University of California, San Diego
Reviewed by John M. Grohol, Psy.D. on April 7, 2014
Pregnant women who don’t produce enough thyroid hormone are nearly four times likelier to give birth to autistic children than their healthy peers, a new study has claimed. Scientists from the Houston Methodist Neurological Institute in US and Erasmus Medical Centre in Rotterdam, Netherlands studied more than 4,000 Dutch mothers and their children. Their results support the growing view that autism spectrum disorders can be caused by a lack of maternal thyroid hormone, which past studies have shown is crucial to the migration of foetal brain cells during embryo development.
“It is increasingly apparent to us that autism is caused by environmental factors in most cases, not by genetics. That gives me hope that prevention is possible,” said lead author Gustavo Roman, a neurologist and neuroepidemiologist who directs the Nantz National Alzheimer Center. The researchers also found that autistic children had more pronounced symptoms if their mothers were severely deficient for T4, also called thyroxine. Mild T4 deficiencies in mothers produced an insignificant increase in autistic children’s symptoms. The most common cause of thyroid hormone deficiency is a lack of dietary iodine – because both the thyroid hormones, T3 and T4, contain that element.
The present work was based on the Generation R Study, conducted by Erasmus Medical Centre doctors and social scientists, in which thousands of pregnant women were voluntarily enrolled between 2002 and 2006. Researchers identified 80 “probable autistic children” from a population of 4,039. Around 159 mothers were identified as being severely T4 deficient (defined as having 5 per cent or less of normal T4, but producing a normal amount of thyroid stimulating hormone), and 136 were identified as mildly T4 deficient.
The researchers found a weak association between mild T4 deficiency and the likelihood of producing an autistic child, but a strong association between severe T4 deficiency and autism (3.89 more likely, as compared with mothers with normal thyroid hormone). The study presents a troubling correlation, but it does not prove that the thyroid function of expecting mothers causes autism in their children, researchers said. The study will be published in the journal Annals of Neurology.