(July 16, 2015) A
larger head size — or macrocephaly — is seen in many children with severe
autism spectrum disorder (ASD). A new stem cell study of these children by Yale
School of Medicine researchers could help predict ASD and may lead to new drug
targets for autism treatment.
The findings are published in the July 16 issue of the
journal Cell.
ASD is known to appear during brain development, but most
cases of the disorder lack a clear origin or genetic basis. Recent studies of
genetic mutations in rare cases of ASD hint that development of the cerebral
cortex in the fetal period is abnormal in autism. The Yale research team sought
to pinpoint what goes wrong as the cerebral cortex develops.
The team simulated early cerebral cortex development using
stem cells generated from skin biopsies of four patients with ASD. They grew
the stem cells into three-dimensional simulated miniature human brains (brain
organoids). They then compared gene expression and developing cell types
between the patients and their family members — typically their fathers —
without ASD. Patients in the study had enlarged heads, which indicates worse
autism outcomes.
“Brain growth abnormalities such as accelerated cell cycles,
overproduction of inhibitory neurons, and synaptic overgrowth may all be
precursors of a trajectory of brain development found in children with severe
ASD,” said the study’s lead author Dr. Flora Vaccarino, the Harris Professor of
Child Psychiatry and Professor of Neurobiology at Yale School of Medicine. “Our
data provides a framework for studying normal human brain development and its
disorders, including autism.”
“We discovered that the patients’ cells divided at a faster
pace, and that they produced more inhibitory neurons and more synapses,”
Vaccarino added. She and her team also noted a 10-fold increase in a gene
called FOXG1, which is important in the early growth and development of neurons
in the embryonic brain.