Imaging tech helps clear up a cloudy disease

The Yale Child Study Center is using new imaging techniques to examine the brains of children with childhood disintegrative disorder.
The Yale Child Study Center is using new imaging techniques to examine the brains of children with childhood disintegrative disorder. Photo by Kamaria Greenfield.

Novel imaging techniques at the Yale Child Study Center are providing the first look at the active brains of children with a rare neurodegenerative disorder.

Childhood disintegrative disorder (CDD), also referred to as late-stage regression in autism, is a disorder where children develop normally for at least three years before undergoing a period of sudden regression, in which they express intense fear, physical discomfort and may engage in self-destructive activities, such as jumping off of high places. Alexander Westphal GRD ’13, one of the major researchers on the CDD project, said this research will be the first to demonstrate that autism, as is commonly understood, is merely a set of symptoms that can be caused by “multiple [possible] paths”.

“The way we think about autism is as a developmental disorder, one where early derailment leads to reduced skills,” Westphal said. “CDD is a derailment that comes out of nowhere, it’s a total mystery.”

Childhood developmental disorder, Westphal said, appears to have fundamentally different causes than classical autism, though the two result in similar permanent conditions. By using a series of brain imaging techniques, both structural and functional, researchers at the center are starting to show that the two disorders have different patterns of brain activity.

Westphal and his colleagues have identified areas in the brain that appear more normal in CDD patients than in patients with classical autism, and areas of the brain that appear more damaged in CDD patients than those with autism. Specifically, compared to the classically autistic, CDD patients exhibit abnormal activity in the amygdala, a brain region responsible for fear and other primal instincts. Westphal said that this finding could account for the intense fear observed in affected children during the regression period.

Jason Schneiderman of the Harvard Psychiatry Neuroimaging Laboratory, said he was excited about the research being done at the Child Study Center.

“From what I’ve seen, the clinical evidence suggests a type of late stage regression that is probably different from classical autism, where phenotypes can be tracked as early as 6 months,” Schneiderman said. “Any research into this would help elucidate diagnoses.”

Westphal said one major challenge was getting children to lie still in the functional magnetic resonance imaging (fMRI) machine. Theoretically, fRMIs are simple scans that can be done on patients of all ages, but children affected by serious neurological disorders may be unable to follow or comprehend simple instructions.

“We have some pretty intensive mock scanning … if they have a thing for Skittles or M&M’s we’ll reward them and incentivize it that way, but sometimes it just doesn’t work,” Westphal said.

To acclimatize the children to the scanning process, multiple dry runs and familiarization sessions are conducted with the children and the machines. Westphal said this level of personal attention had enabled the Yale lab to go beyond any previous research on CDD.

Westphal and other researchers are planning on coordinating their slowly accumulated data with the genomics research of Matthew State, professor of psychiatry at the Yale School of Medicine. State’s lab, also part of the Child Study Center, has been searching for genetic markers for disease in patients with autism, Tourettes and CDD.

“We are determined to improve treatment for serious neuropsychiatric disorders of childhood and believe that identifying genes contributing to these syndromes is a critical first step in doing so,” State said in an email.

CDD is a disease affecting approximately 1.7 of 100,000 children in the developed world according to a study done at McGill in 2002.

Comments

  • Lamplighter

    “off” high places, not “off of.”