Scientists may have identified a biomarker for autism spectrum disorder, which can be difficult to differentiate from other disorders like hyperactivity, and may be challenging to diagnose correctly because it can present so differently. Reporting in Brain Communications, researchers have determined that the levels of a molecule called FABP4 are lower in 4- to 6-year-old children with autism than in children that develop in a typical way. The time of the test is critical, however; FABP4 levels in older children and adults with ASD are normal.
Fat cells are metabolically active and can release hormones that signal to other tissues; some say fat is an organ. One type of molecule that fat cells produce is called adipokines, which can affect brain activity. In this study, the researchers examined the levels of adipokines including FABP4 in young children with and without ASD.
"We previously found lower levels of FABP4 in the hair follicles of patients with schizophrenia," explained the first author of the study, Motoko Maekawa of the RIKEN Center for Brain Science in Japan. "Although the disorders themselves are very different, we knew that FABP4 was an adipokine that can modulate brain function, especially during development."
ASD begins in early life, and its impacts on learning, behavior, and communication fall on a wide spectrum. Young ASD patients seem to be at higher risk for obesity. The RIKEN team wanted to know more about how the disorder was connected to metabolism.
After assessing FABP4 levels and finding them low in young children with ASD, the researchers used a mouse model to deplete FABP4. They observed that the neurons in these mice were changed in ways that were similar to neurons that have been collected from the brains of ASD patients after death.
The scientists also confirmed that preschool-aged kids with ASD had significantly lower levels of FABP4 than children without ASD in two other groups of children. This suggests that at the right age - 4 to 6 - FABP4 levels can serve as an ASD biomarker. Compared to wild-type mice, the mice with low FABP4 levels also had behavioral problems that caused difficulty with spatial learning and memory, as seen in some ASD patients.
"The identification of FABP4 as a biomarker that can detect ASD in four- to six-year-old children is good news," said Maekawa, "especially because early diagnosis and intervention can lead to better long-term prognosis."
After additional analysis of post-mortem brains, the researchers found that in older children with ASD, FABP4 levels are the same as those without ASD. Thus, the amount of FABP4 appears to be too low in children with ASD at a very specific period in development. It might, therefore, not only be a biomarker, it may play a role in disease development.
The RIKEN team, led by Takeo Yoshikawa, plans to continue this work in both patients and their mouse model.
"We hope to replicate our findings in a larger group, which will allow us to determine whether specific ASD symptoms or their severity are related to low levels of FABP4," noted Maekawa. "We also hope to conduct a prospective cohort study of newborns to determine if FABP4 levels at birth can predict the future manifestation of ASD."