From early prenatal development through childhood, the prefrontal cortex of the human brain undergoes an avalanche of developmental activity. In some cases, it also contains seeds of neuropsychiatric illnesses such as autism and schizophrenia, according to a new genetic analysis led by researchers at Yale University and the University of California-San Francisco (UCSF).
Previous studies have identified DNA variants linked to neuropsychiatric illnesses, but it has been unclear just when those variations might trigger functional changes in the dorsal lateral prefrontal cortex, a region closely linked to neuropsychiatric, cognitive, and emotional disorders.
This new study, published April 7 in the journal Cell Reports, added a new dimension to prior research. The scientists also measured the amount of RNA, which provides a picture of overall gene activity, in 176 tissue samples across a variety of developmental stages to determine how and when DNA variants influence brain function.
“This is the first large cohort to profile DNA and RNA both in prenatal and postnatal human brain samples, making it an unprecedented resource for understanding how individual genetic differences might lead to functional differences.” Sirisha Pochareddy, Study Co-Lead author and Associate Research Scientist in Neuroscience, Yale University
“Human brain development is an incredibly complex and dynamic process, and any disruption along the way can have profound consequences on later brain function,” said co-lead author Donna Werling, formerly of UCSF and now at the University of Wisconsin-Madison. “Interestingly, we found that some genetic variants have stronger effects on RNA expression before birth and other variants with strongest effects after birth.”
Studying these age-specific effects can open more doors for learning about the mechanisms behind brain disorders, the authors said.
