Robert Freedman, M.D., editor of the American Journal of Psychiatry (AJP) has selected a paper by Rebecca Birnbaum, M.D. and colleagues at the Lieber Institute for Brain Development (LIBD) as “particularly interesting and important” and featured it in the editors’ selection of noteworthy papers of 2014. The paper, published in AJP in July, reports findings from an investigation as to whether the prenatal expression of specific psychiatric disease-associated genes may ‘kick start’ atypical brain development that can lead to neurodevelopmental disorders including autism spectrum disorder (ASD) and schizophrenia. Dr. Freedman notes that the paper offers an important “puzzle piece” for identifying what causes these disorders to develop.
Dr. Rebecca Birnbaum, Research Fellow at LIBD and first author on the paper, explains the approach. “We scanned the literature to identify sets of genes that have been associated with psychiatric illness and then analyzed their prenatal expression patterns using the LIBD Brain Repository and the associated, publicly available BrainCloud™ database. We asked if the expression of these specific susceptibility genes was more abundant in prenatal vs. postnatal brains to test our hypothesis that glitches in gene regulation during initial brain development can lead to later behavioral symptoms of mental illness.”
The research team found increased fetal expression of susceptibility genes for intellectual disability and ASD, supporting the hypothesis that these genes are relatively over-active when the brain is first developing. The majority of susceptibility genes for schizophrenia were not found to be over-expressed prenatally, but the team did find them to be intrinsically linked to nervous system and brain cell development at the earliest stages.
Dr. Freedman notes that the paper offers an important “puzzle piece” for identifying what causes these disorders [autism spectrum disorder and schizophrenia] to develop.
The article resolves “how the complex genetic architecture of these two illnesses [ASD and schizophrenia] is translated, not directly into clinical illness, but rather into pathological brain development that then forms the basis for what will later become illness,” Dr. Freedman states in his Year in Review commentary.
Daniel R. Weinberger, M.D., Director and CEO of LIBD says that the team is seeking to “create the roadmap for brain development. We are focused on the question of how these illnesses start at the earliest possible stages so that we will be able to develop early intervention and even preventive strategies.”
The team also found a statistically significant fetal under-expression in genes linked to neurodegenerative disorders that develop later in life, offering further evidence that the “signature” for brain function is created while the brain itself is taking shape.
The LIBD BrainCloud™ database is openly accessible for further study and analyses.