Schizophrenia risk linked to brain cell development

Genetic risk factors are known to interfere with brain development in many of these disorders, but little is known about which aspects of this process are affected

The study is the first to find that genetic disruption of specific cellular processes critical to brain development is associated with a broad risk of psychiatric disorders

The findings were published today in the journal Nature Communications

The research was co-led by Dr Andrew Pocklinton from Cardiff University's Division of Psychological Medicine and Clinical Neuroscience and Dr Nju Jenny Shin from Cardiff University's Institute of Neuroscience and Mental Health, now at Keele University work

Dr Pocklington said: "Genetic factors play an important role in determining a person's risk of developing mental illness

Dr Shin said: "To truly understand the root causes of mental illness, we focus on studying the development of brain cells

The scientists used human pluripotent stem cells to study the birth and early development of human brain cells in vitro, a process known as neurogenesis

They found several sets of genes that are activated during neurogenesis -- both in vitro and in the human fetal brain -- and each appears to play a different functional role

"In vitro experiments have shown that when the activation of these groups is disrupted, the shape, movement and electrical activity of developing brain cells are altered, linking alterations in these properties to disease," said Dr.

Disorders associated with disruption of these genes include early-onset conditions (developmental delay, autism, and ADHD) and, more surprisingly, late-onset conditions (bipolar disorder, major depressive disorder), where the early brain Developmental disruption does not play a big role under these conditions

This raises the question of whether some of these genes are turned on long before birth, but remain active later in life and contribute to the maturation of brain function that could potentially be targeted for therapy

Dr Pocklington said: "Previous research has shown that genes active in mature brain cells are enriched for common genetic variants that contribute to schizophrenia

"This suggests that some biological pathways that are initiated early in the prenatal period may remain active later in life, and that genetic variation in these pathways contributes to disease by disrupting developing and maturing brain function

Further work is needed to map the full range of developmental processes that are disrupted in different psychiatric disorders and to explore their long-term effects on the brain

"While much remains to be discovered, our findings provide valuable insights into the developmental origins of psychiatric disorders such as schizophrenia," said Dr.

Journal Reference :

1. Bret Sanders, Daniel D’Andrea, Mark O.