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The Cardiff University study is an "important step" in the search for the developmental origins of schizophrenia and other mental illnesses
.
Scientists at Cardiff University have discovered a new link between disorders in the development of brain cells and the risk of schizophrenia and other mental illnesses
.
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 (January 14, 2022) in the journal Nature Communications
.
The research was co-led by Dr Andrew Pocklinton from Cardiff University's Department of Psychological Medicine and Clinical Neuroscience and Dr Nju Jenny Shin from Cardiff University's Institute of Neuroscience and Mental Health, who is now at Keele University
.
Dr Pocklington said: "Genetic factors play an important role in determining a person's risk of developing mental illness
.
Uncovering the biological processes that are affected by these genetic risk factors is an important step in understanding the causes of disease
Dr Shin said: "To truly understand the root causes of mental illness, we focus on studying the development of brain cells
.
Knowledge gained through this approach may ultimately help guide the development of new treatments, or help explain why some people are Some therapies respond while others do not
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
.
The researchers showed that genetic risk factors for schizophrenia and other psychiatric disorders are highly concentrated in these populations
"In vitro experiments have shown that when the activation of these ensembles is disrupted, the shape, movement and electrical activity of developing brain cells change, linking changes in these properties to disease," said Dr.
Shin
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), which are often considered early Disruption of brain development does not do much
.
This raises the question of whether some of these genes, activated long before birth, remain active later in life and contribute to the maturation of brain function that could potentially be targeted for therapy
.
Dr Pocklington said: "Previous studies have shown that genes that are active in mature brain cells are enriched for common genetic variants that contribute to schizophrenia
.
Much of this enrichment has been captured by early developmental genomes that appear to contain greater common Genetic risk factor burden
"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 disrupts developing and maturing brain function, leading to disease
.
"
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.