0838 GMT January 29, 2020
In the largest ever study of its kind, the team found that disease-linked mutations disrupt specific sets of genes contributing to excitatory and inhibitory signaling, the balance of which plays a crucial role in healthy brain development and function, Tech Times said.
"Our study marks a significant step towards understanding the biology underpinning schizophrenia, which is an incredibly complex condition and has up until very recently kept scientists largely mystified as to its origins. We now have what we hope is a pretty sizeable piece of the jigsaw puzzle that will help us develop a coherent model of the disease, while helping us to rule out some of the alternatives," said lead author Dr. Andrew Pocklington.
"This work builds on our understanding of the genetic causes of schizophrenia ― unraveling how a combination of genetic faults can disrupt the chemical balance of the brain.
The first evidence that schizophrenia mutations interfere with excitatory signaling was uncovered in 2011 by the same team, based at Cardiff University's MRC Centre for Neuropsychiatric Genetics and Genomics.
This work not only confirms their previous findings, but also provides the first strong genetic evidence that disruption of inhibitory signaling contributes to the disorder.
To reach their conclusions, scientists compared the genetic data of 11,355 patients with schizophrenia against a control group of 16,416 people without the condition.
They looked for types of mutation known as copy number variants (CNVs), mutations in which large stretches of DNA are either deleted or duplicated.
Comparing the CNVs found in people with schizophrenia to those found in unaffected people, the team was able to show that the mutations in individuals with the disorder tended to disrupt genes involved in specific aspects of brain function.