Scientists have discovered a delicate chemical balance of inhibitory and excitatory signaling of brain neurons appears to trigger schizophrenia.
The new findings, published in the journal Neuron, may eventually aid in the development of new treatment models, replacing current therapies that have not experienced significant change in 40 years.
Schizophrenia is a condition that affects around one percent of the global population. The symptoms of schizophrenia can be extremely disruptive, impeding a person’s ability to carry out everyday tasks.
In the largest ever study of its kind, the team, led by Cargill University researchers, found that disease-linked mutations disrupt specific sets of genes. The genes, in turn, contribute to excitatory and inhibitory signaling, the balance of which plays a crucial role in healthy brain development and function.
The breakthrough builds on two landmark studies led by members of the Cardiff University team, published last year in the journal Nature.
“We’re finally starting to understand what goes wrong in schizophrenia,” said lead author Dr. Andrew Pocklington. “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.
“A reliable model of disease is urgently needed to direct future efforts in developing new treatments, which haven’t really improved a great deal since the 1970s.”
Professor Hugh Perry, who chairs the Medical Research Council Neuroscience and Mental Health Board said: “This work builds on our understanding of the genetic causes of schizophrenia, unravelling how a combination of genetic faults can disrupt the chemical balance of the brain.
“Scientists in the UK, as part of an international consortium, are uncovering the genetic causes of a range of mental health issues, such as schizophrenia.
“In the future, this work could lead to new ways of predicting an individual’s risk of developing schizophrenia and form the basis of new targeted treatments that are based on an individual’s genetic makeup.”
Having a proper balance between chemical signals is integral to healthy brain function as the signals excite and inhibit nerve cell activity.
Researchers studying psychiatric disorders have previously suspected that disruption of this balance contributes to schizophrenia.
The first evidence that schizophrenia mutations interfere with excitatory signalling was uncovered in 2011 by the same team, based at Cardiff University’s MRC Centre for Neuropsychiatric Genetics and Genomics.
This paper 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.
Source: Cardiff University/EurekAlert!