People suffering from the most severe form of schizophrenia have a considerably higher number of uncommon mutations than people suffering from more normal forms of the disorder, according to a recent discovery by researchers.
It was reported in the journal ‘PNAS’ that the findings of the study had been published.
It is hoped that their discoveries will bring new insight into the genetics of schizophrenia, which will pave the way for the identification of those at risk and the development of tailored medicines for those in need of newer treatments.
In a statement, lead author Anthony W Zoghbi, MD, said, “Our findings highlight a promising strategy for identifying genetic risk factors for neuropsychiatric disorders, which we hope will eventually lead to new and more precise treatments.” Zoghbi conducted the research while at Columbia University and is now an assistant professor of psychiatry and behavioural sciences at Baylor College of Medicine.
Between 60 and 80 per cent of people have schizophrenia, a chronic condition that affects brain functioning and causes hallucinations, delusions, and other cognitive abnormalities. Schizophrenia is highly heritable, with heritability ranging between 60 and 80 percent.
Despite significant progress in identifying genes associated with schizophrenia, scientists have yet to fully understand the genetic mechanisms underlying the disabling disorder that affects more than 3 million people in the United States and use that information to develop more effective treatments for the condition.
As part of the study’s design, the research team adopted a “extreme phenotype” technique, which concentrated on the most severely affected people with schizophrenia who had not shown any improvement with traditional therapies. Extreme treatment resistance was defined as sickness severity that necessitated an individual’s continuous hospitalization for at least five years in a long-term inpatient facility in the state of New York.
We were able to find the highest-burden of uncommon genetic variants described in the schizophrenia literature to date by recruiting patients from this key population, who had hitherto been underrepresented in genetic investigations, said Dr Zoghbi.
The researchers performed whole-genome sequencing on 112 patients with severe, severely treatment-resistant schizophrenia and 218 patients with more typical presentations of schizophrenia, and they compared the results to over 5,000 healthy controls to arrive at their conclusions.
In their study, they discovered that individuals with the most severe form of the disease had a significantly higher number of harmful mutations in genes that are relevant to neuropsychiatric disorders when compared to both individuals with typical forms of schizophrenia and healthy control subjects.
Individuals with very treatment-resistant schizophrenia were more likely than the general population to have at least one of these rare and harmful mutations, compared to approximately 30% of those with typical schizophrenia and 25% of controls.
The discovery of rare variants associated with severe schizophrenia by Jeffrey A. Lieberman, MD, professor and chair of the Department of Psychiatry at Columbia University College of Physicians and Surgeons, and a study co-author, said the discovery of rare variants associated with severe schizophrenia provides a more complete understanding of the genetic architecture of the disease that could not only help predict who is at risk of developing schizophrenia but also be used to develop targeted therapeutics.
According to Dr. Lieberman, “I hope that these findings will provide support for whole genome sequencing of patients diagnosed with schizophrenia during their first episode of illness so that they are not subjected to ineffective treatments and can be more expeditiously considered for treatments based on the products of their gene mutation.”