Researchers have identified a gene variant linked to psychotic symptoms and cognitive impairment in people with bipolar disorder, according to a new study published in the journal Molecular Psychiatry. The findings show a possible mechanism for how the gene variant produces clinical symptoms by affecting levels of specific proteins in the brain.
“We’ve identified a gene variant linked to specific psychotic symptoms and cognitive impairment in people with bipolar disorder,” said Mikael Landén, M.D., Ph.D., researcher at Karolinska Institutet’s Department of Medical Epidemiology and Biostatistics and the Sahlgrenska Academy’s Department of Neuroscience and Physiology.
“The link to cognitive symptoms is particularly interesting, since there are no treatments currently available to improve problems with attention, memory, and concentration, which impact heavily on functional outcome and recoverability.”
Bipolar disorder and schizophrenia are largely dependent on genetic factors. In recent years, scientists have identified specific gene variants that increase the risk of these diseases, but these risk variants only minimally explain why some people are afflicted by the disease while others are not.
Because scientists do not fully understand exactly how these genetic risk factors affect the chemistry of the brain and cause specific symptoms, it has not been possible to design drugs to relieve symptoms in people with a particular genetic variant. So connecting a gene variant with biochemical changes and clinical symptoms related to a heritable psychiatric disorder, as in this present study, is considered a breakthrough.
The research involved patients with bipolar disorder from the St. Göran project in Stockholm and Gothenburg. Besides carefully mapping the participants’ specific symptoms, the scientists also tested their cognitive abilities and measured levels of different proteins in their blood and cerebrospinal fluid (CSF), a fluid that surrounds the brain and can therefore offer a good indication of its chemistry.
After conducting a genome-wide association study (GWAS), they found that a genetic variant of the SNX7 gene was associated with both the levels of a protein in the CSF, known as kynurenic acid, and the disease symptoms.
“We then conducted a series of supplementary experiments to identify a probable signal pathway, from the occurrence of the genetic risk variant to clinical symptoms in the form of psychosis and cognitive impairment,” Landén said.
“The pathway mainly involves signalling via the brain’s immune cells, and thus differs from how today’s drugs operate. What we’re hoping, therefore, is that the new mechanisms we’ve discovered will help in the development of more targeted drugs, where existing immune-modulating drugs can also be of interest.”
While all the study participants suffer from bipolar disorder, the researchers behind the study think that the mechanisms also apply to other psychotic disorders, such as schizophrenia.
Source: Karolinska Institutet