Researchers at Karolinska Institutet, and the
Sahlgrenska Academy at Gothenburg University in
Sweden have identified a gene variant linked to
psychotic symptoms and cognitive impairment in
people with bipolar disorder. The study, which is
published in the journal Molecular Psychiatry,
describes 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,” says Mikael Landén,
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 can largely be
attributed to inherited factors. In recent years,
scientists have identified specific gene variants
that increase the risk of these diseases, but these
risk variants only go some way to explaining why
some people are afflicted by the disease and others
are not. We currently do not know how these genetic
risk factors affect the chemistry of the brain and
cause specific symptoms, so it is not yet possible
for scientists to design drugs to relieve symptoms
shown by people with a particular genetic variant.
To link, at a molecular level, a gene variant with
biochemical changes and clinical symptoms related to
a heritable psychiatric disorder, as in this present
study, is therefore something of a breakthrough.
The study involved people with bipolar disorder from
the St. Göran project being run 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 CSF, a
fluid that surrounds the brain and that thus gives a
good indication of its chemistry. On performing 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,” says Professor Landén. “The
pathway mainly involves signalling via the brains’
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.”
Although the study participants all suffer from
bipolar disorder, the researchers behind the study
think that the mechanisms also apply to other
psychotic disorders, such as schizophrenia.
For more information
Molecular Psychiatry
A genome-wide association study of kynurenic acid in
cerebrospinal fluid: implications for psychosis and
cognitive impairment in bipolar disorder
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Sahlgrenska akademin
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