Nav: Home

Possible mechanism for specific symptoms in bipolar disorder discovered

December 15, 2015

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.
-end-
The study was financed with grants from several bodies, including the Swedish Research Council, the Swedish Foundation for Strategic Research and the Swedish Brain Fund.

Publication: "A genome-wide association study of kynurenic acid in cerebrospinal fluid: implications for psychosis and cognitive impairment in bipolar disorder", Carl M. Sellgren, Magdalena E. Kegel, Sarah E. Bergen, Carl Johan Ekman, Sara Olsson, Markus Larsson, Marquis P. Vawter, Lena Backlund, Patrick F. Sullivan, Pamela Sklar, Jordan W. Smoller, Patrik K.E. Magnusson, Christina M. Hultman, Lilian Walther-Jallow, Camilla I. Svensson, Paul Lichtenstein, Martin Schalling, Göran Engberg, Sophie Erhardt, Mikael Landén, Molecular Psychiatry, online 15 December 2015, doi: 10.1038/MP.2015.186.

http://dx.doi.org/10.1038/MP.2015.186

Karolinska Institutet

Related Bipolar Disorder Articles:

Is bipolar disorder associated with increased risk of Parkinson's disease?
This study, called a systematic review and meta-analysis, combined the results of seven studies with 4.3 million participants to examine a potential association between bipolar disorder with a later diagnosis of Parkinson's disease of unknown cause.
Bipolar disorder may be linked to Parkinson's disease
People who have bipolar disorder may be more likely to later develop Parkinson's disease than people who do not have bipolar disorder, according at a study published in the May 22, 2019, online issue of Neurology®, the medical journal of the American Academy of Neurology.
Probiotics could help millions of patients suffering from bipolar disorder
About 3 million people in the US are diagnosed every year with bipolar disorder, a psychiatric condition characterized by dramatic shifts in mood from depression to mania.
Novel intervention for anxiety symptoms among people with Bipolar Disorder
Psychologists at Lancaster University have devised a novel psychological intervention to address Anxiety in Bipolar Disorder (AIBD).
Mutation links bipolar disorder to mitochondrial disease
Mutations in the gene ANT1 may confer a risk for bipolar disorder through a complex interplay between serotonin and mitochondrial signaling in the brain.
A new path into bipolar disorder comes to light
A new article authored by an international group of researchers reveals a novel potential drug target for bipolar disorder and offers new insights into the underlying biology of this lifelong and devastating mental illness.
After searching 12 years for bipolar disorder's cause, U-M team concludes it has many
Nearly 6 million Americans have bipolar disorder, and most have probably wondered why.
Simple EKG can determine whether patient has depression or bipolar disorder
A groundbreaking Loyola Medicine study suggests that a simple 15-minute electrocardiogram could help a physician determine whether a patient has major depression or bipolar disorder.
Gene breakthrough on lithium treatment for bipolar disorder
Genes linked to schizophrenia in psychiatric patients suffering from bipolar disorder are the reason why such patients don't respond to the 'gold standard' treatment for bipolar -- the drug lithium -- according to international research led by the University of Adelaide.
Shared genetics in schizophrenia and bipolar disorder
A genetic variant associated with multiple psychiatric disorders drives changes in a brain network that may increase an individual's risk of developing bipolar disorder and schizophrenia, finds a study published in JNeurosci.
More Bipolar Disorder News and Bipolar Disorder Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.