New gene variant may explain psychotic features in bipolar disorder

March 5, 2013

Researchers at Karolinska Institutet in Sweden have found an explanation for why the level of kynurenic acid (KYNA) is higher in the brains of people with schizophrenia or bipolar disease with psychosis. The study, which is published in the scientific periodical Molecular Psychiatry, identifies a gene variant associated with an increased production of KYNA. The discovery contributes to the further understanding of the link between inflammation and psychosis – and might pave the way for improved therapies.

Kynurenic acid (KYNA) is a substance that affects several signalling pathways in the brain and that is integral to cognitive function. Earlier studies of cerebrospinal fluid have shown that levels of KYNA are elevated in the brains of patients with schizophrenia or bipolar diseases with psychotic features. The reason for this has, however, not been fully understood.

KMO is an enzyme involved in the production of KYNA, and the Karolinska Institutet team has now shown that some individuals have a particular genetic variant of KMO that affects its quantity, resulting in higher levels of KYNA. The study also shows that patients with bipolar disease who carry this gene variant had almost twice the chance of developing .

KYNA is produced in inflammation, such as when the body is exposed to stress and infection. It is also known that stress and infection may trigger psychotic episodes. The present study provides a likely description of this process, which is more likely to occur in those individuals with the related to higher production of KYNA. The researchers also believe that the discovery can help explain certain features of schizophrenia or development of other psychotic conditions.

"Psychosis related to bipolar disease has a very high degree of heredity, up to 80 per cent, but we don't know which genes and which mechanisms are involved," says Martin Schalling, Professor of at Karolinska Institutet's Department of Molecular Medicine and Surgery, also affiliated to the Center for Molecular Medicine (CMM). "This is where our study comes in, with a new explanation that can be linked to signal systems activated by inflammation. This has consequences for diagnostics, and paves the way for new therapies, since there is a large arsenal of already approved drugs that modulate inflammation."

Explore further: Decline in verbal ability in adolescence linked to psychosis in later life

More information: 'The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and KMO expression', Catharina Lavebratt, Sara Olsson, Lena Backlund, Louise Frisén, Carl Sellgren, Lutz Priebe, Pernilla Nikamo, Lil Träskman-Bendz, Sven Cichon, Marquis P. Vawter, Urban Ösby, Göran Engberg, Mikael Landén, Sophie Erhardt, and Martin Schalling, Molecular Psychiatry, online first 5 March 2013.

Related Stories

Decline in verbal ability in adolescence linked to psychosis in later life

January 22, 2013
(Medical Xpress)—New research from King's College London's Institute of Psychiatry and Karolinska Institutet, Sweden, has found that adolescents whose verbal performance drops off are at increased risk of developing schizophrenia ...

Evidence of familial vulnerability for epilepsy and psychosis

May 2, 2012
Although the two disorders may seem dissimilar, epilepsy and psychosis are associated. Individuals with epilepsy are more likely to have schizophrenia, and a family history of epilepsy is a risk factor for psychosis. It is ...

Replicating risk genes in bipolar disorder

October 15, 2012
One of the biggest challenges in psychiatric genetics has been to replicate findings across large studies.

A risk gene for cannabis psychosis

November 14, 2012
The ability of cannabis to produce psychosis has long been an important public health concern. This concern is growing in importance as there is emerging data that cannabis exposure during adolescence may increase the risk ...

Recommended for you

Study finds gene variant increases risk for depression

July 20, 2017
A University of Central Florida study has found that a gene variant, thought to be carried by nearly 25 percent of the population, increases the odds of developing depression.

Study examines effects of stopping psychiatric medication

July 20, 2017
Despite numerous obstacles and severe withdrawal effects, long-term users of psychiatric drugs can stop taking them if they choose, and mental health care professionals could be more helpful to such individuals, according ...

In making decisions, are you an ant or a grasshopper?

July 20, 2017
In one of Aesop's famous fables, we are introduced to the grasshopper and the ant, whose decisions about how to spend their time affect their lives and future. The jovial grasshopper has a blast all summer singing and playing, ...

Perceiving oneself as less physically active than peers is linked to a shorter lifespan

July 20, 2017
Would you say that you are physically more active, less active, or about equally active as other people your age?

New study suggests that reduced insurance coverage for mental health treatment increases costs for the seriously ill

July 19, 2017
Higher out-of-pocket costs for mental health care could have the unintended consequence of increasing the use of acute and involuntary mental health care among those suffering from the most debilitating disorders, a Harvard ...

Old antibiotic could form new depression treatment

July 19, 2017
An antibiotic used mostly to treat acne has been found to improve the quality of life for people with major depression, in a world-first clinical trial conducted at Deakin University.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.