NARSAD Distinguished Investigator Grantee, Martin Schalling, M.D., Ph.D. was among a team of researchers from the Karolinska Institutet in Sweden who recently discovered a genetic variant of an enzyme in the brain that can lead to psychosis in both schizophrenia and bipolar disorder. The results of this study were reported online in Molecular Psychiatry on March 5th.
Kynurenic Acid (KYNA), a substance in the brain that affects several signaling pathways integral to cognitive function, is found at higher levels in the brains of people with psychosis. It is known that KYNA is produced in inflammation, when the body is responding to stress and/or infection, but it has not been known why the levels are elevated in those patients with psychosis.
Dr. Shalling and team found that individuals with a specific genetic variant of an enzyme called “KMO” have elevated levels of KYNA. The team also discovered that in patients with bipolar disorder with this variant of KMO, the likelihood of developing psychosis nearly doubles.
“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,” said Dr. Schalling, Professor of medical genetics at Karolinska Institutet’s Department of Molecular Medicine and Surgery. “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.”