World-first biomarker test can predict depression and bipolar disorder
Australian scientists have developed and validated a world-first test that is claimed to accurately measure levels of a brain protein known to be associated with depression and bipolar disorder. The new research suggests this test could offer doctors an objective diagnostic tool to assess patients for a variety of mood disorders.
A great deal of research in recent years has circled around a protein called brain-derived neurotrophic factor, or BDNF. This important protein plays a role in replenishing brain cells and promoting healthy neural functions and low levels of it have been linked to Alzheimer’s disease, schizophrenia, multiple sclerosis and mood disorders. Some research has also suggested one way exercise exerts beneficial effects on the brain is by boosting levels of BDNF.
Generally when researchers refer to BDNF they are referring to a particular mature form of the protein (mBDNF). However, the protein can present in two other forms, the precursor of BDNF (referred to as proBDNF), and the prodomain of BDNF.
Studies have indicated these different forms of BDNF have very different biological functions. In some instances the differences between mBDNF and the other two forms are fundamentally opposing, so it is vital current tests can distinguish these protein types. Unfortunately, current commercial assay kits cannot accurately separate the BDNF types.
Australian researchers have now developed a new assay kit than can, for the first time, accurately differentiate the BDNF types.
"As mature BDNF and proBDNF have different biological activities, working in opposition to each other, it is essential that we can distinguish between these two proteins and detect changes in their levels," explains Xin-Fu Zhou, one of the researchers working on the new study. ”The existing commercial BDNF ELISA (enzyme-linked immunosorbent assay) kits are not specific and can cross react with each other. The kit we have developed has an accuracy rate of 80-83 per cent."
The Australian team’s latest study, published in the Journal of Psychiatric Research, set out to test the new BDNF assay and specifically measure mBDNF levels in a broad cohort composed of subjects with major depressive disorder, bipolar disorder or a history of suicide attempts.
The research found low levels of mBDNF did correlate with both clinical depression and bipolar disorder, while severe depression symptoms were linked to even lower mBDNF levels compared to those with moderate symptoms.
Interestingly, mBDNF levels in the suicide group were not unusually low. In fact, that group’s mBDNF levels were similar to those seen in healthy control subjects. Discussing this seemingly discordant finding the researchers suggest the etiology of suicide may be more diverse than previously anticipated. More detailed longitudinal investigations will be necessary to tease out the relationship between suicide and mBDNF levels.
Another compelling finding in the new study is higher levels of mBDNF were detected in major depressive disorder (MDD) subjects currently taking anti-depressants, compared to those MDD subjects not taking antidepressants. This intriguingly suggests testing for acute increases to mBDNF levels may be a useful way to gauge how well a patient is responding to a given antidepressant treatment.
Although the research is still preliminary Zhou suggests a specific mBDNF blood level could serve as an objective diagnostic tool for doctors. In conjunction with clinical assessment, Zhou says mBDNF serum levels less than 12.4 ng/ml may be a diagnostic threshold to classify both bipolar disorder and MDD.
Now that these different types of BDNF can be effectively measured a whole host of new research questions are set to be investigated. Can imbalances between proBDNF and mBDNF be restored using drugs or other types of therapies? Does proBDNF actively contribute to depressive behavior?
"Mood disorders affect millions of people worldwide," says Zhou. "However, about one third of people with depression and bipolar disorder are resistant to antidepressants or alternative therapies. The reasons are not understood but it could have something to do with the imbalances between the different forms of BDNF, which we hope to investigate next.”
The new study was published in the Journal of Psychiatric Research.
Source: University of South Australia