In adults, a protein called brain-derived neurotrophic factor (BDNF) promotes the growth and survival of nerve cells and is known to play a vital role in learning, memory, and maintaining brain flexibility, or “plasticity.”
Psychological stress reduces blood levels of one form of the protein, called mature BDNF (mBDNF), and low levels are associated with depression.
However, commercially available blood tests are unable to differentiate accurately between mBDNF and its precursor, known as proBDNF.
This matters because proBDNF binds to a different receptor and causes inflammation and nerve degeneration.
“Growing evidence indicates that inflammation in brain cells is linked with depressive behaviors, and proBDNF seems to activate the immune system,” says Prof. Xin-Fu Zhou of the University of South Australia in Adelaide. “Therefore, we must separate it from mature BDNF to get an accurate reading.”
Recent studies in animals by Prof. Zhou and his colleagues found that injecting proBDNF into the brain or muscle triggers depressive behaviors.
Prof. Zhou and his team have now developed a test that can measure mBDNF much more accurately.
In collaboration with the University of Adelaide and Kunming Medical University in Yunnan, China, they used the new test to show that people with depression or bipolar disorder have significantly lower levels of mBDNF in their blood than healthy controls.
In a paper that appears in the Journal of Psychiatric Research, the study authors say that doctors could use the test to diagnose these conditions and monitor the success of treatment.
“This could be an objective biomarker, in addition to a clinical assessment by a doctor,” says Prof. Zhou.
This type of test, known as an “enzyme-linked immunosorbent assay,” or ELISA, uses antibodies to detect the presence of specific proteins.
The researchers applied their new test to blood samples from 90 inpatients with major depressive disorder, 15 inpatients with bipolar disorder, and 96 healthy controls. The healthy controls were people who had attended the medical center at the psychiatric hospital for a general medical examination and did not have a severe mental illness.
They also tested samples from 14 other people with a history of suicide attempts in the past 10 years. All of these individuals were living in the community and should, therefore, have had better mental health than the current inpatients.
The test revealed that the participants with major depression or bipolar disorder had significantly lower levels of mBDNF in their blood compared with the controls.
Those with severe symptoms of depression had significantly lower levels than those with moderate symptoms.
In addition, people who were taking antidepressants had higher levels than those who were not.
Interestingly, there was no significant difference in mBDNF levels between the individuals who had attempted suicide in the past and the healthy controls. However, the former group was living in the community at the time of the study and may or may not have had symptoms of depression.
The authors estimate that a diagnostic test based on their assay, with a cutoff point of 12.4 nanograms per milliliter of serum, would have a sensitivity of 82.2% and a specificity of 83.3%. This means that the test will miss approximately 1 in 5 people who have depression and deem 1 in 5 people without depression to be depressed.
There were similar findings in the small subgroup with bipolar disorder.
In the future, the team plans to investigate whether electroconvulsive therapy (ECT) can restore imbalances between proBDNF and mBDNF.
ECT is often effective in patients who do not respond to antidepressants or psychotherapy.
Prof. Zhou explains:
“Mood disorders affect millions of people worldwide. 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 authors acknowledge that their study had some limitations.
For example, they originally wanted to measure serum levels of proBDNF, in addition to mBDNF. However, for technical reasons, this was not possible. As a result, the researchers were unable to determine whether the balance between these two forms of BDNF or their absolute values had the most significant effect.
They also note that confounding variables, such as whether participants smoked and their body mass index (BMI), may have affected the levels of mBDNF in their blood.
It is important to note that the study participants with MDD were inpatients and, therefore, represent a very small proportion of all people with MDD. As the control group was attending a mental health hospital for a general medical examination, they do not represent the general population.
Further studies are necessary to see how the levels of mBDNF in people living in the community with MDD compare with those in the general population. By doing this, researchers could determine the relevance of these findings to psychiatric care for people with depression.