A blood test, still currently in the experimental phase, can determine the activity of a key molecule in depressive disorders and the effect of treatment, without having to wait weeks or months.
Rasenick's team followed this difficult path, first in the laboratory and then in animals, but has now announced in the Nature Group journal Molecular Psychiatry that it has also obtained positive results in humans.
What is this all about? In order to tell you, we need to take a step back. It has long been known that an enzyme called adenylyl cyclase does not work properly in the cells of those suffering from depression. In short, this enzyme regulates how neurons respond to serotonin, noradrenaline and other molecules (neurotransmitters) involved in depression. It is also known that low levels of adenylyl cyclase are 'caused' by the malfunctioning of another protein, Gs alpha, which under normal conditions moves from the outer membrane of cells to their interior, also facilitating the entry of various types of hormones and neurotransmitters. However, in people with depression, it is trapped in a cholesterol-rich matrix of the cell membrane.This prevents adenylyl cyclase from working properly and leads to depressive disorders.
Many drugs try to force Gs alpha to ‘move' from the outer cell membrane to the inside. But how can you tell if they are working, and how long do they take? Now to the University of Illinois' studies.
Researchers have managed to identify and measure a molecule in blood platelets - a mediator, in technical terms, called PGE1 - that makes it possible to quantify the movement of Gs alpha from the membrane into the cells. We thus have an idea of whether or not there is a biological condition that causes depressive symptoms, as well as the effects of therapies. This is the marker we are talking about.
Trial and Error
It has been known for years that about a third of patients do not respond to antidepressants, and that some those who do respond to these drugs become resistant over time. So psychiatrists have to start a treatment and then wait weeks or even several months, before they can tell whether the therapy is working or not, using complex tests.
The same happens when resistance sets in. Depressed people often turn to their G.P., who does not have the specific tests available and can only assess the situation based on what the patient reports. These difficulties make treating depression complicated and, not infrequently, unsuccessful, sometimes with notable side effects.
To test the reliability of their marker, the American researchers chose 49 patients diagnosed with depression and 60 healthy control patients. Using the platelets, they were able to check how Gs alpha moved. They confirmed that less Gs alpha ‘moves' into cells in people suffering from depression than in healthy people. 19 of the depressed patients were then put on a six-week drug therapy, at the end of which 11 of them responded, showing a significant increase in Gs alpha movement compared to those who did not respond (the effect of many antidepressants is to force the Gs alpha protein to break away from the membrane and enter nerve cells).
The marker had an 80% predictive ability.
New tests to be launched soon
This is obviously a very small sample, but data obtained seems encouraging, also because the marker's variations can be detected with a simple blood test every seven days, as the platelets with which the marker is associated have an average lifespan of a week.
Now psychiatrists in Chicago will carry out further research and testing on a larger sample of volunteers to see whether the marker is really a reliable parameter that can be suggested to all doctors to help them diagnose depression and recommend truly effective treatments.
