The success of treatment for depression can be predicted

Specific disease characteristics and the genetic characteristics of a patient allow a prediction of the effects of antidepressants

It is still unclear why drugs at approximately 30 percent of patients not sufficiently effective with depression. Scientists at the Max Planck Institute for Psychiatry in Munich have this phenomenon now being investigated by analysis of genetic and clinical parameters.

Their goal was to clarify which factors determine the success of treatment. They have identified the genetic material of patients first 46 genes that positively influence the effects of antidepressants. A future characterization of these genes promises new insights into the pathogenesis and treatment approaches. The interesting thing: Many of the genetic factors have been shown to also active in metabolic, cardiovascular diseases. In addition, the therapy proceeds particularly low in patients with a high number of positive gene variants, missing anxiety symptoms or young age. (Archives of General Psychiatry, online publication, 8. 2009 September)

Depression can be caused by genetic factors as well as environmental factors. Anatomical changes in certain brain regions, chronic overactivity of stress hormones, cognitive losses and much more show how much a patient changes psychologically and physically during a depression. The drug treatment is still based on antidepressants. These increase neuronal messenger substances that - such as serotonin - play a crucial role in the communication of nerve cells. However, the sad reality is that many patients cannot be completely cured by antidepressants. An improvement in well-being often only occurs after many weeks or months, as many body systems first have to be brought back into balance.

In order to see the patient as a whole, the scientists at the Max Planck Institute for Psychiatry deliberately did not check the influence of a single gene on the effect of antidepressants on the patient. "With regard to the different, but simultaneously acting processes during recovery, we examined the entire genome of the patient", says Marcus Ising, head of the "Molecular Psychology" working group. A total of 1532 patients from three different groups took part in the study. In a multi-stage approach, the researchers initially identified 328 gene variants that had an influence on the success of the treatment. The strongest effects were found for 46 gene variants, which showed either a positive or negative influence on the outcome of therapy in all three patient groups. The more favorable gene variants could be detected in a patient, the faster he responded to antidepressants. Interestingly, genes that have been shown to be active in metabolic, cardiac and vascular diseases could also be associated with depression. It has long been known that these diseases are related. However, this finding allows the first molecular clues for a common disease mechanism.

Since, in addition to genetic information, living conditions also have a decisive influence on depression, clinically relevant criteria such as age at the onset of the disease, diagnosis such as recurring episodes of illness, chronic depression, simultaneous anxiety disorder and the age and gender of the patient were taken into account in the study. It has been shown that patients with a large number of favorable gene variants and without simultaneous anxiety symptoms respond particularly quickly to antidepressants. Obviously, today's antidepressants do not adequately correct disease-related changes that underlie depression with superimposed anxiety disorder.

With the help of the knowledge gained, a targeted study of these processes is now possible. The effects of antidepressants, which were discovered back in the 1950s, can now be elucidated using the methods of genome research. The aim is to understand which body's own molecular control circuits react to the common antidepressants in order to readjust the unbalanced nervous system. "On the basis of this knowledge it will one day be possible to provide targeted and successful therapy and to intervene to prevent disease in people with an increased risk of disease," says Florian Holsboer, Director of the Max Planck Institute.

Original work:

M. Ising, S. Lucae, EB Binder, T. Bettecken, M. Uhr, S. Ripke, MA Kohli, JM Hennings, S. Horstmann, S. Koiber, A. Menke, B. Bondy, R. Rupprecht, K Domschke, BT Baune, V. Arolt, AJ Rush, F. Holsboer, B. Müller-Myhsok A genome-wide association study points to multiple loci predicting antidepressant treatment outcome in depression Archives of General Psychiatry, online publication, September 8 2009

Source: Munich [MPG]