Biology for the soul

Depression is still seen as a disorder suffered by people with character weaknesses who lack the capacity to cope with life’s challenges. Due to the stigmatisation of the disease and the shame experienced by those afflicted with it, depression is the most common cause of death in people under 45 in Germany. Doctor and chemist Florian Holsboer researches the causes of mental illness at the Max Planck Institute of Psychiatry using methods from biochemistry, genetics, imaging processes and model systems, aiming to tackle these misconceptions.

Holsboer constantly pleads for openness in the approach to depressive disorders, which arise from the interaction of genetic mutations and the various external influences to which individuals are exposed. It is important to him to demonstrate that anyone can suffer from depression and must seek professional help. In Holsboer’s view, the prospects for the successful treatment of depression with drugs and psychotherapy are an irrefutable scientific fact.

The focus of scientific interest concerns how depression, anxiety and sleep disorders arise, and can best be treated. A pioneer of personalised medicine, Holsboer’s aim is to create a treatment tailored to the individual characteristics of every patient. His research is funded by donations, including grants from the Max Planck Foundation. The Gunter Sachs Laboratory at the Max Planck Institute in Munich is an example of a facility named in honour of another generous supporter of the scientist’s work.

Florian Holsboer’s research gives rise to new therapeutic approaches and, therefore also, new hope for patients suffering from depression. He and his team at the Max Planck Institute of Psychiatry identify the genetic factors behind depression and anxiety disorders. They study the molecular mechanisms that cause the emergence of depression and the ways in which this clinical condition can be healed with the help of drug therapies.

It emerges from their research that the ways in which patients with depression react to stressful situations is dysfunctional. For example, the researchers discovered that the levels of a protein, which is produced by brain neurons and known as corticotropin-releasing hormone (CRH), increase under stress conditions. This not only causes the release of stress hormones, it also triggers various behavioural changes which are useful for the management of the stressful situation – e.g. increased attentiveness, fearfulness and loss of appetite. However, if the stress continues or the patient is unable to return his or her stress response to a normal balance, depression will arise.

Florian Holsboer used the different core competencies available at the Institute to explain the mechanism whereby the effect of the neuropeptide CHR is triggered in the brain, and how this can be exploited for treatment. What is involved here are the so-called CRH receptor blockers, drugs that prevent the CRH molecule from forwarding the signal in the brain. This transmission process is carried out by receptors known as CRH receptors, which are located in the cell membrane. Experiments on mice using gene technology show, that if this receptor is no longer synthesised, the CRH molecule loses its capacity to trigger behavioural responses. This idea was further pursued up to the drug development stage and an initial clinical trial established that CRH receptor blockers have an anti-depressive effect in a large number of patients. Scientists at the Max Planck institute are now using biomarkers to identify patients suffering from depression, for whom the use of a CRH receptor blocker is particularly promising.

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