How anti-depressants work: new discoveries could improve depression treatment
EU-funded researchers from the Institute of Psychiatry, King's College London in the UK, have discovered for the first time in a human model how anti-depressants make new brain cells, meaning that researchers can now develop better and more efficient drugs to combat depression.
The study was carried out as part of the MOODINFLAME project, funded under the 'Health' Thematic area of the Seventh Framework Programme (FP7).
Whilst previous studies have shown that anti-depressants produce new brain cells, until now it was not known how this happened
The study, published in the journal Molecular Psychiatry, shows that anti-depressants regulate the protein glucocorticoid receptor (GR) - a key protein involved in the stress response. The study also shows that all types of anti-depressant are dependent on the GR to create new cells as it switches on particular genes that turn immature 'stem' cells into adult 'brain' cells.
Lead author of the study Christoph Anacker said: 'For the first time in a clinically relevant model, we were able to show that anti-depressants produce more stem cells and also accelerate their development into adult brain cells. Additionally, we demonstrate for the first time that stress hormones, which are generally very high in depressed patients, show the opposite effect. By increasing the number of new-born cells in the adult human brain, anti-depressants counteract the damaging effects of stress hormones and may overcome brain abnormalities which may cause low mood and impaired memory in depression.'
This research is the latest in a succession of projects into the role of the GR in depression carried out at the Laboratory of Stress, Psychiatry and Immunology (SPI-lab) at King's College London. For this research, the team used human hippocampal stem cells (the source of new cells in the human brain) to test 'in a dish' what kind of an effect anti-depressants have on brain cells.
According to the World Health Organisation (WHO), depression affects about 121 million people worldwide, and is one of the leading causes of disability. Less that 25 % of people who suffer from depression have access to effective treatments.
Recent studies have demonstrated that depressed patients show a reduction in a process called 'neurogenesis', which means they experience a reduction in the development of new brain cells. Reduced neurogenesis may contribute to the debilitating psychological symptoms of depression, such as low mood or impaired memory.
With as much as half of all patients failing to combat depression with currently available treatments, it is imperative that new effective anti-depressant treatments are developed. Although this remains a challenge, identifying new mechanisms to target is a step in the right direction.
MOODINFLAME is a large-scale medical scientific project with a consortium of 18 partners from Belgium, Bulgaria, Germany, Ireland, France, Italy, the Netherlands, Austria, Sweden and the United Kingdom.
The main objectives are to develop blood tests and brain scans to identify mild chronic inflammation in mood disorder patients and individuals who are at risk of suffering from a major mood disorder (children), and to treat patients and individuals at risk of a major mood disorder with anti-inflammatory medicines.
The project will also explore animal models (special mice and rats) of major mood disorders, i.e. animals with a low-grade inflammation of the brain, and study any abnormal mechanisms in the brain in depth before testing different correction possibilities with medicines.
Christoph Anacker says: 'Having identified the glucocorticoid receptor as a key player in making new brain cells, we will now be able to use this novel stem cell system to model psychiatric illnesses in the laboratory, test new compounds and develop much more effective, targeted anti-depressant drugs. However, first it is important that future studies investigate all possible effects that the increase of neurogenesis has on behaviour in humans.'
Category: Project results
Data Source Provider: King's College London
Document Reference: Anacker, C., et al. (2011) Antidepressants, neurogenesis and glucocorticoid receptor. Molecular Psychiatry. DOI: 10.1038/mp.2011.26.
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