Depressie: genen, mechanismen en farmacologie
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- 作者：Mw. dr. Jocelien Olivier (2) (3)
prof. dr. Berend Olivier (4) (5) - 刊名：Neuropraxis
- 出版年：2013
- 出版时间：August 2013
- 年：2013
- 卷：17
- 期：4
- 页码：96-99
- 全文大小：
- 作者单位：Mw. dr. Jocelien Olivier (2) (3)
prof. dr. Berend Olivier (4) (5)
2. Department of Women’s and Children’s Health, Uppsala University, Uppsala, Zweden
3. Division Medicine, Karolinska Institutet, Stockholm, Zweden
4. Divisie Farmacologie, afd. sychofarmacologie, Utrecht Instituut voor Farmaceutische Wetenschappen, Utrecht University, Utrecht, The Netherlands
5. Department of Psychiatry, Yale School of Medicine, New Haven, Verenigde Staten - ISSN：1876-5785
文摘
Major depressive disorder (MDD) is a very severe psychiatric brain disorder. Present therapeutics only provide symptomatic treatment. Most antidepressants influence monoaminergic systems, particularly serotonin, and selective serotonin reuptake blockers (SSRIs), although developed decades ago, are still the treatment of choice. Although heritability of depression is high (up to 40%), no ‘depression’ genes have been found. Depression appears a very heterogeneous disease with hundreds of different genes involved, each gene with a rather small contribution. Lately, the role of the environment (e.g. stress) is coming into the picture. An example is the length polymorphism of the serotonin transporter (SERT). Depending on the number of repeats in the SERT promoter the activity of the SERT is affected. The short version (S-allele) generates less SERT activity than the long (L-allele) version. This S/L polymorphism has an important influence under conditions of severe life events: S-carriers are far more vulnerable to develop depression than L-carriers upon confronting serious life events. The search for new antidepressants, focusing on mechanisms in the brain directly involved in mood mechanisms is still ongoing. The spectacular finding of an acute antidepressant effect of ketamine, an analgesic, has led to a flood of research into NMDA-receptor antagonists. Similarly, L-acetylcarnitine, a diet supplement acetylating proteins in brain areas involved in mood processes, also displayed fast onset antidepressant activity. Such approaches illustrate the feasibility to develop new antidepressants that are not ‘symptom’ relieving’ but work on brain mechanisms and pathology of depression itself. This generates hope for better treatment of this devastating brain disease.