Serotonin 5-HT_2A receptor gene variants influence antidepressant response to repeated total sleep deprivation in bipolar depression

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• 作者：Francesco Benedetti ; Barbara Barbini ; Aless ; ro Bernasconi ; Mara Cigala Fulgosi ; Cristina Colombo ; Sara Dallaspezia ; Chiara Gavinelli ; Elena Marino ; Adele Pirovano ; Daniele Radaelli ; Enrico Smeraldi
• 关键词：5-HT_2A receptor ; Bipolar disorder ; Major depression ; Serotonin ; Sleep deprivation
• 刊名：Progress in Neuro-Psychopharmacology and Biological Psychiatry
• 出版年：2008
• 出版时间：12 December 2008
• 年：2008
• 卷：32
• 期：8
• 页码：1863-1866
• 全文大小：299 K

文摘

5-HT_2A receptor density in prefrontal cortex was associated with depression and suicide.5-HT_2A receptor gene polymorphism rs6313 was associated with 5-HT_2A receptor binding potential, with the ability of individuals to use environmental support in order to prevent depression, and with sleep improvement after antidepressant treatment with mirtazapine. Studies on response to antidepressant drugs gave inconsistent results.

Here we studied the effect of rs6313 on response to repeated total sleep deprivation (TSD) in 80 bipolar depressed inpatients treated with three consecutive TSD cycles (each one made of 36 h awake followed by a night of undisturbed sleep). All genotype groups showed comparable acute effects of the first TSD, but patients homozygotes for the T variant had better perceived and observed benefits from treatment than carriers of the C allele. These effects became significant after the first recovery night and during the following days, leading to a 36 % higher final response rate (Hamilton depression rating < 8).

The higher density of postsynaptic excitatory 5-HT_2A receptors in T/T homozygotes could have led to higher behavioural effects of increased 5-HT neurotransmission due to repeated TSD. Other possible mechanisms involve allostatic/homeostatic adaptation to sleep loss, and a different effect of the allele variants on epigenetic influences. Results confirm the interest for individual gene variants of the serotonin pathway in shaping clinical characteristics of depression and antidepressant response.