Serotonin 5-HT2A receptor gene variants influence antidepressant response to repeated total sleep deprivation in bipolar depression.
5-HT2A receptor density in prefrontal cortex was associated with depression and suicide. 5-HT2A receptor gene polymorphism rs6313 was associated with 5-HT2A 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-HT2A 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.
Benedetti
Francesco
F
Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy. benedetti.francesco@hsr.it
Barbini
Barbara
B
Bernasconi
Alessandro
A
Fulgosi
Mara Cigala
MC
Colombo
Cristina
C
Dallaspezia
Sara
S
Gavinelli
Chiara
C
Marino
Elena
E
Pirovano
Adele
A
Radaelli
Daniele
D
Smeraldi
Enrico
E
D000328:Adult; D000704:Analysis of Variance; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000235:genetics* / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D010147:Pain Measurement; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012892:Sleep Deprivation; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D044402:Receptor, Serotonin, 5-HT2A; D008803:Mianserin; D000078785:Mirtazapine