Acute antidepressant response to sleep deprivation combined with light therapy is influenced by the catechol-O-methyltransferase Val(108/158)Met polymorphism.
Catechol-O-methyltransferase (COMT) inactivates norepinephrine and dopamine via methyl conjugation, and a G-A transition in the COMT gene (rs4680) influences the enzyme activity. It is a current area of debate whether rs4680 can influence antidepressant response in major depressive disorder, and whether this influence extends to bipolar depression. Chronotherapeutic interventions, such as sleep deprivation and light therapy, are multi-target in nature and are effective in bipolar depression. Here we studied the effect of rs4680 on response to sleep deprivation combined with light therapy (36 h awake followed by a night of undisturbed sleep, with 10,000 lx light administered for 30 min during the night awake and upon awakening) in 87 bipolar depressed inpatients. Patients who were homozygotic for the Val/Val variant showed a significantly less efficient antidepressant effect after the night awake than those who were heterozygotic and homozygotic for the Met variant. This effect of rs4680 is similar to its observed influence on response to serotonergic and noradrenergic drug treatments in major depressive disorder. This is the first study reporting an influence of rs4680 on antidepressant response in bipolar depression. This finding supports the hypothesis of a major role for catecholamines in the mechanism of action of chronotherapeutics, and for rs4680 in modulating this effect.
Benedetti
Francesco
F
Division of 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
Dallaspezia
Sara
S
Gavinelli
Chiara
C
Locatelli
Clara
C
Lorenzi
Cristina
C
Pirovano
Adele
A
Radaelli
Daniele
D
Smeraldi
Enrico
E
Colombo
Cristina
C
D000328:Adult; D000483:Alleles; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003131:Combined Modality Therapy; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010789:Phototherapy; D011110:Polymorphism, Genetic / Q000235:genetics*; D012892:Sleep Deprivation; D016896:Treatment Outcome
D002394:Catechol O-Methyltransferase