Screening genetic variability at the CNR1 gene in both major depression etiology and clinical response to citalopram treatment
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The endocannabinoid system has been implicated in the pathogenesis of major depression (MD) as well as in the mediation of antidepressant drug effects.
To analyze CNR1 gene variants in MD and clinical response to citalopram (selective serotonin re-uptake inhibitors [SSRI]).
The role of CNR1 gene (rs806368, rs1049353, rs806371, rs806377 and rs1535255) was investigated in 319 outpatients with MD and 150 healthy individuals. A subsample of 155 depressive patients were treated with citalopram and evaluated for response (fourth week) and remission (12th week) by the 21-item Hamilton Depression Rating Scale (HDRS).
We observed a higher frequency of rs806371 G carriers in MD patients with both presence of melancholia (p = 0.018) and psychotic symptoms (p = 0.007) than in controls. Haplotype frequency distributions between MD sample and controls showed a significant difference for Block 1 (rs806368–rs1049353–rs806371) (p = 0.008). This haplotype finding was consistent when we compared controls with MD subsample stratified by melancholia (p = 0.0009) and psychotic symptoms (p = 0.014). The TT homozygous of the rs806368 and rs806371 presented more risk of no Remission than the C carriers (p = 0.008 and 0.012, respectively). Haplotype frequency distributions according to Remission status showed a significant difference for Block 1 (p = 0.032). Also, we observed significant effect of time–sex–genotype interaction for the rs806368, showing that the C carrier men presented a better response to antidepressant treatment throughout the follow-up than TT homozygous men and women group (p = 0.026).
These results suggest an effect of CNR1 gene in the etiology of MD and clinical response to citalopram.
KeywordsEndocannabinoid system Major depression Clinical response Selective serotonin reuptake inhibitors
This study was supported through research projects funded by the Ministry of Science and Innovation (SAF2008-05674-C03-00/03, FIS07/0815 and IT2009-0016), the Institute of Health Carlos III, CIBER of Mental Health (CIBERSAM), the Comissionat per a Universitats I Recerca del DIUE of the Generalitat de Catalunya (2009SGR827) and the Ministero dell’Istruzione, dell’Università e della Ricerca, Italy (IT107CB8DC).
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