Background: The authors examined the role of dopamine and serotonin transporter genetic polymorphisms in clinical and cognitive features of subjects with late-life depression, and in preferential treatment response to the combination of methylphenidate and citalopram.
Method: The authors studied fifteen outpatients with major depression in a pilot ten-week double-blind trial of methylphenidate combined with citalopram and compared to citalopram and placebo. Response was defined as a score on the Hamilton Depression Rating Scale (24-item) of less than 10. All underwent genotyping to determine the dopamine (DAT VNTR) and serotonin (5HTTLPR) transporter polymorphisms.
Results: Subjects with DAT VNTR 10/10 genotype had greater cognitive executive dysfunction at baseline compared to others. However, they responded preferentially to methylphenidate added to citalopram with a greater reduction in depression severity over time compared to other subjects.
Conclusions: DAT VNTR 10/10 genotype may be associated with an endophenotype of late-life depression with executive dysfunction that responds preferentially to methylphenidate added to a selective serotonin reuptake inhibitor, which warrants replication in a large sample.