The effects of the dopamine and serotonin transporter polymorphisms on clinical features and treatment response in...

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.

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.

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.

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.