Genomic predictors of remission to antidepressant treatment in geriatric depression using genome-wide expression analyses: a pilot study.

Objective: This first pilot study of genome-wide expression as predictor of antidepressant response in late-life depression examined genome-wide transcriptional profiles in a randomized placebo-controlled trial of combined methylphenidate and citalopram.

Methods: Genome-wide transcriptional profiles were examined in peripheral blood leukocytes sampled at baseline and 16 weeks from 35 older adults with major depression, who were randomized to methylphenidate + citalopram, citalopram + placebo, or methylphenidate + placebo. Methylphenidate doses ranged between 10 and 40 mg/day, and citalopram doses ranged between 20 and 60 mg/day. Remission was defined as Hamilton Depression Rating Scale score of 6 or below. Early remission was achieved in the first 4 weeks of treatment. We hypothesized that differential gene expression at baseline can predict antidepressant response.

Results: We analyzed gene expression in 24 remitters and 11 non-remitters. At baseline, we found three genes showing higher expression in all remitters versus non-remitters that satisfied the established level of significance: a fold change of 2 and p-value of 0.05 that included HLA-DRB5, SELENBP1, and LOC388588. Two gene transcripts showed higher expression in early remitters at baseline compared with non-remitters. The first gene was CA1 carbonic anhydrase gene, on chromosome 8 involved in respiratory function (fold change 2.54; p = 0.03). The second gene was the SNCA-α-synuclein gene, implicated, which binds to dopamine transporter (fold change 2.1; p = 0.03).

Conclusions: Remission to antidepressants in geriatric depression may be associated with a particular gene expression profile in monoaminergic and metabolic pathways and needs to be replicated in a larger sample.