Association Study of Genotype by Depressive Response during Tryptophan Depletion in Subjects Recovered from Major...

The brief and reversible mood response to acute tryptophan (TRP) depletion (ATD) is being studied as a trait marker in subjects considered at risk for major depression (MD).

ATD was administered to 64 subjects (54 European-Americans, and10 from other races) with personal and family history of MD. They were in remission and had been medication-free for at least three months. Subjects received an active and sham condition in a random assignment, double-blind crossover design. They were genotyped for serotonin-related candidate genes, and mood response was quantified with the Hamilton Depression Rating Scale (HDRS). Data were analyzed using Poisson regression with repeated measures and latent trajectory models.

Compared to the sham control, active ATD caused modest depressive changes showing significant main effects of test condition (χ²=5.14, df=1, p=0.023) and time (χ²=12.22, df=3, p=0.007), but no significant interaction of time and test condition. Latent trajectory analysis revealed two groups, identified as depletion responders and non-responders. Those with the HTR2A rs6313 CC genotype had significantly higher HDRS scores during ATD (χ²=11.72, df=1, p=.0006).

ATD may help the identification of biological subtypes of MD. These data are consistent with imaging reports implicating 5-HT2A receptor function in ATD phenotypes.