Among patients with major depression, increased inflammatory markers at baseline may predict an anti-depressant response. Reducing inflammation may augment response to psychotropic medications. Few studies have investigated an association between Leukocyte Telomere Length (LTL) and therapeutic response in depression, reporting mixed results. No studies assessed LTL and treatment response with PPAR-γ agonists.

(1) LTL as a predictor of anti-depressant response to PPAR-γ agonist in patients with unremitted depression.

(2) the correlation between LTL and insulin resistance (IR) status.

We aimed to assess LTL as a predictor of antidepressant response to Pioglitazone in groups of insulin resistant and insulin-sensitive subjects using surrogate markers of IR.

Medically stable men and women (n = 42) ages 23–71 with non-remitted depression participated in double-blind placebo controlled add-on of Pioglitazone to treatment-as-usual. Oral glucose tolerance tests were administered at baseline and at 12 weeks.

At baseline, no differences in LTL were detected by depression severity, duration or chronicity. LTL was also not significantly different between insulin-resistant and insulin-sensitive subjects. Subjects with longer telomeres exhibited greater declines in depression severity in the active arm, but not in a placebo arm. LTL also predicted improvement in insulin sensitivity in the group overall and did not differ between the active and placebo arm.

LTL may emerge as a viable predictor of antidepressant response. An association between insulin sensitization and LTL regardless of the baseline IR status points to potential role of LTL as a non-specific moderator of metabolic improvement in these patients.

I, Dr. Natalie Rasgon, am a consultant for Shire Pharmaceuticals and Sunovion Pharmaceuticals.