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Transl Psychiatry. 2016 Jan 5;6:e709. doi: 10.1038/tp.2015.187.

Telomere length as a predictor of response to Pioglitazone in patients with unremitted depression: a preliminary study.

Rasgon N1,2,3, Lin KW1,2,3, Lin J1,2,3, Epel E1,2,3, Blackburn E1,2,3.

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Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
Department of Psychiatry, University of California, San Francisco, San Francisco, CA, USA.


We studied peripheral leukocyte telomere length (LTL) as a predictor of antidepressant response to PPAR-γ agonist in patients with unremitted depression. In addition we examined correlation between LTL and the insulin resistance (IR) status in these subjects. Forty-two medically stable men and women 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. Diagnostic evaluation of psychiatric disorders was performed at baseline and mood severity was followed weekly throughout the duration of the trial. 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 at baseline. Subjects with longer telomeres exhibited greater declines in depression severity in the active arm, but not in a placebo arm, P=0.005, r=-0.63, 95% confidence interval (95% CI)=(-0.84,-0.21). In addition, LTL predicted improvement in insulin sensitivity in the group overall and did not differ between intervention arms, P=0.036, r=-0.44, 95% CI=(-0.74,0.02) for the active arm, and P=0.026, r=-0.50, 95% CI=(-0.78,-0.03) for the 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.


[Indexed for MEDLINE]
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Conflict of interest statement

JL is a co-founder and consultant to Telomere Diagnostics. The company has no role in this study. NR has been a consultant for the following companies: Shire Pharmaceuticals and Sunovion Pharmaceuticals. She has received research support from the following companies: Magceutics, ADA (American Diabetes Association) and Corcept Pharmaceuticals. None of these companies have a potential role in this study. The remaining authors declare no conflict of interest.

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