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Macrophage Migration Inhibitory Factor and Interleukin 1-β mRNA Levels as Predictors of Antidepressant Treatment
Henry R Kranzler1, Annjanette Stone2, Steven A Schichman3
1Kranzler, MD, Veterans Integrated Service Network 4, Mental Illness Research, Education and Clinical Center, Crescenz Veterans Affairs Medical Center and Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Background:
Immunologic measures have been studied as predictors of who will respond to standard antidepressants. Two previous, small studies of pretreatment leukocyte mRNA expression levels of the cytokines macrophage migration inhibitory factor (MIF) and interleukin 1-beta (IL1-β) identified antidepressant treatment responders.
Methods:
We tested these findings in 1,299 patients from the PRIME Care study, a multi-center pharmacogenetic depression treatment trial. Patients underwent 5 depression-symptom assessments over 24 weeks. mRNA was extracted from peripheral blood, purified, and assayed with TaqMan gene expression assays and a known copy number calibrator to yield relative quantification and copy numbers for each sample. In generalized estimating equations models, we regressed the repeated depression measures and a binary treatment response measure on the baseline MIF and IL-1β measures and relevant covariates.
Results:
Participants' depression scores decreased monotonically during treatment, with the treatment response percentage increasing concomitantly. We found no significant associations of the cytokine concentrations with either the change in depression scores or the likelihood of a treatment response. A secondary analysis limited to a subsample of 126 participants selected to remove the potential for confounding also showed no significant associations.
Limitations:
Despite efforts to control for sample and assay method differences, these could have contributed to the lack of replication of prior research.
Conclusions:
We did not replicate prior findings that pre-treatment expression levels for two cytokines predicted antidepressant treatment response. This raises questions about the clinical utility of using these biomarkers in treating depression.
