Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (LiTMUS).

Author(s): Beech RD(1), Leffert JJ(1), Lin A(2), Sylvia LG(3), Umlauf S(4), Mane S(4), Zhao H(5), Bowden C(6), Calabrese JR(7), Friedman ES(8), Ketter TA(9), Iosifescu DV(10), Reilly-Harrington NA(3), Ostacher M(9), Thase ME(11), Nierenberg A(3).

Affiliation(s): Author information: (1)Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. (2)Keck Foundation Biotechnology Biostatistics Resource, Yale University School of Medicine, New Haven, CT, USA. (3)Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. (4)Center for Genome Analysis, Yale University School of Medicine, New Haven, CT, USA. (5)Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA. (6)Departments of Psychiatry and Pharmacology, University of Texas Health Science, San Antonio, TX, USA. (7)Department of Psychiatry, Case Western Reserve University, Cleveland, OH, USA. (8)Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. (9)Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, Stanford, CA, USA. (10)Departments of Psychiatry and Neuroscience, Mount Sinai Medical Center, New York, NY, USA. (11)Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.

Publication date & source: 2014, Pharmacogenomics J. , 14(2):182-91

This study was designed to identify genes whose expression in peripheral blood may serve as early markers for treatment response to lithium (Li) in patients with bipolar disorder. Although changes in peripheral blood gene-expression may not relate directly to mood symptoms, differences in treatment response at the biochemical level may underlie some of the heterogeneity in clinical response to Li. Subjects were randomized to treatment with (n=28) or without (n=32) Li. Peripheral blood gene-expression was measured before and 1 month after treatment initiation, and treatment response was assessed after 6 months. In subjects treated with Li, 62 genes were differentially regulated in treatment responders and non-responders. Of these, BCL2L1 showed the greatest difference between Li responders and non-responders. These changes were specific to Li responders (n=9), and were not seen in Li non-responders or patients treated without Li, suggesting that they may have specific roles in treatment response to Li.