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

• Published in: The pharmacogenomics journal Vol. 14; no. 2; pp. 182 - 191
• Main Authors: Beech, R D, Leffert, J J, Lin, A, Sylvia, L G, Umlauf, S, Mane, S, Zhao, H, Bowden, C, Calabrese, J R, Friedman, E S, Ketter, T A, Iosifescu, D V, Reilly-Harrington, N A, Ostacher, M, Thase, M E, Nierenberg, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2014; Nature Publishing Group
• Subjects: 631/1647/2017; 631/208/212/1728; 692/699/476/1333; 692/700/565/1436; Analysis; bcl-X Protein - biosynthesis; bcl-X Protein - genetics; Biomedical and Life Sciences; Biomedicine; Bipolar disorder; Bipolar Disorder - drug therapy; Bipolar Disorder - genetics; Bipolar Disorder - pathology; Blood Proteins - biosynthesis; Drug metabolism; Female; Gene Expression; Gene Expression Regulation - drug effects; Genes; Genetic aspects; Genetic research; Human Genetics; Humans; Lithium; Lithium - administration & dosage; Male; Oncology; original-article; Patients; Peripheral blood; Pharmacotherapy; Psychopharmacology; bipolar disorder; microarray; lithium-response; gene expression
• ISSN: 1470-269X; 1473-1150; 1473-1150
• DOI: 10.1038/tpj.2013.16

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 1month 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.