Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients

J Mol Neurosci. 2015 Jul;56(3):681-7. doi: 10.1007/s12031-015-0523-8. Epub 2015 Mar 5.

Abstract

Bipolar disorder (BD) is a chronic psychiatric illness with an unknown etiology. Lithium is considered the cornerstone in the management of BD, though about 50-60 % of patients do not respond sufficiently to chronic treatment. Insulin-like growth factor 1 (IGF1) has been identified as a candidate gene for BD susceptibility, and its low expression has been suggested as a putative biomarker for lithium unresponsiveness. In this study, we examined the in vitro effects of insulin-like growth factor 1 (IGF-1) on lithium sensitivity in lymphoblastoid cell lines (LCLs) from lithium responder (R) and non-responder (NR) bipolar patients. Moreover, we evaluated levels of microRNA let-7c, a small RNA predicted to target IGF1. We found that exogenous IGF-1 added to serum-free media increased lithium sensitivity selectively in LCLs from NR BD patients. However, no significant differences were observed when comparing let-7c expression in LCLs from R vs. NR BD patients. Our data support a key role for IGF-1 in lithium resistance/response in the treatment of bipolar disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / metabolism*
  • Cell Line
  • Drug Resistance
  • Female
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Lithium / pharmacology*
  • Lithium / therapeutic use
  • Lymphocytes / drug effects*
  • Lymphocytes / metabolism
  • MicroRNAs / genetics

Substances

  • Biomarkers
  • MicroRNAs
  • mirnlet7 microRNA, human
  • Insulin-Like Growth Factor I
  • Lithium