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

Elena Milanesi, Adva Hadar, Elisabetta Maffioletti, Haim Werner, Noam Shomron, Massimo Gennarelli, Thomas G. Schulze, Marta Costa, Maria Del Zompo, Alessio Squassina, David Gurwitz

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)681-687
Number of pages7
JournalJournal of Molecular Neuroscience
Volume56
Issue number3
DOIs
Publication statusPublished - 2015

Keywords

  • Bipolar disorder
  • Insulin-like growth factor 1 (IGF-1)
  • Let-7c
  • Lithium
  • Lymphoblastoid cell lines (LCLs)
  • Somatomedin C

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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