Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients.
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.
Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel, elena.k.milanesi@gmail.com.
Elena
E
Milanesi
Adva
A
Hadar
Elisabetta
E
Maffioletti
Haim
H
Werner
Noam
N
Shomron
Massimo
M
Gennarelli
Thomas G
TG
Schulze
Marta
M
Costa
Maria
M
Del Zompo
Alessio
A
Squassina
David
D
Gurwitz
D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism*; D002460:Cell Line; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics
D015415:Biomarkers; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D007334:Insulin-Like Growth Factor I; D008094:Lithium