Insulin-like Growth Factor 1 Differentially Affects Lithium Sensitivity of Lymphoblastoid Cell Lines from Lithium Responder and Non-responder Bipolar Disorder Patients
- 531 Downloads
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.
KeywordsInsulin-like growth factor 1 (IGF-1) Somatomedin C Let-7c Lithium Bipolar disorder Lymphoblastoid cell lines (LCLs)
Insulin-like growth factor 1
Lymphoblastoid cell lines
Receptor-related protein 1
Insulin-like growth factor binding protein 2
Insulin-like growth factor binding protein 1
Insulin-like growth factor binding protein 3
The authors thank the patients involved in the study for the generous collaboration. This study was supported by the US Israel Binational Science Foundation (BSF) Grant No. 2013223 (to DG). DG is supported by the Shalom and Varda Yoran Institute for Human Genome Research at Tel Aviv University. Elena Milanesi is a post-doctoral fellow supported by the Shabbetai Donnolo Fellowships between Italy and Israel. MG and Elisabetta Maffioletti are supported by grants from the Italian Ministry of Health (Ricerca Corrente). AS is a post-doctoral fellow funded by a grant from the Sardinia Regional Government (P.O.R. Sardegna F.S.E. Operational Program of the Autonomous Region of Sardinia, European Social Fund 2007-2013–Axis IV Human Resources, Objective l.3, Line of Activity l.3.1.).
- Åberg MAI, Åberg ND, Hedba H et al (2000) Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. Endocrinology 20:2896–2903Google Scholar
- Bezchlibnyk YB, Xu L, Wang J-F, Young LT (2007) Decreased expression of insulin-like growth factor binding protein 2 in the prefrontal cortex of subjects with bipolar disorder and its regulation by lithium treatment. Brain Res 1147:213–217. doi: 10.1016/j.brainres.2007.01.147 PubMedCrossRefGoogle Scholar
- Morag A, Pasmanik-Chor M, Oron-Karni V (2011) Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker. Pharmacogenomics 171–184Google Scholar
- Palomino A, González-pinto A, Martinez-cengotitabengoa M et al (2013) Progress in neuro-psychopharmacology & biological psychiatry relationship between negative symptoms and plasma levels of insulin-like growth factor 1 in first-episode schizophrenia and bipolar disorder patients. Prog Neuropsychopharmacol Biol Psychiatry 44:29–33. doi: 10.1016/j.pnpbp.2013.01.008 PubMedCrossRefGoogle Scholar
- Werner H, Leroith D (2014) Insulin and insulin-like growth factor receptors in the brain: Physiological and pathological aspects. Eur Neuropsychopharmacol 1–7. doi: 10.1016/j.euroneuro.2014.01.020