title: Insulin-like growth factor 1 (IGF-1) expression is up-regulated in lymphoblastoid cell lines of lithium responsive bipolar disorder patients.
abstract: Bipolar disorder (BD) is a debilitating psychiatric disease characterized by alternating episodes of mania and depression. Among mood stabilizers, lithium is the mainstay for the treatment of BD, with approximately one-third of patients showing remission from episode recurrence. While there is evidence suggesting genetic load for lithium response in BD, its molecular underpinnings are still not completely understood. To identify genes potentially involved in (or correlated with) lithium response, we carried out a genome-wide expression analysis on lymphoblastoid cell lines (LCLs) from 10 BD patients responders (R) and 10 non-responders (NR) to lithium. We compared expression levels of the two groups and tested whether in vitro lithium treatment had different effects in LCLs of R compared to NR. At basal, 2060 genes were differentially expressed between R and NR while no genes were differentially regulated by lithium in the two groups. After pathway analysis based on the 2060 genes, 9 genes were selected for validation with qRT-PCR. Eight genes were validated in the same sample of LCLs while only insulin-like growth factor 1 (IGF-1) was significantly over-expressed in R compared to NR in the same sample as well as in an independent sample comprised of 6 R and 6 NR (sample 1, fold change=1.94; p=0.005; sample 2, fold change=2.21; p=0.005). IGF-1 was also significantly over-expressed in R but not in NR when compared to a sample of non-psychiatric controls. Our findings suggest that IGF-1 may be involved in lithium response, supporting further investigation on its potential as a biomarker.
authors.affiliation: Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Monserrato, Cagliari 09042, Italy. squassina@unica.it
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.forename: Marta
authors.initials: M
authors.lastname: Costa
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.forename: Mirko
authors.initials: M
authors.lastname: Manchia
authors.forename: Andrea
authors.initials: A
authors.lastname: Angius
authors.forename: Valeria
authors.initials: V
authors.lastname: Deiana
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ardau
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Severino
authors.forename: Stefano
authors.initials: S
authors.lastname: Calza
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy / Q000235:genetics*; D002460:Cell Line; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D018020:Lithium Compounds / Q000627:therapeutic use*; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015854:Up-Regulation
chemical_list: D018692:Antimanic Agents; C583557:IGF1 protein, human; D018020:Lithium Compounds; D007334:Insulin-Like Growth Factor I