Psychiatric disorders often result from dysregulation in cellular and molecular mechanisms at the level of the brain. Unable to directly study brain tissues in patients affected by psychiatric conditions, researchers have created alternative experimental models that use different and easy to collect tissues. The underlying assumption is that by studying these "proxy" tissues, it is possible to obtain information on biological mechanisms that is a good approximation of what would be detected in the brain. One of the most established experimental models are lymphoblastoid cell lines derived from B-lymphocytes. Lymphocytes are present in the peripheral blood and can be easily collected and stored virtually forever after undergoing a special laboratory procedure that immortalize them. These cell lines have proved to be very useful in genetic and pharmacogenetic research and, using these, the investigators want to investigate the cellular effects of a mood stabilizing drug called lithium on this specific procedure that makes them virtually immortal. Two main reasons lead us to study this drug: 1) it is the most effective treatment in bipolar disorder, where approximately 30% of patients achieve complete illness remission with prevention of episode recurrence; 2) it has well established regulatory effects on the expression of specific target genes and proteins. The investigators can take advantage of these well-established properties of lithium in regulating the expression of genes, proteins, and enzymes in a stable manner. Conversely, these biological measures could be used as markers for the effects of lithium on the gene expression. The purpose of this study is to learn more about the changes in the activity of genes in cells sampled from healthy individuals treated with lithium. By studying these cellular changes, the investigators hope to understand if lymphoblastoid cell lines are valid tools in psychiatric genetics research. Specifically, the investigators want to see how specially treated lymphoblastoid cell lines are influenced by external conditions and specifically lithium treatment at the moment of sampling. To do so, the investigators will measure the gene expression (i.e. how much gene is in the cell) of lymphoblastoid cell lines and compare the levels between those sampled before and after one month of lithium treatment.
Name: Lithium CarbonateDescription: The dose has been selected in order to achieve a therapeutic range of 0.6 - 0.8 mmol/L. Dose titration Day 1: 1 capsule of 300 mg at bedtime Days 2 to 7: 1 capsule of 600 mg at bedtime Day 8: lithium serum levels will be tested and the dose will be adjusted proportionally to a target range of 0.6 - 0.8 mmol/L by increments of 150 mg or 300 mg.Type: Drug
Single Group Assignment
There is one SNP
Two recent studies (Machado-Vieira et al., 2011, Uemura et al., 2011) demonstrated that, in individuals with BD, BCL2 gene expression regulated by the single nucleotide polymorphism (SNP) rs956572 directly impacted intracellular Ca2+ homeostasis dysregulation, a molecular signalling pathway proved to play a significant role in the pathogenesis of BD. 2) Using a genome wide gene expression approach (GWGE) on multiple prostate human cancer cell lines that were incubated with lithium, Sun and coworkers 11 showed a marked downregulation of genes involved in DNA replication.