It is however clear from the literature that the gene is expressed, though at more basal levels, in lymphoblasts as well as many other cell types. Despite their peripheral origin, studying transformed LCLs offers the benefit of performing in vitro assays on cells from patients and studying putative factors in their endogenous expression Dimesna context. However, results from these experiments should be considered with a level of scepticism, as the relevance of SYN2 expression in this cell type is unclear. Environmental factors could be involved in Li’s regulatory role, which might account for the observed patient-specific effects in Liresponders. To investigate this possibility we computed correlations with a number of environmental factors relating to age of patients, Li therapy, and family history of other psychiatric disorders. However, none of the potential covariates correlated with SYN2a or SYN2b expression values, suggesting that the source of variation may be related to genetic or possibly epigenetic differences between patients. For example, variants in CREB genes or GSK3B, have been shown to associate with Li-treatment response. Similarly, it is possible that epigenetic factors may increase SYN2 expression variance among patients. Though this is of interest, to our knowledge, no studies have investigated the role of Li treatment on epigenetic modifications in the human brain. However, valproate, another widely used mood stabilizer, is well known for its Indinavir sulfate inhibitory effect on histone deacetylases and therefore, it is possible that at least part of Li’s action may be related to epigenetic regulation. Another epigenetic regulatory level where lithium��s effect could be confounded is microRNA-mediated regulation. Studies in LCLs and animal models have shown the drug��s global effect on this class of molecules. For a variety of biological reasons, each patient��s LCLs could be enriched in a combination of regulatory factors which could then impact the response to Li treatment. Since our LCL results do not automatically represent what is occurring in the brain, we sought to determine if Li would have a cell-type-specific effect on SYN2 expression in model cell lines representative of the brain, and showed a significant change in the neuronal cell line SK-N-AS only. There was an effect at 1.0 and 2.0 mM Li, but not at 0.5 mM, suggesting that this concentration was not high enough to elicit a response. Interestingly, the effect was specific to the SYN2a variant, as the SYN2b variant remained unchanged between conditions. Originally, SYN2 had been believed to display neuron-specific expression in the brain; however, further studies demonstrated the gene’s expression in other cell types, though at considerably lower concentrations. SYN2 is expressed at basal levels in various cell types and thus lithium likely modulates its expression to a certain degree in these cells.