Lithium is one of the most effective drugs for treating bipolar disorder, but not everyone’s symptoms are relieved.
New research shows that a patient’s response to the drug is based on a gene-level reaction, especially in the triggering or repression of genes which affect the levels of cell death (known as apoptosis).
For example, the gene called BCL2 — known to play an important role in the therapeutic effects of lithium — did not increase in non-responders. This can be measured in the blood of patients within four weeks of treatment.
For the study, researchers from Yale University School of Medicine measured the changing levels of gene activity in the blood of 20 depressed adult participants with bipolar disorder before treatment, and then again every 14 days once treatment with lithium had begun.
Throughout the eight weeks of treatment there were significant differences in the levels of gene expression between those who responded to lithium (measured using the Hamilton Depression Rating Scale) and those who did not respond.
“We found 127 genes that had different patterns of activity (turned up or down) and the most affected cellular signaling pathway was that controlled programmed cell death (apoptosis),” said reearcher Dr. Robert Beech.
For bipolar patients who responded to lithium, the genes which protect against cell death (including Bcl2 and IRS2) were increased, while those which promote cell death were decreased, including the genes known as BAD and BAK1.
“This positive swing in regulation of apoptosis for lithium responders was measurable as early as four weeks after the start of treatment, while in non-responders there was a measureable shift in the opposite direction. It seems then, that increased expression of BCL2 and related genes is necessary for the therapeutic effects of lithium,” said Beech.
“Understanding these differences in genes expression may lead towards personalized treatment for bipolar disorder in the future.”