Lithium is considered the gold standard for treating bipolar disorder (BD), but nearly 70 percent of people with BD don’t respond to it. This leaves them at risk for debilitating, potentially life-threatening mood swings. Researchers at the Salk Institute have found that the culprit may lie in gene activity–or lack of it.
A new study published in the journal Molecular Psychiatry on January 4, 2021, shows that decreased activation of a gene called LEF1 disrupts ordinary neuronal function and promotes hyperexcitability in brain cells–a hallmark of BD. The work could result in a new drug target for BD as well as a biomarker for lithium nonresponsiveness.
Shani Stern, Co-first author on the study, Zuckerman Faculty Scholar and a Salk visiting scientist explains: “When we silenced the LEF1 gene, the neurons became hyperexcitable”
“And when we used valproic acid, expression of LEF1 increased, and we lowered the hyperexcitability. That shows there is a causative relationship, and that’s why we think LEF1 may be a possible target for drug therapy.”
LEF1 may also help researchers develop a screening test for responsiveness. Currently, clinicians can only determine whether a patient is responsive to lithium by administering a complete course of treatment, which could take a year. Now, subdued activity of LEF1 may be an indicator that a patient won’t respond to lithium, enabling a faster and more efficient way to approach therapy.