Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD. Now, Salk Institute researchers have discovered differences in growth patterns of neurons of SSRI-resistant patients. The work, published in Molecular Psychiatry on March 22, 2019, has implications for depression as well as other psychiatric conditions such as bipolar disorder and schizophrenia that likely also involve abnormalities of the serotonin system in the brain.
“With each new study, we move closer to a fuller understanding of the complex neural circuitry underlying neuropsychiatric diseases, including major depression,” says Salk Professor Rusty Gage, the study’s senior author, president of the Institute, and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease. “This paper, along with another we recently published, not only provides insights into this common treatment, but also suggests that other drugs, such as serotonergic antagonists, could be additional options for some patients.”
The most commonly prescribed antidepressants, selective serotonin reuptake inhibitors (SSRIs), lift the fog of depression for many people. But for around a third of people with major depressive disorder, SSRIs don’t make much of a difference. Now, researchers from the Salk Institute have pinned down a possible reason why — the neurons in at least some of these patients’ brains may become hyperactive in the presence of the drugs. The study appeared in Molecular Psychiatry on January 30, 2019.
“This is a promising step toward understanding why some patients don’t respond to SSRIs and letting us better personalize treatments for depression,” says Salk Professor Rusty Gage, the study’s senior author, president of the Institute, and the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease.
Depression affects 300 million people around the world, and more than 6 percent of the US population experiences an episode of major depressive disorder (MDD) in any given year. MDD has been linked to an imbalance in serotonin signaling, although the exact mechanism is not well understood.