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.
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 cause of depression is still unknown, but scientists believe the disease is partly linked to the serotonergic circuit in the brain. This is largely because SSRIs, which increase levels of the neurotransmitter serotonin at neuron connections, help alleviate the symptoms of many people diagnosed with depression. Yet, the mechanism of why some people respond to SSRIs, while others do not, remains a mystery. Unraveling the puzzle of SSRI resistance has been challenging because it requires studying the 300,000 neurons that use the neurotransmitter serotonin for communication within a brain of 100 billion total neurons. One-way scientists have recently overcome this obstacle is to generate these serotonergic neurons in the lab.
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Image: Human serotonergic neuron projections (red) and cell bodies (green). CREDIT: Salk Institute
