MD Anderson researchers identify shared neuroimmune mechanisms in rapid-acting antidepressants

Researchers from The University of Texas MD Anderson Cancer Center, co-led by Gregory Jones, M.D., have discovered that rapid-acting antidepressants like ketamine and psychedelics share common neuroimmune pathways. By altering communication between the immune system and the brain, these therapies trigger similar molecular changes in brain cells. The exploratory findings, which link treatment response to IL-15, IL-7, and B cell signaling, could help identify which patients will benefit most.

Rapid-acting antidepressant mechanisms

• ▪Rapid-acting antidepressants trigger a common set of molecular changes related to the immune system in brain cells.
• ▪Rapid-acting antidepressants can reduce symptoms in difficult-to-treat depression and may help identify patients most likely to benefit from these treatments.

Treatment-resistant depression

• ▪Treatment-resistant depression occurs when symptoms do not improve after multiple treatments with traditional antidepressants or talk therapy.
• ▪Rapid-acting antidepressants, such as ketamine and psilocybin, have demonstrated significant, rapid symptom improvement in some patients with treatment-resistant depression.

Ketamine psychedelic neuroimmune pathways

• ▪Ketamine and psychedelics work by changing communication signals between the immune system and the brain, sharing certain neuroimmune pathways.
• ▪Researchers observed matching immune-related changes in patients' blood along with related shifts in brain electrical activity after ketamine treatment.

IL-15 treatment response biomarkers

• ▪Participants who responded to ketamine showed lower IL-15 pathway activity and higher B cell signaling before treatment than nonresponders.
• ▪Future research will determine whether IL-15, IL-7, and related biomarkers can predict treatment response before therapy.
• ▪Rapid antidepressant response may involve restoring balance between IL-7 and IL-15, with downstream effects on B cells and brain activity.

B cell signaling changes

• ▪The findings regarding neuroimmune pathways and B cell signaling are exploratory and need validation in larger, prospective studies.
• ▪The lower IL-15 pathway activity and higher B cell signaling observed in ketamine responders reversed after treatment.

Depression in cancer patients

• ▪The study, published in Molecular Psychiatry, was co-led by Gregory Jones, an assistant professor of Psychiatry at The University of Texas MD Anderson Cancer Center.
• ▪Depression is not uncommon in patients facing a cancer diagnosis, and researchers hope to use these findings to better treat them.

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