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Researchers identify possible biomarker for depression

Researchers have observed a neural response in depressed patients’ visual cortex, specifically to emotional stimuli, after treatment with the antidepressant drug scopolamine, according to new findings published in JAMA Psychiatry. The neural activity may serve as a biomarker for identifying patients who will respond favorably to treatment.

“The identification of biomarkers that accurately predict treatment response may prove particularly useful for guiding treatment decisions and hastening clinical response,” the researchers wrote. “Importantly, the use of antidepressant agents that produce a rapid clinical onset offers the potential for the assessment and identification of biomarkers that can predict treatment response prior to or early in treatment.”

Maura L. Furey, PhD, of the National Institute of Mental Health, and colleagues conducted a double blind, placebo-controlled crossover study of 15 outpatients who met DSM-IV criteria for recurrent major depressive disorder (MDD) and 21 healthy participants aged 18 to 55 years. During seven sessions, all participants received a 15-minute intravenous infusion of either scopolamine (Transderm Scop, Novartis) 4 mcg/kg or placebo. Participants underwent functional magnetic resonance imaging(fMRI) scans while performing face-identity and face-emotion working memory tasks.

Patients’ response to scopolamine was measured relative to their scores on the Montgomery-Asberg depression rating scale (MADRS).

Participants with MDD showed a significant reduction in depressive symptoms (P<.001), ranging from 10% to 99%. Among participants receiving scopolamine, 11 showed a clinical response — defined as ≥50% reduction in MADRS scores — and four participants did not respond to the drug. Those who received scopolamine did not experience a worsening of depression severity (P>.20).

The researchers observed a neural response in the bilateral middle occipital cortex during the emotion working memory task, which was associated with treatment response magnitude. After scopolamine administration, participants also showed a change in neural activity in overlapping areas in the middle occipital cortex while performing the same task, which also correlated with a clinical response. At baseline, healthy participants exhibited greater activity in the same visual regions vs. participants with MDD.

“The need to improve current methods of treatment selection for individual patients is clear, and the identification of biomarkers of response has the potential to do so,” the researcher wrote.

Disclosure: Furey and study researcher Wayne C. Drevets, MD, have been identified as the co-inventors of the use of scopolamine in the treatment of depression in a patent pending in the United States and an existing patent in Europe. Study researcher Carlos A. Zarate Jr., MD, is listed as a co-inventor on a patent application for the use of ketamine in major depression. Zarate will share a percentage of royalties related to that patent.