There is a novel phenotype of elevated monoamine oxidase B (MAO-B) level in the prefrontal cortex of patients with major depressive episodes (MDEs) secondary to major depressive disorder (MDD), a new study found. The case-control study included 20 patients with MDEs without current psychiatric comorbidities and 20 age-matched controls who underwent carbon 11-labeled [11C]SL25.1188 positron emission tomography screening to measure MAO-B distribution volume (MAO-B VT). All participants were drug and medication free, nonsmoking, and otherwise healthy. Researchers found:
- 50% of patients with MDEs had MAO-B VT values in the prefrontal cortex exceeding those of healthy controls.
- MAO-B distribution volume was significantly elevated in the prefrontal cortex of patients with MDEs compared with health controls (mean, 26%).
- Duration of illness was significantly and positively correlated with MAO-B distribution volume in the prefrontal cortex.
Moriguchi S, Wilson AA, Miler L, et al. Monoamine oxidase B total distribution volume in the prefrontal cortex of major depressive disorder: An [11C]SL25.1188 positron emission tomography study. JAMA Psychiatry. [Published online ahead of print March 6, 2019]. doi:10.1001/jamapsychiatry.2019.0044.
This paper by Moriguchi et al. contributes to the idea that major depressive disorder (MDD) is a disease state in that by using PET technology we may be able to identify in certain chronic, non-comorbid depressives that there may be a defining biological cause. We have often reverse engineered our hypotheses about the causes of MDD. For example, the antihypertensive reserpine lowered the monoamines causing the side effect of MDD which likely created the monoamine hypothesis. It posits that low monoamines cause MDD. Using this paper’s findings, perhaps we can extrapolate that possibly 50% of our patients (if similar to those in this study) likely have aggressive MAO-B enzymes in cortical neurons that unfortunately degrade norepinephrine and dopamine excessively causing low monoamine levels and then possibly hypofrontality of cortical neurocircuitry which in turn allows for some phenotypic MDD symptoms to emerge. Could this prove the monoamine hypothesis? Regarding treatment, the authors suggest that if we could easily identify patients with aggressive MAO-B genotypes or PET scan positive endophenotypes that perhaps starting an MAO inhibitor sooner, or even initially in treatment might directly address the cause of the MDD. This would go against most guidelines where MAOi agents are typically used last in the armamentarium. Alternatively, a psychopharmacologist could use tricyclics or NDRI antidepressants, but these agents would only indirectly help by raising synaptic dopamine and/or norepinephrine but would directly address the patient’s disease and would not slow down the patient’s aggressive MAO-B activity. Clinicians would have to decide to indirectly treat the neurophysiological monoamine deficit or target it directly perhaps with the riskier MAOi agent earlier in the course of MDD management. —Thomas L. Schwartz, MD; Senior Associate Dean of Education, Interim Chair/Professor of Psychiatry, SUNY Upstate Medical University.