Exploring Possible Sex Difference in Raphe Nuclei Metabolism in Major Depressive Disorder

Major Depressive Disorder (MDD) is more prevalent in females. Serotonin may play a role in this differential presentation. Our group has demonstrated differential expression of the serotonin autoreceptor 1A (5-HT1A) in the raphe nuclei (RN). In MDD, males had higher 5-HT1A binding than females. The principal effect of presynaptic 5-HT1A activation by serotonin is to decrease RN serotonergic firing rate through hyperpolarization. Consequently, we hypothesized male RN metabolic rate of glucose uptake (MRGlu) would be lower than female RN MRGlu due to differential decrease in energetically expensive neuronal firing through hyperpolarization.