Neurokinin-I receptors are decreased in major depressive disorder

Treatment with an antagonist at the neurokinin-I (NK-I) receptor may alleviate depression, however the brain region(s) in which the NK-I receptor antagonist exerts its therapeutic effect is unknown. [I-125]BH-Substance P was used to measure NK-I receptors postmortem in cytoarchitectonically defined areas of rostral orbito-frontal cortex (Brodmann's area 47) of subjects with major depressive disorder (n = 12, six females) and psychiatrically normal subjects (n = 11, five females). Six subjects with depression died by suicide. Subjects with depression showed decreased binding to NK-I receptors across all cortical layers (p = 0.024). The pathophysiology of depression, and the reported therapeutic benefit of NK-I receptor antagonists, may thus involve NK-I receptors in prefrontal cortex.