Substance P (NK1) receptors in the cingulate cortex in unipolar and bipolar mood disorder and schizophrenia

The substance P receptor (neurokinin-1 receptor) has been implicated in stress responses and anxiety traits in the rodent, and neurokinin-1 receptor antagonism may have antidepressant and anxiolytic effects. This suggests that the function and/or expression of neurokinin-1 receptor might be affected in subjects with mood disorders.

We measured neurokinin-1 receptor densities in the anterior cingulate cortex in subjects with unipolar (major) depression (n = 13), bipolar disorder (n = 13), schizophrenia (n = 14), and controls (n = 14) using quantitative autoradiography with [125I]BH-substance P. The anterior cingulate cortex was chosen for initial analysis since recent positron emission tomography, magnetic resonance imaging, and neuropathological data suggest its involvement in mood disorders.

Neurokinin-1 receptor densities were higher in superficial than in deep laminae. Neurokinin-1 receptor densities increased with age and declined with prolonged autopsy interval. No differences were seen between the four groups. However, the ratio of superficial to deep laminar binding was lower in the subjects with unipolar depression compared with all other groups (p < .01) Neurokinin-1 receptor binding and the laminar ratio were unaffected by sex, medication history, pH, suicide, comorbid substance abuse, or a family psychiatric history.

No overall change in neurokinin-1 receptor densities occurs in the cingulate cortex in subjects with mood disorders or schizophrenia. However, the changed laminar ratio in unipolar depression may reflect alterations in specific neural circuits expressing neurokinin-1 receptor.