A possible role of neuropeptide Y in depression and stress

Neuropeptide Y (NPY) mediates its physiological effects through at least four receptors known as Y1, Y2, Y4, and Y5. This peptide is one of the most abundant peptides in the central nervous system and is highly conserved throughout evolution. The most abundant receptors of the NPY family, the Y1 and Y2 receptors, are densely expressed in the cortex, hippocampus, and amygdala. These brain regions are particularly associated with mood disorders, stress responses, and memory processing. With this in mind, researchers suggested the involvement of NPY as well as the Y1 and Y2 receptors in affective disorders. Earlier studies showed that NPY and the Y1 and Y2 receptors mediate some aspects of depression-like disorders and stress responses in rodents. Recent research also suggests the involvement of the Y4 and Y5 receptors in emotion-related processes in rodents. In addition, human studies have consistently suggested a role for NPY in stress responses, whereas conflicting data have been obtained in relation to the role of NPY in depression-related illnesses. However, novel evidence from polymorphisms in the prepro-NPY gene has shed new light on the potential clinical relevance of NPY in depression. In this article, we review the literature from both animal and human studies regarding the contribution of NPY and its receptors in depression and stress.