Alterations in arginine vasopressin neurons in the suprachiasmatic nucleusin depression

Background: Circadian rhythm disturbances are frequently found in depressed subjects. Although it has been presumed that these disturbances ma); refle ct a disorder of the circadian pacemaker, this has never been established. The suprachiasmatic nucleus (SCN) is the pacemaker of the circadian timing system in mammals, and arginine vasopressin (AVP) is one of its major neuro peptides. 45 peptide content is often taken as a measure for activity, we h ypothesized that a decreased number of AVP-immunoreactive (AVP-IR) neurons and amount of AVP-messenger RNA (mRNA) would be present in the SCN of depre ssed subjects. Methods: Brains of Il subjects suffering from major depression (8 cases) an d bipolar disorder (3 cases), and of Il controls, matched for sex, age, and clock time at death, were collected. The number of AVP-IR neurons in the S CN was determined by means of a digitizer (CalComp Inc, Reading, England). The amount of AVP-mRNA expression in the SCN was quantified with the Intera ktive Bild Analyse System image analysis system (Kontron, Munich, Germany). Results: In depressed subjects, the number of AVP-IR neurons in the SCN was more than one and a half times higher than in controls, while the total ma sked area of silver grains, as an estimate of the amount of AVP-mRNA, was a bout one half that of controls. Conclusions: Contrary to our hypothesis, an increase in the number of AVP-I R neurons in the SCN in depression was found, together with an expected dec rease in AVP-mRNA. These findings suggest that, in depressed patients, both the synthesis and release of AVP in the SCN is reduced, resulting in an im paired functional ability. A disbalance between AVP production acid transpo rt needs further investigation in future studies.