A MULTIPLE TIMEPOINT STUDY OF N‐TERMINAL PRO‐OPIOMELANOCORTIN IN DEPRESSION USING A TWO‐SITE RECOGNITION IMMUNORADIOMETRIC ASSAY

SUMMARY N‐pro‐opiomelanocortin (N‐POMC) is secreted from the same precursor as ACTH and β‐endorphin. Elevated plasma ACTH and β‐endorphin β‐lipotro‐phin concentrations have been reported in depression, however there have been no previous studies of N‐POMC. Twenty‐five patients with major depression and 18 control subjects were studied at five timepoints to examine diurnal rhythm and the effect of a dexamethasone suppression test. N‐POMC was measured using a newly developed two‐site recognition immunoradiometric assay (IRMA). This demonstrated advantages of sensitivity, specificity and simplicity compared with existing radioimmunoassays. N‐POMC exhibited a pattern of diurnal rhythm and suppression in response to dexamethasone as described for other POMC derived peptides. Depressed subjects had higher levels of N‐POMC at 0900 h post‐dexamethasone than did control subjects. In conclusion, the results of this study are consistent with a hypothesis of cosecretion of POMC‐derived peptides. N‐POMC has a similar pattern of abnormal concentrations to ACTH and β‐endorphin /β‐Iipotrophin in depression. This constitutes probable evidence of POMC‐derived peptide resistance to glucocorticoid feedback in this condition.