HYPOTHALAMIC CORTICOTROPIN-RELEASING HORMONE SUPPRESSION DURING THE POSTPARTUM PERIOD - IMPLICATIONS FOR THE INCREASE IN PSYCHIATRIC MANIFESTATIONS AT THIS TIME

The third trimester of human pregnancy is characterized by a hyperacti ve hypothalamic-pituitary-adrenal ards, possibly driven by progressive ly increasing circulating levels of placental CRH and gradually decrea sing levels of CRH-binding protein. The postpartum period, on the othe r hand, is characterized by an increased vulnerability to psychiatric manifestations (postpartum ''blues,'' depression, and psychosis), a ph enomenon compatible with suppressed hypothalamic CRH secretion. To inv estigate the hypothesis that the postpartum period is associated with suppression of hypothalamic CRH secretion, we studied prospectively 17 healthy euthymic women (mean +/- SE age, 32.0 +/- 1.1 yr) with no pri or history of depression, starting at the 20th week of gestation. Psyc hometric testing was performed monthly during pregnancy and postpartum on day 2 and weeks 2, 3, 6, 8, 12, 16, and 20, whereas serial ovine ( o) CRH tests were performed postpartum at 3, 6, and 12 weeks. While pr egnant, all 17 subjects remained euthymic; in the postpartum period, 7 women developed the ''blues,'' and 1 developed depression. Overall, t he mean plasma ACTH response to an iv bolus of 1 mu g/kg oCRH was mark edly blunted at 3 and 6 weeks, but normal at 12 weeks postpartum, wher eas the mean plasma cortisol response was at the upper limit of normal at all 3 times. These data are compatible with a suppressed hypothala mic CRH neuron that gradually returns to normal while hypertropic adre nal cortexes are progressively down-sizing. When the postpartum ACTH r esponses to oCRH were analyzed separately for the euthymic women and t he women who had the ''blues'' or depression, the blunting of ACTH was significantly more severe and long lasting in the latter group; this was observed at all 3 times of testing. We conclude that there is cent ral suppression of hypothalamic CRH secretion in the postpartum, which might explain the increased vulnerability to the affective disorders observed during this period. The suppressed ACTH response to oCRH migh t serve as a biochemical marker of the postpartum ''blues'' or depress ion.