The etiology of postpartum depression remains unclear. Changes in the reproductive hormonal milieu associated with pregnancy and the postpartum period have been postulated to play a role in mood regulation.⁵⁶ It has been hypothesized that the precipitous fall in estrogen concentration after delivery may contribute to the onset of depressive symptoms. Thyroid dysfunction may also contribute to postpartum mood disturbances.

In the 6 months after delivery,  women experience thyroid dysfunction at a rate of up to 7%^57–59 compared with a rate of 3% to 4%⁶⁰ in the general population. In a prospective study⁶¹ of 303 pregnant euthyroid women, 21 (7%) developed postpartum thyroid disorders. Depression was identified in 8 (38%) of the 21 mothers and resolved with treatment of the thyroid dysfunction. 

Thyroid dysfunction,  however, does not appear to account for the majority of cases of postpartum depression. While certain hormones, such as estradiol and corticotropin, merit further exploration, studies have been negative or contradictory for most biological variables thought to be etiologic for postpartum mood disturbance.⁵⁶ Data on the extent to which breast-feeding or weaning may affect mood are similarly inconclusive. Blood sampling in many studies does not control for breast-feeding. Lactation not only influences levels of prolactin, progesterone, estrogen, oxytocin, and cortisol, but also has been associated with both positive and negative mood states.

Prophylactic antidepressant treatment administered immediately after delivery has been noted to dramatically reduce the recurrence of postpartum major depression.

A total of 23 pregnant women with histories of at least one previous postpartum episode that fit the DSM-III-R criteria for nonbipolar major depression without psychotic features were evaluated in an open clinical trial.⁶²

Patients who began antidepressant treatment within 24 hours after delivery relapsed at a rate of 6.7% compared with a rate of 62.5% in women who deferred antidepressant prophylaxis.

Manic Depression (Bipolar Disorder)

The postpartum period is a time of exceptionally high risk for episodes of depression,  mania,  or psychosis in women with manic depressive illness. The rate of postpartum relapse in women with manic depressive illness varies but has been estimated at 20%  to 50%.^63–65  Women with manic depression have a 100-fold greater risk than women with no previous psychiatric history for developing a postpartum psychosis.

⁶⁶ Although postpartum psychosis can present with features that distinguish it from a typical manic episode (i.e., delirium-like symptoms and confusion),⁶⁷  several follow-up studies of women with postpartum psychosis demonstrate recurrence of episodes of manic depression^68,69 or schizoaffective illness,⁷⁰ an illness characterized by chronic psychotic symptoms and recurrent manic and depressive episodes.

A few studies have addressed the role of moodstabilizing medications in preventing a postpartum relapse of manic depressive illness. In a retrospective comparison of recurrence rates and survival functions after lithium discontinuation⁴  in 101 women with manic depression, symptoms increased sharply during the postpartum period. Among subjects who remained stable during the first 40 weeks after lithium discontinuation (i.e., during pregnancy), postpartum recurrences (70%) were 2.9 times more frequent than recurrences in non-childbearing women (24%)  during weeks 41 through 64. 

Stewart et al.⁷¹ studied 21 women with a prior history of postpartum psychosis who were treated with lithium either during the third trimester or immediately after delivery of a subsequent pregnancy. Only 2 women (10%) had a recurrence of psychotic illness while on prophylactic lithium. A retrospective study⁶³  of 27 women with manic depressive disorder found that only 1 (7%) of 14 women taking prophylactic mood-stabilizing agents during the acute puerperium experienced a postpartum relapse compared with 8 (61%) of 13 women who received no antimanic drugs and showed evidence of recurrent affective instability during the 3-month postpartum period. All of these studies underscore the significant morbidity associated with the natural course of manic depressive disorder in new mothers who are not treated prophylactically.