Neurochemistry and Postpartum Depression

	I recently saw a woman who reported that she experienced severe hypoactive sexual desire disorder and postpartum depression following the birth of her first baby. She is pregnant with her second child now, and asked me about any new research in the area and any advice that I could give her to avoid a recurrence.
	Pregnancy and the postpartum period are characterized as times of tremendous psychological, social, and biological changes that place some vulnerable women at greater risk for developing or relapsing into an affective or mood-related illness.1 Sanjuan and colleagues2 have suggested that the most likely time for a woman to become depressed is after childbirth.

Two major categories of mood-related disorders that arise following childbirth are postpartum blues and postpartum depression (PPD).³ Approximately 80% of these cases involve postpartum blues, manifested by increased crying, irritability, and a feeling of being overwhelmed. These symptoms generally develop within days of delivery and resolve on their own shortly thereafter.^3,4 Ten percent to 20% of these cases entail more pervasive, intense, long-lasting symptoms that represent postpartum depression.⁴ PPD, as listed in The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,⁵ generally presents within 4 weeks of delivery and persists for at least 2 weeks. However, some sources suggest that symptom onset of PPD may occur any time up to 1 year following delivery.^3,4

An important factor related to the development of mood-related illnesses during pregnancy and/or the postpartum period is the assortment of physiologic changes associated with these life stages.¹ Burt and Quezada⁶ have noted that, because of genetically primed alterations in mood in response to changing hormones during reproductive transitions, women are at increased risk for mood instability at puberty; during the premenstrum, pregnancy, the postpartum period, and perimenopause; and following miscarriage.

Recent efforts in reproductive research have focused on the role of neurotransmitters, particularly serotonin and dopamine, and neurohormones with relation to various aspects of mood and sexual motivation in women. Similarly, new research has focused on the effect of certain neurochemicals that may promote the development of PPD and other mood disorders.^4,7,8 Research has focused primarily on understanding how regulation of the hypothalamic–pituitary–adrenal (HPA) axis is related to PPD development, suggesting that major depression is characterized by disordered HPA activity. Gjerdingen⁴ stated that pregnancy causes dramatic increases in levels of endogenous glucocorticoids and estrogens—levels that subsequently fall dramatically following delivery. This dramatic shift produces a temporary hypoactivation of the HPA axis. Furthermore, decreased activation of the HPA axis has been found to be more severe and longer-lasting in women who develop symptoms of postpartum blues and PPD than in those who do not.⁴

Research by Rich-Edwards and colleagues⁷ has shown that elevated levels of corticotropin-releasing hormone (CRH) in cerebrospinal fluid may represent changes in the HPA axis associated with depressive symptoms both before and during the postpartum transition. Experimental data indicate that women with prenatal depression symptoms have higher levels of plasma CRH at mid-pregnancy than do women without depression symptoms. These findings are consistent with observations made regarding cerebrospinal CRH levels in non-pregnant individuals with major depressive disorder.

Yim and colleagues⁸ evaluated the impact of varying levels of placental CRH (pCRH) during pregnancy with reference to potential development of PPD. These investigators noted that elevated rates of pCRH at 25 weeks’ gestation serve as a statistically significant indicator for PPD development. Statistical analysis showed that this predictive finding was consistent, even after prenatal depressive symptoms were controlled for in analysis.

Another recent area of investigation related to PPD and endocrine functioning is the 5-HTT genotype/tryptophan interaction.² Tryptophan depletion may be a contributing factor to depressive symptoms. Because tryptophan depletion is a natural occurrence during pregnancy and postpartum, serum tryptophan levels may serve as a potential indicator of risk for PPD development. Results of an investigation by Sanjuan et al² have suggested that high-expression 5-HTT genotypes may increase a woman’s risk for development of depressive symptoms following childbirth, but the effect seems to be moderated by environmental factors such as presence or absence of social support.

Getting out of the home for at least a few minutes each day. Sitting on a porch or patio and taking “fresh air time” for herself and baby can be revitalizing and spirit lifting;

Avoiding isolation. Suggestions include visiting frequently with friends and family and asking someone to take her and the baby for a long ride in the car;

Eating well by following a complete nutritional program that includes pure omega-3 oils; and

Never being afraid or ashamed to ask for help. Support is available from the National Post Partum Depression Hotline at 1-800-PPD-MOMS (773-6667).

Your patient may be at risk for recurrence of the symptoms she experienced after her first pregnancy. You can inform her that an emerging body of research suggests that a connection exists between hormonal/neurochemical changes and mood-related problems during the post¬partum period.¹ In the future, these findings may lead to development of prenatal serum testing to determine a woman’s risk for PPD development and may alter some of the adverse consequences to both mother and child that are associated with this disorder.⁸