Postpartum depression: psychoneuroimmunological underpinnings and treatment

Abstract

Postpartum depression (PPD) is common, occurring in 10%-15% of women. Due to concerns about teratogenicity of medications in the suckling infant, the treatment of PPD has often been restricted to psychotherapy. We review here the biological underpinnings to PPD, suggesting a powerful role for the tryptophan catabolites, indoleamine 2,3-dixoygenase, serotonin, and autoimmunity in mediating the consequences of immuno-inflammation and oxidative and nitrosative stress. It is suggested that the increased inflammatory potential, the decreases in endogenous anti-inflammatory compounds together with decreased omega-3 poly-unsaturated fatty acids, in the postnatal period cause an inflammatory environment. The latter may result in the utilization of peripheral inflammatory products, especially kynurenine, in driving the central processes producing postnatal depression. The pharmacological treatment of PPD is placed in this context, and recommendations for more refined and safer treatments are made, including the better utilization of the antidepressant, and the anti-inflammatory and antioxidant effects of melatonin.

Keywords: IDO; SSRI; TDO; kynurenine; melatonin.

Figure 1

The predisposing, pregnancy and CUMS factors that contribute to PPD, both directly and via “baby blues” induce TDO and IDO, increasing TRYCATs, including KYNA and QUIN, as well as increasing PiCs and O&NS. Notes: Such increased immuno-inflammation drives down serotonin, melatonin, and á7nAChr, whilst increasing autoimmunity, somatization, and relative amygdalae–cortex activity. Along with decreased omega-3 polyunsaturated fatty acids, this increases PPD. Treatments include psychotherapy and antidepressants. Estrogen can enhance the efficacy of SSRIs, whilst melatonin may provide a safer treatment for both mother and child. Some antidepressants are not recommended if breastfeeding, including those where no relevant data exist. Abbreviations: á7nAChr, alpha 7 nicotinic acetylcholine receptor; CUMS, chronic unpredictable mild stress; E2, estradiol; EDO, indoleamine 2,3-dioxygenase; kyn, kynurenine; KYNA, kynurenic acid; MDD, major depressive disorder; O&NS, oxidative and nitrosative stress; PIC, proinflammatory cytokine; PPD, postpartum depression; QUIN, quinolinic acid; SES, socioeconomic status; SSI, selective serotonin reuptake inhibitor; T3, thyroid hormone; TDO, tryptophan 2,3-dioxygenase; TRYCAT, tryptophan catabolite.