Baby blues

Pregnancy and the post-partum period are sensitive times for both mother and baby. Two recent papers address different aspects of maternal depression during this period. Noorlander et al. show that exposure to antidepressants in utero can have long-lasting effects on the offspring's serotonin system, and Maguire and Mody describe a convincing mouse model of post-partum depression (PPD) which suggests that altered sensitivity of GABA (γ-aminobutyric acid) type-A receptors (GABA_ARs) might predispose women to the disorder.

The pregnancy-related surge in sex-hormone levels and their subsequent fall after giving birth are thought to play a part in the aetiology of PPD, but it is unclear why some women develop depression whereas others do not. Sex-hormone derivatives called neurosteroids bind to several receptor types, including GABA_ARs. Maguire and Mody therefore set out to determine whether altered sensitivity of GABA_ARs for neurosteroids might underlie PPD.

They found that, in mice, expression of GABA_AR γ-subunits and δ-subunits decreased during pregnancy but quickly returned to pre-pregnancy levels after birth. Similarly, both tonic (mediated by δ-subunit-containing GABA_ARs) and phasic (mediated by γ-subunit-containing GABA_ARs) inhibition of granule cells in the dentate gyrus were reduced during pregnancy and normalized post partum.

To study the possible behavioural effects of changes in GABA_AR-mediated inhibition during and after pregnancy, the authors examined mice that lacked the δ-subunit of GABA_ARs ( Gabrd ^−/− mice). These mice displayed reduced tonic inhibition of dendate gyrus granule cells (relative to virgin wild-type mice) before and during pregnancy. Furthermore, unlike in wild-type mice, the lower levels of inhibition remained reduced after pregnancy. Post-partum, Gabrd^−/− mice showed higher levels of depressive-like behaviour and increased anhedonia compared with wild-type and virgin Gabrd^−/− mice.

Gabrd^−/− mice also showed abnormal maternal behaviour in the post-partum period, characterized by impaired nest building and reduced pup gathering. Approximately 40% of pups of Gabrd^−/− mothers died owing to neglect or cannibalism. The reduced survival rate was not caused by a lack of GABA_AR in the pups themselves, as wild-type pups fostered to Gabrd^−/− mice were also more likely to die. Restoring GABA_AR function in Gabrd^−/− mothers by adding a GABA_AR δ-subunit agonist to the drinking water increased the pups' survival rate.

Research into the causes of PPD has so far been hampered by a lack of adequate animal models for the disorder, but these findings suggest that Gabrd^−/− mice might provide a useful model of PPD, as they show both depressive-like behaviour and abnormal maternal care. Moreover, the data indicate that impaired restoration of GABA_AR levels post partum might have a role in the development of PPD.

Women who are prone to PPD or women who are depressed during pregnancy are often advised to take antidepressant medication while pregnant. Noorlander et al. examined the effects that this might have on the fetus and found that, in mice, fetal exposure to clinical doses of a selective serotonin-reuptake inhibitor reduced post-natal survival of the pups and, in adulthood, caused decreased serotonin transporter levels in the raphe nucleus and anxiety-like behaviour.

Together these papers highlight not only the importance of developing animal models of depression during and after pregnancy, but also the value of research into the short- and long-term effects of antidepressant medication on offspring.