Abstract
Despite common use of antidepressants to treat postpartum depression, little is known about the impact of antidepressant use on postpartum brain activity. Additionally, although oxytocin has been investigated as a potential treatment for postpartum depression, the interaction between antidepressants and exogenous oxytocin on brain activity is unknown. We explored postpartum depressed women’s neural activation in areas identified as important to emotion and reward processing and potentially, antidepressant response: the amygdala, nucleus accumbens and ventral tegmental area. We conducted a secondary analysis of a functional imaging study of response to sexual, crying infant and smiling infant images in 23 postpartum depressed women with infants under six months (11 women taking antidepressants, 12 unmedicated). Participants were randomized to receive a single dose of oxytocin or placebo nasal spray. There was significantly higher amygdala activation to sexual stimuli than either neutral or infant-related stimuli among women taking antidepressants or receiving oxytocin nasal spray. Among unmedicated women receiving placebo, amygdala activation was similar across stimuli types. There were no significant effects of antidepressants nor oxytocin nasal spray on reward area processing (i.e., in the nucleus accumbens or ventral tegmental area). Among postpartum women who remain depressed, there may be significant interactions between the effects of antidepressant use and exogenous oxytocin on neural activity associated with processing emotional information. Observed effect sizes were moderate to large, strongly suggesting the need for further replication with a larger sample.
Highlights
Antidepressants are a standard treatment for postpartum depression (PPD) [1]
We selected the amygdala, ventral tegmental area (VTA), and nucleus accumbens (NAc) as our regions of interest (ROI): each has been shown relevant for antidepressant response, each undergoes significant re-organization during the postpartum period, and each has been shown to be responsive to oxytocin
There was a significant interaction between medication, nasal spray condition, and stimuli type (Left: F(2, 13) = 6.85, p = .01, η2partial = 0.51; Right: F(2, 12) = 3.67, p = .04, η2partial = 0.48; see Fig 1); we conducted follow-up contrasts to examine the nature of the interaction
Summary
While gestational stress appears to disrupt typical neuroplasticity in postpartum rats, these effects are reversed with fluoxetine treatment [37, 43] Based on these data, we selected the amygdala, VTA, and NAc as our regions of interest (ROI): each has been shown relevant for antidepressant response (including in PPD), each undergoes significant re-organization during the postpartum period, and each has been shown to be responsive to oxytocin. As antidepressants have been shown to amplify reward activation in non-postpartum contexts [32, 48], we hypothesized that PPD women taking antidepressants would have significantly higher VTA and NAc activation to positive emotional images (smiling infants, sexual images) relative to unmedicated women This means we expected different effects of antidepressants on amygdala vs reward area processing of sexual images: decreasing activation in the former while increasing the latter. Given the dearth of prior research, we did not have a priori hypotheses regarding how the combination of exogenous oxytocin and antidepressants would impact contrasts between stimuli types, or differences in activation of amygdala vs. reward processing areas
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