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Often referred to as the “hormone of love”, oxytocin is a pro-social hormone and plays an important role in childbirth, maternal behavior, social affiliation, and sexual pleasure.  Oxytocin activity increases in response to stress, as well as to warm social or physical contact. As a mother cares for her new baby, oxytocin levels surge in both the mother and her infant and facilitate breastfeeding, maternal caregiving, the formation of a strong bond between mother and infant.  

Lower Oxytocin Levels in the Children of Depressed Mothers

Researchers at the Bar-Ilan University in Israel followed a group of mothers who were consistently depressed during the first year of their children’s lives and a control group of women who were not depressed.  At six years of age,  they assessed the children.  They discovered that  61% of the children with depressed mothers displayed some sort of psychiatric disorder, mainly anxiety and oppositional defiant disorder, compared to 15% of the children of nondepressed mothers.  The children of depressed mothers also demonstrated less social engagement with their mothers, less playfulness and creativity, and lower social involvement than children in the control group.

Since oxytocin is the hormone which mediates social engagement, the researchers wondered if some of the behaviors observed in the children of depressed mothers might be related to lower oxytocin levels.  They found that oxytocin levels were lower in the mothers with depression and in their children.  

In addition, they discovered that the depressed mothers and their children were also three times more likely than the children in the control group to have the GG homozygous genotype variant of the oxytocin receptor (OXTR).  Presence of a single OXTR A allele (GA or AA genotype) in depressed mothers markedly decreased the risk of child psychopathology.  This finding parallels research studies in older children, which demonstrated that adolescent girls with this oxytocin receptor GG variant and had exposure to early adverse life events were more likely than girls with the GA or AA OXTR genotype to experience higher levels of depression and anxiety.

Oxytocin To Treat Postpartum Depressive Symptoms

What would happen if we administered oxytocin to mothers with postpartum depression?  Would it help with the depression or improve bonding and social engagement with the child? Thus far, there have been a handful of studies which have looked at the effects of oxytocin administered to women with postpartum depression.  One study found that oxytocin did not make depressed mothers happier but their perception of the relationship with their baby improved (Mah et al, 2013). In another study, researchers found that depressed mothers who received intranasal oxytocin became more protective of their children (Mah et al, 2015).  

In a double-blind, placebo-controlled, randomiZed controlled trial, Baron-Cohen (not the comedian but his neuroscientist brother) and colleagues assessed the impact of intranasal oxytocin on mood in a group of postpartum women.  The study included 58 mothers between 3 and 9 months postpartum.  Depressive symptoms were assessed using  the Edinburgh Postnatal Depression Scale (EPDS), and the participants were divided into two groups: probable depression cases (N = 26, scoring 9 or greater) and controls (N = 32, scoring less than 9).  

The researchers used a cross-over design, such that at the first visit the participant received either oxytocin or placebo, and at the next visit (a week later) she received the other treatment.  Participants rated their current mood on the Positive and Negative Affect Scale (PANAS) at three timepoints: baseline (before treatment), at Condition 1 (after first oxytocin or placebo administration) and at Condition 2 (after second oxytocin or placebo administration).

Administration of intranasal oxytocin did not affect mood in women with EPDS scores above the cut-off point; however oxytocin did significantly reduce negative mood in those scoring below the cut-off point. To explore if a particular subgroup was driving this finding, they compared participants with mild (EPDS 0-5), moderate (EPDS 6-10) and severe (EPDS above 11) depressive symptoms. Oxytocin administration did not significantly reduce negative mood in women with clinical levels of PPD but did reduce negative mood symptoms in those with depressive symptoms of moderate severity (EPDS scores 6-10).

Why does there appear to be no benefit in women with more severe depressive symptoms? The authors postulate that women with more severe depressive symptoms may require a higher dose or longer duration of oxytocin administration.  They also speculate that women with more severe symptoms may have reduced plasticity of the oxytocin system and/or reduced oxytocin receptor responsiveness.  It is also possible that “normal” negative mood symptoms are distinct from the negative mood symptoms observed in women with postpartum depression. I also wonder about the timing of the treatment.  The women included in this study were 3-9 months postpartum.  Would women treated earlier during the postpartum period be more sensitive to the effects of oxytocin?

While these findings are very interesting, studies regarding the use of oxytocin in this setting have been mixed.  Further investigations are needed to explore the timing, dose-response and monitoring of unwanted side effects of administered oxytocin in order to better understand the clinical utility of oxytocin in postpartum women.

Ruta Nonacs, MD PhD

Baron-Cohen KL, Feldman R, Fearon P, Fonagy P.  Intranasal oxytocin administration improves mood in new mothers with moderate low mood but not in mothers with elevated symptoms of postnatal depression: a randomised controlled trial.  J Affect Disord. 2021 Nov 26:S0165-0327(21)01292-1. 

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