Neuropsychopharmacology (2011) 36, 1886–1893& 2011 American College of Neuropsychopharmacology. All rights reserved 0893-133X/11
www.neuropsychopharmacology.org

Plasma Oxytocin Concentration during Pregnancy is
associated with Development of Postpartum Depression
Marta Skrundz1, Margarete Bolten1,2, Irina Nast1, Dirk H Hellhammer3 and Gunther Meinlschmidt*,1,4
1SesamFSwiss Etiological Study of Adjustment and Mental HealthFNational Centre of Competence in Research, Faculty of Psychology,
University of Basel, Basel, Switzerland; 2Child and Adolescents Psychiatric Clinic, Department of Developmental Psychopathology, Universityof Basel, Basel, Switzerland; 3Division of Theoretical and Clinical Psychobiology, University of Trier, Trier, Germany; 4Department of ClinicalPsychology and Epidemiology, Faculty of Psychology, University of Basel, Basel, Switzerland

Postpartum depression (PPD) affects up to 19% of all women after parturition. The non-apeptide oxytocin (OXT) is involved inadjustment to pregnancy, maternal behavior, and bonding. Our aim was to examine the possible association between plasma OXT
during pregnancy and the development of PPD symptoms. A total of 74 healthy, pregnant women were included in this prospective
study. During the third trimester of pregnancy and within 2 weeks after parturition, PPD symptoms were assessed using the Edinburgh
Postnatal Depression Scale (EPDS). Blood samples for plasma OXT assessment were collected in the third trimester. Following theliterature, participants with postpartum EPDS scores of 10 or more were regarded as being at risk for PPD development (rPPD group).
In a logistic regression analysis, plasma OXT was included as a potential predictor for being at risk for PPD. Results were controlled for
prepartal EPDS score, sociodemographic and birth-outcome variables. Plasma OXT concentration in mid-pregnancy significantly
predicted PPD symptoms at 2 weeks postpartum. Compared with the no-risk-for-PPD group, the rPPD group was characterized bylower plasma OXT concentrations. To our knowledge, this is the first study to show an association between prepartal plasma OXT
concentration and postpartal symptoms of PPD in humans. Assuming a causal relationship, enhancing OXT release during pregnancy
could serve as a potential target in prepartum PPD prevention, and help to minimize adverse effects of PPD on the mother–childrelationship.
Neuropsychopharmacology (2011) 36, 1886–1893; doi:10.1038/npp.2011.74; published online 11 May 2011
Keywords: postpartum depression; oxytocin; pregnancy; EPDS; adaptation to motherhood

INTRODUCTION
Postpartum depression (PPD) affects up to 19% of allmothers and adversely influences maternal adaptation tomotherhood (Gavin et al, 2005) with negative effects onchild development, as children of depressive mothers are
more vulnerable to develop mental disorders in later life
(Grace et al, 2003).
The etiology of PPD is closely related to psychologicaldeterminants and experiences during pregnancy (O’Hara
and Swain, 1996). Identification of psychological risk factors
for PPD has been an important issue in the recent years.
Major identified risk factors are a history of previous PPD
or affective disorders in general, stressful life events, lack ofsocial support, and low self-esteem (Beck, 2006; Robertson
et al, 2004). Additionally, the early postpartum period is*Correspondence: Dr G Meinlschmidt, SesamFSwiss Etiological Studyof Adjustment and Mental Health, Institute of Psychology, University ofBasel, Missionsstrasse 60–62, Basel CH-4055, Switzerland,
Tel: + 41 61 267 0275, Fax: + 41 61 267 0659,
E-mail: gunther.meinlschmidt@unibas.chReceived 5 December 2010; revised 24 February 2011; accepted 21
March 2011

seen as a time of increased emotional vulnerability, partly
caused by dysregulations of the endocrinological homeostasis (Wisner and Stowe, 1997). Because of the challenging
reorganization of physiological processes that comes alongwith pregnancy and parturition, research started to address
endocrine factors as potential determinants in the etiology
of PPD. From animal models of PPD, we know thatwithdrawal from high doses of estradiol and progesterone,comparable to the respective amounts available during
pregnancy, is followed by depression-like symptoms (Greenet al, 2009). Addtionally, the regulation of the hypothalamic–
pituitary–adrenal (HPA) axis seems to be disturbed inwomen with PPD (Brummelte and Galea, 2010) or shortperiods of Postpartum Blues (Ehlert et al, 1990). However,existing findings are not consistent (Bloch et al, 2003). One
biological parameter that has not yet been considered in
PPD etiology, is the non-apeptide oxytocin (OXT). OXT issynthesized in the paraventricular nucleus (PVN) and thesupraoptic nucleus (SON) of the hypothalamus and released
peripherally into the blood and centrally into different brain
regions (Gimpl and Fahrenholz, 2001). In context ofpregnancy, OXT is known for its involvement in theprocess of delivery (Russell et al, 2003) and its physiologicalOxytocin and postpartum depression
M Skrundz et al1887

role in the onset and maintenance of lactation (Sala andAlthabe, 1968).
Beyond its physiological functions in the periphery,
animal studies provide evidence for a major role of OXT
in behavioral adaptation to pregnancy and motherhood.
Characteristic maternal behaviors (pup-grooming, hoverover offspring and respond latency) are impaired, if OXT
availability is diminished (Higuchi and Kaba, 1997; Olazabal
and Young, 2005; Pedersen et al, 2006). Furthermore,maternal OXT functioning influences reciprocal affective
behaviors between mother and offspring in mammalian
species (Nelson and Panksepp, 1998). Recently, this association was also shown in humans. Parents showing more
affectionate and stimulatory behaviors in interactions with
their children were characterized by higher plasma OXT
concentrations (Gordon et al, 2010). Further, Feldman et al.
(2007) reported associations between prepartum-assessed
OXT concentrations and postpartum maternal adaptation.
The maternal plasma OXT level, measured during early andlate pregnancy, as well as in the first month postpartum,
predicted maternal behavior (mother’s gaze at infant,motherese vocalizations and affectionate touch) in interaction with the child. A study assessing plasma OXT twice
during pregnancy showed higher postpartum maternal–fetal
attachment-scores in women with a OXT rise between thefirst and third trimester compared with women with stableor decreasing patterns of OXT (Levine et al, 2007). In nonpregnant women, OXT is known to promote interpersonal
relationships and enhance feelings of love and trust(Heinrichs and Domes, 2008).
On the basis of current evidence, lower OXT levels
in pregnancy could result in impaired emotional adaptation
to motherhood, which is a major risk factor for PPD
development and subsequently affects the quality ofmaternal behavior (Murray et al, 1993; Stein et al, 2010).
Therefore, the aim of this study was to assess a
potential association between OXT during pregnancy
and postpartum PPD symptoms in a sample of healthy
pregnant women. We expected, that lower plasma OXT
levels during the third trimester of pregnancy would
result in an increased risk for PPD, as assessed postpartum. Results could help to elucidate the etiopathology
of PPD and provide new targets for prepartal preventionof PPD.

METHODS
Subjects
Data were collected within a larger longitudinal study
conducted with 100 pregnant women in the area of Basel,
Switzerland. All participants were recruited between their
21st and 32nd week of gestation. Recruitment methods
included local newspaper announcements, promotion of thestudy at local hospitals and a call for participants on local
TV. A detailed study description was given to all interested
women and, if any arised, questions were answered.
All participants were screened for the following inclusion
criteria: (a) no current mental illness, (b) no severe medical
complications (acute or chronic physical diseases, such as
gestational diabetes, metabolic diseases, hypertension andthyroid dysfunction), (c) no signs of fetal malformation,

Figure 1

Flowchart of study participants.

(d) a pre-pregnancy BMI below 32, (e) no smoking beyond
the 10th week of gestation and (f) good knowledge ofGerman language. Data for analyses of the present
paper were available for 73 participants, of which 16
were characterized by at least one lifetime depressive
episode. All lifetime episodes of depression occured morethan 2 years before participation in the study. A flowchart ofstudy participants is displayed in Figure 1. Comparisons
between the 73 women providing complete data and the 27
excluded women indicated no significant differences on age,parity, socioeconomic status and PPD symptoms.
Informed written consent was obtained from all participants. The study protocol was approved by the local ethics
committee and is consistent with the revised Helsinki
Declaration of 1975.

Blood Sampling and OXT Measurement
All blood samples were obtained between the 30th and 34th
week of gestation. Participants visited the study centre foran experimental session, which included blood sampling
and other physiological assessments. The samples for the
OXT assessment were collected at the beginning of thesession, starting between 1300 hours and 1500 hours.
Participants were seated on a examination couch and astudy nurse sampled 2.7 ml of blood into vacutainer tubes
containing lithium heparin and 108 ml of Aprotinin(BioChemica, Germany). Tubes were kept on ice and centrifuged within 10 min at 6 1C at 3000 g for 10 min. Supernatants were pipetted into safe-lock devices and stored at
80 1C until analysis.
Samples were analyzed at the Department of Behavioural
Neuroendocrinology, Max Plank Institute of Psychiatry,
Munich, Germany, using a radioimmunoassay, as described
elsewhere (Landgraf et al, 1995). This assay was reported
to have an antiserum cross-reactivity of less than 0.7%, witha detection limit of 0.1 pg per sample. All samples wereanalyzed in duplicates. The intra-assay and inter-assay
coefficients of variability were 6–8 and 8–10%, respectively.
Neuropsychopharmacology

Oxytocin and postpartum depression
M Skrundz et al

1888

Assessment of Demographic and Psychological
Characteristics
After inclusion, participants were interviewed for assessing
possible present, recent or life-time depression and anxiety
disorders using the German translation of corresponding
sections of the Computer Assisted Personal Interview(CAPI) version of the Composite International Diagnostic
Interview (Wittchen et al, 1998; Wittchen and Pfister, 1997;
World Health Organization, 1990) and general socioeconomic data.
Depressive symptoms were assessed within 2 weeks after
delivery using the Edinburgh Postnatal Depression Scale(EPDS), a scale originally developed as a screening measurefor depression, showing good reliability (split-half: 0.82;
standardized a ¼ 0.81) (Bergant et al, 1998). A total of
10 items, dealing with typical PPD symptoms are answeredon a 4-point scale. As a control variable, the prepartal EPDS
score was assessed between the 32nd and 34th week ofgestation.
Information on length of gestation and birth outcome
were collected from medical records.

analyzed using SPSS 16.0.2 for Mac OS X. The level ofsignificance for all analyses was set at a ¼ 0.05.

RESULTS
Sample and Group Characteristics
Demographic and pregnancy-related sample and groupcharacteristics are displayed in Table 1. A group variable
was introduced according to the postpartum EPDS score. In
all, 14 participants were identified as having a postpartum
EPDS score of 10 or more and were assigned to the rPPD
group, representing a higher risk for the development of
PPD. The remaining 59 participants were assigned to thenPPD group. Groups were tested for significant differences
regarding sociodemographic and birth characteristics.
Groups differed only in length of gestation. Participants in
the rPPD group had a significantly shorter length of gestation (M ¼ 39.02 weeks) compared with participants in the
nPPD group (M ¼ 39.73 weeks) (T (71) ¼ 2.049; Po0.05).
Therefore length of gestation was included as a potential
mediator in further analysis of the relationship between
OXT and PPD symptoms.

Data Analyses
All variables were checked for normal distribution, missing
data and outliers (defined as more than two standard
deviations below or above the mean) by the Kolmogorov–
Smirnof test and visual inspection. Outliers were checked
for validity and excluded if reasonable. If necessary,
variables were subjected to transformation by natural
logarithm before further analyses. Differences on demographic, biological and psychological characteristics between included and excluded study participants were tested
by t and w2 tests. Participants were divided into a risk-for
PPD group (rPPD) and a no-risk-for PPD group (nPPD),
according to the respective postpartum EPDS score. On thebasis of the proposals of Bergant et al. (1998) and Jardri
et al. (2006), the chosen cut-off score for being at risk for
PPD was 10 or more within the first 2 weeks postpartum.
T and w2 tests were computed between the groups, toidentify possible confounders among the demographicaland medical variables. Descriptive statistics of EPDS scoresand OXT values are reported. The postpartal EPDS scores ofnursing and not nursing mothers were compared using thet-test. The bivariate correlation was computed between the
pre- and postpartal EPDS score. The association between
OXT and PPD symptoms was tested by conducting a binary
logistic regression analysis with the group variable as
outcome variable and OXT concentration as the potential
predictor in the first run. In a second run the prepartal
EPDS score was added, to control for potential confounding
by previous depressive symptoms. Further analyses werecomputed including OXT concentration as the firstpredictor and other potential predictors, identified throughprevious group comparisons. Because of the expected,
unequal group sizes, every logistic regression analysis was
conducted with not more than two predictors, of which thefirst one was always OXT concentration. Because accurateclassification of participants is difficult when groups are not
evenly split, primary emphasis was placed on prediction
rather than classification of being at risk for PPD. Data were
Neuropsychopharmacology

Pre and Postpartal EPDS Scores
Postpartal EPDS scores did not differ between nursing andnot nursing mothers (T (69) ¼ 0.025; P ¼ 0.98). Prepartal
EPDS scores (Range 0–17) were significantly correlated with
postpartal EDPS scores (Range 0–22) (r ¼ 0.232; p ¼ 0.048).
Mean prepartal and postpartal total EPDS scores were
4.77 and 5.85 respectively.

Plasma OXT Concentrations
Plasma OXT concentrations had a range of 14.39–245.71 pg/ml
and mean OXT concentration for the overall sample was
80.81 pg/ml (SD ¼ 48.81 pg/ml). Three outliers with OXT
values above 200 pg/ml were identified. Information on thesethree subjects did not provide a clear reason for exclusion ofthese cases or any indication for invalidity of assessments.
Therefore, they were retained in the analyses. All further
analyses were conducted with the log-transformed OXT
concentrations to assure normal distribution. The bivariate
correlation between prepartal EPDS scores and OXT concentrations was not significant (r ¼ 0.086; p ¼ 0.467).

The Association between OXT Concentration in
Pregnancy and Postpartum PPD Symptoms
The test statistics of the logistic regression analyses, with
OXT predicting PPD symptoms are displayed in Table 2.
Plasma OXT level significantly predicted PPD symptoms(Exp (b) ¼ 0.290; po0.05). The coefficient of association
between OXT concentration and PPD was below one,indicating lower OXT levels in the rPPD group and higher
OXT levels in the nPPD group. The addition of the prepartal
EPDS score as a further covariate in a second analysis
did not improve the model fit (Dw2 (1) ¼ 0.302; P40.05).
According to the results of descriptive statistics, length ofgestation was tested as a potential mediator in a third
analysis. Length of gestation did not predict PPD symptoms

Oxytocin and postpartum depression
M Skrundz et al

1889

Table 1 Sample and Group Characteristics and Tests for Group Differences

Maternal age (years)

Total sample
M (SD)/%(N ¼ 73)

nPPD group
M (SD)/%(n ¼ 59)

rPPD group
M (SD)/%(n ¼ 14)

Test between nPPD
and rPPD
P-value

31.05 (4.70)

31.22 (4.69)

30.36 (4.88)

0.541a0.928bIncome category
Low

8.70

8.90

7.70

Average/high

73.90

73.20

76.90

Very high

17.40

17.90

15.40

22.31 (3.47)

22.10 (3.26)

23.32 (4.40)

Primiparae

74.0

71.20

85.70

Multiparae

26.0

28.80

14.30

39.6 (1.2)

39.7 (1.1)

39.1 (1.4)

23.3

23.70

21.40

Pre-pregnancy BMI

0.292aParityLength of gestation (weeks)

0.044aBirth mode
Cesarean section
Mother is nursing

90.0

89.7

92.3

3338.56 (378.44)

3345.93 (359.21)

3307.50 (465.02)

Female

46.6

50.8

28.6

Male

53.4

49.2

71.4

Infant birth weight (g)0.735aInfant sex

Monthly income categories low ¼ 0–3750 swiss franks, average/high ¼ 3750–11250 swiss franks, very high ¼ above 11250 swiss franks; nPPD ¼ no risk for postpartum
depression; rPPD ¼ at risk for postpartum depression; BMI ¼ body mass-index.
at-test.
b 2
w -testTable 2 Binary Logistic Regression Analysis Fort he Prediction of Being at Risk for Postpartal Depression
Model statistics

First analysis

Predictor statistics

v2 (df)

P

R2NK

2 LL

6.195 (1)

0.013

0.130

65.169Plasma oxytocin
Second analysis

6.497 (2)

0.039

0.137

Wald’s v2 (df)pExp(b)

95% CI for Exp(b)5.555 (1)

0.018

0.290

0.103–0.812

64.867

Plasma oxytocin

5.366 (1)

0.021

0.294

0.105–0.828

Prepartal EPDS score0.299 (1)

0.584

1.254

0.557–2.828

Plasma oxytocin

5.250 (1)

0.022

0.294

0.103–0.838

Length of gestation

3.447 (1)

0.063

0.931

0.864–1.004

Change of model fit compared with first analysis: Dw2 (1) ¼ 0.302; p ¼ 0.583
Third analysis

9.702 (2)

0.008

0.200

61.662

2

Change of model fit compared with first analysis: Dw (1) ¼ 3.507; p ¼ 0.061
R2NK ¼ Nagelkerke R2; 2 LL ¼ 2 log likelihood (deviance); EPDS ¼ Edinburgh Postnatal Depression Scale.

(Exp (b) ¼ 0.931; p40.05) and the model fit did not
improve either (Dw2 (1) ¼ 3.507; P40.05).
With OXT as predictor of PPD symptoms, 83.6% of thesample was classified correctly into the nPPD and rPPD
group. To visualize the difference in OXT values between
the groups, mean OXT concentrations are displayed in
Figure 2.

Repeating the analyses, excluding the three cases with
outlying OXT concentrations, did not change the results.

DISCUSSION
In line with our hypothesis, we could show that OXT during
pregnancy was negatively associated with a positive screen
Neuropsychopharmacology

Oxytocin and postpartum depression
M Skrundz et al

1890

Figure 2 Graph shows individual oxytocin concentrations in the twogroups and group means. Oxytocin values are shown on a logarithmic scale.

on the EPDS at greater than or equal to 10, indicating ahigher risk for the development of PPD. This suggests
an increased occurrence of depressive symptoms in thefirst 2 weeks after delivery in individuals with low plasma
OXT concentrations during pregnancy. The relationshippersisted after controlling for prepartal EPDS scores.
Our findings are in agreement with the only human study
addressing the link between plasma OXT during pregnancy
and postpartal maternal behavior. Plasma OXT concentrations during pregnancy were found to be positively
associated with a set of maternal bonding behaviors, suchas positive affect and gaze in interactions, as well as cognitive attachment representations towards the newborn in theearly postpartum period (Feldman et al, 2007). In women
suffering from PPD the same behaviors are impaired,accompanied by feelings of overload and difficulties inemotional attachment development towards their child(Beck, 2006; Martins and Gaffan, 2000). Correspondingly
studies with rodents report deficits in maternal behavior,such as less protective behavior and less pup-licking, andlonger latencies in postpartal onset of maternal behavior inanimals with decreased central OXT availability (Pedersen
et al, 2006; van Leengoed et al, 1987). Non-human primate
mothers show increased maternal affiliation towards offspring when central OXT is enhanced (Holman and Goy,
1995). The present findings are also in agreement withhuman studies reporting relationships between plasma
OXT, assessed in the 2nd and 6th month postpartum andaffectionate maternal behavior during mother–child interactions (Gordon et al, 2010). Again, mothers’ OXT concentrations were positively correlated with the behavioral
indicators of attachment, such as motherese vocalization,affectionate touch and positive affect. As anxiety and excessive preoccupation are other important symptoms of PPD,
Neuropsychopharmacology

our results also match reports of OXT acting as anxiolytic
and enhancing positive emotional affiliation in non-pregnant humans (Uvnas-Moberg, 1998). There is also evidence
for decreased plasma OXT concentrations in individuals
suffering from major depression or reporting increased
depressive symptoms (Frasch et al, 1995; Ozsoy et al, 2009;
Scantamburlo et al, 2007).
The herein observed prevalence of subjects above cutoff
resembles to those of other studies using the same screening
instrument. Here, we identified 19.18% of the sample having
an EPDS score of 10 or more. Other comparable studies
found a rate of 20% at 5 days postpartum (Bergant et al,1998) and 16% at 2 months postpartum (Yim et al, 2009).
Group comparisons revealed a significantly shorter
gestation among women within the rPPD group. In womenwith lower OXT availability in pregnancy, the oxytocinergic
inhibition of the HPA axis could be decreased. Decreased
HPA axis inhibition would enhance the exponential increaseof placental corticotropin-releasing factor that promotes theonset of labor (Smith, 1998). However, the length ofgestation variable did not reach significance in the following
prediction of PPD symptoms. It remains to be elucidated
whether length of gestation has a mediating role in therelationship between OXT and PPD in samples includingpremature deliveries.
The range of OXT concentrations found in the present
sample, is in line with those of previous studies (Dawood
et al, 1979; De Geest et al, 1985). One often-mentioned issue
concerning OXT assessment in human samples is that
central OXT release is not necessarily related to peripheral
OXT release, and therefore associations between centrally
regulated psychological variables and peripheral measured
OXT should be handled with caution (Jones et al, 1983;
Landgraf and Neumann, 2004). However, in animals, there
are also studies accounting for joint control mechanisms ofcentral and peripheral OXT release in context of fear-related
stress responses (Wotjak et al, 1998), and for autostimulatory effects at the level of the hypothalamus, in terms of
peripheral OXT release activation by centrally released OXT(McKenzie et al, 1995; Neumann et al, 1994). Given thecurrent evidence from animal studies and the difficulties inthe determination of central OXT release in humans, it
seems justifiable to revert to peripheral OXT assessment.
This is supported by several findings reporting relations
between peripheral OXT in humans and various psychological constructs, all representing aspects of humanaffiliation and attachment (Feldman et al, 2007; Lightet al, 2004; Tops et al, 2007; Wismer Fries et al, 2005).
The mechanisms behind the observed association between OXT and PPD symptoms remain to be elucidated.
Although we cannot rule out residual confounding by
unknown factors, the prospective design and the inclusionof pre-pregnancy EPDS scores as a covariate make a causal
relationship imaginable. There already exists evidence thatOXT concentrations are lower in mothers characterized bydepressive symptoms and negative affect during pregnancy,
when assessed postpartum (Light et al, 2004). Further, OXT
is known to reduce psychological and physiological stressresponses (Heinrichs et al, 2003) and to inhibit hyperactive
fear-responses of the amygdala (Labuschagne et al, 2010).
There is also evidence that the properties of endocrine
systems during pregnancy have programming functions forOxytocin and postpartum depression
M Skrundz et al1891

the postpartal period (Meinlschmidt et al, 2010; Pop et al,1993). In our study, an interplay between low OXT andeffects on amygdala reactivity and the HPA axis inpregnancy could indicate an increased reactivity to stressful
stimuli at that time and promote the development ofdepressive symptoms after birth, when mothers arechallenged by a bulk of potentially stressful new conditions.
Additionally, expectations of the social environment and thegrowing demands of the child may promote feelings of fear
and insecurity. Notably, a study comparing the symptomatology of postpartum and non-postpartum depression
found more anxious features among the investigated PPD
group (Hendrick et al, 2000). As we know from animalstudies, besides the general importance of OXT in theformation of social bonds in females (Insel, 1997), thepositive feedback mechanism of the oxytocinergic system is
supposed to provide long-lasting stimulation of maternal
behaviors after parturition (DaCosta et al, 1996). It may beless efficient, if OXT availability is diminished. Adopted tohuman mothers, this would be reflected by the difficulties
depressed mothers have in implementing maternal behaviors and forming a relationship with their child (Beck,
1995; Cooper and Murray, 1998). Considering the profoundphysiological challenge caused by endocrinological changes
over the course of gestation and the following abrupt shift
after parturition, it is not possible to form a biologicalmodel for PPD development, that accounts for all contributing factors yet. Future studies should try to experimentally modify OXT concentrations in mid-pregnancy, toverify, whether OXT during pregnancy contributes to thegeneration of depressive symptoms during the postpartum
period.
There are some limitations of the study. First, our findingneeds to be confirmed in future studies with more than one
OXT assessment over the course of pregnancy to clarify, if
the relationship is specific to OXT concentrations between
the 30th and 34th week of gestation. Studies assessing OXT
at different stages of gestation suggest individually different
patterns of OXT fluctuations over time, indicating that there
might be a functional difference between women with stable
OXT levels and those with rising ones (Dawood et al, 1979;
Levine et al, 2007). But high intra-individual stability ofvalues has also been reported (Feldman et al, 2007; Leakeet al, 1981; van der Post et al, 1997). From our point of view,
the present results refer to plasma OXT levels between the
30th and 34th week of gestation only, as we did not assess
potential alterations in peripheral OXT release over thecourse of gestation. Second, the sample consisted of womenwith mostly medium to high socioeconomic status. Consequently, results need to be replicated with more heterogenous samples. Third, PPD symptoms were assessed byquestionnaire (EPDS), which should be complemented infuture studies by structured or standardized interviews toverify the presence of a diagnosis of PPD. It should be notedthat as yet, estimations of the sensitivity and specificity of
the EPDS to detect PPD vary across studies, warranting
further attention of this issue (Eberhard-Gran et al, 2001;
Gaynes et al, 2005; Gibson et al, 2009). Nevertheless there
are validation studies reporting good sensitivity andspecificity values for the EPDS within comparable study
designs and according to DSM-III and ICD-10 criteria(Harris et al, 1989; Jardri et al, 2006). Important to note, ouruse of the EPDS within a period of 2 weeks postpartum does
not provide information on the diagnosis of PPD, which
requires the presence of symptoms for at least 2 weeks.
Moreover, heightened EPDS scores in this early postpartum
period may still be picking up the tail end of postpartum
blues, which itself is a risk factor for the development of
PPD. Finally, future studies should clarify, if the association
between prepartal OXT and depressive symptoms during
the postpartum period remains stable beyond the first 2
weeks up to several months postpartum, and if thisrelationship holds true for individuals with diagnosed
episodes of PPD, as not all women with increased depressive
symptoms after delivery develop a full-blown affective
disorder.
In summary, our findings suggest that OXT is involved in
the etiology of depressive symptoms during the postpartum
period, and need to be further elaborated in studies
assessing neuroendocrinological aspects of PPD. If replicated, the presented results will have important clinicalrelevance. Prepartal identification of subjects at risk for
PPD could allow for early preventive interventions andminimize adverse effects for the physiological and psychological wellbeing of mother and child.

ACKNOWLEDGEMENTS
This work is part of the National Centre of Competence in
Research (NCCR) Swiss Etiological Study of Adjustment
and Mental Health (sesam). The Swiss National Science
Foundation (SNF) (project no. 51A240-104890), the University of Basel, the Hoffmann-La Roche Corp. and the Basel
Scientific Society provided core support for the NCCR
sesam. We are grateful to the Max Planck Institute of
Psychiatry, Munich, Germany for the biochemical analyses.
Further, we thank Andrea H Meyer, PhD, for his statisticalsupport.

DISCLOSURE
The authors declare no conflict of interest.

REFERENCES
Beck CT (1995). The effects of postpartum depression on maternalinfant interaction: A meta-analysis. Nurs Res 44: 298–304.
Beck CT (2006). Postpartum depression. Am J Nurs 106: 40–50.
Bergant AM, Nguyen T, Heim K, Ulmer H, Dapunt O (1998).
German version and validation of the Edinburgh postnatal
depression scale (EPDS)). Deutsche Medizinische Wochenschrift
123: 35–40.
Bloch M, Daly RC, Rubinow DR (2003). Endocrine factors in
the etiology of postpartum depression. Compr Psychiatry 44:
234–246.
Brummelte S, Galea LAM (2010). Depression during pregnancy
and postpartum: Contribution of stress and ovarian hormones.
Prog Neuro-Psychopharmacol Biol Psychiatry 34: 766–776.
Cooper PJ, Murray L (1998). Postnatal depression. Br Med J 316:
1884–1886.
DaCosta APC, GuevaraGuzman RG, Ohkura S, Goode JA, Kendrick
KM (1996). The role of oxytocin release in the paraventricular
nucleus in the control of maternal behaviour in the sheep.
J Neuroendocrinol 8: 163–177.
Neuropsychopharmacology

Oxytocin and postpartum depression
M Skrundz et al

1892
Dawood MY, Ylikorkala O, Trivedi D, Fuchs F (1979). Oxytocin
in maternal circulation and amniotic-fluid during pregnancy.
J Clin Endocrinol Metabol 49: 429–434.
De Geest K, Thiery M, Piron-Possuyt G, Vanden Driessche R(1985). Plasma oxytocin in human pregnancy and parturition.
J Perina Med 13: 3–13.
Eberhard-Gran M, Eskild A, Tambs K, Opjordsmoen S, Samuelsen SO(2001). Review of validation studies of the Edinburgh postnatal
depression scale. Acta Psychiatrica Scandinavica 104: 243–249.
Ehlert U, Patalla U, Kirschbaum C, Piedmont E, Hellhammer DH(1990). Postpartum blues: salivary cortisol and psychologicalfactors. J Psychosomat Res 34: 319–325.
Feldman R, Weller A, Zagoory-Sharon O, Levine A (2007).
Evidence for a neuroendocrinological foundation of humanaffiliation - Plasma oxytocin levels across pregnancy and the
postpartum period predict mother-infant bonding. Psychol Sci
18: 965–970.
Frasch A, Zetzsche T, Steiger A, Jirikowski GF (1995). Reduction ofplasma oxytocin levels in patients suffering from major
depression. In: Ivell R, Russell JA (eds). OxytocinFCellular
and Molecular Approaches in Medicine and Research. Plenum
Press Div Plenum Publishing Corp: New York. Vol 395,
pp 257–258.
Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G,
Swinson T (2005). Perinatal depressionFA systematic review ofprevalence and incidence. Obstetr Gynecol 106: 1071–1083.
Gaynes BN, Gavin N, Meltzer-Brody S, Lohr KN, Swinson T,
Gartlehner G et al (2005). Perinatal depression: prevalence,screening accuracy, and screening outcomes. Evid Rep Technol
Assess (Summ) 119: 1–8.
Gibson J, McKenzie-McHarg K, Shakespeare J, Price J, Gray R(2009). A systematic review of studies validating the Edinburgh
postnatal depression Scale in antepartum and postpartum
women. Acta Psychiatrica Scandinavica 119: 350–364.
Gimpl G, Fahrenholz F (2001). The Oxytocin receptor system:
Structure, function, and regulation. Physiol Rev 81: 629–683.
Gordon I, Zagoory-Sharon O, Leckman JF, Feldman R (2010).
Oxytocin and the development of parenting in humans. Biol
Psychiatry 68: 377–382.
Grace SL, Evindar A, Stewart DE (2003). The effect of postpartum
depression on child cognitive development and behavior: areview and critical analysis of the literature. Arch Womens Ment
Health 6: 263–274.
Green AD, Barr AM, Galea LAM (2009). Role of estradiol
withdrawal in ‘anhedonic’ sucrose consumption: A model of
postpartum depression. Physiol Behav 97: 259–265.
Harris B, Huckle P, Thomas R, Johns S, Fung H (1989). The use of
rating-scales to identify post-natal depression. Br J Psychiatry
154: 813–817.
Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003).
Social support and oxytocin interact to suppress cortisol andsubjective responses to psychosocial stress. Biol Psychiatry 54:
1389–1398.
Heinrichs M, Domes G (2008). Neuropeptides and social
behaviour: effects of oxytocin and vasopressin in humans. Adv
Vasopressin Oxytocin: from Genes to Behav to Disease 170:
337–350.
Hendrick V, Altshuler L, Strouse T, Grosser S (2000). Postpartumand nonpostpartum depression: Differences in presentation andresponse to pharmacologic treatment. Depress Anxiety 11: 66–72.
Higuchi T, Kaba H (1997). Neuromodulatory role of oxytocin in
the control of maternal behavior. In: Maeda K-I, Tsukamura H,
Yokoyama A (eds). Neural control of reproduction: Physiology
and behavior. S. Karger AG: New York. pp 237–248.
Holman SD, Goy RW (1995). Experiential and hormonal correlatesof care-giving in rhesus macaques. In: Pryce CR, Martin RD,
Skuse D (eds). Motherhood in Human and Nonhuman Primates.
Karger: Basel. pp 87–93.
Neuropsychopharmacology

Insel TR (1997). A neurobiological basis of social attachment.
Am J Psychiatry 154: 726–735.
Jardri R, Pelta J, Maron M, Thomas P, Delion P, Codaccioni X et al(2006). Predictive validation study of the Edinburgh postnatal
depression scale in the first week after delivery and risk analysis
for postnatal depression. J Affect Disord 93: 169–176.
Jones PM, Robinson I, Harris MC (1983). Release of oxytocin intoblood and cerebrospinal-fluid by electrical-stimulation of the
hypothalamus or neural lobe in the rat. Neuroendocrinology
37: 454–458.
Labuschagne I, Phan KL, Wood A, Angstadt M, Chua P, Heinrichs
M et al (2010). Oxytocin attenuates amygdala reactivity to fear ingeneralized social anxiety disorder. Neuropsychopharmacology
35: 2403–2413.
Landgraf R, Kubota M, Holsboer F, Wotjak CT (1995). Release ofvasopressin and oxytocin within the brain and into blood:
Microdialysis and antisense targeting. Neurohypophysis 1098:
243–256.
Landgraf R, Neumann ID (2004). Vasopressin and oxytocin release
within the brain: a dynamic concept of multiple and variable
modes of neuropeptide communication. Front Neuroendocrinol
25: 150–176.
Leake RD, Weitzman RE, Glatz TH, Fisher DA (1981). Plasma
oxytocin concentrations in men, non-pregnant women, andpregnant-women before and during spontaneous labor. J Clin
Endocrinol Metabol 53: 730–733.
Levine A, Zagoory-Sharon O, Feldman R, Weller A (2007).
Oxytocin during pregnancy and early postpartum: Individual
patterns and maternal-fetal attachment. Peptides 28: 1162–1169.
Light KC, Grewen KM, Amico JA, Boccia M, Brownley KA,
Johns JM (2004). Deficits in plasma oxytocin responses andincreased negative affect, stress, and blood pressure inmothers with cocaine exposure during pregnancy. Addict Behav
29: 1541–1564.
Martins C, Gaffan EA (2000). Effects of early maternal depression
on patterns of infant-mother attachment: A meta-analytic
investigation. J Child Psychol Psychiatry 41: 737–746.
McKenzie DN, Leng G, Dyball REJ (1995). Electrophysiologicalevidence for mutual excitation of oxytocin cells in the supraoptic nucleus of the rat hypothalamus. J Physiol London 485:
485–492.
Meinlschmidt G, Martin C, Neumann ID, Heinrichs M (2010).
Maternal cortisol in late pregnancy and hypothalamic-pituitaryadrenal reactivity to psychosocial stress postpartum in women.
Stress-the Int J Biol Stress 13: 163–171.
Murray L, Kempton C, Woolgar M, Hooper R (1993). Depressed
Mothers Speech to Their Infants and Its Relation to Infant
Gender and Cognitive-Development. J Child Psychol Psychiatry
34: 1083–1101.
Nelson EE, Panksepp J (1998). Brain substrates of infant-motherattachment: Contributions of opioids, oxytocin, and norepinephrine. Neurosci Biobehav Rev 22: 437–452.
Neumann I, Koehler E, Landgraf R, Summylong J (1994).
An Oxytocin receptor antagonist infused into the supraoptic
nucleus attenuates intranuclear and peripheral release ofoxytocin during suckling in conscious rats. Endocrinology 134:
141–148.
O’Hara MW, Swain AM (1996). Rates and risk of postpartum
depressionFA meta-analysis. Int Rev Psychiatry 8: 37–54.
Olazabal DE, Young LJ (2005). Oxytocin receptors in the nucleus
accumbens facilitate ‘spontaneous’ maternal behavior in female
prairie voles. Hormones Behav 48: 177.
Ozsoy S, Esel E, Kula M (2009). Serum oxytocin levels in patientswith depression and the effects of gender and antidepressanttreatment. Psychiatry Res 169: 249–252.
Pedersen CA, Vadlamudi SV, Boccia ML, Amico JA (2006).
Maternal behavior deficits in nulliparous oxytocin knockout
mice. Genes Brain Behav 5: 274–281.

Oxytocin and postpartum depression
M Skrundz et al1893
Pop VJM, Derooy HAM, Vader HL, Vanderheide D, Vanson MM,
Komproe IH (1993). Microsomal antibodies during gestation in
relation to postpartum thyroid-dysfunction and depression. Acta
Endocrinologica 129: 26–30.
Robertson E, Grace S, Wallington T, Stewart DE (2004). Antenatal
risk factors for postpartum depression: a synthesis of recent
literature. Gen Hosp Psychiatry 26: 289–295.
Russell JA, Leng G, Douglas AJ (2003). The magnocellular oxytocinsystem, the fount of maternity: adaptations in pregnancy. Front
Neuroendocrinol 24: 27–61.
Sala NL, Althabe O (1968). The milk ejecting effect induced byoxytocin during human lactation. Acta Physiol Lat Am 18: 96–103.
Scantamburlo G, Hansenne M, Fuchs S, Pitchot W, Marechal P,
Pequeux C et al (2007). Plasma oxytocin levels and anxiety inpatients with major depression. Psychoneuroendocrinology 32:
407–410.
Smith R (1998). Alterations in the hypothalamic pituitary adrenal
axis during pregnancy and the placental clock that determines
the length of parturition. J Reprod Immunol 39: 215–220.
Stein A, Arteche A, Lehtonen A, Craske M, Harvey A, Counsell N
et al (2010). Interpretation of infant facial expression in thecontext of maternal postnatal depression. Infant Behav Dev 33:
273–278.
Tops M, Van Peer JM, Korf J, Wijers AA, Tucker DM (2007).
Anxiety, cortisol, and attachment predict plasma oxytocin.
Psychophysiology 44: 444–449.
Uvnas-Moberg K (1998). Oxytocin may mediate the benefits ofpositive social interaction and emotions. Psychoneuroendocrinology 23: 819–835.
van der Post JAM, van Buul BJA, Hart AAM, van Heerikhuize JJ,
Pesman G, Legros JJ et al (1997). Vasopressin and oxytocinlevels during normal pregnancy: Effects of chronic dietarysodium restriction. J Endocrinol 152: 345–354.
van Leengoed E, Kerker E, Swanson HH (1987). Inhibition of
postpartum maternal-behavior in the rat by injecting an
oxytocin antagonist into the cerebral-ventricles. J Endocrinol
112: 275–282.
Wismer Fries AB, Ziegler TE, Kurian JR, Jacoris S, Pollak SD(2005). Early experience in humans is associated with changes inneuropeptides critical for regulating social behavior. Proc Natl
Acad Sci USA 102: 17237–17240.
Wisner KL, Stowe ZN (1997). Psychobiology of postpartum mooddisorders. Sem Reprod Endocrinol 15: 77–89.
Wittchen H-U, Lachner G, Wunderlich U, Pfister H (1998). Testrestes reliability of the computerized DSM-IV version of theMunich Composite International Diagnostic Interview (M-CIDI).
Soc Psychiatry Psychiatric Epidemiol 33: 568–578.
Wittchen HU, Pfister H (1997). Instruktionsmanual zur Durchführung von DIA-X-Interview). Swets Test Services: Frankfurt.
World Health Organization (1990). Composite International
Diagnostic Interview (CIDI): a) CIDI-interview (version 1.0), b)
CIDI-user manual, c) CIDI-training manual, d) CIDI-computer
programs. World Health Organization: Geneva.
Wotjak CT, Ganster J, Kohl G, Holsboer F, Landgraf R, Engelmann
M (1998). Dissociated central and peripheral release ofvasopressin, but not oxytocin, in response to repeated swim
stress: New insights into the secretory capacities of peptidergic
neurons. Neuroscience 85: 1209–1222.
Yim IS, Glynn LM, Schetter CD, Hobel CJ, Chicz-DeMet A,
Sandman CA (2009). Risk of postpartum depressive symptoms
with elevated corticotropin-releasing hormone in human pregnancy. Arch Gen Psychiatry 66: 162–169.

Neuropsychopharmacology