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Impact of Maternal Depression Across the First 6 Years of Life on the Child’s Mental Health, Social Engagement, and Empathy: The Moderating Role of Oxytocin
Yael Apter-Levy, M.A.; Michal Feldman, M.A.; Adam Vakart, M.A.; Richard P. Ebstein, Ph.D.; Ruth Feldman, Ph.D.
Am J Psychiatry 2013;170:1161-1168. doi:10.1176/appi.ajp.2013.12121597
View Author and Article Information

All authors report no financial relationships with commercial interests.

Supported by the Israel Science Foundation (grant 08-1310), the NARSAD Independent Investigator Award to Dr. Feldman, and the Katz Family Foundation.

From the Department of Psychology and Gonda Multidisciplinary Brain Center, Bar-Ilan University, Ramat-Gan, Israel; and the Department of Human Genetics, National University of Singapore.

Address correspondence to Dr. Feldman (feldman@mail.biu.ac.il).

Copyright © 2013 by the American Psychiatric Association

Received December 20, 2012; Revised February 25, 2013; Revised March 28, 2013; Accepted April 08, 2013.


Objective  Maternal depression across the postbirth period has long-term negative consequences for infant development. Little is known of the neurobiological underpinnings, but they could involve oxytocin, a neuropeptide that is dysfunctional in depression and is implicated in birth and parenting.

Method  The authors recruited a community cohort of women with high or low depression scores 2 days after childbirth and measured depression again at 6 and 9 months. When the child was 6, the authors evaluated the families of 46 chronically depressed mothers and 103 mothers reporting no depression since childbirth. The child was assessed for psychiatric diagnoses, social engagement, and empathy. Mother, father, and child were tested for salivary oxytocin level and variation in the rs2254298 single nucleotide polymorphism on the OXTR gene.

Results  Of the children of the chronically depressed mothers, 61% displayed axis I disorders, mainly anxiety and oppositional defiant disorder, compared with 15% of the children of nondepressed mothers. In the depressed mothers’ families, salivary oxytocin was lower in mothers, fathers, and children, and the children had lower empathy and social engagement levels. The rs2254298 GG homozygous genotype was overrepresented in depressed mothers and their families, and it correlated with lower salivary oxytocin. Presence of a single rs2254298 A allele (GA or AA genotype) in depressed mothers markedly decreased risk of child psychopathology.

Conclusions  The negative effect of chronic maternal depression on child social outcomes was related to genetic and peripheral biomarkers of the oxytocin system. This suggests a potential for oxytocin-based interventions.

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FIGURE 1. Identification of Chronic Depression in Mothers From Birth of Child to Age 6 Yearsa

a The mothers were recruited from maternity wards and had no contextual risk factors for depression. Those with Beck Depression Inventory scores in the highest and lowest quartiles were selected for the study. The mothers designated as chronically depressed when the child reached age 6 had scores above 11 on the Beck Depression Inventory at childbirth, 6 months, and 9 months and were diagnosed with major depression at 9 months and again at 6 years. Those who were considered never depressed had depression scores of 8 or lower at childbirth, 6 months, and 9 months and had no axis I disorders at 9 months and 6 years.

FIGURE 2. Psychiatric Diagnoses at Age 6 in Children of Chronically Depressed and Never-Depressed Mothersa

a Significant difference in overall rate of axis I diagnoses between children of depressed mothers (61%) and children of nondepressed mothers (15%) (χ2=32.85, df=1, p<0.001).

b Significant between-group difference (χ2=14.51, df=1, p<0.001).

c Significant between-group difference (χ2=7.97, df=1, p=0.006).

d Significant between-group difference (χ2=5.69, df=1, p=0.02).

FIGURE 3. Child Social Outcomes at Age 6 and Salivary Oxytocin Levels in Members of Families With Chronically Depressed or Never-Depressed Mothers

a Significant between-group difference (F=6.95, df=1, 146, p=0.01).

b Significant between-group difference (F=6.75, df=1, 146, p=0.02).

c Significant between-group differences in levels of mothers (F=4.83, df=1, 145, p=0.03), fathers (F=4.77, df=1, 145, p=0.04), and children (F=5.19, df=1, 145, p=0.03).

FIGURE 4. Relation of Axis I Disorders in 6-Year-Old Children of Chronically Depressed and Never-Depressed Mothers to Mother’s Genotype for the rs2254298 Variant of the OXTR Gene


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Among families of chronically depressed mothers, the oxytocin system may be dysfunctional in which of the following groups, as evidenced by lower peripheral oxytocin levels?
In cases of maternal depression across the first years of the child's life, the risk for the child to exhibit axis I psychopathology by school entry is:
Genetic risk in the oxytocin system to maternal depression and its cross-generational influence may be a result of which of the following?
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