0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

Articles   |    
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.

Abstract

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.

Abstract Teaser
Figures in this Article

Your Session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

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
+

References

Parsons  CE;  Young  KS;  Rochat  TJ;  Kringelbach  ML;  Stein  A:  Postnatal depression and its effects on child development: a review of evidence from low- and middle-income countries.  Br Med Bull 2012; 101:57–79
[CrossRef] | [PubMed]
 
Conroy  S;  Pariante  CM;  Marks  MN;  Davies  HA;  Farrelly  S;  Schacht  R;  Moran  P:  Maternal psychopathology and infant development at 18 months: the impact of maternal personality disorder and depression.  J Am Acad Child Adolesc Psychiatry 2012; 51:51–61
[CrossRef] | [PubMed]
 
Kingston  D;  Tough  S;  Whitfield  H:  Prenatal and postpartum maternal psychological distress and infant development: a systematic review.  Child Psychiatry Hum Dev 2012; 43:683–714
[CrossRef] | [PubMed]
 
Goodman  SH:  Depression in mothers.  Annu Rev Clin Psychol 2007; 3:107–135
[CrossRef] | [PubMed]
 
Zbozinek  TD;  Rose  RD;  Wolitzky-Taylor  KB;  Sherbourne  C;  Sullivan  G;  Stein  MB;  Roy-Byrne  PP;  Craske  MG:  Diagnostic overlap of generalized anxiety disorder and major depressive disorder in a primary care sample.  Depress Anxiety 2012; 29:1065–1071
[CrossRef] | [PubMed]
 
Feldman  R:  Oxytocin and social affiliation in humans.  Horm Behav 2012; 61:380–391
[CrossRef] | [PubMed]
 
Kappeler  L;  Meaney  MJ:  Epigenetics and parental effects.  Bioessays 2010; 32:818–827
[CrossRef] | [PubMed]
 
Champagne  FA:  Epigenetic mechanisms and the transgenerational effects of maternal care.  Front Neuroendocrinol 2008; 29:386–397
[CrossRef] | [PubMed]
 
Feldman  R;  Gordon  I;  Schneiderman  I;  Weisman  O;  Zagoory-Sharon  O:  Natural variations in maternal and paternal care are associated with systematic changes in oxytocin following parent-infant contact.  Psychoneuroendocrinology 2010; 35:1133–1141
[CrossRef] | [PubMed]
 
Feldman  R;  Gordon  I;  Zagoory-Sharon  O:  The cross-generation transmission of oxytocin in humans.  Horm Behav 2010; 58:669–676
[CrossRef] | [PubMed]
 
Weisman  O;  Zagoory-Sharon  O;  Feldman  R:  Oxytocin administration to parent enhances infant physiological and behavioral readiness for social engagement.  Biol Psychiatry 2012; 72:982–989
[CrossRef] | [PubMed]
 
Atzil  S;  Hendler  T;  Feldman  R:  Specifying the neurobiological basis of human attachment: brain, hormones, and behavior in synchronous and intrusive mothers.  Neuropsychopharmacology 2011; 36:2603–2615
[CrossRef] | [PubMed]
 
Bartz  JA;  Zaki  J;  Bolger  N;  Ochsner  KN:  Social effects of oxytocin in humans: context and person matter.  Trends Cogn Sci 2011; 15:301–309
[PubMed]
 
Frasch  A;  Zetzsche  T;  Steiger  A;  Jirikowski  GF:  Reduction of plasma oxytocin levels in patients suffering from major depression.  Adv Exp Med Biol 1995; 395:257–258
[PubMed]
 
Scantamburlo  G;  Hansenne  M;  Fuchs  S;  Pitchot  W;  Maréchal  P;  Pequeux  C;  Ansseau  M;  Legros  JJ:  Plasma oxytocin levels and anxiety in patients with major depression.  Psychoneuroendocrinology 2007; 32:407–410
[CrossRef] | [PubMed]
 
Gordon  I;  Zagoory-Sharon  O;  Schneiderman  I;  Leckman  JF;  Weller  A;  Feldman  R:  Oxytocin and cortisol in romantically unattached young adults: associations with bonding and psychological distress.  Psychophysiology 2008; 45:349–352
[CrossRef] | [PubMed]
 
Skrundz  M;  Bolten  M;  Nast  I;  Hellhammer  DH;  Meinlschmidt  G:  Plasma oxytocin concentration during pregnancy is associated with development of postpartum depression.  Neuropsychopharmacology 2011; 36:1886–1893
[CrossRef] | [PubMed]
 
Feldman  R:  Parent-infant synchrony and the construction of shared timing; physiological precursors, developmental outcomes, and risk conditions.  J Child Psychol Psychiatry 2007; 48:329–354
[CrossRef] | [PubMed]
 
Ebstein  RP;  Israel  S;  Chew  SH;  Zhong  S;  Knafo  A:  Genetics of human social behavior.  Neuron 2010; 65:831–844
[CrossRef] | [PubMed]
 
Brüne  M:  Does the oxytocin receptor (OXTR) polymorphism (rs2254298) confer ‘vulnerability’ for psychopathology or ‘differential susceptibility’? insights from evolution (opinion).  BMC Med 2012; 10:38
[CrossRef] | [PubMed]
 
Lerer  E;  Levi  S;  Salomon  S;  Darvasi  A;  Yirmiya  N;  Ebstein  RP:  Association between the oxytocin receptor (OXTR) gene and autism: relationship to Vineland Adaptive Behavior Scales and cognition.  Mol Psychiatry 2008; 13:980–988
[CrossRef] | [PubMed]
 
Costa  B;  Pini  S;  Gabelloni  P;  Abelli  M;  Lari  L;  Cardini  A;  Muti  M;  Gesi  C;  Landi  S;  Galderisi  S;  Mucci  A;  Lucacchini  A;  Cassano  GB;  Martini  C:  Oxytocin receptor polymorphisms and adult attachment style in patients with depression.  Psychoneuroendocrinology 2009; 34:1506–1514
[CrossRef] | [PubMed]
 
Chen  FS;  Barth  ME;  Johnson  SL;  Gotlib  IH;  Johnson  SC:  Oxytocin receptor (OXTR) polymorphisms and attachment in human infants.  Front Psychol 2011; 2:200
[PubMed]
 
Feldman  R;  Zagoory-Sharon  O;  Weisman  O;  Schneiderman  I;  Gordon  I;  Maoz  R;  Shalev  I;  Ebstein  RP:  Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 genes.  Biol Psychiatry 2012; 72:175–181
[CrossRef] | [PubMed]
 
Champagne  F;  Meaney  MJ:  Like mother, like daughter: evidence for non-genomic transmission of parental behavior and stress responsivity.  Prog Brain Res 2001; 133:287–302
[PubMed]
 
Beck  AT;  Steer  RA;  Brown  GK:  Beck Depression Inventory, 2nd ed, Manual.  San Antonio, Tex,  Psychological Corp, 1996
 
First  MB;  Spitzer  RL;  Gibbon  M;  Williams  JBW:  Structured Clinical Interview for DSM–IV Axis I Disorders — Clinician Version (SCID-CV) .  Washington, DC,  American Psychiatric Press, 1997
 
Goodman  R;  Ford  T;  Richards  H;  Gatward  R;  Meltzer  H:  The Development and Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology.  J Child Psychol Psychiatry 2000; 41:645–655
[CrossRef] | [PubMed]
 
Mansbach-Kleinfeld  I;  Apter  A;  Farbstein  I;  Levine  SZ;  Ponizovsky  AM:  A population-based psychometric validation study of the Strengths and Difficulties Questionnaire—Hebrew version.  Front Psychiatry 2010; 1:151
[CrossRef] | [PubMed]
 
Feldman  R:  Parenting behavior as the environment where children grow, in  The Cambridge Handbook of Environment in Human Development . Edited by Mayes  LC;  Lewis  M.  New York,  Cambridge University Press, 2012, pp 535–567
 
Hirosawa  T;  Kikuchi  M;  Higashida  H;  Okumura  E;  Ueno  S;  Shitamichi  K;  Yoshimura  Y;  Munesue  T;  Tsubokawa  T;  Haruta  Y;  Nakatani  H;  Hashimoto  T;  Minabe  Y:  Oxytocin attenuates feelings of hostility depending on emotional context and individuals’ characteristics.  Sci Rep 2012; 2:384
[CrossRef] | [PubMed]
 
Wermter  AK;  Laucht  M;  Schimmelmann  BG;  Banaschweski  T;  Sonuga-Barke  EJ;  Rietschel  M;  Becker  K:  From nature versus nurture, via nature and nurture, to gene x environment interaction in mental disorders.  Eur Child Adolesc Psychiatry 2010; 19:199–210
[CrossRef] | [PubMed]
 
Belsky  J;  Jonassaint  C;  Pluess  M;  Stanton  M;  Brummett  B;  Williams  R:  Vulnerability genes or plasticity genes? Mol Psychiatry 2009; 14:746–754
[CrossRef] | [PubMed]
 
Furman  DJ;  Chen  MC;  Gotlib  IH:  Variant in oxytocin receptor gene is associated with amygdala volume.  Psychoneuroendocrinology 2011; 36:891–897
[CrossRef] | [PubMed]
 
Bickart  KC;  Wright  CI;  Dautoff  RJ;  Dickerson  BC;  Barrett  LF:  Amygdala volume and social network size in humans.  Nat Neurosci 2011; 14:163–164
[CrossRef] | [PubMed]
 
Dunbar  RI:  The social brain meets neuroimaging.  Trends Cogn Sci 2012; 16:101–102
[CrossRef] | [PubMed]
 
Field  T;  Diego  M;  Hernandez-Reif  M:  Prenatal depression effects and interventions: a review.  Infant Behav Dev 2010; 33:409–418
[CrossRef] | [PubMed]
 
Meyer-Lindenberg  A;  Domes  G;  Kirsch  P;  Heinrichs  M:  Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine.  Nat Rev Neurosci 2011; 12:524–538
[CrossRef] | [PubMed]
 
Feldman  R;  Granat  A;  Pariente  C;  Kanety  H;  Kuint  J;  Gilboa-Schechtman  E:  Maternal depression and anxiety across the postpartum year and infant social engagement, fear regulation, and stress reactivity.  J Am Acad Child Adolesc Psychiatry 2009; 48:919–927
[CrossRef] | [PubMed]
 
Prenoveau  J;  Craske  M;  Counsell  N;  West  V;  Davies  B;  Cooper  P;  Rapa  E;  Stein  A:  Postpartum GAD is a risk factor for postpartum MDD: the course and longitudinal relationships of postpartum GAD and MDD.  Depress Anxiety ( Epub ahead of print, Jan 3, 2013 ) 
 
Martin  EI;  Ressler  KJ;  Binder  E;  Nemeroff  CB:  The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology.  Clin Lab Med 2010; 30:865–891
[CrossRef] | [PubMed]
 
References Container
+
+

Self-Assessment Quiz

Did you know? You can add a subscription now to earn CME Credits!

1.
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?
2.
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:
3.
Genetic risk in the oxytocin system to maternal depression and its cross-generational influence may be a result of which of the following?
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 1

Related Content
See Also...
Articles
Books
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 50.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 50.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 43.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 43.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 52.  >
Topic Collections
Psychiatric News
PubMed Articles