Genetic Regulation of Maternal Oxytocin Response and Its Influences on Maternal Behavior

We interrogated the genetic modulation of maternal oxytocin response and its association with maternal behavior using genetic risk scores within the oxytocin receptor (OXTR) gene. We identified a novel SNP, rs968389, to be significantly associated with maternal oxytocin response after a challenging mother-infant interaction task (Still Face Paradigm) and maternal separation anxiety from the infant. Performing a multiallelic analysis across OXTR by calculating a cumulative genetic risk score revealed a significant gene-by-environment (G × E) interaction, with OXTR genetic risk score interacting with adult separation anxiety to modulate levels of maternal sensitivity. Mothers with higher OXTR genetic risk score and adult separation anxiety showed significantly reduced levels of maternal sensitivity during free play with the infant. The same G × E interaction was also observed for the extended OXTR cumulative genetic risk score that included rs968389. Moreover, the extended cumulative OXTR genetic risk score itself was found to be significantly associated with maternal separation anxiety as it specifically relates to the infant. Our results suggest a complex montage of individual and synergistic genetic mediators of maternal behavior. These findings add to specific knowledge about genetic regulation of maternal oxytocin response in relation to maternal adjustment and infant bonding through the first few months of life.

[1]  T. Insel,et al.  The neurobiology of attachment , 2001, Nature Reviews Neuroscience.

[2]  C. Hopwood,et al.  Evocative gene–environment correlation in the mother–child relationship: A twin study of interpersonal processes , 2013, Development and Psychopathology.

[3]  Yanjie Su,et al.  The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy. , 2012, Journal of affective disorders.

[4]  Ilanit Gordon,et al.  Natural variations in maternal and paternal care are associated with systematic changes in oxytocin following parent–infant contact , 2010, Psychoneuroendocrinology.

[5]  E. Hock,et al.  Maternal separation anxiety: mother-infant separation from the maternal perspective , 1989 .

[6]  Kimberly Matheson,et al.  A paradoxical association of an oxytocin receptor gene polymorphism: early-life adversity and vulnerability to depression , 2013, Front. Neurosci..

[7]  R. Menon,et al.  Salivary oxytocin concentrations in response to running, sexual self-stimulation, breastfeeding and the TSST: The Regensburg Oxytocin Challenge (ROC) study , 2015, Psychoneuroendocrinology.

[8]  J. Leckman,et al.  Primary parental preoccupation: circuits, genes, and the crucial role of the environment , 2004, Journal of Neural Transmission.

[9]  N. Bolger,et al.  Social effects of oxytocin in humans: context and person matter , 2011, Trends in Cognitive Sciences.

[10]  U. Fischbacher,et al.  Oxytocin Shapes the Neural Circuitry of Trust and Trust Adaptation in Humans , 2008, Neuron.

[11]  R. Ebstein,et al.  Affiliation buffers stress: cumulative genetic risk in oxytocin–vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children , 2014, Translational Psychiatry.

[12]  Orna Zagoory-Sharon,et al.  Evidence for a Neuroendocrinological Foundation of Human Affiliation , 2007, Psychological science.

[13]  Raja Parasuraman,et al.  Oxytocin Receptor Genetic Variation Promotes Human Trust Behavior , 2012, Front. Hum. Neurosci..

[14]  Larry J. Young,et al.  Neuropeptidergic regulation of affiliative behavior and social bonding in animals , 2006, Hormones and Behavior.

[15]  E. Hock,et al.  Maternal separation anxiety: its developmental course and relation to maternal mental health. , 1992, Child development.

[16]  G. Kempermann Faculty Opinions recommendation of Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. , 2015 .

[17]  T. Brazelton,et al.  The infant's response to entrapment between contradictory messages in face-to-face interaction. , 1978, Journal of the American Academy of Child Psychiatry.

[18]  O. Koós,et al.  Maternal oxytocin response predicts mother-to-infant gaze , 2014, Brain Research.

[19]  Orna Zagoory-Sharon,et al.  The cross-generation transmission of oxytocin in humans , 2010, Hormones and Behavior.

[20]  A. Myers,et al.  Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress. , 2014, Journal of psychiatric research.

[21]  M. Dadds,et al.  Separation Anxiety, Attachment and Inter-Personal Representations: Disentangling the Role of Oxytocin in the Perinatal Period , 2014, PloS one.

[22]  Zuoxin Wang,et al.  Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles , 2003, Neuroscience.

[23]  Carol Carter Porges Neuroendocrine perspectives on social attachment and love , 1998 .

[24]  P. Fonagy,et al.  Adult attachment predicts maternal brain and oxytocin response to infant cues , 2009, Neuropsychopharmacology.

[25]  D. Silove,et al.  A self-report questionnaire for measuring separation anxiety in adulthood. , 2003, Comprehensive psychiatry.

[26]  P. Cooper,et al.  The impact of postnatal depression and associated adversity on early mother-infant interactions and later infant outcome. , 1996, Child development.

[27]  Jun S. Liu,et al.  The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans , 2015, Science.

[28]  J. Cohn,et al.  Mother infant face to face interaction influence is bidirectional and unrelated to periodic cycles in either partner's behavior , 1988 .

[29]  B. Bradley,et al.  Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms. , 2016, Child development.

[30]  Susan C. McDonough,et al.  Emotion Regulation in Context: Situational Effects on Infant and Caregiver Behavior , 2002 .

[31]  R. Landgraf,et al.  Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice , 2013, Psychoneuroendocrinology.

[32]  T. Price,et al.  Genotype-environment correlations: implications for determining the relationship between environmental exposures and psychiatric illness. , 2008, Psychiatry.

[33]  Philip B. Mitchell,et al.  Oxytocin Increases Gaze to the Eye Region of Human Faces , 2008, Biological Psychiatry.