Fetal and Neonatal Neurobehavior and Prenatal Antidepressant Exposure: Outcomes Through Early Childhood

Approximately 600,000 infants born each year are exposed to maternal depression. At least 30% of those infants will also be exposed to psychotropic medication. Fetal exposure during pregnancy to maternal depression and the medications to treat the disorder have been associated with neurobehavioral differences in infants. It has been suggested that these differences are transient and it is not known if they are related to the mother's depression or the medication used to treat the depression. This study has been following a group of children their families from the time before birth through age 7 to examine the effects of prenatal antidepressant exposure and untreated maternal depression on sleep, neurobiological rhythms, and socio-emotional development with the goals of identifying guidelines for the treatment of depression during pregnancy and biomarkers for developmental psychopathology. We are in the final year of this project and are currently examining the role of maternal MDD and prenatal SRI exposure on child sensory-motor integration, gross and fine motor control (kinematics), temperament, behavioral and emotional development, and sleep state with circadian biomarkers (urinary melatonin sulfate levels) related to psychiatric symptoms. We are also identifying potential epigenetic markers associated with these effects. The rationale for the proposed research is that once we know how early SRI exposure affects these key areas related to serotonin function, we will be able to identify specific mechanistic pathways, including epigenetic targets and biomarkers, for psychopathology. The expected outcomes will have a positive impact because they will lead to informed risk-benefit decision-making for pregnant women with MDD and provide new preventive and therapeutic targets for psychopathology in children. This will further translate into enormous reductions in overall costs due to the social and functional disability that may result from such conditions. Primary Investigators: Amy Salisbury PhD. 

Of Mice and Methylation

Psychotropic drugs (SRIs) are often used to treat maternal depression during depression. These drugs can affect the infant and perhaps have negative long-term consequences.  Translational research is often used to study mechanisms that cannot be studied in humans. In this study we are developing a mouse model of prenatal SSRI exposure to compare with human infant data to study epigenetic mechanisms that may be responsible for the effects of these drugs on newborn neurobehavior. Primary Investigators: Kevin Bath PhD, Barry Lester PhD.

Walking Reduces Stress in Pregnant Women with Depression

Depressive symptoms are prevalent among pregnant women and consistently linked with adverse outcomes for both women and infants.  Few interventions have been developed to reduce prenatal depressive symptoms.  Because pregnant women are often reluctant to take antidepressants, a pressing need exists to evaluate interventions that are efficacious in reducing symptoms and more acceptable and accessible to pregnant women.  The American College of Obstetricians and Gynecologists strongly recommends regular physical activity throughout pregnancy, yet, in practice, many pregnant women are unsure of how to safely adhere to this recommendation.  Findings from our research indicate that a tailored, supported physical activity intervention would be acceptable to depressed pregnant women and would be preferable over pharmacotherapy.  No study to date, however, has evaluated physical activity as an intervention for depressed pregnant women. Our team recently developed a gentle, 10-week, pedometer-based walking intervention designed for pregnant women, the Prenatal Walking Program (PWP), including detailed intervention manuals, interventionist training programs, and adherence scales. The current study is a RCT to evaluate PWP in comparison with a perinatal-focused Health Education Control (HEC) condition. The primary aim is to examine whether the PWP group has greater reductions in depressive symptoms relative to healthy controls. In addition, infant neurobehavioral exams (NNNS) will evaluate possible benefits from the intervention.  Potential mechanisms will also be tested, including behavioral factors (behavioral activation, decreased avoidance), psychological factors (increased self-efficacy), and physiological factors (decreased inflammation, improved sleep).  Primary Investigators: Cynthia Battle PhD, Amy Salisbury PhD.