Fetal and Infant Response to SRI Treatment

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. The F.I.R.S.T. is studying the clinical course of newborns' symptoms directly after birth and for the infants' first 30 days after birth. Fetal neurobehavior measures are obtained by ultrasound and fetal heart rate evaluation at 28-30 and 32-34 weeks gestational age. After delivery, we observe the infants motor patterns, reflexes, behavior, sleep, and attention. Primary Investigator: 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 studies 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.

Preschool Neurobehavior and Prenatal Antidepressant Exposure

Over 400,000 pregnant women and their fetuses experience Major Depressive Disorder (MDD) every year in the United States.   Serotonin/Norepinephrine Reuptake Inhibitors (SRIs) are the most commonly chosen antidepressant medications for MDD during pregnancy.  The original prenatal project focused on prenatal and postnatal development of infants whose mothers had MDD during pregnancy, with and without SRI treatment, compared to non-depressed mothers.  Our early findings suggest that prenatal MDD and SRI exposure are both associated with alterations in sensory-motor development in the fetal period and early infancy. We are now following these children and their families through the preschool years. We hypothesize that the early motor effects of prenatal SRI exposure are related to alterations in fetal serotonin development and that these effects will diminish in exposed children by preschool age.  By comparison, effects attributed to maternal MDD will be longer-lasting.  We 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.