Specific aims:

Oxytocin plays an essential role in maternal behavior, social bonding, prosocial behaviors, establishment of trust, anxiety reduction, and the modulation of stress. This research is significant in determining the impact of exposures and experiences on oxytocin pathways. Our approach is twofold in seeking to determine the impact of oxytocin on social development trajectory and outcomes. We will examine both exogenous oxytocin administered at birth and effects of exposure and experiences on exogenous oxytocin. Thus there are three factors that are to be studied in oxytocin pathways: exogenous administration, genetic polymorphisms, and epigenetic effects. Finally, our research is significant in examining interactive effects of maternal behavior on the child and the child's behavior on the mother.

1. To determine prosocial and atypical social developmental trajectories and outcomes from infancy through adolescence in the ALSPAC birth cohort and to correlate these findings with indices of OT pathways. We hypothesize that these outcomes will be moderated by (a) exogenous administration of synthetic oxytocin (syntocinon) at birth and dose response, (b) polymorphisms in genes for OT and the OT receptor, genetic and epigenetic regulation of OT receptor expression during development, related perinatal variables, and (c) epigenetic modification of genes in this pathway during development.

2. To empirically derive developmental trajectories from infancy to childhood and adolescence and correlate these trajectories to OT pathways related to:

a. prosocial behavior

b. autistic traits

c. social anxiety

d. social communication deficits

e. anti-social and disruptive behaviors

3. To determine the impact of the following perinatal experiences on social developmental trajectory and outcomes:

a. dosage of synthetic OT (syntocinon/pitocin)

b. caesarian section

c. maternal illness (diabetes, eclampsia) and alcohol and substance use/abuse

d. type of anesthesia or analgesia (e.g. opiates, and "caine" drugs) or other medications administered during the birth process

e. physiologic stress on the mother (e.g. hypertension) and emotional stress (anxiety, depression) in the parents

f. physiologic stress in the newborn e.g. fetal monitoring measures and Apgar score

g. breast feeding (incidence and duration)

h. maternal diet (omega fatty acids)

i. demographic variables ( e.g. parental age, family history of disorder, SES.)

j. post natal experiences (family adversity index, abuse, etc)

4. To examine polymorphisms and unique genetic variants in genes in the OT/vasopressin pathways (peptides, receptors and other factors regulating the release or functions of these peptides) on differences in social behaviors and developmental trajectories listed in Specific Aim 2. Because polymorphisms in the OT receptor are associated with social behaviors we hypothesize that those polymorphisms may modulate human behavior to have a direct effect on developmental trajectories in the ALSPAC cohort.

5. To examine the effects of exogenously administered synthetic OT and its dose response, along with the perinatal variables listed in Specific Aim 3, on the epigenetic expression of genes in the OT pathway on developmental trajectories in Specific Aim 2. We hypothesize that the regulation of the OT receptor (e.g. methylations in the CpG island) may affect social developmental trajectories and that early exposure to synthetic OT will have dose-dependent and long-lasting consequences for gene expression for the OT receptor.