Offspring of parents with bipolar disorder (BD) are at high risk for psychiatric disorders, but mechanisms conferring risk are not well understood. Identifying and understanding factors that increase offspring vulnerability may inform intervention efforts. Three studies examined the following risk factors: (1) obstetric complications (OCs); (2) family functioning; and (3) clinical characteristics of parental BD. Investigations included cross-sectional data from two Massachusetts General Hospital studies of 109 BD parents and 206 offspring. Study 1 examined associations between: (1) maternal lifetime comorbid anxiety and OCs in pregnancy/delivery; (2) OCs and development of offspring psychopathology. Associations emerged between maternal anxiety and OCs. OCs, particularly during delivery, also correlated with offspring anxiety disorders. Path analyses revealed that delivery complications mediated the relationship between maternal and offspring anxiety. Study 2 examined associations between family functioning (cohesion, expressiveness, conflict) and offspring psychopathology, and explored moderation by offspring age and sex. Higher conflict and lower cohesion correlated with offspring internalizing and externalizing symptoms. Lower cohesion correlated with offspring mood disorders. Moderation analyses indicated that the link between cohesion and internalizing symptoms was stronger for younger compared to older children. Also, conflict and mood disorder were associated in younger boys, but not in older boys or in girls. Study 3 classified parents according to BD course presentation using latent class analysis, and examined associations between parental class membership and offspring psychopathology. The best-fitting model yielded three parent groups that were based on 8 illness characteristics. Some notable patterns differentiated classes: Class 1 and 2 parents had earlier illness onset, whereas Class 3 parents had later onset; Class 2 consisted of parents with Bipolar-II Disorder, whereas Class 1 parents had Bipolar-I Disorder. Class differences emerged for offspring anxiety disorders, but only among females. Class 3 parents had girls with fewer anxiety disorders compared to the other classes, with girls of Class 2 parents at greatest risk. Altogether, these studies identify several specific environmental mechanisms that increase psychopathology risk in offspring of BD parents. Such findings have important implications for targeted prevention and intervention.

abstract: The main objective of this study was to use a genetically-informative design to examine the putative influences of maternal perceived prenatal stress, obstetrical complications, and gestational age on infant dysregulation, competence, and developmental maturity. Specifically, whether or not prenatal and obstetrical environmental conditions modified the heritability of infant outcomes was examined. A total of 291 mothers were interviewed when their twin infants were 12 months of age. Pregnancy and twin birth medical records were obtained to code obstetrical data. Utilizing behavioral genetic models, results indicated maternal perceived prenatal stress moderated genetic and environmental influences on developmental maturity whereas obstetrical complications moderated shared environmental influences on infant competence and nonshared environmental influences on developmental maturity. Gestational age moderated the heritability and nonshared environment of infant dysregulation, shared and nonshared environmental influences on competence, and nonshared environmental influences on developmental maturity. Taken together, prenatal and obstetric conditions were important nonlinear influences on infant outcomes. An evolutionary perspective may provide a framework for these findings, such that the prenatal environment programs the fetus to be adaptive to current environmental contexts. Specifically, prenatal stress governs gene expression through epigenetic processes. Findings highlight the utility of a genetically informative design for elucidating the role of prenatal and obstetric conditions in the etiology of infant developmental outcomes. / Dissertation/Thesis / Ph.D. Psychology 2011