Emotion processing and regulatory deficits have been well established in individuals diagnosed with bipolar disorder (BD). Both structural and functional neural deficits have been associated with the presence of psychiatric symptoms in BD. In Chapter 2, we reviewed cortical thickness deficits found in patients with BD. It is unclear however, how early these deficits appear; whether they contribute to risk, or whether these deficits develop as a consequence of the onset of symptoms. To address this, many researchers have turned to high-risk offspring populations. These high-risk offspring are at much greater risk of developing BD by virtue of having a parent diagnosed with BD. Moreover, the presence of anxiety, depression or ADHD related symptoms in this population suggest these children are at even greater risk to develop BD. By comparing high-risk offspring with and without the symptoms can help to elicudate neural correlates associated with risk and resilience for BD. It was the aim of this thesis research to investigate the behavioural, structural and functional correlates of risk. Specifically, presented in this thesis, we compared the gray matter integrity, through volume (Chapter 3) and cortical thickness (Chapter 4) techniques, in symptomatic and asymptomatic high-risk offspring to healthy children of healthy parents. We also compared the ability of these offspring to perform an emotion-labelling task (Chapter 5) and engage in emotional conflict monitoring and conflict adaptation during an fMRI scan (Chapter 6). Altogether, our results provide evidence for the presence of gray matter volume, emotion labelling, and conflict monitoring and conflict adaptation functional deficits in high-risk offspring compared to healthy children of healthy parents. With the exception of cortical thickness, we found that the deficits between symptomatic and asymptomatic high-risk offspring were comparable. This suggests that behavioural, structural and functional deficits may reflect neural correlates of risk and are not associated with the presence of symptoms. / Thesis / Doctor of Philosophy (PhD)

Purpose: This thesis investigated whether perceived parental care and overprotection predicted accuracy of face emotion recognition in psychiatrically healthy youth. The study also examined whether child gender and having a parent with a history of anxiety moderated the relationship between parental bonding and facial emotion recognition, and whether behavioural inhibition mediated this relationship. Methods: The sample comprised 176 males and females aged 7-18 years. Participants completed the Parental Bonding Instrument, Childhood Self-Report of Inhibition, and the Ekman emotion recognition task. Results: Child gender and parental history of anxiety moderated the relationship between perceived parenting style and affect recognition. In boys, overprotection by father predicted deficits in recognizing fearful faces; in children with parental anxiety, low paternal care predicted deficits in recognizing angry faces; and in boys with parental anxiety, negative maternal bonding predicted deficits in recognizing expressions of surprise. Also, maternal overprotection predicted intensity of subjective anxiety while viewing expressions of surprise and happiness for all offspring, and behaviour inhibition mediated these relationships. Implications: The present study provides preliminary evidence that parental bonding interacts with risk group and gender in predicting accuracy of facial affect recognition in healthy youth. Further research is needed to confirm these findings and determine whether the interaction between gender, risk group and deficits in social cognition increase risk for developing pathological anxiety.

The objective of this thesis was to determine the association between exposure to parental BD during childhood and risk of mood disorder. Offspring of one parent with BD completed annual clinical assessments as part of a 16-year prospective cohort study. Clinical data in the parents from Ottawa and Halifax were mapped onto the first decade of their offspring’s life to estimate the timing, duration and severity of exposure to their illness. The duration of parental BD was associated with a 2 to 2.5 fold increased risk of any psychopathology (HR: 1.9, 95%CI: 1.0-4.0), and unipolar depression (HR: 2.6, 95%CI: 0.9-7.5), and a 7 fold increased risk of substance use disorders (HR: 7.1, 95%CI: 1.8-37.0). A longer duration of exposure to parental BD may be an important indicator of mood and non-mood psychopathology risk in offspring. This has implications for early intervention and preventive efforts in high-risk youth.

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.