Current Projects: Bipolar Disorder
BAS and Bipolar Disorder: Prospective Biobehavioral High Risk Design
Despite the great public health significance of bipolar disorder (BD), it has been understudied, especially from an integrative biopsychosocial perspective. This project is relevant to NIMH’s mission to understand the causes of BD and targets for prevention. Although current work underscores the strong promise of the Behavioral Approach System (BAS)/reward system hypersensitivity theory of BD, research designs to date are inadequate to determine whether “BAS/reward hypersensitivity” indeed provides vulnerability to BD. Thus, the overarching goal of this project is to use a biobehavioral high-risk design to test whether BAS/reward hypersensitivity, either alone or in combination with BAS/reward-relevant life events, provides vulnerability to 1st onset of BD during a critical “age of risk.”
To this end, a large-scale prospective, longitudinal study of 400 14-19 year old adolescents (including males and females and Caucasian and minority Ps), selected to be at high vs. low risk for BD based on high BAS (n = 200) vs. moderate BAS (n = 200) sensitivity, but with no prior history of BD, is being conducted. At Time 1, we comprehensively assess these Ps’ BAS (and BIS) sensitivity vulnerability profiles (with EEG, behavioral task, cognitive style, and self-report), as well as their impulsivity, social/circadian rhythms, lifetime and family history of psychopathology, and current symptoms/impairment. Ps’ family history of psychopathology is also assessed. Ps are followed prospectively every 6 months with assessments of BAS/reward-relevant life events, cognitions, and the development of 1st onsets and recurrences of BD episodes, symptoms, and/or course and progression of their BD.
Results will contribute to the development of assessments that may identify individuals with a bipolar endophenotype who are likely to develop BD before such dysfunction occurs and, thus, who can most benefit from early preventive interventions. Finally, the project will contribute to development of BAS-targeted interventions for treatment and prevention of BD.
Risk for Bipolar Disorder: Reward-related Brain Function & Social Rhythms
Adolescence is a developmental period involving both heightened reward sensitivity and risk for bipolar spectrum disorders (BSDs). Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to BSDs.
Recent exciting research provides strong and consistent support for a Behavioral Approach System (BAS)/reward hypersensitivity theory of BSDs that shows great promise for elucidating and integrating the neurobiological, behavioral, and environmental mechanisms underlying risk along the bipolar spectrum. In addition, research on social and circadian rhythm models of BSDs is also very promising, but has proceeded independently of research on reward sensitivity. Yet, our recent work demonstrates influences of reward sensitivity on social rhythm disruption and mood symptoms, leading us to a novel integration of reward sensitivity and social rhythm dysregulation in this application. Thus, the overarching goal of this project is to use an innovative biobehavioral high-risk design in adolescents to examine two interrelated processes that may help explain the association between reward hypersensitivity and BSDs: 1) heightened activation of a “reward-related” neural network involving the ventral striatum and orbitofrontal cortex; and 2) influences of reward sensitivity/activation on social rhythm disruption.
We are continuing to follow High and Moderate BAS/reward sensitive adolescents as they further age into the period of risk for BSDs with self-report and behavioral measures of reward sensitivity/processing, BAS-relevant cognitive styles, social rhythms, BAS-relevant and social rhythm disruption life events, and mood symptoms/diagnoses. We also are conducting a new and novel neuroimaging study. We are comparing High BAS adolescents who have developed BSD (HBAS+BSD), High BAS adolescents who have not yet exhibited, but are at risk for, BSD (HBAS), and Moderate BAS adolescents without BSD (MBAS) on reward-related brain activity and connectivity in response to the anticipation and receipt of monetary rewards in an fMRI study. In addition, we are examining the influence of reward sensitivity/ activation and social rhythm dysregulation on mood symptoms in these same three groups of adolescents.
This research program is the first to examine neural trait markers and social rhythm dysregulation in adolescents at risk for BSDs based on a hypothesized psychobiological vulnerability. It will provide tools for the early identification of adolescents at risk for first onset and a worse course of BSD, inform our understanding of specific etiological pathways and biobehavioral mechanisms involved in illness onset, recurrence, and progression, and contribute to the development of early psychosocial, pharmacological, and neuroprotective strategies targeted at ameliorating reward processing abnormalities.
Social and Circadian Rhythms, Reward Sensitivity, and Risk for Bipolar Disorder
Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to bipolar spectrum disorders (BSDs).
Social and circadian (24-h) rhythm models of BSD risk hypothesize that mood episodes may be a result of circadian rhythm abnormalities caused by life events that disrupt social rhythms (e.g., bedtimes, mealtimes) that normally entrain circadian rhythms. Recent research also provides strong support for a Behavioral Approach System (BAS)/reward hypersensitivity theory of BSDs. Although research on these distinctive theoretical models has proceeded in parallel, our recent work demonstrates influences of reward sensitivity on social rhythm disruption and mood symptoms, leading us to a novel integration of reward sensitivity and social/circadian disruption in this project. Our overarching goal is to use an innovative biobehavioral high-risk design to examine bidirectional influences of reward sensitivity and social and circadian rhythm disruption as risk factors for BSD mood symptoms/ episodes.
We plan to prospectively follow 210 participants (Ps) drawn in part from an existing sample of High and Moderate BAS/reward sensitive Ps at an age of risk for BSDs. We will compare High BAS Ps with a BSD diagnosis, High BAS Ps who have not yet exhibited but are at risk for BSD, and Moderate BAS Ps with no BSD to determine whether reward hypersensitivity influences social and circadian rhythm disruption following the occurrence of reward-relevant events to predict manic and depressive symptoms/episodes. This 3-group design will allow us to test whether reward hypersensitivity and its relationship with social and circadian rhythm disruption are pre-existing vulnerabilities or consequences of BSD, or both. Social rhythm regularity and reward sensitivity will be assessed at baseline. Reward-relevant life events, social rhythm disruption from these events, and mood symptoms/episodes will be assessed prospectively for up to 4 years. Ps will complete a 20-day ecological momentary assessment (EMA) study including 5 day baseline, 10 day high BAS/reward activation, and 5 day reward-outcome periods to assess bidirectional influences between social and circadian rhythm disruption and reward sensitivity and their synergistic effects on BSD symptoms. In the EMA study, Ps will complete daily measures of life events, social rhythms, and sleep diaries, continuous measures of sleep/wake (actigraphy) and circadian rhythms (skin temperature), and repeated within-day measures of mood, symptoms, and reward motivation. Dim light melatonin onset will be assessed three times to determine circadian melatonin phase changes.
This research program will provide valuable insights into the mechanisms underlying vulnerability to BSDs and contribute to the development of targeted intervention and prevention strategies.