Lauren B. Alloy - US grants

This competing continuation is part of a 2-site collaborative research grant with an identical application submitted concurrently by Dr. Lyn Y. Abramson at the University of Wisconsin. Prior research did not provide an adequate test of the hopelessness theory (HT) and Beck's theory (BT) of depression and may have been misleading about those cognitive theories' validity. Thus, the overarching goal of this project is to provide a more powerful test of HT's and BT's predictions about the etiology of depression and a validation of the Hopelessness Depression subtype. To this end, a large scale, 5.5-year prospective study was conducted at both sites. Initially nondepressed, non-psychopathological Ss (n=349) who were at either high or low cognitive risk for depression were followed prospectively with independent and blind self-report and interview assessments of stressful life events, cognitions, social support, coping, and psychiatric status/symptoms in order to predict onsets and subsequent recurrences of depression. Familial and developmental origins of cognitive vulnerability to depression were also examined, including assessment of the parents(n=335) of high-risk and low-risk Ss. In this renewal, differential predictors of first onsets vs. recurrences of depression, factors that increase resilience among high-risk Ss and promote depression among low-risk Ss, factors that mediate and moderate change in cognitive vulnerability, and different models of cognitive vulnerability-stress relations are also investigated. This project contributes to: 1) the scientific understanding of the etiology and course of a subset of the mood disorders; 2) a more valid nosology of the depressive disorders; 3) an understanding of the origins and continuity/change of cognitive vulnerability to depression; 4) an understanding of factors that promote resilience to depression; and 5) the development of interventions for treating and preventing depression.

In evaluating research to test the hopelessness theory and Beck's theory of depression, we have arrived at a very disturbing conclusion: the various research strategies used to test these theories do not provide an adequate test of their basic postulates and may produce results that mislead investigators about their validities. In our view, the problems associated with past research strategies result, in part, from investigators' failure to appreciate the full methodological implications of the kinds of causal relations specified in the cognitive theories and, as a corollary, the heterogeneity that may exist among the depressive disorders. Indeed, researchers have not appreciated that these cognitive theories actually hypothesize the existence in nature of an, as yet, unidentified subtype of depression - "negative cognition depression." Thus, the overarching goal of this collaborative grant is to provide a more powerful test of the hopelessness theory's and Beck's theory's predictions regarding the etiology and subsequent course of negative cognition depression and a validation of this subtype of depression. To this end, we plan to conduct a large scale, two-year prospective study designed to test the etiological hypotheses of the cognitive theories of depression. In the Vulnerability Study, 420 currently nondepressed, non- psychopathological individuals who are at either high, medium or low risk for depression based on their cognitive styles will be followed prospectively for 2 years, on a monthly basis, with independent and blind self-report and interview assessments of stressful life events, cognitions and psychiatric status/symptomatology in order to predict onsets and subsequent relapses/recurrences of depression. These studies will contribute to the scientific understanding of the etiology of a subset of the affective disorders, to more valid nosology of the depressive disorders and to the development of interventions for treating and preventing the negative cognition subtype of depression.

DESCRIPTION (Applicant's abstract): This revised application is part of a site collaborative research grant (R10) with an identical (except for budget/personnel) application submitted concurrently by Dr. Lyn Y. Abramson of University of Wisconsin at Madison under the same title. Although much important biological research has been conducted on Bipolar disorder, little methodologically rigorous or theory guided work has examined psychosocial factors in the onset and course of this disorder. Moreover, although individuals exhibiting Cyclothymia, a subsyndromal form of Bipolar disorder, are at high risk for developing full blown syndromal Bipolar I or II disorder, little is known about: 1) the predictors of which cyclothymic individuals eventually do develop syndromal Bipolar disorder and which do not; or 2) the mechanisms involved in the development of syndromal Bipolar disorders among cyclothymics. Thus, the overarching goal of this proposal is to provide a theoretically consistent and methodologically rigorous examination of life events, cognitive processes, and personality factors in the course of Cyclothymia and initial onset and course of full blown syndromal Bipolar disorder among Cyclothymics. The application of the cognitive diathesis-stress theories (Beck's Theory and the Hopelessness Theory), which have been so useful for unipolar depression, will be examined for Cyclothymia and Bipolar disorder. To this end, a large scale, 3-year prospective study designed to examine life events, cognition, and personality factors in the course of Cyclothymia and initial onset and course of Bipolar I or II disorder will be conducted. Three hundred Cyclothymics with not lifetime history of major depressive or full syndromal manic episodes and 300 demographically-matched normal controls with not lifetime history or any psychopathology will be followed prospectively with independent and blind self-report and interview assessments (every 16 weeks) of life events, cognition, and psychiatric status/symptoms in order to predict onset, course, and subsequent relapses/recurrences of syndromal and subsyndromal depression and mania. This study will contribute to: 1) knowledge about psychosocial factors in the course of Cyclothymia and initial onset and subsequent course of full blown Bipolar disorder; 2) elucidation of the relationship between unipolar and bipolar depression; 3) development of interventions for treating and preventing bipolar disorder.

[unreadable] DESCRIPTION (provided by applicant): This application is part of a two-site collaborative renewal grant with an identical (except for budget/personnel) application submitted concurrently by Dr. Lyn Y. Abramson (University of Wisconsin) under the same title. Although important biological work has been conducted on Bipolar (Bi) disorder, less work has examined psychosocial factors in the onset, course, and progression of this disorder. Thus, in this proposal, theories implicating the Behavioral Approach System (BAS) in Bi Spectrum disorders are integrated with work on - psychosocial factors these conditions to provide a theoretically consistent and methodologically rigorous biopsychosocial framework to guide a prospective study of the course and progression of Bi disturbance. In the current grant, a unique sample of 206 Ss initially exhibiting milder Bi disturbance (Cyclothymia [Cyc] and Bi II), many of whom now are progressing to a more severe course, and 214 demographically-matched Normal controls (Nors) with no lifetime history of any psychopathology has been assembled and followed prospectively for an average of 21 months with independent and blind self-report and interview assessments (every 16 weeks) of life events, cognition, and psychiatric status/symptoms. At the outset of the proposed continued follow-up of this sample, laboratory assessments of BAS profiles, both in the resting state and in response to BAS-relevant cues, using psychophysiological (EEG assessments of left frontal cortical activity), behavioral (task persistence vs. helplessness), and subjective affect (euphoria, anger/irritability, depression) indices will be conducted to test the hypothesis that Bi Ss exhibit dysregulated BAS activity compared to Nor Ss. Moreover, life events, with a focus on those that are BAS-relevant, laboratory BAS profile, and cognitive vulnerability will be examined in the prediction of Hypomania/Mania and Depression symptoms and episodes among Bi and Nor Ss in the continued 3-year prospective follow-up. Finally, these same factors will be examined to predict general worsening of course and progression to Bi II and Bi I status among the Bi Ss.

[unreadable] DESCRIPTION (provided by applicant): This application is part of a 2-site collaborative revised grant with an identical (except for budget/personnel) application submitted concurrently by Dr. Lauren B. Alloy (Temple University). Despite the great public health significance of bipolar disorder (BD), it has been understudied, especially from an integrative biopsychosocial perspective. This application 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) Hypersensitivity Theory of BD, research designs to date are inadequate to determine whether "BAS hypersensitivity" indeed provides vulnerability to BD. Thus, the overarching goal of this application is to use a biobehavioral high-risk design to test whether BAS hypersensitivity, either alone or in combination with BAS-relevant life events, provides vulnerability to first onset of BD during a critical "age of risk." To this end, a large-scale prospective, longitudinal study of 400 (both sites) 15-19 year old individuals (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, will be conducted. At Time 1, we will 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' mothers will also be assessed on BAS (and BIS) sensitivity, as well as their own and the Ps' fathers' history of psychopathology and family history of psychopathology. Ps will be followed prospectively every 6 months with assessments of BAS-relevant life events, cognitions, and social support, and the development of first onsets and recurrences of BD episodes, symptoms, and/or course and progression of their BD. Yearly, we will assess the cyclicity of Ps' BAS locomotor activity and their social/circadian rhythms with 2 weeks of actigraphy. 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. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): This application is part of a two-site collaborative renewal grant with an identical (except for budget/personnel) application submitted concurrently by Dr. Lyn Y. Abramson (University of Wisconsin) under the same title. Although important biological work has been conducted on Bipolar (Bi) disorder, less work has examined psychosocial factors in the onset, course, and progression of this disorder. Thus, in this proposal, theories implicating the Behavioral Approach System (BAS) in Bi Spectrum disorders are integrated with work on - psychosocial factors these conditions to provide a theoretically consistent and methodologically rigorous biopsychosocial framework to guide a prospective study of the course and progression of Bi disturbance. In the current grant, a unique sample of 206 Ss initially exhibiting milder Bi disturbance (Cyclothymia [Cyc] and Bi II), many of whom now are progressing to a more severe course, and 214 demographically-matched Normal controls (Nors) with no lifetime history of any psychopathology has been assembled and followed prospectively for an average of 21 months with independent and blind self-report and interview assessments (every 16 weeks) of life events, cognition, and psychiatric status/symptoms. At the outset of the proposed continued follow-up of this sample, laboratory assessments of BAS profiles, both in the resting state and in response to BAS-relevant cues, using psychophysiological (EEG assessments of left frontal cortical activity), behavioral (task persistence vs. helplessness), and subjective affect (euphoria, anger/irritability, depression) indices will be conducted to test the hypothesis that Bi Ss exhibit dysregulated BAS activity compared to Nor Ss. Moreover, life events, with a focus on those that are BAS-relevant, laboratory BAS profile, and cognitive vulnerability will be examined in the prediction of Hypomania/Mania and Depression symptoms and episodes among Bi and Nor Ss in the continued 3-year prospective follow-up. Finally, these same factors will be examined to predict general worsening of course and progression to Bi II and Bi I status among the Bi Ss.

DESCRIPTION (provided by applicant): Why does depression surge so dramatically in adolescence, especially for females? Despite the great scientific and public health significance of this question, the mechanisms underlying the surge in depression and emergence of gender differences in depression during adolescence remain elusive. This application is relevant to NIMH's mission to understand the causes of depression in youth, role of minority and gender status in depression, and targets for early intervention. The aims of this application are to examine the generality to African-Americans of this surge in depression and emergence of gender differences as well as to examine the mechanisms underlying these developmental phenomena from the perspective of an innovative genetic-cognitive vulnerability X transactional stress model, embedded within a normative adolescent brain and cognitive development context. To this end, a large-scale prospective, longitudinal study of 600 12-year old community youth (evenly divided between males and females and Caucasians and African-Americans) and their parents will be conducted. Assessments of children's cognitive and genetic (serotonin transporter gene polymorphism;Year 2 only) vulnerability, normative cognitive development, racial identity, and psychiatric diagnoses will be conducted at Time 1 and yearly thereafter. Assessments of psychiatric symptoms, negative life events, hopelessness, emotional abuse and peer victimization, perceived discrimination, body image, and pubertal status will occur every 6 months. In addition, assessments of parental psychopathology and parental cognitive vulnerability will be obtained from Ps'mothers at Time 1. Finally, information about parenting styles and parental inferential feedback will be obtained from Ps'mothers at Time 1 and yearly. Results will have very significant implications for prevention of depression. Knowledge of mechanisms underlying the adolescent surge in depression would suggest interventions for short-circuiting it and the great impairment it portends for young adulthood. Specifically, results will suggest optimal features of preventive interventions for depression in youth regarding: identification of youth to target, timing, psychological or biological processes to target, and interventions for girls vs. boys and African-Americans vs. Caucasians. PUBLIC HEALTH RELEVANCE: This application is unique in that it will provide a major prospective study of the generality across ethnic groups of the adolescent surge in depression and emergence of gender differences and test mechanisms underlying these two developmental phenomena from the perspective of an integrated cognitive vulnerability-stress/genetic vulnerability- stress model. In addition, developmental trajectories of executive functions relevant to the genesis of cognitive vulnerability to depression, informed by knowledge of normative adolescent brain and cognitive development, will be examined. By isolating the risk factors and mechanisms underlying the development of depression in adolescence, the project's findings will have significant implications for the prevention of depression, particularly in the area of optimal timing and targeting (i.e., high cognitive and/or genetic risk) of interventions that could be tailored appropriately to address gender and ethnic differences.

DESCRIPTION (provided by applicant): Why does depression surge so dramatically in adolescence, especially for females? Despite the great scientific and public health significance of this question, the mechanisms underlying the surge in depression and emergence of gender differences in depression during adolescence remain elusive. This application is relevant to NIMH's mission to understand the causes of depression in youth, role of minority and gender status in depression, and targets for early intervention. The aims of this application are to examine the generality to African-Americans of this surge in depression and emergence of gender differences as well as to examine the mechanisms underlying these developmental phenomena from the perspective of an innovative genetic-cognitive vulnerability X transactional stress model, embedded within a normative adolescent brain and cognitive development context. To this end, a large-scale prospective, longitudinal study of 600 12-year old community youth (evenly divided between males and females and Caucasians and African-Americans) and their parents will be conducted. Assessments of children's cognitive and genetic (serotonin transporter gene polymorphism; Year 2 only) vulnerability, normative cognitive development, racial identity, and psychiatric diagnoses will be conducted at Time 1 and yearly thereafter. Assessments of psychiatric symptoms, negative life events, hopelessness, emotional abuse and peer victimization, perceived discrimination, body image, and pubertal status will occur every 6 months. In addition, assessments of parental psychopathology and parental cognitive vulnerability will be obtained from Ps' mothers at Time 1. Finally, information about parenting styles and parental inferential feedback will be obtained from Ps' mothers at Time 1 and yearly. Results will have very significant implications for prevention of depression. Knowledge of mechanisms underlying the adolescent surge in depression would suggest interventions for short-circuiting it and the great impairment it portends for young adulthood. Specifically, results will suggest optimal features of preventive interventions for depression in youth regarding: identification of youth to target, timing, psychological or biological processes to target, and interventions for girls vs. boys and African-Americans vs. Caucasians. PUBLIC HEALTH RELEVANCE: This application is unique in that it will provide a major prospective study of the generality across ethnic groups of the adolescent surge in depression and emergence of gender differences and test mechanisms underlying these two developmental phenomena from the perspective of an integrated cognitive vulnerability-stress/genetic vulnerability- stress model. In addition, developmental trajectories of executive functions relevant to the genesis of cognitive vulnerability to depression, informed by knowledge of normative adolescent brain and cognitive development, will be examined. By isolating the risk factors and mechanisms underlying the development of depression in adolescence, the project's findings will have significant implications for the prevention of depression, particularly in the area of optimal timing and targeting (i.e., high cognitive and/or genetic risk) of interventions that could be tailored appropriately to address gender and ethnic differences.

DESCRIPTION (provided by applicant): Rates of depressive symptoms and diagnoses rise markedly between ages 15-18. Despite the scientific and public health significance, the mechanisms responsible for the adolescent surge in depression are not fully understood. Cognitive vulnerability - stress models have contributed importantly to our understanding of the increased incidence of depression in adolescence; however, these models do not adequately explain some of the somatic symptoms or incorporate biological stress mechanisms through which cognitive vulnerability evokes depression. A separate exciting body of research on immune correlates of depression has highlighted the role of proinflammatory pathways; yet, only some depressed individuals exhibit inflammation. This project provides a novel and compelling integration of the cognitive vulnerability - stress framework and the proinflammatory model of depression as applied to adolescence. The research has the potential to solve puzzles and limitations faced by both models when considered separately. The findings may help to account for the full spectrum of depressive symptoms and identify cognitively vulnerable individuals as especially likely to evince signs of cytokine dysregulation and increased reactivity to stressful events. Moreover, it is known that early childhood adversity contributes to both the development of cognitive vulnerability and a proinflammatory bias. The primary goal is to determine the role of inflammatory states in combination with cognitive vulnerabilities, stress, and childhood adversity as contributors that underlie the rise in adolescent depression. A multiwave, 4-year prospective study will be conducted with an existing, well-characterized community sample of 300 adolescents, including similar numbers of males and females and Caucasians and African-Americans, just reaching the critical age when the dramatic rise in depression begins. We will conduct yearly blood draws to assess proinflammatory and regulatory cytokines (a multicytokine array of 7 cytokines) and C-reactive protein (CRP), in parallel with ongoing assessments of life stress and depression and anxiety symptoms every 6 months. Cognitive vulnerabilities and depression and anxiety diagnoses will be obtained yearly, along with a history of childhood adversity in this unique cohort of urban adolescents. We also will examine interleukin-6 (IL- 6) reactivity to an acute stressor (Trier Social Stress Test) to determine how individual variation in cognitive reactivity translates into increased IL-6 release. This project fills a crucial knowledge gap about normal development of immunity in adolescence and its role in the dramatic rise in adolescent depression. It may lead to novel interventions for depression that target cognitive influences on cytokine responses to stress, as well as pharmacological manipulations of cytokines to address symptoms such as fatigue, anhedonia, and withdrawal.

DESCRIPTION (provided by applicant): 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 proposal 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 will continue 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 will conduct a new and novel neuroimaging study. We will compare 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 will examine 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.

DESCRIPTION (provided by applicant): 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 proposal. 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 will 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 4-wk ecological momentary assessment (EMA) study including 1-wk baseline, 2-wk high BAS/reward activation, and 1-wk 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 3 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.

7. Project Summary/Abstract Adolescence is an ?age of risk? for the emergence of first onset of bipolar spectrum disorders (BSD). Despite their prevalence and public health significance, major unanswered questions exist regarding the mechanisms involved in vulnerability to BSDs. BSDs are associated with hypersensitivity to reward and elevated reward- related brain function. However, research has not yet tested whether chronically high reward responsivity (RR) or increases in RR development during adolescence, beyond baseline RR, predicts first onset of BSD. A separate literature documents circadian rhythm disruption in BSDs, and social rhythm disruption (SRD) can trigger BSD episodes. Yet, research has not tested whether baseline circadian dysregulation, chronic social and circadian rhythm disruptions, or increases in these rhythm disruptions during adolescence predict onset of BSD. Further, circadian and reward approaches to BSDs mostly have proceeded in parallel. However, we and others have proposed integrated reward-circadian models of BSDs based on evidence the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. This proposal is the first systematic test of a novel, integrated reward-circadian model for first onset of BSD. We will use an innovative biobehavioral high-risk design to examine bidirectional relationships between multiple indices and domains (monetary, social) of RR and multiple indices of social and circadian rhythms and their joint prediction of first onset of BSD and increases in bipolar symptoms. Three hundred twenty 14-16 year old participants (Ps) will complete a prospective 3-year longitudinal study. Ps with no prior BSD will be selected along the entire dimension of self-reported RR, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, Ps will complete assessments of reward-relevant and SRD life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, Ps also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social RR, and a 7-day EMA period. During each EMA period, Ps will complete continuous measures of sleep/wake and activity (actigraphy) and 3 within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and SRD, monetary and social reward responsivity, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan and DLMO procedure will occur on the day before the start of each EMA period, excluding weekends. This proposal is an innovative integration of research on reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate reward and social/circadian rhythm interventions to treat, and ideally prevent, BSD.