Rates of depression rise sharply during adolescence, becoming a leading cause of lifetime disability with high rates of recurrence and chronic impairment. Despite progress in efficacious treatments, only 50% of treated adolescents attain sustained remission. Recent insights from developmental affective neuroscience suggest that there may be windows of brain plasticity during adolescence when certain skills for effectively managing affect (emotions and motivations) may best be acquired. To this end, the candidate's long term career objective is to develop more effective treatments for affective disorders among youth by utilizing a developmental affective neuroscience framework to guide this effort. The candidate's immediate focus is to target positive affective functioning among adolescents with depression, and to investigate growing evidence that adolescence may be an opportune maturational period for intervention. Normative remodeling of key neural substrates of positive affect and reward systems at puberty plays a role in the development of depression during adolescence. These changes may signal a relatively sensitive period (surrounding pubertal maturation) when practicing key skills for managing positive affect may have an enduring impact on brain-behavior mechanisms of depression. The current Mentored Patient Oriented Career Development Award will uniquely position the candidate to advance this agenda. Her background includes specialized training in child clinical psychology, treatment development for adolescent depression, psychosocial approaches to affective functioning, basic multivariate statistics, and a broad exposure to the basics of developmental affective neuroscience. To most effectively bridge developmental affective neuroscience with treatment innovation she seeks to deepen and extend her training to include: 1) a more intricate understanding of brain-behavior theories of positive affective functioning, particularly as they relate to the development of depression, 2) advanced statistics and methods for examining brain-behavior mechanisms in the context of pediatric treatment trials, and 3) strategies for treatment development that translate these brain-behavior theories and methods to clinical practice. The University of Pittsburgh is an outstanding environment in which to engage in the interdisciplinary training required to achieve these training goals. The candidate's mentors-David Brent, Ronald Dahl and Greg Siegle-have combined expertise in adolescent depression and treatment development, neuro-developmental pathways to affective disorders, and multi-method approaches to measuring brain-behavior mechanisms of treatment response. In addition to their individual productivity and strong mentoring histories, this team of investigators has collaborated on large-scale, interdisciplinary projects to advance the scientific understanding and treatment of affective disorders among youth. The proposed project draws on this training and expertise to develop a treatment module (6 sessions) for improving features of positive affective functioning among adolescents with depression. The Positive Affect Stimulation and Sustainment [PASS] module teaches strategies for sustaining positive affective states, with the goal of strengthening key neural circuitry during this period of developmental plasticity. Relative deficits in features of positive affective functioning are central to the development and clinical course of depression;yet, few treatments target these deficits. Behavioral activation increases exposure and reinforcement related to pleasant events, but emerging evidence suggests that affective states quickly fade for depressed individuals following positive experiences. As such, PASS may augment behavioral activation by extending affective experiences. The candidate's prior research supports the feasibility of PASS, as well as changes in subjective positive emotion and depressive symptoms. The current study proposes to extend this work with a randomized controlled trial (RCT) in which adolescents with depression (n=60;ages 12-17) will be randomized to PASS or Cognitive Therapy (a comparison treatment that does not target positive affective functioning) for 6 weeks. Participants will complete self report and behavioral assessments of targeted mechanisms and symptoms, and 34 participants will complete neuroimaging tasks designed to elicit positive affect and activate underlying neural circuitry (e.g. fronto-mesolimbic circuits). The primary goals of the current trial include: 1) establish feasibility and acceptability of PASS, 2) employ a multi-method approach to measure PASS related change in targeted mechanisms, and 3) explore PASS-related changes in sustainability and connectivity in key circuits within the fronto-mesolimbic network. All of these goals will inform iterative refinements of the manual, and will generate more specific hypotheses and methods for a future, large-scale RCT. Based on the results of this work, future trials may, e.g., include an augmentation design to determine if PASS adds value above and beyond behavioral activation, and may test hypotheses regarding opportune developmental windows (e.g. early vs. mid puberty) for the treatment approach.

Public Health Relevance

Rates of depression rise sharply during adolescence, becoming a leading cause of lifetime disability with high rates of recurrence and chronic impairment. Despite progress in efficacious treatments, only 50% of treated adolescents attain sustained remission. By developing novel approaches for intervening during key periods of development and brain maturation, the proposed research and training carries potential not only to alleviate immediate symptoms, but also to reduce mortality, and alter morbidity and well being across the lifetime.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Interventions Committee for Disorders Involving Children and Their Families (ITVC)
Program Officer
Sarampote, Christopher S
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University of Pittsburgh
Schools of Medicine
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Ricketts, Emily J; Price, Rebecca B; Siegle, Greg J et al. (2018) Vigilant attention to threat, sleep patterns, and anxiety in peripubertal youth. J Child Psychol Psychiatry 59:1309-1322
McMakin, Dana L; Ricketts, Emily J; Forbes, Erika E et al. (2018) Anxiety Treatment and Targeted Sleep Enhancement to Address Sleep Disturbance in Pre/Early Adolescents with Anxiety. J Clin Child Adolesc Psychol :1-14
Wallace, Meredith L; McMakin, Dana L; Tan, Patricia Z et al. (2017) The role of day-to-day emotions, sleep, and social interactions in pediatric anxiety treatment. Behav Res Ther 90:87-95
McMakin, Dana L; Dahl, Ronald E; Buysse, Daniel J et al. (2016) The impact of experimental sleep restriction on affective functioning in social and nonsocial contexts among adolescents. J Child Psychol Psychiatry 57:1027-37
Olino, Thomas M; McMakin, Dana L; Nicely, Terri A et al. (2016) Maternal Depression, Parenting, and Youth Depressive Symptoms: Mediation and Moderation in a Short-Term Longitudinal Study. J Clin Child Adolesc Psychol 45:279-90
McMakin, Dana L; Alfano, Candice A (2015) Sleep and anxiety in late childhood and early adolescence. Curr Opin Psychiatry 28:483-9
Brent, David A; McMakin, Dana L; Kennard, Betsy D et al. (2013) Protecting adolescents from self-harm: a critical review of intervention studies. J Am Acad Child Adolesc Psychiatry 52:1260-71
Rofey, Dana L; McMakin, Dana L; Shaw, Daniel et al. (2013) Self-regulation of sleep, emotion, and weight during adolescence: implications for translational research and practice. Clin Transl Sci 6:238-43
McMakin, Dana L; Olino, Thomas M; Porta, Giovanna et al. (2012) Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression. J Am Acad Child Adolesc Psychiatry 51:404-11
McMakin, Dana L; Siegle, Greg J; Shirk, Stephen R (2011) Positive Affect Stimulation and Sustainment (PASS) Module for Depressed Mood: A preliminary investigation of treatment-related effects. Cognit Ther Res 35:217-226

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