The aim of this proposed Mentored Patient-Oriented Research Career Development (K23) Award is to provide the candidate with the training in affective neuroscience necessary to examine the functional neural mechanisms associated with individual differences in response to treatments for depression. Despite abundant empirical support demonstrating the efficacy of several different treatment modalities, no treatment works equally well for all patients. The goal of the proposed award is to utilize functional neuroimaging techniques to examine whether depressed patients who differ on specific facets of personality that are strongly associated with differential treatment response also differ in the functioning of specific automatic and voluntary components of the emotion regulation neural system. The long-term goal of this research is to identify reliable, biologically based markers of individual differences among depressed patients that could lead to the development of more effective, individually tailored treatments. The candidate possesses expertise in the identification of patient variables that are associated with differential response to treatments for depression. Through the proposed career development award, the candidate is seeking to build on this skill set by learning to examine the functional neural mechanisms that may underlie the predictors of differential treatment response that he and others have reported. He will acquire these skills by receiving training in three related areas of affective and translational neuroscience: 1) functiona neuroanatomy of emotion regulation and depression; 2) advanced neuroimaging techniques, and 3) the use of neuroimaging measures to inform clinical treatment research. In order to achieve these training goals, the candidate has proposed to participate in four types of training activities: weekly meetings and didactics with mentors, directed readings and training with expert consultants, formal coursework, and participation in scientific conferences. To ensure that the candidate meets his goal of becoming an independent scientist who can utilize the tools of affective neuroscience to answer important questions about the mechanisms underlying individual differences in treatment response, he has assembled an expert team of mentors and consultants. Each of these experts has a strong record of training junior scientists and fostering their development into successful independent investigators. The candidate's mentors, Drs. Mary Phillips and Ellen Frank, have extensive and complementary sets of expertise. Dr. Phillips is an expert in the functional neuroimaging of emotion regulation in the context of mood disorders, and Dr. Frank is expert in the assessment and treatment of depression. Together, their guidance will ensure that the candidate successfully meets his research and career development goals. The proposed research and training activities will take place in the Department of Psychiatry at the University of Pittsburgh School of Medicine. This is an ideal setting for the proposed project. The department has a longstanding track record of excellence in affective neuroscience, personality, and depression research. Senior faculty from each of these research domains are represented on the proposed mentorship and consultant team. The candidate will have access to extensive resources in each of these research areas throughout the proposed award period. The candidate's training will be further advanced by the proposed study, in which individual differences in the functioning of the automatic and voluntary emotion regulation neural systems will be examined among depressed adults who are high and low on facets of personality associated with differential treatment response. The study will examine functional neuroimaging measures of neural activity and connectivity within and between key prefrontal cortical and subcortical regions associated with emotion regulation. Neuroimaging, symptom, and personality data will be acquired in a sample of 60 currently depressed adults (30 with low scores on the personality facets of interest and 30 with high scores), as well as 30 psychiatrically healthy control participants.
The aims of the proposed project are to examine whether depressed patients who differ on the personality facets associated with differential treatment response also differ in the functioning of the automatic and voluntary emotion regulation neural systems. Abnormalities in the functioning of these neural systems will be assessed using tasks that target: 1) automatic emotion regulation during the processing of conflicting emotional information; 2) voluntary emotion regulation during the cognitive reappraisal of negative emotions; and 3) voluntary emotion regulation during the cognitive reappraisal of negative self-beliefs.
The specific aims of the proposed project match well with the strategic goals of the National Institute of Mental Health, and the results of this study can b expected to help identify reliable markers of individual difference among patients with depression. These findings could have enormous clinical utility and could lead to future work attempting to refine existing treatment strategies to make them more effective for patients with functional deficits in the emotion regulation system.

Public Health Relevance

The proposed work seeks to describe clinically meaningful individual differences in brain functioning among depressed patients. It is hoped that these results will help to clarify why some depressed patients respond to one treatment, whereas other patients respond to a different treatment. These findings could ultimately lead to the development of more effective, individually tailored treatments that can target the specific mechanisms involved in a particular patient's illness state.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Adult Psychopathology and Disorders of Aging Study Section (APDA)
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Chavez, Mark
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University of Pittsburgh
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Fournier, Jay C; Chase, Henry W; Greenberg, Tsafrir et al. (2017) Neuroticism and Individual Differences in Neural Function in Unmedicated Major Depression: Findings from the EMBARC Study. Biol Psychiatry Cogn Neurosci Neuroimaging 2:138-148
Jones, Neil P; Fournier, Jay C; Stone, Lindsey B (2017) Neural correlates of autobiographical problem-solving deficits associated with rumination in depression. J Affect Disord 218:210-216
Bertocci, M A; Bebko, G; Versace, A et al. (2016) Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth. Mol Psychiatry 21:1194-201
Jones, N P; Chase, H W; Fournier, J C (2016) Brain mechanisms of anxiety's effects on cognitive control in major depressive disorder. Psychol Med 46:2397-409
Fournier, Jay C; Chase, Henry W; Almeida, Jorge et al. (2016) Within- and Between-Session Changes in Neural Activity During Emotion Processing in Unipolar and Bipolar Depression. Biol Psychiatry Cogn Neurosci Neuroimaging 1:518-527
Chase, Henry W; Fournier, Jay C; Greenberg, Tsafrir et al. (2015) Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study. PLoS One 10:e0126326
Fournier, Jay C; DeRubeis, Robert J; Amsterdam, Jay et al. (2015) Gains in employment status following antidepressant medication or cognitive therapy for depression. Br J Psychiatry 206:332-8
Hafeman, Danella M; Bebko, Genna; Bertocci, Michele A et al. (2014) Abnormal deactivation of the inferior frontal gyrus during implicit emotion processing in youth with bipolar disorder: attenuated by medication. J Psychiatr Res 58:129-36
Derubeis, Robert J; Gelfand, Lois A; German, Ramaris E et al. (2014) Understanding processes of change: how some patients reveal more than others-and some groups of therapists less-about what matters in psychotherapy. Psychother Res 24:419-28
Fournier, Jay C; Chase, Henry W; Almeida, Jorge et al. (2014) Model specification and the reliability of fMRI results: implications for longitudinal neuroimaging studies in psychiatry. PLoS One 9:e105169

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