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Multi-PI (Blanchard & Schackman):  Using Multimodal Neuroimaging and Real-World Experience Sampling to Understand Negative Affect and Paranoid Ideation in Psychosis

NIMH 1R01MH121409-01A1.  Dates 06/01/2020 to 04/20/2025 ($3,701,474 total costs).

GRANT ABSTRACT:  Paranoid ideation—the mistaken belief that intentional harm is likely to occur—spans a continuum, from mild suspicion to persecutory delusions. Among individuals with schizophrenia and other psychosis disorders, elevated levels of paranoia are common, debilitating, and challenging to treat. The cues (public environments, strangers) and processes (anxiety) that promote paranoia have grown increasingly clear, but the brain bases of these pathways are unknown, thwarting the development of mechanistic models and, ultimately, the development of more effective or tolerable biological interventions. Leveraging our team’s unique multidisciplinary expertise and productive track record of NIH-sponsored research, this project will use an innovative combination of paranoia assessments, advanced neuroimaging techniques, and smartphone-based experience sampling to clarify the factors governing paranoia. We will enroll the full spectrum of paranoia without gaps or discontinuities—including psychosis patients with frank persecutory delusions and matched community controls. These data will allow us to rigorously examine the hypothesized contribution of brain circuits responsible for triggering anxiety and
evaluating the threat potential of everyday social cues, such as faces. Integrating neuroimaging measures with experience-sampling data will enable us to extend these insights to the real world—a key step to establishing therapeutic relevance—for the first time. It has become increasingly clear that categorical psychiatric diagnoses
(e.g. schizophrenia) present significant barriers to understanding pathophysiology. Our focus on dimensional measures of paranoia overcomes many of these barriers and dovetails with the National Institute of Mental Health’s Strategic Objectives and Research Domain Criteria (RDoC) initiative. This work would provide a potentially transformative opportunity to test and refine theory, deepen our understanding of etiology, guide the development of new translational models, discover new treatment targets, and provide an integrative biopsychosocial framework for unifying research across investigators, approaches, and scholarly guilds.

Principal Investigator:  Understanding Social Affiliative Deficits in Psychopathology.  NIMH 1R01MH110462.   Dates: 08/2016 to 05/2021 ($2,222,490 total costs).

GRANT ABSTRACT:  As defined by the Research Domain Criteria (RDoC) Social Processes Workshop, affiliation is the engagement in positive social interactions with others. The desire to affiliate has been described as a fundamental human motivation. However, impairments in the drive to affiliate occur across multiple clinical disorders and these affiliative impairments have devastating consequences for individuals, their family members, and society. Despite the major clinical significance of impairments in social affiliation, the factors that contribute to affiliative impairment are poorly understood. We propose a multi-method assessment of a large and diverse clinical sample to examine how social affiliative deficits are associated with a) the social regulation of neural systems relating to emotion as assessed through a novel fMRI paradigm for studying the in vivo social regulation of emotion in the context of affiliative relationships, b) neural processes associated with social reward, c) learning of the positive affective value of others, and d) behavioral affiliative skills. Consistent with the RDoC, this application will include assessment of affiliation processes across units of analyses including circuits, behavior, and self-report within a transdiagnostic sample of individuals with psychotic disorders.  With regard to the study of neural systems, a powerful mechanism that may underlie the motivation for social contact is the social regulation of emotion, particularly the social regulation of threat responding.  We propose the use of a novel paradigm to create affiliative relationships within the lab and subsequently will examine how this affiliative relationship regulates emotional responding to a stressor (a key function of affiliative relationships) within an fMRI scan.  Specifically, we will examine the hypothesis that affiliative deficits are associated with the failure of social contact to down regulate neural activity in the context of a stressor.  In addition to the benefits that affiliation provides when responding to threat, the motivation for social relationships may derive from activation of neural systems involved in reward.  We will also explore the contribution of reward circuits to affiliative impairment using both social and monetary reward paradigms.  Beyond neural responding, the proposed study will examine how individuals form behavior-based impressions of others in ways that may facilitate or impede social affiliation.  We will examine the hypothesis that deficits in affiliation are associated with impairments in the ability to use behavior-based person information to form positive impressions concerning the affective value of others in the social environment.  Finally, behavioral social skills form the basis for effective communication and are thought to be critical to social competence.  We will examine the hypothesis that impairments in social affiliation are specifically related to deficits in behavioral affiliative skills. The proposed study will provide an integrative perspective to advance our understanding of the neural and behavioral factors that give rise to impairments in social affiliation within clinical populations and this research will provide insights that will inform the development of interventions to address such impairments in affiliation.

Co-Investigator:  Improving Negative Symptoms and Community Engagement in Veterans with Schizophrenia (PI: Bennett).  Veteran Administration RR&D 1I01RX001293-01A2), 06/01/15 – 05/31/20.  

GRANT ABSTRACT:  Negative symptoms are a central and enduring feature of schizophrenia and are related to pervasive deficits in residential independence, occupational functioning, and quality of life for veterans living with this illness. Currently there is no effective treatment for this critical domain of the illness.  This application is focused evaluating a tailored intervention package targeting negative symptoms in Veterans with schizophrenia who receive mental health services at 3 VAMCs. EnCoRE will include motivational, cognitive, and behavioral skills training strategies aimed at teaching individuals ways to (1) understand and overcome deficits in anticipatory pleasure, (2) increase intrinsic motivation for pleasant and goal directed activities, (3) reduce negative expectancies for success and performance, and (4) perform skillfully in new social situations. The primary objectives of this project are to (1) Train therapists and refine the EnCoRE manual in a preliminary trial with 10 Veterans with schizophrenia and negative symptoms; (2) Conduct a randomized clinical trial (RCT; n=108, medium effect, alpha=.05) to test the efficacy of EnCoRE in producing positive changes at post-treatment and 3-month follow-up on the primary outcomes of negative symptoms and social and community functioning; and (3) Examine qualitative interviews completed by Veterans who participated in EnCoRE and Mental Health Providers to determine aspects of EnCoRE that were perceived as more or less helpful, interesting, and valuable in order to inform a larger, multi-site implementation trial. Secondary objectives include assessing the modifying effects of cognitive ability and psychotic symptoms on intervention effectiveness, and examining recovery, self-efficacy, and program satisfaction.  Project Methods: This project will include a period of training followed by an RCT with 108 participants. Participants will complete assessments at baseline, post-treatment, and 3-months. We will monitor fidelity, feasibility, and acceptability; study Veteran’s experience in the program; measure symptom and functional outcomes; and evaluate potential moderators of outcomes.  


Project Title:  Collaboration to Advance Negative Symptom Assessment in Schizophrenia (CANSAS)
Agency: NIMH (R01 MH082839)
PI: Jack J. Blanchard

Project Title:  Schizophrenia Research Training Program
Agency: NIMH (T32 MH020075)
PI: Jack J. Blanchard

Project Title:  Understanding Emotion and Social Impairment in Schizophrenia

Agency: NIMH (K02 MH079231)

PI:  Jack J. Blanchard

Project Title:  Social Anhedonia and Schizophrenia Proneness

Agency:  NIMH (R01 MH051240)

PI:  Jack J. Blanchard

Project Title:  Anhedonia and Emotion in Schizophrenia

Agency:  NIMH (R29 MH051240)

PI:  Jack J. Blanchard