CRHD Dimensional Connectomics of Anxious Misery

Study Overview

Every year more than 30% (2 billion) of the world’s population and 75 million adult Americans suffer from disorders that have been lumped under the term “anxious misery.” Among patients who receive treatment, a large number remain with debilitating symptoms, often for years or decades. Recently, the NIMH has led efforts to define constructs within the Negative Valence System (NVS) that cut across such disorders in order to spur research on underlying mechanisms. The Dimensional Connectomics of Anxious Misery Project will focus on potential brain circuitry and behaviors associated with loss and responses to sustained threat, two of the most central NVS dimensions. By considering these brain circuits jointly, we can disentangle these dimensions for more specific targeting of disabling symptoms. Recent improvements in treatment efficacy have been shown in studies that target regions by mapping individual anatomy and connectivity patterns. This project will comprehensively characterize NVS spectrum disorders using the Research Domain Criteria (RDoC) framework, focusing on brain circuits important in pathophysiology across the spectrum of loss and responses to sustained threat.

Project Timespan: April 1, 2016 - March 31, 2020

Investigators

Yvette Sheline

Yvette Sheline, M.D. - UPENN Principal Investigator

Contact: Email

Study Protocol Overview

Data being collected

  • Imaging:  This project will use the 2-session HCP ‘Lifespan” protocol implemented on a single Siemens 3T Prisma MRI scanner.  Scans will begin with background-suppressed pseudo-continuous arterial spin labeling (pCASL) to quantify whole-brain cerebral blood flow.  In addition to standard HCP Lifespan task-based fMRI data for working memory, face recognition, social cognition, and gambling, we will add a task-fMRI acquisition designed to measure implicit emotional conflict.  Finally, an optimized T2-weighted image sequence with ultra-high in-plane resolution will be acquired through the temporal lobe for use in hippocampal and amygdala segmentations.
  • Clinical: Neuropsychological testing, multiple phenotypic measures including the SCID.
  • Genetics: blood samples and/or saliva samples.
  • Behavioral: Neurocognitive data using the NIH Toolbox and Penn Computerized Neurocognitive Battery, results from startle task, and self-reporting of mood. 


Cohort Description

This study will recruit 50 control participants and 200 participants with anxious misery symptoms from the Outpatient Clinics of the University of Pennsylvania. All subjects will be 18-45, male or female, any race, and English speaking. Likewise, all subjects will have the capacity to give informed consent and follow study procedures.  Participants will be recruited to the University of Pennsylvania, where they will undergo an extensive multi-modal assessment to characterize the cross-sectional phenomenology of these Negative Valence domains and a one-year follow up to assess subsequent symptoms. 


Data Release Plans

Analyzed data on all subjects, gathered up to that point, will be released during year 2 of the project.  Analyzed data for all 250 subjects will be released at the conclusion of the study in year 4. 


Keywords

Human Connectome Project, Negative Valence System, Anxious Misery, Brain Imaging

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