title: Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder: protocol for the baseline-follow up Research domain criteria Anxiety and Depression ("RAD") project.
abstract: BACKGROUND
  Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression ("RAD") project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time.
  
  
  METHODS
  Here we present the protocol for the "RAD" project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who "walk through the door" of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain-based subgroups over time and to assess whether these subgroups predict real-world functional capacity over time. First enrollment was August 2013, and is ongoing.
  
  
  CONCLUSIONS
  This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT02220309 . Registered: August 13, 2014.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA. lea.williams@stanford.edu.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA. lea.williams@stanford.edu.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Williams
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Goldstein-Piekarski
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
authors.forename: Nowreen
authors.initials: N
authors.lastname: Chowdhry
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Grisanzio
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Psychology, Palo Alto University, 1791 Arastradero Road, Palo Alto, CA, 94304, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Haug
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Samara
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Etkin
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: O'Hara
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
authors.forename: Trisha
authors.initials: T
authors.lastname: Suppes
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, 94305, USA.|Sierra-Pacific Mental Illness Research, Education, and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, 94304, USA.
authors.forename: Jerome
authors.initials: J
authors.lastname: Yesavage
mesh_terms: D001008:Anxiety Disorders / Q000175:diagnosis* / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D003863:Depression; D003866:Depressive Disorder / Q000503:physiopathology; D005500:Follow-Up Studies; D006801:Humans; D019964:Mood Disorders / Q000175:diagnosis* / Q000503:physiopathology*; D009315:National Institute of Mental Health (U.S.); D009488:Neurosciences; D015203:Reproducibility of Results; D012107:Research Design; D014481:United States
keywords: Anxiety; Brain circuits; Brain imaging; Cognition; Depression; Emotion; Research Domain Criteria (RDoC)