In this study the investigators will seek to improve our understanding of how positive and
negative valence systems, cognition, and arousal/interoception are inter-related in
disorders of mood, substance use, and eating behavior. The investigators will recruit 1000
individuals and use a wide range of assessment tools, neuroimaging measures, blood and
microbiome collections and behavioral tasks to complete the baseline and follow-up study
visits. Upon completion, the investigators aim to have robust and reliable dimensional
measures that quantify these systems and a set of assessments that should be recommended as
a clinical tool to enhance outcome prediction for the clinician and assist in determining
who will likely benefit from what type of intervention.
Neuroscience has made tremendous progress in understanding the basic neural circuitry that
underlies important processes such as attention, memory, and basic emotion processing. Yet,
little progress has been made to utilize these insights to apply them to psychiatric
populations in order to make clinically meaningful predictions. The connection between
psychiatric disorders and their underlying neurobiology has been difficult to establish. The
overarching theme of this study is to determine how biological and objective behavioral
measures can contribute to improving assessment and treatment of psychiatric patients. The
investigators will use the National Institute of Mental Health (NIMH) Research Domain
Criteria (RDoC) framework as a heuristic approach that integrates neuroscience and
psychopathology to study the positive and negative valence systems, cognition and
arousal/interoception domains. Within this framework we will study a group of treatment
seeking individuals with mental health conditions to determine how dysfunctions of affect,
substance use, and eating behavior organize across different levels and whether these latent
factors can be used to generate clinically useful prediction.
Using self-report, behavior, physiology, neural circuit, cell, molecule, and gene unit of
analysis measures, the investigators propose to enroll 1000 individuals from four different
cohorts over 5 years: (1) anxiety and/or depression; (2) eating problems; (3) substance use
problems; and (4) healthy controls. Each individual will undergo a multi-level assessment
that consists of (a) a standardized diagnostic assessment, (b) self-report questionnaires,
(c) behavioral tasks, (d) physiological measurements, (e) structural and functional magnetic
resonance imaging (fMRI) and EEG, (f) biomarker and microbiome assessments, (g) blood to
derive induced pluripotent stem cells, (h) and genetic and epigenetic assessments. These
individuals will be followed up for one year and will be re-assessed using a multi-domain
assessment of functioning, which will include: (a) symptom severity and duration, (b)
subjective well-being, (c) psychosocial function, (c) occupational function, (d) physical
health, (e) utilization of mental health resources (treatment), and (f) compliance with
1. Referred or seeking treatment, as defined by answering yes to "have you sought help
for problems with":
1. Anxiety and/or depressive symptoms
2. Problems related to substance use
3. Problems related to eating behavior
2. Screened positive for problems in (1) as indicated by:
1. Patient Health Questionnaire (PHQ-9) ≥ 10 and/or Overall Anxiety Severity and
Impairment Scale (OASIS) ≥ 8.
2. Drug Abuse Screening Test (DAST-10) score > 2
3. Eating Disorder Screen (SCOFF) score ≥ 2
3. Have a body mass index between 17 to 38 kg/m²
4. Able to provide written informed consent.
5. Have sufficient proficiency in English language to understand and complete
interviews, questionnaires, and all other study procedures.
1. No telephone or easy access to telephone.
2. Has a history of unstable liver or renal insufficiency; glaucoma; significant and
unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic,
hematologic, rheumatologic, or metabolic disturbance; or any other condition that, in
the opinion of the investigator, would make participation not be in the best interest
(e.g., compromise the well-being) of the subject or that could prevent, limit, or
confound the protocol-specified assessments.
3. A positive test for drugs of abuse, including alcohol (breath test), cocaine,
marijuana, opiates, amphetamines, methamphetamines, phencyclidine, benzodiazepines,
barbiturates, methadone, and oxycodone.
4. Has any of the following DSM-V disorders:
1. Schizophrenia Spectrum and Other Psychotic Disorders
2. Bipolar and Related Disorders
3. Obsessive-Compulsive and Related Disorders
4. Antisocial Personality Disorder
5. Moderate to severe traumatic brain injury or other neurocognitive disorder
6. Active suicidal ideation with intent or plan.
7. Change in the dose or prescription of a medication within the 6 weeks before
enrolling in the study that could affect brain functioning
8. Prescription of a medication outside of the accepted range, as determined by the best
clinical practices and current research.
9. Taking drugs that affect the fMRI hemodynamic response (e.g., methylphenidate,
acetazolamide, excessive caffeine intake > 1000 mg/day)
10. MRI contraindications
11. Unwillingness or inability to complete any of the major aspects of the study protocol
12. Non-correctable vision or hearing problems