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 treatment.

Inclusion Criteria:

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.

Exclusion Criteria:

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

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