Characterization of Phenotypic and Genotypic Regressors for Imaging

Objective: To determine genetic variants as well as behavioral measures across different
study group populations. Results of these will be used as regressors to help explain
inter-individual differences in data collected across IRP protocols.

Study Population: The study population will include 1) healthy non-smoking, participants with
no substance use disorders 2) healthy individuals with nicotine use disorder 3) healthy
individuals with other substance use disorders 4) individuals with other psychiatric
disorders and 5) treatment-seeking individuals with substance use disorders. Participants
must be under evaluation for another NIDA-IRP protocol, generally healthy, and age 18 or
older.

Design: The main study will require approximately 4-6 hours at the NIDA-IRP. Main study
procedures may be done in 1 visit or multiple visits, and may be done in conjunction with
another NIDA-IRP study. After being consented into the main study, the participant will be
asked to submit a blood sample, an MRI scan, complete various questionnaires,
characterization instruments and several behavioral tasks. Blood will only be drawn once,
provided there are no technical problems (such as sample damage during collection,
preparation, shipping or assay) requiring a repeat draw. Participants in more than one
NIDA-IRP protocol will be asked to repeat a few of the time-sensitive questionnaires in this
protocol during subsequent MRI visits, as required by other IRP imaging protocols in which
the subject may be participating. Data acquired in this protocol will be compared to data
acquired in other NIDA-IRP protocols.

An arm of this protocol will be used to pilot test a phenotyping battery developed by the
NIDA CTN. This battery overlaps with several of the assessments in the main protocol.
Participants in the NIDA CTN pilot study who also meet criteria for the main study may
participate in the main study as well.

Outcome Measures: The primary outcome measures in this study are the genetic, behavioral and
phenotypic factors that are related to addiction. Secondary outcome measures are to compare
the genetic, behavioral and phenotypic factors to imaging and behavioral data acquired across
other IRP protocols.

- INCLUSION CRITERIA: Main Study.

All participants must be:

1. under evaluation for another NIDA-IRP study or the NIDA CTN pilot portion of this
study. Justification: data acquired under other studies will be compared to data
collected in this protocol.

2. greater than or equal to 18 years of age. Justification: Some NIDA-IRP studies have
includeed teens, aged 13 - 17, but no current studies include them so we will only
include adults in this study for now.

EXCLUSION CRITERIA: Main Study.

Exclusion criteria are limited to those in the NIDA IRP protocol for which the subject is
being considered or has been consented.

Exclusion for MRI portion:

1. History of neurological illnesses including but not limited to CVA, CNS tumor, head
trauma, MS or other demyelinating diseases, epilepsy, movement disorders, or migraine
in treatment. Assessment tool: phone screen and history and physical (H&P). Rationale:
Neurological illnesses may impair ability to tolerate the procedures and alter
neuronal activity, adding noise to the data.

2. Cognitive impairment (unless this population of subjects is included in another IRP
protocol in which the subject is also participating). Assessment tool: self-report
during H&P, of special education classes, history of specific learning disability or
mental retardation. Rationale: Cognitive impairment may impair ability to tolerate the
procedures and alter neuronal activity, adding noise to the data.

3. Current major mood, anxiety or psychotic disorder (unless this population of subjects
is included in another IRP protocol in which the subject is also participating).
Assessment tool: self-report, H&P computerized SCID with follow up clinical interview
and/or the Mini International Neuropsychiatric Interview (M.I.N.I). Rationale: Current
major mood or psychotic disorders may impair ability to tolerate

the procedures and alter neuronal activity, adding noise to the data.

4. Pregnancy. Assessment tool: Urine pregnancy test. Rationale: fMRI is not accepted as a
safe procedure purely for research purposes during pregnancy.

5. HIV positive individuals. Assessment tool: oral HIV test with serum confirmation of
positive results. Rationale: potential liver/metabolic/vascular disease can interfere
with the physiological transduction mechanisms for fMRI (i.e. making the measurement
unreliable).

6. Unable to undergo MRI scanning due to possible pregnancy, metallic devices in the
body, claustrophobia or body morphometry.

7. Currently using respiratory, cardiovascular or anticonvulsant medications that may
interfere with the BOLD MRI signal.

8. Left-handed. Assessment tool: Edinburgh Handedness Inventory (under screening
protocol). Rationale: Differences in hemispheric dominance will be a confound in
structural and functional scans.

Inclusion criteria: NIDA CTN Pilot Study

All participants must:

1. Either have a current DMS-5 nicotine, cocaine, marijuana or opiate use disorder,
possibly in combination, or have no current DSM-5 substance use disorder (control
participants). Justification: The NIDA CTN has requested pilot data on these
participant groups.

2. Be greater than or equal to 18 years of age. Justification: The NIDA CTN will use this
battery in adults.

Exclusion criteria: NIDA CTN Pilot Study

Participants may not have:

1. A DSM-5 major psychiatric diagnoses unrelated to a substance use disorder including
but not limited to bipolar disorder and schizophrenia. Diagnoses secondary to
substance use disorder will be allowable providing the participant s symptoms do not
interfere with the ability to complete assessments. Assessment tool: self-report, H&P,
Mini International Neuropsychiatric Interview (M.I.N.I).

Rationale: Current major mood or psychotic disorders may impair ability to complete
the assessments and would add unnecessary noise to the data.

2. Cognitive impairment. Assessment tool: self-report during H&P, of special education
classes, history of specific learning disability or mental retardation. Rationale:
Cognitive impairment may impair ability to complete the assessments and would add
unnecessary noise to the data.