Individual Differences in Reward and Impulse Control

Background: Even under similar drug use patterns, the risk for drug addiction varies from
individual to individual. However, the neurobiological mechanisms underlying this variability
are poorly understood and characterized. Studies suggest that certain traits observed in
substance dependent individuals may actually precede drug use, and could augur future
substance dependence. Understanding how the presence of these traits increases vulnerability
to substance addiction could aid in the development of early intervention, preventative
measures, as well as better treatment strategies.

Objective: The primary goal of this protocol is to improve our understanding of increased
susceptibility to developing substance addiction. We focus here on particular gene x
environment interactions as increased risk factors for substance dependence. The emphasis is
on monoaminergic neurotransmitter-related genes thought to influence adaptability to the
environment, and, therefore, on cognitive domains related to dopamine and serotonin: reward
and punishment learning, and impulse control. To achieve the above objective, the study will
be implemented by using cognitive, genetic and neuroimaging testing in adult addicted
individuals along with matched controls.

Subject Population: We focus on adult (18-55 years old) smokers and matched non-smoking
controls.

Experimental Design: This study involves cognitive, pharmacological and functional magnetic
resonance imaging (fMRI) testing in a between-subject design involving neuroimaging and
cognitive testing.

Outcome Measures: The primary outcome measures will be BOLD fMRI activation and behavioral
performance on various cognitive tasks that deal with impulse control and reward learning, as
a function of gene x environment interactions.

- INCLUSION CRITERIA FOR ALL PARTICIPANTS:

Between 18 and 55 years old (inclusive);

Must be able to provide informed consent;

Blood pressure (BP) and heart rate (HR) while sitting at or below the following values
after five min rest: Systolic BP (SBP) 140 mm Hg, diastolic BP (DBP) 90 mm Hg, heart rate
(HR) 100 bpm;

No history of placement in special-education classes as a consequence of serious learning
problems (to be assessed during the History and Physical assessment).

Right-handed (based on Edinburgh Handedness Inventory);

Eligible to enter the MRI scanner, as determined though self report on the MRI screening
form (from the screening protocol 06-DA-N415).

INCLUSION CRITERIA FOR SMOKERS:

Smoked for at least 2 years, and has generally smoked 10 cpd in the past year and
consistently for the past 30 days.

Be able to refrain from smoking for up to 4hrs during the study.

Carry 2 or more plasticity alleles (assessed through protocol # 10-DA-N457 or other IRP
protocols)

INCLUSION CRITERIA FOR NON-SMOKERS:

Not have a history of daily cigarette smoking lasting more than a month and no smoking
within the past 2 years.

Carry 2 or more plasticity alleles (assessed through protocol # 10-DA-N457 or other IRP
protocols)

EXCLUSION CRITERIA FOR ALL PARTICIPANTS:

Report of a history of significant medical/neurological illness that might interfere with
imaging data such as HIV positive status, cerebral vascular accident (CVA), central nervous
system (CNS) tumor, traumatic brain injury, multiple sclerosis (MS) or other demyelinating
diseases, epilepsy, or movement disorders;

History of psychosis or any current DSM-IV axis I disorder (other than simple phobia);

Current use of psychotropic medication that may alter attentional functioning (e.g.,
Clonidine, antipsychotics, Venlafaxine, stimulants);

Current use of substances on the study visit that might influence performance on tasks as
assessed by self-report, carbon monoxide (CO) monitoring, alcohol breathalyzer and urine
testing; (and neuromotor evaluation, when needed). If participant is intoxicated at the
time of the study visit; he/she will be rescheduled for a later visit.

Meets criteria for abuse, or DSM-IV dependence, or dependence in partial remission, on any
drug except nicotine. Past abuse of marijuana or alcohol is acceptable provided it is at
least 1 year in the past.

Pregnancy, which will be assessed by history during screening and by urine testing on scan
days;

Claustrophobia by self report, or through response to the mock-scanner environment, severe
enough to preclude toleration of the scanning environment.