The Effect of Positive and Negative Emotions on Brain Activity in Alcoholics and Nonalcoholics

Objective: The purpose of this protocol is two-fold: 1) to determine how individual
differences in evoked brain responses relate to generalized trait personality and behavior
differences (as assessed by psychometric questionnaire instruments and behavioral measures),
and 2) to determine whether individual differences in evoked brain responses relate
specifically to genetic polymorphisms in genes governing neurotransmitter activity.

Study population: Healthy non-alcoholic adult volunteers, healthy adolescents aged 12 to 17
years (with or without a family history of alcohol use disorder), inpatient or outpatient
alcoholics, and recovering alcoholics.

Design: In this event-related functional magnetic resonance imaging (fMRI) study we will
attempt to evoke positive and negative affect via several different standardized methods
including: (1) pictures of emotion-arousing stimuli; (2) pictures of emotional facial
expression; (3) cues signaling reward or punishment. This protocol is designed to cover many
different functional magnetic imaging studies all using similar techniques to evoke and
measure positive and negative affect in the brain. Most subjects will not participate in
studies involving all the methods described in the protocol.

Outcome measures: The outcome measure is differences in blood oxygenation dependent level
(BOLD) signal measured using standard fMRI techniques and analyzed using AFNI software.

- INPATIENT ALCOHOLICS:

- We will study up to 150 male and 150 female individuals who meet criteria for alcohol
use disorders and are between the age of 18 and 65 years. Inpatient alcoholics will be
recruited from the NIAAA protocol 05-AA-0121, Assessment and treatment of people with
alcohol drinking problems.

- Inclusion criteria

- (1) Are physically healthy;

- (2) Are between 18-65 years of age (since age effects FMRI signal in ways that
have not yet been well-characterized);

- (2) Are right handed.

- Exclusion criteria:

- (1) Have ferromagnetic objects in their bodies which might be adversely affected
by MRI including implanted pacemakers, medication pumps, aneurysm clips; metallic
prostheses (including metal pins and rods, heart valves or cochlear implants,
shrapnel fragments, permanent eye liner or small metal fragments in the eye that
welders and other metal works may have- any doubt about presence of these objects
will result in exclusion from this study), or if candidates are uncomfortable in
small closed spaces (have claustrophobia), or cannot lie comfortably on their
back for up to one hour;

- (2) Test HIV positive (since AIDS-related dementia compromises brain function);

- (3) Are not cleared on a neuromotor examination during the screening physical by
the medically responsible staff;

- (4) Are currently receiving psychotropic medication for emotional distress;

- (5) Are pregnant or lactating;

- (6) Have symptoms of alcohol withdrawal as indicated by the most recent
measurement within the past 30 days, as measured by the Clinical Institute
Withdrawal Assessment (CIWA) score greater than 8;

- (7) Have active homicidal or suicidal ideation.

- RECOVERING ALCOHOLICS

- We will study up to 50 male and 50 female individuals who in the past have met
criteria for alcohol use disorders and are between the age of 18 and 65 years.
Recovering alcoholics must be at least 3 month without alcohol use, and will be
recruited from the NIAAA protocol 05-AA-0121, Assessment and treatment of people with
alcohol drinking problems.

- Inclusion criteria: Same as inpatient alcoholics.

- Exclusion criteria: Same as inpatient alcoholics.

-HEALTHY NON-ALCOHOLICS:

- We will study up to 150 male and 150 female individuals who have never met criteria
for an alcohol use disorder and are between the age of 18 and 65 years and will be
recruited from the NIAAA protocol 98-AA-0009, Screening Evaluation for NIAAA
Protocols.

- Inclusion criteria: Same as inpatient alcoholics.

- Exclusion criteria: Same as inpatient alcoholics (item 6 does not apply).

-CHILDREN OF ALCOHOLICS:

- We will study up to 90 male and 90 female individuals who are biological children of
at least one parent who met criteria for alcohol dependence and are between the age of
12 and 17 years.

- Inclusion criteria: Same as inpatient alcoholics except age range is between 12 and 17
years.

- Exclusion criteria: Same as inpatient alcoholics except age range is between 12 and 17
years (item 6 does not apply).

-CHILDREN OF NON-ALCOHOLICS:

- We will study up to 90 male and 90 female individuals neither of whose biological
parents met criteria for alcohol dependence and are between the age of 12 and 17
years.

- Inclusion criteria: Same as inpatient alcoholics except age range is between 12 and 17
years.

- Exclusion criteria: Same as inpatient alcoholics except age range is between 12 and 17
years (item 6 does not apply).

-PARENTS OF CHILDREN WHO HAVE AT LEAST ONE PARENT WITH A HISTORY OF ALCOHOL
DEPENDENCE:

- We will study up to 180 individuals who are the parent of a child who has at least one
parent with a history of alcohol dependence. The person providing consent may be
either a parent with the history of alcohol dependence or a parent without such a
history.

- Inclusion criteria: Legally able to consent for child.

- Exclusion criteria: None.

-PARENTS OF CHILDREN WITH NO FAMILY HISTORY OF ALCOHOL DEPENDENCE

- We will study up to 180 individuals who are the parent of a child neither of whose
parents have a history of alcohol dependence.

INCLUSION CRITERIA:

- Inclusion criteria: Legally able to consent for child.

- Exclusion criteria: None.