Traits Associated With Early Life Stress Among Treatment-Seeking Alcoholics

Objective:

The primary objective of the study is to evaluate the role of early life stress (ELS),
alcohol dependence (AD), and their interaction in psychophysiology and neural mechanisms of
fear conditioning and extinction.

The main outcome of interest is fear extinction, as measured by laboratory-based and fMRI
paradigms. Secondary objectives of the study include: (1) explore the impact of early life
stress on behavioral and endocrine response to challenge procedures among individuals with
AD; (2) explore differences in reward processing, emotion processing, and neural response to
alcohol beverages as measured by fMRI as a function of AD and ELS; and (3) examine the
relationship between fear extinction and clinical outcomes in our patient sample.

Study Population:

The study sample includes four groups: 1) treatment-seeking individuals with alcohol
dependence (AD) and ELS exposure; 2) treatment seeking individuals with alcohol dependence
without ELS exposure; 3) healthy social drinkers without alcohol use disorders (AUD) but
with ELS exposure; and 4) healthy social drinkers without AUD and without ELS exposure.
Target accrual for each of these groups is 25.

Design:

All participants will be evaluated for fear conditioning and extinction using two separate
paradigms: an out-of-the scanner shock conditioning extinction procedure that utilizes
acoustic startle, and a shock conditioning extinction procedure combined with fMR
imaging that utilizes galvanic skin response. In addition, the two alcohol dependent groups
will be evaluated for several biomarkers including a guided imagery procedure designed to
induce stress and/or craving for alcohol, and an assessment of
hypothalamic-pituitary-adrenal (HPA) axis function.

Outcome Measures:

Primary outcome measures include fear-potentiated startle responses and galvanic skin
responses; and neural BOLD fMRI responses during presentation of fear associated stimuli.
Secondary and exploratory measures in alcohol dependent subjects include measures of
distress and craving for alcohol in response to guided imagery scripts; neuroendocrine
stress responses and clinical outcomes (alcohol consumption and self-reported anxiety and
mood symptoms).

- INCLUSION CRITERIA:

Inclusion criteria for AD+/ELS+ group:

- Between 21 and 65 years of age

- Ability to provide written informed consent as determined by successful completion of
consent quiz prior to signing consent

- Females: Negative urine pregnancy test, not currently breastfeeding

- Diagnosed with alcohol dependence according to Diagnostic and Statistical Manual for
Mental Disorders-Fourth Edition (DSM IV)

- Alcohol consumption within the past month provided by self-report

- Specify alcohol as their preferred drug in a clinical interview

- Minimum score of moderate level of exposure for at least two categories of ELS or
score of severe level of exposure for at least on category of ELS as measured by the
CTQ (categories include: physical, sexual, and emotional abuse; and physical and
emotional neglect; severity level varies by category, and is standardized by the
creators of the CTQ)

Inclusion criteria for AD+/ELS- group:

- Between 21 and 65 years of age

- Ability to provide written informed consent as determined by successful completion of
consent quiz prior to signing consent

- Females: Negative urine pregnancy test, not currently breastfeeding

- Diagnosed with alcohol dependence according to DSM IV

- Alcohol consumption within the past month provided by self-report

- Specify alcohol as their preferred drug in a clinical interview

Inclusion criteria for AD-/ELS+ group:

- Between 21 and 65 years of age

- Ability to provide written informed consent as determined by successful completion of
consent quiz prior to signing consent

- Females: Negative urine pregnancy test, not currently breastfeeding

- Minimum score of moderate level of exposure for at least two categories of ELS or
score of severe level of exposure for at least on category of ELS as measured by the
CTQ (categories include: physical, sexual, and emotional abuse; and physical and
emotional neglect; severity level varies by category, and is standardized by the
creators of the CTQ)

Inclusion criteria for AD-/ELS- group:

- Between 21 and 65 years of age

- Ability to provide written informed consent as determined by successful completion of
consent quiz prior to signing consent

- Females: Negative urine pregnancy test, not currently breastfeeding

EXCLUSION CRITERIA:

Exclusion criteria for AD+/ELS+ group:

- Neurological symptoms of the wrist or arm, e.g., carpal tunnel syndrome, as
determined by history and physical exam

- Chronic use of psychotropic medications within four weeks of the study, with the
exception of fluoxetine, for which the exclusionary time period is six weeks.
Incidental use of psychotropic medications is allowed but any use must be
discontinued prior to the study for a time period exceeding 5 half-lives of the
medication in question.

- Presence of any current or past DSM IV diagnosis of bipolar disorder, or psychotic
disorder (e.g, schizophrenia, schizoaffective disorder), or substance dependence
other than alcohol, nicotine, or caffeine.

- Major medical problems (e.g., central nervous system (CNS), cardiovascular,
respiratory, gastrointestinal (GI), hepatic, renal, endocrine, reproductive) that in
the judgment of the MAI, in consultation with relevant Clinical Center consult
services, cannot be adequately managed at the Clinical Center

- Presence of ferromagnetic objects in the body, fear of enclosed spaces, or other
standard contraindication to MRI, as determined by self-report

- Left-handedness

Exclusion criteria for AD+/ELS- group:

- Neurological symptoms of the wrist or arm, e.g., carpal tunnel syndrome, as
determined by history and physical exam

- Chronic use of psychotropic medications within four weeks of the study, with the
exception of fluoxetine, for which the exclusionary time period is six weeks.
Incidental use of psychotropic medications is allowed but any use must be
discontinued prior to the study for a time period exceeding 5 half-lives of the
medication in question.

- Presence of any current or past DSM IV diagnosis of bipolar disorder, or psychotic
disorder (e.g, schizophrenia, schizoaffective disorder), or substance dependence
other than alcohol, nicotine, or caffeine.

- Major medical problems (e.g., CNS, cardiovascular, respiratory, GI, hepatic, renal,
endocrine, reproductive) that in the judgment of the MAI, in consultation with
relevant Clinical Center consult services, cannot be adequately managed at the
Clinical Center

- Presence of ferromagnetic objects in the body, fear of enclosed spaces, or other
standard contraindication to MRI, as determined by self-report

Score above minimal for one or more categories of ELS as measured by the CTQ

-Left-handedness

Exclusion criteria for AD-/ELS+ group:

- Neurological symptoms of the wrist or arm, e.g., carpal tunnel syndrome, as
determined by history and physical exam

- Chronic use of psychotropic medications within four weeks of the study, with the
exception of fluoxetine, for which the exclusionary time period is six weeks.
Incidental use of psychotropic medications is allowed but any use must be
discontinued prior to the study for a time period exceeding 5 half-lives of the
medication in question.

- Presence of any current or past DSM IV diagnosis of bipolar disorder, or psychotic
disorder (e.g, schizophrenia, schizoaffective disorder), or substance dependence
other than alcohol, nicotine, or caffeine.

- Major medical problems (e.g., CNS, cardiovascular, respiratory, GI, hepatic, renal,
endocrine, reproductive) that in the judgment of the MAI, in consultation with
relevant Clinical Center consult services, cannot be adequately managed at the
Clinical Center

- Presence of ferromagnetic objects in the body, fear of enclosed spaces, or other
standard contraindication to MRI, as determined by self-report

- Current or past DSM IV diagnosis of alcohol dependence or abuse

- Currently seeking treatment for alcohol problems as assessed by self-report

- Positive urine drug test at screening (for opiates, cannabinoids, amphetamines,
cocaine, benzodiazepines)

- Positive breathalyzer test at screening

- Alcohol abstainer

- Left-handedness

Exclusion criteria for AD-/ELS- group:

- Neurological symptoms of the wrist or arm, e.g., carpal tunnel syndrome, as
determined by history and physical exam

- Chronic use of psychotropic medications within four weeks of the study, with the
exception of fluoxetine, for which the exclusionary time period is six weeks.
Incidental use of psychotropic medications is allowed but any use must be
discontinued prior to the study for a time period exceeding 5 half-lives of the
medication in question.

- Presence of any current or past DSM IV diagnosis of bipolar disorder, or psychotic
disorder (e.g, schizophrenia, schizoaffective disorder), or substance dependence
other than alcohol, nicotine, or caffeine.

- Major medical problems (e.g., CNS, cardiovascular, respiratory, GI, hepatic, renal,
endocrine, reproductive) that in the judgment of the MAI, in consultation with
relevant Clinical Center consult services, cannot be adequately managed at the
Clinical Center

- Presence of ferromagnetic objects in the body, fear of enclosed spaces, or other
standard contraindication to MRI, as determined by self-report

- Score above minimal for one or more categories of ELS as measured by the CTQ

- Current or past DSM IV diagnosis of alcohol dependence or abuse

- Currently seeking treatment for alcohol problems as assessed by self-report

- Positive urine drug test at screening (for opiates, cannabinoids, amphetamines,
cocaine, benzodiazepines)

- Positive breathalyzer test at screening

- Alcohol abstainer

- Left-handedness