Epi-Genetic Modulators of Fear Extinction in Alcohol Dependence

NCT02438969 | Completed

• 2 other identifiers: 15012715-AA-0127
• Study Type: observational
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Researchers want to learn if people with alcohol dependence have more difficulty learning to feel calm, or learn to fear things more easily. They also want to study how early life stress (ELS) affects the ability to learn to feel calm. Objective: \- To see if people with alcohol dependence and/or ELS have a harder time learning to feel calm than people without these. Also, to see if DNA is changed by ELS and if this change affects fear conditioning and extinction. Eligibility:

• Adults ages 21-65 with and without an alcohol use disorder (AUD) and with and without ELS.
• Healthy volunteers. Design:
• Participants will be screened with:
• Medical history
• Physical exam
• Blood and urine tests
• Psychological tests
• Treatment for symptoms of alcohol withdrawal, if needed
• Healthy volunteers will have 1 overnight visit (2 days, 1 night). AUD participants will stay at the clinic for about 4 weeks.
• Participants will:
• Rate alcohol use/craving, depression, anxiety, and childhood trauma.
• Have psychophysiological measures: electrodes and mild electric shock.
• Have a functional magnetic resonance imaging (MRI) scan. Participants will lie on a table in a metal cylinder with a coil over their head. In the first scanning session, they will see pictures, do a simple task, and may get shocks. Participants will also do a second scanning session in which they will perform the aforementioned fear conditioning and extinction task, as well as a facial expression matching task, an affective word processing task, and a task measuring valuation of monetary rewards.
• Answer questions about their emotions (some participants).
• Have blood drawn from an arm vein or intravenous (IV) line.
• AUD participants will get a dexamethasone pill. The next day, they will get a hormone injected in and have blood drawn from an IV line.
• AUD participants will have 3 follow-up visits with questions and blood and lab tests.

Conditions

Alcohol Dependence; Fear; Stress

Keywords

Alcohol; Alcohol Dependence; Stress; Fear Conditioning; Natural History

Outcome Measures

Primary Outcomes (1)

• The primary objective of the study is to evaluate the role and interaction of epigenetic/genetic factors, ELS exposure, and AUD on neuronal mechanisms of fear conditioning and extinction.

  1\) Fear extinction (extinction learning) is disrupted in AUD and differs between normal controls with or without ELS and AUD with or without ELS as measured by behavior (skin conductance response) and by fMRI (region of interest BOLD activation). 1a) AUD with ELS will have more severe disruption in their extinction learning phenotype. 2) Neuronal mechanisms involved in abnormal fear extinction in AUD include decreased vmPFC activation during fear which results in impaired inhibitory top-down control of the amygdala by the mPFC resulting in anxiety.

  ongoing

Study Arms (4)

AUD/ELS-

Treatment seeking or non-treatment seeking individuals with AUD without ELS exposure

AUD/ELS+

Treatment-seeking or non-treatment seeking individuals with AUD and early life stress (ELS) exposure

non-AUD/ELS-

non-AUD controls without ELS exposure

non-AUD/ELS+

Non-AUD controls with ELS exposure

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

AUD participants will be recruited from participants in the NIAAA screening platform protocols 14-AA-0181. Non-AUD participants will be recruited from participants in the NIAAA protocol 14-AA-0181. We will recruit all racial and ethnic groups in the greater Washington DC area

You may not qualify if:

• 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, agree to abstain or use accepted form of contraception
• Diagnosed with current 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
• AA-0009 and/or 14-AA-0181 screening consents signed
• Cleared venous access assessment
• 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, agree to abstain or use accepted form of contraception
• AA-0009 and/or 14-AA-0181 screening consents signed
• Cleared venous access assessment
• Neurological symptoms of the wrist or arm, e.g., carpal tunnel syndrome, as determined by history and physical exam
• Presence of any current or past DSM IV diagnosis of bipolar disorder, or psychotic disorder (e.g, schizophrenia, schizoaffective disorder), or current substance dependence other than alcohol, nicotine, or caffeine.

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Pickering RP, Kaplan K. Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry. 2004 Aug;61(8):807-16. doi: 10.1001/archpsyc.61.8.807.

  PMID: 15289279 BACKGROUND

• Heilig M, Thorsell A, Sommer WH, Hansson AC, Ramchandani VA, George DT, Hommer D, Barr CS. Translating the neuroscience of alcoholism into clinical treatments: from blocking the buzz to curing the blues. Neurosci Biobehav Rev. 2010 Nov;35(2):334-44. doi: 10.1016/j.neubiorev.2009.11.018. Epub 2009 Nov 24.

  PMID: 19941895 BACKGROUND

• Goldman D, Oroszi G, Ducci F. The genetics of addictions: uncovering the genes. Nat Rev Genet. 2005 Jul;6(7):521-32. doi: 10.1038/nrg1635.

  PMID: 15995696 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Alcoholism

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Falk W Lohoff, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2015
• First Posted: May 8, 2015
• Study Start: August 13, 2015
• Primary Completion: December 30, 2022
• Study Completion: December 31, 2022
• Last Updated: February 17, 2026

Record last verified: 2026-02-13

Locations

US (1)