Neural Mechanisms Underlying Alcohol Induced Disinhibition

Collaboration on Alcohol Self Administration in Adolescents and Young Adults - Specific Aim 2: To Examine the Effect of Acute Alcohol Administration on Forebrain Disinhibition Using Functional Magnetic Resonance Imaging (fMRI)

Forty 18-year-old social drinkers will be selected from the sample tested in specific aim 1 ("Prospective Assessment of Adolescent Drinking Trajectories With Computer-Assisted Self-administration of Ethanol (CASE)"; ClinicalTrials.gov identifier: NCT01063166). The functional magnetic resonance imaging blood-oxygen-level-dependent (fMRI BOLD) activity related to disinhibition measured with the Stop Signal task will be assessed during a continuous infusion of alcohol, clamping the arterial Breath Alcohol Concentration (aBAC) at 60 mg% for approximately one hour. It will be examined whether this fMRI BOLD activity is associated with the initial drinking trajectories and the alcohol consumption at age 18 and at age 20 identified in specific aim 1. Furthermore, fMRI will be used with the Taylor Aggression Paradigm to determine which brain areas mediate increased physical aggression during the same continuous infusion of alcohol as described above. All participants will undergo an alcohol and a placebo fMRI session.

Study Overview

• Status: Completed
• Conditions: Alcoholism
• Intervention / Treatment: Drug: Ethanol; Drug: Placebo - half-normal saline

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• Germany
  • Saxony
    • Dresden, Saxony, Germany, 01187
      • Technische Universitaet Dresden - Dresden fMRT-Neuroimaging Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 19 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Residents living within 15 km (9.5 miles) from downtown Dresden

Description

Inclusion Criteria:

• male and female Caucasian volunteers aged 18 years/0 months to 19 years/11 months;
• written informed consent by the subject;
• habitual social drinking during the two months preceding participation, defined by at least one drinking day in any two weeks-interval;
• at least one prior experience of alcohol intoxication
• being able to abstain from tobacco use for four hours without developing nicotine withdrawal symptoms;
• effective contraception in female participants;
• consenting to abstain from any illegal substance use for 2 weeks prior to participation;
• living within 15 km (9.5 miles) from downtown Dresden;
• sufficient information concerning alcohol use in both parents and in at least four second-degree relatives

Exclusion Criteria:

• prior medical treatment due to alcohol use;
• current or prior history of any serious disease, including CNS, cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, alcohol or drug dependence, but not alcohol abuse;
• current history of Axis-I psychiatric illness, including premenstrual dysphoric disorder;
• current or prior history of alcohol-induced flushing reactions;
• positive urine screen for cannabinoids, cocaine, amphetamines, opiates, or benzodiazepines;
• light or non-drinkers: averaging less than 2 standard drinks per week in the preceding two months;
• intention to become pregnant
• pregnancy or positive urine pregnancy screening or breast-feeding;
• any alcohol intake on the test day or the day before;
• use of medications known to interact with alcohol within 2 weeks of the study;
• positive hepatitis or HIV at screening, provided the subject consented to these tests
• any conditions posing safety issues with the fMRI scan, such as ferromagnetic implants, cardiac pacemakers or insulin pumps

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alcohol consumption	Alcohol consumption, as measured by a Timeline Followback Interview.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute perfusion levels assessed with arterial spin labeling	1 week
Behavioural Stop Signal Reaction Time (SSRT)	1 week
BOLD fMRI correlate of aggression	1 week
Taylor aggression score	1 week
BOLD fMRI correlate of disinhibition	1 week

Collaborators and Investigators

• Sponsor: Technische Universität Dresden
• Collaborators: Indiana University School of Medicine
• Investigators: Principal Investigator: Michael N. Smolka, Prof. Dr., Technische Universitaet Dresden - - Faculty of Medicine Carl Gustav Carus - Department of Psychiatry and Psychotherapy; Principal Investigator: Ulrich S. Zimmermann, Dr., Universitaetsklinikum Carl Gustav Carus at the Technische Universitaet Dresden

Publications and helpful links

General Publications

• Gan G, Guevara A, Marxen M, Neumann M, Junger E, Kobiella A, Mennigen E, Pilhatsch M, Schwarz D, Zimmermann US, Smolka MN. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex. Biol Psychiatry. 2014 Nov 1;76(9):698-707. doi: 10.1016/j.biopsych.2013.12.017. Epub 2014 Jan 15.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: March 11, 2010
• First Submitted That Met QC Criteria: March 31, 2010
• First Posted (ESTIMATE): April 1, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): March 12, 2013
• Last Update Submitted That Met QC Criteria: March 11, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: U01 AA017900 SA2