Functional Neuroimaging of Alcoholism Vulnerability (PIT)
Condition: Healthy
MeSH terms: Alcoholism
Intervention: Memantine; Placebo
Intervention description: Memantine is a low-side-effect NMDA receptor antagonist usually administered therapeutically to elderly persons with moderately severe Alzheimer's disease in typical doses of 10-20 mg daily. In this study, single doses of 40 mg are administered.; Identically appearing sugar pill, given orally
Intervention MeSH terms: Memantine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: All subjects received both the study drug and placebo. Family history was the main variable of interest, and randomization was stratified by this variable.
Masking: Double (Participant, Care Provider)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Reward Circuitry; Impulsivity; Family History of Alcoholism; NMDA/DA Interactions

Summary:

      This project compares Family History Positive (FHP) for alcoholism subjects to matched Family
      History Negative (FHN) subjects derived from the project Principal Investigator's National
      Institute on Alcohol Abuse and Alcoholism-funded longitudinal study of drinking behavior in a
      2000 college freshman population (known as the Brain and Alcohol Research in College Students
      study (BARCS)). The age of these subjects is a valuable one at which to capture the
      transition from harmful use to abuse/dependence. This project explores the effects of
      memantine in a double-blind, randomized, counterbalanced manner on alcoholism risk-relevant
      tasks. More specifically, this project studies functional MRI tasks related to different
      aspects of reward and/or impulsivity-related behavior in different contexts, compares the
      underlying neural circuitry across tasks, and uses a pharmacologic probe of the glutamatergic
      system to examine NMDA/DA interactions. The combined measures provide the opportunity to
      advance our understanding of specific aspects of brain function related to familial
      alcoholism vulnerability in an already well-characterized population as some members evolve
      into alcohol abuse. In addition to conventional within-task analyses, functional network
      connectivity and allied approaches will be used to examine brain networks across tasks.

      The investigators will study adult male and female subjects in equal numbers who are either
      offspring of an alcoholic parent or are FHN matched controls. The investigators will recruit
      and assess a total of 84 (42 FHP and 42 matched FHN) subjects between the ages of 18-21 years
      on initial BARCS contact. The investigators will use 4 cognitive tasks during the functional
      MRI (fMRI) which include: 1) a Monetary Incentive Delay Task that distinguishes networks
      engaged in motivational (anticipation) and consummatory (outcome) components of reward
      processing; 2) a Go/No-Go Task that measures the ability to inhibit response to a pre-potent
      stimulus; 3) an Alcohol Cue Reactivity Task that examines Nucleus Accumbens response to
      alcohol-related versus matched soft drink stimuli; and 4) a Pavlovian-to-Instrumental
      Transfer (PIT) Task that dissects a component of the Monetary Incentive Delay (MID) Task, and
      provides an imaging assay of a transfer-like process that can be related to real-world
      drinking behavior, thus informing upon and extending the key findings from CTNA-2.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Biological father with a history of Alcoholism

          -  A least 1 other first- or second-degree relative with a history of Alcoholism.

        Exclusion Criteria:

          -  Cannot be an only child

          -  A diagnosis of DSM-IV-TR Axis I psychotic disorders screened with the Mini
             International Neuropsychiatric Interview (MINI), done in the BARCS study (with the
             exception of Alcohol Abuse)

          -  Report of psychotic disorder in a 1º relative

          -  Prenatal exposure to alcohol (mother reported to drink 3 or more drinks on an occasion
             or more than 3 times per month during pregnancy

          -  Not speaking English fluently or being a non-native English speaker, or being educated
             in a primary language other than English >grade 1

          -  Mental retardation (Full Scale IQ<70)

          -  Traumatic brain injury with loss of consciousness > 30 minutes or concussion in last
             30 days

          -  Presence or history of any medical/neurologic illness that may affect brain physiology
             (e.g., epilepsy, Multiple Sclerosis), including focal brain lesion seen on structural
             MRI (all structural scans are read by a licensed radiologist)

          -  Current pregnancy (all females will be tested with urine screens on the day of MRI)

          -  Any positive alcohol screen will result in exclusion

          -  Inability to comprehend the consent form appropriately

          -  Other specific fMRI exclusions include metal devices, clips or fragments in body
             (orbital x-ray performed if needed)

          -  Female participants under 125 pounds will be excluded from participating due to the
             strength and side effects in this segment of the population.