| Eligibility |
-INCLUSION CRITERIA:
-All Participants
1. Between 30 and 75 years of age.
2. Ability to provide written informed consent as determined by physical examination and
verbal communication. Capacity to consent will be determined by those giving the
informed consent.
3. Females: Negative urine pregnancy test and not currently breastfeeding.
Post-menopausal or surgically sterile (tubal ligation or hysterectomy); or not
sexually active with a male partner and able to get pregnant; or documented agreement
to use an effective form of birth control. Acceptable forms of contraception include:
hormonal contraceptives (birth-control pills, injectable hormones, vaginal-ring
hormones); IUD; diaphragm with spermicide; condom with spermicide.
-Specific For AD Participants
4. DSM-IV diagnosis of alcohol dependence or alcohol abuse or DSM-5 diagnosis of moderate
or severe alcohol use disorder (established through history and clinical exam). We
include subjects that drink high doses of alcohol since alcohol's detrimental effects
are greater with larger doses and particularly with binge drinking.
5. Participants seeking treatment for their AD as well as those not seeking treatment for
their AD will be included.
6. Minimum 5 year history of heavy drinking (self-report).
7. Must consume at least 20 alcoholic drinks per week (male) or 15 per week (female)
(self-report).
8. Must have had the last drinking episode (females 3 or more drinks; and males 4 or more
drinks) within 1 week of baseline PET scan (self-report).
9. Alcohol specified as the preferred drug (self-report).
EXCLUSION CRITERIA:
- All Participants
1. Unwilling or unable to refrain from use within 24 hours of scheduled study
procedures: psychoactive medications or medication that may affect study results
(e.g., analgesics [non narcotic], antibiotics (must finish course at least 24
hours prior to a scheduled procedure), antidiarrheal preparations,
anti-inflammatory drugs (systemic corticosteroids are exclusionary),
antinauseants, cough/cold preparations) (self-report, medical history). The
following medications are allowable for entry on this study: analgesics
(non-narcotic); antacids; antiasthma agents that are not systemic
corticosteroids; antifungal agents for topical use; antihistamines
(non-sedating); H2-Blockers/PPI (proton pump inhibitors); laxatives. The use of
antihyperlipidemics and/or diuretics are permitted as long as they have been
taken for at least 1 month before procedure visits and dose has been stabilized.
The use of benzodiazepines such as alprazolam (( )Xanax), diazepam (( )Valium)
and lorazepam (( )Ativan), will not exclude participants from this study.
2. Current or past DSM-IV or DSM-5 diagnosis of a psychiatric disorder (other than
alcohol in AD participants and nicotine/caffeine use disorders) that required
hospitalization (any length), or chronic medication management (more than 4
weeks) and that could impact brain function at the time of the study as
determined by history and clinical exam. The following chronically used
medications are exclusionary from the study: analgesics containing narcotics;
anorexics (sibuteramine); antianginal agents; antiarrhythmics; antiasthma agents
that are systemic corticosteroids; antibiotics; anticholinergics; anticoagulants;
anticonvulsants; antidepressants; antidiarrheal preparations; antifungal agents
(systemic); antihistamines (sedating); antihypertensives; anti-inflammatory drugs
(systemic); antineoplastics; antiobesity; antipsychotics; antivirals (except for
treatment of HSV with agents without CNS activity, e.g. acyclovir, ganciclovir,
famciclovir, valacyclovir); anxiolytics; cough/cold preparations
(dextromethorphan preparations, pseudoephedrine); hormones (exceptions: thyroid
hormone replacement, oral contraceptives, and estrogen replacement therapy);
insulin; lithium; muscle relaxants; psychotropic drugs not otherwise specified
(nos) including herbal products (no drugs with psychomotor effects or with
anxiolytics, stimulant, antipsychotic, or sedative properties);
sedatives/hypnotics. Note that nicotine and/or caffeine use will not exclude
participants.
3. Major medical problems that can permanently impact brain function (e.g., CNS,
cardiovascular, metabolic, autoimmune, endocrine) as determined by history and
clinical exam.
4. Any clinically significant laboratory finding as determined during the screening
procedures that could impact brain function or study procedures (evidenced from
clinical laboratory results).
5. Have had previous radiation exposure (from X-rays, PET scans, or other exposure)
that with the exposure from this study, would exceed NIH annual research limits
(self-report, medical history)
6. Head trauma with loss of consciousness for more than 30 minutes (self-report,
medical history);
7. Positive test for alcohol on the day of the PET, the MRI or the NP tests
(clinical laboratory results).
8. Urine positive for psychoactive drugs (clinical laboratory results) on study days
involving imaging (PET and MRI) and neuropsychological testing.
9. Pregnant or breast feeding (self-report)
10. History of coagulation disorder (clinical laboratory results, medical history)
11. Have a history of allergic reaction to lidocaine (self-report, medical history)
12. Presence of ferromagnetic objects in the body that are contraindicated for MRI of
the head, fear of enclosed spaces, or other standard contraindication to MRI
(self-report checklist).
13. Cannot lie comfortably flat on your back for up to 2 hours in the PET and MRI
scanners (self-report).
14. Body weight > 250 kg. The MR scanner bed is tested to a weight limit of 250 kg
(~550 lbs).
15. Have a positive HIV test (clinical laboratory results, medical history).
16. Homozygosity for the rs6971 polymorphism on TSPO that results in LB (Owen et al
2011) (genotyping results).
17. NIH employees who meet criteria as AD subjects. Although we will include NIH
employees as healthy volunteers, study investigators and their superiors,
subordinates and immediate family members (adults children, spouses, parents,
siblings) will be excluded.
EXCLUSION CRITERIA SPECIFIC FOR CONTROL PARTICIPANTS:
- Consumption of moderate to high levels of alcohol. That includes if female, currently
(within past 6 months) consuming more than 2 drinks on a given episode and if male,
consuming more than 3 drinks on a given episode; and/or consuming if female, more than
a total of 7 drinks a week or if male, more than 10 drinks a week (self-report).
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