Effect of Polyunsaturated Fatty Acids on Cardiovascular and Motor Responses Under Stress

The central aim of this protocol is to determine if the omega-3 fatty acids eicosapentaenoic
acid (EPA) and docosahexaenoic and (DHA) reduce aggressive behaviors among alcoholics in a
randomized, double blind, placebo controlled trial. Aggression will be measured in a
well-established behavioral test, the Point Subtraction Aggression Paradigm. Secondary and
tertiary aims are to determine if supplementation will improve neurochemical mechanisms and
cardiovascular abnormalities that are linked to the pathophysiology of aggression. A testing
battery will be done before supplementation (baseline) and compared to the same battery
repeated after three months of supplementation. This battery will include 1) psychometric
measures (aggression, depression and impulsivity), 2) a neurochemical measure (a lumbar
puncture for assessment of cerebrospinal fluid 5-hydroxyindolacetic acid [CSF 5-HIAA], a
metabolite of serotonin), and 3) a measure of cardiovascular physiology (heart rate
variability). The research participants will be randomized to consume four 1-gram capsules/
d containing either 1.88 grams of DHA plus EPA (active) or reference oils containing corn
oil and 1% fish oil for flavor blinding (placebo). Research participants will be aggressive
recovering alcoholics defined as scoring 20 or more on the Coccaro Lifetime History of
Aggression Scale and who eat seafood no more than once per week. If these inexpensive
nutrients reduce aggression or the related neurochemical and cardiovascular measures, these
findings will be readily applicable to many aggressive populations.

- INCLUSION CRITERIA:

A primary diagnosis of alcohol dependence within the last three months.

Male or female research participants with a Coccaro Lifetime History of Aggression score
of 20 or more.

Reported consumption of seafood no greater than twice per week.

Age of 18 years or older.

Must have been sober for 21-60 days.

Laboratory history and physical exam findings that are without significant abnormalities
(significant abnormality would include laboratory deviations that require medical
intervention or that indicate a major medical disorder).

EKG and chest X-ray are without clinically significant abnormalities as determined by the
physician interpreting the studies.

Educational level and degree of understanding that is sufficient to provide informed
consent, sign the consent forms and to allow for clear and intelligent communication
between research participant, investigators and staff.

EXCLUSION CRITERIA:

Lifetime history of an axis I psychiatric disorders specifically psychotic, schizophrenic,
bipolar affective disorder type I or eating disorders or premenstrual phase dysphoric
disorder. Major depression, depressive disorder NOS, panic and other anxiety disorders are
not exclusionary. Axis II personality disorders are not exclusionary.

Major medical disorders or major neurological disorders.

Determination by the Principal Investigator that the subject's use of prescription or
illicit drugs within the last six months will interfere with the dependent endpoints of
the study.

Regular use of prescription medications with psychotropic effects including side effects
or medications that modify lipid metabolism, within the last month. Use of NSAIDS, aspirin
or Tylenol not more than five times total per week, will be allowed.

Current psychotherapy to reduce aggression or depression.

Extensive use of home remedies, vitamins or nutritional supplements within three months.
Use of multi-vitamins one time per day will be allowed.

Pacemaker or other metal implants, which might be a contraindication for a MRI, scan.

Laboratory tests which indicate presence of the HIV.

Pregnancy.

Allergy to fish or seafood.