Amplitude of Visual P3 Event-Related Potential as a Phenotypic Marker for a Predisposition to Alcoholism: Preliminary Results from the COGA Project

Authors

  • B. Porjesz,

    Corresponding author
    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • H. Begleiter,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • T. Reich,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • P. Van Eerdewegh,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • H. J. Edenberg,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • T. Foroud,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • A. Goate,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • A. Litke,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • D. B. Chorlian,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • A. Stirnus,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • J. Rice,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • J. Blangero,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • L. Almasy,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • J. Sorbell,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • L. O. Bauer,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • S. Kuperman,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • S. J. O'Connor,

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author
  • J. Rohrbaugh

    1. SUNY Health Science Center at Brooklyn (B.P., H.B., A.L., D.C., A.S.), Brooklyn, New York; Washington University (T.R., P.V, A.G., J.Ri., J.Ro.), St. Louis, Missouri; Indiana University Medical Center (H.J.E., T.F., J.S., S.J.O.), Indianapolis, Indiana; The Southwest Foundation for Biomedical Research (J.B., L.A.), San Antonio, Texas; University of Connecticut Health Center (L.O.B.), Farmington, Connecticut; and University of Iowa (S.K.), Iowa City, Iowa.
    Search for more papers by this author

  • This study was supported by U.S. Public Health Service Grants AA08401 and AA08403. Some of the results of this paper were obtained by using the program package SAGE, which is supported by a U.S. Public Health Service Resource Grant (1 P41 RR03655) from the National Center for Research Resources.

  • The COGA Project (H. Begleiter, SUNY Health Science Center at Brooklyn, Principal Investigator; Ted Reich, Washington University, Co-Principal Investigator) includes six different centers where data collection takes place. The six sites and principal investigator and co-investigators are: Indiana University (J. Numberger, Jr., P. M. Conneally); Universiv of Iowa (R. Crowe, S. Kuperman); University of California at San Diego and Scripps Institute (M. Schuckit, F. Bloom); University of Connecticut (K Hessel brack); State University of New York, Heafth Science Center at Brooklyn (B. Porjesz, H. Begleiter); and Washington University in St. Louis (1 Reich, C. R. Cloninger).

Reprint requests: B. Porjesz, SUNY Health Science Center at Brooklyn, 450 Clarkson Avenue, Box 1203, Brooklyn, NY 11203.

Abstract

Recent data collected at six identical electrophysiological laboratories from the large national multisite Collaborative Study on the Genetics of Alcoholism provide evidence for considering the P3 amplitude of the event-related potential as a phenotypic marker for the risk of alcoholism. The distribution of P3 amplitude to target stimuli at the Pz electrode in individuals 16 years of age and over from 163 randomly ascertained control families (n= 687) was compared with those from 219 densely affected alcoholic families (n= 1276) in which three directly interviewed first-degree relatives met both DSM-III-R and Feighner criteria at the definite level for alcohol dependence (stage II). The control sample did not exclude individuals with psychiatric illness or alcoholism to obtain incidence rates of psychiatric disorders similar to those of the general population. P3 amplitude data from control families was converted to Z-scores, and a P3 amplitude beyond 2 SD's below the mean was considered an “abnormal trait.” When age- and sex-matched distributions of P3 amplitude were compared, members of densely affected stage II families were more likely to manifest low P3 amplitudes (2 SD below the mean) than members of control families, comparing affected and unaffected offspring, and all individuals; all comparisons of these distributions between groups were significant (p < 0.00001). P3 amplitude means were also significantly lower in stage II family members, compared with control family members for all comparisons, namely probands, affected and unaffected individuals (p < 0.000l), and offspring (p < 0.01). Furthermore, affected individuals from stage II families, but not control families, had significantly lower P3 amplitudes than unaffected individuals (p 0.001). Affected males from stage II families had significantly lower P3 amplitudes than affected females (p < 0.001). Recent linkage analyses indicate that visual P3 amplitude provides a biological phenotypic marker that has genetic underpinnings.

Ancillary