OBJECTIVE:The Danish Longitudinal Study of Alcoholism utilized a prospective, high-risk research paradigm to identify putative markers of adult male alcoholism from a comprehensive database that began with the birth of the subject and extended over three decades. This article focuses on measures antedating abusive drinking that predicted lifetime alcohol abuse/dependence at age 30 years.METHOD:The original 330 subjects of this study were drawn from a large Danish birth cohort (N = 9,125) born between 1959 and 1961. The sample included 223 sons of treated alcoholic fathers (high-risk group) and 107 matched sons whose biological fathers had no record of treatment for alcoholism (low-risk group). This sample has been thoroughly investigated with a variety of methods representing multiple domains that included perinatal records, pediatric records, school records, teacher ratings, school physician records and a series of structured interviews and psychometric tests at ages 19-20 and 30 years. The present analysis focuses on the degree to which premorbid differences between the high- and low-risk groups later predicted lifetime drinking problems at age 30 (n = 241).RESULTS:As expected lifetime alcohol abuse/dependence by age 30 was reported significantly more often in the high-risk group. Of the 394 premorbid variables tested, 68 were found to distinguish the high- from the low-risk group before any subjects had developed a drinking problem. Of these 68 variables, 28 (41%) were also associated with DSM-III-R alcohol abuse/dependence at age 30. These 28 putative markers were reduced to 12 that were entered into a multiple regression analysis to search for the most powerful unique predictors of alcoholism. Four of the 28 putative markers were independently associated with problem drinking at age 30: low birth weight, number of life crises in childhood, ratings of childhood unhappiness and antisocial personality disorder. The regression model accounted for 46% of the drinking outcome variance. A father's alcoholism by itself no longer independently contributed to the prediction of his son's drinking and with one exception, did not systematically interact with the putative markers to facilitate the prediction of alcohol dependence at age 30.CONCLUSIONS:Risk itself. which significantly predicted problem drinking at age 30, was not uniquely associated with the development of alcoholism in adulthood. These findings, rather, provide broad support for the biopsychosocial model of alcoholism, especially for those models that emphasize the cumulative influence over time of internal and external variables in biologically vulnerable individuals.

Back to table of contents Previous article Next article Letter to the EditorFull AccessDr. Schiffman and Colleagues ReplyJASON SCHIFFMAN, M.A., MORTEN EKSTROM, M.D., JOSEPH LaBRIE, M.A., FINI SCHULSINGER, M.D., HOLGER SORENSEN, M.D., and SARNOFF MEDNICK, Ph.D., Dr.Med., JASON SCHIFFMAN, M.A., MORTEN EKSTROM, M.D., JOSEPH LaBRIE, M.A., FINI SCHULSINGER, M.D., HOLGER SORENSEN, M.D., and SARNOFF MEDNICK, Ph.D., Dr.Med., Los Angeles, Calif.Published Online:1 Feb 2003https://doi.org/10.1176/appi.ajp.160.2.394AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Dr. Kelly's letter makes an interesting point that we did not address in our article. There is a gradient of disorders related to schizophrenia (e.g., schizotypal personality disorder, quasi-psychotic conditions); each of these related disorders may, in part, have its origins in errors of fetal development. Each error of fetal development may be signaled by a specific set of minor physical anomalies. To a significant degree, the nature of the specific minor physical anomaly observed may be determined by the timing of disturbances during the process of gestation. This same timing of developmental disturbance may also help determine the nature of the neural developmental deficit and the associated behavioral disorder. Note that these conditions tend to result in the set of findings summarized by Dr. Kelly.We have presented evidence (1) that a maternal influenza infection in the second trimester of gestation increases the risk of adult schizophrenia in affected offspring. More recently, we examined this same relationship in a large cohort of military recruits in Finland (2). The large size of the cohort enabled us to study exposure during a narrow window of gestation. We reported that maternal influenza in the 23rd week of gestation increased the risk for schizotypal personality disorder (assessed by the Minnesota Multiphasic Personality Inventory). In an article in preparation for publication, we report a higher risk for schizotypal personality disorder among young adults in Tangshan, China, who had been exposed to a severe earthquake (7.8 on the Richter scale) during their 23rd week of gestation (unpublished study by Machon et al.).Perhaps the specific narrow window of development that is disturbed helps to determine the nature of the neural deficit and the consequent behavioral pathology, as well as the superficial minor physical anomaly indicants we observe.References1. Mednick SA, Machon RA, Huttunen MO, Bonet D: Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 1988; 45:189-192Crossref, Medline, Google Scholar2. Machon RA, Huttunen MO, Mednick SA, Sinivuo J, Tanskanen A, Bunn Watson J, Henriksson M, Pyhala R: Adult schizotypal personality characteristics and prenatal influenza in a Finnish birth cohort. Schizophr Res 2002; 54:7-16Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 160Issue 2 February 2003Pages 394-394 Metrics History Published online 1 February 2003 Published in print 1 February 2003

Univariate prediction models of schizophrenia may be adequate for hypothesis testing but are narrowly focused and limited in predictive efficacy. Therefore, we used a multivariate design to maximize the prediction of schizophrenia from premorbid measures and to evaluate the relative importance of various predictors. Two hundred twelve Danish subjects with at least one parent diagnosed in the schizophrenia spectrum (high risk) and 99 matched subjects with no such parent (low risk) were assessed on 25 premorbid variables in seven domains (genetic risk, birth factors, autonomic responsiveness, cognitive functioning, rearing environment, personality, and school behavior) when the subjects averaged 15 years of age. Twenty-five years later, 33 subjects had received lifetime diagnoses of schizophrenia. Discriminant function analyses were used to discriminate schizophrenia outcomes from no mental illness and nonschizophrenia outcomes on the basis of premorbid measures. Regardless of the comparison group used, schizophrenia was predicted by the interaction of genetic risk with rearing environment, and disruptive school behavior. Within the high-risk group, two-thirds of schizophrenia outcomes were correctly predicted by these premorbid measures; three-quarters of those with no mental illness were also correctly predicted. Prediction was enhanced among those with two schizophrenia spectrum parents, lending support to a multiplicative gene x environment model. Implications for early identification/primary prevention efforts are discussed.

There are mixed findings in research on the relationship between risk of developing schizophrenia and early rearing factors such as family dysfunction and parental loss or separation. These relationships, however, seem clearer when the vulnerability resulting from a genetic liability to schizophrenia is taken into consideration. It appears that when combined with genetic risk for schizophrenia, disruptive early rearing circumstances contribute significantly to later schizophrenic outcome.

OBJECTIVE:The authors' goal was to determine whether early termination of breast-feeding contributes to later alcohol dependence, as proposed more than 200 years ago by the British physician Thomas Trotter.METHOD:In 1959-1961, a multiple-specialty group of physicians studied 9, 182 consecutive deliveries in a Danish hospital, obtaining data about prepartum and postpartum variables. The present study concentrates on perinatal variables obtained from 200 of the original babies who participated in a 30-year high-risk follow-up study of the antecedents of alcoholism.RESULTS:Of the 27 men who were diagnosed as alcohol dependent at age 30, 13 (48%) came from the group weaned from the breast before the age of 3 weeks; only 33 (19%) of the 173 non-alcohol-dependent subjects came from the early weaning group. When challenged by other perinatal variables in a multiple regression analysis, early weaning significantly contributed to the prediction of the severity of alcoholism at age 30.CONCLUSIONS:The data support the hypothesis that early weaning may be associated with a greater risk of alcohol dependence later in life.

BACKGROUND In 1979 through 1980, electroencephalographic (EEG) responses to an alcohol challenge in 19 year-old sons of alcoholics as well as in sons of nonalcoholic control subjects were examined. The familial risk status of the subjects and greater EEG sensitivity to alcohol were hypothesized to predict the development of alcoholism 10 years later. METHODS In 1990 through 1992, diagnostic interviews were completed to ascertain alcohol and other substance use disorders in these subjects and to update their family history. RESULTS Updated family history of alcoholism predicted the development of substance dependence. Density of alcoholic relatives (the number of alcoholic relatives divided by the number of known relatives) was positively related to the severity of alcohol use disorders in the probands. Contrary to expectation, a greater EEG response at age 19 years was not related to the later development of alcohol dependence. Instead, the opposite was observed: a smaller EEG alpha frequency response to alcohol at age 19 years was related to the development of alcohol dependence and high quantity and frequency of alcohol consumption 10 years later. CONCLUSIONS Lower EEG response to a small dose of alcohol may be associated with the later development of alcohol dependence. This result is based on a small number of subjects and should be interpreted with caution. Although this result is opposite to our 1980 hypothesis, it is consistent with much of the recent literature.

Annals of the New York Academy of SciencesVolume 708, Issue 1 p. 97-101 Thirty-Year Follow-Up of Men at High Risk for Alcoholism DONALD W. GOODWIN, DONALD W. GOODWIN University of Kansas Medical Center Kansas City, Kansas 66160Search for more papers by this authorJOACHIM KNOP, JOACHIM KNOP The Institute for Preventive Medicine Copenhagen, DenmarkSearch for more papers by this authorPER JENSEN, PER JENSEN The Institute for Preventive Medicine Copenhagen, DenmarkSearch for more papers by this authorWILLIAM F. GABRIELLI JR., WILLIAM F. GABRIELLI JR. Kansas City VA Medical Center and University of Kansas Medical Center Kansas City, Kansas 66160Search for more papers by this authorFINI SCHULSINGER, FINI SCHULSINGER The Institute for Preventive Medicine Copenhagen, DenmarkSearch for more papers by this authorELIZABETH C. PENICK, ELIZABETH C. PENICK University of Kansas Medical Center Kansas City, Kansas 66160Search for more papers by this author DONALD W. GOODWIN, DONALD W. GOODWIN University of Kansas Medical Center Kansas City, Kansas 66160Search for more papers by this authorJOACHIM KNOP, JOACHIM KNOP The Institute for Preventive Medicine Copenhagen, DenmarkSearch for more papers by this authorPER JENSEN, PER JENSEN The Institute for Preventive Medicine Copenhagen, DenmarkSearch for more papers by this authorWILLIAM F. GABRIELLI JR., WILLIAM F. GABRIELLI JR. Kansas City VA Medical Center and University of Kansas Medical Center Kansas City, Kansas 66160Search for more papers by this authorFINI SCHULSINGER, FINI SCHULSINGER The Institute for Preventive Medicine Copenhagen, DenmarkSearch for more papers by this authorELIZABETH C. PENICK, ELIZABETH C. PENICK University of Kansas Medical Center Kansas City, Kansas 66160Search for more papers by this author First published: February 1994 https://doi.org/10.1111/j.1749-6632.1994.tb24701.xCitations: 13AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume708, Issue1Types of Alcoholics: Evidence from Clinical, Experimental, and Genetic ResearchFebruary 1994Pages 97-101 RelatedInformation

A sample of 19 DSM-III-R schizophrenics and 94 controls with no mental illness from the Copenhagen high-risk project was used to test the hypothesis that social class of origin is related to adult CT measures of ventricular, sulcal, Sylvian fissure and anterior interhemispheric fissure enlargement, cerebellar pathology, and brain volume. The schizophrenics and controls were divided into high and low SES-of-origin. No significant differences emerged between the high and low SES-of-origin subjects within the schizophrenic and control groups on any of the six CT measures.

Acta Psychiatrica ScandinavicaVolume 83, Issue S364 p. 130-132 Summary and conclusion of the baseline study Susan Reynolds Whyte, Susan Reynolds WhyteSearch for more papers by this authorFini Schulsinger, Fini SchulsingerSearch for more papers by this authorRalph Kempinski, Ralph KempinskiSearch for more papers by this author Susan Reynolds Whyte, Susan Reynolds WhyteSearch for more papers by this authorFini Schulsinger, Fini SchulsingerSearch for more papers by this authorRalph Kempinski, Ralph KempinskiSearch for more papers by this author First published: May 1991 https://doi.org/10.1111/j.1600-0447.1991.tb03093.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume83, IssueS364May 1991Pages 130-132 RelatedInformation

Acta Psychiatrica ScandinavicaVolume 83, Issue S364 p. 55-58 Baseline study for the evaluation of the mental health programme Fini Schulsinger, Fini SchulsingerSearch for more papers by this author Fini Schulsinger, Fini SchulsingerSearch for more papers by this author First published: May 1991 https://doi.org/10.1111/j.1600-0447.1991.tb03088.xCitations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume83, IssueS364May 1991Pages 55-58 RelatedInformation

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