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Biomedical subjects

S A Mednick

Publications and source records attributed to S A Mednick.

At least 55 records · Page 3Linked to original sources
PubMed1994

Prenatal influenza infections and adult schizophrenia.

We reported previously that residents of Greater Helsinki, Finland, whose mothers were exposed to the 1957 influenza epidemic during their second trimester of gestation had a significantly elevated risk of developing adult schizophrenia. The majority of the replication studies to date have not determined whether the mothers actually contracted an infection or the stage of gestation based on mother's last menstruation. We read prenatal clinic records of the mothers of the Helsinki-born schizophrenia subjects to determine timing of infection, as noted by the prenatal clinic obstetric nurse at a time close to the actual infection. Schizophrenia subjects who were exposed in the second trimester had a significantly higher rate of definite influenza infection (86.7%) in that period compared to those who were exposed during the first and third trimesters (20.0%). These results are interpreted with caution because of the small number of cases.

Adult↗
PubMed1994

Prenatal factors in the pathogenesis of schizophrenia.

The excess of winter-spring births among individuals suffering from schizophrenia provides strong evidence for the existence of some prenatally occurring factors in the pathogenesis of schizophrenia. Recent epidemiological findings suggest that maternal viral infections during the second trimester of pregnancy may play a crucial role in the aetiology of adult schizophrenia. A 'two-hit window' hypothesis of the mechanism of action of prenatal factors in the pathogenesis of schizophrenia suggests at least two time-specific prenatal aetiological events. The observed association between prenatal viral infection and increased incidence of adult schizophrenia need not be a direct cytotoxic result of the viral infection, but may be caused indirectly, for example from foetal minor cerebral haemorrhages produced by the anticoagulant effects of aspirin.

Female↗
PubMed1993

Developmental brain abnormalities in the offspring of schizophrenic mothers. I. Contributions of genetic and perinatal factors.

OBJECTIVE: We examined the contributions of genetic risk for schizophrenia and obstetric complications to brain morphological abnormalities in the offspring of schizophrenic and normal patents. METHODS: We used a cohort analytic study of 60, 72, and 25 individuals with neither, one, or two parents, respectively, who were affected with schizophrenia spectrum disorders, evaluated initially in 1962 when they were on average 15 years old, and reexamined from 1986 through 1989 with psychiatric interviews and computed tomographic scans of the brain. RESULTS: After controlling for the effects of age, gender, substance abuse, and history of organic brain syndromes and head injuries, there were significant stepwise, linear increases in cortical and ventricular cerebrospinal fluid-brain ratios with increasing level of genetic risk for schizophrenia. Genetic risk for schizophrenia also interacted with prospectively assessed birth complications in predicting selectively to enlargement of the ventricular system; ie, the effect of birth complications on ventricular enlargement was greater among those with two affected parents compared with those with one affected parent, and greater among those with one affected parent compared with those with normal parents. Perinatal exposure to ether anesthesia was associated with a generalized increase in brain abnormality, which varied in severity according to level of genetic risk for schizophrenia. CONCLUSIONS: The type and degree of brain abnormalities shown by adult offspring of schizophrenic and normal parents are strongly predicted by the independent and interacting influences of genetic risk for schizophrenia and obstetric complications. The findings further substantiate the hypothesis that structural brain abnormalities in schizophrenia are at least in part neurodevelopmental in origin.

Adolescent↗
PubMed1993

Lifetime DSM-III-R diagnostic outcomes in the offspring of schizophrenic mothers. Results from the Copenhagen High-Risk Study.

OBJECTIVES: To perform a long-term prospective follow-up of children at high risk for schizophrenia to identify risk factors for the development of this disorder. DESIGN: Prospective follow-up population study of children of schizophrenic mothers and their matched controls from age 15 years to age 42 years, with multiple diagnostic assessments performed by senior clinicians using structured interviews blindly with respect to the group membership of the subject. PARTICIPANTS: Two hundred seven offspring of schizophrenic mothers and 104 control children without schizophrenic parents matched to the index group on age, sex, paternal socioeconomic status, urban/rural residence, and the amount of time spent during childhood in institutional rearing. MAIN OUTCOME MEASURE: The prevalence of the DSM-III-R disorders during the subjects lifetime. RESULTS: A significant aggregation of schizophrenia (16.2%) and other nonaffective, nonorganic psychosis (4.6%), and Cluster A personality disorders (21.3%) occurred among the offspring of schizophrenic mothers compared with the controls (1.9%, 0.9%, and 5%, respectively). No evidence of increased aggregation of (psychotic and nonpsychotic) affective disorders was noted among the offspring of schizophrenics. CONCLUSION: These results coincide with the results of other family studies in demonstrating a significant and specific familial aggregation of schizophrenia and nonpsychotic schizophrenia spectrum disorders among the biological relatives of schizophrenics.

Adolescent↗
PubMed1993

Research experiences with Fini Schulsinger.

For the past 31 years (1961-1992) Fini Schulsinger and I have been exploring the origins of schizophrenia. We have started a number of longitudinal projects that are still keeping us rather busy; after all, retirement just means more time for research. Through our students and these projects, our collaboration may never end.

Adolescent↗
PubMed1993

Genetic perspectives on crime.

This article examines the empirical evidence for a genetic influence in the etiology of antisocial behavior. This review relates the results of studies from 3 approaches to genetic investigation. The first, family studies, provides valuable information about the increased risk for deviance among the family members of affected individuals. Family studies provide few conclusions about genetic etiology, however, because members of families share environments as well as genes. A second approach, the study of twins, offers a somewhat better separation of genetic and environmental effects. The twin studies compare monozygotic (MZ) twins, who are genetically identical, to fraternal, same-sex, dizygotic (DZ) twins who have no more genes in common than other siblings (50%). The research design assumes that the effect of hereditary factors is demonstrated if the MZ twins have more similar outcomes (concordance for deviance) than DZ twins. The twins are reared together in almost all studies, and the environmental influences for MZ pairs may be more similar than for DZ pairs. A third approach, the adoption study, largely overcomes the possibility of confounding genetic and environmental factors which limit inferences from the results of twin studies. In this method, the deviant outcomes of adopted children (separated early in life from their biological parents) are compared with the outcomes of their adoptive parents and their biological parents. Similarity in outcome between adoptees and biological parents indicates a genetic effect.

Adoption↗
PubMed1993

The schizophrenia high-risk project in Copenhagen: three decades of progress.

We describe the design, theoretical approach and major recent findings of a prospective longitudinal study of the offspring of schizophrenic mothers and controls, initiated in 1962 by Sarnoff Mednick and Fini Schulsinger in Copenhagen, Denmark. Over 90% of the original 207 high-risk and 104 low-risk subjects have been successfully followed up since the initial assessment. At the time of the most recent assessment (1989), the subjects averaged 42 years of age and were nearly completely through the risk period for developing schizophrenia. By relating the lifetime psychiatric diagnoses of the subjects back to information on their premorbid experiences and functioning, we have identified several precursors of schizophrenia. This paper reviews our recent findings concerning whether outcomes of schizophrenia that differ in the relative prominence of negative versus positive symptoms represent discrete longitudinal syndromes. Predominantly negative and predominantly positive symptom schizophrenia were found to follow different patterns of symptom development from adolescence through the adult course of illness and were predicted by different combinations of genetic and environmental influences. Taken together, the findings suggest that the pathological processes underlying these two forms of schizophrenia are 1) partly independent of each other, 2) at least partly active during the premorbid state and 3) to some degree stable in the adult course of illness.

Adolescent↗
PubMed1993

A 30-year follow-up study of the sons of alcoholic men.

The nature-nurture question in the etiology of alcoholism is discussed. The research results from twin and adoption studies indicate a considerable genetic (= biological) component in the etiology of alcoholism. A longitudinal high-risk study of alcoholism is presented. The sons of alcoholic men and matched controls have been followed prospectively since before birth. The main results from previous phases of the study and a recent 30-year follow-up assessment are presented.

Adolescent↗
PubMed1992

Adult third ventricle width and infant behavioral arousal in groups at high and low risk for schizophrenia.

Previous research has demonstrated: (1) Subjects who are at genetic high risk for schizophrenia and who suffer delivery complications are at increased risk to evidence a widened third ventricle. (2) A widened third ventricle is related to decreased ANS arousal and, among schizophrenics, is related to negative symptom schizophrenia. (3) Adult schizophrenics evidence behavioral analogues of negative symptom schizophrenia premorbidly. This study compared adult CT scans to ratings of infant behavior in 179 subjects (104 at high genetic risk for schizophrenia) with the hypothesis that widened third ventricles would be related to underaroused infant behavior. Results of an ANOVA suggest that subjects who are at genetic high risk for schizophrenia and who evidence a widened third ventricle are more likely to have shown signs of behavioral underarousal as infants. Possible explanations, implications and limitations of the study are discussed.

Adolescent↗
PubMed1992

Third ventricle enlargement and lower heart rate levels in a high-risk sample.

Heart rate activity and computed tomographic measures of structural brain abnormalities were evaluated in 32 individuals with a genetic risk for schizophrenia (offspring of schizophrenic mothers). Heart rate activity was assessed in 1962 when the subjects were a mean age of 15.1 years. Diagnostic and computed tomography assessments were conducted in 1980. Compared to individuals with normal third ventricles, individuals with enlarged third ventricles evidenced significantly lower heart rate levels overall and significantly lower heart rate during rest and during the periods preceding conditioning and test for conditioning stimulus trials. These effects were independent of age, psychiatric diagnosis, and abnormalities in other brain regions. Difficulties in interpretation posed by the index of brain abnormality employed and by the 18-year time interval between the heart rate and computed tomography assessments are discussed. Together with prior evidence of a relationship between third ventricle enlargement and reduced electrodermal responsiveness in the same subjects, these findings provide a preliminary indication that enlargement of the third ventricle may involve damage to diencephalic structures involved in autonomic nervous system activity.

Adolescent↗
PubMed1990

Antecedents of predominantly negative- and predominantly positive-symptom schizophrenia in a high-risk population.

We reanalyzed the Copenhagen schizophrenia high-risk project data set to test recently developed models of the antecedents of predominantly negative and predominantly positive forms of schizophrenia. Among a group of 138 high-risk individuals, those at elevated genetic risk who suffered severe delivery complications and who were autonomic nonresponders during adolescence were significantly more likely than those without this pattern to evidence outcomes of schizophrenia with predominantly negative symptoms (86% vs 0.8%, respectively). Among a group of 160 high-risk subjects, those who escaped delivery complications, who evidenced a high degree of autonomic responsiveness in adolescence, and who experienced severe disruption of the early family rearing environment were significantly more likely than those without this pattern to evidence outcomes of schizophrenia with predominantly positive symptoms (40% vs 1.2%, respectively). In late childhood and early adolescence, predominantly negative-symptom schizophrenics were rated by their teachers as passive, socially isolated, and unresponsive to praise; predominantly positive-symptom schizophrenics were rated as overactive, irritable, distractible, and aggressive. The study is limited by the fact that the hypotheses were based in part on previous analyses of the same data set, by the small number of schizophrenic subjects of each subtype, and by the use of simplified theoretical and statistical models that do not address the multidetermination of negative and positive symptoms.

Adolescent↗
PubMed1990

Exposure to influenza epidemics during gestation and adult schizophrenia. A 40-year study.

We attempted to replicate earlier findings of an association between exposure to influenza in the second trimester of gestation and adult schizophrenia. The number of live births, of births of future schizophrenics, and of cases of influenza reported to the Ministry of Health in Denmark was ascertained by month from 1911 to 1950. The relationship between fetal exposure to influenza and adult schizophrenia was examined. It is possible that unknown factors produce excesses of both influenza and schizophrenia in the winter, creating an artifactual association. To control for this coincidence, the effects of season were removed from the monthly influenza and schizophrenic birth-rates by several methods. Using the residual scores, it was found that influenza rates higher than seasonally expected, occurring in the sixth month of gestation, were associated with rates of births of schizophrenics greater than seasonally expected. This association was not attributable to some winter-related, third factor or to climatic variables.

Adult↗
PubMed1990

Childhood antecedents of antisocial behavior: parental alcoholism and physical abusiveness.

Hierarchical logistic regression was used to assess the independent and interactive effects of paternal alcoholism and physical child abuse on antisocial behavior in young adult men. Men with alcoholic fathers (N = 131) did not report or exhibit more antisocial behavior than comparison subjects (N = 70). Men with physical abuse histories, however, reported more aggressive and antisocial behaviors during a clinical interview and were rated by a clinical interviewer as more likely to act out aggression. Arrest records did not distinguish the groups. There was no evidence that paternal alcoholism and childhood victimization interacted to increase the risk of antisocial behavior.

Acting Out↗
PubMed1989

Genetic and perinatal determinants of structural brain deficits in schizophrenia.

Using a subsample from the Copenhagen schizophrenia high-risk project, we examined the contributions of schizophrenic genetic liability and perinatal complications to computed tomographic (CT) measurements of ventricular enlargement and cortical and cerebellar abnormalities. A factor analysis of six CT measurements yielded two significant factors. One factor reflected multisite neural deficits as evidenced by abnormality of the cerebellar vermis and widening of the sylvian and interhemispheric fissures and cortical sulci. The other factor reflected periventricular damage as evidenced by enlargement of the third and lateral ventricles. Because all of the subjects had schizophrenic mothers, the major source of genetic variation is contributed by the diagnostic status of their fathers. In a stepwise multiple-regression analysis, it was determined that the multisite neural deficits factor was significantly related to genetic risk for schizophrenia (as measured by schizophrenia spectrum illness in the subjects' fathers) but was unrelated to pregnancy or delivery complications or to weight at birth. Periventricular damage was highly and significantly correlated with the number of complications suffered at delivery, but only among subjects with an elevated genetic risk. Although limited by a small sample size, these results suggest that the two types of CT abnormalities in schizophrenia may reflect partially independent processes based on different combinations of genetic and perinatal influences.

Adolescent↗
PubMed1989

Fetal neural development and schizophrenia.

The conference on Fetal Neural Development and Schizophrenia which was held in Washington, DC, May 31-June 1, 1988, focused on factors of possible etiological significance in fetal development. Schizophrenia researchers joined experts in brain imaging, neuropathological, and neurochemical changes in brain development and investigators of potential genetic and neurobehavioral causes of psychosis. The combined evidence suggested dysfunction in frontal and parieto-occipital neocortex, basal ganglia, hippocampus, and amygdala. Dopamine transmission was implicated both in basal ganglia deficits and in widespread neocortical disturbances. Viral infection, or excessive stress, during the second trimester of pregnancy, as well as obstetrical complications, minor physical anomalies, and brain defects, correlated positively with incidence of adult schizophrenia. Autonomic nonresponding, birth complications, and ventricular enlargement were found to be closely related to negative symptom schizophrenia in high-risk populations. A dual factor model of schizophrenia was suggested, where genetic and environmental influences combine to produce psychosis.

Brain↗
PubMed1989

Minor physical anomalies and recidivistic adult violent criminal behavior.

Minor physical anomalies (MPA) result from disruptions of gestation, and may be used as signs of central nervous system defects in development. Utilizing a Danish birth cohort, we tested the hypothesis that MPA predict adolescent and adult recidivistic violent criminal behavior. The number of MPA was measured at 11 to 13 years of age and police records of criminal behavior were ascertained at 20 to 22 years of age. Recidivistic violent offenders evidenced an elevated level of MPA compared with subjects with one violent offense or subjects with no violent offenses.

Abnormalities, Multiple↗
PubMed1989

Biosocial longitudinal research into antisocial behavior.

This paper reviews all longitudinal studies of antisocial and criminal behavior which have employed both biological and social measures. Psychophysiological measures which are particularly important in the prediction of antisocial behavior include reduced frequency of skin conductance orienting responses, poorer skin conductance conditioning, and lower resting heart rate levels. Two general themes emerge from this review. Firstly, where antisociality is of a mild or non-violent form, biological factors predispose to antisociality when the individual has experienced a benign home background. Secondly, where violence or seriously recidivistic crime is concerned, biological factors predispose to such behavior in those who have experienced adverse early rearing conditions. It is argued that this difference between mild and severe antisociality is in part a result of the differential contributions of genetic and perinatal factors to these sub-types of crime.

Antisocial Personality Disorder↗