Biomedical subjects

I I Gottesman

Publications and source records attributed to I I Gottesman.

At least 19 recordsLinked to original sources

PubMed1995

A twin study of non-alcohol substance abuse.

Except for alcohol abuse, little is known about the familial aggregation for substance abuse. Here we report twin resemblance for non-alcohol substance use in the Washington University Twin Series, wherein probands were identified by consecutive admission to psychiatric facilities in the St. Louis area. A 5-point substance abuse scale was constructed with values anchored by never used drugs (1) to drug dependence (5). Year of birth was the most powerful predictor of drug use--younger twins scored far higher than older twins. Either heritability or common environment had to be included in the regression model to avoid a significant drop in explained variance, but which was more important could not be resolved. The correlation for identical twins exceeded that for fraternal twins, suggesting the possibility of a heritable factor.

Adolescent↗

PubMed1995

Schizoaffective psychoses: genetical clues to classification.

The diagnostic classification of schizoaffective psychoses has varied much since Kasanin introduced the concept in 1933. The various classifications have agreed that schizoaffective psychoses present a combination of schizophreniform and affective symptoms, but the diagnostic criteria differ as to the number, quality, and time sequence of the symptoms even in recent classifications like RDC, DSM-III-R, and ICD-10. The classifications are syndromatical, and the etiology of the schizoaffective psychoses is still undetermined apart from evidence for a strong genetic factor. Results from family, twin, and adoption studies are divergent, but all the same, support a separate classification of broadly defined schizoaffective psychoses as possibly being phenotypical variations or expressions of genetic interforms between schizophrenia and affective psychoses.

Bipolar Disorder↗

PubMed1995

The New York High-Risk Project. Psychoses and cluster A personality disorders in offspring of schizophrenic parents at 23 years of follow-up.

BACKGROUND: We herein present lifetime prevalence rates of psychoses and DSM-III-R cluster A personality disorders in sample A of the New York High-Risk Project, a prospective study following offspring of parents with schizophrenia (HRSz subjects) and affective illness (HRAff subjects) and of psychiatrically normal parents (NC subjects) from midchildhood to adulthood. METHODS: We interviewed the offspring in adulthood with the Schedule for Affective Disorders and Schizophrenia, Lifetime Version, for Axis I disorders and the Personality Disorder Examination for Axis II disorders. RESULTS: Lifetime prevalence rates (+/- SE) of schizophrenia and unspecified psychosis were 11.1% +/- 4.3% and 5.6% +/- 3.1%, respectively, in the HRSz group and 0% in the HRAff and NC groups. Rates of schizoaffective disorder subclassified as mainly schizophrenic, however, were highest in the HRAff group. Rates of psychotic affective disorders did not differ between the HRSz and other groups. Age-corrected morbidity risks were similar to lifetime prevalence rates. Rates of the three cluster A personality disorders did not differ among the groups, but the combined rate was greater in the HRSz and HRAff groups than in the NC group. CONCLUSIONS: Our data strongly support a specific familial liability to narrowly defined schizophrenia that is not shared by families of probands with affective disorder. Schizoaffective disorder and cluster A personality disorders, however, occur in families of both schizophrenic probands and probands with affective disorder. Psychotic affective disorders, which are not increased in HRSz subjects, do not appear to be an expression of the liability to schizophrenia.

Adolescent↗

PubMed1992

Second-trimester markers of fetal size in schizophrenia: a study of monozygotic twins.

OBJECTIVE: Since the second prenatal trimester is the critical period of massive neural cell migration to the cortex, and fingertip dermal cells migrate to form ridges during this same period, the authors sought to determine whether there are differences in fingertip ridge count in pairs of monozygotic twins discordant for schizophrenia, possibly indicating that a prenatal anatomical insult affected the twins differently. METHOD: The fingertip dermal ridges of 30 pairs of monozygotic twins (23 pairs in which the twins were discordant for schizophrenia and seven pairs in which both twins were normal) were counted by two persons trained in anthropometric research. Intrapair differences in the counts were then measured, and the differences among the pairs of normal twins were compared with the differences among the pairs discordant for schizophrenia. RESULTS: The twins discordant for schizophrenia had significantly greater absolute intrapair differences in total finger ridge count and significantly greater percent intrapair differences than the normal twins; i.e., their fingerprints were significantly less "twin-like." CONCLUSIONS: The study suggests that various second-trimester prenatal disturbances in the epigenesis of one twin in a pair discordant for schizophrenia may be related to the fact that only one of the twins expresses his or her genetic predisposition toward schizophrenia. This is consistent with a "two-strike" etiology of schizophrenia: a genetic diathesis plus a second-trimester environmental stressor.

Adult↗

PubMed1992

Schizophrenia--a high-risk factor for suicide: clues to risk reduction.

Suicide is the chief cause of premature death among schizophrenic persons. The lifetime incidence of suicide for patients with schizophrenia is 10% to 13% compared to a general population estimate of about 1%, and is quite close to that observed among those with major affective disorder. The magnitude of increased risk for suicide among schizophrenics peaks before middle age and declines thereafter, although schizophrenic persons tend to be at increased risk throughout the life span. Among psychiatric patients, schizophrenics are overrepresented among suicides, and often schizophrenics constitute the majority of inpatient suicides. It is important in evaluating suicide risk among schizophrenic persons to assess depression and suicidal ideation especially during index admission and during acute phases of the illness. It is noteworthy that schizophrenic persons often commit suicide as the overall level of psychopathology decreases during a nonpsychotic phase. Research has yielded salient risk factors for suicide in schizophrenic persons and "types" of especially vulnerable patients, even though statistical prediction of individual suicides has not proven effective.

Adolescent↗

PubMed1991

Body fat in identical twins reared apart: roles for genes and environment.

We report analyses of data on body fat from a cohort of 34 separated monozygotic twin pairs (MZA) and a matched sample of 38 pairs of monozygotic twins reared together (MZT) originally studied by James Shields. The correlation for MZA pairs was .61 and the correlation for MZT pairs was .75. These correlations did not differ significantly, nor did correlations differ between MZA pairs subclassified as having been raised in relatively more or less similar environments. Our results suggest important roles for both genes and environment in the accumulation of body fat and support other adoption studies in suggesting that adult environments rather than rearing environments are the most important nongenetic determinants of levels of body fat in adults.

Adipose Tissue↗

PubMed1991

The genetic epidemiology of schizophrenia and the design of linkage studies.

There are three aspects of schizophrenia that are challenges to the design of linkage studies. First, analysis of twin and family data have consistently failed to identify a single major gene effect. Second, ascertainment of multiplex families does not guarantee the sampling of families in whom a major gene is segregating even if such a gene exists. Third, environmental influences appear to play an essential role in the etiology of at least some schizophrenia. The implications of these features for linkage strategies in schizophrenia are discussed.

Cross-Sectional Studies↗

PubMed1991

(Hu)man versus mean revisited: MMPI group data and psychiatric diagnosis.

A meta-analysis of Minnesota Multiphasic Personality Inventory (MMPI) data from 403 control and psychiatric samples was used to (a) examine demographics associated with previously published MMPI studies, (b) test Goldberg's (1972) indexes for predicting normal versus deviant and neurotic versus psychotic group membership, (c) compare multiple regression, discriminant function, and logistic regression analyses commonly used to study the relation between the MMPI and diagnostic group membership, and (d) examine the signal within the MMPI as it relates to current psychiatric diagnosis. Group data were found to be efficient indicators of the relation between the MMPI and diagnosis, although efficiency is compromised by within-sample heterogeneity. The 3 statistical methods examined obtained equivalent results. Regression models related to group prediction are presented.

Adult↗

PubMed1991

Biological and genetic contributors to violence--Widom's untold tale.

In her review of the literature on the intergenerational transmission of violent behaviors, Widom (1989a) addressed the social issues but omitted all references to the relevant biological and genetic literature. This addition to her review introduces studies of criminality, delinquency, and violence from a behavioral genetic standpoint. There is clear evidence for a genetic role in criminality and for a physiological basis for violent behavior. The inclusion of such genetic and biological evidence is necessary for a more complete understanding of the transmission of violence from one generation to another.

Adolescent↗

PubMed1991

Negative association between schizophrenia and rheumatoid arthritis.

Persuasive evidence has accumulated demonstrating a strong negative association between rheumatoid arthritis and schizophrenia at the population level. Explanations for this phenomenon have taken into consideration immunological, biochemical, and genetic factors. In this article, we examine these and other factors in closer detail. We then propose hypotheses at the molecular level that might account for the negative association between the two diseases. These hypotheses may provide clues for our colleagues in molecular biology as they search for candidate genes, "anti-genes," and molecular mechanisms relevant to schizophrenia.

Arthritis, Rheumatoid↗

PubMed1991

Replicated psychometric correlates of schizophrenia.

OBJECTIVE: The authors' goals are to use scales from the MMPI hypothesized in their previous research to be correlates of liability to schizophrenia to differentiate DSM-III schizophrenia from bipolar and unipolar affective illness and to cross-validate these correlates in an independently ascertained sample of patients with Research Diagnostic Criteria (RDC) schizophrenia or affective disorder. METHOD: The criterion sample consisted of 83 patients consecutively admitted to a state-operated community mental health center. Diagnosis of schizophrenia; bipolar disorder, manic; and major depression were assigned by using DSM-III. The replication sample consisted of 60 adults with RDC diagnoses of schizophrenia, schizoaffective disorder, bipolar disorder, and unipolar disorder who were parents of children in two samples collected for a study of offspring at high risk for schizophrenia and other psychopathology. After the patients in the criterion sample were classified by logistic regression analysis, the results were used to classify patients in the replication sample. RESULTS: The MMPI indicators had adequate sensitivity, specificity, and predictive power for classifying schizophrenia, and there was a moderately high rate of diagnostic agreement between the MMPI and DSM-III. Cross-validation in the replication sample was successful. Overall, the MMPI index was an adequate inclusion and exclusion criterion not only for DSM-III-defined but also for RDC-defined schizophrenia. CONCLUSIONS: A psychometric index composed of the paranoid schizophrenia, psychoticism, and manifest hostility scales from the MMPI would be a cost-effective measure to increase diagnostic efficacy in future schizophrenia research and clinical practice.

Adult↗

PubMed1990

Transmission of a psychometric indicator for liability to schizophrenia in normal families.

The genetic analysis of schizophrenia would be facilitated by identification of a heritable correlate of liability. Deviance on an index of Minnesota Multiphasic Personality Inventory (MMPI) signs is associated with the disease phenotype; the familial aggregation and mode of transmission of this continuous psychometric indicator have yet to be established. In this paper, we examine the indicator through commingling analysis and segregation analysis with both the mixed and unified models on 65 nuclear families containing 211 normal individuals. Evidence for a high degree of familiality is found. Analysis of untransformed data under a conditional likelihood provides evidence for Mendelian transmission of a major gene with commingling of two distributions. The frequency of the "high index score" allele is 0.15, with the gene accounting for 31% of the total population variance; such a locus would be relevant to the study of psychopathology as 28% of the population would carry at least one deviant allele. When power-transformed scores are used to eliminate skewness, there is evidence for one distribution and it is not possible to distinguish single gene from multifactorial (polygenic or cultural) inheritance. While our findings regarding mode of transmission must be interpreted cautiously and confirmation of a single locus requires further study, demonstration of familiality warrants continued investigation of the index as an indicator of liability for schizophrenia.

Adolescent↗

PubMed1990

Estimation of disease risk under bivariate models of multifactorial inheritance.

Adjunct consideration of both qualitative (affection status) and quantitative (correlated liability indicator) information to define a bivariate phenotype can increase considerably the accuracy and efficiency of disease risk estimation. A general approach for calculating morbid risks to offspring on the basis of parental affection status and an offspring quantitative trait is presented. We also describe two different bivariate models of multifactorial inheritance, as implemented in the computer programs POINTER and YPOINT, and make explicit their assumptions/constraints when estimating the within-person and parent-offspring correlations necessary for calculation of morbid risks. We use psychometric family data on schizophrenia from the New York High-Risk Project to estimate these correlations and illustrate our methods. Our results show that even when a trait is only moderately correlated with liability, incorporation of quantitative trait information can lead to resolution of a range of risk to offspring that is not possible through reliance on parental affection status alone. Bivariate models provide a useful methodology for incorporating quantitative indicators of liability in the investigation of genetically complex diseases.

Mathematics↗

PubMed1990

Mixed-model segregation analysis of schizophrenia in the Lindelius Swedish pedigrees.

To test if familial transmission of schizophrenia is consistent with a model of monogenic inheritance with a multifactorial background, a mixed-model segregation analysis was applied to Swedish pedigrees consisting of 270 probands in 263 nuclear families. Results of the best-fitting mixed-model solutions are consistent with multifactorial transmission and no major gene. However, numerical instabilities prevented formal hypothesis testing, so an irrefutable genetic mechanism remains unidentified. Alternative research strategies that exploit recent advances in molecular genetics are discussed.

Female↗

PubMed1990

Psychometric deviance in offspring at risk for schizophrenia: I. Initial delineation of a distinct subgroup.

Psychometric signs from the Minnesota Multiphasic Personality Inventory (MMPI), which measure substantive disturbances in thinking, social relatedness, volition, and affective expressivity, were evaluated as possible indicators of transmissible liability specific to schizophrenia. Children of three criterion groups in the New York High-Risk Project--offspring at high risk (HR) for schizophrenia, psychiatric comparison (PC) offspring at risk for affective disorders, and normal comparison (NC) offspring not at augmented risk for psychiatric morbidity--were tested before the expression of schizophrenic psychopathology, when the subjects ranged in age from 13 to 26 years. The rate of psychometric deviance in the HR group (23%) was significantly higher than that in either the PC (7%) or NC (2%) groups, and profile analyses showed that the HR subgroup could be delineated by qualitative distinctions in personality functioning. Our results support the utility of MMPI indicators in etiologic investigations of schizophrenia.

Adolescent↗

PubMed1990

Psychometric deviance in offspring at risk for schizophrenia: II. Resolving heterogeneity through admixture analysis.

The longitudinal and prospective study of offspring at risk for schizophrenia is complicated by within-group heterogeneity in liability, as only a subgroup of those at risk will ultimately become affected. Here, we attempt to resolve such heterogeneity in the New York High-Risk Project by conducting an admixture analysis of values on a psychometric index of liability to schizophrenia derived from the Minnesota Multiphasic Personality Inventory (MMPI). We fit mixtures of components to the overall distribution in 171 children from three criterion groups: offspring at risk (HR) for schizophrenia, psychiatric comparison (PC) offspring at risk for affective illness, and normal comparison (NC) offspring not at increased risk for psychiatric morbidity. The distribution of psychometric scores was bimodal, and separation of two latent classes showed that there is a valid and nonarbitrary distinction between a subgroup of MMPI-deviant (primarily HR) offspring and a larger homogeneous group of MMPI-nondeviant HR, PC, and NC subjects. While continued followup is required to demonstrate a correspondence between these two classes and an underlying taxonomy of liability to schizophrenia, our findings demonstrate the utility of objective psychometric measurement and admixture analysis for resolving within-group heterogeneity in high-risk research. The wider implications of including our MMPI indicators in other genetic investigations of schizophrenia are discussed.

Adolescent↗

PubMed1990

Hedonic capacity in schizophrenics and their twins.

Audio-taped interviews recorded in the Gottesman-Shields schizophrenic twin series (17 pairs of identical twins, 14 pairs of fraternal same-sex twins, and 12 unpaired twins) were rated for level of hedonic capacity. Schizophrenics who were not hospitalized at the time of their interview were rated significantly lower (more impaired) on hedonic capacity than their normal co-twins. A significant negative correlation was also found between hedonic capacity and severity of illness. Hedonic capacity was found to be genetically influenced, although it appeared to be less heritable than the global diagnosis of schizophrenia. These results are consistent with Meehl's suggestion that reduced hedonic capacity is a heritable personality trait which potentiates the development of schizophrenia among those who are genetically predisposed to the disorder. The results suggest that anhedonia is not a phenotypic vulnerability marker for schizophrenia.

Affective Symptoms↗

PubMed1990

Problems and pitfalls of the family history positive and negative dichotomy: response to Dalén.

The authors defend the proposition that the simple division of schizophrenia into family history positive versus family history negative in the hope of uncovering etiological heterogeneity is too naive for a multifactorial disorder as contrasted with rare, mendelizing genetic conditions. Dalén is correct to forecast that a monolithic homogeneity view about the origins of schizophrenia is likely to be refuted and that it is important to pursue such a strategy. Using computed tomographic brain scan results and the simple dichotomy of family history positive versus family history negative as an illustration, we show the weakness (lack of statistical power) of the strategy. The problem arises from the fact that a negative family history for schizophrenia characterizes the vast majority of schizophrenic patients just as it does for insulin-dependent diabetes, another genetically influenced multifactorial disorder. A continuum from more genetic to less genetic variation in the etiology of schizophrenia fits the available familial patterns of risk.

Diseases in Twins↗