Fifty years of the Nuremberg Code: a time for retrospection and introspection.
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Codes of Ethics↗
Biomedical subjects
I I Gottesman
Publications and source records attributed to I I Gottesman.
Twins: en route to QTLs for cognition.
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Aged↗
The New York High-Risk Project. Prevalence and comorbidity of axis I disorders in offspring of schizophrenic parents at 25-year follow-up.
BACKGROUND: The New York High-Risk Project is a study of offspring of patients with schizophrenia (HRSz group) or affective illness (HRAff group) and psychiatrically normal parents (NC group) observed prospectively from childhood to adulthood. We herein present lifetime prevalence and comorbidity rates of Axis I disorders in subjects and their siblings from sample A of the project. METHODS: Schedule for Affective Disorders and Schizophrenia-Lifetime Version interviews conducted with the offspring in adulthood were used to obtain diagnoses of Axis I disorders. RESULTS: Schizophrenia and unspecified psychoses occurred only in the HRSz group. However, schizoaffective and psychotic affective disorders occurred equally in the HRSz and HRAff groups. Total rates of psychosis in these groups were significantly higher than in the NC group. All groups had similar rates of nonpsychotic affective and substance abuse disorders. The HRAff group, however, had significantly more total affective illness than the NC group and tended to have more anxiety disorders than the other groups. Comorbidity rates in the HRSz and HRAff groups were nearly twice those of the NC group. CONCLUSIONS: The familial liabilities to schizophrenia and affective disorders show specificities and commonalities, differing markedly from each other in their expression of some disorders and sharing others. Patterns of comorbidity are generally, although not entirely, similar to these liabilities.
Adolescent↗
Epigenetic approaches to developmental psychopathology.
We evaluate the usefulness of 11 key epigenetic concepts from the behavior genetic research paradigm for advancing the field of developmental psychopathology. Key assumptions, empirical examples, and caveats in interpreting results are presented. We emphasize the usefulness of incorporating both dimensional (e.g., temperament trait) and categorical (e.g., diagnosis) variables, environmental measures, direct behavioral assessments, and multiple, theoretically relevant occasions of study into classic twin and family studies. We highlight contemporary techniques for identifying specific chromosomal regions associated with behavioral patterns, and the importance of considering nonmendelizing genetic influences when discerning the panorama of genetic influences on behavior.
Adolescent↗
Behavioral genetics '97: ASHG statement. Recent developments in human behavioral genetics: past accomplishments and future directions.
The field of behavioral genetics has enormous potential to uncover both genetic and environmental influences on normal and deviant behavior. Behavioral-genetic methods are based on a solid foundation of theories and methods that successfully have delineated components of complex traits in plants and animals. New resources are now available to dissect the genetic component of these complex traits. As specific genes are identified, we can begin to explore how these interact with environmental factors in development. How we interpret such findings, how we ask new questions, how we celebrate the knowledge, and how we use or misuse this knowledge are all important considerations. These issues are pervasive in all areas of human research, and they are especially salient in human behavioral genetics.
Adoption↗
At issue: genes, experience, and chance in schizophrenia--positioning for the 21st century.
Genetic factors make important contributions to the etiologies of schizophrenia. The mode of familial inheritance remains unknown, but it is highly likely that multiple genes and idiosyncratic environmental factors are involved. Rapidly evolving genetic technologies have been applied in the genetic analysis of schizophrenia, and several genomic regions have been posited as harboring susceptibility genes. Currently, the strongest evidence implicates chromosomes 6 and 8, but these linkages are not yet confirmed. In this article we discuss genetic risk factors, gene-environment interaction, the feasibility of genetic testing, psychiatric genetic counseling, and the dangers of genetic discrimination as they apply to schizophrenia. We also address and correct specific misconceptions about the genetics of schizophrenia held by many in the scientific community and in the media, and discuss a blueprint for future genetic research and informed dissemination of findings to the public and to lawmakers.
Diseases in Twins↗
HIV/AIDS risks as a consequence of schizophrenia.
Given both the rapid rise in the prevalence of HIV infection among adolescent and adult males (0.6%) and females (0.1%) in the United States from 1984 to 1992 and the associations among HIV, injection drug abuse, homosexuality, and sexual promiscuity, it is important to determine whether individuals diagnosed with schizophrenia are at a higher than average risk of HIV infection. Stereotypes from the recent past about sexuality in both male and female patients were examined as an integral part of a literature review. Data from a dozen or so studies conducted since 1990 confirm and strengthen the impressions that persons with schizophrenia should be considered a group with a much higher than average risk for developing HIV/AIDS and that they have special needs for protection as a public health measure. Mental health service providers need to be aware of these findings.
Acquired Immunodeficiency Syndrome↗
Schizophrenia genetics at the millennium: cautious optimism.
As the new millennium approaches, research into the genetic aspects of schizophrenia has already made an impressive start toward an integrated model which is discovering roles for genetic agents, environmental agents and experiences, and chance factors. The best model follows that proposed for understanding such complex diseases as coronary artery disease and diabetes. Genetic information has come from both genetic epidemiology and molecular genetics. Evidence for gene regions on 6p and 8p gives the strongest support for harboring schizophrenia susceptibility genes, based on international collaborative studies that "generally" replicate one another; evidence for regions on 3p, 5q, 9p, 20p, and 22q, while less compelling, will encourage focused work. Determining the steps between the regions and the phenotype will challenge the next generation of scientists.
Chromosomes↗
Legacy of German psychiatric genetics: hindsight is always 20/20.
The history of psychiatric genetics is informed by this paper, which serves to review the legacy of German psychiatric genetics and its antecedents during the twentieth century. It also serves as an introduction to two new annotated abstracts of basic research papers on family studies of schizophrenia by Ernst Rüdin in 1916 and by Bruno Schulz in 1932, submitted by Kenneth Kendler and Edith Zerbin-Rüdin, together with another paper by them describing the origin and activities of Rüdin's Munich School of Psychiatric Genetics (1917-1945). Our paper also introduces an invited critical summary of the work of Ernst Rüdin by his biographer Matthias M. Weber, a medical historian working in the Historical Archives of the Clinical Institute of the Max Planck Institute of Psychiatry in Munich. We raise a number of bioethical questions in the context of the uses and misuses made of genetic information in the service of the Nazi programs of eugenics, "euthanasia," and genocide.
Adolescent↗
Heritability of MMPI personality indicators of psychopathology in twins reared apart.
This report presents Minnesota Multiphasic Personality Inventory (MMPI) findings from the Minnesota Study of Twins Reared Apart. Data from 65 unique pairs of monozygotic twins reared apart (MZA) and 54 unique pairs of dizygotic twins reared apart (DZA) were analyzed. As in other results from this sample, MZA twins evidenced substantial similarity, highlighting the influence of shared genes. Biometric modeling yielded estimates of heritability for the MMPI's standard validity and clinical scales and for the Wiggins content scales ranging from .26 to .62 (M = .44), echoing previous findings from the twin and adoption literature on personality. The pattern of MZA and DZA correlations suggested nonadditive genetic effects for 3 MMPI scales. Multivariate profile analyses also suggested genetic influence on both profile elevation and shape.
Adolescent↗
Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22.
Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis. In order to replicate these results, we performed the transmission test for linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their 226 parents. Evidence for potential linkage disequilibrium was obtained between schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P = 0.02). The results of our study suggest a detectable oligogenic gene in a multigene system for schizophrenia closely linked to D22S278 on the long arm of chromosome 22. If confirmed by others, this finding could lead to the identification of a schizophrenia susceptibility gene.
Adolescent↗
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↗
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↗
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↗
Normal personality characteristics in identical twins discordant for schizophrenia.
The authors examined normal personality characteristics of monozygotic (MZ) twins discordant for schizophrenia. Twenty pairs of discordant twins were analyzed; 11 pairs of MZ twins concordant for schizophrenia served as a comparison group. Personality was assessed using the Multidimensional Personality Questionnaire (MPQ; A. Tellegen, 1995). Among discordant twin pairs, twins with schizophrenia were more deviant than normal co-twins on all but 4 of the MPQ's scales. Analysis of MZ twin correlations among the discordant twin pairs revealed substantial erosion of personality similarity as compared to normal individuals, although a cluster of scales related to Constraint/Psychoticism showed significant correlations. The results highlight striking personality divergence related to nonshared environmental influences. It is not possible to determine the point at which the twins diverged, although previous findings from this sample suggest that the observed personality differences may reflect effects of schizophrenia on normal personality.
Adult↗
Schizophrenia: sex and familial morbidity.
Several recent studies have found a greater risk of schizophrenia among the relatives of female schizophrenic probands than the relatives of male schizophrenic probands. These results are contradictory to those of earlier studies. The current investigation, using family data collected in the 1950's and 1960's in Sweden, did not find a difference in the risk of schizophrenia among the relatives of male and female schizophrenic probands. However, significantly more relatives of female probands than relatives of male probands had manic-depressive psychosis. These findings suggest that the earlier studies may have included some female schizophrenic probands who would be classified as having manic-depression by modern criteria.
Female↗
Complications to the complex inheritance of schizophrenia.
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Humans↗
Schizophrenia epigenesis: past, present, and future.
Sociopolitical and ideological attacks on the various genetically oriented programs of research into the causes of schizophrenia, even when well-motivated to prevent genetic discrimination in all its forms, endangers the enterprise. Although there have been no replicated successes in finding genes linked or associated to markers for schizophrenia yet, the solid foundation for the fact that genetic factors are importantly involved in the etiology of schizophrenia derives from replicated studies using the strategies of genetic epidemiology--families, twins, adoptees. The models to emulate in schizophrenia research should follow the paths of researchers on coronary artery disease, diabetes, and Alzheimer's disease. All are complex diseases with multifactorial and multigenic components. Even when the necessary genotype is present, it may not be expressed as clinical disease at the phenotypic level.
Diseases in Twins↗