Biomedical subjects

M T Tsuang

Publications and source records attributed to M T Tsuang.

At least 19 recordsLinked to original sources

PubMed1992

Linkage studies of schizophrenia: a stimulation study of statistical power.

In planning for a linkage study, it is important to determine the number of pedigrees needed to show linkage. Our study overcomes some of the limitations of previous power studies by simulating multigeneration pedigrees to be compatible with the demographic and genetic epidemiological features of schizophrenia; these are variable age at onset, reduced fertility, and increased mortality after onset. We evaluate the power of these pedigrees by first simulating an ascertainment rule requiring at least three ill family members per pedigree and then simulating the trait and marker genotypes according to a single gene model known to fit epidemiological family study data. Our analysis allows for incomplete and age-dependent penetrance, phenocopies, and interpedigree heterogeneity. We present the power to detect linkage at several lod score thresholds since the multiple tests and phenotypic models required for complex diseases may necessitate using a lod score significance level greater than three. The sample size needed to achieve sufficient power is feasible if 50% of the pedigrees are linked to the marker under test. It may not be feasible to detect linkage if only 25% of the pedigrees are linked, even if a very closely linked marker is used. Our results indicate that to be certain of adequate statistical power, linkage analyses of schizophrenia will require very large samples that do not have a marked degree of genetic heterogeneity.

Adult↗

PubMed1992

Elementary methods for the analysis of dichotomous outcomes in unselected samples of twins.

This paper presents an elementary statistical method for analyzing dichotomous outcomes in unselected samples of twin pairs using stratified estimators of the odds ratio. The methodology begins by first randomly designating one member of each twin pair as an "index" twin and the other member as the "co-twin." Stratifying on zygosity, odds ratios are used to measure the association between disease in the index twin and disease in the co-twin. From these zygosity-specific tables we calculate the Woolf-Haldane estimator of the common odds ratio (psi F, the weighted average of the zygosity-specific odds ratios), the Mantel-Haenszel test statistic (chi 2M-H) for the common odds ratio, and a test (chi 2G) for the difference in the zygosity-specific odds ratios. In this application, psi F provides an estimate of the familial association for disease and the accompanying chi 2M-H provides a test of the null hypothesis, psi F = 1 (i.e., there is no evidence for a familial influence on disease). The chi 2G is a test of the null hypothesis that psi MZ = psi DZ; a significant value for chi 2G suggests a genetic influence on disease (assuming that the observed odds ratios follow a pattern where psi MZ greater than psi DZ). A new test statistic (chi 2c) is proposed that incorporates the expectation that psi MZ = psi 2DZ under a purely additive genetic model with no common environmental effects. A significant value of chi c2 indicates that the different odds ratios across zygosity are partly due to common environmental influences. Conversely, a nonsignificant value of chi 2c is an indication that the zygosity-specific odds ratios are due solely to additive genetic effects and not to common environment. This basic approach is extended to examine the effects of measured indicators of the specific environment and the assessment of certain forms of gene by environment interaction. All of the methods are easily understood, highly flexible, readily computed using a hand calculator, and incorporate the inherent genetic information contained within twin samples.

Data Interpretation, Statistical↗

PubMed1992

Gender and the familial risk for schizophrenia. Disentangling confounding factors.

Recent studies of the effect of gender on the familial risk for schizophrenia have shown that relatives of females have a higher risk for schizophrenia than relatives of males. This study attempts to explain the effect by examining factors found to differentiate schizophrenic men and women and found to be related to the familial risk for schizophrenia. Cox proportional hazard regression model was used to examine the simultaneous effects of age at onset, season of birth, and premorbid history, controlled for symptoms that have been found to differ by gender (dysphoria, paranoia, and flat affect). Results showed that the effect of gender on the transmission of schizophrenia could not be explained by gender differences in age at onset, symptom expression, premorbid history, and winter birth. However, premorbid history had an effect on familial risk independent of gender, indicating that probands with a poor premorbid history had a lower familial risk for schizophrenia than those with a good premorbid history. Implications of the findings are discussed.

Adult↗

PubMed1992

Attention/information-processing factors in psychotic disorders. Replication and extension of recent neuropsychological findings.

The scores of attention/information-processing measures derived from neuropsychological testing of 34 chronic psychotic, primarily schizophrenic patients were subjected to a principal components analysis. Measures were chosen a priori on the basis of a previous factor-analytic study by A.F. Mirsky (1987, Behavioral and psychophysiological markers of disordered attention, Environmental Health Perspectives 74:191-199). The factor pattern in the present study was strikingly similar to that reported by Mirsky on a largely nonpsychotic sample. In both studies, four factors emerged that may be identified as: a) perceptual motor speed; b) mental control (numerical-mnemonic); c) flexibility; and d) vigilance. This replication provides support for previously postulated types of attention and suggests that schizophrenic and other psychotic disorders are not associated with atypical organization of attention/information-processing dimensions. The authors discuss questions raised by Mirsky's previous results in light of the present findings. In particular, it was concluded that the flexibility factor requires further clarification. Implications of the findings for clinical evaluation and research in schizophrenia are discussed as well.

Attention↗

PubMed1992

Using vulnerability indicators to compare conceptual models of genetic heterogeneity in schizophrenia.

The search for indicators of vulnerability has been important in schizophrenia research, but, as in many areas, progress has been impeded due to the heterogeneity of schizophrenic disorders. How one conceptualizes the observed heterogeneity is dependent upon the particular genetic model to which one subscribes. In this article, we delineate several models that may account for the distributions of vulnerability indicators in groups of schizophrenic patients and their ill and well relatives. We present these models for heuristic purposes so that they may serve to guide the interpretation of data with respect to the issue of teasing apart familial and nonfamilial environmental components of putative vulnerability indicators. It is suggested that investigators will profit by: a) efforts to combine psychiatric genetic paradigms in order to maximize the yield of family study data, and b) thinking in terms of comparing the ability of different models to account for research findings.

Data Interpretation, Statistical↗

PubMed1992

Contested boundaries of bipolar disorder and the limits of categorical diagnosis in psychiatry.

The authors' primary objective is to outline the phenomenology, importance, and available data on issues concerning the boundaries between bipolar disorder and diagnoses such as schizophrenia, unipolar depression, and personality disorders. In addition, by illuminating the many difficulties with the boundaries of one of psychiatry's more robust diagnoses, they hope to awaken in the reader a healthy skepticism about current psychiatric nosology. For a topic of this scope, a literature review must be selective. For each boundary area, a mixture of classic and recent papers covering a range of validating criteria is included whenever possible. Good summary data are cited when available, as are a selection of relevant theoretical papers. The review indicates that current diagnostic criteria for bipolar disorder are generally reasonable, but there are many problem areas, most of which cannot be solved by changes in criteria. Notable among these are 1) the possibility of future manic episodes in unipolar disorder, 2) schizoaffective disorder, bipolar type, and 3) borderline personality disorder with prominent mood swings. The disputes concerning the boundaries of bipolar disorder illustrate the limitations of categorical diagnosis which result from the implementation of diagnostic criteria, the criteria themselves, the fundamental nosologic process, and the phenomena themselves. If these limitations are to be extended, it may be necessary to explore alternative ways of defining psychiatric diagnoses for different settings in research and clinical practice.

Bipolar Disorder↗

PubMed1992

Prediction of outcome in mania by mood-congruent or mood-incongruent psychotic features.

OBJECTIVE: The aim of this study was to determine the significance of mood congruence of psychotic features in mania as a predictor of outcome. METHOD: Fifty-four patients with bipolar disorder were followed prospectively for 4 years after recovery from an episode of mania with psychotic features. Assessments of residential and occupational status, interepisode symptoms, and episode recurrences were made at 6 and 48 months after recovery. Categorical outcomes were evaluated by logistic regression and recurrence risk with survival analysis. RESULTS: Mood-incongruent psychotic features during the index manic episode predicted a shorter time in remission at 4 years (hazard ratio = 2.6), and Schneiderian first-rank symptoms predicted poor residential status at 4 years (odds ratio = 20.1). CONCLUSIONS: Differentiation of mood congruence of psychotic features in mania evidently has prognostic validity and, therefore, has utility as a nosological characteristic.

Adult↗

PubMed1991

Evidence of familial association between attention deficit disorder and major affective disorders.

With the use of family study methods and assessments by "blinded" raters, we tested hypotheses about patterns of familial association between DSM-III attention deficit disorder (ADD) and affective disorders (AFFs) among first-degree relatives of clinically referred children and adolescents with ADD (73 probands, 264 relatives) and normal controls (26 probands, 92 relatives). Among the 73 ADD probands, 24 (33%) met criteria for AFFs (major depression, n = 15 [21%]; bipolar disorder, n = 8 [11%]; and dysthymia, n = 1 [1%]). After stratification of the ADD sample into those with AFFs (ADD + AFF) and those without AFF (ADD), familial risk analyses revealed the following: (1) the relatives of each ADD proband subgroup were at significantly greater risk for ADD than were relatives of normal controls; (2) the age-corrected morbidity risk for ADD was not significantly different between relatives of ADD and ADD + AFF (27% vs 22%); however, these two risks were significantly greater than the risk to relatives of normal controls (5%); (3) the risk for any AFF (bipolar disorder, major depressive disorder, or dysthymia) was not significantly different between relatives of ADD probands and ADD + AFF probands (28% and 25%), but these two risks were significantly greater than the risk to relatives of normal controls (4%); (4) ADD and AFFs did not cosegregate within families; and (5) there was no evidence for nonrandom mating. These findings are consistent with the hypothesis that ADD and AFFs may share common familial vulnerabilities.

Adolescent↗

PubMed1991

Neuropsychological probes of fronto-limbic system dysfunction in schizophrenia. Olfactory identification and Wisconsin Card Sorting performance.

Schizophrenic patients and normal control subjects took the University of Pennsylvania Smell Identification Test (UPSIT) and Wisconsin Card Sorting Test (WCST) as dual neuropsychological 'probes' of orbitofrontal (OF) and dorsolateral (DL) prefrontal function respectively. Patients were significantly impaired on both tasks compared to controls. UPSIT and WCST performance were uncorrelated in patients but were positively correlated in controls. The lack of correlation found in the patients suggests that the tasks may be tapping independent dysfunctions in schizophrenia reflecting differential impairment in fronto-limbic brain systems. Individual profiles of preserved and impaired performance on the UPSIT and WCST suggested that three schizophrenic patients had OF dysfunction, five had DL dysfunction and seven had a generalized (OF and DL) frontal system dysfunction. The reduced ability of schizophrenic patients to identify odors was largely independent of many deficits or confounds typically associated with schizophrenia and did not appear to be simply a function of generalized deficit. These data are preliminary and require replication with larger samples and validation with other measures of fronto-limbic system dysfunction.

Adolescent↗

PubMed1991

Wisconsin Card Sorting Test performance over time in schizophrenia. Preliminary evidence from clinical follow-up and neuroleptic reduction studies.

Two groups of schizophrenic patients took the Wisconsin Card Sorting Test (WCST) in separate follow-up studies; a naturalistic clinical follow-up (n = 12, study 1) and a neuroleptic reduction study (n = 10, study 2). 11 of 22 subjects (50%) performed well on the task at one or both time points. In each study no group differences were found between time 1 and time 2 performance on three WCST variables. However, correlational analyses revealed considerable within-subject variation on the WCST in the study 1 sample, which was composed of younger and more acute patients than those in study 2. This variation was present despite within-subject stability on the WAIS-R Vocabulary and Block Design subtests. For the sample combined, a trend was found (p = 0.12) linking better WCST performance at either time period with higher WAIS-R Vocabulary scores. This intra-subject variability may reflect fluctuations in neuropsychological performance in schizophrenics who maintain the residual capacity to do the task. These findings highlight the importance of longitudinal studies of neuropsychological functioning in schizophrenia. Studies of larger samples are needed to confirm these initial results.

Activities of Daily Living↗

PubMed1991

Separation of DSM-III attention deficit disorder and conduct disorder: evidence from a family-genetic study of American child psychiatric patients.

Using family study methodology and assessments by blind raters, this study tested hypotheses about patterns of familial association between DSM-III attention deficit disorder (ADD) and antisocial disorders (childhood conduct (CD) and oppositional disorder (OPD) and adult antisocial personality disorder) among 457 first-degree relatives of clinically referred children and adolescents with ADD (73 probands, 264 relatives), psychiatric (26 probands, 101 relatives) and normal controls (26 probands, 92 relatives). Among the 73 ADD probands, 33 (45%) met criteria for OPD, 24 (33%) met criteria for CD, and 16 (22%) had no antisocial diagnosis. After stratifying the ADD sample into those with CD (ADD + CD), those with OPD (ADD + OPD) and those with neither (ADD) familial risk analysis revealed the following: (1) relatives of each ADD proband subgroup were at significantly greater risk for ADD than relatives of both psychiatric and normal controls: (2) the morbidity risk for ADD was highest among relatives of ADD + CD probands (38%), moderate among relatives of ADD + OPD (17%) and ADD probands (24%) and lowest among relatives of psychiatric and normal controls (5% for both); (3) the risk for any antisocial disorder was highest among relatives of ADD + CD (34%) and ADD + OPD (24%) which were significantly greater than the risk to relatives of ADD probands (11%), psychiatric (7%) and normal controls (4%); and (4) both ADD and antisocial disorders occurred in the same relatives more often than expected by chance alone. Although these findings suggest that ADD with and without antisocial disorders may be aetiologically distinct disorders, they are also consistent with a multifactorial hypothesis in which ADD, ADD + OPD and ADD + CD fall along a continuum of increasing levels of familial aetiological factors and, correspondingly, severity of illness.

Adolescent↗

PubMed1991

A family-genetic study of girls with DSM-III attention deficit disorder.

OBJECTIVE: The authors evaluated family-genetic risk factors in girls with attention deficit disorder and compared these results to findings in the authors' previous study of boys with attention deficit disorder. METHOD: Twenty-one girls with attention deficit disorder and 20 normal comparison girls were consecutively ascertained from a pool of existing and new referrals from a pediatric psychopharmacology unit and a medical pediatric unit of the same urban hospital. First-degree relatives of the attention deficit disordered girls (N = 69) and of the normal girls (N = 71) were also assessed. Both groups of girls and their relatives were evaluated on the basis of structured diagnostic interviews conducted by raters who were blind to the clinical status of the probands. RESULTS: The relatives of the girls with attention deficit disorder had higher risks for attention deficit disorder, antisocial disorders, major depression, and anxiety disorders. The higher risk for attention deficit disorder could not be accounted for by gender or generation of relative, age of proband, social class, or family intactness. These findings are highly consistent with the findings in the authors' previous study of boys with attention deficit disorder, which was conducted with identical methods. CONCLUSIONS: This study provides further support for the validity of the diagnosis of attention deficit disorder in girls and suggests that the genders share a common biological substrate.

Adolescent↗

PubMed1991

Familial association between attention deficit disorder and anxiety disorders.

BACKGROUND AND METHOD: This study tested hypotheses about patterns of familial association between attention deficit disorder (ADD) and anxiety disorders among 356 first-degree relatives of 73 clinically referred children with ADD and 26 normal comparison children. Through structured diagnostic interviews with trained raters, relatives were assessed for adult and childhood psychopathology. After stratifying the sample of ADD probands into those with anxiety disorders and those without, the authors examined patterns of aggregation of ADD and anxiety disorders in the relatives of these probands as well as in the relatives of the normal comparison subjects. RESULTS: Familial risk analyses revealed that 1) familial risk for anxiety disorders was higher among all ADD probands than among the normal subjects; 2) familial risk for ADD was similar in the relatives of the ADD probands and of the probands with ADD and anxiety disorder; 3) the relatives of the ADD probands with and without anxiety disorders were at greater risk for ADD than the relatives of the normal subjects; 4) the risk for anxiety disorders was two times higher in the relatives of the probands who had ADD with anxiety disorder than in those of the ADD probands without anxiety disorders; and 5) there was a tendency for ADD probands' relatives who themselves had ADD to have a higher risk for anxiety disorders than ADD probands' relatives who did not have ADD (cosegregation). CONCLUSIONS: The results were most consistent with the hypotheses indicating that ADD and anxiety disorders segregate independently in families.

Adolescent↗

PubMed1991

Morbidity risks of schizophrenia and affective disorders among first-degree relatives of patients with schizoaffective disorders.

Of 510 patients consecutively admitted and diagnosed as schizophrenic, 310 who failed to meet research criteria for schizophrenia were labelled as having 'atypical psychosis'. This heterogeneous group of patients was then subtyped into more homogeneous subgroupings according to their clinical characteristics, independent of their family data. One subgroup resembled schizophrenia, one resembled affective disorders and a third (n = 57), which did not resemble either schizophrenia or affective disorder, was defined as 'schizoaffective'. Comparing the morbidity risks for schizophrenic and affective disorders in the relatives of this schizoaffective group with those of the relatives of 'typical' groups of schizophrenia and affective disorder, showed that this group was different from those with schizophrenic and affective disorders.

Adolescent↗

PubMed1990

Outcome in Mania. A 4-year prospective follow-up of 75 patients utilizing survival analysis.

A 4-year follow-up of 75 patients was conducted to investigate outcome after recovery from an episode of mania. Predictors of an unfavorable outcome included poor occupational status prior to index episode, history of previous episodes, history of alcoholism, psychotic features and symptoms of depression during the index manic episode, male gender, and interepisode affective symptoms at 6 months' follow-up. The mortality risk during the follow-up period was 4%. The identification of specific risk factors depended on the definition of outcome and the length of follow-up.

Adult↗

PubMed1990

Four-year follow-up of twenty-four first-episode manic patients.

Twenty-four first-episode manic patients were followed to investigate the 4-year outcome after recovery from a manic episode. Patients had no documented previous manic or depressive episodes. The presence of psychotic features during the index episode and a history of alcoholism were statistically significant predictors of a shorter time in remission. Low occupational status at baseline predicted poor global social adjustment at 4 years. Also, a larger correlation among outcome measures was found at 48 than at 6 months. The importance of controlling for presence of multiple episodes in outcome studies is emphasized.

Bipolar Disorder↗

PubMed1990

Genetic transmission of major affective disorders: quantitative models and linkage analyses.

We comprehensively reviewed 2 types of studies aimed at specifying the mode of inheritance of major affective disorders: quantitative models and linkage analyses. Quantitative models attempt to represent the genetic mechanism responsible for the familial distribution of a disorder. Despite efforts to refine models by incorporating the bipolar-unipolar distinction or the sex effect, consistent support for a specific mode of transmission has not been found. Some mixed genetic models support single major locus inheritance, but transmission probabilities do not conform to Mendelian expectations. Linkage analysis is a more powerful technique used for testing the single gene hypothesis. Linkage results have also been inconsistent, showing moderate support for an X-linked variant of bipolar-related disorder and equivocal support for linkages to Chromosomes 6 and 11. However, relatively few genetic loci have been examined. Methodological factors, genetic heterogeneity, and phenotypic heterogeneity are discussed as potential explanations for inconsistent findings.

Bipolar Disorder↗

PubMed1990

Impact of substance abuse on the course and outcome of schizophrenia.

Numerous pharmacological agents have been shown to have powerful effects on cognitive behavior. Schizophrenia-like reactions have been reported in some instances. There have also been persistent reports of drug abuse among psychiatric patients before and during hospitalization. These phenomena have led to speculation that psychoactive substances are affecting the course and outcome of psychiatric illnesses, and in particular, schizophrenia. This report first reviews the evidence for psychotomimetic effects of various drugs, and then focuses on reports of the effect that substance abuse has on the course of schizophrenia and long-term outcome. The evidence to date indicates that there is a need for a large epidemiological analysis of the interplay between drug abuse and schizophrenia as well as more intensive case studies of afflicted individuals. This discussion concludes with suggestions for improved research methods and two designs for future investigations.

Follow-Up Studies↗