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M T Tsuang

Publications and source records attributed to M T Tsuang.

At least 145 records · Page 8Linked to original sources

Measuring diagnostic accuracy in the absence of a "gold standard".

OBJECTIVE: As the nation debates issues of national health care reform, psychiatrists seek equal status with other medical colleagues. To defend psychiatry in the national arena, the accuracy of psychiatric diagnoses must be measured. Indexes of accuracy such as sensitivity and specificity provide valuable information, yet they are rarely computed because there is no "gold standard" with which to compare them. The goal of this article is to show how this problem can be overcome and to encourage nosologists to use accuracy statistics in assessing the adequacy of psychiatric diagnoses. METHOD: The authors reviewed the literature on medical decision making to find methodological approaches to assessing diagnostic accuracy in the absence of gold standards. RESULTS: A lack of such standards is not unique to psychiatry and has been addressed with a variety of novel analytic procedures. Although these methods differ in many respects, each recognizes that the conventional 2 x 2 table of interrater agreement does not provide enough data for estimating diagnostic accuracy. After defining the data needed, each method provides a mathematical model that estimates accuracy statistics and the prevalence of a disorder. Most of these methods are variants of latent class analysis. The authors reanalyzed data from one of the reviewed papers to show that similar inferences about accuracy of diagnoses could be drawn from a conventional latent class analysis. CONCLUSIONS: There are potential pitfalls in using latent structure methods, but their cautious use would provide valuable information for psychiatric nosology. These methods supplement, but do not replace, data about outcome, family history, laboratory studies, and other validating criteria in making accurate diagnoses.

Female↗

Gender differences in age at onset of schizophrenia.

Numerous studies have found that male schizophrenic patients have earlier ages at onset than females. However, none of these studies have corrected the observed ages for known gender differences in the age distribution of the population. Using a pre-existing data set, we applied a non-parametric method to correct the male and female distributions of observed age at onset for sex-specific age distributions. The distributions of observed age at onset indicated earlier onset among males. After correction, the age-at-onset distributions shifted toward older ages, but the difference between males and females remained statistically significant. Thus, gender differences in the age at onset of schizophrenia are not artefactual.

Adult↗

Unipolar relatives in bipolar pedigrees: a search for indicators of underlying bipolarity.

In an effort to identify features indicative of underlying bipolarity within the unipolar relatives of bipolar probands, we compared unipolar relatives of bipolars with unipolar relatives of unipolars. Using data from the Collaborative Study of the Psychobiology of Depression, we compared a number of demographic and clinical features individually, and then developed a logistic regression model for the differences found. Unipolar relatives of bipolars were somewhat more likely to be male and to have subthreshold bipolar features, and less likely to have panic symptoms. In addition, they had a small but significant decrease in the number of depressive symptoms and a large decrease in all treatment indicators. A multiple logistic regression model for these differences was highly significant, but had limited ability to discriminate between the two groups. These differences are not large enough to effectively discriminate between the groups for the purposes of classification. These particular results may result from a number of factors, most likely the choice of comparison group. Nonetheless, the work demonstrates a potential method for the construction of caseness indices for use in genetic studies of bipolar and other psychiatric disorders.

Adult↗

A strategy for assembling samples of adult twin pairs in the United States.

In this paper we develop a methodology for the identification of large numbers of U.S. adult twin pairs. Data for this study derive from the U.S. Department of Defense and the Vietnam Era Twin (VET) Registry. The Department of Defense identified potential male twins (n = 10,002) using a computerized record linkage algorithm based on the same last name, same date of birth, and the same first five digits of the Social Security number. Twinship was confirmed by comparison with the Vietnam Era Twin Registry. We developed a logistic regression model that predicts the probability that a paired record identifies twins based on the absolute difference in the last four digits in the Social Security number, the age of issuance of the Social Security number, and the frequency of occurrence of the last name. We used the estimated coefficients derived from this regression model to assign predicted probabilities of being a twin to each matched record. There is a close correspondence between the observed and expected number of twins when evaluated across deciles of predicted probabilities of being a twin; the value of the Harrell's c index (c = 0.68 +/- 0.0004) indicates the overall predictive accuracy of the regression equation. The results from this study demonstrate the feasibility of identifying adult male-male twin pairs from any large computerized database that contains name, date of birth and Social Security number. However, the selection criteria used in the creation of the computer database must be clearly specified to avoid constructing a biased sample of twins.

Adult↗

Do genes influence exposure to trauma? A twin study of combat.

Data from 4,029 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975) were used to examine genetic and non-genetic factors that influence wartime exposure to traumatic events. Specific events examined were volunteering for service in Vietnam, actual service in Southeast Asia, a composite index of 18 combat experiences, and information from military records about being awarded combat decorations. Correlations within monozygotic (MZ) and dizygotic (DZ) twin pairs for volunteering for service in Vietnam were 0.40 and 0.22, respectively. For actually serving in Southeast Asia, the MZ correlation was 0.41 and the DZ correlation was 0.24. Analysis of twin pairs in which both siblings served in Southeast Asia (n = 820) demonstrated a correlation for self-reported combat experiences within MZ and DZ pairs of 0.53 and 0.30, respectively. Heritability estimates ranged from 35 to 47%. The family environment did not have a significant effect on any of the variables. Analyses of data from military records regarding being awarded a combat decoration provided very similar results to those found for self-reported combat experiences.

Adult↗

Pregnancy/delivery complications and psychiatric diagnosis. A prospective study.

We examined the hypothesis that pregnancy and delivery complications result in increased risk for the development of psychiatric disorders. The study sample included 1068 pregnancies classified as chronic fetal hypoxia, other complications, preterm birth, or normal pregnancy/delivery that had initially been studied prospectively from the prenatal period through age 7 years. Subjects were recontacted (ages 18 to 27 years) and lifetime psychiatric diagnoses made with the Diagnostic Interview Schedule. Preterm subjects had significantly higher rates of cognitive impairment. Subjects with chronic fetal hypoxia had higher rates of both cognitive impairment and psychotic disorders, although these differences failed to reach statistical significance due to the small number of cases. With these exceptions, the data did not support the hypothesis that rates of psychiatric disorders are higher among subjects born with complications of pregnancy and delivery than among normal controls born without complications.

Adolescent↗

Estimating age at onset distributions: the bias from prevalent cases and its impact on risk estimation.

Since many disorders have a variable age at onset, knowing the age at onset distribution of a disease facilitates epidemiologic analyses in several ways. The age at onset distribution is commonly used to estimate morbidity risks or the recurrence risks in genetic counseling. Unfortunately, estimation of a disease's age at onset distribution is not straightforward. The observed age at onset distribution obtained from prevalent cases is usually used in these epidemiologic analyses. Through simulation studies, we show that, in certain situations, the observed age at onset distribution has a non-negligible downward bias. This bias can lead to a substantial underestimation of the morbidity risk or the recurrence risk. The simulations also demonstrate that a non-parametric approach for correcting the age at onset distribution works well even when mortality increases after onset. The results have implications for diseases that have adult onset and/or increased mortality after onset. We suggest that researchers should use corrected age at onset distributions, rather than relying on observed distributions, in the calculation of either morbidity risks or recurrence risks.

Adolescent↗

Identification of the phenotype in psychiatric genetics.

Statistical procedures and molecular genetic techniques have attained a fine degree of resolution. Their ability to find disease genes has revolutionized medicine and raised hopes for breakthroughs in psychiatry. However, such breakthroughs may require an equally discriminating nosology. A psychiatric genetic nosology seeks to classify patients into categories that correspond to distinct genetic entities by addressing the problem of diagnostic accuracy: the degree to which a diagnosis correctly classifies people with and without a putative genetic illness. We review methods that deal with misclassification in genetic studies. These are clinical and epidemiological approaches that deal directly with how to define the observable manifestation of a putative genotype. We discuss two groups of methods: those that use known phenotypes and those that design new phenotypes.

Aged↗

A family study of self-reported personality traits and DSM-III-R personality disorders.

Personality traits and DSM-III-R personality disorders of first-degree relatives of patients with psychoses were studied using the NEO Five-Factor Inventory (NEO-FFI) and the Personality Diagnostic Questionnaire-Revised (PDQ-R), two self-report instruments. The relatives were compared on their scores for the five personality factors in the NEO-FFI, the prevalence of individual DSM-III-R personality disorders, and their scores for each personality disorder scale in the PDQ-R. The results suggest that there is no difference in personality traits and prevalence of personality disorders, including schizophrenia spectrum disorders, when relatives of patients with schizophrenia, bipolar disorder, and major depression are compared to each other. Relatives of patients with "atypical psychosis," psychotic disorders that do not meet DSM-III-R criteria for any specific nonorganic psychotic disorder, may be a distinctive group.

Adult↗

Haloperidol response and plasma catecholamines and their metabolites.

Eleven acutely psychotic patients with schizophrenia or schizoaffective disorder underwent a 5-7 day drug-washout period (with lorazepam allowed) prior to participating in a 6-week controlled dose haloperidol trial. Patients were evaluated longitudinally with clinical ratings and with plasma measures of the catecholamines dopamine (pDA) and norepinephrine (pNE) and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG). All patients exhibited clinical improvement with haloperidol; the decrease in their Brief Psychiatric Rating Scale (BPRS) scores ranged from 32 to 89%. Measures of pHVA increased within the first week of treatment and returned to baseline by week 5. The pattern of change of pDA resembled that of pHVA. The pattern of change of pNE and pMHPG revealed a decrease over the course of treatment. The early increase and the subsequent decrease in pHVA were strongly correlated with improvement in positive symptoms on the BPRS. These data are consistent with previous reports on the change in pHVA and pMHPG during clinical response to haloperidol. The data on change of pDA and pNE further describe the nature of the biochemical response to this drug.

Adult↗

Gender and mortality in schizophrenia: do women act like men?

The effect of gender on mortality was explored for a sample of DSM-III diagnosed schizophrenics followed for up to 42 years. The data for 332 cases and 304 matched normal controls were from the retrospective cohort family studies, the Iowa 500 and non-500. Survival analysis and Cox regression models were used to test the effects of gender, illness status and their interaction on the risks for natural and unnatural deaths. The control men experienced significantly more unnatural deaths than the control women, which was not found for schizophrenic men and women. The unnatural death rate among schizophrenic women was similar to the rate for schizophrenic and control men, and significantly higher than for control women during the early phase of the illness. Findings suggest that some factors that predict suicide may be similar for schizophrenic women and men.

Adult↗

Efficiency of diagnostic criteria for attention deficit disorder: toward an empirical approach to designing and validating diagnostic algorithms.

Using structured psychiatric interviews, 73 attention deficit disorder (ADD) patients, 26 psychiatric control patients, 26 normal controls, and all available first degree relatives of these index children were examined. ADD subgroups with and without comorbid psychiatric disorders did not differ on rates of specific ADD symptoms. The construct of ADD is internally consistent as measured by Cronbach's alpha. The diagnostic efficiency of individual items is presented. A receiver operating characteristic-based procedure is used to create an ADD diagnostic algorithm that is more efficient in discriminating ADD children from controls than the DSM-III-based clinical diagnosis. Cross-validation with family study data shows this procedure to be superior to the procedure used for the DSM-III-R diagnosis. The results show that proponents of conditional probability and receiver operating characteristic analyses are correct in asserting that the examination of symptom combinations may result in better diagnostic algorithms.

Algorithms↗

Convergence of the Child Behavior Checklist with structured interview-based psychiatric diagnoses of ADHD children with and without comorbidity.

We evaluated the convergence of CBCL scales with the diagnosis of ADHD and comorbid disorders in 133 ADHD and 118 normal control boys, aged 6-17 years old. We evaluated the strength of association between each CBCL scale and structured-interview derived diagnoses with Total Predictive Value (TPV) and the odds-ratio (OR). Excellent convergence was found between the CBCL Attention Problems scale with the diagnosis of ADHD, between the Delinquent Behavior scale and the diagnosis of CD, and between the Anxiety/Depression scale and the diagnoses of Anxiety Disorders. These findings indicate that the CBCL could serve as a rapid and useful screening instrument to identify comorbid and non-comorbid cases of ADHD.

Adolescent↗

The role of gender in understanding the familial transmission of schizoaffective disorder.

The purpose of this study was to test the effect of gender on the familial risk for schizophrenia and affective disorders in probands with schizoaffective disorder. The sample consisted of 42 DSM-III schizoaffective probands and 149 first-degree relatives from the retrospective cohort family studies, the Iowa 500 and non-500. Survival analysis estimated differences in morbidity risks, analysed by sex of proband and of relative. Findings showed that, among probands, relatives of females had significantly higher rates of schizophrenia and unipolar disorder than relatives of males. Further, among relatives, males were at significantly higher risk for schizophrenia spectrum disorders than females. Results were similar when probands were subdivided into their primary symptom patterns, that is 'mainly schizophrenic' or 'mainly affective', as well as by 'schizoaffective, depressed' or 'schizoaffective, manic'. Implications for the taxonomy of schizoaffective disorder suggest a stronger relationship with schizophrenia, although the relationship with affective disorder remains unclear.

Adolescent↗

Family history models of alcoholism: age of onset, consequences and dependence.

The association of a family history of alcoholism to susceptibility to alcoholism has been well documented over the past 3 decades. The classification of a family history of alcoholism commonly involves the division of subjects into family history positive and negative groupings. However, diverse definitions are used to define positive family histories. These diverse definitions of family alcoholism impede the comparison of results from different studies. The present study evaluates several classification schemes and compares them with a new method for the analysis of family patterns of alcoholism (FPA). A sample of 220 male alcoholic veteran inpatients were assessed for age of onset of alcoholism, consequences of drinking and the severity of their dependence. Multiple regression equations were estimated for several dichotomous family history models and each model was evaluated against a comparable FPA model that included the same family members. Comparisons of the classification models with the equivalent FPA analysis model facilitated comparisons of the contribution of each family history designation to changes in amount of explained variance. In all instances, the FPA analyses explained more variance than did the comparable dichotomous family history models. In addition, the FPA analyses reveal the relative explanatory power of each family member and indicate that maternal relatives often have a more important contribution than has been indicated previously.

Adult↗

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↗