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M T Tsuang

Publications and source records attributed to M T Tsuang.

At least 55 records · Page 3Linked to original sources

Maternal recall of pregnancy history: accuracy and bias in schizophrenia research.

Most investigations that report a positive association between obstetric complications and schizophrenia have been case-control studies that are often based on long-term maternal recall of events during pregnancy. We tested the hypothesis that mothers of adult offspring with schizophrenia or other psychoses systematically overreport obstetric complications compared with mothers of unaffected offspring. Subjects were selected from the New England cohorts of the National Collaborative Perinatal Project, a large prospective cohort with well-documented records of pregnancy and delivery. Mothers of 39 offspring with psychosis and 39 control offspring were recontacted and completed a structured interview regarding their pregnancy history. Accuracy of maternal recall varied greatly in relation to the type of pregnancy event, and recall was inaccurate for many specific events. For the control sample only, maternal recall of the total number of complications corresponded closely to chart information. Contrary to the study hypothesis, mothers of offspring with psychosis report fewer complications than indicated in their obstetric records, with no evidence of positive recall bias. These results suggest that previous reports of a positive association between obstetric complications and schizophrenia are not likely to have resulted from biased maternal recall.

Adult↗

Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study.

OBJECTIVE: Epidemiologic evidence linking obstetric complications to schizophrenia has been positive but inconclusive. One reason for the lack of conclusive evidence may be the inconsistency in measuring disturbances of fetal/neonatal brain development based on general obstetric markers of maternal health. The authors used data from the National Collaborative Perinatal Project to examine the relationship between schizophrenia and other nonaffective psychoses and a theoretically derived measure of hypoxic-ischemia-related fetal/neonatal complications. METHOD: Six hundred ninety-three men and women (average age 23) born to a community sample of women between 1959 and 1966 were followed up an average of 19 years after early childhood assessments. Subjects with DSM-IV schizophrenia and other nonaffective psychoses were identified using the Diagnostic Interview Schedule and best-estimate consensus diagnoses. RESULTS: Hypoxic-ischemia-related fetal/neonatal complications were associated with a doubling of the risk of developing a psychotic disorder, compared with no relevant complications (6.9% versus 1.4%). When mood disorders were excluded from the group of psychotic diagnoses, the risk of schizophrenia and other nonaffective psychoses associated with hypoxic-ischemia-related fetal/neonatal complications was strikingly elevated, compared with no relevant complications (5.75% versus 0.39%). Nonpsychotic mood disorders were unrelated to these fetal/neonatal complications. Schizophrenia and other nonaffective psychoses were most strongly associated with hypoxic-ischemia-related fetal/neonatal complications of disordered growth and development. CONCLUSIONS: The data show a strikingly elevated, graded, independent risk of schizophrenia and other nonaffective psychoses associated with this classification of antecedent hypoxic-ischemia-related fetal/neonatal complications.

Adolescent↗

Toward reformulating the diagnosis of schizophrenia.

OBJECTIVE: The authors assess implications of DSM criteria for schizophrenia by reviewing the criteria's 1) emphasis on psychotic features, 2) dissociation of symptoms from their etiology, 3) exclusive reliance on clinical features but exclusion of biological indicators, and 4) classification of schizophrenia as a discrete category. The authors then discuss alternative conceptions of schizophrenia that take into account recent data concerning its genetic and neurodevelopmental origins and its pathophysiological substrates. METHOD: The historical development of diagnostic criteria for schizophrenia is reviewed in the context of recent published data on the biology and development of schizophrenia. RESULTS: Growing evidence suggests that symptoms of psychosis may be a common end-state in a variety of disorders, including schizophrenia, rather than a reflection of the specific etiology of schizophrenia. Features occurring before the advent of psychosis that are clinical, biological, and/or neuropsychological in nature may constitute evidence of a genetic predisposition toward schizophrenia ("schizotaxia") and may provide more specific information about the genetic, pathophysiological, and developmental origins of schizophrenia. CONCLUSIONS: The success of efforts to treat and prevent schizophrenia will depend to an important extent on an accurate understanding of its causes. This goal can be furthered by conducting field trials to develop research criteria to assess the value of a developmentally sensitive, biologically informed approach to classification that would consider schizotaxia with psychosis (schizophrenia) and schizotaxia alone as distinct diagnostic conditions.

Genetic Predisposition to Disease↗

Lifetime prevalence of mood and anxiety disorders in twin pairs discordant for schizophrenia.

There have been long questions about the relationship of schizophrenia to other mental disorders. Lifetime DSM-III-R diagnoses of mood and anxiety disorders in twins with clinically diagnosed schizophrenia (n = 24) and their non-affected co-twins (n = 24) were compared with twins from pairs without schizophrenia (n = 3327) using a sample from the Vietnam Era Twin Registry. Schizophrenic probands had significantly elevated rates of all included disorders (bipolar disorder, major depression, dysthymia, generalized anxiety disorder, panic disorder, and PTSD) compared with controls (P<0.01). The odd ratios comparing co-twins of schizophrenic probands with controls was greater than three for every disorder, but did not attain statistical significance. A similar pattern was observed when analyses were restricted to only monozygotic twins (n = 12). Consistent with other studies, schizophrenics appeared to have higher rates of a range of mental disorders. Our results suggest that schizophrenia per se represents a risk factor for other psychiatric disorders, but the absence of significantly elevated risk among non-schizophrenic co-twins suggested that family environmental and/or genetic factors that contribute to risk of schizophrenia do not increase the risk of mood and anxiety disorders to the same extent that the risk of these other disorders is increased by the presence of schizophrenia.

Adult↗

Psychiatric epidemiology.

Psychiatric epidemiology is considered one of the main scientific foundations of psychiatry. This article reviews methodological issues and major studies in psychiatric epidemiology. Methods such as measures of frequency and association are discussed. Selection, observation, and confounding, the main sources of bias in epidemiological studies, are described. Types of study designs, such as cross-sectional, cohort, and case-control, are detailed. A historical perspective of major population-based and clinical studies is presented. Major findings of the Epidemiologic Catchment Area Study and the National Comorbidity Survey are also included. Finally, future directions in the field are discussed.

Adolescent↗

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion.

The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

Chromosomes, Human, Pair 10↗

Poor perception of nonverbal social-emotional cues in relatives of schizophrenic patients.

The present study compared nonverbal social perception in relatives of schizophrenic patients (n = 21) with that of normal controls (n= 19). We hypothesized that relatives would display deficits in social perception and we sought to determine the skills that are associated with this deficit. Relatives performed significantly worse than controls on the Profile of Nonverbal Sensitivity Test (PONS), despite comparable performance on skills hypothesized to be related to nonverbal social perception: visual perception, nonverbal problem solving, facial recognition, facial affect recognition, naming, social judgment, and vigilance. To further explore the relationships among these skills, we calculated correlations between the PONS score and associated skills separately within both the relative and control groups and assessed whether the values of these correlations differed between groups. Correlations that differed significantly indicated a greater association, within relatives, between slower reaction times on vigilance tasks and poor PONS performance. Further research is needed to clarify the nature of this relationship, to better characterize social perception deficits in relatives, and to determine whether these perceptual deficits are part of the genetic diathesis to schizophrenia.

Adult↗

Thalamic and amygdala-hippocampal volume reductions in first-degree relatives of patients with schizophrenia: an MRI-based morphometric analysis.

BACKGROUND: Schizophrenia is characterized by subcortical and cortical brain abnormalities. Evidence indicates that some nonpsychotic relatives of schizophrenic patients manifest biobehavioral abnormalities, including brain abnormalities. The goal of this study was to determine whether amygdala-hippocampal and thalamic abnormalities are present in relatives of schizophrenic patients. METHODS: Subjects were 28 nonpsychotic, and nonschizotypal, first-degree adult relatives of schizophrenics and 26 normal control subjects. Sixty contiguous 3 mm coronal, T1-weighted 3D magnetic resonance images of the brain were acquired on a 1.5 Tesla magnet. Cortical and subcortical gray and white matter and cerebrospinal fluid (CSF) were segmented using a semi-automated intensity contour mapping algorithm. Analyses of covariance of the volumes of brain regions, controlling for expected intellectual (i.e., reading) ability and diagnosis, were used to compare groups. RESULTS: The main findings were that relatives had significant volume reductions bilaterally in the amygdala-hippocampal region and thalamus compared to control subjects. Marginal differences were noted in the pallidum, putamen, cerebellum, and third and fourth ventricles. CONCLUSIONS: Results support the hypothesis that core components of the vulnerability to schizophrenia include structural abnormalities in the thalamus and amygdala-hippocampus. These findings require further work to determine if the abnormalities are an expression of the genetic liability to schizophrenia.

Adult↗

Interrelationship of genetic and environmental influences on conduct disorder and alcohol and marijuana dependence symptoms.

Data from the Vietnam Era Twin (VET) Registry were analyzed to explore the degree to which the same genetic and environmental factors contribute to childhood conduct disorder symptoms and to alcohol and marijuana dependence symptoms. Data on conduct disorder and alcohol and marijuana dependence were obtained from administration of the Diagnostic Interview Schedule to 1,856 monozygotic and 1,479 dizygotic male-male twin pair members of the VET Registry. Multivariate genetic models were compared to determine the genetic and environmental influences common and or specific to all three phenotypes. A full model that allowed for common genetic and environmental influences to all three phenotypes gave a good fit to the data, but the best fitting reduced model did not allow for a genetic influence on conduct disorder symptoms. Under the best fitting reduced model, genes explained 44.7% of the variance in risk for alcohol dependence symptoms. The genetic liability for symptoms of marijuana dependence was due to a 36.3% specific contribution and a 7.6% contribution from genes common with alcohol dependence symptoms. Family environmental contributions common to all three phenotypes explained 46.7%, 11.9%, and 21.3% of variance in risk for symptoms of conduct disorder, alcohol dependence, and marijuana dependence, respectively. Common family environmental factors contribute to risk of conduct disorder symptoms and alcohol and marijuana dependence symptoms. Common genetic influences contribute to risk of symptoms of alcohol dependence and marijuana dependence. While our findings suggest genes do not contribute to co-morbid conduct disorder symptoms, comparisons with other twin studies suggest that the role of genes in risk for conduct disorder remains uncertain.

Adult↗

Treatment of nonpsychotic relatives of patients with schizophrenia: four case studies.

BACKGROUND: Substantial evidence now shows that the genetic vulnerability to schizophrenia can be manifested clinically in first-degree relatives of people with schizophrenia, even without the full manifestations of the disorder. One pattern of problems observed involves the combination of negative symptoms and neuropsychological deficits. We have investigated whether a low dose of a novel antipsychotic medication, risperidone, could attenuate these clinical problems in non-psychotic, first-degree relatives, and report here findings from our first 4 cases. METHODS: Twelve adults who were first-degree relatives of patients with schizophrenia were evaluated for the presence of negative symptoms and neuropsychological deficits (in attention and working memory, long-term verbal memory and executive functions). Four subjects who met our predetermined criteria, and who did not demonstrate medical contraindications, were enrolled in a 6-week trial of risperidone. Clinical and medical measures were assessed before, during and after treatment. Doses of risperidone started at 0.25 mg and were increased to 1.0-2.0 mg/day. RESULTS: These subjects showed substantial reductions in negative symptoms, and one subject showed modest reductions. All four subjects showed substantial improvements on some tests of attention and working memory. Side effects of risperidone were temporary and mainly mild. CONCLUSIONS: These initial findings support two conclusions. First, clinical deficits in non-psychotic first-degree relatives of people with schizophrenia are identifiable, and to a significant extent, reversible. Second, risperidone may eventually serve as an effective treatment for people whose lives are impaired by similar or related problems.

Adult↗

Sexual orientation and suicidality: a co-twin control study in adult men.

BACKGROUND: Several recent studies have found a higher lifetime prevalence of suicide attempts in homosexual males compared with heterosexual control subjects or population rates. These studies used either convenience samples, most without controls, or population-based samples in which confounding factors such as depression and substance abuse were not measured. METHODS: This study used twins from the population-based Vietnam Era Twin Registry, Hines, Ill. An analytic sample of 103 middle-aged male-male twin pairs from the registry was identified in which one member of the pair reported male sex partners after age 18 years while the other did not. Four lifetime symptoms of suicidality as measured by the Diagnostic Interview Schedule were analyzed: thoughts about death, wanting to die, thoughts about committing suicide, and attempted suicide. A composite measure of reporting at least one suicidality symptom was also assessed. RESULTS: Same-gender sexual orientation is significantly associated with each of the suicidality measures. Unadjusted matched-pair odds ratios follow: 2.4 (95% confidence interval [CI], 1.2 - 4.6) for thoughts about death; 4.4 (95% CI, 1.7 - 11.6) for wanted to die; 4.1 (95% CI, 2.1 - 8.2) for suicidal ideation; 6.5 (95% CI, 1.5 - 28.8) for attempted suicide; and 5.1 (95% CI, 2.4 - 10.9) for any of the suicidal symptoms. After adjustment for substance abuse and depressive symptoms (other than suicidality), all of the suicidality measures remain significantly associated with same-gender sexual orientation except for wanting to die (odds ratio, 2.5 [95% CI, 0.7 - 8.81). CONCLUSIONS: The substantially increased lifetime risk of suicidal behaviors in homosexual men is unlikely to be due solely to substance abuse or other psychiatric comorbidity. While the underlying causes of the suicidal behaviors remain unclear, future research needs to address the inadequacies in the measurement of both sexual orientation and suicidality in population-based samples.

Adult↗

Cortical abnormalities in schizophrenia identified by structural magnetic resonance imaging.

BACKGROUND: Relatively few magnetic resonance imaging studies of schizophrenia have investigated the entire cerebral cortex. Most focus on only a few areas within a lobe or an entire lobe. To assess expected regional alterations in cortical volumes, we used a new method to segment the entire neocortex into 48 topographically defined brain regions. We hypothesized, based on previous empirical and theoretical work, that dorsolateral prefrontal and paralimbic cortices would be significantly volumetrically reduced in patients with schizophrenia compared with normal controls. METHODS: Twenty-nine patients with DSM-III-R schizophrenia were systematically sampled from 3 public outpatient service networks in the Boston, Mass, area. Healthy subjects, recruited from catchment areas from which the patients were drawn, were screened for psychopathologic disorders and proportionately matched to patients by age, sex, ethnicity, parental socioeconomic status, reading ability, and handedness. Analyses of covariance of the volumes of brain regions, adjusted for age- and sex-corrected head size, were used to compare patients and controls. RESULTS: The greatest volumetric reductions and largest effect sizes were in the middle frontal gyrus and paralimbic brain regions, such as the frontomedial and frontoorbital cortices, anterior cingulate and paracingulate gyri, and the insula. In addition, the supramarginal gyrus, which is densely connected to prefrontal and cingulate cortices, was also significantly reduced in patients. Patients also had subtle volumetric increases in other cortical areas with strong reciprocal connections to the paralimbic areas that were volumetrically reduced. CONCLUSION: Findings using our methods have implications for understanding brain abnormalities in schizophrenia and suggest the importance of the paralimbic areas and their connections with prefrontal brain regions.

Adult↗

The genetics of schizophrenia.

Behavioral genetic studies provide overwhelming evidence that genes contribute to schizophrenia. Recently, genetic studies have provided promising evidence that schizophrenia genes are linked to several chromosomal locations in affected family members. Despite this progress, individual genes for schizophrenia have yet to be identified. Future progress will depend, in part, on the selection of phenotypes that best reflect effects of etiologic genes. One such phenotype is schizotaxia, a clinically meaningful syndrome that reflects the genetic liability to schizophrenia in nonpsychotic individuals. The potential importance of schizotaxia, or similar concepts, for use in genetic studies, is discussed.

Chromosome Mapping↗

Sociodemographic and health status characteristics with prostate cancer screening in a national cohort of middle-aged male veterans.

OBJECTIVES: To characterize variables associated with obtaining prostate cancer screening in a nonclinical, nationally distributed, middle-aged male population. METHODS: Telephone interviews were administered to 2652 individual members of the Vietnam Era Twin Registry in 1992 and 1995. Dependent variables were self-report measures of having had a digital rectal examination (DRE) and/or a prostate-specific antigen (PSA) test in the past 5 years. Independent variables were current measures of age, household income, education, race, insurance, source of care, and lifetime measures of physical condition, psychiatric illness, and alcohol and nicotine dependence. RESULTS: Thirty-five percent of the sample reported having had a PSA and DRE within the past 5 years. Prevalence of obtaining either a PSA or DRE varied with age, income, education, and race. Subjects with a regular source of care, a regular physician, and health insurance reported higher rates of having had a DRE or PSA and DRE. Persons with a physical or psychiatric illness reported more screening. A multiple regression model revealed that having a regular source of care, having a regular physician, physical illness, psychiatric illness, minority status, higher income, and age predicted having had some form of screening. CONCLUSIONS: A substantial portion of middle-aged men have had both a PSA and DRE performed at least once in the preceding 5 years. It may be possible to further improve prostate cancer screening participation by directing educational programs at men who are not in contact with the healthcare system. If the PSA and DRE screening guidelines that are finally adopted discourage screening among low-risk men younger than age 50, educational programs that emphasize age screening criteria may be warranted.

Health Status↗

Genetic and environmental influences on transitions in drug use.

Genetic and environmental factors influence drug abuse, but abuse represents the culmination of a sequence of events. Different levels of use may have different determinants and these determinants may differ across drug types. Approximately 3200 male-male twin pairs from the Vietnam Era Twin Registry were interviewed by telephone. Data were obtained regarding exposure to six categories of illicit drugs, initiation of use, continuation of use, regular usage, and diagnosis of drug abuse/dependence. Genetic, common environmental, and unique environmental influences on transitions of drug involvement, defined as movement from one level of drug use to the next, were investigated. Marijuana had the highest conditional probability for the transition from exposure to use, from use to use more than five times, and from use more than five times to regular use. The rate of transition to regular use of heroin was higher than the rate for amphetamine, cocaine, sedatives, and psychedelics. Cocaine had the highest conditional probability for the transition from regular use to abuse/dependence. Significant genetic influences were observed for a number of transitions in marijuana, amphetamine, and cocaine usage.

Adult↗