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M T Tsuang

Publications and source records attributed to M T Tsuang.

At least 37 records · Page 2Linked to original sources
PubMed2001

Genetic counseling for psychiatric disorders.

Like other medical conditions, some psychiatric disorders are inherited, whereas others are not. Human genetics research is moving at a rapid pace. Genes for over 450 genetic disorders have been cloned and many disease-causing mutations have also been identified. The explosion of this new knowledge has created many new exciting opportunities in the diagnosis of these heritable disorders. The rapid pace of gene discovery will aid the identification of susceptibility genes for psychiatric disorders. Indeed, we can look forward to answers to many clinical and research questions. These are some of the gifts that the expanding field of human genetics research will continue to bring to medical science. However, as genetic tests for the detection of psychiatric disorders become available, many ethical, legal, and social implications will need to be considered. In this article, we review the principles of genetic counseling for psychiatric disorders, as well as the social and ethical dilemmas that genetic testing may bring. Although medical and scientific advances may bring many gifts, we should approach this new knowledge with caution, as one of the gifts may be a Pandora's box.

Ethics, Medical↗
PubMed2001

Antidepressant use and the risk of breast cancer: a non-association.

OBJECTIVE: Animal studies have suggested that some antidepressant medications may act as breast tumor promoters and recent epidemiologic studies of antidepressant use and breast cancer outcomes in humans have also reported such associations. DESIGN: Retrospective cohort study. STUDY POPULATION: 38,273 women who filled a prescription for any of a number of antidepressants and 32,949 who filled a prescription for any other medication during 1989-1991; all were > or =20, enrolled in Medicare, Medicaid or the Pharmaceutical Assistance to the Aged and Disabled (PAAD) programs of New Jersey, and free of evidence of breast cancer. DATA COLLECTION: Antidepressant use was assessed over a period lasting up to 24 months. Subjects were followed for a maximum of 7.5 years; those who had a first diagnosis of breast cancer in the New Jersey Cancer Registry at least 3 months after their index date were considered incident breast cancer cases. Other covariates, including demographic, clinical, and health care utilization variables were also assessed. MAIN OUTCOME OF INTEREST: Adjusted hazard ratio (HR) of developing breast cancer, based on multivariable proportional hazards models. RESULTS: Use of antidepressants was unrelated to the development of breast cancer (adjusted HR = 1.04; 95% CI 0.87-1.25). No elevated risks were found for specific antidepressants, including agents found to be breast tumor promoters in animal studies, as well as drugs thought to be associated with breast cancer in prior epidemiologic studies. There was no suggestion that breast cancer risks were increased with more intensive use of antidepressants or that antidepressant use is associated with a more severe stage of cancer at diagnosis. CONCLUSIONS: Despite recent reports from much smaller epidemiologic studies or laboratory animals, these results provide reassurance that antidepressant use is not associated with the development of breast cancer.

Adult↗
PubMed2001

Finding incident breast cancer cases through US claims data and a state cancer registry.

OBJECTIVE: With the increasing availability of automated health-care data, new methods are available to screen large populations for the presence of cancer diagnoses. However, it is crucial to evaluate how completely incident cancer cases can be ascertained using these data sources. METHODS: We used capture-recapture techniques to estimate the total number of incident breast cancer cases occurring within one state during a 3-year period. We then compared the ascertainment of these cases by the following two data sources: claims for breast cancer surgery recorded in Medicaid and Medicare data vs a cancer registry in the same state. RESULTS: Medicaid-Medicare breast cancer surgery claims identified 68% of the total estimated number of incident breast cancer cases while cancer registry data identified 78%. Case ascertainment improved markedly to 91% when both registry and Medicare-Medicaid data sources were used together. The sensitivity of ascertainment was lower for Medicaid-Medicare data among those aged under 65 and non-white; ascertainment was lower for the registry among women who were aged under 65, poor, and non-white. CONCLUSIONS: Combining health insurance claims data with a population-based cancer registry improved the identification of incident cases of breast cancer, and may be particularly useful among demographic groups found to be at highest risk of under-ascertainment such as younger women, the poor, and racial minorities.

Adult↗
PubMed2001

The genetics of pathological gambling.

Problem and pathological gambling (PG) occurs in about 5% of Americans. Gambling is associated with substantial psychosocial and psychiatric health problems, and the increasing ease of access to gambling may increase its future prevalence. Therefore, it is important to gain greater insight into the causes of PG. Family studies of PG are consistent with a substantial familial impact on vulnerability to PG. However, family studies cannot distinguish genetic from family environmental influences. By contrast, the study of twin pairs permits the genetic and environmental influences on PG to be estimated. The study of gambling behavior among 3,359 twin pair members of the Vietnam Era Twin Registry suggests that: (1) inherited factors explain a substantial proportion of the variance in the report of symptoms of gambling; (2) there is a single continuum of genetic vulnerability that underlies gambling problems of varying severities; and, (3) the co-occurrence of PG with conduct disorder, antisocial personality disorder, and alcohol abuse/dependence is partially explained by genes that influence both PG and these other psychiatric disorders. Neurophysiological correlates of gambling problems and genetically based differences in neurotransmitter systems may provide biological mechanisms that explain the genetic basis for a predisposition to PG.

Adoption↗
PubMed2001

Normal sexual dimorphism of the adult human brain assessed by in vivo magnetic resonance imaging.

The etiology and consistency of findings on normal sexual dimorphisms of the adult human brain are unresolved. In this study, we present a comprehensive evaluation of normal sexual dimorphisms of cortical and subcortical brain regions, using in vivo magnetic resonance imaging, in a community sample of 48 normal adults. The men and women were similar in age, education, ethnicity, socioeconomic status, general intelligence and handedness. Forty-five brain regions were assessed based on T(1)-weighted three-dimensional images acquired from a 1.5 T magnet. Sexual dimorphisms of adult brain volumes were more evident in the cortex, with women having larger volumes, relative to cerebrum size, particularly in frontal and medial paralimbic cortices. Men had larger volumes, relative to cerebrum size, in frontomedial cortex, the amygdala and hypothalamus. A permutation test showed that, compared to other brain areas assessed in this study, there was greater sexual dimorphism among brain areas that are homologous with those identified in animal studies showing greater levels of sex steroid receptors during critical periods of brain development. These findings have implications for developmental studies that would directly test hypotheses about mechanisms relating sex steroid hormones to sexual dimorphisms in humans.

Adult↗
PubMed2001

"Schizotaxia": clinical implications and new directions for research.

We sought to show that (1) schizotaxia (Meehl's term for the predisposition to schizophrenia) is a clinically consequential condition, and (2) distinguishing it from schizotypal personality disorder may be useful from both clinical and scientific perspectives. We review the features of schizotaxia that may be relevant in clinical settings and discuss their implications for the diagnosis, psychosocial functioning, family intervention and treatment of people in schizophrenia families. Our review indicates that prior work finds some of the nonpsychotic and nonschizotypal relatives of schizophrenia patients to have a psychiatric syndrome characterized by negative symptoms, neuropsychological impairment, and psychosocial dysfunction. Following Meehl, we call this constellation of clinical and neurobiological features schizotaxia. The studies we review suggest it may be worthwhile to consider schizotaxia as a separate diagnostic class. Doing so would alert clinicians to a neurobehavioral syndrome not adequately covered by current diagnostic criteria and would motivate researchers to develop diagnostic and therapeutic approaches aimed at helping schizotaxic individuals and, perhaps, preventing the onset of schizophrenia.

Diagnosis, Differential↗
PubMed2001

Genes, environment and schizophrenia.

BACKGROUND: Data from family, twin and adoption studies show overwhelming evidence of a substantial genetic component in schizophrenia and although molecular genetic studies have been more difficult to replicate, recent improvements in technology have resulted in the implication of genes at several chromosomal loci. Nevertheless, it remains clear that environmental factors both add to and interact with genetic factors to produce the disorder. AIMS: To incorporate genetic and environmental risk factors into a neurodevelopmental model in order to conceptualise the liability to schizophrenia. METHOD: A representative selection of the literature related to this issue is reviewed, together with a reformulation of Meehl's term 'schizotaxia' to describe the liability to the disorder. RESULTS: The literature supports a multi-factorial view of the liability to schizophrenia, which includes both genetic and environmental components. CONCLUSIONS: Schizotaxia provides a useful way to conceptualise both the liability for schizophrenia, and also the development of treatment strategies aimed at the eventual prevention of the illness.

Diseases in Twins↗
PubMed2000

Towards the prevention of schizophrenia.

There is a growing emphasis on attempts to identify the early signs and symptoms of schizophrenia, largely because early detection and treatment of psychosis (i.e., secondary prevention) are associated with relatively favorable clinical outcomes. This raises the issue of whether prevention of psychosis itself is possible. The achievement of this goal will require the identification of a premorbid state that could serve as the foundation for treatment strategies aimed ultimately at the prevention of schizophrenia. Fortunately, evidence for such a state is emerging, in part because schizophrenia may result from a neurodevelopmental disorder that is associated with a variety of clinical, neurobiological, and neuropsychologic features occurring well before the onset of psychosis. These features may serve as both indicators of risk for subsequent deterioration and the foundation of treatment efforts. We reformulated Meehl's term schizotaxia to describe this liability and discuss here how its study could form the basis for future strategies of prevention. We also include a description of our initial attempts to devise treatment protocols for schizotaxia. It is concluded that schizotaxia is a feasible concept on which to base prevention efforts, and that treatment of adult schizotaxia may be among the next steps in the process.

Humans↗
PubMed2000

Age and neuropsychologic function in schizophrenia: a decline in executive abilities beyond that observed in healthy volunteers.

BACKGROUND: Kraepelin originally conceptualized schizophrenia as a degenerative brain disorder. It remains unclear whether the illness is characterized by a static encephalopathy or a deterioration of brain function, or periods of each condition. Assessments of cognitive function, as measured by neuropsychologic assessment, can provide additional insight into this question. Few studies of patients with schizophrenia have investigated the effect of aging on executive functions, in an extensive neuropsychologic battery across a wide age range, compared to healthy volunteers. METHODS: We examined the interaction of aging and neuropsychologic function in schizophrenia through a cross-sectional study in patients (n = 87) and healthy control subjects (n = 94). Subjects were divided into three age groups (20-35, 36-49, and 50-75), and performance on an extensive neuropsychologic battery was evaluated. RESULTS: Compared to control subjects, patients with schizophrenia demonstrated similar age-related declines across most neuropsychologic functions, with the exception of abstraction ability, in which significant evidence of a more accelerated decline was observed. CONCLUSIONS: These results are consistent with previous reports indicating similar age effects on most aspects of cognition in patients with schizophrenia and healthy adults, but they support the hypothesis that a degenerative process may result in a more accelerated decline of some executive functions in older age in schizophrenia.

Adult↗
PubMed2000

Neuropsychologic functioning among the nonpsychotic relatives of schizophrenic patients: the effect of genetic loading.

BACKGROUND: We previously reported that the nonpsychotic relatives of schizophrenic patients exhibited disturbances in executive functioning, verbal and visual memory, auditory attention, mental control, and verbal ability. In a 4-year follow-up, we showed that the discriminating power of most of these tests was stable over time. METHODS: In this report we compare 41 nonpsychotic persons who have only one schizophrenic first-degree relative (simplex families) with 36 nonpsychotic persons who have two schizophrenic first-degree relatives (multiplex families). Our goal was to test a hypothesis that neuropsychologic deficits would be worse among the latter. RESULTS: Relatives from multiplex families differed significantly from controls on estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. In contrast, in comparisons with controls, relatives from simplex families only differed on immediate logical memories. Comparisons between relatives from multiplex and simplex families showed that the former group had significantly worse scores for estimated intelligence, immediate and delayed logical memories, and immediate visual reproductions. We also found group x gender interactions: the worse performance of the multiplex group was seen for females. CONCLUSIONS: These results are consistent with the idea that neuropsychologic deficits in relatives of schizophrenic patients reflect their degree of genetic predisposition to schizophrenia. They also suggest hypotheses about gender differences in the familial transmission of the disorder.

Adolescent↗
PubMed2000

Department of Veterans Affairs Cooperative Studies Program genetic linkage study of schizophrenia: ascertainment methods and sample description.

To help clarify the genetics of schizophrenia, the Department of Veterans Affairs Cooperative Studies Program has completed data collection for a genetic linkage study of schizophrenia. This article describes the methodological details of the data collection. Subsequent articles will describe the results of our genome scan, which is now in progress. The data collection protocol included the Diagnostic Interview for Genetic Studies, the Family Interview for Genetic Studies, a review of medical records, and the collection of blood for transformation into lymphoblast cell lines. Among relatives of schizophrenic probands, we assessed auditory attention and verbal memory with neuropsychological tests. Among the 166 families ascertained for the study, 143 had a single affected sib-pair, 17 had three affected siblings, one had five affected siblings and five had two sets of affected siblings. There was a total of 216 affected sib-pairs in these families. Using the n-1 rule, these families contain 188 independent affected sib-pairs.

Adult↗
PubMed2000

Self-Reported zygosity and the equal-environments assumption for psychiatric disorders in the Vietnam Era Twin Registry.

The equal-environments assumption (EEA) in twin studies of psychiatric disorders assumes that the family environment which contributes to risk for a disorder is equally correlated between monozygotic (MZ) and dizygotic (DZ) twin pairs. In a study of psychiatric disorders in female twins, Kendler and colleagues (1993) have demonstrated the utility of a test of the EEA which includes a specified family environmental factor defined by using measures of perceived zygosity. We tested the EEA assumption among 3155 male-male twin pair members of the Vietnam Era Twin Registry for the following DSM-III-R lifetime disorders: alcohol dependence, marijuana dependence, any illicit drug dependence, nicotine dependence, major depression, and posttraumatic stress disorder. The majority of MZ (81.6%; n = 1593) and DZ (90.2%; n = 1086) twin pairs agreed with the investigator's assigned zygosity. The best-fitting model for each of these disorders did not allow for a specified family environmental influence. These results support the usefulness of perceived zygosity in tests of the EEA. In male twin pairs, perceived zygosity has little impact on twin similarity for common psychiatric disorders.

Adult↗
PubMed2000

The paradox of normal neuropsychological function in schizophrenia.

Mounting evidence suggests that compromised neurocognitive function is a core feature of schizophrenia. However, some studies have found neuropsychologically normal schizophrenia patients. To address this apparent contradiction, we blindly rated individual neuropsychological profiles of 75 schizophrenia patients and 91 control participants on the basis of methods developed by L. J. Seidman, S. V. Faraone, W. S. Kremen, J. R. Pepple, M. J. Lyons, and M. T. Tsuang (1993). Almost one-quarter of the patients were classified as neuropsychologically within normal limits (WNL). Despite significantly worse neuropsychological performance, WNL patients had higher estimated premorbid ability than did controls. Compared to a subset of controls matched on overall neuropsychological function, WNL patients had higher estimated premorbid ability and current IQs. Our results favor the view that even neuropsychologically normal schizophrenia patients have compromised cognitive function relative to their presumed expected or premorbid level of intellectual ability.

Adult↗
PubMed2000

The problem of obstetrical complications and schizophrenia.

The use of the term "obstetrical complications" (OCs) and its variations to encompass diverse physiological mechanisms (e.g., genetic, ischemic, hemorrhagic, infectious) of disruption to fetal/neonatal brain development has engendered inconsistency, confusion, and controversy. The principal reason is that the term OCs belies the absence of a fully adequate conceptual framework for characterizing neurodevelopmental risk. We propose that neurodevelopmental risk factors for schizophrenia can be assessed more clearly if broad OC scales are replaced by measures representing more homogeneous pathways of disturbed brain development. Using a new OC classification, we found that disordered growth related to hypoxic-ischemic compromise to early brain development may confer an elevated risk of schizophrenia and other adult-onset psychoses, particularly in the presence of familial risk. Abnormal fetal and neonatal brain growth and development in schizophrenia and OCs may also, at least in part, result from genetic factors and could help explain the relation between seemingly inconsistent OCs identified in prior research.

Birth Injuries↗
PubMed2000

The relationship of prenatal and perinatal complications to cognitive functioning at age 7 in the New England Cohorts of the National Collaborative Perinatal Project.

Previous literature shows that children who later develop schizophrenia have elevated rates of prenatal and perinatal complications (PPCs) and neuropsychological deficits in childhood. However, little is known about the relationship of these risk factors to each other. We evaluated the relationship between PPCs and neuropsychological functioning at age 7 in a large epidemiological study of pregnancy, birth, and development: the National Collaborative Perinatal Project (NCPP). Thirteen standardized measures of cognitive abilities were acquired on 11,889 children at approximately age 7. Principal components analysis was used to create three neuropsychological measures: academic achievement skills, verbal-conceptual abilities, and perceptual-motor abilities. We measured the relationship between these factors and three measures of PPCs: low birth weight (LBW), probable hypoxicischemic complications, and chronic hypoxia. All three measures of PPCs were significantly associated with lower neuropsychological performance, after controlling for various confounders. LBW had the strongest association with neuropsychological performance, followed by an index of presumed hypoxic insults. The effect sizes between PPCs and cognitive factors at age 7 were consistently largest with perceptual-motor abilities, followed by academic achievement skills and verbal-conceptual abilities. Future studies will evaluate the effects of specific PPCs and genetic risk factors for psychosis on cognitive functioning in childhood.

Birth Injuries↗
PubMed2000

Impact of genetic vulnerability and hypoxia on overall intelligence by age 7 in offspring at high risk for schizophrenia compared with affective psychoses.

Risk factors for schizophrenia, such as genetic vulnerability and obstetric complications, have been associated with cognitive deficits in schizophrenia. We tested the association of these risk factors with general intellectual ability in offspring at high risk for psychoses and normal control subjects. Offspring of 182 parents with DSM-IV schizophrenia or affective psychoses were recruited and diagnosed from the Boston and Providence cohorts of the National Collaborative Perinatal Project (NCPP). Control subjects from the NCPP were selected to be comparable with affected parents based on the parent's age, ethnicity, study site, number of offspring enrolled in the NCPP, and payment status, and on the offspring's age, sex, and history of obstetric complications. Based on data prospectively acquired from pregnancy and events of gestation, labor, delivery, and the neonatal period, we derived a measure of probable hypoxic-ischemic insult. We also report on standardized measures of general intelligence (intelligence quotient [IQ]) collected at age 7. General linear mixed models were used to test for the simultaneous effects of genetic vulnerability, defined as parental diagnosis, and probable hypoxic insult on age 7 IQ. Specificity of the effects for schizophrenia compared with affective psychoses and sex effects were also tested. Low IQ at age 7 was significantly associated with genetic vulnerability to psychoses, in particular with schizophrenia.

Adult↗