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Biomedical subjects

M T Tsuang

Publications and source records attributed to M T Tsuang.

At least 109 records · Page 6Linked to original sources
PubMed1997

Revisiting the factor structure for positive and negative symptoms: evidence from a large heterogeneous group of psychiatric patients.

OBJECTIVE: The factor structures of individual positive and negative symptoms as well as global ratings were examined in a diagnostically heterogeneous group of subjects. METHOD: Subjects were identified through a clinical and family study of patients with major psychoses at a VA medical center and evaluated with the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. For the examination of global-level factor structures (N = 630), both principal-component analysis and factor analysis with orthogonal rotation were used. Factor analysis was used for the examination of item-level factor structures as well (N = 549). RESULTS: The principal-component analysis of global ratings revealed three factors: negative symptoms, positive symptoms, and disorganization. The factor analysis of global ratings revealed a negative symptom factor and a positive symptom factor. The item-level factor analysis revealed two negative symptom factors (diminished expression and disordered relating), two positive symptom factors (bizarre delusions and auditory hallucinations), and a disorganization factor. CONCLUSIONS: The generation of additional meaningful factors at the item level suggests that important information about symptoms is lost when only global ratings are viewed. Future work should explore clinical and pathological correlates of the more differentiated item-level symptom dimensions.

Adult↗
PubMed1997

How do genes influence marijuana use? The role of subjective effects.

This study investigated determinants of the subjective effects of marijuana and the relationship of subjective effects to marijuana use. Subjects were 8169 twins drawn from the Vietnam Era Twin Registry. Subjects who used marijuana more than five times (n = 2513) reported whether they experienced each of 23 subjective reactions. Factor analysis identified a positive (pleasant) reaction factor and a negative (unpleasant) reaction factor. Both factors were related to duration and frequency of use. Pairs in which both members used marijuana more than five times (MZ = 352 pairs; DZ = 255 pairs) were examined to assess determinants of subjective effects. Approximately one-quarter of the variance in each factor was determined by additive genetic influences; the remaining variance was determined by environmental factors that are not shared by members of a twin pair. The shared or family environment had no detectable influence on either subjective reaction factor.

Adult↗
PubMed1997

Genetic and environmental contributions to smoking.

We estimate the magnitude of genetic and shared environmental contributions to risk of initiation and maintenance of smoking. Genetic models were fitted to data from 2,204 male-male monozygotic and 1,793 male-male dizygotic twin pairs from the Vietnam Era Twin Registry who responded to smoking questions on a 1987 mail and telephone survey. The best fitting model allowed for both genetic and shared environmental effects on smoking initiation, accounting for 50% and 30% of the variance in risk, but allowed for only genetic effects, (accounting for 70% of the variance in risk), on persistence in smoking among those who had become regular smokers. This finding of a major genetic influence on smoking persistence confirms similar results from studies in Scandinavia and Australia. The role of heritable traits such as nicotine sensitivity should be addressed in smoking prevention and cessation efforts.

Adult↗
PubMed1996

The influence of familial and non-familial factors on the association between major depression and substance abuse/dependence in 1874 monozygotic male twin pairs.

The co-occurrence of major depression (MD) with alcohol and illicit substance abuse/dependence (A/D) has been repeatedly observed. However, prior research has been unable to determine whether or not the co-occurrence is a result of familial vulnerability or non-familial influences. The present study examines the association of the lifetime diagnosis of MD with alcohol, cannabis, amphetamine, cocaine, and sedative A/D (DSM-III-R criteria) before and after controlling for familial factors in a non-clinical sample of 1874 middle aged, monozygotic male twin pairs. A lifetime diagnosis of MD was significantly associated with lifetime diagnosis of alcohol and illicit substance A/D prior to accounting for familial factors (odds ratios: 1.8-4.5). After employing a co-twin analytical technique to control for familial factors, a lifetime diagnosis of MD remained significantly associated only with lifetime diagnoses of cannabis, amphetamine and sedative A/D (odds ratios: 2.3-10.9). These results suggest that the association between MD and alcohol A/D is influenced by familial factors. In contrast, the association between MD and illicit substances of A/D is largely explained by non-familial factors.

Adult↗
PubMed1996

MRI brain abnormalities in chronic schizophrenia: one process or more?

It has been suggested that schizophrenia is primarily a prefrontal-temporal-limbic circuitry disorder. Further, it has been argued that primary neurologic vulnerability to the illness is established only during early stages of brain development and is not progressive. We tested the hypothesis of whether brain volume losses in prefrontal and temporal-limbic regions have occurred either before or after brain growth was hypothesized to be complete in schizophrenia. Nineteen chronic schizophrenic patients and 19 age- and sex-matched normal controls underwent magnetic resonance imaging (MRI). All scans were segmented into gray and white matter and cerebrospinal fluid (CSF) compartments for the frontal and temporal lobes and posterior cerebral hemispheres. Multivariate analysis of variance was used to analyze absolute intracranial cerebrum and subregion volumes, i.e., gray, white and CSF, absolute tissue (i.e., gray plus white) volumes, and tissue to intracranial volume (TCV) ratios. Patients showed significant intracranial volume reductions only in the frontal lobes but highly significantly lower TCV ratios (i.e., greater relative tissue loss) in all three major regions. It is suggested that the observed decreases in frontal intracranial volumes reflect a pathologic process in schizophrenia that impacted the frontal regions before brain growth was complete. We hypothesize that the generalized lower patient TCV ratios are attributable to a process that affected the whole cerebrum over a time period after brain volume had reached its maximum levels.

Adult↗
PubMed1996

Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs.

Research and clinical experience indicate that drug use disorders tend to run in families. The objective of this study was to distinguish between the family environment and genetic factors as the source of this observed family resemblance. Data were collected by telephone interview from members of the Vietnam Era Twin Registry, comprising male twin pairs who served in the U.S. military between 1965 and 1975. There were 3,372 pairs in which both twins participated. Drug use disorder was defined as receiving a diagnosis of drug abuse or dependence according to DSM-III-R; 10.1% of the sample had abused or been dependent on at least one illicit drug. A significant difference between concordance rates for monozygotic (26.2%) vs. dizygotic (16.5%) twins indicated a genetic influence on drug use disorder. Biometrical modeling indicated that genetic factors (34% of the variance), the environment shared by twins (28% of the variance), and the nonshared environment (38% of the variance) had significant influences of similar magnitudes on the individual's risk of developing a drug use disorder. These results support the application of molecular genetic approaches to elucidate the genetic influence on drug use disorder, as well as the potential efficacy of environmental intervention to reduce risk.

Adult↗
PubMed1996

New phenotype definition of attention deficit hyperactivity disorder in relatives for genetic analyses.

The goal of the present investigation was to create a phenotype definition in relatives of probands that reflects a more genetic form of attention deficit hyperactivity disorder (ADHD). Logistic regression was applied to the first-degree relatives of ADHD and normal control probands to create a quantitative phenotype that combined information across psychiatric, cognitive, and demographic domains. Models were run separately in mothers, fathers, sisters, and brothers. Although there was some overlap between the variables retained in each model, no two models had exactly the same variables. Our results suggest that the use of fitted logits may be valuable as a potential index of caseness. Since different characteristics were included in different groups of relatives, our results suggest that gender and generation may moderate the expression of ADHD.

Adolescent↗
PubMed1996

Assessing risk for the Tourette spectrum of disorders among first-degree relatives of probands with Tourette syndrome.

Previous studies have indicated that genetic investigations of Tourette syndrome (TS) should focus on a phenotype that includes not only TS, but chronic tics (CT) and obsessive-compulsive disorder (OCD) as well. These studies have shown that sex may play a role in determining which of the disorders in the TS spectrum is expressed in a susceptible individual. Female relatives of TS probands far more often express OCD, while male relatives more often express TS or CT. Data from the Yale Family Study of TS were used to model risk to first-degree relatives of probands with TS for a variety of TS disease phenotypes. Risk to relatives was modeled using multivariate Cox regression analysis, a method appropriate for assessing risk when there is correlation among disease onsets. This is the first known application of this method to family data. The study identified two proband characteristics that increase the risk for disease onset among both male and female relatives for all TS spectrum disorders, lending credence to the hypothesis that TS spectrum disorders share a common etiology. These were a relatively younger age-at-onset, and no experience of simple motor tics. The predictive ability of two additional factors varied by both sex and disease phenotype. These characteristics, i.e., proband onset with compulsive tics, and proband onset with range, appear to increase risk primarily in female relatives, and for the OCD part of the spectrum.

Adult↗
PubMed1996

Neuropsychological functioning among the elderly nonpsychotic relatives of schizophrenic patients.

In our prior work with a young sample (age < 60), we showed that three neuropsychological functions were impaired among relatives of schizophrenic patients: abstraction, verbal memory, and auditory attention. In the present work we show that these results do not generalize to an older sample aged 60 years and greater. Thus, although we and others have put forth measures of neuropsychological function as indicators of the schizophrenia genotype, the present study suggests that conclusions may be limited to non-elderly samples. Further work is needed to address this issue definitively.

Aged↗
PubMed1996

Diagnostic accuracy and confusability analyses: an application to the Diagnostic Interview for Genetic Studies.

The dominant, contemporary paradigm for developing and refining diagnoses relies heavily on assessing reliability with kappa coefficients and virtually ignores a core component of psychometric practice: the theory of latent structures. This article describes a psychometric approach to psychiatric nosology that emphasizes the diagnostic accuracy and confusability of diagnostic categories. We apply these methods to the Diagnostic Interview for Genetic Studies (DIGS), a structured psychiatric interview designed by the NIMH Genetics Initiative for genetic studies of schizophrenia and bipolar disorder. Our results show that sensitivity and specificity were excellent for both DSM-III-R and RDC diagnoses of major depression, bipolar disorder, and schizophrenia. In contrast, diagnostic accuracy was substantially lower for subtypes of schizoaffective disorder-especially for the DSM-III-R definitions. Both the bipolar and depressed subtypes of DSM-III-R schizoaffective disorder had excellent specificity but poor sensitivity. The RDC definitions also had excellent specificity but were more sensitive than the DSM-III-R schizoaffective diagnoses. The source of low sensitivity for schizoaffective subtypes differed for the two diagnostic systems. For RDC criteria, the schizoaffective subtypes were frequently confused with one another; they were less frequently confused with other diagnoses. In contrast, the DSM-III-R subtypes were often confused with schizophrenia, but not with each other.

Bipolar Disorder↗
PubMed1996

Mortality among patients with schizophrenia.

Results from a 40-year followup study of psychotic patients are presented to illustrate some of the major findings and unanswered questions about excess mortality in schizophrenia and to suggest analytical approaches that take full account of the potential effects of sample heterogeneity. In this study, hospital-diagnosed schizophrenia patients were at increased mortality risk whether or not they met research criteria for schizophrenia. In addition, mortality outcomes of several major diagnostic groups were similar despite substantial clinical and demographic differences between the groups at baseline. These results suggest that both diagnosis-specific and nondiagnostic factors are needed to account for excess mortality in patients with major psychiatric disorders. The issue of heterogeneity is also crucial for the clinical purposes of predicting and ultimately reducing the mortality risk of psychiatric patients, for example, in delineating profiles of high-risk patients who are not necessarily typical of other patients with the same diagnosis.

Adult↗
PubMed1996

A prospective four-year follow-up study of children at risk for ADHD: psychiatric, neuropsychological, and psychosocial outcome.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a familial disorder that places the siblings of ADHD children at high risk for ADHD, conduct, mood, and anxiety disorders. Although the pattern of psychiatric risk has been well documented by prior family studies, neither the short- nor long-term outcome of these high-risk siblings has been prospectively examined. OBJECTIVE: To document the 4-year psychiatric, psychosocial, and neuropsychological outcome of the siblings of children with ADHD. METHOD: DSM-III-R structured diagnostic interviews and blind raters were used to conduct a 4-year follow-up of siblings from ADHD and control families. The siblings were also evaluated for cognitive, achievement, social, school, and family functioning. RESULTS: At follow-up, significant elevations of behavioral, mood, and anxiety disorders were found among the siblings of ADHD children. The high-risk siblings had high rates of school failure and showed evidence of neuropsychological and psychosocial dysfunction. These impairments aggregated among the siblings who had ADHD. CONCLUSIONS: The siblings of ADHD children are at high risk for clinically meaningful levels of psychopathology and functional impairment. In addition to supporting hypotheses about the familial transmission of ADHD, the results suggest that the high-risk siblings might be appropriate targets for primary preventive interventions.

Adolescent↗
PubMed1996

The association of antisocial personality symptoms with marijuana abuse/dependence. A monozygotic co-twin control study.

This study examines the association of symptoms of lifetime antisocial personality disorder (ASP) with marijuana abuse/dependence in Vietnam-era veteran male monozygotic twin pairs. In 1992, 1,874 monozygotic twin pairs responded to a structured psychiatric interview that obtained data on lifetime history of drug use and ASP. Among randomly selected individuals from each twin pair, 8 of 10 ASP symptoms were significantly more prevalent in persons with a lifetime history of marijuana abuse/dependence compared with those who had never abused any drug (p < .001). Among 99 marijuana discordant twin pairs, however, only two ASP symptoms, "failure to conform to social norms" (odds ratio, 2.8; 95% confidence interval, 1.5 to 5.5) and "reckless regard of own or other's personal safety" (odds ratio, 2.4; 95% confidence interval, 1.0 to 5.4) were significantly increased in marijuana abusing/dependent twins compared with their non-abusing/nondependent twin brother. After adjustment for conduct disorder, alcohol abuse/dependence, and exposure to combat in Vietnam, only "failure to conform to social norms of lawful behavior" (odds ratio, 2.42; 95% confidence interval, 1.12 to 5.21) remained significantly increased in twins with marijuana abuse/dependence.

Antisocial Personality Disorder↗
PubMed1996

Models of treatment seeking for alcoholism: the role of genes and environment.

We investigated the relative influence of genes and environment on the decision to seek treatment for alcoholism under three models of health care utilization. Lifetime alcohol dependence and two measures of treatment seeking for alcohol problems were determined from a 1992 telephone administration of the Diagnostic interview Schedule. Data were analyzed from 1,864 monozygotic and 1,492 dizygotic male twin respondents from the Vietnam Era Twin Registry. Genetic and environmental contributions to the decision to seek treatment for alcoholism were assessed under competing models for the relationship between genetic influences on alcoholism risk and genetic influences on treatment seeking among those who became alcoholics. Under the best-fitting model, genetic influence accounted for 41% of the variance in treatment seeking and 55% of the liability for alcoholism. Shared environment explained none of the variance in liability for alcoholism, but 40% of the variance in treatment seeking. The severity of alcoholism alone is an inadequate model of treatment seeking, because decisions to seek alcohol treatment are also influenced by substantial genetic and or shared environmental factors unrelated to the determinants of alcoholism.

Adult↗
PubMed1996

Genetics of Alzheimer's disease.

We briefly reviewed methods of psychiatric genetics and showed how these have elucidated genetic aspects of Alzheimer's disease. Although some cases of Alzheimer's disease are not familial, clinicians and researchers have identified many families in which the disease occurs in multiple generations in approximately 50% of family members. Linkage analyses have implicated several genes as causes or risk factors for Alzheimer's disease in different families: the amyloid precursor protein gene, the apolipoprotein-E gene (E4 subtype) on chromosome 19, the S182 gene on chromosome 14 and the STM2 gene on chromosome 1. These linkage findings have been replicated in independent laboratories and, thus, provide strong evidence for genetic heterogeneity of this disease. The discovery of these genes may lead to a better understanding of the etiology and pathophysiology of Alzheimer's disease and also raises the possibility of genetic counseling for patients with familial Alzheimer's disease.

Alzheimer Disease↗