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M T Tsuang

Publications and source records attributed to M T Tsuang.

At least 73 records · Page 4Linked to original sources
PubMed1999

Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a 4-year follow-up study.

In a prior study of 54 relatives of patients with schizophrenia and 72 control participants, 3 neuropsychological functions met the criteria for risk indicators of the schizophrenia genotype: executive functioning, memory, and auditory attention. In an assessment of the stability of these findings, the sample was reexamined 4 years after the initial assessment. Three test scores were found to differ between groups (Immediate Verbal Memory, Delayed Verbal Memory, and Dichotic Listening Digits Detected) or to show a significant Group x Gender interaction (immediate and delayed verbal and visual memories). None of the test scores showed Group x Time interactions, suggesting that the discriminating power of the tests was stable over time. Evidence for deficits in working memory and rule learning on the object alternation test was also found. These results support the idea that neuropsychological dysfunction among relatives of patients with schizophrenia is a stable trait caused by the familial predisposition to schizophrenia.

Adult↗
PubMed1999

The heritability of alcoholism symptoms: "indicators of genetic and environmental influence in alcohol-dependent individuals" revisited.

There is consistent evidence from twin and adoption studies implicating genetic factors in the etiology of alcoholism, yet few studies have examined the role of genetic influences on individual symptoms of alcoholism. In a previous study of 113 male twins, Johnson et al. (1996a) identified 7 alcoholism symptoms that were more "genetic" and 14 that were more "environmental" (that is, non-genetic) in their etiology by examining symptom concordances among monozygotic and dizygotic twin pairs. The present study represents an attempt to replicate the results of this previous study and extend them by estimating the contribution of genetic factors to the variation in liability for different alcoholism symptoms. Subjects were 3356 male twin pairs from the Vietnam Era Twin Registry. Lifetime histories of alcoholism symptoms were assessed by a structured psychiatric telephone interview. The results of the previous study were not replicated. The correlations between symptom classifications as genetic and non-genetic in the present and previous study were nonsignificant and ranged from -0.27 to 0.11. However, within the present study the correlation between symptom classifications as genetic and non-genetic was statistically significant across random split-half subsamples (r = 0.59); nine alcoholism symptoms were consistently classified as genetic and six symptoms as non-genetic in their etiology. Model-fitting analyses applied to different alcoholism symptoms yielded heritability estimates ranging from 0.03 to 0.53 with broad and overlapping confidence intervals around these estimates, ranging from 0.00 to 0.65. The results of this study highlight the difficulty of identifying more or less heritable phenotypes in twin research, and suggest that it may not be possible to identify specific alcoholism symptoms that are more genetic in their etiology than others. Nevertheless, there appears to be potentially important variation in the relative magnitude of genetic influences for individual alcoholism symptoms, and exploring these differences may lead to further insights into the nosology and etiology of alcohol-related problems.

Adult↗
PubMed1999

The concept of target features in schizophrenia research.

Target features are clinical or neurobiological characteristics that are expressions of the underlying predisposition to an illness. They comprise a wide range of phenomena, from the classic signs and symptoms of psychopathology to sophisticated measures of brain structure and function. For schizophrenia, many target features have been identified. These include eye tracking dysfunction, attentional impairment, allusive thinking, neurological signs, thought disorder, characteristic auditory evoked potentials, neuropsychological impairment, structural brain abnormalities and functional brain abnormalities. In their most pathological forms, these features are present among many schizophrenic patients, yet it is their presence among their non-psychotic relatives that shows them to be target features. We discuss the theoretical background for target features, present examples and describe how the discovery of target features has implications for schizophrenia research.

Brain↗
PubMed1999

The impact of sociodemographics, comorbidity and symptom recency on health-related quality of life in alcoholics.

OBJECTIVE: To obtain estimates of the relationship between alcoholism and health-related quality of life (HRQL) in twin pairs discordant for alcohol dependence. METHOD: In 1995, 1,258 male-male twin pair members of the Vietnam Era Twin Registry (total Registry N = 7.375 pairs) were administered a modified Medical Outcomes Study 36 Item Short Form (SF-36) and the Diagnostic Interview Schedule (DIS) to obtain measures of HRQL and a DSM-III-R criteria lifetime diagnosis of alcohol dependence. Mean within pair differences on eight separate SF-36 subscales were calculated for 436 remitted (no alcohol symptoms in the past 5 years) alcohol-dependent discordant twin pairs and for 194 recent (at least one alcohol symptom in the past 5 years) alcohol-dependent discordant pairs before and after adjustment for covariates. Covariates included lifetime physical illness, lifetime psychiatric disorders, lifetime drug dependence, lifetime nicotine dependence, current marital status, current income and severity. RESULTS: In the unadjusted analysis remitted alcoholic twins compared to their nonalcoholic co-twins reported significantly lower mean scores for six of eight SF-36 subscales. Recent alcoholic twins, compared to their nonalcoholic co-twins, reported significantly lower mean scores for all of the SF-36 subscales. However, after simultaneous adjustment for all covariates, no SF-36 subscale mean, except "vitality" among recent alcoholic twins, was significantly different between alcoholic twins and their nonalcoholic co-twins. CONCLUSIONS: Differences in HRQL between alcoholic and nonalcoholic co-twins is due to covariation from physical and psychiatric problems, drug and nicotine dependence, marital status, income and severity.

Adult↗
PubMed1998

Sex differences in self-reported schizotypal traits in relatives of schizophrenic probands.

We used the Schizotypal Personality Questionnaire to evaluate schizotypal traits in 44 normal volunteers and 40 non-psychotic, biological relatives of schizophrenic probands. Relatives endorsed more cognitive-perceptual traits than did controls; a group-by-sex interaction indicated that male relatives accounted for this difference. Although not statistically significant, a similar pattern was observed for interpersonal traits. Thus, elevated rates of some schizotypal traits appear to be more prominent in male than in female relatives of schizophrenic probands, at least when assessed by self-report. Subscale analysis indicated that differences were accounted for primarily by suspiciousness and ideas of reference, suggesting that paranoid-like phenomena from both the cognitive-perceptual and interpersonal factors may constitute an important dimension of schizotypy in relatives. Unlike previous studies, we did not find any differences in constricted affect or disorganization signs. Interviews and other non-self-report techniques are probably best suited for an assessment of these features, although the question remains as to whether the combination of both approaches might provide some incremental discriminatory power.

Adult↗
PubMed1998

The effects of increasing resource demand on vigilance performance in adults with schizophrenia or developmental attentional/learning disorders: a preliminary study.

The goal of this study was to assess whether degree of information processing load differentially affects vigilance performance in patients with schizophrenia as compared to normal controls or patients with other attentional disorders. We contrasted the performance of clinically stable outpatients with schizophrenia (n = 18), with that of normal controls (n = 17), and adults with developmental attentional/learning disorders (n = 13) on simple and demanding versions of a visual continuous performance test (CPT). Patients with schizophrenia were significantly impaired on both versions of the CPT compared to normal controls, and showed a significant decline in perceptual sensitivity and significantly more omission errors with increased processing demands. Compared to adults with developmental attentional/learning disorders, patients with schizophrenia manifested a tendency toward a decline in perceptual sensitivity. There were no significant differences between groups on a measure of response bias. The data support the hypothesis that patients with schizophrenia have insufficient information processing resources to cope with higher processing demands on effortful attention tasks. Further study comparing schizophrenic patients with patients who have other neuropsychiatric disorders, controlling for severity of illness, is required to determine the specificity of this deficit in schizophrenia.

Adult↗
PubMed1998

Hemispheric asymmetry of frontal and temporal gray matter and age of onset in schizophrenia.

BACKGROUND: Investigators have reported lack of normal asymmetry of lateralization in some schizophrenic patients, as measured postmortem and by preference and/or performance. It has been suggested that this lack of asymmetry is related to early onset of schizophrenia. The present study extends the inquiry by magnetic resonance imaging (MRI) measurement of volumetric asymmetry. METHODS: Hemispheric asymmetry of volume in regional gray matter was examined in 16 schizophrenic patients who had undergone MRI of brain volume. RESULTS: Low levels of hemispheric asymmetry in the frontal and temporal areas were strongly associated with early onset of schizophrenia, the association with frontal volume being more marked than with temporal volume. No relationship was found in the other brain areas that were scanned. The findings were not artifacts of chronological age, nor of extreme scores in a small sample. CONCLUSIONS: These findings are consistent with the hypothesis that failure to develop asymmetry is an important component of the pathology underlying some forms of schizophrenia.

Adult↗
PubMed1998

Neuropsychological risk indicators for schizophrenia: a preliminary study of female relatives of schizophrenic and bipolar probands.

Evidence of subtle neuropsychological deficits in relatives of schizophrenic probands (REL-SZs) suggests that these are risk indicators for schizophrenia, but little is known about whether neuropsychological performance in REL-SZs differs from that in other groups of relatives. We compared neuropsychological function in female REL-SZs (n = 39), relatives of primarily psychotic bipolar disorder probands (REL-BPs; n = 15), and a normal control group (n = 44). After adjustment for expected intellectual ability (based on reading recognition), REL-SZs showed deficits in verbal and visual memory (Wechsler Memory Scale-Revised logical memories, visual reproductions), and auditory attention (dichotic digits) compared with either REL-BPs or control subjects. Memory, but not dichotic listening differences remained significant after adjusting for current IQ; however, average effect sizes after controlling for either reading or IQ were roughly comparable for these three parameters (d = 0.80, 0.71, and 0.69, respectively). REL-BPs and control subjects showed little difference. Although both schizophrenic and bipolar patients often manifest neuropsychological dysfunction, these preliminary findings indicate subtle neuropsychological deficits only in REL-SZs. Such differences suggest different underlying processes; neuropsychological impairment may, in part, reflect an expression of genetic liability to schizophrenia but not bipolar disorder. Replication with a larger REL-BP sample and with male relatives is needed to evaluate the generalizability of the results.

Adolescent↗
PubMed1998

Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative.

Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the alpha7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia.

Chromosomes, Human, Pair 15↗
PubMed1998

Genome-wide search for schizophrenia susceptibility loci: the NIMH Genetics Initiative and Millennium Consortium.

Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment.

Adolescent↗
PubMed1998

NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees.

The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere.

Adolescent↗
PubMed1998

Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.

The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs. Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241-247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241-247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P = .0004) and its neighbor, D10S582 (NPL Z = 3.2, P = .0006).

Adolescent↗
PubMed1998

Association of neuropsychological vulnerability markers in relatives of schizophrenic patients.

We investigated the association of neuropsychological risk indicators in a matched sample of first-degree relatives of schizophrenic patients (n = 54) and normal controls (n = 72). We focussed on three functions previously identified in a smaller, initial sample as putative risk indicators of the schizophrenia genotype: abstraction, verbal memory and auditory attention. The expanded sample of relatives displayed significantly lower scores than controls on abstraction, verbal memory and auditory attention. The relatives demonstrated significant intercorrelations among these three functions. The significant correlations among relatives between attention and verbal memory and between attention and abstraction differed significantly from these correlations among controls. We discuss how the use of multiple risk indicators may help us better identify those relatives that carry the schizophrenia genotype.

Adult↗
PubMed1998

Co-occurrence of abuse of different drugs in men: the role of drug-specific and shared vulnerabilities.

BACKGROUND: Previous research has demonstrated genetic and environmental influences on abuse of individual substances, but there is less known about how these factors may influence the co-occurrence of abuse of different illicit drugs. METHODS: We studied 3372 male twin pairs from the Vietnam Era Twin Registry. They were interviewed using the Diagnostic Interview Schedule, Version III, Revised to investigate the extent to which the abuse of different categories of drugs occurs together within an individual, as well as the possibility that genetic and environmental factors are responsible for observed co-occurrence. Co-occurrence was quantified using odds ratios and conditional probabilities. Multivariate biometrical modeling analyses were used to assess genetic and environmental influences on co-occurrence. RESULTS: Abusing any category of drug was associated with a marked increase in the probability of abusing every other category of drugs. We found evidence for a shared or common vulnerability factor that underlies the abuse of marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. This shared vulnerability is influenced by genetic, family environmental, and nonfamily environmental factors, but not every drug is influenced to the same extent by the shared vulnerability factor. Marijuana, more than other drugs, was influenced by family environmental factors. Each category of drug, except psychedelics, had genetic influences unique to itself (ie, not shared with other drug categories). Heroin had larger genetic influences unique to itself than did any other drug. CONCLUSION: There are genetically and environmentally determined characteristics that comprise a shared or common vulnerability to abuse a range of illicit drugs.

Adult↗
PubMed1998

A registry-based twin study of depression in men.

BACKGROUND: The only large, registry-based twin study of depression using diagnostic criteria assessed by structured interview included only women. We present results from a comparable study of men. METHODS: Data were collected using a standardized telephone interview of men from the Vietnam Era Twin Registry. Both twins from 3372 pairs participated. Proband-wise concordance rates and biometric modeling were used to analyze the data. RESULTS: The diagnosis of major depression (MD), as defined by DSM-III-R, and the subtype of severe/psychotic MD were significantly affected by genetic (h2=0.36 and 0.39, respectively) and nonshared environmental (e2=0.64 and 0.61, respectively) factors but not by family environmental factors. Dysthymia and mild and moderate MD were affected by family environmental (c2=0.27, 0.08, and 0.14, respectively) and nonshared environmental (e2=0.73, 0.92, and 0.86, respectively) factors but not by genetic factors. Early-onset (before age 30 years) and late-onset (after age 30 years) MD were significantly affected by genetic (h2=0.47 and 0.10, respectively) and nonshared environmental (e2=0.53 and 0.90, respectively) factors. Early-onset MD was significantly more heritable than late-onset MD. CONCLUSIONS: The magnitude of genetic and environmental effects on depression in men is similar to that previously reported in women. Also similar to previous findings, more severe and earlier-onset depression may be more strongly affected by genetic factors, but differences in the reliability of reports of depression associated with severity may inflate estimates of the effect of the unique environment and deflate heritability estimates for less severe depression.

Adult↗
PubMed1998

Recent advances in genetic research on schizophrenia.

Evidence for genetic factors in schizophrenia is reviewed with regard to family, twin and adoption studies, and recent advances in molecular genetic technology are applied to explore possible gene loci susceptible to schizophrenia. Application of neuropsychological and neuroimaging methodologies are also reviewed with an aim to develop criteria for defining phenotypes for genetic studies.

Adoption↗
PubMed1998

Factor structure of the Wisconsin Card Sorting Test: dimensions of deficit in schizophrenia.

The aim of this study was to explore the factorial structure of the Wisconsin Card Sorting Test (WCST) and to identify the dimensions of deficit in schizophrenia. WCST scores in patients with schizophrenia and schizophrenia-related psychosis (n = 292), 1st degree relatives of schizophrenic patients (n = 91), and normal controls (n = 141) were subjected to a principal factor analysis followed by orthogonal rotation. This led to 3 factors, perseveration, failure to maintain set, and idiosyncratic sorting. The detected factor structure was found to be invariant across the schizophrenic and control subsamples. Moreover, it replicated previous findings from 2 smaller samples. Only perseverations and, to a lesser degree, idiosyncratic sorting appeared to differentiate schizophrenic patients from comparisons. Only perseveration had good sensitivity and specificity, as well as the most robust significant correlations with estimates of IQ, attention, and other measures of executive functioning. Thus, perseveration appears to be the most diagnostically useful and characteristic WCST feature of schizophrenia.

Adult↗