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Biomedical subjects

M T Tsuang

Publications and source records attributed to M T Tsuang.

At least 127 records · Page 7Linked to original sources
PubMed1995

Genetic heterogeneity may in part explain sex differences in the familial risk for schizophrenia.

The purpose of this study was to attempt, in part, to explain significant sex differences in the familial risk (FMR) for schizophrenia found in previous studies. We hypothesized that, like probands, relatives of male vs. female probands may express different forms or subsyndromal symptoms of schizophrenia, i.e., differential expression of flat affect. Studied were 332 schizophrenic probands defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (DSM-III), criteria and 725 first-degree relatives from well-known retrospective cohort family studies. Results showed that relatives of male probands were at significantly higher risk for expressing flat affect than relatives of female probands, which did not hold for relatives of normal controls. Logistic regression was used to show that when flat affect was incorporated into the definition of affected among relatives, sex differences in FMR disappeared.

Adult↗
PubMed1995

The '3 Rs' and neuropsychological function in schizophrenia: a test of the matching fallacy in biological relatives.

The 'matching fallacy' suggests that matching schizophrenic patients and normal control subjects on education or IQ may cause systematic mismatching of theoretically expected ability. This study supports a modest version of the matching fallacy effect in nonpsychotic biological relatives of schizophrenic patients. At equivalent levels of education, relatives and control subjects had similar Reading and Spelling scores on the Wide Range Achievement Test-Revised--measures that are largely unimpaired by schizophrenia-related processes. However, relatives showed a deficit in IQ (primarily verbal IQ) compared with what would be predicted from their Reading scores. A similar deficit in Arithmetic scores was found in non-college-educated relatives, but college-educated relatives showed an advantage. We discuss possible implications of the findings with regard to genetic and environmental factors.

Adult↗
PubMed1995

Frontal brain volume and context effects in short-term recall in schizophrenia.

In a group of schizophrenic patients, magnetic resonance imaging (MRI) measures of relative frontal brain volume (total frontal volume/total cerebral volume) correlated highly with the capacity to use context as an aid to recall in a verbal memory task. The dorsolateral area of the prefrontal cortex appears to have contributed most to this effect. Recall of simple word lists without contextual features revealed no correlation with relative frontal volume. With increasing contextual organization of the material, correlations between frontal volume and recall scores increased significantly. These findings are consistent with the general proposition that impairment in the use of informational redundancy is a significant component of schizophrenic pathology.

Adult↗
PubMed1995

Differential heritability of adult and juvenile antisocial traits.

BACKGROUND: Studies of adult antisocial behavior or criminality usually find genetic factors to be more important than the family environment, whereas studies of delinquency find the family environment to be more important. We compared DSM-III-R antisocial personality disorder symptoms before vs after the age of 15 years within a sample of twins, rather than comparing across studies. METHODS: We administered the Diagnostic Interview Schedule Version III-revised by telephone to 3226 pairs of male twins from the Vietnam Era Twin Registry. Biometrical modeling was applied to each symptom of antisocial personality disorder and summary measures of juvenile and adult symptoms. RESULTS: Five juvenile symptoms were significantly heritable, and five were significantly influenced by the shared environment. Eight adult symptoms were significantly heritable, and one was significantly influenced by the shared environment. The shared environment explained about six times more variance in juvenile anti-social traits than in adult traits. Shared environmental influences on adult antisocial traits overlapped entirely with those on juvenile traits. Additive genetic factors explained about six times more variance in adult vs juvenile traits. The juvenile genetic determinants overlapped completely with genetic influences on adult traits. The unique environment (plus measurement error) explained the largest proportion of variance in both juvenile and adult antisocial traits. CONCLUSIONS: Characteristics of the shared or family environment that promote antisocial behavior during childhood and early adolescence also promote later antisocial behavior, but to a much lesser extent. Genetic causal factors are much more prominent for adult than for juvenile antisocial traits.

Adolescent↗
PubMed1995

The case for heterogeneity in the etiology of schizophrenia.

To confirm etiological heterogeneity, it is required that schizophrenic patients may be separated into at least two classes having different known etiologies and, perhaps, different pathophysiological signatures. In contrast, the homogeneity hypothesis asserts that there is a single necessary and sufficient cause or configuration of causes of schizophrenia. Because the link between phenotypic heterogeneity and etiological heterogeneity is tenuous, attempts to use purely phenotypic data to infer etiologic heterogeneity must be viewed cautiously. We examined three candidate causes for schizophrenia: genes, obstetric complications and viral infection. Cytogenetic studies show that some rare cases of schizophrenia are due to gross abnormalities of chromosomes. As for the large majority of schizophrenic patients, the candidate cause data most certainly reject the most parsimonious version of the hypothesis of etiological homogeneity: that all schizophrenia is caused by exactly the same pattern of genetic mutations, birth related complications and exposure to the same viral infections. We conclude that the heterogeneity debate should consider the possibility of rewording the question: 'Heterogeneity: yes or no?' to 'Heterogeneity: how much?'

Chromosome Aberrations↗
PubMed1995

Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficiency analysis.

Numerous studies suggest that the relatives of schizophrenic patients exhibit neuropsychological impairments that are milder yet similar to those seen among schizophrenic patients. The authors assessed 35 nonpsychotic relatives of schizophrenic patients and 72 normal controls using a clinical and experimental neuropsychological test battery. Three neuropsychological functions met criteria for risk indicators of the schizophrenia genotype: abstraction, verbal memory, and auditory attention. These findings could not be attributed to parental socioeconomic status, education, general visual-spatial ability, or psychopathology. Furthermore, exploratory analyses were performed to determine whether the diagnostic efficiency of the indicators could be adjusted to meet the needs of genetic linkage analyses. These analyses suggest that psychometric considerations may help to create measures for genetic linkage studies.

Adolescent↗
PubMed1995

Correlates of psychosis proneness in relatives of schizophrenic patients.

The Magical Ideation Scale (MIS), Perceptual Aberration Scale (PABS), Social Anhedonia Scale (SAS), and Physical Anhedonia Scale (PAS) were administered to 98 relatives of schizophrenic patients along with a measure of personality disorders (the Personality Diagnostic Questionnaire--Revised). Hierarchical regression analysis indicated that the schizotypal and borderline personality disorder (PD) scales explained significant variance in both the MIS and PABS; the avoidant PD scale also explained significant variance in the PABS. The schizoid, paranoid, and avoidant PD scales explained significant variance in the SAS. Sibling intraclass correlations indicated a significant heritability of 0.62 for the PABS.

Adult↗
PubMed1995

Attention deficit hyperactivity disorder and comorbid disorders: issues of overlapping symptoms.

OBJECTIVE: Since some symptoms are shared by both attention deficit hyperactivity disorder (ADHD) and comorbid psychiatric conditions, it is possible that a diagnosis of ADHD is an artifact of the overlapping symptoms. This article focuses on the assessment of the influence of overlapping symptoms on the diagnosis of ADHD. METHOD: Three groups of subjects were studied: a group of clinically referred children and adolescents, a group of nonreferred adults who were the parents of these children and adolescents, and a group of clinically referred adults with ADHD. The authors assessed the extent of symptom overlap between ADHD and the disorders that frequently co-occur with ADHD; major depression, bipolar disorder, and generalized anxiety disorder. To determine the degree to which this symptom overlap influences these diagnoses, each individual was rediagnosed on the basis of two different techniques that corrected for the overlapping symptoms, a subtraction method and a proportion method. RESULTS: The majority of subjects who had both ADHD and a comorbid psychiatric disorder maintained their diagnosis of ADHD when the overlapping symptoms were subtracted. Moreover, when overlapping ADHD symptoms were subtracted, on average, 79% maintained their diagnosis of major depression, 56% maintained their diagnosis of bipolar disorder, and 75% maintained their diagnosis of generalized anxiety disorder. CONCLUSIONS: These findings show that ADHD is not an artifact of symptoms shared with other psychiatric disorders and that the comorbid conditions themselves are not an artifact of overlapping ADHD symptoms.

Adolescent↗
PubMed1995

Diagnostic accuracy and linkage analysis: how useful are schizophrenia spectrum phenotypes?

OBJECTIVE: Numerous studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit psychiatric and other features that discriminate them from normal comparison subjects. These features have been put forth as "spectrum" phenotypes that may be variant manifestations of the schizophrenia genotype. However, most of these studies do not address a key measurement question: does the diagnostic accuracy of these spectrum classifications warrant their use in genetic linkage studies of schizophrenia? METHOD: The authors reviewed 30 studies of putative indicators of the schizophrenic genotype: schizotypal personality disorder, eye tracking dysfunction, attentional impairment, auditory evoked potentials, neurological signs, neuropsychological impairment, and allusive thinking. RESULTS: Although each of 42 measures of these indicators discriminated the relatives of schizophrenic patients from the normal comparison subjects, a diagnostic accuracy analysis suggested that only six of these would improve the informativeness of genetic linkage data. CONCLUSIONS: Many proposed spectrum phenotypes for schizophrenia may not be useful for linkage analysis because of high false positive rates (poor specificity). Future work aimed at describing and developing phenotypes for linkage analysis should assess the diagnostic accuracy of proposed measures.

Attention↗
PubMed1995

Adolescent problem behaviors as predictors of adult alcohol diagnoses.

Young adult alcohol problems based on DIS/DSM III diagnoses were predicted from a number of adolescent risky/antisocial behaviors in a sample of 693 subjects. The number of times an individual was intoxicated before his/her sixteenth birthday was the best indicator of adult alcohol "abuse" and /or dependence, with adolescent fighting, arrests, and lack of participation in religious activities also serving as important problem behavior predictors. Results of correlational and principal-components analyses of adolescent problem behaviors are similar to previous work on Problem Behavior Theory. The results suggest that prevention efforts should begin before adolescence, prior to the time when individuals are exposed to, or begin practicing, adult health-threatening activities.

Adolescent↗
PubMed1995

Genetic heterogeneity of schizophrenia.

The cumulative evidence from over a century of research overwhelmingly implicates genes in the etiology of Schizophrenia. Twin studies consistently find higher rates of schizophrenia among cotwins of monozygotic compared with dizygotic twins and adoption studies show that familial transmission is mediated by genetic, not adoptive relationships. Nevertheless, the hunt for schizophrenia genes with molecular genetic technologies has been disappointing. Although the available literature suggests that cytogenetic abnormalities cause some cases of schizophrenia, these abnormalities must account for only a small fraction of all schizophrenia. Attempts to scan the entire genome with DNA markers spaced at regular intervals have failed to produce unequivocal linkage findings. Notably, several groups have reported findings suggestive of linkage to chromosome 22 and other work provides weak evidence of a gene on the sex chromosomes. The search for schizophrenia genes has been complicated by its unknown mode of transmission, the possibility of phenocopies and genetic heterogeneity.

Female↗
PubMed1994

Comparison of schizotypal relatives of schizophrenic versus affective probands.

In order to investigate possible heterogeneity in schizotypal personality disorder (SPD), two groups of schizotypals, one related to schizophrenic probands (FSPD) (n = 34) and one related to affective disorder probands (NFSPD) (n = 14), ascertained in the same family study, were compared. The FSPD group had more inadequate rapport; the groups did not differ in the frequency of any other symptoms of SPD. NFSPDs had higher rates of comorbid histrionic PD and a trend for higher rates of impulsive/dramatic cluster PDs. FSPDs had a trend for higher rates of anxiety disorders. There was a higher risk of bipolar disorder in the relatives of NFSPDs and higher risk for anxiety disorders in the relatives of FSPDs. The relatives of NFSPDs had higher rates for histrionic, narcissistic, and atypical PDs and for having at least one PD.

Adult↗
PubMed1994

Relationship of prefrontal and temporal lobe MRI measures to neuropsychological performance in chronic schizophrenia.

This preliminary study focused on the relationship between prefrontal and temporal lobe MRI measures and neuropsychological performance in chronic schizophrenia. Seventeen schizophrenic inpatients received an MRI and a neuropsychological test battery after clinical stabilization, on average 2 months after admission. The central finding was a significant inverse correlation between neurocognitive measures of prefrontal function and dorsolateral prefrontal cortex (DLPFC) area, strongest in the left hemisphere. Neurocognitive performance did not correlate significantly with orbital frontal area or total temporal lobe volume. The correlations of neuropsychological performance with total frontal volume and whole brain volume were generally not significant, although the pattern was similar to that associated with the DLPFC. Because a number of executive-attention and abstraction measures were significantly associated with the DLPFC, dysfunctions of this region may underlie a syndrome of cognitive dysfunctions. Long-term memory functions were also significantly correlated with the DLPFC, raising the possibility that recall memory defects in schizophrenia are, in part, associated with prefrontal contributions of attention, abstract reasoning, and executive function. This study needs replication with a larger sample of patients and more comprehensive volumetric morphometric analyses.

Adolescent↗
PubMed1994

Systematized delusions and neuropsychological function in paranoid and nonparanoid schizophrenia.

We extended research originating with the Tsuang-Winokur criteria for paranoid and nonparanoid schizophrenia. To partially resolve problems of subtype instability, 41 consecutive admissions meeting DSM-III-R criteria for schizophrenia were subdivided according to whether they ever experienced prominent systematized delusions. Neuropsychological profiles for paranoid patients and nonparanoids with a history of systematized delusions were extremely similar. When combined, this 'systematized' group had significantly better general verbal ability and verbal memory than patients who never manifested systematized delusions. There was also a significant neuropsychological function-by-group interaction. The neuropsychological data suggested that systematized patients had better premorbid cognitive functioning as well as a greater discrepancy between premorbid verbal ability and current attentional functioning. No between-group differences were found on a measure of prefrontal-executive function, nor were there any neuropsychological differences between traditionally defined (DSM-III-R) paranoid and nonparanoid subgroups. This study suggests a possible shift in the dividing line between paranoid and nonparanoid subtypes and illustrates the potential value of neuropsychological data for refining psychiatric nosologies.

Adult↗
PubMed1994

Neuropsychological risk indicators for schizophrenia: a review of family studies.

We reviewed potential neuropsychological risk indicators for schizophrenia by addressing two broad questions about neuropsychological performance in biological relatives of schizophrenia patients: (1) Is there evidence of deficits, and, if so, (2) are those deficits similar to deficits found in schizophrenia patients themselves? There has not yet been adequate validation of most neuropsychological risk indicators, but promising leads have emerged from studies of relatives of persons with schizophrenia. The strongest evidence of impairment in relatives was in sustained attention, perceptual-motor speed, and concept formation and abstraction; to a slightly lesser extent, mental control/encoding (primarily with distraction) was implicated as well. Impairments in verbal memory and verbal fluency were also found, although these have been less well studied. The pattern of deficits paralleled that found in schizophrenia patients, thus suggesting dysfunction in prefrontal, temporal-limbic, and attentional systems. Findings were similar for children and adult relatives of schizophrenia patients. It is suggested that future studies (1) emphasize comprehensive test batteries, (2) develop composite neuropsychological measures, (3) use profile and deviant-responder analyses, (4) include psychiatric comparison groups, and (5) integrate neuropsychological assessments with brain imaging techniques.

Adolescent↗
PubMed1994

Estimating the morbidity risk for diseases having a variable age at onset.

The morbidity risk assesses the risk of manifesting illnesses having a variable age at onset. We reviewed the conceptual derivation and critical assumptions of various methods for estimating morbidity risk by classifying them into two approaches. One approach uses an age at onset distribution as a weighting system. A second approach uses methods from survival analysis. Because survival methods estimate the morbidity risk and age at onset distribution simultaneously, they are preferable to weighting methods. Among weighting methods, Strömgren's estimator or Risch's maximum likelihood estimate are the methods of choice; the Kaplan-Meier estimator is the preferred survival analysis approach.

Age of Onset↗