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M J Lyons

Publications and source records attributed to M J Lyons.

At least 73 records · Page 4Linked to original sources
PubMed1993

A strategy for assembling samples of adult twin pairs in the United States.

In this paper we develop a methodology for the identification of large numbers of U.S. adult twin pairs. Data for this study derive from the U.S. Department of Defense and the Vietnam Era Twin (VET) Registry. The Department of Defense identified potential male twins (n = 10,002) using a computerized record linkage algorithm based on the same last name, same date of birth, and the same first five digits of the Social Security number. Twinship was confirmed by comparison with the Vietnam Era Twin Registry. We developed a logistic regression model that predicts the probability that a paired record identifies twins based on the absolute difference in the last four digits in the Social Security number, the age of issuance of the Social Security number, and the frequency of occurrence of the last name. We used the estimated coefficients derived from this regression model to assign predicted probabilities of being a twin to each matched record. There is a close correspondence between the observed and expected number of twins when evaluated across deciles of predicted probabilities of being a twin; the value of the Harrell's c index (c = 0.68 +/- 0.0004) indicates the overall predictive accuracy of the regression equation. The results from this study demonstrate the feasibility of identifying adult male-male twin pairs from any large computerized database that contains name, date of birth and Social Security number. However, the selection criteria used in the creation of the computer database must be clearly specified to avoid constructing a biased sample of twins.

Adult↗
PubMed1993

Do genes influence exposure to trauma? A twin study of combat.

Data from 4,029 male-male twin pairs who served in the United States military during the Vietnam era (1965-1975) were used to examine genetic and non-genetic factors that influence wartime exposure to traumatic events. Specific events examined were volunteering for service in Vietnam, actual service in Southeast Asia, a composite index of 18 combat experiences, and information from military records about being awarded combat decorations. Correlations within monozygotic (MZ) and dizygotic (DZ) twin pairs for volunteering for service in Vietnam were 0.40 and 0.22, respectively. For actually serving in Southeast Asia, the MZ correlation was 0.41 and the DZ correlation was 0.24. Analysis of twin pairs in which both siblings served in Southeast Asia (n = 820) demonstrated a correlation for self-reported combat experiences within MZ and DZ pairs of 0.53 and 0.30, respectively. Heritability estimates ranged from 35 to 47%. The family environment did not have a significant effect on any of the variables. Analyses of data from military records regarding being awarded a combat decoration provided very similar results to those found for self-reported combat experiences.

Adult↗
PubMed1993

A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms.

We studied 4042 Vietnam era veteran monozygotic and dizygotic male twin pairs to determine the effects of heredity, shared environment, and unique environment on the liability for 15 self-reported posttraumatic stress disorder symptoms included in the symptom categories of reexperiencing the trauma, avoidance of stimuli related to the trauma, and increased arousal. Quantitative genetic analysis reveals that inheritance has a substantial influence on liability for all symptoms. Symptoms in the reexperiencing cluster and one symptom in the avoidance and numbing cluster are strongly associated with combat exposure, and monozygotic pairs are more highly concordant for combat exposure than dizygotic pairs. By fitting a bivariate genetic model, we show that there are significant genetic influences on symptom liability, even after adjusting for differences in combat exposure; genetic factors account for 13% to 30% of the variance in liability for symptoms in the reexperiencing cluster, 30% to 34% for symptoms in the avoidance cluster, and 28% to 32% for symptoms in the arousal cluster. There is no evidence that shared environment contributes to the development of posttraumatic stress disorder symptoms.

Asia, Southeastern↗
PubMed1993

Identification of the phenotype in psychiatric genetics.

Statistical procedures and molecular genetic techniques have attained a fine degree of resolution. Their ability to find disease genes has revolutionized medicine and raised hopes for breakthroughs in psychiatry. However, such breakthroughs may require an equally discriminating nosology. A psychiatric genetic nosology seeks to classify patients into categories that correspond to distinct genetic entities by addressing the problem of diagnostic accuracy: the degree to which a diagnosis correctly classifies people with and without a putative genetic illness. We review methods that deal with misclassification in genetic studies. These are clinical and epidemiological approaches that deal directly with how to define the observable manifestation of a putative genotype. We discuss two groups of methods: those that use known phenotypes and those that design new phenotypes.

Aged↗
PubMed1993

A family study of self-reported personality traits and DSM-III-R personality disorders.

Personality traits and DSM-III-R personality disorders of first-degree relatives of patients with psychoses were studied using the NEO Five-Factor Inventory (NEO-FFI) and the Personality Diagnostic Questionnaire-Revised (PDQ-R), two self-report instruments. The relatives were compared on their scores for the five personality factors in the NEO-FFI, the prevalence of individual DSM-III-R personality disorders, and their scores for each personality disorder scale in the PDQ-R. The results suggest that there is no difference in personality traits and prevalence of personality disorders, including schizophrenia spectrum disorders, when relatives of patients with schizophrenia, bipolar disorder, and major depression are compared to each other. Relatives of patients with "atypical psychosis," psychotic disorders that do not meet DSM-III-R criteria for any specific nonorganic psychotic disorder, may be a distinctive group.

Adult↗
PubMed1992

Stripe selection: an intrinsic property of some pattern-forming models with nonlinear dynamics.

In two-dimensional pattern formation, the genesis of stripped rather than spotted patterns may involve preexisting spatial asymmetries, such as unidirectional gradients or asymmetric shape of the pattern-forming domain. In the absence of such asymmetries, some kinds of nonlinear dynamics still lead to striped rather than spotted patterns. We have studied the latter effect both by extensive computer experiments on a range of nonlinear models and by mathematical analysis. We conclude that, when the dynamic equations are written in terms of departure from the unpatterned state, the presence of nonlinearities which are odd functions of these departures (e.g., cubic terms) together with absence of even nonlinearities (e.g., quadratic terms) ensures stripe formation. In computer experiments, we have studied the dynamics of two-morphogen reaction-diffusion models. The mathematical analysis presented in the Appendix shows that the same property exists in more generalized models for pattern formation in the primary visual cortex.

Animals↗
PubMed1992

Elementary methods for the analysis of dichotomous outcomes in unselected samples of twins.

This paper presents an elementary statistical method for analyzing dichotomous outcomes in unselected samples of twin pairs using stratified estimators of the odds ratio. The methodology begins by first randomly designating one member of each twin pair as an "index" twin and the other member as the "co-twin." Stratifying on zygosity, odds ratios are used to measure the association between disease in the index twin and disease in the co-twin. From these zygosity-specific tables we calculate the Woolf-Haldane estimator of the common odds ratio (psi F, the weighted average of the zygosity-specific odds ratios), the Mantel-Haenszel test statistic (chi 2M-H) for the common odds ratio, and a test (chi 2G) for the difference in the zygosity-specific odds ratios. In this application, psi F provides an estimate of the familial association for disease and the accompanying chi 2M-H provides a test of the null hypothesis, psi F = 1 (i.e., there is no evidence for a familial influence on disease). The chi 2G is a test of the null hypothesis that psi MZ = psi DZ; a significant value for chi 2G suggests a genetic influence on disease (assuming that the observed odds ratios follow a pattern where psi MZ greater than psi DZ). A new test statistic (chi 2c) is proposed that incorporates the expectation that psi MZ = psi 2DZ under a purely additive genetic model with no common environmental effects. A significant value of chi c2 indicates that the different odds ratios across zygosity are partly due to common environmental influences. Conversely, a nonsignificant value of chi 2c is an indication that the zygosity-specific odds ratios are due solely to additive genetic effects and not to common environment. This basic approach is extended to examine the effects of measured indicators of the specific environment and the assessment of certain forms of gene by environment interaction. All of the methods are easily understood, highly flexible, readily computed using a hand calculator, and incorporate the inherent genetic information contained within twin samples.

Data Interpretation, Statistical↗
PubMed1992

Using vulnerability indicators to compare conceptual models of genetic heterogeneity in schizophrenia.

The search for indicators of vulnerability has been important in schizophrenia research, but, as in many areas, progress has been impeded due to the heterogeneity of schizophrenic disorders. How one conceptualizes the observed heterogeneity is dependent upon the particular genetic model to which one subscribes. In this article, we delineate several models that may account for the distributions of vulnerability indicators in groups of schizophrenic patients and their ill and well relatives. We present these models for heuristic purposes so that they may serve to guide the interpretation of data with respect to the issue of teasing apart familial and nonfamilial environmental components of putative vulnerability indicators. It is suggested that investigators will profit by: a) efforts to combine psychiatric genetic paradigms in order to maximize the yield of family study data, and b) thinking in terms of comparing the ability of different models to account for research findings.

Data Interpretation, Statistical↗
PubMed1992

Virus-induced obesity in mice: association with a hypothalamic lesion.

In an earlier study we found that a substantial percentage of mice surviving infection with canine distemper virus (CDV) slowly developed a morbid obesity syndrome. In the present study we wished to explore the role of the virus in the development of this syndrome. The distribution of viral antigen(s) in brains of pre-obese animals shortly after intracerebral infection was mapped using immunocytochemical procedures. A distinctive pattern of cell labeling was found, extending from the anterior periventricular hypothalamus ventrally and caudally toward the posterior hypothalamus. The heaviest concentration of labeled cells was found in the arcuate-ventromedial area. Viral antigen-containing cells were not found in obese brain specimens. However, the latter revealed, by glial fibrillary acidic protein immunostaining, a gliotic lesion of the hypothalamus that approximated topographically the pattern of virus tropism. Examination of the arcuate area revealed a significant reduction in tyrosine hydroxylase immunoreactive and pro-opiomelanocortin mRNA positive perikarya. We suggest that the loss of critical populations of hypothalamic neurons as a result of an antecedent viral infection led ultimately to the development of morbid obesity.

Animals↗
PubMed1990

Depletion of tissue glutathione with diethyl maleate enhances hyperbaric oxygen toxicity.

Rats exposed to hyperbaric hyperoxia experience severe central nervous system and lung toxicity. Exogenous glutathione administration has been shown to protect rats from the effects of hyperbaric hyperoxia. To explore the hypothesis that decreases in tissue glutathione (GSH) could increase the susceptibility of rats to hyperbaric hyperoxia, we administered diethyl maleate (DEM) (a compound that conjugates with GSH and rapidly lowers tissue levels) and measured tissue GSH levels. DEM administration decreased plasma GSH by 86%, liver GSH by 82%, and brain GSH by 45% between 2 and 4 h after injection with values returning to normal by 24 h. We then treated rats with DEM or saline and began exposure at 2 h after treatment to 100% oxygen at 4 ATA. Time-to-convulsion and time-to-death were recorded. Rats that received DEM 2 h before exposure seized earlier and died earlier than controls. Intraperitoneal administration of GSH to DEM-treated rats abolished the enhanced toxicity occurring during a hyperbaric hyperoxic exposure. DEM appears to increase the toxicity of rats exposed to hyperbaric hyperoxia by lowering tissue GSH levels, and replenishment of lung and brain GSH by exogenous administration reverses these effects.

Animals↗
PubMed1990

Heterogeneity of schizophrenia. Conceptual models and analytic strategies.

Schizophrenia is clinically heterogeneous but it is not known whether this is due to the existence of discrete subtypes. For the purpose of explication, 'indicators' of schizophrenia are divided into three levels: phenomenology, pathophysiology, and aetiology. Five heterogeneity models and a number of quantitative approaches are described. It is imperative to apply rigorous methods of study to the comparison of unitary models and competing heterogeneity models of schizophrenia.

Humans↗
PubMed1987

Sex differences in affective disorder: genetic transmission.

Epidemiological studies have consistently found women to be at greater risk than men for affective disorders. This sex effect may help clarify genetic transmission and heterogeneity. Data from eight family studies of unipolar and eight family studies of bipolar probands were used to calculate family resemblance sex ratios. These observed sex ratios were then compared to sex ratios predicted by X-linked and nonfamilial effects models. Maximum likelihood estimation of competing models revealed that X linkage was not a good fit to the unipolar data. The bipolar studies were not consistent with either the X-linked or the nonfamilial effects model.

Bipolar Disorder↗
PubMed1987

Production of potent polyclonal antibodies to bacterial membrane amphiphiles.

Lipid A (LA), ketodeoxyoctonate (KDO) and lipoteichoic acids (LTA) were used to produce homologous polyclonal antibodies. These haptens were administered to rabbits in differing immunogenic forms, using multiple intradermal and intraperitoneal injections with complete Freund adjuvant. Booster injections were either made intradermally with incomplete Freund adjuvant or intravenously in saline. The immune-response was monitored regularly with an enzyme-immunoassay. Lipid A and KDO covalently linked to bovine serum albumin (BSA), with hapten densities per BSA molecule of 17 and 9, respectively, produced nondetectable immune-response. Acid-hydrolysed and intact cells of Salmonella minnesota Re 595 used as LA and KDO immunogens, respectively, produced significant immune-response when administered intradermally or intraperitoneally. Good immune-response was obtained with LTA covalently linked to BAS. However, a better result was obtained with crude LTA, containing 21.5% proteins. Generally, the lengthy immunization schedules used produced IgG antibodies to the antigens and the highest reciprocal titres attained were 75,000, 55,000 and 150,000 for LA, KDO and LTA, respectively. Meaningful expression of antisera titres by enzyme-immunoassay is discussed. We defined titre as the reciprocal antiserum dilution of the intercept of the mid-point on the linear section ending at 0.2 absorbance on the antiserum dilution curve.

Animals↗
PubMed1987

Problems of diagnoses in family studies.

This paper discusses applications of advances in psychiatric diagnostic practice to genetic research. Diagnostic misclassification and unreliability can lead to spurious conclusions about patterns of familial aggregation and co-aggregation of psychiatric disorders. Subject, occasion, information, observation and criterion variance are the major components of unreliability in diagnosis. Structured diagnostic criteria are useful for reducing errors; they may, however, lead to unjustified confidence due to their algorithmic and semi-quantitative format. Six misconceptions regarding such criteria are discussed. The choice of instruments and method of implementation must take into account the qualifications of interviewers and the need for blindness in the experimental design. A fundamental design decision in psychiatric genetic research is the choice between the family history or family study method. The costs and benefits of each method are examined. Finally, the psychiatric geneticist must face the problem of defining the ill phenotype. This is made difficult by the presence of phenocopies and the possibility that milder spectrum disorders and some symptom-free individuals may carry the genotype that underlies the phenotype of the more severe clinical form of the disorder.

Diagnosis, Differential↗
PubMed1986

Inhibition of acute experimental allergic encephalomyelitis in mice by colchicine.

Colchicine was found to inhibit the clinical and histopathological manifestations of monophasic experimental allergic encephalomyelitis in mice. For inhibition of actively induced disease, inoculation of colchicine at the time of encephalitogenic challenge was found to be most effective. In adoptive transfer experiments, lymph node cells (LNC) from colchicine treated donors failed to transfer the disease. Additionally, colchicine treatment of recipients receiving an otherwise disease-inducing level of sensitized LNC prevented the development of disease. Experiments involving delayed-type hypersensitivity expression support an inhibitory role for the drug on event(s) of the efferent pathway of the cellular immune response.

Animals↗
PubMed1985

Immunological relationships between Salmonella flagella and their potential application for salmonellae detection by immunoassay.

Native flagella of ten Salmonella serotypes were shown to possess serotype-specific antigenic determinants as well as a multiple of common antigenic determinants, which varied in concentration. Each common antigenic determinant was shared by certain, but not all, serotypes. This has been demonstrated from agglutination and radioimmunometric assay (RIMA) results, using ten antisera raised in rabbits against purified polymeric flagellins from ten Salmonella serotypes as immunogens. The minimum detectable populations of salmonellae, as determined by RIMA varied considerably, due to variation in concentrations (and possibly types) of common antigenic determinants. However, the results demonstrated the feasibility of utilizing RIMA for the qualitative detection of salmonellae, using a mixture of only the ten antisera and 125I-labelled protein A as a general tracer. In this way, 77 different salmonellae were detected in less than 8 h after culturing in selective broth. The RIMA developed was specific for salmonellae and showed no cross-reactions with high populations of other members within the family Enterobacteriaceae.

Agglutination↗