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Biomedical subjects

C R Cloninger

Publications and source records attributed to C R Cloninger.

At least 145 records · Page 8Linked to original sources
PubMed1985

Pentametric distribution of platelet monoamine oxidase activity.

The distribution of catalytic activity of platelet monoamine oxidase (MAO) with both tryptamine and phenylethylamine as substrates was examined in 1,129 Swedish men at age 18 years. A mixture of five components was needed to describe the distribution, even when the original scale was transformed to remove skewness. The proportions of admixture were 2% for the extremely low component with a mean of -2.3 sigma, 29% for moderately low MAO (mean -0.8 sigma), 51% for intermediate MAO (mean 0.0 sigma), 15% for moderately high MAO (mean + 1.3 sigma), and 3% for extremely high MAO (mean + 3.0 sigma). Thus, the upper and lower deciles each contain contributions from two extreme components that differ from a much larger intermediate component with activity near the mean of the general population. This is compatible with a minimum of three alleles at a single major locus or with at least two polymorphic loci. The hypothesis that MAO activity is controlled by two alleles at a single locus was tested and rejected. The demonstration of at least five distinct components to the distribution of MAO warrants further research to characterize the biochemical structure and function of MAO enzyme variants as well as study of the behavioral correlates of the components.

Adolescent↗
PubMed1985

Genetics of alcoholism.

Great progress has been made by research on the contribution genetic factors make to a vulnerability toward alcoholism. Animal studies have demonstrated the importance of genetics in ethanol preference and levels of consumption, and human family, twin, and adoption research have revealed a 4-fold higher risk for offspring of alcoholics, even if they were adopted out at birth. The work presented in this symposium reviews the ongoing search for genetic trait markers of a vulnerability toward alcoholism. Dr. Li has used both animal and human research to demonstrate the possible importance of the genetic control of enzymes involved in ethanol metabolism and has worked to help develop an animal model of alcoholism. The possible importance of subgroups with different levels of predisposition toward alcoholism is emphasized by Dr. Cloninger. An overview of the studies of sons of alcoholics, given by Dr. Schuckit, reveals the potential importance of a decreased intensity of reaction to ethanol as part of a predisposition toward alcoholism and discusses the possible impact of some brain waves and ethanol metabolites to an alcoholism vulnerability. Dr. Deitrich reviews interrelationships between studies of animals and humans in the search for factors involved in a genetic vulnerability toward alcoholism. Taken together, these presentations underscore the importance of genetic factors in alcoholism, review animal and human research attempting to identify markers of a vulnerability, and reveal the high level of interaction between human and animal research.

Adoption↗
PubMed1985

Alcohol misuse and depression in women criminals.

The interaction of alcohol misuse and major depressive syndromes was examined in 66 convicted women felons. At an initial (index) evaluation and during a 6-yr follow-up, alcohol misuse and depression, although both highly prevalent, were not significantly related. Alcohol misusing and nonmisusing depressives had similar rates of treatment for depression. Follow-up alcohol misuse, occurring in one-quarter of those reinterviewed, was not predicted by an index history of depression even among index alcohol misusers. Nonsignificant trends did suggest some association between the two symptom groups. Depressive subjects with a history of alcohol misuse had a greater rate of depression during follow-up than nonmisusing index depressives. Follow-up misusers had a greater rate of follow-up depression than nonmisusers. Alcohol-related depression could not be discounted simply as a consequence of alcohol misuse. Depression in the context of alcohol misuse was highly predictive of future depression and suicide attempts. The relative independence of alcohol misuse and depression in this group underscores the complexity of their interaction, especially in a population with multiple disorders such as women criminals. The contention that phenomenologically defined major depressive disorders are heterogeneous is supported.

Adult↗
PubMed1985

Frequency and differential diagnosis of depressive syndromes in schizophrenia.

The frequency, differential diagnosis, and implications of depression occurring in the course of schizophrenia are considered in light of recently reported findings from a follow-up and family study of 500 psychiatric outpatients (the St. Louis 500 Study). Problems in diagnosis are illustrated in an interview of a schizophrenic patient with a history of depression. Nearly 60% of the schizophrenics studied had suffered a depressive syndrome during the course of their schizophrenic illness, supporting the observations of others. The majority of patients with a history of depression who were otherwise diagnosable as schizophrenic had a course of illness consistent with schizophrenia during follow-up. The pattern of illness among first-degree relatives suggested that intercurrent depression did not represent a biologic unity with primary affective disorder. Intercurrent depression should not be overinterpreted in excluding a diagnosis of schizophrenia.

Adult↗
PubMed1984

An adoption study of somatoform disorders. I. The relationship of somatization to psychiatric disability.

The relationship between psychiatric impairment and disability due to somatic complaints was studied in 859 women adopted at an early age by nonrelatives in Sweden. The clinical data were derived from the comprehensive registrations for all medical treatment and sick-leave compensation that are kept about Swedish residents by the National Health Insurance Board. The adoptees were compared with nonadopted controls who were individually matched for social and demographic variables. We identified a somatization syndrome that is consistently associated with psychiatric impairment and repeated brief periods of disability with chief complaints of headache, backache, and abdominal distress on different occasions. A method for clinically distinguishing "somatizers" from other women was derived in one sample and was shown to have a classification accuracy of 97% in a replication sample. Somatizers accounted for 36% of all cases of psychiatric disability and 48% of all sick-leave occasions in adopted women. Compared with nonadoptees, there was an excess of somatizers in adoptees, a population known to have an excess of biological parents who are criminal and/or alcoholic.

Adoption↗
PubMed1984

An adoption study of somatoform disorders. II. Identification of two discrete somatoform disorders.

linical heterogeneity among women with prominent somatization was studied in a population of 859 adopted women in Sweden. We distinguished two groups of "somatizers" who differ in both the diversity of their somatic complaints and the frequency of their periods of disability. Type 1 or high-frequency somatizers have a high frequency of psychiatric, abdominal, and back complaints. Type 2 or diversiform somatizers have less frequent disability, but a greater diversity of complaints per occasion than do other somatizers. Diversiform somatizers have psychiatric chief complaints or backache in a lower proportion of their sick periods than either high-frequency somatizers or nonsomatizers. Quantitative measures of frequency and diversity were derived in a series of discriminant analyses. The distribution of scores on these measures indicated that high-frequency somatization and diversiform somatization were discrete disorders with little clinical overlap and rare intermediate cases. This demonstration of two discrete types of somatizers was confirmed in a replication sample.

Adolescent↗
PubMed1984

An adoption study of somatoform disorders. III. Cross-fostering analysis and genetic relationship to alcoholism and criminality.

The genetic and environmental antecedents of two clinically distinct somatoform disorders were compared in 859 Swedish women adopted at an early age by nonrelatives. The characteristics of both the biological and adoptive parents of high-frequency "somatizers" were different from those of diversiform somatizers. The risk of diversiform somatization was increased in the adopted-away daughters of men treated for male-limited (type 2) alcoholism, but not in daughters of milieu-limited (type 1) alcoholics. In contrast, the biological fathers of high-frequency somatizers often had a history of recurrent convictions for violent crimes since adolescence, but no treatment for alcoholism. Similarly, alcohol abuse by the adoptive father was associated with increased risk of diversiform but not high-frequency somatization. Thus, high-frequency and diversiform somatization are not only clinically distinct, but also have different genetic and environmental backgrounds. The association of diversiform somatization with male-limited alcoholism, and not with milieu-limited alcoholism, also provides independent support for our earlier distinction between these two types of alcoholism.

Adolescent↗
PubMed1984

Detection of major gene for Gilles de la Tourette syndrome.

The families of 250 consecutive, unselected patients with Tourette syndrome (TS) were analyzed. If the parents had either motor or vocal tics, but not both, there was an increased risk of both TS and tics in the offspring. The mode of inheritance of the combined tic-Tourette trait was evaluated in both nuclear families and extended pedigrees. Complex segregation analysis was carried out allowing for possible contributions from both a major autosomal locus and multifactorial inheritance of variation in the background of each genotype. The most likely mode of inheritance was a major semidominant gene, Ts, with low heritability of the multifactorial background variation. This was true regardless of assumptions about the prevalence of the disorder. The hypothesis of strict multifactorial inheritance could not be rejected with nuclear family data alone. However, the hypothesis of no major gene effect was rejected using data on 3 generations for any estimate of lifetime risk less than 12 per 1,000 in the general population. A pure recessive major gene effect was also rejected. With a gene frequency of approximately .5%, the penetrance was estimated to be about 94% in abnormal Ts/Ts homozygotes, 50% in Ts/ts heterozygotes, and less than 0.3% in normal ts/ts homozygotes. More than two of every three cases are heterozygotes, and nearly all other cases are phenocopies or new mutations. This is the first demonstration by segregation analysis of a major gene in a human neuropsychiatric disorder with a frequency approaching 1% of the population.

Alleles↗
PubMed1983

Lithium ion transport and affective disorders within families of bipolar patients. Identification of a major gene locus.

We have identified a genetic polymorphism in which one allele results in elevated RBC lithium ion ratios and also contributes to vulnerability to some forms of affective disorders. Interindividual variability in the lithium ion ratio (the ratio of the RBC to the plasma lithium ion concentration) is determined by variability in a lithium ion ratio (the ratio of the RBC to the plasma lithium ion concentration) is determined by variability in a lithium-sodium ion counterflow mechanism. Segregation analyses were conducted on lithium ion ratios in vitro in members of 120 normal families and on both the lithium ion ratio and the history of affective disorder in first-degree relatives of 31 bipolar patients. These analyses provided evidence for an autosomal major gene locus that influences the lithium ion ratio both in members of normal families and in relatives of bipolar patients. The allele at the major locus resulting in elevated lithium ion ratios was associated with an increased likelihood of psychiatric hospitalization among relatives of bipolar patients.

Alleles↗
PubMed1983

An adoption study of depressive disorders and substance abuse.

Registered psychiatric illness was studied in the biologic and adoptive parents of 115 adoptees with affective disorders or histories of substance abuse. The parents of these patients were compared with those of 115 control subjects who were pairwise matched for demographic and social variables and who had no psychiatric illness. Psychiatric patients had a fivefold excess of adoptive fathers who had psychiatric illness compared with fathers of their matched controls. This was due to an excess of affective disorders in adoptive fathers regardless of the sex or diagnosis of the adopted child. Biologic mothers of female patients had a threefold increase in psychiatric illness compared with mothers of their matched controls and a fourfold increase compared with mothers of male adoptees. However there was no significant concordance between specific diagnoses in biologic parents and their adopted-away children. Subdivision of depressive patients according to psychotic-nonpsychotic and reactive-nonreactive dichotomies did not yield subgroups with distinct family histories.

Adolescent↗
PubMed1983

A follow-up and family study of schizophrenia.

The Washington University Psychiatry Clinic, St Louis, study began with the systematic clinical evaluation of a cross section of 500 of the clinic's patients. This was followed by a "blind" follow-up of the index subjects and a blind study of first-degree relatives. This report deals with the diagnosis of schizophrenia at index, at follow-up, and among the first-degree relatives. The results indicate that the criteria used for the diagnosis of schizophrenia select patients who show a high degree of diagnostic consistency over many years, although not all patients who meet these criteria after follow-up receive the diagnosis of schizophrenia initially. Most important, the diagnostic criteria select cases associated with a strong familial increase in the risk of schizophrenia (nearly fivefold). The follow-up results indicate also that Feighner-positive schizophrenics often experience intercurrent depressions, but that the presence of such depressions does not affect the familial incidence of either schizophrenia or primary affective disorders.

Depressive Disorder↗
PubMed1983

Predictors of mortality in alcoholic women: prospective follow-up study.

An 11-year follow-up of 100 alcoholic women who were systematically interviewed and diagnosed during hospitalization found 31% dead, the majority as a result of alcohol-related causes. There were over 4 times as many deaths in alcoholic women as expected in the general population. The life span of alcoholic women was shortened by over 15 years. Only those women who had abstained during the interval following hospitalization had fewer than expected deaths. Five variables correctly predicted survival status for 79% of the subjects (80% of survivors and 77% of those who died): older age at index, onset of alcoholism before age 30, history of frequent benders, primary diagnosis of antisocial personality, and short-term drinking status.

Adolescent↗
PubMed1983

A defense of path analysis in genetic epidemiology.

Contemporary models of multifactorial inheritance are described and justified from the perspective of their intended use in genetic epidemiology and their developmental sequence. Substantial empirical data and statistical theory support the practical adequacy of the assumptions of path analysis for most multifactorial traits that show vertical inheritance. The choice of scale for quantitative traits must be considered on an individual basis. From both biological and statistical perspectives, transformations of scale may be more appropriate for analysis than the measurements are themselves. Recent criticism of contemporary models and computational procedures is based on a caricature of path analysis rather than on the method as it is actually practiced. The utility of path analysis is primarily limited by an investigator's biological insight and analytical skill, not by the method's assumptions. Model-free descriptive statistics are inherently inadequate to characterize the stable and autonomous features of the underlying mechanisms that generate observable variation in multifactorial traits. In contrast, path analysis has led to remarkably stable estimates of structural parameters for a wide variety of important biological traits. While exploratory methods can be useful for preliminary data inspection, they cannot substitute for formal tests of hypotheses based on explicit, falsifiable models.

Genetics, Medical↗
PubMed1983

Genetic diversity, genome organization, and investigation of the etiology of psychiatric diseases.

Recent advances in our understanding of the structure and organization of the human genome have strong implications for investigations of the diagnosis and etiology of psychiatric disorders. The concept of human genes as contiguous regions of DNA has been discarded and replaced by the concept of a gene split in separate pieces that must be spliced in order to make its protein products. The 'one gene - one enzyme' concept has also been modified to allow for the observation that many functional proteins are composed of multiple subunits, each coded by separate genes, whose expression is regulated by many other genetic and environmental factors. Consequently, the development of a complex phenotype cannot be predicted from knowledge of even the entire DNA sequence, and exploratory methods that rely entirely on genetic linkage analysis are unlikely to be fruitful. It is recommended that investigations reverse the natural development sequence and begin with studies at a phenotypic level, proceeding down to the genotypic level. Studies at a purely clinical level can define independent familial subtypes, which can in turn be studied at several levels of observation (social, physiological, biochemical, genetic) to identify multiple biosocial risk factors. Recent advances in genetic epidemiology now provide quantitative methods to detect major gene effects, resolve cultural inheritance from biological inheritance, and identify the influence of multiple risk factors on the development and expression of psychiatric disease.

Chromosome Mapping↗