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C R Cloninger

Publications and source records attributed to C R Cloninger.

At least 109 records · Page 6Linked to original sources
PubMed1991

A genetic study of platelet adenylate cyclase activity: evidence for a single major locus effect in fluoride-stimulated activity.

The activity of membrane-bound platelet adenylate cyclase, when stimulated in vitro by several compounds (including fluoride), is significantly reduced in alcoholics compared with control subjects. We have begun a study of the genetics of this enzyme activity. Complex segregation analysis of basal (unstimulated) platelet adenylate cyclase activity in families reveals a mode of inheritance that cannot be accounted for by a simple mixed model of transmission. By contrast, adenylate cyclase activity stimulated by fluoride ion reveals a single major locus effect with a modest multifactorial background. These results suggest that a single factor in the second-messenger pathway may (a) account for the majority of individual differences in stimulation of adenylate cyclase of fluoride and (b) help explain the reduced activities previously observed in alcoholics.

Adenylyl Cyclases↗
PubMed1990

Comorbidity of anxiety and depression.

Many factors obscure the diagnosis of psychogenic disorders, especially anxiety and depression. The factors involved include an overlap of symptoms, discrepancies in diagnostic criteria, and the unreliability of self- and observer-reporting. Differentiation among the various personality disorders is, however, extremely important, both for identifying the most appropriate treatment plan for a given patient and for evaluating the therapeutic activity of newly developed pharmacologic agents. Emerging factors that may have an impact on differential diagnoses of anxiety and depression include age at onset, family history, and personality traits associated with different types of psychopathology.

Anxiety Disorders↗
PubMed1990

Solvent use and psychiatric comorbidity.

From a family study of 286 alcoholics, 157 felons, 60 control subjects, and 1640 of their relatives, 130 solvent users were retrospectively identified. Risk for diagnosis of antisocial personality disorder was significantly elevated for all solvent users. Relatives, though not probands, were more likely to receive diagnoses of alcoholism and secondary depression, but this relationship appeared to be mediated by the presence of antisocial personality disorder. Solvent users were not at increased risk for primary depression or other psychiatric illnesses. Subjects reporting any solvent use also had significantly increased risk of suicidal ideation and suicide attempt compared to non-users, with half of the solvent users reporting suicidal ideation and 30% reporting a history of suicide attempt. However, risk for suicidal ideation and suicide attempt among solvent users appeared to covary with presence of antisocial personality disorder, alcoholism, and secondary depression rather than being specifically associated with solvent use.

Adult↗
PubMed1990

No evidence for linkage between chromosome 5 markers and schizophrenia.

Linkage between chromosome 5 markers and schizophrenia has been proposed for a small number of Icelandic and English families. Three subsequent reports have failed to replicate this report. To increase the number of tested kindreds, we collected seven North American families with schizophrenia and genotyped them at 4 loci that span the region 5p13-5q11-14, including the two markers used in the single positive linkage report. The data were analyzed with models of affection status similar to those utilized in the positive report. We observed no evidence of linkage between these markers and psychiatric disorders, regardless of the definition of affection status. Additionally, we can exclude most of the region for linkage with schizophrenia in these families. This and other negative reports of linkage between schizophrenia and chromosome 5 markers suggest that genetic defects in this region are rarely, if ever, etiologically related to schizophrenia.

Chromosomes, Human, Pair 5↗
PubMed1989

Schizophrenia and the question of genetic heterogeneity.

Despite major advances in psychiatric diagnosis during the past 20 years, boundaries of the schizophrenic syndrome remain elusive. Moreover, in pedigrees containing cases of schizophrenia there are marked between-pedigree differences with respect to prognosis, familial patterns of psychiatric illness, drug response, and especially association of affected status with a specific chromosomal locus. Such between-pedigree differences suggest the syndrome may be made up of several different diseases. Linkage of affected status to specific loci may aid in resolving genetic heterogeneity. Large multigenerational informative pedigrees may permit the separation into those that do and do not link to a genomic locus of interest. Admixture analysis of smaller informative pedigrees may permit separation of linked and unlinked pedigrees on the basis of differences in the recombination fraction. Finally, biological "markers" can be used before the genetic analysis to separate putative linked and unlinked pedigrees. The combined study of genetic linkage and clinical heterogeneity will aid in the resolution of etiological heterogeneity of schizophrenia and the delineation of meaningful diagnostic boundaries.

Genetic Linkage↗
PubMed1988

Familial resemblance in energy intake: contribution of genetic and environmental factors.

Total energy intake and intakes of carbohydrate, fat, and protein as well as the percentage of energy derived from these nutrients were calculated from a 3-d dietary record in 1597 subjects living in 375 families of French descent. Familial correlations were computed in pairs of biological relatives and relatives by adoption and used in the path-analysis BETA model to determine the contribution of genetic and nongenetic factors in the familial resemblance observed in energy intake. No significant genetic effect was found for intake of any nutrient tested (h2 less than or equal to 11%) and cultural inheritance was found to be more important than genetic inheritance. Nontransmitted environmental factors, including home environmental effects, were found to account for more than 50% of the variation observed in the energy-intake components. These results suggest that the average genetic influence on nutrient intake is negligible and that nongenetic effects associated mainly with home environmental effects are the major affecters of energy intake.

Adolescent↗
PubMed1988

Secular trends in the familial transmission of alcoholism.

This is a study of the familial transmission of alcoholism in the families of 60 female and 240 male alcoholics ascertained in four psychiatric hospital units and in a local parole office. Eight hundred and thirty-one interviewed first-degree relatives and 125 spouses are included. The lifetime population prevalences of alcoholism in white males and females based on the Epidemiological Catchment Area Study in St. Louis were compared with the family rates. A semistructured comprehensive interview schedule (Home Environment and Lifetime Psychiatric Evaluation Record) was used and diagnoses made according to Feighner criteria for alcoholism. The methods of Survival Analysis established the presence of strong secular trends in the age-of-onset and lifetime prevalence of alcoholism in these families and in the general population. Accordingly, new methods for the analysis of family data that incorporate secular variation were developed. The Multifactorial Model of Disease Transmission was used to estimate familial correlations and these were parameterized by the "Tau" model of Familial Transmission. The model does not assume that all familial resemblance is due to genetic factors, but also includes the possibility of nongenetic transmission. Our analyses confirmed that more recently born cohorts of individuals had increased expected lifetime prevalences of alcoholism and decreased ages of onset, when compared with older cohorts. Separate age-of-onset distributions were required for males and females and the secular trends in age-of-onset were greatest in females. The differences between males and females were least in more recently born cohorts suggesting that sex-specific differences in the family and population distribution of alcoholism are decreasing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Psychopathology in children of alcoholic and antisocial parents.

In this controlled family study the frequency of psychiatric disorder in children of alcoholic parents was found to be higher than in children of nonalcoholic parents. The rate in children of two alcoholic parents was distinctly higher than in those of one alcoholic parent. Comparison was also made between children of antisocial parents (usually coexisting with alcoholism) and children of parents with alcoholism only; no significant differences in the rates of childhood disorder were found between these two groups. Structured diagnostic interviews independently administered to both parents and children between 6 and 17 years old were used to assess psychopathology in the children. The types of disorders in the children of alcoholic parents reflected a mixed diagnostic picture with the reports of both parents and children yielding similar results.

Adolescent↗
PubMed1988

Childhood personality predicts alcohol abuse in young adults.

431 children (233 boys, 198 girls) born in Stockholm, Sweden, had a detailed behavioral assessment at 11 years of age, including a detailed interview with their school teachers, and at age 27 years were reevaluated to identify alcoholism or alcohol abuse. Specific predictions from a neurobiological learning theory about the role of heritable personality traits in susceptibility to alcohol abuse were tested in this prospective longitudinal study. Three dimensions of childhood personality variation were identified and rated without knowledge of adult outcome. These three dimensions (novelty-seeking, harm avoidance, and reward dependence) were largely uncorrelated with one another, and each was predictive of later alcohol abuse. Absolute deviations from the mean of each of the three personality dimensions were associated with an exponential increase in the risk of later alcohol abuse. High novelty-seeking and low harm avoidance were most strongly predictive of early-onset alcohol abuse. These two childhood variables alone distinguished boys who had nearly 20-fold differences in their risk of alcohol abuse: the risk of alcohol abuse varied from 4 to 75% depending on childhood personality.

Adult↗
PubMed1988

Alcohol-related symptoms in heterogeneous families of hospitalized alcoholics.

Heterogeneity in the clinical symptoms of alcohol abuse was examined in 243 men and 305 women from families of hospitalized alcoholics, who had demonstrated different patterns of inheritance of susceptibility to alcoholism. Discriminant analysis was utilized to identify nine alcoholic symptoms that distinguished male relatives of alcoholic men from those of alcoholic women. Inability to abstain from alcohol, fighting and reckless driving while intoxicated, and alcohol treatment other than Alcoholics Anonymous were more prevalent in families of male probands. Male relatives of female probands experienced later onset of loss of control over drinking associated with benders, and cirrhosis and feelings of guilt. Female relatives of alcoholic men and women showed a marked predominance of the latter (Type 1) features, whereas male relatives had different clinical features, depending on the associated mode of inheritance.

Adult↗
PubMed1988

Genetic heterogeneity and the classification of alcoholism.

Recent progress toward a systematic pathophysiological model of alcoholism has led to identification of two distinct subtypes of alcoholism. These subtypes may be distinguished in terms of distinct alcohol-related symptoms, personality traits, ages of onset, and patterns of inheritance. Type 1 alcoholism is characterized by anxious (passive-dependent) personality traits and rapid development of tolerance and dependence on the anti-anxiety effects of alcohol. This leads to loss of control, difficulty terminating binges once they start, guilt feelings, and liver complications following socially encouraged exposure to alcohol intake. In contrast, type 2 alcoholism is characterized by antisocial personality traits and persistent seeking of alcohol for its euphoriant effects. This leads to early onset of inability to abstain entirely, as well as fighting and arrests when drinking. Empirical findings about sex differences, ages of onset, associated personality traits, and longitudinal course are described in a series of adoption and family studies in Sweden and the United States. Implications for future research and clinical practice are discussed.

Adoption↗
PubMed1988

A unified biosocial theory of personality and its role in the development of anxiety states: a reply to commentaries.

The comments by Gray, Gelder, Liebowitz, Eysenck, Nurnberger, Roy and Linnoila are discussed. Most of the recommendations in the comments have already been carried out and the others are under way. Specifically, practical assessment instruments have been developed, and their psychometric properties are under investigation. Explicit criteria for systematic diagnosis of personality disorders have been developed. Longitudinal studies have been carried out to evaluate the predictive validity of the scales. Empirical tests have confirmed the predicted relationship between novelty seeking and somatic anxiety, as well as between harm avoidance and cognitive anxiety. A more detailed model of the underlying neural processes has been described. Growing evidence of norepinephrine's role in reward dependence has been reported. Finally, a more comprehensive learning model has been developed that can account for both the higher-order and the lower-order factor structure of personality in terms of specific stimulus-response characteristics. Several commentators have provided additional evidence supporting the predicted role of the monoamines in modulating personality and learning. Finally, predictions from my model about pain sensitivity, stimulus intensity modulation, and the factor structure of personality have been compared to those of Gray and Eysenck. The predictions are confirmed for my model, but not those of Gray or Eysenck.

Adaptation, Psychological↗
PubMed1988

On the properties of maximum likelihood estimators of familial correlations under variable sibship size.

Selected distributional properties of the maximum likelihood estimator and its z-transformation of three familial correlations (parental, parent-offspring, filial) were investigated numerically for the case of nuclear families with variable sibship size. This investigation was based on six different sets of the three correlations, and four different sample sizes, defining 24 sampling conditions, which were replicated 1,000 times each. It was found that the distributional properties of the correlation estimator are affected by the magnitude of the correlations even in large samples although approximate normality is achieved locally. Fisher's z-transformation, here used only in its interclass form, achieves reduction of skewness, stabilization of variance, and approach to normality already in small samples, except for the filial correlation (where it may be deemed inappropriate) in smaller samples. For both the correlation estimator and its z-transformation, the (estimated) relative efficiency was shown to be high (better than 90% in most sampling conditions), suggesting that the estimated minimum variance bound is a satisfactory estimator of the sampling variance. It is concluded that the maximum likelihood estimation of familial correlations under variable sibship size is feasible and, when prudently applied, especially in the form of their z-transformations, provides an appropriate method in analyses of family studies.

Family Characteristics↗
PubMed1987

Neurogenetic adaptive mechanisms in alcoholism.

Clinical, genetic, and neuropsychopharmacological studies of developmental factors in alcoholism are providing a better understanding of the neurobiological bases of personality and learning. Studies of the adopted-away children of alcoholics show that the predisposition to initiate alcohol-seeking behavior is genetically different from susceptibility to loss of control after drinking begins. Alcohol-seeking behavior is a special case of exploratory appetitive behavior and involves different neurogenetic processes than do susceptibility to behavioral tolerance and dependence on the antianxiety or sedative effects of alcohol. Three dimensions of personality have been described that may reflect individual differences in brain systems modulating the activation, maintenance, and inhibition of behavioral responses to the effects of alcohol and other environmental stimuli. These personality traits distinguish alcoholics with different patterns of behavioral, neurophysiological, and neuropharmacological responses to alcohol.

Alcoholism↗