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C R Cloninger

Publications and source records attributed to C R Cloninger.

At least 73 records · Page 4Linked to original sources
PubMed1995

The tridimensional personality questionnaire as a predictor of response to nefazodone treatment of depression.

Personality traits have emerged as the strongest identified predictors of response to antidepressant treatment of major depressive disorder (Peselow et al., 1992; Joyce et al., 1994). 18 subjects in the midst of a major depressive episode were treated with nefazodone in an open trial. All subjects completed Cloninger's tridimensional personality questionnaire (TPQ) before beginning treatment. A multiple regression analysis was performed in an attempt to replicate Joyce et al.'s (1994) finding that temperament type, as assessed by the TPQ, is a strong predictor of antidepressant response. A model involving TPQ reward dependence and harm avoidance scores, and their interaction, was found to significantly predict the response to nefazodone (r2 = 0.47, P < 0.027). When response was defined as a 50% decrease in HAM-D score at last visit, high reward dependence score alone significantly separated responders from nonresponders (Fisher's exact P = 0.050, df = 1). These results raise the intriguing possibility that TPQ scores may have direct clinical applications.

Adult↗
PubMed1995

Personality antecedents of alcoholism in a national area probability sample.

Kraepelin viewed alcoholism as a symptom complex caused by heritable individual differences in emotional predisposition and volitional control. Recent clinical and genetic research has distinguished subtypes of alcoholics with different personality traits, symptoms, course, mode of inheritance, and response to treatment. The heritable personality traits that influence the initiation, continuation, and severity of alcoholism were examined by interview of a national area probability sample of 1019 non-institutionalized adults across the continental United States of America. We found that harm avoidance inhibits the initiation and frequency of drinking, but increases the risk of developing problems once frequent drinking has begun. Novelty seeking increases the initiation of drinking and the probabilities of frequent and problem drinking. This supports Kraepelin's description of the etiology and course of alcoholism as a symptom complex related to individual differences in emotional predisposition.

Adolescent↗
PubMed1995

DSM-IV field trial: testing a new proposal for somatization disorder.

OBJECTIVE: The purpose of this study was to evaluate for APA a proposed strategy to diagnose somatization disorder for possible inclusion in DSM-IV. METHOD: Five sites--Washington University, University of Kansas, University of Iowa, University of Arkansas, and Mount Sinai Medical Center in New York--participated in a collaborative field trial. Female subjects (N = 353) were recruited from several different services (psychiatry, internal medicine, and family practice) and were evaluated for the presence or absence of the disorder. This assessment was performed with a new instrument constructed by combining all the criteria for somatization disorder from the proposed criteria for DSM-IV, DSM-III, DSM-III-R, Perley-Guze, and proposed criteria for ICD-10. RESULTS: A high level of concordance was found between the proposed diagnostic strategy for DSM-IV and the current criteria (DSM-III-R), as well as the earlier criteria (Perley-Guze and DSM-III). The ICD-10 criteria agreed poorly with all other criteria sets. The level of experience of the rater (expert versus novice) with the earlier (Perley-Guze, DSM-III) and current (DSM-III-R) criteria did not influence the identification of cases by use of DSM-IV criteria. No racial effect was introduced by any of the criteria sets. CONCLUSIONS: The strategy for DSM-IV is an accurate and simpler method of diagnosing somatization disorder that does not require special expertise for proper use.

Adult↗
PubMed1994

Turning point in the design of linkage studies of schizophrenia.

Despite extensive genomic scans, linkage studies of multiplex pedigrees have been unable to produce replicable evidence of genes predisposing to schizophrenia. This indicates that it is unlikely that a single gene accounts for a majority of cases of schizophrenia, even in multiplex pedigrees. It is most likely that schizophrenia is caused by the nonlinear interaction of multiple genetic and environmental factors influencing brain development and function. This conclusion has strong implications for the design of linkage and association studies. Recently designed linkage studies involve several improvements to deal with extensive locus heterogeneity and multiplicative interaction. These improvements include much larger samples of pedigrees, systematic ascertainment and sequential extension rules, and standardized procedures at multiple sites to facilitate collaboration and replication. Future improvements are likely to require advances in the assessment of clinical and neurobiological variability in multiplex pedigrees, more systematic environmental assessment, and advances in analytic methods to deal with multiplicative interaction. Rather than focusing only on schizophrenia as one or more discrete disorders, future linkage efforts should also consider the etiology of individual clinical syndromes or dimensional components of risk that interact to cause the complex pattern of syndromal comorbidity observed within schizophrenics and their families.

Chromosome Mapping↗
PubMed1994

Platelet MAO activity in type I and type II alcoholism.

Lowered activity of the enzyme MAOB in the platelets and other tissues of alcoholics than of nonalcoholics is the most replicated biological finding in genetic research in alcoholism. Data presented here and elsewhere also indicate that the relationship between MAOB activity and alcoholism extends to the clinical subtypes referred to as Type I and Type II alcoholism. A detailed examination of the relationship between in vitro platelet MAOB activity levels, alcoholic subtype, and general mental health status among the relatives of the probands suggests that low MAOB activity is a marker of increased risk overall and that the families of Type II alcoholics have a higher genetic risk loading than do the families of Type I alcoholics. This increased genetic loading is probably due to the classification of Type II alcoholics on the basis of features related to severity of illness and additional psychiatric features such as personality disorders. Although the families of alcoholics tend to have higher levels of psychiatric illness compared to the general population, the overall risk is compounded in the families of Type II alcoholics, and these differences in underlying risk are reflected in the observed differences in MAOB activities. Thus, MAOB is not a biological/genetic marker of alcoholism sensu stricto but is rather a biological/genetic marker of an underlying pathophysiologic process leading to alcoholism and other psychiatric illness. The task now before us is to understand this process and how the activity of MAOB is involved.

Alcoholism↗
PubMed1994

Linkage disequilibria at the D2 dopamine receptor locus (DRD2) in alcoholics and controls.

Because of its central role in the neuromodulation of appetitive behaviors, the D2 dopamine receptor gene (DRD2) has received considerable scrutiny as a possible candidate that may affect susceptibility to additive behaviors--especially alcoholism. Association studies that compare the frequencies of anonymous restriction fragment length polymorphisms (RFLPs) in alcoholics and controls have yielded equivocal results, suggesting that any role played by this receptor will account for only part of the variation. Since these RFLPs are not located in coding regions, the hypothesis has been advanced that the association seen in some studies results from linkage disequilibrium between these markers and one or more functional DRD2 alleles that affect susceptibility. To test this hypothesis, we have assayed four DRD2 RFLPs that span coding regions as well as a 3' flanking RFLP in an expanded sample of 88 unrelated Caucasian alcoholics and 89 unrelated race-matched controls. No significant difference for any RFLP frequency between these samples was observed, although for one marker (phD2-244), the alcoholic sample showed a significant departure from the Hardy-Weinberg equilibrium. The pattern of pairwise composite disequilibrium coefficients is broadly similar in the two samples, although when the five-marker haplotype frequencies are compared, a significant difference is revealed. This difference appears to be due to greater linkage disequilibrium of the control sample. These results do not support the involvement of the DRD2 region in the etiology of alcoholism.

Adult↗
PubMed1994

Temperament predicts clomipramine and desipramine response in major depression.

Clinical predictors of drug response in major depression have been weak and inconsistent. Eighty-four patients suffering from a current major depressive episode completed a 6-week double-blind trial of either clomipramine or desipramine. Temperament, as measured by the Tridimensional Personality Questionnaire, accounted for 35% of the variance in treatment outcome, compared with less than 5% predicted by clinical variables. In the more severely depressed patients, temperament predicted nearly 50% of the variance in treatment outcome, which is the first time that such a substantial predictor of drug response has been identified. Within depressed women, temperament also predicted response to different antidepressant drugs. The potential importance of temperament, and the need for replication of these findings is discussed.

Adult↗
PubMed1994

Temperament and personality.

Recent efforts to integrate psychometric and neurobiological data about personality have stimulated diverse interdisciplinary applications. The dissociation of major brain systems linked to procedural and propositional memory and learning has clarified the clinical distinction between two components of personality: temperament and character. Temperament can be defined in terms of individual differences in percept-based habits and skills (i.e. related to procedural memory and learning), which are regulated by the amygdala, hypothalamus, striatum, and other parts of the limbic system. In contrast, character can be defined in terms of individual differences in concept-based goals and values (i.e. related to propositional memory and learning), which are encoded by the hippocampal formation and cerebral neocortex. Recent descriptive, developmental, genetic, and neurobehavioral studies indicate that at least four dimensions of temperament and three dimensions of character can be uniquely described and functionally dissociated.

Animals↗
PubMed1994

Family study of schizophrenia and personality.

The purpose of this study was to determine whether the abnormal characteristics observed in relatives of schizophrenics represent variations in normal personality. Relatives (N = 340) of patients with schizophrenia, affective disorder, and medical or surgical conditions were personally interviewed about psychiatric symptoms and completed the Multidimensional Personality Questionnaire. Relatives who were themselves ill had elevated scores on some scales. Relatives of schizophrenics had normal scores on all personality scales, but relatives of affectively ill probands differed from other relatives on Well-Being and measures of Negative Emotionality. When schizophrenic probands were subtyped by symptoms, relatives of emotionally blunted schizophrenics were found to have slightly lower scores on Social Closeness than did relatives of controls. Overall, these results suggest that schizophrenia is unrelated to normal personality.

Adolescent↗
PubMed1994

Testing a model for the genetic structure of personality: a comparison of the personality systems of Cloninger and Eysenck.

Genetic analysis of data from 2,680 adult Australian twin pairs demonstrated significant genetic contributions to variation in scores on the Harm Avoidance, Novelty Seeking, and Reward Dependence scales of Cloninger's Tridimensional Personality Questionnaire (TPQ), accounting for between 54% and 61% of the stable variation in these traits. Multivariate genetic triangular decomposition models were fitted to determine the extent to which the TPQ assesses the same dimensions of heritable variation as the revised Eysenck Personality Questionnaire. These analyses demonstrated that the personality systems of Eysenck and Cloninger are not simply alternative descriptions of the same dimensions of personality, but rather each provide incomplete descriptions of the structure of heritable personality differences.

Adult↗
PubMed1994

Temperament and hypercortisolemia in depression.

OBJECTIVE: The authors examined the relationships among depression severity, melancholia, and cortisol level and the relationship between temperament, as measured with the Tridimensional Personality Questionnaire, and cortisol level. METHOD: Morning and afternoon cortisol levels of 40 healthy comparison subjects and 96 patients with major depression were measured. The depressed patients were rated for depression severity and melancholia, and they completed the Tridimensional Personality Questionnaire. RESULTS: Temperament, especially dependence and extravagance, but not depressive symptoms, was the major determinant of the hypercortisolemia observed in the depressed patients. CONCLUSIONS: For research in biological psychiatry to advance, more attention needs to be paid to the individual differences in biology that underlie any state-dependent biologic dysfunction.

Adult↗
PubMed1994

A new, semi-structured psychiatric interview for use in genetic linkage studies: a report on the reliability of the SSAGA.

Within- and cross-center test-retest studies were conducted to study the reliability of a new, semistructured, comprehensive, polydiagnostic psychiatric interview being used in a multisite genetic linkage study of alcoholism. Findings from both studies indicated that reliability for the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) was high for DSM-III-R substance dependence disorders, but less so for substance abuse disorders. Reliability of depression was good in both studies, but mixed for antisocial personality disorder (ASP). Findings are presented in terms of specific substance dependence and abuse diagnoses, as well as for depression and ASP. Criterion-specific reliabilities are examined by type of substance used. Although SSAGA was designed to provide for broad phenotyping of alcoholism, review of its new features suggests its suitability for a variety of family studies, not just those focusing on substance abuse.

Adolescent↗
PubMed1994

Monoamine oxidases and alcoholism: studies in unrelated alcoholics, normal controls and alcoholic families.

Monoamine oxidases (A and B) are of great interest in connection with alcoholism. Low MAO activity has been found in the brains and the platelets of alcoholics and their relatives supporting the hypothesis that low MAO activity is a biological marker for vulnerability to misuse. In order to determine the role of the MAO genes in alcoholism we have measured MAO-B activity and typed two simple sequence repeats (one in the MAO-A gene and one in the MAO-B gene) in a sample of 133 unrelated alcoholics, 300 subjects from 30 two- and three-generation pedigrees ascertained through an alcoholic proband, and 92 normal controls. The unrelated alcoholic group did not differ in MAO-B activity from normal controls nor were there significant differences between subtypes. We did, however, find significant differences between alcoholic males and females (t = 2.836, p = .005), a difference that was not present in controls. A two-way analysis of variance of MAO-B activity as a function of the allelic variation of each marker locus and diagnosis among male subjects was performed. There was no evidence for mean differences in activity levels for different alleles. The distribution of MAO-A and MAO-B "alleles" in the alcoholic sample differed from that of the control sample. Affected sib pair linkage analysis of MAO genes and alcoholism showed no evidence for an excess of concordant affected sib pairs suggesting that this region of the X-chromosome does not harbor a susceptibility locus.

Adult↗
PubMed1993

Association of monoamine oxidase (MAO) activity with alcoholism and alcoholic subtypes.

A familial/genetic study of platelet monoamine oxidase (MAO) activity in alcoholics was carried out. MAO activities were determined using phenylethylamine (PEA) as substrate at Km concentration (1.2 microM) and at saturating concentration (12.0 microM). Complex segregation analysis of familial data indicated a single major gene mode of transmission of activity at both substrate concentrations. In addition, the present sample size (13 families, 108 members) proved sufficient to allow correlation analysis of enzyme activity with affection status and clinical subtypes of affecteds. MAO activity was significantly correlated with alcoholism at both Km and saturating substrate concentrations and a significant correlation between low MAO activity and Cloninger Type II alcoholism was seen at Km substrate concentration. These results confirm a hierarchical cosegregation of platelet MAO activity and alcoholism suggesting that MAO activity warrants continued status as a marker in alcoholism.

Adult↗
PubMed1993

A psychobiological model of temperament and character.

In this study, we describe a psychobiological model of the structure and development of personality that accounts for dimensions of both temperament and character. Previous research has confirmed four dimensions of temperament: novelty seeking, harm avoidance, reward dependence, and persistence, which are independently heritable, manifest early in life, and involve preconceptual biases in perceptual memory and habit formation. For the first time, we describe three dimensions of character that mature in adulthood and influence personal and social effectiveness by insight learning about self-concepts. Self-concepts vary according to the extent to which a person identifies the self as (1) an autonomous individual, (2) an integral part of humanity, and (3) an integral part of the universe as a whole. Each aspect of self-concept corresponds to one of three character dimensions called self-directedness, cooperativeness, and self-transcendence, respectively. We also describe the conceptual background and development of a self-report measure of these dimensions, the Temperament and Character Inventory. Data on 300 individuals from the general population support the reliability and structure of these seven personality dimensions. We discuss the implications for studies of information processing, inheritance, development, diagnosis, and treatment.

Character↗