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C Robert Cloninger

Publications and source records attributed to C Robert Cloninger.

27 records · Page 2Linked to original sources

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia.

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (R(avg)) and then weighted for sample size (N(sqrt)[affected casess]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P(AvgRnk)) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P(ord)). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk<.000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both P(AvgRnk) and P(ord)<.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with P(ord)<.05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.

Bipolar Disorder↗

Persistence and brain circuitry.

The orbitofrontal and adjacent medial prefrontal cortex may play an important role in normal social functioning and affect modulation. Recent anatomical studies of this area of the prefrontal cortex have demonstrated a striking correspondence of fine-grained architectonic partitioning schemes in humans and nonhuman primates. This finding allows neurophysiological recording and anatomical connectivity data in animals to be considered together with functional imaging data and lesion studies in humans. In a functional MRI study, we show that individual differences in Persistence, a dimensional trait assessed with a seven-factor personality model, may be linked to specific areas in the lateral orbital and medial prefrontal cortex and the ventral striatum. These areas are part of an anatomical circuit that has been defined in nonhuman primates and has been implicated in functions related to behavioral persistence. These findings represent a fresh approach to linking normal individual differences in personality and behavior to specific neuronal structures and subsystems.

Adult↗

Functional variation in promoter region of monoamine oxidase A and subtypes of alcoholism: haplotype analysis.

Monoamine oxidase (MAO) is a mitochondrial enzyme involved in the degradation of certain neurotransmitter amines. MAO-A, due to its function in central nervous system, has been one of the important candidate genes involved in the development of neuropsychiatric disorders. A functional polymorphism in the promoter region of the MAO-A gene has been identified. This variation affects the transcriptional efficiency of the gene. To determine the role of this MAO-A functional polymorphism in the development of subtypes of alcoholism, a sample of alcoholics and normal controls were screened with this marker. The allele frequency differences between total alcoholics, Types I and II alcoholics, and normal controls was not significant. Comparison of male alcoholics to male normal controls for the frequencies of two-loci and three-loci haplotypes was statistically significant. After Bonferroni's correction for multiple tests none of the results remained significant at P < 0.05. Our results indicate that MAO-A may play a role in the development of alcoholism but the gene effect is very small.

Alcoholism↗

Personality and depressive symptoms: a multi-dimensional analysis.

BACKGROUND: The relationship of temperamental aspects of personality to symptoms of depression in a community-based sample of 804 individuals was examined using a multi-dimensional approach to account for heterogeneity in symptom patterns. METHOD: The Temperament and Character Inventory (TCI) was used to assess personality and the Center for Epidemiologic Studies Depression scale (CES-D) was used to measure depressive symptoms. Canonical correlation analysis was used to relate CES-D item combinations to temperament traits in multiple dimensions. The relationships between temperament and various conditions correlated with depression were examined using logistic regression. RESULTS: Temperamental aspects of personality are related not only to total CES-D score, but also to the patterns of CES-D items endorsed by subjects. High Harm Avoidance is related to total CES-D score; high Reward Dependence combined with high Persistence is associated with restless sleep and subjective symptoms; high Reward Dependence combined with low Persistence is negatively associated with appetite loss and low energy; high Novelty Seeking is related to maintenance of positive affect and inability to concentrate. High Novelty Seeking is also associated with past suicide attempts, after adjusting for total CES-D score. LIMITATIONS: Cross-sectional data prevent analysis of causation; the severest cases of clinical depression may not be represented in a general population sample. Depressive symptoms are self-reported. CONCLUSION: Substantial differences in level of symptoms and in symptom patterns exist among individuals in a continuum of depressed states and those differences are partially explained by temperament traits.

Adolescent↗

Temperament, childhood environment and psychopathology as risk factors for avoidant and borderline personality disorders.

OBJECTIVE: To evaluate childhood experiences (neglect and abuse), temperament and childhood and adolescent psychopathology as risk factors for avoidant and borderline personality disorders in depressed outpatients. METHOD: One hundred and eighty depressed outpatients were evaluated for personality disorders. Risk factors of childhood abuse, parental care, temperament, conduct disorder symptoms, childhood and adolescent anxiety disorders, depressive episodes, hypomania and alcohol and drug dependence were obtained by questionnaires and interviews. RESULTS: Avoidant personality disorder can be conceptualized as arising from a combination of high harm avoidance (shy, anxious), childhood and adolescent anxiety disorders and parental neglect. Borderline personality disorder can be formulated as arising from a combination of childhood abuse and/or neglect, a borderline temperament (high novelty seeking and high harm avoidance), and childhood and adolescent depression, hypomania, conduct disorder and alcohol and drug dependence. CONCLUSIONS: Combinations of risk factors from the three domains of temperament, childhood experiences and childhood and adolescent psychopathology make major contributions to the development of avoidant and borderline personality disorders.

Adolescent↗

Application of the seven-factor model of personality to early childhood.

The seven-factor model of personality developed by Cloninger and colleagues describes personality as a function of developmental aspects of character superimposed on heritable dimensions of temperament. The objective of this study was to determine whether this model could be applied to early childhood. We tested a preschool version of the Temperament and Character Inventory (the preschool TCI) in 305 children aged 2-5 years. Exploratory factor analysis provided support for the presence of distinct domains of temperament (comprising four factors) and character (comprising three factors). The preschool TCI demonstrated high internal consistency for each of the seven factors (Cronbach's alpha values: 0.70-0.93). Inter-individual differences in novelty seeking, reward dependence and cooperativeness were highly preserved (Pearson's r values 0.75, 0.64 and 0.80, respectively) in 29 subjects who were studied over a 3-year period from toddlerhood to early school age. Future studies are warranted to test the extent to which early childhood measurements of the seven factors might predict the development of personality disorders.

Character↗

Personality as a mediator of demographic risk factors for suicide attempts in a community sample.

The aim of this study was to determine whether personality might partially explain associations between sociodemographic factors and self-reported suicide attempts. This analysis was motivated by reports that certain personality traits are logical targets for intervention, whereas sociodemographic characteristics are not generally modifiable. Data were from a postal survey sent to community residents who were previously selected at random (N = 912). Age, gender, health-insurance status, education, self-reported health, and marital history were identified as relevant sociodemographic predictors of having made one or more lifetime suicide attempts. Risk associated with each of these variables was mediated by the personality traits of self-directedness (SD) and harm avoidance (HA). In a multiple logistic-regression analysis constrained to sociodemographic predictors, only young age, female sex, poor self-reported health, and Medicaid status remained as predictors of suicide attempts. When personality factors were added to the model, all of the sociodemographic predictors except Medicaid status were rendered nonsignificant or marginally significant. Risk associated with gender was primarily related to HA, risk associated with poor self-reported health was mediated by both HA and SD, and the risk associated with young age was primarily mediated by SD; the last was the largest mediation effect observed. In contrast, risk associated with receipt of Medicaid, presumed to indicate low socioeconomic status, was not mediated by personality. We conclude that risk associated with certain nonmodifiable demographic factors is often mediated by potentially modifiable intrapersonal factors, such as SD.

Adolescent↗