Claude Robert Cloninger

Relationship between serotonin and the Temperament and Character Inventory

The unified biosocial theory of personality, proposed by Cloninger, conceptualises personality as a combination of heritable, neurobiologically based traits (temperament dimensions), and traits reflecting sociocultural learning (character dimensions). The temperament dimensions are thought to be related to activity in specific central neurotransmitter systems. The relationship of the dimensions of the Temperament and Character Inventory, particularly harm avoidance (HA), and platelet 5-HT2 receptor sensitivity was investigated in a sample of undergraduate student volunteers (N = 49). Serotonin-receptor binding results in Ca2+ release from intracellular stores. The concentration of serotonin required to produce half maximal Ca2+ response (EC50) is indicative of 5-HT2 receptor sensitivity such that the lower the EC50 serotonin concentration, the greater the 5-HT2 receptor sensitivity. A significant inverse correlation was found between HA and EC50 (r = -0.644, P < 0.001). Self-directedness was also significantly correlated with EC50 (r = 0.391, P = 0.005). Novelty seeking, a personality trait similar to sensation seeking, was not significantly correlated with serotonin.

Risk architecture of schizophrenia: the role of epigenetics.

Purpose of review To systematize existing data and review new findings on the cause of schizophrenia and outline an improved mixed model of schizophrenia risk. Recent findings Multiple and variable genetic and environmental factors interact to influence the risk of schizophrenia. Both rare variants with large effect and common variants with small effect contribute to genetic risk of schizophrenia, with no indication for differential impact on its clinical features. Accumulating evidence supports a genetic architecture of schizophrenia with multiple scenarios, including additive polygenic, heterogeneity, and mixed polygenic-heterogeneity. The epigenetic mechanisms that mediate gene–environment (GxE) interactions provide a framework to incorporate environmental factors into models of schizophrenia risk. Environmental pathogens with small effect on risk have robust effects in the context of family history of schizophrenia. Hence, genetic risk for schizophrenia may be expressed in part as sensitivity to environmental factors. Summary We propose an improved mixed model of schizophrenia risk in which abnormal epigenetic states with large effects are superimposed on a polygenic liability to schizophrenia. This scenario can account for GxE interactions and shared family environment, which in many cases are not explained by a single structural variant of large effect superimposed on polygenes (the traditional mixed model).

Parental care-giving and home environment predicting offspring's temperament and character traits after 18 years

Although many personality theories emphasize the role of parental behaviors in shaping personality development, empirical data from longitudinal studies remain scarce. It is also not known, if parental behaviors affect character development more strongly than temperament or vice versa. In a prospective study, 1083 volunteer participants of the Young Finns study completed the Temperament and Character Inventory (TCI). Parents of the participants had answered questions about parenting attitudes, socioeconomic status, health behaviors, and role satisfaction 18 years before. We studied the univariate and the cumulative effects of parental care-giving and family environment on offsprings personality traits. Parental care-giving and home-environment were more strongly associated with offspring character traits reflecting personality maturity (Self-directedness and Cooperativeness) than with offspring temperament traits (Novelty seeking, Harm avoidance, Reward dependence and Persistence) reflecting emotional and behavioral tendencies. The differences were most evident in the cumulative effects model. Maternal variables were stronger predictors than paternal variables. The present findings suggest that not all personality traits are similarly predicted by parental care-giving and home-environment. In particular, character development is more strongly related to such measures than temperament. Parental care-giving and home-environment are more strongly related to psychological maturity (character) than emotional and behavioral tendencies (temperament).

Personality differences according to age and sex in a Mexican sample using the Temperament and Character Inventory-Revised.

OBJECTIVES The objectives of the study were to compare personality features according to age and sex cohorts in a community sample of Mexico City using the Temperament and Character Inventory-Revised (TCI-R) and to examine the TCI-R psychometric properties according to age and sex parameters. METHOD A total of 2076 adults filled out the Spanish version of TCI-R. RESULTS Younger subjects exhibited higher novelty seeking. Self-directedness and cooperativeness scores increased with age. Harm avoidance and self-transcendence were lower in younger adults when compared with older subjects. Women scored higher than men in harm avoidance and reward dependence. Men between 26 and 45 years old reported higher novelty seeking. Women older than 25 years scored higher in self-transcendence, and those older than 45 years exhibited higher cooperativeness scores. The identified TCI-R structure corresponded to the original one. Internal consistency of the higher-order dimensions was good in all age cohorts, in men and women, and in the total sample (αs >.80). CONCLUSION Our results give further support to personality specific dominant features in men and women. Differences in age cohorts may be explained by maturity and personal experiences acquired during life. The TCI-R psychometric properties and score distributions by age and sex cohorts may be useful for future studies with clinical samples and for cross-cultural comparison purposes.

Role of allelic variants of FK506-binding protein 51 (FKBP5) gene in the development of anxiety disorders.

Anxiety disorders exhibit remarkably high rates of comorbidity with major depressive disorder (MDD). Mood and anxiety disorders are considered stress‐related diseases. Genetic variations in the co‐chaperone FK506‐binding protein 51, FKBP5, which modulates the function of glucocorticoid receptors, have been associated with an increased risk for the development of posttraumatic stress disorder, but data regarding its role in MDD are controversial. The aims of this study were to clarify the role of the FKBP5 gene in depression and anxiety disorders through a case–control study and an association study with personality traits using the Temperament and Character Inventory (TCI) in healthy subjects.

Associations between dimensional personality measures and preclinical atherosclerosis: The cardiovascular risk in Young Finns study

OBJECTIVE To assess how multidimensional personality-trait theories, such as the Psychobiological Model of Temperament and Character, and the Five-factor Model of Personality, are associated with subclinical atherosclerosis as indicated by carotid intima-media thickness (IMT). The analysis was designed to tolerate non-linear development in which the same personality profiles can have multiple final outcomes and different antecedent profiles can have the same final outcome. METHODS 605 men and 844 women (average age 31.6year, s.d.=5.0, range=24-39) provided data on IMT and traits of the psychobiological model, 725 men and 1011 women were assessed for IMT and the five-factor model (age 37.7year, s.d.=5.0, range=30-45). Robust multidimensional Hotellings T(2) statistic was used to detect personality differences between participants with high IMT and others. Model-based clustering method further explored the effect. RESULTS Those with a high level of subclinical atherosclerosis within the sample (highest IMT-decile) had a combined higher persistence (i.e., were perseverative or perfectionistic), more disorganized (schizotypal) character, and more antisocial temperamental configuration than others (P=0.019). No effect was found for the five-factor model (P=0.978). Traditional methods that did not account for multidimensionality and nonlinearity did not detect an association. CONCLUSION Psychological well-being may have positive effects on health that reduce atherosclerosis in the population as a whole. Increased subclinical atherosclerosis was associated with a profile that combines known risk factors, such as cynical distrust and hostile tendencies. More frequent use of statistical procedures that can cope with non-linear interactions in complex psychobiological systems may facilitate scientific advances in health promotion.

PGMRA: a web server for (phenotype × genotype) many-to-many relation analysis in GWAS

It has been proposed that single nucleotide polymorphisms (SNPs) discovered by genome-wide association studies (GWAS) account for only a small fraction of the genetic variation of complex traits in human population. The remaining unexplained variance or missing heritability is thought to be due to marginal effects of many loci with small effects and has eluded attempts to identify its sources. Combination of different studies appears to resolve in part this problem. However, neither individual GWAS nor meta-analytic combinations thereof are helpful for disclosing which genetic variants contribute to explain a particular phenotype. Here, we propose that most of the missing heritability is latent in the GWAS data, which conceals intermediate phenotypes. To uncover such latent information, we propose the PGMRA server that introduces phenomics—the full set of phenotype features of an individual—to identify SNP-set structures in a broader sense, i.e. causally cohesive genotype–phenotype relations. These relations are agnostically identified (without considering disease status of the subjects) and organized in an interpretable fashion. Then, by incorporating a posteriori the subject status within each relation, we can establish the risk surface of a disease in an unbiased mode. This approach complements—instead of replaces—current analysis methods. The server is publically available at http://phop.ugr.es/fenogeno.

PCLO gene: Its role in vulnerability to major depressive disorder

BACKGROUND A recent genome-wide association study on Major Depressive Disorder (MDD) identified a specific association with a non-synonymous polymorphism (rs2522833) of a gene encoding the presynaptic protein piccolo (PCLO). A high percentage of patients who develop MDD have particular temperamental traits, such as passivity, pessimism, indecisiveness, and low self-esteem, which are related to the subsequent development of depression. The aims of this study were to perform a replicate case-control study and to conduct the first association study between the rs2522833 polymorphism and depression-related personality traits using the Temperament and Character Inventory (TCI) in a healthy subject sample. METHODS A total of 522 MDD patients and 375 healthy volunteers were enrolled in the study. Two hundred and forty-six controls agreed to fill out the TCI. RESULTS The results showed that rs2522833 CC homozygotes were more frequent among the depressed patients than in the controls (p<0.01). The C allele distribution showed a trend in the same direction (p=0.08). Among controls, we found that the C allele carriers were associated with personality traits increasing vulnerability to depression, including higher Harm Avoidance (HA) and lower in Novelty Seeking (NS). In particular, C allele carriers were more fearful (HA2) and fatigable (HA4), and less impulsive/more deliberate (NS2) and less extravagant/more frugal (NS3). LIMITATIONS The absence of possible epistatic interaction effect. CONCLUSIONS These results provide further support for the involvement of the PCLO gene in MDD and show that this effect may be mediated by influencing personality traits that increase the risk of major depression.

Active reward processing during human sleep: Insights from sleep-related eating disorder

In this paper, we present two carefully documented cases of patients with sleep-related eating disorder (SRED), a parasomnia which is characterized by involuntary compulsive eating during the night and whose pathophysiology is not known. Using video-polysomnography, a dream diary and psychometric examination, we found that both patients present elevated novelty seeking and increased reward sensitivity. In light of new evidence on the mesolimbic dopaminergic implication in compulsive eating disorders, our findings suggest a role of an active reward system during sleep in the manifestation of SRED.

Prediction of Neurocognitive Deficits by Parkinsonian Motor Impairment in Schizophrenia: A Study in Neuroleptic-Naïve Subjects, Unaffected First-Degree Relatives and Healthy Controls From an Indigenous Population

BACKGROUND Neurocognitive deficits are among the most debilitating and pervasive symptoms of schizophrenia, and are present also in unaffected first-degree relatives. Also, multiple reports reveal parkisonian motor deficits in untreated subjects with schizophrenia and in first-degree relatives of affected subjects. Yet, the relation between motor and cognitive impairment and its value as a classifier of endophenotypes has not been studied. AIMS To test the efficacy of midbrain hyperechogenicity (MHE) and parkinsonian motor impairment (PKM) as predictors of neurocognitive impairment in subjects with or at risk for schizophrenia, that could be used to segregate them from first-degree relatives and healthy controls. METHOD Seventy-six subjects with chronic schizophrenia never exposed to antipsychotic medication, 106 unaffected first-degree relatives, and 62 healthy controls were blindly assessed for cognitive and motor function, and transcranial ultrasound. RESULTS Executive function, fluid intelligence, motor planning, and hand coordination showed group differences. PKM and MHE were significantly higher in untreated schizophrenia and unaffected relatives. Unaffected relatives showed milder impairment, but were different from controls. CONCLUSIONS PKM and MHE predict cognitive impairment in neuroleptic-naive patients with schizophrenia and their unaffected first-degree relatives and may be used to segregate them from first-degree relatives and healthy controls.