A genome-wide association study of Cloninger's temperament scales: Implications for the evolutionary genetics of personality

Variation in personality traits is 30-60% attributed to genetic influences. Attempts to unravel these genetic influences at the molecular level have, so far, been inconclusive. We performed the first genome-wide association study of Cloninger's temperament scales in a sample of 5117 individuals, in order to identify common genetic variants underlying variation in personality. Participants’ scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained.     

Investigating Age Differences in the Genetic and Environmental Structure of the Tridimensional Personality Questionnaire in Later Adulthood

In this study we examined cross-sectional age differences in means, phenotypic covariance structure, and the underlying genetic and environmental structure of four personality constructs from Cloninger's personality system: Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS). Study participants were same-sex female twins between the ages of 50 and 96, drawn from the American Association of Retired Persons (AARP) twin sample. We examined age differences by comparing younger (age 50–65) and older (age 661) cohorts (based on a median split of the sample) and by estimating biometrical model parameters as linear and quadratic functions of continuous age. Results indicated modest, but significant, mean-level declines across this age range for NS, RD, and PS. HA showed no significant mean differences. We found moderate heritability estimates for all of the TPQ higher-order personality dimensions, ranging from 0.16 to 0.62. No significant age differences in the proportion of genetic and environmental influences on the TPQ dimensions were found. For HA, RD, and PS there were no significant age-related differences in total variance. However, for NS we observed a decline in total phenotypic variance across age cohorts.     

Widespread Evidence for Non-Additive Genetic Variation in Cloninger’s and Eysenck’s Personality Dimensions using a Twin Plus Sibling Design

Studies using the classical twin design often conclude that most genetic variation underlying personality is additive in nature. However, studies analyzing only twins are very limited in their ability to detect non-additive genetic variation and are unable to detect sources of variation unique to twins, which can mask non-additive genetic variation. The current study assessed 9672 MZ and DZ twin individuals and 3241 of their siblings to investigate the environmental and genetic architecture underlying eight dimensions of personality: four from Eysenck’s Personality Questionnaire and four from Cloninger’s Temperament and Character Inventory. Broad-sense heritability estimates from best-fitting models were two to three times greater than the narrow-sense heritability estimates for Harm Avoidance, Novelty Seeking, Reward Dependence, Persistence, Extraversion, and Neuroticism. This genetic non-additivity could be due to dominance, additive-by-additive epistasis, or to additive genetic effects combined with higher-order epistasis. Environmental effects unique to twins were detected for both Lie and Psychoticism but accounted for little overall variation. Our results illustrate the increased sensitivity afforded by extending the classical twin design to include siblings, and may provide clues to the evolutionary origins of genetic variation underlying personality.     

Temperament and Character Inventory (TCI) as predictors of depression among Japanese college students

To examine the predictive power of Cloninger's psychobiology model of depression, 167 Japanese college students were studied on two occasions, with an interval of approximately three months. At Time 1 (T1), the Temperament and Character Inventory (TCI) and Self-rating Depression Scale (SDS) were distributed. At Time 2 (T2), the SDS was distributed again. The T2 SDS score was positively correlated with Harm Avoidance and negatively correlated with Reward Dependence and Self-directedness at T1. However, after controlling for the T1 SDS score, the T2 SDS score was predicted only by T1 Self-directedness. These data suggest that lower Self-directedness can be predictive of depression, whereas higher Harm Avoidance and lower Reward Dependence are state-dependent.     

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.     

Relationship between personality trait and regional cerebral glucose metabolism assessed with positron emission tomography

There have been no studies systematically investigating relationships between biogenetic temperament dimensions and patterns of brain glucose metabolism. Nineteen healthy subjects were evaluated regarding the biogenetic temperament using Cloninger's Temperament and Character Inventory (TCI). In addition, [¹⁸F] fluorodeoxyglucose (FDG) positron emission tomography (PET) was used to measure regional brain glucose metabolism. Voxel-based correlation analysis was used to test correlations between regional brain glucose metabolism and scores on the TCI. We identified that each temperament dimension, such as Novelty Seeking, Harm Avoidance, and Reward Dependence, was significantly correlated with specific brain regions. The majority of correlations were observed in the areas of paralimbic regions and temporal lobes. The current study provides evidence linking each biogenetic temperament dimension with specific brain areas and provides a promising base for future personality research.     

Mood states and personality traits.

In this article we analyze the relationship between personality traits assessed by the Tridimensional Personality Questionnaire, and six mood states assessed by the Profile of Mood States-bipolar form. Our data suggest that large portions of personality and/or behavior, e.g., higher order dimensions of Novelty Seeking and Reward Dependence, can be relatively independent from current mood. In contrast, the Harm Avoidance dimension covaries with mood and anxiety. Also, we analyze the psychometric properties of the Profile of Mood States-bipolar form, and discuss some practical aspects of our findings.     

D2 and D4 dopamine receptor polymorphisms and personality

The relationship of various dimensions of temperament, measured by the Tridimensional Personality Questionnaire (TPQ), to polymorphisms of the D₂ dopamine receptor (DRD2) and D₄ dopamine receptor (DRD4) genes was determined in 119 healthy Caucasian boys who had not yet begun to consume alcohol and other drugs of abuse. Total Novelty Seeking score of the TPQ was significantly higher in boys having, in common, all three minor (A1,B1, and Intron 6 1) alleles of the DRD2 compared to boys without any of these alleles. Boys with the DRD4 7 repeat (7R) allele also had a significantly higher Novelty Seeking score than those without this allele. However, the greatest difference in Novelty Seeking score was found when boys having all three minor DRD2 alleles and the DRD4 7R allele were contrasted to those without any of these alleles. Neither the DRD2 nor the DRD4 polymorphisms differentiated total Harm Avoidance score. Whereas subjects having all three minor DRD2 alleles had a significantly higher Reward Dependence 2 (Persistence) score than subjects without any of these alleles, no significant difference in this personality score was found between subjects with and without the DRD4 7R allele. In conclusion, DRD2 and DRD4 polymorphisms individually associate with Novelty Seeking behavior. However, the combined DRD2 and DRD4 polymorphisms contribute more markedly to this behavior than when these two gene polymorphisms are individually considered. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:257–267, 1998. © 1998 Wiley-Liss, Inc.     

Testing a genetic structure of blood-injury-injection fears

Multivariate genetic analyses were used to examine the genetic and environmental contributions to individual differences in fears of blood, injury, and injections in 659 twin pairs who completed questions concerning fear and fainting around blood, injury, and injections, and fainting in situations not involving blood, as well as the personality scales of Neuroticism, and Harm Avoidance. There was significant familial aggregation of blood fears but univariate analyses were unable to distinguish between additive genetic or shared environmental variables, or both, as the cause. The same was true of blood fainting. Non-blood-injury fainting was best explained by a model assuming shared and unique environmental variables. However, multivariate genetic analyses, which capitalise on extra information contained by all the covariance terms, indicated that the variance in blood-injury-injection fear was principally attributable to unique environmental events specific to this fear and additive genetic factors shared with fainting. The data are discussed in the context of models of blood-injury phobia that identify the need to consider separate etiological mechanisms for fear and fainting. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:377–384, 1998. © 1998 Wiley-Liss, Inc.     

事件相关电位P300和人格的相关研究

目的 :探讨事件相关电位P30 0与气质性格量表 (theTemperatureandCharacterInventory,TCI )人格维度的关系。方法 :采用oddball作业和Cloninger的气质性格量表 (TCI)对 2 0名被试进行测量。结果 :P30 0的振幅与TCI的持续性、损害回避人格维度呈负相关 ,P30 0潜伏时与TCI的新奇性探求人格维度呈负相关。结论 :健康被试的人格维度与事件相关电位P30 0特征有一定相关     

Temperament and personality features in patients with major depression, panic disorder and mixed conditions.

METHOD: Forty-two patients with Panic Disorder (P), 18 with Major Depression (MD), 35 with both conditions (MIX) and 45 healthy subjects (C) were tested with the Tridimensional Personality Questionnaire and the Structured Interview for DSM-III-R Personality Disorders. RESULTS: A different prevalence of Dependent (P = 16.7%, MD = 5.6%, MIX = 41.4%, C = 2.1%) (P < 0.001), Obsessive-Compulsive (P = 4.8%, MD = 27.8%, MIX = 3.4%, C = 0%) (P < 0.001) and Histrionic (P =23.8%, MD = 0%, MIX = 31%, C = 4.2%) (P = 0.001) personality disorders (PD) was found among groups. Harm Avoidance (HA) (P < 0.001) and Reward Dependence (RD) (P <0.001) were higher in patients than in controls. As expected the patients with comorbid conditions (MIX) showed higher HA levels (P < 0.01) and a greater prevalence of PDs, particularly of Cluster C compared to patients with pure disorders. CONCLUSIONS: This study suggests that high HA and RD scores are associated with P, MD and MIX, and the former dimension is even higher in MIX patients.     

The relationship of Kraepelian affective temperaments (as measured by TEMPS-I) to the tridimensional personality questionnaire (TPQ)

BACKGROUND: There is considerable uncertainty in the current literature about the relationship between personality dimensions and affective temperaments. METHOD: We compared-in a non-ill 14-26-year-old Italian student population of 1010-the affective temperaments of classic psychiatry conceived as subaffective traits [and measured through the Temperament Assessment of Memphis, Pisa, Paris and San Diego-Interview Version (TEMPS-I) in the Akiskal and Mallya Operationalization] with Cloninger's revised Tridimensional Personality Questionnaire (TPQ) deriving from the experimental psychology tradition. RESULTS: The Depressive Temperament (DT) and Harm Avoidance (HA), loaded positively on the same canonical variate, whereas the hyperthymic (HT) strongly, and Novelty Seeking (NS) moderately, loaded negatively. In contrast, the Cyclothymic Temperament (CT) loaded highly positively on a second variate, on which both Novelty Seeking strongly and Harm Avoidance moderately loaded positively. Reward Dependence (RD), Persistence (P), and Irritable Temperament (IT) did not significantly relate to any temperamental and personality constructs. At a subdimensional level of TPQ 'shyness with strangers', 'stoic rigidity', 'detachment', 'fear of uncertainty', 'reflection', and 'anticipatory worry' correlated best with the DT. 'Gregariousness', 'exploratory excitability', 'uninhibited optimism', 'attachment', 'confidence', 'extravagance', 'independence', 'vigor', and 'impulsiveness' correlated best with HT. Lastly, 'anticipatory worry', 'disorderliness', 'sentimentality', and 'fatigability' correlated best with CT. CONCLUSIONS: The data provide concurrent validity to TEMPS-I and, as earlier suggested by Cloninger, indicate that (as expected) high HA and DT are related. High NS is both related to the HT and CT, and (somewhat unexpectedly), the CT is related to high HA. In a more theoretical vein, hyperthymic-novelty seeker can be predicted to be overrepresented among those with high achievement; on the other hand, a moody, restless disposition (a cyclothymic-harm avoidant type) may engage in outrageous behavior and be liable to negative affective arousal. We submit that these considerations could shed some light on the origin of socially adaptive behavior ('sunny' or sanguine types) on the one hand, and borderline conditions, anxious-hostile bipolarity ('dark' types) on the other.     

Temperament and character properties of male psoriasis patients

Personality properties have an effect on the onset and triggering of psoriasis. The current study aimed to examine the personality of psoriasis patients in relation to the severity of the illness. Psoriasis and healthy participants completed the Beck Depression Inventory, Beck Anxiety Inventory, Maudsley Obsessive Compulsive Inventory, Temperament and Character Inventory. Severity of psoriasis was evaluated by the PASI. MANCOVA results revealed significantly higher Novelty Seeking, Harm Avoidance, Reward Dependence and Self-Transcendence scores for psoriasis group. Severity of PASI was predicted by harm avoidance and reward dependence. Personality properties should be evaluated while planning therapeutic interventions for psoriasis patients.     

Personality of seasonal affective disorder analyzed by Tri-dimensional Personality Questionnaire

BACKGROUND: Although there have been numerous reports in personality of mood disorders, there have been few reports in regard with personality of winter seasonal affective disorder (SAD). Furthermore, no reports have been published concerning summer SAD personality characteristics. Thus, this study was conducted to assess the personality of winter and summer SAD using Tri-dimensional Personality Questionnaire (TPQ) that have been used in a variety of mental disorders. METHODS: A total of 6135 Japanese were evaluated with TPQ, the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Self-rating Depression Scale (SDS). Winter, summer and non-SAD groups were classified by SPAQ. We compared the difference of personality trait among these three groups in consideration of gender, age and SDS score influence. RESULTS: Winter SAD demonstrated higher "Novelty Seeking" and "Harm Avoidance"; summer SAD showed higher "Harm Avoidance" than the non-SAD group. "Harm Avoidance" in both SAD groups was re-analyzed using SDS score as a covariate, and "Novelty Seeking" in winter SAD using age as a covariate. As a result, the significance of high "Novelty Seeking" and high "Harm Avoidance" in winter SAD was excluded. However, "Harm Avoidance" remained the significant difference between summer and non-SAD. LIMITATION: SAD was diagnosed only by SPAQ and not by interview. The state-dependency of "Harm Avoidance" was not confirmed in identical patients over lapse of time. CONCLUSION: Patients with winter SAD have high "Harm Avoidance" dependent on the depressive state that is in accordance with non-seasonal depression. Patients with summer SAD have high "Harm Avoidance" possibly independent from the depressive state.     

Characterization of impulsivity in suicide completers: clinical, behavioral and psychosocial dimensions

BACKGROUND: Impulsivity is a personality trait thought to be linked to suicide. Yet, not all suicides are highly impulsive. We aimed to better understand clinical, behavioral and psychosocial correlates of the association between suicide and impulsive behavior. METHODS: One hundred sixty four suicide cases with impulsivity scores based on the Barratt Impulsivity Scale (BIS) were investigated. To examine the most extreme phenotypes, one hundred suicide cases, representing subjects with BIS scores above the 70th percentile and below the 30th percentile, were compared on clinical, behavioral and psychosocial suicide risk factors assessed by way of structured psychological autopsy methods with best informants. RESULTS: The impulsive suicide cases were significantly younger, exhibited higher measures of aggressive behavior, and were more likely to have a cluster B diagnosis as well as lifetime and 6-month prevalence of alcohol and drug abuse/dependence. They also differed significantly from their non-impulsive counterparts on all subscales of the TCI except for Harm Avoidance and Reward Dependence. Impulsive suicide completers were more likely to have had a history of childhood abuse and to have experienced a triggering life event up to a week preceding their death. A multivariate analysis indicated that 6-month prevalence of substance abuse/dependence and high aggressive behavior remained significant even after controlling for other significant variables. LIMITATIONS: This study was carried out using proxy-based interviews. CONCLUSIONS: Most of the known clinical and behavioral risk factors commonly associated with suicide are particularly valid for impulsive suicide completers. Further, triggering and adverse life events seem to play a role primarily in impulsive suicide.     

Shared Environmental Influences on Personality: A Combined Twin and Adoption Approach

In the past, shared environmental influences on personality traits have been found to be negligible in behavior genetic studies (e.g., Bouchard and McGue, J Neurobiol 54:4–45, 2003). However, most studies have been based on biometrical modeling of twins only. Failure to meet key assumptions of the classical twin design could lead to biased estimates of shared environmental effects. Alternative approaches to the etiology of personality are needed. In the current study we estimated the impact of shared environmental factors on adolescent personality by simultaneously modeling both twin and adoption data. We found evidence for significant shared environmental influences on Multidimensional Personality Questionnaire Absorption (15 % variance explained), Alienation (10 %), Harm Avoidance (14 %), and Traditionalism (26 %) scales. Additionally, we found that in most cases biometrical models constraining parameter estimates to be equal across study type (twins vs. adoptees) fit no worse than models allowing these parameters to vary; this suggests that results converge across study design despite the potential (sometimes opposite) biases of twin and adoption studies. Thus, we can be more confident that our findings represent the true contribution of shared environmental variance to personality development.     

Anxiety proneness linked to epistatic loci in genome scan of human personality traits

A genome-wide scan between normal human personality traits and a set of genetic markers at an average interval of 13 centimorgans was carried out in 758 pairs of siblings in 177 nuclear families of alcoholics. Personality traits were measured by the Tridimensional Personality Questionnaire. We detected significant linkage between the trait Harm Avoidance, a measure of anxiety proneness, and a locus on chromosome 8p21–23 that explained 38% of the trait variance. There was significant evidence of epistasis between the locus on 8p and others on chromosomes 18p, 20p, and 21q. These oligogenic interactions explained most of the variance in Harm Avoidance. There was suggestive evidence of epistasis in other personality traits. These results confirm the important influence of epistasis on human personality suggested by twin and adoption studies. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:313–317, 1998. © 1998 Wiley-Liss, Inc.     

The relationship of psychological well-being to distress and personality

BACKGROUND: The concept of psychological well-being has been neglected for a long time in scientific literature. Over the last decades, however, many psychometric instruments have been developed to measure it. The aim of the present study was to analyze the concept of psychological well-being and its relationship to distress and personality traits. It is clinically and empirically important to establish where the measures of well-being are located in relation to symptomatology indices and personality traits. METHODS: A sample of 450 subjects in the general population completed three self-rating scales for the assessment of symptomatology (Kellner's Symptom Questionnaire), psychological well-being (Ryff's Psychological Well-Being Scales, PWB), and personality traits (Cloninger's Tridimensional Personality Questionnaire). The assessment was repeated after 1 month. Pearson's coefficient was used to analyze PWB test-retest reliability and correlations between well-being, distress and personality indicators. Exploratory factor analysis was performed for both assessments. RESULTS: Test-retest Pearson's coefficients were satisfactory for all six PWB scales. Exploratory factor analyses showed a 4- or 5-factor structure, where well-being, distress and personality remained separated. PWB scales were negatively and significantly correlated with all symptom scales, but only with one personality dimension, TPQ Harm Avoidance. Mean-level differences by gender showed that in general women significantly presented with lower levels of well-being (except in Positive Relations) and higher levels of distress and personality disturbances. CONCLUSIONS: The results suggest that the relationship of well-being to distress and personality is complex. Psychological well-being could not be equated with the absence of symptomatology or with personality traits. PWB scales measure an attitude toward optimal functioning that is crucial for a comprehensive consideration of individuals in clinical settings.     

Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity

Background: According to recent theories, suicidal behaviour is associated with depressive disorders that are commonly induced by social stressors in persons with a trait-dependent vulnerability. Stressor-induced increased cortisol secretion may interfere with this vulnerability that can be defined in terms of (possibly inter-related) biological and psychological or personality-related characteristics. Delineation of such trait-like characteristics may increase the specificity in the prediction of suicidal behaviour and thus lead to new approaches to the treatment and prevention of suicidal behaviour. Methods: Psychiatric symptomatology, personality dimensions (Cloninger’s Temperament and Character), peripheral markers of serotonergic (whole blood serotonin, platelet MAO activity) and noradrenergic (plasma MHPG) activity, and urinary cortisol were measured in a random sample of patients with a history of violent suicidal behaviour and compared to those of patients without such a history. Results: When compared to patients without a history of violent suicidal behaviour (n=23), patients with such a history (n=17) were characterised by higher urinary cortisol levels, a significantly lower mean score on Reward Dependence, a borderline significantly increased score on Novelty Seeking and a significantly lower mean plasma MHPG level. Urinary cortisol level correlated significantly with Reward Dependence and Novelty Seeking scores. There were no differences between patient groups regarding severity of anxiety or depressive symptomatology. No differences with regard to the biological parameters were found between patients who recently attempted suicide and those with a history of suicidal behaviour. Limitations: Limitations of this study included a relatively small number of study subjects and the use of peripheral markers to assess central neurotransmission functions. Conclusions: Violent suicidal behaviour is associated with increased cortisol secretion, a personality profile defined by low Reward Dependence (reflecting the degree of sensitivity to social stressors) and a tendency of increased Novelty Seeking (related to impulsivity and the regulation of anger), and reduced noradrenergic functioning (possibly reflecting an inability to adapt to stressors).     

Comparison of the effects of fluoxetine,imipramine and placebo on personality in atypical depression

BACKGROUND: Atypical depression is associated with elevated rates of personality disorders. Studies have confirmed the efficacy of a several antidepressants in the treatment of atypical depression. Whether their pathological dimensions of personality diminish after benefitting from effective medication treatment is unclear. AIMS: To determine the extent that pathological dimensions of character improved among patients who benefitted from treatment. METHOD: One-hundred and fifty-four outpatients with DSM-IV Major Depression who met Columbia criteria for atypical depression were randomized to receive fluoxetine, imipramine or placebo for a 10-week double-blind clinical trial. The Temperament and Character Inventory (TCI) was administered at the initiation of treatment and 8 weeks later. Low scores on either of two Character dimensions (Self-Directiveness or Cooperativeness) indicate psychopathology. RESULTS: Responders had a substantial reduction in Harm Avoidance, but post-treatment scores remained significantly higher than the normal control group (NCG). Fluoxetine and Imipramine did not produce different changes on personality, except for Self-Transcendence. LIMITATIONS: High proportion of missing data, inadequate sample size, post-hoc analysis. CONCLUSIONS: Among responders, Self-Directiveness improved and normalized; Harm Avoidance also improved but did not normalize. These data suggests that effective treatments reduce some pathological personality traits as well as improving mood.