Temperament, character, and personality disorders: etiologic, diagnostic, treatment issues.

OBJECTIVE: In this paper, we explore the underlying dimensional structure of personality disorder, propose a novel approach to its diagnosis, and outline our concepts of its etiology and treatment based on the seven factor psychobiological model of temperament and character. METHOD: Temperament and character traits were evaluated in a consecutive series of 109 psychiatric out-patients, with or without personality disorder and varying mood and anxiety states. RESULTS: Low scores on character dimensions consistently correlated with high symptom counts for personality disorder. Each subtype of personality disorder created a unique combination of correlations with the four temperament traits. CONCLUSION: Temperament and Character Inventory (TCI) temperament and character traits efficiently diagnose personality disorder and differentiate its individual subtypes. Character traits are used to diagnose the presence and the severity of personality disorder, whereas temperament traits are used for differential diagnosis. The distinction between temperament and character provides an attractive theoretical basis for etiological postulates and treatment of personality disorder.

Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).

The transmission/disequilibrium test was used for fine mapping of the linkage of schizophrenia to the chromosome 15q13-14 region, the site of a candidate gene, the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7), in parent-child triads from the NIMH Schizophrenia Genetics Initiative families. This candidate gene was identified from neurobiological studies of deficits in schizophrenics of the inhibitory gating of the P50 auditory evoked potential. The neurobiological deficit was also used as a phenotype for subsequent linkage analysis. In the present study, significant genotype-wise disequilibrium (P < 0.007) was found at D15S165, a polymorphic simple sequence marker physically located within 1 megabase of both CHRNA7 and a partially duplicated, expressed sequence that includes exons 5-10 of CHRNA7. Replication of this result was found in an additional set of families. The results support this region as a chromosomal location involved in the genetic transmission of schizophrenia.

Evidence for the multigenic inheritance of schizophrenia.

Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the alpha 7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci.

Suggestive linkage of chromosome 10p to schizophrenia is not due to transmission ratio distortion.

The genome scan of the European-American schizophrenia families from the Human Genetics Initiative of the National Institute of Mental Health (NIMH) reported a suggestive linkage to chromosome 10p. Subsequently, Paterson and Petronis [1999] reported evidence for transmission ratio distortion on 10p to females. They suggested that transmission ratio distortion to females might have created spurious evidence for linkage to 10p. To address this issue, we reanalyzed our 10p data using only male-male affected sibling pairs. The two chromosome 10p markers that gave the most evidence for linkage in our prior report continued to show evidence for linkage: D10S1423 (NPL Z = 3.0, P = 0.001) and its neighbor D10S582 (NPL Z = 2.9, P = 0.002). These data suggest that our prior report of suggestive linkage of schizophrenia to markers on 10p cannot be attributed to the transmission ratio distortion to females reported by Paterson and Petronis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:607-608, 1999.

The Junior Temperament and Character Inventory: preliminary validation of a child self-report measure.

A preliminary effort to validate the Junior Temperament and Character Inventory with a convenience sample of 322 children ages 9 to 12 years is described.

Genome-wide search for schizophrenia susceptibility loci: the NIMH Genetics Initiative and Millennium Consortium.

Schizophrenia has a complex pattern of inheritance, indicative of interactions among multiple genes and environmental factors. The detection and replication of specific susceptibility loci for such complex disorders are facilitated by the availability of large samples of affected sib pairs and their nuclear families, along with standardized assessment and systematic ascertainment procedures. The NIMH Genetics Initiative on Schizophrenia, a multisite collaborative study, was established as a national resource with a centralized clinical data base and cell repository. The Millennium Schizophrenia Consortium has completed a genome-wide scan to detect susceptibility loci for schizophrenia in 244 individuals from the nuclear families of 92 independent pairs of schizophrenic sibs ascertained by the NIMH Genetics Initiative. The 459 marker loci used in the scan were spaced at 10-cM intervals on average. Individuals of African descent were higher than those of European descent in their average heterozygosity (79% vs. 76%, P < .0001) and number of alleles per marker (9.2 vs. 8.4, P < .0001). Also, the allele frequencies of 73% of the marker loci differed significantly (P < .01) between individuals of European and African ancestry. However, regardless of ethnic background, this sample was largely comprised of schizophrenics with more than a decade of psychosis associated with pervasive social and occupational impairment.

NIMH Genetics Initiative Millenium Schizophrenia Consortium: linkage analysis of African-American pedigrees.

The NIMH Genetics Initiative is a multi-site collaborative study designed to create a national resource for genetic studies of complex neuropsychiatric disorders. Schizophrenia pedigrees have been collected at three sites: Washington University, Columbia University, and Harvard University. This article-one in a series that describes the results of a genome-wide scan with 459 short-tandem repeat (STR) markers for susceptibility loci in the NIMH Genetics Initiative schizophrenia sample-presents results for African-American pedigrees. The African-American sample comprises 30 nuclear families and 98 subjects. Seventy-nine of the family members were considered affected by virtue of having received a DSMIII-R diagnosis of schizophrenia (n = 71) or schizoaffective disorder, depressed (n = 8). The families contained a total of 42 independent sib pairs. While no region demonstrated evidence of significant linkage using the criteria suggested by Lander and Kruglyak, several regions, including chromosomes 6q16-6q24, 8pter-8q12, 9q32-9q34, and 15p13-15q12, showed evidence consistent with linkage (P = 0.01-0.05), providing independent support of findings reported in other studies. Moreover, the fact that different genetic loci were identified in this and in the European-American samples, lends credence to the notion that these genetic differences together with differences in environmental exposures may contribute to the reported differences in disease prevalence, severity, comorbidity, and course that has been observed in different racial groups in the United States and elsewhere.

Genome scan of European-American schizophrenia pedigrees: results of the NIMH Genetics Initiative and Millennium Consortium.

The Genetics Initiative of the National Institute of Mental Health (NIMH) was a multisite study that created a national repository of DNA from families informative for genetic linkage studies of schizophrenia, bipolar disorder, and Alzheimer's disease. The schizophrenia families were collected by three sites: Washington University, Harvard University, and Columbia University. This article, one in a series that describes the data collected for linkage analysis by the schizophrenia consortium, presents the results for the European-American sample. The European-American sample comprised 43 nuclear families and 146 subjects. Ninety-six of the family members were considered affected by virtue of having received a DSM-III-R diagnosis of schizophrenia (N = 82) or schizoaffective disorder, depressed (N = 14). The families contained a total of 50 independent sib-pairs. Using the significance threshold criteria suggested by Lander and Kruglyak [(1995): Nat Genet 241-247], no region showed statistically significant evidence for linkage; two markers on chromosome 10p showed statistical evidence suggestive of linkage using the criteria of Lander and Kruglyak [(1995): Nat Genet 241-247]: D10S1423 (nonparametric linkage (NPL) Z = 3.4, P = .0004) and its neighbor, D10S582 (NPL Z = 3.2, P = .0006).

Further investigation of a chromosome 15 locus in schizophrenia: analysis of affected sibpairs from the NIMH Genetics Initiative.

Linkage of a neurophysiological deficit associated with schizophrenia, i.e., the failure to inhibit the auditory P50 response, was previously reported at chromosome 15q14. The marker with the highest pairwise lod score, D15S1360, was isolated from a yeast artificial chromosome containing a candidate gene, the alpha7-nicotinic acetylcholine receptor gene. In the present study, this linkage was further investigated in a subset of the NIMH Genetics Initiative schizophrenia families. These families have not been studied neurophysiologically, as were the families in the original report. Therefore, the DSMIII-R diagnosis of schizophrenia was used as the affected phenotype. Twenty families fulfilled the criteria of at least one sibpair concordant for schizophrenia, along with their two parents or another affected relative outside the nuclear family, available for genotyping. Sibpair analysis showed a significant proportion of D15S1360 alleles shared identical-by-descent (0.58; P < 0.0024). The results further support the involvement of this chromosomal locus in the genetic transmission of schizophrenia.

Measurement of temperament and character in mood disorders: a model of fundamental states as personality types.

BACKGROUND: Personality assessment may allow reliable measurement of risk of mood disorders. METHODS: A group of adults (804) representative of the general population were assessed by questionnaire. Personality types were measured by the Temperament and Character Inventory (TCI). RESULTS: Specific TCI configurations define personality types that can be described as hyperthymic, cyclothymic, irritable, and depressive. Each type had a unique profile of emotions, suicide attempts, and hospitalization. CONCLUSIONS: TCI traits are associated with mood disorders. LIMITATIONS: Different ways of measuring Kraepelinean subtypes may disagree. Whether differences in personality cause psychopathology, or vice versa, remains uncertain. CLINICAL RELEVANCE: Personality profiles help in assessing suicidality and planning treatment.

Integrative psychobiological approach to psychiatric assessment and treatment.

A Developmental approach to integrative psychobiology provides a flexible framework for both clinical assessment and treatment planning. Assessment of seven dimensions of personality using the Temperament and Character Inventory (TCI) allows for comprehensive description of individual differences in feelings, thoughts, and actions. Four temperament factors that are stable throughout life can be decomposed in terms of their underlying genetic structure. Character factors that mature in response to social learning can be decomposed in terms of the components that unfold in a stepwise fashion from infancy through adulthood. Pharmacotherapy and psychotherapy can be systematically matched to the personality structure and stage of character development of each individual. This provides comprehensive paradigm that integrates psychodynamic, cognitive-behavioral, interpersonal, and neurobiological insights into case formulation. Use of the TCI in clinical assessment and treatment planning was illustrated by a case independently assessed by Mardi Horowitz using another approach.

Role of personality self-organization in development of mental order and disorder.

Normal and abnormal personality development can be quantified in terms of 15 specific steps in the self-organization of character as a complex adaptive system. Character is measured as three dimensions of Self-directedness, Cooperativeness, and Self-transcendence, each with five components corresponding to steps in personality development. Each of these steps is differentially influenced by heritable temperament dimensions, antecedent steps in character development, and life experiences. Predictions about the nonlinear dynamics of personality development, such as equifinality and multifinality, are confirmed in longitudinal data about individuals representative of the general population. The stepwise development of character determines large differences between individuals in their risk of psychopathology, as well as varying degrees of maturity and health.

Dimensional assessment of personality in an out-patient sample: relations of the systems of Millon and Cloninger.

The Cloninger Temperament and Character Inventory (TCI) and the Millon Clinical Multiaxial Inventory (MCMI-II) are both self-report inventories that can be used to assess personality reliably in clinical samples. Both instruments were administered to 103 consecutive psychiatric out-patients with or without personality disorders. The goals were to assess the convergent validity of the two instruments, to replicate the findings of Svrakic et al. (1993) Archives of General Psychiatry, 50, 991-999, about the differential diagnosis of Axis II disorders, and to analyse the relations of Millon's measures of Axis I disorders with Cloninger's measures. We observed a strong convergent validity between the instruments; the seven dimensions of the TCI accounted for most of the variance in MCMI-II measures of both Axis 1 and Axis 2 disorders. As reported by Svrakic et al. (1993) Archives of General Psychiatry, 50, 991-999, in in-patients, low self-directedness and low cooperativeness were confirmed to be the essential features of all personality disorders in out-patients. In addition, self-transcendence, the third of Cloninger's character dimensions, was observed to be a strong correlate of severe Axis-1 psychopathology, including manic and delusional disorders.

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.

Personality disorders: model for conceptual approach and classification. Part II: Proposed classification.

In Part II of this article we propose a model for classification of normal and deviant personality types. First, we outline a matrix that classifies normal and deviant behaviors by combining three levels of functioning (normal, neurotic, and borderline) with specific long term behavior types. Second, we describe in some detail eight discrete syndromes that meet criteria for PDs presented in Part I of the article (Vol. 47, No. 4, pp. 558-571, this Journal).

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.

Differential diagnosis of personality disorders by the seven-factor model of temperament and character.

We used multiaxial structured interviews and questionnaires to evaluate the ability of self-reports on seven personality dimensions to predict independent interview diagnoses of DSM-III-R personality disorders. We studied 136 consecutive adult psychiatric inpatients, excluding those with psychosis, organic mental disorders, and severe agitation. Sixty-six patients had interview diagnoses of DSM-III-R personality disorders. Most also had mood disorders. We confirmed the hypotheses that self-reports of low self-directedness and cooperativeness strongly predicted the number of personality symptoms in all interview categories, whereas the other factors distinguished among subtypes as predicted. Self-directedness and cooperativeness also predicted the presence of any personality disorder by differentiating patients varying in risk from 11% to 94%. Patients in clusters A, B, and C were differentiated by low reward dependence, high novelty seeking, and high harm avoidance, respectively. We conclude that low self-directedness and cooperativeness are core features of all personality disorders and are validly measured by the seven-factor Temperament and Character Inventory, but not the five-factor Neuroticism-Extraversion-Openness inventory. Each DSM-III-R personality disorder category is associated with a unique profile of scores in the seven-factor model, providing an efficient guide to differential diagnosis and treatment.

Personality disorders: model for conceptual approach and classification. Part I: General model.

In this article we present data suggesting that one core deficit in personality represents a common dimension extending across most categories of personality disorders (PDs), whereas clinically discrete syndromes classified as PDs in DSM IIIR are categorical maladaptive types related orthogonally to the common borderline dimension. In a sample of 121 subjects with PDs and 67 controls, persons with PDs and without PDs manifested similar profiles on the Millon Clinical Multiaxial Inventory (MCMI) scales for various behavior styles. Conversely, the two groups consistently differed with respect to the MCMI borderline scale: in contrast to non-PD persons, those with PDs were strikingly more borderline and typically scored above 75 points (the latter has been established as the cut off for the diagnosis of Borderline PD). Likewise, persons with PDs scored significantly higher on the Diagnostic Interview for Borderlines than the control group. These results suggest that: i) most symptoms usually considered typical of the borderline personality characterize other PDs as well; ii) borderline features seem to be characteristic of persons with PDs and can be used to distinguish PDs vs. non-PDs. Therefore, symptoms widely regarded as typical of the borderline personality characterize other PDs as well. This shared dimension may explain the overlap in categorical diagnoses of individual PDs. Moreover, this shared dimension may be efficiently used as the classificatory principle for PDs. In Part II of this article, we present a model that classifies deviant behaviors in a systematic way, i.e., combines three levels of functioning (normal, neurotic, and borderline) with a limited number of categories of (mal) adaptive behavior types.

The relationship of personality to mood and anxiety states: a dimensional approach.

This study evaluates the relationship of personality to mood and anxiety states in a sample of 50 psychiatric out patients. In order to overcome arbitrariness inherent in categorical diagnoses of affective, personality and anxiety disorders, we use a dimensional approach to personality, mood and anxiety. According to our results, mood and anxiety states affect personality domains differentially. Namely, relatively large portions of personality and behavior, such as higher-order traits of novelty seeking and reward dependence, seem independent from mood and anxiety states. In contrast, the higher-order dimension of harm avoidance and its corresponding lower-order traits reflect changes in mood and anxiety to a much greater extent. Both the likelihood that large portions of personality may be independent from current mood and the likelihood that some precisely delineated personality domains tend to change simultaneously with current mood may improve our understanding of the relationship of personality to emotionality and affective disorders.

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.