Personality characteristics of women before and after recovery from an eating disorder

BACKGROUND: Previous studies of personality characteristics in women with eating disorders primarily have focused on women who are acutely ill. This study compares personality characteristics among women who are ill with eating disorders, recovered from eating disorders, and those without eating or other Axis I disorder pathology. METHOD: Female participants were assessed for personality characteristics using the Temperament and Character Inventory (TCI): 122 with anorexia nervosa (AN; 77 ill, 45 recovered), 279 with bulimia nervosa (BN; 194 ill, 85 recovered), 267 with lifetime histories of both anorexia and bulimia nervosa (AN + BN; 194 ill, 73 recovered), 63 with eating disorder not otherwise specified (EDNOS; 31 ill, 32 recovered), and 507 without eating or Axis I disorder pathology. RESULTS: Women ill with all types of eating disorders exhibited several TCI score differences from control women, particularly in the areas of novelty-seeking, harm avoidance, self-directedness, and cooperativeness. Interestingly, women recovered from eating disorders reported higher levels of harm avoidance and lower self-directedness and cooperativeness scores than did normal control women. CONCLUSIONS: Women with eating disorders in both the ill and recovered state show higher levels of harm avoidance and lower self-directedness and cooperativeness scores than normal control women. Although findings suggest that disturbances may be trait-related and contribute to the disorders' pathogenesis, additional research with more representative community controls, rather than our pre-screened, normal controls, is needed to confirm these impressions.     

Evaluating the state dependency of the Temperament and Character Inventory dimensions in patients with major depression: a methodological contribution

BACKGROUND: Little is known as to whether or not the seven personality dimensions of Cloninger's theory, particularly the three character dimensions newly included in the theory, are independent of the states of depression. METHODS: One hundred and eight patients with major depression filled out the Temperament and Character Inventory (TCI) before and after a 16-week antidepressant treatment. RESULTS: The level of depression, as assessed by the Hamilton Rating Scale for Depression, was correlated positively to the harm avoidance score and negatively to the self-directedness and cooperativeness scores. During the treatment, the scores on these three dimensions significantly changed toward normal values in treatment-responders, but were stable in treatment-nonresponders. The changes in these dimensions were significantly explained by the change in the depression severity during treatment. Scores on novelty seeking, reward dependence, persistence, and self-transcendence were not correlated significantly to the level of depression and did not change significantly during the treatment in either treatment-responders or nonresponders. LIMITATIONS: The changes in the TCI scores during treatment in this study may reflect a non-specific tendency for the scores to change on retest. CONCLUSIONS: The results suggest that a depressive state can significantly affect assessments of harm avoidance, self-directedness, and cooperativeness in major depression. The administration of the TCI during a depressive episode may elevate the HA score, and may lower the SD and C scores. These findings highlight the importance of considering the state of depression before drawing conclusions about the TCI personality traits, when a patient with major depression is still experiencing a depressive episode.     

A possible association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and the personality trait of harm avoidance in Japanese healthy subjects

Catechol-O-methyltransferase (COMT) is an enzyme that degrades various biogenic amines, which have been hypothesized to be associated with personality traits. We investigated a possible relationship between the COMT Val158Met polymorphism and personality traits assessed by the Temperament and Character Inventory (TCI) in 139 healthy subjects in a Japanese population. The number of Met alleles of the COMT Val/Met genotype tended to relate to harm avoidance (HA) scores parametrically, while no significant difference was observed between genotype groups in either novelty seeking, reward dependence, persistence, self-directedness, cooperativeness or self-transcendence. These results suggest that the Val/Met polymorphism of the COMT gene may play a role in HA in Japanese population.     

Personality and eating disorders: a decade in review

Personality traits have been implicated in the onset, symptomatic expression, and maintenance of eating disorders (EDs). The present article reviews literature examining the link between personality and EDs published within the past decade, and presents a meta-analysis evaluating the prevalence of personality disorders (PDs) in anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) as assessed by self-report instruments versus diagnostic interviews. AN and BN are both consistently characterized by perfectionism, obsessive-compulsiveness, neuroticism, negative emotionality, harm avoidance, low self-directedness, low cooperativeness, and traits associated with avoidant PD. Consistent differences that emerge between ED groups are high constraint and persistence and low novelty seeking in AN and high impulsivity, sensation seeking, novelty seeking, and traits associated with borderline PD in BN. The meta-analysis, which found PD rates of 0 to 58% among individuals with AN and BN, documented that self-report instruments greatly overestimate the prevalence of every PD.     

The relationship of dysfunctional attitudes to personality in depressed patients.

AIM: To examine the relationship between dysfunctional attitudes and personality in depressed patients. METHOD: One hundred depressed patients completed both the Dysfunctional Attitudes Scale (DAS) and the Temperament and Character Inventory (TCI). RESULTS: Scores on the DAS correlated with duration of depression, age of onset of depression, age, harm avoidance and self-directedness. In a multiple regression analysis three measures explained 45% of the DAS score. These were duration of depression, reward dependence and self-directedness. In both the univariate analyses and multiple regression the strongest predictor of dysfunctional attitudes was the character dimension of self-directedness. CONCLUSION: The character dimension of self-directedness in the TCI which assesses an individuals' self-concept, relates highly with the dysfunctional attitudes score on the DAS. Given that the TCI assesses personality within a broader framework of a psychobiologic and developmental model, self-directedness may have a wider application as a measure of self-concept than the DAS.     

Stability of attachment‐related anxiety and avoidance and their relationships with the five‐factor model and the psychobiological model of personality

Objectives. The stability of attachment‐related anxiety and avoidance and their relationship with influential personality models are issues worth further investigation. Studying discriminant validity with respect to aspects of personality deemed as prevalently heritable, such as temperament, is particularly important. Our aims were to examine the stability of attachment dimensions and to study their relationship with psychological distress, the Big Five factors, and temperament and character dimensions. Methods. The Experiences in Close Relationships (ECR) questionnaire, the State‐Trait Anxiety Inventory (STAI), the Zung depression scale (ZDS), the Temperament and Character Inventory (TCI‐125), and the Big Five Questionnaire (BFQ) were administered to 222 undergraduate and graduate students. After 1 month, 115 participants completed again the ECR, the STAI, and the ZDS. Results. Attachment‐related anxiety was modestly correlated with depression and anxiety, while attachment‐related avoidance was modestly correlated with depression. The test–retest reliability of ECR scores was high. Changes in attachment‐related anxiety were not related to changes in depression or anxiety, and changes in attachment‐related avoidance were modestly correlated with changes in depression. In separate multiple regression models also including gender and age, attachment‐related anxiety was correlated with harm avoidance, reward dependence, low novelty seeking, low self‐directedness and low cooperativeness; low energy/extraversion and low emotional stability; attachment‐related avoidance was correlated with low reward dependence and tended to be correlated with low self‐directedness. Conclusions. These findings corroborate the reliability and the convergent and discriminant validity of the ECR, and support the notion that the attachment dimensions are only modestly related to psychological distress and are not redundant with constructs developed within influential personality models such as the five‐factor model and the psychobiological model.     

Self-reported early trauma as a predictor of adult personality: a study in a military sample

Exposure to early trauma has frequently been linked to adult psychopathology, including personality disorders. This cross-sectional study explored the relationship between personality and retrospectively rated levels of early trauma in 242 soldiers. Multiple regression analyses showed a significant relationship between early trauma and adult personality as exposure to emotional trauma predicted levels of self-directedness and cooperativeness on the Temperament and Character Inventory (TCI; C. R. Cloninger, T. R. Przybeck, D. M. Svrakic, & R. D. Wetzel, 1994). Overall, these results suggest that early emotional trauma may be related to personality dimensions associated with poor impulse control and interpersonal behavior. These results are noteworthy considering that they were obtained in a healthy sample. They show that early trauma may become ingrained in personality and hamper the potential to effectively engage in social interactions, increasing the risk of emotional and cognitive problems.     

A multivariate analysis of 59 candidate genes in personality traits: the temperament and character inventory

Cloninger (Cloninger CR. Neurogenetic adaptive mechanisms in alcoholism. Science 1987: 236: 410-416) proposed three basic personality dimensions for temperament: novelty seeking, harm avoidance, and reward dependence. He suggested that novelty seeking primarily utilized dopamine pathways, harm avoidance utilized serotonin pathways, and reward dependence utilized norepinephrine pathways. Subsequently, one additional temperament dimension (persistence) and three character dimensions (cooperativeness, self-directedness, and self-transcendence) were added to form the temperament and character inventory (TCI). We have utilized a previously described multivariate analysis technique (Comings DE, Gade-Andavolu R, Gonzalez N et al. Comparison of the role of dopamine, serotonin, and noradrenergic genes in ADHD, ODD and conduct disorder. Multivariate regression analysis of 20 genes. Clin Genet 2000: 57: 178-196; Comings DD, Gade-Andavolu R, Gonzalez N et al. Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder. Clin Genet 2000: in press) to examine the relative role of 59 candidate genes in the seven TCI traits and test the hypothesis that specific personality traits were associated with specific genes. While there was some tendency for this to be true, a more important trend was the involvement of different ratios of functionally related groups of genes, and of different genotypes of the same genes, for different traits.     

Personality dimensions harm avoidance and self-directedness predict the cortisol awakening response in military men

To account for individual differences in vulnerability for stress-related disorders, studies have examined the relationship between hypothalamic-pituitary-adrenal (HPA) axis functioning and personality. The present study examined the relationship between the free fraction of cortisol in saliva after awakening and personality as measured with Cloninger's Temperament and Character Inventory [Cloninger, C.R., Przybeck, T.R., Svrakic, D.M., Wetzel, R.D., 1994. The Temperament and Character Inventory (TCI): A Guide to its Development and Use. Washington University, Center for Psychobiology of Personality, St. Louis, MO] in 107 healthy male soldiers. Harm avoidance explained 9% of variance in cortisol levels after awakening (AUCG), and harm avoidance and self-directedness predicted 10% of variance in mean cortisol increase. The cortisol awakening response (CAR) was lower in participants with low scores on harm avoidance, and mean cortisol increase after awakening was higher in soldiers high on self-directedness and harm avoidance. These results show that the CAR is related to personality and that it can be used to examine individual differences in HPA (re)activity.     

Bipolar disorder: I. Temperament and character

BACKGROUND: The nature of the relationship between personality and bipolar affective disorders is an important but unanswered question. METHODS: We have studied personality in bipolar patients by using the Temperament and Character Inventory (TCI). TCI were administered to 100 euthymic bipolar patients and 100 controls from the normal population. RESULTS: Bipolar patients were significantly higher in harm avoidance (HA) and lower in reward dependence (RD), self-directedness (SD), and cooperativeness (CO) than controls. Bipolar patients are more fatigable, less sentimental, more independent, less purposeful, less resourceful, less empathic, less helpful, less pure-hearted, and have less impulse control than controls. Bipolar II patients are more impulsive, more fatigable, less resourceful, and have less impulse control than bipolar I patients. LIMITATIONS: Our results are limited to euthymic bipolar patients and cannot be generalized to affective disorders. CONCLUSIONS: Even when clinically euthymic on lithium maintenance, bipolar patients continue to have a characteristic cognitive deficit. This is in agreement with cognitive theories about cognitive deficits in depression that are regarded as important vulnerability factors in mood disorders.     

Alexithymia and the temperament and character model of personality

OBJECTIVE: In our study we explored the associations between alexithymia (Toronto Alexithymia Scale 20, TAS-20) and the dimensions and subscales of Cloninger's theoretically based and empirically validated psychobiological model of personality to further clarify the relationship between alexithymia and personality traits. METHODS: Psychiatric in- and outpatients (n = 254) were investigated with the TAS-20, the Temperament and Character Inventory (TCI) and the Symptom Check List SCL-90-R to control for the severity of current psychopathology. Correlation and regression analyses were performed. RESULTS: The regression analysis identified the TCI dimensions low self-directedness (SD), low reward dependence (RD) and to a minor degree harm avoidance (HA) as independent predictors for alexithymia. At the level of subscales, interpersonal detachment (RD3), low resourcefulness (SD3), low responsibility and blaming (SD1) and shyness with strangers (HA3) were predictors for alexithymia. The degree of explained variance of the TAS-20 scores by the TCI dimensions and subscales ranged between 43 and 45% whereas the inclusion of the general severity index into the regression models accounted for an additional 5% of the variance. CONCLUSIONS: Alexithymia is best explained by a mixture across different dimensions and subscales within Cloninger's psychobiological model of personality. However, alexithymia is captured only partly by current concepts of personality, and additional contributing psychological and biological factors need to be identified to understand alexithymia more extensively.     

P300 and personality: an investigation with the Cloninger's model.

The relationships between P300 and personality have been explored mainly in reference to the model of personality described by Eysenck because of its biological bases. Recently, Cloninger and his colleagues have proposed a model of personality based on four temperaments and three characters. The Temperament and Character Inventory (TCI) is a 226-item self-questionnaire developed to assess these seven dimensions of personality. In the present study, the relationships between these dimensions of personality and P300 have been investigated in 43 normal subjects. The results show that P300 amplitude is positively correlated with the novelty seeking dimension and negatively correlated with the harm avoidance dimension. In contrast, the other dimensions of the TCI were not related to P300 amplitude. Moreover, P300 latency and reaction time were not associated with the TCI dimensions of personality. This study confirms that personality is related to P300.     

Lack of association between polymorphisms of the dopamine receptor D4 and dopamine transporter genes and personality traits in a Korean population

Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.     

High harm avoidance and low self-directedness in euthymic young adults with recurrent, early-onset depression

BACKGROUND: The personality dimensions of harm avoidance (HA) and self-directedness (SD), as measured by the Temperament and Character Inventory (TCI), have been widely associated with depression and there is preliminary evidence that they may represent trait markers for depression. However, many studies in this area are limited by the use of heterogeneous samples of depressed patients and by the confounding effect of depressed mood during personality testing. The current study compares TCI personality dimension scores in a group of euthymic young adults with recurrent early-onset major depressive disorder (RE-MDD) to well-matched euthymic controls. METHODS: Fifty-two young adults with a past history of RE-MDD were recruited from consecutive referrals to a psychiatric clinic at a university health service. Eighty nine controls were also recruited. Euthymia was established in patients by a score of less than 9 on the Hamilton Rating Scale for Depression (HRSD) and in controls by a Becks Depression Inventory (BDI) score of less than 10. All participants completed the TCI-125. RESULTS: Patients and controls were well matched in terms of sociodemographic profile. Euthymic RE-MDD patients scored significantly higher than controls on the temperament dimension of harm avoidance (HA; mean score 14.5 versus 7.8, p<0.0001) and significantly lower than controls on the character dimension of self-directedness (SD; mean score 14.1 versus 19.9, p<0.0001). Covariance analysis suggested that both HA and SD contributed independently to the familial risk of depression. LIMITATIONS: Subjects and controls all came from relatively affluent social backgrounds-these findings may not generalise to more socioeconomically diverse populations. The possibility of a 'scarring effect' of depressive episodes on self-reported personality dimension scores cannot be excluded. CONCLUSIONS: High HA and low SD represent trait markers for liability to recurrent major depressive disorder in young adults. Further research is needed to replicate these findings and to assess the contribution that the experience of depressive episodes makes to self-reported personality dimension scores.     

Dropout from brief psychotherapy in anorexia nervosa

BACKGROUND: Dropout from psychotherapy is an important issue that has received little systematic attention. This study investigated the phenomenon of dropout from brief psychotherapy for anorexia nervosa (AN). METHODS: 99 outpatients suffering from AN of the restrictor type (n = 53) or binge/purging type (n = 46) were evaluated. Their clinical and personal characteristics were recorded, and body mass index was calculated for participants. They were administered the Eating Disorder Inventory-II (EDI-II), the State-Trait Anger Expression Inventory (STAXI) and the Temperament and Character Inventory (TCI). RESULTS: Significant differences in some baseline psychopathologic (EDI-II, STAXI) and personality (TCI) variables emerged from the comparison between dropouts and completers. Patients who dropped out of the treatment showed higher levels of anger temperament, anger expression-in and expression-out and lower scores for the dimensions of character (low self-directedness and low cooperativeness). No differences were found between the two groups regarding sociodemographic and clinical variables. CONCLUSIONS: Dropout from brief psychotherapy seems to be related to either psychopathologic or personality aspects, such as the tendency to repress anger, which is encountered also in psychosomatic disorders, and the presence of more compromised dimensions of character, typical of subjects with personality disorders. This study of dropout from brief psychotherapy in AN provided interesting results that will need further confirmation. Possible implications for treatment are addressed.     

Temperamental commonalities and differences in euthymic mood disorder patients, creative controls, and healthy controls

OBJECTIVE: Understanding of mood disorders can be enhanced through assessment of temperamental traits. We explored temperamental commonalities and differences among euthymic bipolar (BP) and unipolar (MDD) mood disorder patients, creative discipline graduate student controls (CC), and healthy controls (HC). METHODS: Forty-nine BP, 25 MDD, 32 CC, and 47 HC completed self-report temperament/personality measures including: The Affective Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A); the Revised NEO Personality Inventory (NEO-PI-R); and the Temperament and Character Inventory (TCI). RESULTS: Euthymic BP, MDD, and CC, compared to HC, had significantly increased cyclothymia, dysthymia and irritability scores on TEMPS-A; increased neuroticism and decreased conscientiousness on NEO-PI-R; and increased harm avoidance and novelty seeking as well as decreased self-directedness on TCI. TEMPS-A cyclothymia scores were significantly higher in BP than in MDD. NEO-PI-R openness was increased in BP and CC, compared to HC, and in CC compared to MDD. TCI self-transcendence scores in BP were significantly higher than in MDD, CC, and HC. LIMITATIONS: Most of the subjects were not professional artists, and represented many fields; temperament might be different in different art fields. CONCLUSIONS: Euthymic BP, MDD, and CC compared to HC, had prominent temperamental commonalities. However, BP and CC had the additional commonality of increased openness compared to HC. BP had particularly high Cyclothymia scores that were significantly higher then those of MDD. The prominent BP-CC overlap suggests underlying neurobiological commonalities between people with mood disorders and individuals involved in creative disciplines, consistent with the notion of a temperamental contribution to enhanced creativity in individuals with bipolar disorders.     

Anger, depression and personality dimensions in patients with migraine without aura

BACKGROUND: Migraine without aura causes acute and chronic pain and partially compromises patients' social functioning and work performance. Over the past years, psychiatric comorbidities were frequently observed in these patients, together with coping difficulties and typical personality traits. The aim of this study was to identify whether migraine patients and controls share distinctive personality traits. METHODS: 105 consecutive patients suffering from migraine without aura referred to the Headache Center of Turin University were enrolled in the study and compared to a control group of 79 healthy subjects. Patients and controls completed several psychometric questionnaires, including the Temperament and Character Inventory, the Beck Depression Inventory and the State-Trait Anger Expression Inventory. RESULTS: Patients suffering from migraine show more depressive symptoms, difficult anger management with a tendency to hypercontrol, and a distinctive personality profile with high harm avoidance, high persistence and low self-directedness. When a logistic regression was performed, the only significant predictors of migraine were temperament variables. CONCLUSIONS: The results suggest that the personality traits and psychosomatic mechanisms of migraine patients may make them vulnerable to stress and less skilled in coping with pain. These traits correlate with dysregulated neurotransmitter systems which may also be part of the psychobiological components of personality, depressive disorders and migraine itself.     

Stability of alexithymia and its relationships with the 'big five' factors, temperament, character, and attachment style

BACKGROUND: Controversy still exists concerning the stability of the alexithymia construct. Also, although alexithymia has been found to be related in a theoretically meaningful way to other personality constructs such as the 'Big Five' factors, few studies have investigated its relationship with influential constructs such as temperament and character, and attachment security. METHODS: Two hundred twenty-one undergraduate and graduate students were administered the Toronto Alexithymia Scale (TAS-20), the State-Trait Anxiety Inventory (STAI), the Zung Depression Scale (ZDS), the Temperament and Character Inventory (TCI-125), the Big Five Questionnaire (BFQ), and the Experiences in Close Relationships (ECR) questionnaire. After 1 month, 115 participants completed again the TAS-20, STAI, and ZDS. RESULTS: Alexithymia was only moderately correlated with depression and anxiety. Both the absolute and relative stability of TAS-20 total and subscale scores was high, and a negligible portion of their change over time was accounted for by changes in depression or anxiety. In separate multiple regression models including also gender, age, depression and anxiety, TAS-20 total and subscale scores were correlated with low energy/extraversion, low emotional stability, openness, low friendliness/agreeableness; harm avoidance, low self-directedness, low cooperativeness, low reward dependence; attachment-related avoidance and anxiety. CONCLUSIONS: Our findings lend support for both absolute and relative stability of alexithymia, corroborate an association between alexithymia and insecure attachment, and contribute to a coherent placing of alexithymia in the broader theoretical network of personality constructs.     

Prefrontal 5-HT2a receptor binding index,hopelessness and personality characteristics in attempted suicide

BACKGROUND: Depression, hopelessness, impaired problem solving capacities and deficient serotonergic functions have been identified as major causes of suicidal behaviour. In general, the relation between biological markers of attempted suicide and psychological functions has been investigated using indirect peripheral markers of, e.g. the serotonergic system. Recently, functional neuroimaging techniques with radioligands allow direct in vivo assessment of the neurobiological status of the central nervous system. METHODS: We studied the binding index of serotonin-(2a) (5-HT(2a)) receptors in the frontal cortex of attempted suicide patients (n=9) and normal controls (n=13) using [123I]5-I-R91150, a highly selective 5-HT(2a) receptor ligand. Moreover, we measured personality characteristics (using Cloninger's Temperament and Character Inventory) and levels of hopelessness (using Beck's Hopelessness Scale), and studied the association between 5-HT(2a) receptor binding index, hopelessness and these personality dimensions. RESULTS: When compared to normal controls, attempted suicide patients had a significantly lower binding potential of frontal 5-HT(2a) receptors, a higher level of hopelessness, a higher score on the temperament dimension harm avoidance and lower scores on the character dimensions self-directedness and cooperativeness. A significant correlation was found between harm avoidance, hopelessness and binding index in the population of patients that attempted suicide. LIMITATIONS: The limited number of patients and potential ingestion of psychotropic drugs may influence the results of the study. CONCLUSIONS: Lower central serotonergic function, hopelessness and harm avoidance are interrelated phenomena, which may increase the probability of the occurrence of attempted suicide.     

Heritability and linkage analysis of personality in bipolar disorder

Background

The many attempts that have been made to identify genes for bipolar disorder (BD) have met with limited success, which may reflect an inadequacy of diagnosis as an informative and biologically relevant phenotype for genetic studies. Here we have explored aspects of personality as quantitative phenotypes for bipolar disorder through the use of the Temperament and Character Inventory (TCI), which assesses personality in seven dimensions. Four temperament dimensions are assessed: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Three character dimensions are also included: self-directedness (SD), cooperativeness (CO), and self-transcendence (ST).

Methods

We compared personality scores between diagnostic groups and assessed heritability in a sample of 101 families collected for genetic studies of BD. A genome-wide SNP linkage analysis was then performed in the subset of 51 families for which genetic data was available.

Results

Significant group differences were observed between BD subjects, their first-degree relatives, and independent controls for all but RD and PS, and all but HA and RD were found to be significantly heritable in this sample. Linkage analysis of the heritable dimensions produced several suggestive linkage peaks for NS (chromosomes 7q21 and 10p15), PS (chromosomes 6q16, 12p13, and 19p13), and SD (chromosomes 4q35, 8q24, and 18q12).

Limitations

The relatively small size of our linkage sample likely limited our ability to reach genome-wide significance in this study.

Conclusions

While not genome-wide significant, these results suggest that aspects of personality may prove useful in the identification of genes underlying BD susceptibility.