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fferent temperament and character dimensions correlate with panicsorder comorbidity in bipolar disorder and unipolar depression

rco Mula a, Stefano Pini a,*, Palmiero Monteleone b, Paolo Iazzetta a, Matteo Preve a,onso Tortorella b, Emilia Amato b, Luca Di Paolo a, Ciro Conversano a, Paola Rucci a,vanni B. Cassano a, Mario Maj b

partment of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, University of Pisa, via Roma 67, 56100 Pisa, Italy

partment of Psychiatry, University of Naples SUN, Naples, Italy

ntroduction

Temperament refers to the biological or constitutionale of personality features that refer to reactivity,iability, and intensity of emotional dispositions (Akiskal,4). It can be distinguished from character which mainlytes to interpersonal operations and individual differ-es in self object relationships, which develop in a stage-manner as a result of non-linear interactions among

perament, family environment and individual lifeerience (Cloninger, 1994; Cloninger, Bayon, & Svrakic,8). Kraepelin described four basic affective tempera-

nts (manic, depressive, irritable and cyclothymic) andgested that they could color the symptoms pattern of

acute mood episodes (Kraepelin, 1921). In that tradition,Akiskal proposed the characterization of baseline affectivetemperament, emphasizing the role of the latter for the finalphenomenology and prognosis of mood disorders (Akiskal,Djenderedjian, Rosenthal, and Khani, 1977).

The concept of ‘‘anxious temperament’’ has beengenerally less apparent to psychiatry when compared toaffective temperaments (Akiskal, 1988; Cloninger, 1986).Janet used the term ‘‘anxiete consistutionelle’’ to refer toindividuals who were anxious by nature (Janet, 1919), andsome authors speculated about the putative defensive roleof constitutional anxiety proneness (Nesse, 1990; Perugiet al., 1998). Recognized anxious temperaments includethe anxious-avoidant, the anxious-phobic and the general-ized anxious (Akiskal, 1985). The anxious-avoidant typederives from the works of Kretschmer (1936) and Millon(1969) and refers to timid individuals who are over-sensitive to criticism, disapproval and exaggerate risks in

T I C L E I N F O

le history:

ived 21 November 2007

ived in revised form 15 February 2008

pted 26 February 2008

ords:

lar disorder

ic disorder

perament

orbidity

or depression

A B S T R A C T

Background: This study aimed to investigate temperament and character correlates of

panic disorder (PD) comorbidity in euthymic patients with bipolar disorder (BD) or

unipolar depression (UD).

Methods: Temperament and character were assessed using the Temperament and

Character Inventory Revised (TCI-R) in 181 patients (70 patients with BD-I, 51 patients

with BD-II and 60 with UD) in a euthymic state for at least 2 months.

Results: PD was diagnosed in 14.3% of BD-I patients, 31.4% of BD-II and 40% of UD. BD

patients with PD, when compared with BD patients without PD, had higher scores on harm

avoidance (OR = 1.04; 95% CI = 1.02–1.07; p = 0.002). Patients with UD and PD, when

compared to patients with UD without PD, had higher scores on social acceptance

(OR = 1.27; 95% CI = 1.08–1.49; p = 0.004).

Conclusion: Different temperament and character dimensions correlated with PD

comorbidity in BD and UD patients, suggesting different underlying pathophysiological

mechanisms.

� 2008 Elsevier Ltd. All rights reserved.

Corresponding author. Tel.: +39 050993559; fax: +39 050835420.

E-mail address: s.pini@med.unipi.it (S. Pini).

Contents l is ts ava i lab le at Sc ienceDirect

Journal of Anxiety Disorders

7-6185/$ – see front matter � 2008 Elsevier Ltd. All rights reserved.

10.1016/j.janxdis.2008.02.004

ease cite this article in press as: Mula, M, et al., Different temperament and character dimensions correlate with panicisorder comorbidity in bipolar disorder and unipolar depression, J Anxiety Disord (2008),oi:10.1016/j.janxdis.2008.02.004

M. Mula et al. / Journal of Anxiety Disorders xxx (2008) xxx–xxx2

ANXDIS-862; No of Pages 6

routine. The anxious-phobic temperament originated fromFreud’s concept of ‘‘free-floating anxiety’’ (Freud, 1894)and, nowadays, refers to anxiety sensitivity and avoidanceof specific situations that may be perceived as dangerous.Finally, the generalized anxious temperament, as sug-gested by Akiskal (1998), refers to an uncontrollableconstitutional disposition to worry. However, it needs tobe acknowledged that, with respect to recurrent mooddisorders, anxious traits may be easily overshadowed bythe great emotional intensity of the affective tempera-ments (Akiskal, 1998). Nevertheless, it is evident thatinformation about temperament features, can be of greatvalue for the understanding of mood–anxiety disorderscomorbidity and may have important clinical implications.Temperament features may predispose to the develop-ment of the mood disorder or modify the natural history ofthe illness, comorbidity patterns and response to treat-ment. Alternatively, temperament features may be inter-preted as subclinical expressions of the underlyingvulnerability and may be altered by current or past moodstate (Cloninger et al., 1998).

Comprehensive methods have been developed for theassessment of temperament and character features thatare highly reliable and efficient, using self-reports, expertinterviews or collateral informants, thereby producingratings that show strong agreement across methods(Zimmerman, 1994). Among the variety of alternativedimensional models proposed, Cloninger’s psychobiologi-cal model received a large empirical support for studyingtemperament. This model consists of four dimensions oftemperament (novelty seeking, NS; harm avoidance, HA;reward dependence, RD; persistence, P) and three dimen-sions of character (self-directedness, SD; cooperativeness,C; self-transcendence, ST) (Cloninger, Przybeck, Svrakic, &Wetzel, 1994). According to Cloninger et al., NoveltySeeking is defined as the tendency to respond actively tonovel stimuli leading to pursuit of rewards and escapefrom punishment. Harm Avoidance corresponds to thetendency toward an inhibitory response to signals ofaversive stimuli that leads to avoidance of punishment andnon-reward. Reward Dependence is defined as a positiveresponse to signals of reward to maintain or resistbehavioral extinction. Persistence seems to be very closeto the Reward Dependence component. Among characterdimensions, Self-directedness refers to the ability of anindividual to control, regulate and adapt his behavior to fitthe situation in agreement with individually chosen goalsand values. Cooperativeness accounts for individualdifferences in identification with and acceptance of otherpeople while Self-transcendence is a character associatedspirituality (Cloninger, Svrakic, & Przybeck, 1993; Clonin-ger et al., 1994; Cloninger, Bayon, and Svrakic, 2004).

In mood disorders, temperament dysregulations arecommonly reported with rates ranging between 20% and80% (Akiskal et al., 2006). Previous authors attempted toclarify temperamental correlates in individuals with panicdisorder (PD) or bipolar disorder (BD) or major depression(UD) (Engstrom, Brandstrom, Sigvardsson, Cloninger, &Nylander, 2003, 2004). On the contrary, there are nostudies, to the best of our knowledge, investigatingtemperament and character features in patients with

different mood disorders in relation to the presence/absence of PD comorbidity. The importance of such anissue stems from different sources. First, epidemiologicaldata demonstrate that PD occurs frequently in bipolar andunipolar depression and, in some studies, such a comor-bidity seems to represent the rule rather than theexception (Dilsaver et al., 1997; Kessler, Rubinow, Holmes,Abelson, and Zhao, 1997). Second, literature suggests thatthe co-occurrence of PD in BD patients is associated withpoorer response to treatment, earlier onset of BD, elevatedrates of comorbid psychopathology, greater levels ofdepression, more suicidal ideation and increased familialrisk of affective disorders (Frank et al., 2002; Pini et al.,1997). Third, a number of studies supports the hypothesisthat bipolar-panic comorbidity may constitute a uniqueentity from a clinical, neurobiological and genetic point ofview (Goodwin & Hoven, 2002; MacKinnon & Zamoiski,2006). These data altogether configure the bipolar-panicconnection as an entity with strong common under-pinnings which, in turn, may be associated with peculiartemperamental correlates. From such a perspective, in thisstudy, we aimed at investigating temperament andcharacter correlates of PD comorbidity, using Cloninger’spsychobiological model, in patients with BD and to verifywhether the same temperamental features were alsodetectable in UD patients.

2. Methods

Data were drawn from a multicenter Italian study,performed in euthymic patients between 2003 and 2006,aimed to evaluate clinical, biological and psychosocialfeatures of BD-II and to compare them with those ofpatients with BD-I and UD.

To be enrolled, patients had to fulfill the followingcriteria: (1) DMS-IV criteria for BD-I, BD-II, or UD,confirmed by the Structured Clinical Interview for DSM-IV-Patient Edition (SCID-I); (2) be in a euthymic state for atleast 2 months, confirmed by a HAM-D total score<8 and aYMRS<6; 3) age between 18 and 60 years; (4) be willing toprovide a written informed consent to undergo theexperimental procedures; and (5) absence of brain and/or severe physical illnesses. The protocol was reviewed andapproved by the local ethic committee of the five Italiancenters.

Current and lifetime PD comorbidity in all patients wasinvestigated using the SCID-I. In the early phase of thestudy, inter-rater reliability of diagnoses was ascertained,showing a good reliability with a Cohen kappa coefficientof 0.89.

Temperament and character were assessed using theTemperament and Character Inventory Revised (TCI-R), animproved version of the former TCI, developed on the basisof the Tridimensional Personality Questionnaire (Clonin-ger et al., 1994). It is a 240 items questionnaire organizedinto 29 subscales exploring four temperamental dimen-sions (Novelty Seeking, Harm Avoidance, Reward Depen-dence, Persistence) and three character dimensions(Self-Directedness, Cooperativeness, Self-Transcendence).The psychometric properties of the Italian version of theinstruments have been investigated, showing acceptable

Please cite this article in press as: Mula, M, et al., Different temperament and character dimensions correlate with panicdisorder comorbidity in bipolar disorder and unipolar depression, J Anxiety Disord (2008),doi:10.1016/j.janxdis.2008.02.004

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M. Mula et al. / Journal of Anxiety Disorders xxx (2008) xxx–xxx 3

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rnal consistency (median alpha = 0.72, 25th percen-= 0.56, 75th percentile 0.74) and 1-month test–retestability ranging between 0.52 and 0.80 for differentscales (Fossati et al., 2007). All subjects filled out the-R. Scores on this instrument were calculated using thethod suggested by Cloninger and non-transformed rawres were analyzed.The frequency of categorical variables was comparedong groups using the chi-square test. One-way analysisvariance (ANOVA) with post-hoc pairwise Tukey’sparisons was used to compare continuous demo-

phic variables and domain and subdomain scores of the-R among the three groups of patients (BD-I, BD-II and). The probability level was set to 0.016 (0.05/3) touce the Type-I error associated with multiple compar-s. Domain and subdomain scores of TCI-R werepared between patients with and without PD, usingindependent-sample t-test. Effect size was used topare differences (Cohen, 1988). Cohen defined effects as small (d = 0.2), medium (d = 0.5) and large (d = 0.8).ackward stepwise logistic regression analysis waslied to identify relevant dimensions correlated to PDorbidity in BD and UD patients. All statistical analyses

re 2-tailed and conducted using SPSS, version 12.0.

esults

The study sample includes 70 patients with BD-I, 51ients with BD-II and 60 subjects with UD. Demographic

clinical characteristics of the study groups are shownTable 1. A current or lifetime comorbid diagnosis ofic disorder was found in 14.3% of patients with BD-I,

4% of BD-II and 40% of UD.Initially, we investigated major TCI dimensions anddimensions among BD-I, BD-II and UD patients. There

s no difference between BD-I and BD-II. UD patientswed higher scores on HA than BD-I and BD-II (F = 10.0,0.001; post-hoc comparisons with significance at0.016 UD > BD-I, p < 0.001 and UD > BD-II, p = 0.015),icipatory worry (HA1) (F = 10.78, p < 0.001; post-hocparisons with significance at p = 0.016 UD > BD-I,0.001), fear of uncertainty (HA2) (F = 5.08, p = 0.007;t-hoc comparisons with significance at p = 0.016> BD-II, p = 0.004) and shyness (HA3) (F = 7.71,0.001; post-hoc comparisons with significance at0.016 UD > BD-I, p < 0.001). Conversely, the UD group

significant lower scores on some subdimensions ofelty seeking (NS) such as exploratory excitability (NS1)5.39, p = 0.005; post-hoc comparisons with significance= 0.016 BD-I > UD, p = 0.006) and extravagance (NS3)5.27, p = 0.006; post-hoc comparisons with significance

p = 0.016 BD-I > UD, p = 0.013, BD-II > UD, p = 0.015).sidering character dimensions, BD had higher scores

n UD patients on two subscales of self-directedness (SD),ely purposefulness (SD2) (F = 5.28, p = 0.004; post-hocparisons with significance at p = 0.016 BD-I > UD,

0.004) and resourcefulness (SD3) (F = 6.46, p = 0.001;t-hoc comparisons with significance at p = 0.016 BD-UD, p = 0.001). TCI dimensions and subdimensionsres were compared in the three groups of patients

differences were analogous to those reported above in thegeneral study sample.

Subsequently, we investigated significant differences inmajor TCI dimensions and subdimensions in BD patientswith comorbid PD (BD–PD) as compared to BD patientswithout PD (BD–noPD) and UD–PD patients as comparedto UD–noPD. BD–PD patients did not differ in demographiccharacteristics or pattern of other comorbid Axis-Idisorders as compared to BD–noPD patients. The samefor UD–PD subjects as compared to UD–noPD. Moreover,there was no difference in the number of lifetime moodepisodes in BD–PD patients as compared to BD–noPD (totalnumber, t = 1.515, p = 0.148; number depressive episodes,t = 1.354, p = 0.192; number manic episodes, t = 0.621,p = 0.536; number ipomanic episodes, t = 1.332, p = 0.201).The same for UD–PD as compared to UD–noPD (t = 1.382,d.f. = 118, p = 0.188).

BD–PD had higher scores on HA than BD–noPD (Table 2)(Effect size was medium, Cohen’s d = 0.596). On theindividual TCI subdimensions, the BD–PD group hadhigher scores on anticipatory worry (HA1) (t = 3.89,p < 0.001, Cohen’s d = 0.717), fatigability (HA4) (t = 2.53,p = 0.013, Cohen’s d = 0.471), sentimentality (RD1)(t = 1.99, p = 0.049, Cohen’s d = 0.370) and lower onresponsibility (SD1) (t = �2.36, p = 0.019, Cohen’sd = 0.433). Effect sizes were medium for anticipatoryworry and responsibility and small for fatigability andsentimentality. In a logistic regression model includingHA1, HA4, RD1 and SD1 none of them was associated withPD. In a separate model of logistic regression analysis, HAshowed a significant association with PD (OR = 1.04; 95%CI = 1.02–1.07; p = 0.002).

In the UD group, there were no between-groupsdifferences on higher-order dimensions for temperamentand character in relation to PD comorbidity (Table 2), whileon individual subscales patients with UD–PD had higher

Table 1

Demographic characteristics of the sample (n = 181)

BD (n = 121) UD (n = 60)

BD-I (n = 70) BD-II (n = 51)

Age mean (S.D.) 41.3 (11.6) 48.1 (11.7) 49.2 (11.0)

Gender (%)

Male 43 43 30

Female 57 57 70

Age at onset mean (S.D.) 26.9 (8.3) 34.6 (11.4) 33.0 (11.2)

Marital status (%)

Married 35.7 52.9 65

Separated/divorced 14.3 9.8 13.3

Never married 50 37.3 21.7

Education (%)

Less than 8th grade 10 13.7 25

9th to 11th grade 24.3 11.8 16.7

High school diploma 38.6 31.4 28.3

University degree 27.1 43.1 30

Work status (%)

Employed 50 60.8 60

Unemployed 28.6 23.5 23.3

Retired 21.4 15.7 16.7

res on transpersonal identification (ST2) (t = 2.26,

-I, BD-II, UD) without PD comorbidity. Observed sco

ease cite this article in press as: Mula, M, et al., Different temperament and character dimensions correlate with panicisorder comorbidity in bipolar disorder and unipolar depression, J Anxiety Disord (2008),oi:10.1016/j.janxdis.2008.02.004

M. Mula et al. / Journal of Anxiety Disorders xxx (2008) xxx–xxx4

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p = 0.027, Cohen’s d = 0.595) and social acceptance (C1)(t = 3.37, p = 0.001, Cohen’s d = 0.885). Effect sizes werelarge for social acceptance and medium for transpersonalidentification. In a logistic regression model including ST2and C1, only C1 was significantly correlated with PD(OR = 1.27; 95% CI = 1.08–1.49; p = 0.004).

4. Discussion

Our finding that patients with BD-I and BD-II are similaron the high dimensions of temperament and character is inkeeping with previous studies performed in euthymicsubjects with bipolar disorder (Engstrom et al., 2004) andsupport our decision to investigate PD comorbidityconsidering BD patients as a group. Main differences intemperament and character dimensions between patientswith BD and those with UD are in keeping with a number ofprevious studies linking high HA (defined as a tendency torespond intensely to signals of aversive stimuli, therebylearning to avoid punishment and novelty) and low SD(defined as the ability of an individual to adapt, regulateand control behavior to fit situations in accord with hischosen goals and values) to unipolar depression (Hiranoet al., 2002; Smith, Duffy, Stewart, Muir, & Blackwood,2005).

It is interesting that UD patients presented with lowerscores in NS dimension than BD patients, especially BD-I.NS is defined as the tendency to respond actively to novelstimuli leading to pursuit of rewards and escape frompunishment. A previous study, aimed to investigatetemperamental differences in euthymic mood disorderpatients, showed no difference in NS comparing BD and UDsubjects. However, Nelsen and Dunner (1995) showed thattreatment resistant patients with UD have a lower score inNS dimensions than non-treatment-resistant patients.Hansenne, Pitchot, Gonzalez Moreno, Machurot, andAnnseau (1998) pointed out that low NS scores, especiallyin exploratory excitability (NS1), correspond to thedifficulty for depressed patients to initiate novel behaviorand to produce active exploration of the environment. Ourfindings would be in keeping with current literaturelinking BD to motivational behavioral disinhibition and UDto behavioral inhibition to the unfamiliar (Rottenberg &Johnson, 2007) and, interestingly, they do not seem to beinfluenced by PD comorbidity. It is, thus, evident thatfurther studies are needed to evaluate what actually linksNS dimensions to BD and UD and the possible clinicalsignificance.

To best of our knowledge, there are no studies thatspecifically investigated, using Cloninger’s model, thehypothesis that different temperament and characterfeatures lie behind PD comorbidity in patients with BDand UD.

We observed that HA dimension was significantly morerepresented among patients with BD comorbid with PDthan among those BD patients without comorbid PD.Conversely, C1 (Social Acceptance) dimension was sig-nificantly higher among UD patients with comorbid PDthan among depressed patients with no PD comorbidity.

Our results about temperament and character corre-lates of PD comorbidity can be interpreted in the light ofexisting literature, especially for what concerns HAdimension. Previous authors reported higher HA scoresin patients with UD and comorbid PD than in patients withUD alone or UD comorbid with other Axis I disorders(Ampollini, Marchesi, Signifredi, & Maggini, 1997; Ampol-lini et al., 1999; Mulder, Joyce, & Cloninger, 1994).However, it is important to point out that, contrary toNS and RD dimensions, which remain stable in patientswith UD over time, HA showed to be highly affected by themood state of the patient. In fact, HA is elevated duringdepressive states (Chien & Dunner, 1996; Mulder & Joyce,1994), correlates with the severity of depression, asmeasured by the HAM-D (Hansenne et al., 1999) andchanges greatly toward normal values during effectiveantidepressant treatment (Hirano et al., 2002). Moreover,high HA scores are not specific to depression since thesame result has been observed in other disorders such asobsessive compulsive disorder (Pfohl, Black, Noyes, Kelley,& Blum, 1990), PD (Starcevic & Bogojevic, 1997), post-traumatic stress disorder (Wang et al., 1997) and schizo-phrenia (Van Ammers, Sellman, & Mulder, 1997). Thus, ithas been speculated that elevated HA scores may not be atrait characteristic of UD patients, but only reflect theseverity of general psychopathology and the long-standingpersonality alteration caused by mood disruption (Hiranoet al., 2002). In our study, we assessed subjects who hadbeen euthymic for at least two months, reducingconsiderably the bias due to patient’s current mood states.It is, therefore, tempting to speculate that the observedcorrelation between higher HA scores and bipolar-paniccomorbidity may reflect basic neurobiological alterationsin this group of patients which are independent of thepolarity of mood state. This is further supported by the lackof difference in the number of depressive episodes amongthe different groups. Our data are consistent with a

Table 2

High order dimensions of temperament and character in bipolar and unipolar patients with and without comorbid panic disorder

BD (n = 121) UD (n = 60)

BD–PD (n = 26) BD–noPD (n = 95) UD–PD (n = 24) UD–noPD (n = 36)

NS mean (S.D.) 97.9 (15.9) 101.0 (12.6) 93.3 (14.9) 94.7 (12.8)

HA mean (S.D.) 112.1 (17.4)a 98.7 (18.9) 118.5 (21.7) 112.4 (19.1)

RD mean (S.D.) 96.8 (17.9) 97.2 (17.3) 98.0 (13.3) 95.5 (13.4)

PS mean (S.D.) 98.0 (18.3) 105.0 (22.6) 100.8 (22.6) 102.1 (23.6)

SD mean (S.D.) 125.7 (18.2) 129.7 (22.1) 121.5 (16.9) 122.4 (18.9)

C mean (S.D.) 131.9 (15.5) 127.0 (21.1) 131.5 (14.0) 126.9 (10.3)

ST mean (S.D.) 70.6 (15.4) 68.9 (17.6) 75.6 (16.7) 68.7 (16.2)

a vs. BD–noPD, t = 3.25, p = 0.001.

Please cite this article in press as: Mula, M, et al., Different temperament and character dimensions correlate with panicdisorder comorbidity in bipolar disorder and unipolar depression, J Anxiety Disord (2008),doi:10.1016/j.janxdis.2008.02.004

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ber of studies supporting the hypothesis that bipolar-ic comorbidity may deserve attention as a separate andependent entity from a clinical, neurobiological andetic viewpoint (Doughty, Wells, Joyce, Olds, & Walsh,4; Frank et al., 2005; Goodwin & Jamison, 2007;dwin & Hoven, 2002; Henry et al., 2003; MacKinnon &oiski, 2006; Pini et al., 1997).

The lack of association between PD comorbidity andh HA scores in UD patients is of interest. Although this isusibly related to patients’ state of euthymia at the timeassessment, the correlation with a subdimension ofperativeness, namely social acceptance (C1), maygest a relevance of character rather than temperamentensions in UD patients with comorbid PD. Alterna-ly, some can argue that the high C1 scores may be

ounted for by difference in age between the two groups,ng cooperativeness correlated with age (Cloninger et al.,3). However, the fact that the unipolar group with PDnot differ on mean age from the unipolar group withoutmakes such a hypothesis unlikely. Moreover, it is

ikely that it could be due to possible differences in ratesxis II comorbidity. In fact, a previous study by Lott andner (1996/1997), exploring the relationship between

perativeness and personality disorders amongressed patients, provided negative results.

Our findings are rather consistent with theories aboutnitive deficits in depression regarded as importantnerability factors for depression (Beck, 1999). Subjectsh high C1 scores are expected to be submissive, touchy,er-sensitive to loss of social support and to rejection or

rayal of their trust, aspects partly shared by differentchiatric conditions especially atypical depression andendent personality features (Cloninger et al., 1998).data would be in keeping with recent studies, showing

t patients with atypical depression are more likely toe a diagnosis of PD comorbidity than subjects with non-pical depression (Parker, Parker, Mitchell, & Wilhelm,5), having a two-fold increased risk (Matza, Revicki,idson, & Stewart, 2003). This is the first study reportingassociation between UD, PD comorbidity and suchsonality features and, if our results are replicated, it issible to speculate that psychotherapeutic efforts, toress comorbid PD among UD subjects, might focus onosure and cognitive reconstructing to address issues ofial acceptance. Conversely, interventions for BDients with PD might more explicitly address harmidance.Limits of our study need to be taken into account. First,small sample size reduces the strength of our findings

other differences may become evident in largerulations. In fact, effect sizes for negative findings were

all to moderate. Second, we did not specifically examinerent and lifetime panic comorbidity separately, but only

latter was explored, still, severity of PD was notermined. It is, therefore, possible that HA scores areuenced by the occurrence of panic symptoms and theerity of PD; however, the fact that the mood disorders in remission, at the time of the assessment, and the

of significant difference in number of mood episodesween patients with and without PD, probably reduced

Third, our results may not be representative for BD, UD andPD patients in general because our population represents ahighly selected sample coming from tertiary referralcenters.

In conclusion, the observation that different tempera-ment and character dimensions correlate with PD comor-bidity in BD and UD may contribute to elucidate furtherissues in the complex and multifactorial pathophysiologyof PD comorbidity in mood disorders, suggesting thatdifferent genetic and biological mechanisms need to beinvestigated in BD and UD patients.

BD–PD comorbidity is likely to refer to automaticresponses to emotional stimuli that have a heritablecomponent and relate to a number of brain structuresmediating response to fear. Conversely, UD–PD comorbid-ity may be more related to individual differences in self-object relationships, which develops as a result ofindividual experiences, and relies on a different neuro-biological background.

Further studies are warranted to replicate our findingsand establish the role of temperament and characterfeatures in individuals with mood disorders with comorbidPD.

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Please cite this article in press as: Mula, M, et al., Different temperament and character dimensions correlate with panicdisorder comorbidity in bipolar disorder and unipolar depression, J Anxiety Disord (2008),doi:10.1016/j.janxdis.2008.02.004