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Gender-related distribution of personality disorders in a sample of patients with panic disorder
Eur Psychiatry 2001 ; 16 : 173-9 © 2001 Editions scientifiques et medicales Elsevier SAS. All rights reserved S0924933801005600/FLA
ORIGINAL ARTICLE
Gender-related distribution of personality disorders in a sample of patients with panic disorder G. Barzega, G. Maina*, S. Venturello, F. Bogetto Department of Neuroscience, Psychiatry, Section Via Cherasco 11 10126, Torino, Italy (Received 31 January 2000; revised 10 January 2001; accepted 12 January 2001)
Summary – Objective. We examined gender differences in the frequency of DSM-IV personality disorder diagnoses in a sample of patients with a diagnosis of panic disorder (PD). Method. One hundred and eighty-four outpatients with a principal diagnosis of PD (DSM-IV) were enrolled. All patients were evaluated with a semi-structured interview to collect demographic and clinical data and to generate Axis I and Axis II diagnoses in accordance with DSM-IV criteria. Results. Males were significantly more likely than females to meet diagnoses for schizoid and borderline personality disorder. Compared to males, females predominated in histrionic and cluster C diagnoses, particularly dependent personality disorder diagnoses. A significant interaction was found between female sex and agoraphobia on personality disorder (PD) distribution. Conclusions. Male PD patients seem to be characterized by more severe personality disorders, while female PD patients, particularly with co-morbid agoraphobia, have higher co-morbidity rates with personality disorders belonging to the ‘anxious-fearful cluster’. © 2001 Editions scientifiques et medicales Elsevier SAS agoraphobia / gender / panic disorder / personality disorders
INTRODUCTION Several studies showed evidence of gender-related epidemiologic and clinical differences in psychiatric disorders. Gender differences in the distribution of personality disorders have also been reported. Reviewing the literature on gender differences in the distribution of personality disorders in clinical samples, controversial results have been found. Males had significantly higher rates of all cluster A personality disorders, antisocial, narcissistic and compulsive personality disorders [1, 9, 10, 13, 22, 23, 27]. Females predominated in histrionic, dependent and avoidant personality disorders; however, some studies have reported that females do not predominate in any diagnoses [1, 9, 10]. The borderline personality disorder was diagnosed
*Correspondence and reprints.
either more frequently among females or equally in both sexes [9, 10, 14, 19]. Different methodological problems can be shown in the research to date: only a few studies controlled for the presence of Axis I diagnoses, there is an excessive heterogeneity of Axis I disorders in the samples investigated and, finally, different diagnostic criteria have been applied (DSM-III, DSM-III-R, DSM-IV). There is evidence that differing Axis I disorders are associated with differing frequencies of Axis II psychopathology [2]. It is also possible that differing co-morbid Axis I disorders may differentially affect the rate and distribution of Axis II disorders in males and females. Focusing attention on panic disorder (PD), several studies [2, 4, 5, 8, 12, 15, 18, 24] investigated the co-morbidity between PD and personality disorders, showing vari-
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able though generally high (between 35 and 95%) rates of co-occurrence between them. Although research on this topic gives controversial results, authors generally agree that cluster C personality disorders (dependent and avoidant) and cluster B personality disorders (histrionic and borderline) were the most commonly diagnosed in PD patients. Recently, Latas et al. [17] studied several predictors (gender, age, duration of illness, parental perception, childhood separation anxiety and traumatic experiences) of co-morbid personality disorders in a sample of patients with PD and agoraphobia. Their results suggested some specificity only for the association between parental overprotection in childhood and personality disturbance, particularly cluster B personality disorders, in patients with PD with agoraphobia; no association resulted between gender and personality disorders. No studies to our knowledge have focused attention on gender-related differences in the rates of personality disorders among PD patients, although recently several studies have provided evidence for gender-related clinical differences between men and women with PD [6, 7, 21, 25, 26]. The characterization of gender-related differences in patterns of co-morbidity with personality disorders could further the evidence of a different clinical presentation and treatment response of PD according to gender. The aim of the present study was to investigate gender-related differences in the distribution of personality disorder diagnoses in a sample of outpatients with a principal diagnosis of PD (DSM-IV) [3]. METHOD Subjects Two hundred and five subjects were enrolled from outpatients consecutively referred to the Servizio per i disturbi depressivi e d’ansia (Department of Neuroscience, Psychiatric Unit, University of Turin, Italy). Patients were referred to our ambulatory service by family members or friends in 35% of cases, by general practitioners in 30%, by medical specialists in 15%, and 20% were self-referred. All patients, aged over 18 years, had a principal diagnosis of PD according to DSM-IV diagnostic criteria. Exclusion criteria were current or previous diagnosis of schizophrenia or other psychotic disorders, a current diagnosis of major depressive episode or substance-related disorder (including alcohol abuse) (the disorder was considered current if diagnosed in the last 6 months), and the presence of
organic brain syndrome, mental retardation, severe neurologic or general medical conditions. All patients had to give their informed consent after the procedure had been fully explained. One hundred and eighty-four of the admitted patients completed all the assessment procedures; 11 subjects did not complete all the assessment and ten subjects denied their consent to complete the procedure. There were no differences in completion rates between males and females. Interviews Data were obtained through the administration of a semi-structured interview with a format that covered the following areas: – demographic data: sex, age, educational level, marital status; – diagnosis: Axis 1 diagnoses of any current or longitudinal psychiatric disorder were assessed with the use of the Structured Clinical Interview for DSM-IV (SCID). Personality status was also assessed by the authors using the Structured Clinical Interview for DSM-IV Personality Disorders; this evaluation was guided by items previously affirmed by the patients on the SCID-PQ. Items not affirmed on the SCID-PQ were assumed to be true negatives. However, if an interviewer had any reason to believe these were false negatives, further items were assessed. This method is in accordance with instructions for using the SCID-II, and enabled personality disorder symptomatology to be based upon clinical contact combined with a structured clinical interview. To assess personality disorder diagnoses all patients included in the study also completed two self-report measures: the Millon Clinical Multiaxial Inventory and the Personality Disorder Questionnaire (DSM-IV). In addition, the following rating scales were included in the assessment of patients with PD: the Sheehan Clinician Rated Anxiety Scale (SCRAS), the Hamilton Anxiety Rating Scale (HAM-A), the 17-item Hamilton Depression Rating Scale (HAM-D) and the Global Assessment of Functioning Scale (GAS). Particular care must be exercised in assigning personality disorder diagnoses to individuals who are currently affected by anxiety disorders, so this study’s goal was remarkable for comparing the prevalence of personality disorders in two acutely anxious groups of patients who showed equal panic symptoms and eventually depressive symptoms and who had similar functional impairment. Eur Psychiatry 2001 ; 16 : 173–9
Gender-related distribution and panic disorder
Interviewers and raters All semi-structured interviews were conducted in person by three investigators: three psychiatrists (GB, GM and SV), each with at least 4 years of post-graduate clinical experience, and one main investigator, who is a senior Italian psychiatrist (FB). Inter-rater reliability In the early phase of the study, inter-rater agreement between rater pairs on the diagnosis of PD and co-morbid psychiatric Axis I and Axis II disorders were ascertained. For all evaluations, relevant clinical data concerning PD or Axis II diagnoses were eventually submitted to the main investigator (FB) who, following an abbreviated face-to-face clinical interview with the patient, assigned definitive diagnoses. The inter-rater reliability of DSM-IV diagnoses was found to be good: Kappa coefficients were over 0.80 for the presence of any lifetime Axis I disorder and over 0.75 for the presence of any personality disorder. Pearson’s correlation coefficient between rater pairs and intraclass coefficients demonstrated excellent agreement for the SCRAS of ten PD patients assessed before the beginning of the study (P < .0001). In ten depressed subjects, scores obtained by our raters of the HAM-D correlated above .90. To assess reliability of Axis II diagnoses, subjects were randomly selected to be re-interviewed with the SCID-II by an assessing clinician who previously had no contact with the patients and was blind to personality disorder diagnoses. Comparison of Axis II diagnoses across raters showed good reliability. Test-retest reliability (N = 15) assessed by k for the presence of any personality disorder was .75. All semi-structured interviews were conducted by the authors. Statistical analysis The PD sample was divided into two groups on the basis of gender. Significant differences between the two groups refer to the t-test or χ2 respectively to compare continuous or categorical variables. A P-value of less than 0.05 was considered statistically significant; conservatively, we used two-tailed t-tests. The effects of gender and co-morbidity with lifetime agoraphobia, and the interaction between these variables were examined on mean scores on the HAM-A, HAM-D and SCRAS and on the mean number of personality disorEur Psychiatry 2001 ; 16 : 173–9
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ders using a 2 × 2 (gender × co-morbidity) analysis of variance (ANOVA). RESULTS The sample selected included 72 males (39.1%) and 112 females (60.9%); mean index age was respectively 31.5 ± 10.6 years and 32.0 ± 9.3 years, without statistical difference. The mean SCRAS, HAM-D, HAM-A and GAS scores did not differ between the two groups. Women had significantly higher rates of co-morbid agoraphobia. The description of the sample is reported in table I. At least one Axis II co-morbid disorder was observed in 68% of the whole sample; among females the percentage observed was higher than among males, but the difference was not statistically significant. The mean number of diagnoses for each patient was 1.1 ± 0.9, without differences between the two groups. Patterns of co-morbidity with personality disorders according to gender are reported in table II. Cluster A personality disorders were significantly more common in the male subgroup: in particular, a schizoid personality disorder was observed in 12.5% of male patients and in 2.7% of female patients, with a statistically significant difference. Cluster B personality disorders were also more common among males, but the difference was not significant. However, a borderline personality disorder was diagnosed significantly more frequently among males, while a histrionic personality disorder was significantly more common among females. At least one cluster C personality disorder was observed in more than half of the female group, and the percentage was higher than the percentage observed in the male group, with a trend toward significance. All three cluster C diagnoses were frequently observed in the whole sample; a dependent personality disorder was significantly more common in the female group. When examining gender differences in mean scores on rating scales at evaluation and on the mean number of personality disorders for each patient, we investigated also the potential interactions between gender and other clinical characteristics, which are unequally distributed between men and women, in modifying such outcome variables using the ANOVA. The analysis of variance confirmed that gender did not influence mean scores on rating scales at the time of evaluation and the mean number of personality disorders for each patient, while the presence of co-morbid agoraphobia did not influence mean scores on rating scales but
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Table I. Clinical and demographic characteristics of the PD patients: comparison between males and females. Statistical comparison between male ands female patients was performed.
Variable Age (years ± SD) Education (years) Marital status: N (%) single married widowed divorced Employed full-time: N (%) Variable Age at onset (years ± SD) Age at first PA (years ± SD) History of PA preceding PD onset: N (%) GAF (mean ± SD) SCRAS (mean ± SD) HAM-A (mean ± SD) HAM-D (mean ± SD) Agoraphobia: N (%) Substance-related disorders (excluding actual): N (%)
Total N = 184
Males N = 72
Females N = 112
31.8 ± 9.8 11.4 ± 3.9
31.5 ± 10.6 10.4 ± 3.1
32.0 ± 9.3 12.0 ± 4.2
52 (28.3) 116 (63.0) 4 (2.2) 12 (6.5) 101 (54.9)
24 (33.3) 45 (62.5) 1 (1.4) 2 (2.8) 56 (77.8)
28 (25.0) 71 (63.3) 3 (2.7) 10 (9.0) 45 (40.2)
30.2 ± 10.3 26.8 ± 10.2 27 (14.7) 52.6 ± 8.3 48.8 ± 5.8 23.5 ± 4.3 13.9 ± 2.1 116 (63.0) 8 (4.3)
29.8 ± 10.5 25.4 ± 10.0 8 (11.1) 51.8 ± 7.4 49.0 ± 5.3 23.3 ± 3.8 13.8 ± 1.4 38 (52.8) 7 (9.7)
30.4 ± 9.3 27.0 ± 10.4 19 (17.0) 53.6 ± 6.1 48.7 ± 6.1 23.7 ± 4.7 14.0 ± 2.4 78 (69.6) 1 (0.89)
DF
Statistics χ2/t-value
P
182 182 3
–.322 –.281 3.960
.748 .006 .266
1
25.022
< .001
182 182 1 182 182 182 182 1 –
–.448 –.994 1.199 –.683 –.414 –.739 –.897 5.350 –
.655 .322 .273 .513 .679 .464 .371 .021 .006*
PA: panic attacks; PD: panic disorder. GAF: Global Assessment of Functioning; SCRAS: Sheehan Clinical Rated Anxiety Scale; HAM-A: Hamilton Anxiety Rating Scale; HAM-D: Hamilton Depression Rating Scale. *Fisher’s exact test.
turned out to be a significant predictor of a higher mean number of personality disorders for each patient, in
particular cluster C diagnoses. A significant interaction was found between gender and co-morbidity with ago-
Table II. Diagnoses of personality disorders (Axis II) in panic disorder (PD) patients: comparison between males and females. Males (N = 72) Diagnosis At least one Axis II disorder Cluster A Paranoid Schizoid Schizotypal At least one cluster A Cluster B Antisocial Borderline Histrionic Narcissistic At least one cluster B Cluster C Avoidant Dependent Obsessive-compulsive At least one cluster C
Females (N = 112)
Statistics χ2
DF
P
.889
1
.346
1.8 2.7 0 2.7
– – – –
– – – –
1.000* .013* .391* .013*
0 8 18 3 26
0 7.1 16.1 2.7 23.2
– 10.123 12.826 – 0.487
– 1 1 – 1
– .001 .001 .435* .485
24 38 19 57
21.4 34.0 17.0 50.9
0.016 7.802 0.312 3.168
1 1 1 1
.899 .005 .576 .075
N
%
N
%
46
63.9
79
70.5
1 9 1 9
1.4 12.5 1.4 12.5
2 3 0 3
0 17 0 4 20
0 23.6 0 5.6 27.8
16 11 10 27
22.2 15.3 13.9 37.5
*Fisher’s exact test. Eur Psychiatry 2001 ; 16 : 173–9
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Gender-related distribution and panic disorder Table III. Mean number of personality disorders for each patient and ANOVA results. Agoraphobia Mean HAM-A score Mean HAM-D score Mean SCRAS score Mean number of PD for each patient Mean number of cluster C PD Mean number of A and B PD
Males Yes No N = 38 N = 34
Females Yes No N = 78 N = 34
23 1207 49.6 1.192 .588 .474
23.5 12.5 49.1 1.342 .961 .361
23.8 13.1 48.3 0.735 .105 .853
23.7 11.9 48.2 1.118 .473 .303
Gender F
P
.569 1.266 0.12 0.836 17.273 11.045
.452 .262 .912 0.362 .0001 0.001
Statistical test of effects Agoraphobia F P .08 .432 .374 7.182 3.191 2.586
.778 .512 .542 0.008 0.057 0.1095
Interaction F P .171 .451 .68 4.379 5.8 4.816
.679 .503 .411 0.038 0.017 0.03
ANOVA: analysis of variance; PD: personality disorder. HAM-A: Hamilton Anxiety Rating Scale; HAM-D: Hamilton Depression Rating Scale; SCRAS: Sheehan Clinical Rated Anxiety Scale.
raphobia: females with agoraphobia had the highest mean number of personality disorders for each patient (1.3 diagnoses), while males without agoraphobia had the lowest (0.7 diagnoses). The interaction was statistically significant also when we considered the mean number of cluster C diagnoses. The results of the ANOVA analysis are reported in table III. DISCUSSION Patients of both sexes did not differ in index age and age at onset. Female patients had a significantly higher educational level, but this result is difficult to interpret for its implications on the assessment of personality disorder diagnoses. According to literature data [6, 7, 21, 25, 26], mean scores on rating scales did not show any statistically significant difference in the severity of the disorder at the baseline evaluation between the two groups, while women had a higher rate of co-morbid agoraphobia. The prevalence of personality disorders observed in our sample (68.5%) is in agreement with those proposed by several literature studies focusing on PD (35–95%) [2, 4, 8, 12, 15, 24]. Interestingly, the pattern of personality diagnoses differs between males and females. The most common diagnoses of personality disorders belonged to the ‘anxious-fearful cluster’ and more than half of the female group had at least one cluster C diagnosis with a trend toward significance compared to the male group. In particular, females had significantly higher rates of dependent personality disorder. Cluster B diagnoses were more common in male patients with significantly higher percentages of borderline personality disorder. Moreover, among cluster B personality disorders, female patients seemed to be characterized by significantly higher percentages of histrionic personality disorder. Diagnoses belonging to Eur Psychiatry 2001 ; 16 : 173–9
the ‘odd cluster’ were less frequent in the sample, but they were significantly more common among males, and the most common disorder observed was schizoid personality disorder. Our results are in accordance with literature data on co-morbid Axis II disorders among PD patients that showed high co-morbidity rates with cluster C personality disorders (dependent and avoidant) and cluster B personality disorders (histrionic and borderline) [2, 4, 5, 8, 12, 15, 18, 24]. The findings of higher percentages of dependent and histrionic personality disorder among females is in accordance with literature data focusing on gender-related differences in the distribution of personality disorders [1, 10]. Our findings show evidence of a higher frequency of borderline personality disorder in male patients; data on borderline personality disorder and gender are controversial [11, 14, 19]. None of our patients met diagnostic criteria for antisocial personality disorder, although the presence of such a diagnosis was not an exclusion criteria. This finding can be related to the exclusion from the study of patients with actual co-morbid substance-related disorders and to the type of recruitment (outpatients referred to a specialist service for depressive and anxiety disorders). Our data also showed a relatively high percentage of co-morbidity with personality disorders belonging to the ‘odd cluster’, particularly schizoid personality disorder among males. Studies in the literature reported that schizoid personality disorder is more commonly observed in male patients. The observed differences in the pattern of co-morbidity with personality disorders according to gender in our sample of PD patients are in agreement with data reported among patients with other Axis I disorders and in the general population. This result suggests that men and women with PD had patterns of co-morbidity with personality disorders similar to men
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and women in the general population and that a diagnosis of PD on Axis I seems not to influence the distribution of personality disorders. Moreover, males and females did not differ either in rates of patients with at least one personality disorder nor in mean number of personality disorder diagnoses for each patient, but when we considered the interaction between gender and co-morbid agoraphobia we observed that women with PD and agoraphobia were characterized by a higher mean number of personality disorders, particularly cluster C personality disorders. According to literature data female patients with PD are characterized by higher co-morbidity with agoraphobia and by a more chronic course of illness [6, 7, 21, 25, 26]. Our results confirmed that women more commonly had PD with agoraphobia and suggested that panic-agoraphobic females commonly also had an underlying ‘anxiousfearful’ personality. In agreement with these observations it can be hypothesized that among women PD with agoraphobia represents a state anxiety disorder, which develops in subjects with traits characteristic of anxiety. Recently Langs et al. [16] suggested that the development of agoraphobic avoidance in panic patients is influenced by specific factors, such as earlier age at onset, fear of losing control and chills or hot flushes, and perhaps an increased ‘phobia proneness’. We can hypothesize that female sex and an underlying anxiousfearful personality contribute to the phobia proneness among PD patients. However, Latas and collegues [17] recently suggested that some of the cluster C personality disorders observed in patients with PD and agoraphobia may be a consequence of the long-lasting panicagoraphobic illness. Although the comparison of mean scores on rating scales for anxiety, depression and global assessment did not show any significant difference between the sexes, male patients seem to be characterized by the presence of more severe Axis II diagnoses: they had significantly higher percentages of borderline and schizoid personality disorder. This finding seems to confirm the hypothesis that PD not only represents a disorder in the sense of a psychiatric entity but that it may also be encountered as a syndrome in a variety of clinical pictures, which are more complex from a psychopathological point of view. Moreover, in these cases PD is less frequently complicated by the presence of co-morbid agoraphobia. In agreement with literature findings, lifetime co-morbidity with substance-related disorder characterized male PD patients; however, we considered actual co-morbidity with substance dependence/
abuse an exclusion criteria. We can hypothesize that the co-morbidity with substance-related disorders and the presence of severe personality disorders should have a clinically significant relationship in male patients, but we can’t perform this analysis and we need further studies to evaluate this association. In particular, while early studies reported alcoholism to be frequently a secondary superimposed condition with respect to PD, more recent reports showed interesting evidence that in some cases the onset of alcohol abuse precedes PD onset [20]. We may hypothesize that in some cases male patients with PD and substance-related disorder are characterized by an underlying personality disorder, particularly cluster B and A diagnoses. The complex relationship between panic, gender, and personality seems to show evidence of a possible heterogeneity among PD patients, with subgroups of subjects who specifically show different underlying personality characteristics. There are several limitations to the study. Firstly, the mode of recruitment: although we did not find any bias in the recruitment between male or female patients, our sample derives from a specialist service and may not be representative of the whole population of PD patients. Secondly, most subjects had Axis I co-morbidity, largely consisting of other anxiety disorders and mood disorders, which are commonly found in PD patients. The relatively high rate of Axis I co-morbidity observed in our sample is consistent with the high rate of co-morbid Axis I disorders reported in the literature. This should make our findings generalizable to many patients suffering from PD, but reduce the specificity of the results. For example, a relevant percentage of patients with PD also met diagnostic criteria for lifetime major depression, and recently authors reported that PD patients and patients with PD and co-morbid major depression differ in co-morbid Axis II conditions [4, 5, 15]. In our study a current diagnosis of major depression was considered exclusion criteria because the involvement of state depression on assessment of personality disorders is still a matter of controversy. Moreover, the lifetime co-morbidity with major depression that we observed among our PD patients did not show a different distribution according to gender. In conclusion, our data show that among women PD is frequently associated with co-morbid agoraphobia and that these Axis I disorders seems to develop on an underlying anxious-fearful personality. The presence of an anxious trait may explain other characteristics of PD in female patients, in particular the more chronic course Eur Psychiatry 2001 ; 16 : 173–9
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of illness. Among men PD is more commonly associated with a more severe personality psychopathology: PD may represent one of the possible syndromic manifestations of the underlying personality psychopathology. REFERENCES 1 Alnaes K, Torgersen S. DSM-III symptom disorders (Axis I) and personality disorders (Axis II) in an outpatient population. Acta Psychiatr Scand 1988 ; 78 : 348-55. 2 Alnaes K, Torgersen S. DSM-III personality disorders among patients with major depression, anxiety disorders, and mixed conditions. J Nerv Ment Dis 1990 ; 178 : 693-8. 3 American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: APA; 1994. 4 Ampollini P, Marchesi C, Signifredi R, Maggini C. Temperament and personality features in panic disorder with or without comorbid mood disorders. Acta Psychiatr Scand 1997 ; 95 : 420-3. 5 Ampollini P, Marchesi C, Signifredi R, Ghinaglia E, Scardovi F, Codeluppi S, et al. Temperament and personality features in patients with major depression, panic disorder and mixed conditions. J Affect Disord 1999 ; 52 : 203-7. 6 Bekker MHL. Agoraphobia and gender: a review. Clin Psychol Rev 1996 ; 16 : 129-46. 7 Cox BJ, Swinson RP, Shulman ID, Kuch K, Reichman JT. Gender effects and alcohol use in panic disorder with agoraphobia. Behav Res Ther 1993 ; 31 : 413-6. 8 Friedman CJ, Shear MK, Frances AF. DSM-III personality disorders in panic patients. J Pers Disord 1987 ; 1 : 132-5. 9 Golomb M, Fava M, Abraham M, Rosenbaum JF. Gender differences in personality disorders. Am J Psychiatry 1995 ; 152 : 579-82. 10 Grilo CM, Becker DF, Walker ML, Edell WS, McGlashan TH. Gender differences in personality disorders in psychiatrically hospitalized young adults. J Nerv and Ment Dis 1996 ; 184 : 754-7. 11 Grilo CM, Becker DF, Fehon DC, Walker ML, Edell WS, McGlashan TH. Gender differences in personality disorders in psychiatrically hospitalized adolescents. Am J Psychiatry 1996 ; 153 : 1089-91. 12 Hoffart A, Thornes K, Hedley LM, Strand J. DSM-III-R Axis I and Axis II disorders in agoraphobic patients with and without panic disorder. Acta Psychiatr Scand 1994 ; 89 : 186-91.
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13 Jackson HJ, Whiteside HL, Bates GW, Bell R, Rudd RP, Edwards J. Diagnosing personality disorders in psychiatric inpatients. Acta Psychiatr Scand 1991 ; 83 : 206-13. 14 Kroll J, Sines L, Martin K, Lari S, Pyle R, Zander J. Borderline personality disorder: construct validity of the concept. Arch Gen Psychiatry 1981 ; 38 : 1021-6. 15 Langs G, Quehenberger F, Fabisch K, Klug G, Fabisch H, Zapotoczky HG. Prevalence, patterns and role of personality disorders in panic disorder patients with and without comorbid (lifetime) major depression. Acta Psychiatr Scand 1998 ; 98 : 116-23. 16 Langs G, Quehenberger F, Fabisch K, Klug G, Fabisch H, Zapotoczky HG. The development of agoraphobia in panic disorder: a predictable process? J Affect Disord 2000 ; 58 : 43-50. 17 Latas M, Starcevic V, Trajkovic G, Bogojevic G. Predictors of comorbid personality disorders in patients with panic disorder with agoraphobia. Compr Psychiatry 2000 ; 41 : 28-34. 18 Mavissakalian MR, Hamman MS, Abou Haidar S, de Groot CM. DSM-III personality disorders in generalized anxiety, panic/agoraphobia, and obsessive-compulsive disorders. Compr Psychiatry 1993 ; 34 : 243-8. 19 Mc GI, shan TH. The Chestnut Lodge Follow-Up Study, III: long-term outcome of borderline personalities. Arch Gen Psychiatry 1986 ; 43 : 20-30. 20 Merikangas KR, Stevens DE, Fenton B, et al. Co-morbidity and familial aggregation of alcoholism and anxiety disorders. Psychol Med 1998 ; 28 : 773-88. 21 Oei TPS, Wanstall K, Evans L. Sex differences in panic disorder with agoraphobia. J Anxiety Disord 1990 ; 4 : 317-24. 22 Reich J. Sex distribution of DSM-III personality disorders in psychiatric outpatients. Am J Psychiatry 1987 ; 144 : 485-8. 23 Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD Jr, et al. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984 ; 41 : 949-58. 24 Sanderson WC, Wetzler S, Beck AT, Betz F. Prevalence of personality disorders among patients with anxiety disorders. Psychatry Res 1993 ; 51 : 167-74. 25 Starcevic V, Djordjevic A, Latas M, Bogojevic G. Characteristics of agoraphobia in women and men with PD with agoraphobia. Depress Anxiety 1998 ; 8 : 8-13. 26 Yonkers KA, Zlotnick C, Allsworth J, Warshaw M, Shea T, Keller MB. Is the course of panic disorder the same in women and men? Am J Psychiatry 1998 ; 155 : 596-602. 27 Zimmerman M, Coryell WH. DSM-III personality disorder dimensions. J Nerv Ment Dis 1990 ; 178 : 686-92.
ORIGINAL ARTICLE
Gender-related distribution of personality disorders in a sample of patients with panic disorder G. Barzega, G. Maina*, S. Venturello, F. Bogetto Department of Neuroscience, Psychiatry, Section Via Cherasco 11 10126, Torino, Italy (Received 31 January 2000; revised 10 January 2001; accepted 12 January 2001)
Summary – Objective. We examined gender differences in the frequency of DSM-IV personality disorder diagnoses in a sample of patients with a diagnosis of panic disorder (PD). Method. One hundred and eighty-four outpatients with a principal diagnosis of PD (DSM-IV) were enrolled. All patients were evaluated with a semi-structured interview to collect demographic and clinical data and to generate Axis I and Axis II diagnoses in accordance with DSM-IV criteria. Results. Males were significantly more likely than females to meet diagnoses for schizoid and borderline personality disorder. Compared to males, females predominated in histrionic and cluster C diagnoses, particularly dependent personality disorder diagnoses. A significant interaction was found between female sex and agoraphobia on personality disorder (PD) distribution. Conclusions. Male PD patients seem to be characterized by more severe personality disorders, while female PD patients, particularly with co-morbid agoraphobia, have higher co-morbidity rates with personality disorders belonging to the ‘anxious-fearful cluster’. © 2001 Editions scientifiques et medicales Elsevier SAS agoraphobia / gender / panic disorder / personality disorders
INTRODUCTION Several studies showed evidence of gender-related epidemiologic and clinical differences in psychiatric disorders. Gender differences in the distribution of personality disorders have also been reported. Reviewing the literature on gender differences in the distribution of personality disorders in clinical samples, controversial results have been found. Males had significantly higher rates of all cluster A personality disorders, antisocial, narcissistic and compulsive personality disorders [1, 9, 10, 13, 22, 23, 27]. Females predominated in histrionic, dependent and avoidant personality disorders; however, some studies have reported that females do not predominate in any diagnoses [1, 9, 10]. The borderline personality disorder was diagnosed
*Correspondence and reprints.
either more frequently among females or equally in both sexes [9, 10, 14, 19]. Different methodological problems can be shown in the research to date: only a few studies controlled for the presence of Axis I diagnoses, there is an excessive heterogeneity of Axis I disorders in the samples investigated and, finally, different diagnostic criteria have been applied (DSM-III, DSM-III-R, DSM-IV). There is evidence that differing Axis I disorders are associated with differing frequencies of Axis II psychopathology [2]. It is also possible that differing co-morbid Axis I disorders may differentially affect the rate and distribution of Axis II disorders in males and females. Focusing attention on panic disorder (PD), several studies [2, 4, 5, 8, 12, 15, 18, 24] investigated the co-morbidity between PD and personality disorders, showing vari-
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able though generally high (between 35 and 95%) rates of co-occurrence between them. Although research on this topic gives controversial results, authors generally agree that cluster C personality disorders (dependent and avoidant) and cluster B personality disorders (histrionic and borderline) were the most commonly diagnosed in PD patients. Recently, Latas et al. [17] studied several predictors (gender, age, duration of illness, parental perception, childhood separation anxiety and traumatic experiences) of co-morbid personality disorders in a sample of patients with PD and agoraphobia. Their results suggested some specificity only for the association between parental overprotection in childhood and personality disturbance, particularly cluster B personality disorders, in patients with PD with agoraphobia; no association resulted between gender and personality disorders. No studies to our knowledge have focused attention on gender-related differences in the rates of personality disorders among PD patients, although recently several studies have provided evidence for gender-related clinical differences between men and women with PD [6, 7, 21, 25, 26]. The characterization of gender-related differences in patterns of co-morbidity with personality disorders could further the evidence of a different clinical presentation and treatment response of PD according to gender. The aim of the present study was to investigate gender-related differences in the distribution of personality disorder diagnoses in a sample of outpatients with a principal diagnosis of PD (DSM-IV) [3]. METHOD Subjects Two hundred and five subjects were enrolled from outpatients consecutively referred to the Servizio per i disturbi depressivi e d’ansia (Department of Neuroscience, Psychiatric Unit, University of Turin, Italy). Patients were referred to our ambulatory service by family members or friends in 35% of cases, by general practitioners in 30%, by medical specialists in 15%, and 20% were self-referred. All patients, aged over 18 years, had a principal diagnosis of PD according to DSM-IV diagnostic criteria. Exclusion criteria were current or previous diagnosis of schizophrenia or other psychotic disorders, a current diagnosis of major depressive episode or substance-related disorder (including alcohol abuse) (the disorder was considered current if diagnosed in the last 6 months), and the presence of
organic brain syndrome, mental retardation, severe neurologic or general medical conditions. All patients had to give their informed consent after the procedure had been fully explained. One hundred and eighty-four of the admitted patients completed all the assessment procedures; 11 subjects did not complete all the assessment and ten subjects denied their consent to complete the procedure. There were no differences in completion rates between males and females. Interviews Data were obtained through the administration of a semi-structured interview with a format that covered the following areas: – demographic data: sex, age, educational level, marital status; – diagnosis: Axis 1 diagnoses of any current or longitudinal psychiatric disorder were assessed with the use of the Structured Clinical Interview for DSM-IV (SCID). Personality status was also assessed by the authors using the Structured Clinical Interview for DSM-IV Personality Disorders; this evaluation was guided by items previously affirmed by the patients on the SCID-PQ. Items not affirmed on the SCID-PQ were assumed to be true negatives. However, if an interviewer had any reason to believe these were false negatives, further items were assessed. This method is in accordance with instructions for using the SCID-II, and enabled personality disorder symptomatology to be based upon clinical contact combined with a structured clinical interview. To assess personality disorder diagnoses all patients included in the study also completed two self-report measures: the Millon Clinical Multiaxial Inventory and the Personality Disorder Questionnaire (DSM-IV). In addition, the following rating scales were included in the assessment of patients with PD: the Sheehan Clinician Rated Anxiety Scale (SCRAS), the Hamilton Anxiety Rating Scale (HAM-A), the 17-item Hamilton Depression Rating Scale (HAM-D) and the Global Assessment of Functioning Scale (GAS). Particular care must be exercised in assigning personality disorder diagnoses to individuals who are currently affected by anxiety disorders, so this study’s goal was remarkable for comparing the prevalence of personality disorders in two acutely anxious groups of patients who showed equal panic symptoms and eventually depressive symptoms and who had similar functional impairment. Eur Psychiatry 2001 ; 16 : 173–9
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Interviewers and raters All semi-structured interviews were conducted in person by three investigators: three psychiatrists (GB, GM and SV), each with at least 4 years of post-graduate clinical experience, and one main investigator, who is a senior Italian psychiatrist (FB). Inter-rater reliability In the early phase of the study, inter-rater agreement between rater pairs on the diagnosis of PD and co-morbid psychiatric Axis I and Axis II disorders were ascertained. For all evaluations, relevant clinical data concerning PD or Axis II diagnoses were eventually submitted to the main investigator (FB) who, following an abbreviated face-to-face clinical interview with the patient, assigned definitive diagnoses. The inter-rater reliability of DSM-IV diagnoses was found to be good: Kappa coefficients were over 0.80 for the presence of any lifetime Axis I disorder and over 0.75 for the presence of any personality disorder. Pearson’s correlation coefficient between rater pairs and intraclass coefficients demonstrated excellent agreement for the SCRAS of ten PD patients assessed before the beginning of the study (P < .0001). In ten depressed subjects, scores obtained by our raters of the HAM-D correlated above .90. To assess reliability of Axis II diagnoses, subjects were randomly selected to be re-interviewed with the SCID-II by an assessing clinician who previously had no contact with the patients and was blind to personality disorder diagnoses. Comparison of Axis II diagnoses across raters showed good reliability. Test-retest reliability (N = 15) assessed by k for the presence of any personality disorder was .75. All semi-structured interviews were conducted by the authors. Statistical analysis The PD sample was divided into two groups on the basis of gender. Significant differences between the two groups refer to the t-test or χ2 respectively to compare continuous or categorical variables. A P-value of less than 0.05 was considered statistically significant; conservatively, we used two-tailed t-tests. The effects of gender and co-morbidity with lifetime agoraphobia, and the interaction between these variables were examined on mean scores on the HAM-A, HAM-D and SCRAS and on the mean number of personality disorEur Psychiatry 2001 ; 16 : 173–9
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ders using a 2 × 2 (gender × co-morbidity) analysis of variance (ANOVA). RESULTS The sample selected included 72 males (39.1%) and 112 females (60.9%); mean index age was respectively 31.5 ± 10.6 years and 32.0 ± 9.3 years, without statistical difference. The mean SCRAS, HAM-D, HAM-A and GAS scores did not differ between the two groups. Women had significantly higher rates of co-morbid agoraphobia. The description of the sample is reported in table I. At least one Axis II co-morbid disorder was observed in 68% of the whole sample; among females the percentage observed was higher than among males, but the difference was not statistically significant. The mean number of diagnoses for each patient was 1.1 ± 0.9, without differences between the two groups. Patterns of co-morbidity with personality disorders according to gender are reported in table II. Cluster A personality disorders were significantly more common in the male subgroup: in particular, a schizoid personality disorder was observed in 12.5% of male patients and in 2.7% of female patients, with a statistically significant difference. Cluster B personality disorders were also more common among males, but the difference was not significant. However, a borderline personality disorder was diagnosed significantly more frequently among males, while a histrionic personality disorder was significantly more common among females. At least one cluster C personality disorder was observed in more than half of the female group, and the percentage was higher than the percentage observed in the male group, with a trend toward significance. All three cluster C diagnoses were frequently observed in the whole sample; a dependent personality disorder was significantly more common in the female group. When examining gender differences in mean scores on rating scales at evaluation and on the mean number of personality disorders for each patient, we investigated also the potential interactions between gender and other clinical characteristics, which are unequally distributed between men and women, in modifying such outcome variables using the ANOVA. The analysis of variance confirmed that gender did not influence mean scores on rating scales at the time of evaluation and the mean number of personality disorders for each patient, while the presence of co-morbid agoraphobia did not influence mean scores on rating scales but
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Table I. Clinical and demographic characteristics of the PD patients: comparison between males and females. Statistical comparison between male ands female patients was performed.
Variable Age (years ± SD) Education (years) Marital status: N (%) single married widowed divorced Employed full-time: N (%) Variable Age at onset (years ± SD) Age at first PA (years ± SD) History of PA preceding PD onset: N (%) GAF (mean ± SD) SCRAS (mean ± SD) HAM-A (mean ± SD) HAM-D (mean ± SD) Agoraphobia: N (%) Substance-related disorders (excluding actual): N (%)
Total N = 184
Males N = 72
Females N = 112
31.8 ± 9.8 11.4 ± 3.9
31.5 ± 10.6 10.4 ± 3.1
32.0 ± 9.3 12.0 ± 4.2
52 (28.3) 116 (63.0) 4 (2.2) 12 (6.5) 101 (54.9)
24 (33.3) 45 (62.5) 1 (1.4) 2 (2.8) 56 (77.8)
28 (25.0) 71 (63.3) 3 (2.7) 10 (9.0) 45 (40.2)
30.2 ± 10.3 26.8 ± 10.2 27 (14.7) 52.6 ± 8.3 48.8 ± 5.8 23.5 ± 4.3 13.9 ± 2.1 116 (63.0) 8 (4.3)
29.8 ± 10.5 25.4 ± 10.0 8 (11.1) 51.8 ± 7.4 49.0 ± 5.3 23.3 ± 3.8 13.8 ± 1.4 38 (52.8) 7 (9.7)
30.4 ± 9.3 27.0 ± 10.4 19 (17.0) 53.6 ± 6.1 48.7 ± 6.1 23.7 ± 4.7 14.0 ± 2.4 78 (69.6) 1 (0.89)
DF
Statistics χ2/t-value
P
182 182 3
–.322 –.281 3.960
.748 .006 .266
1
25.022
< .001
182 182 1 182 182 182 182 1 –
–.448 –.994 1.199 –.683 –.414 –.739 –.897 5.350 –
.655 .322 .273 .513 .679 .464 .371 .021 .006*
PA: panic attacks; PD: panic disorder. GAF: Global Assessment of Functioning; SCRAS: Sheehan Clinical Rated Anxiety Scale; HAM-A: Hamilton Anxiety Rating Scale; HAM-D: Hamilton Depression Rating Scale. *Fisher’s exact test.
turned out to be a significant predictor of a higher mean number of personality disorders for each patient, in
particular cluster C diagnoses. A significant interaction was found between gender and co-morbidity with ago-
Table II. Diagnoses of personality disorders (Axis II) in panic disorder (PD) patients: comparison between males and females. Males (N = 72) Diagnosis At least one Axis II disorder Cluster A Paranoid Schizoid Schizotypal At least one cluster A Cluster B Antisocial Borderline Histrionic Narcissistic At least one cluster B Cluster C Avoidant Dependent Obsessive-compulsive At least one cluster C
Females (N = 112)
Statistics χ2
DF
P
.889
1
.346
1.8 2.7 0 2.7
– – – –
– – – –
1.000* .013* .391* .013*
0 8 18 3 26
0 7.1 16.1 2.7 23.2
– 10.123 12.826 – 0.487
– 1 1 – 1
– .001 .001 .435* .485
24 38 19 57
21.4 34.0 17.0 50.9
0.016 7.802 0.312 3.168
1 1 1 1
.899 .005 .576 .075
N
%
N
%
46
63.9
79
70.5
1 9 1 9
1.4 12.5 1.4 12.5
2 3 0 3
0 17 0 4 20
0 23.6 0 5.6 27.8
16 11 10 27
22.2 15.3 13.9 37.5
*Fisher’s exact test. Eur Psychiatry 2001 ; 16 : 173–9
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Gender-related distribution and panic disorder Table III. Mean number of personality disorders for each patient and ANOVA results. Agoraphobia Mean HAM-A score Mean HAM-D score Mean SCRAS score Mean number of PD for each patient Mean number of cluster C PD Mean number of A and B PD
Males Yes No N = 38 N = 34
Females Yes No N = 78 N = 34
23 1207 49.6 1.192 .588 .474
23.5 12.5 49.1 1.342 .961 .361
23.8 13.1 48.3 0.735 .105 .853
23.7 11.9 48.2 1.118 .473 .303
Gender F
P
.569 1.266 0.12 0.836 17.273 11.045
.452 .262 .912 0.362 .0001 0.001
Statistical test of effects Agoraphobia F P .08 .432 .374 7.182 3.191 2.586
.778 .512 .542 0.008 0.057 0.1095
Interaction F P .171 .451 .68 4.379 5.8 4.816
.679 .503 .411 0.038 0.017 0.03
ANOVA: analysis of variance; PD: personality disorder. HAM-A: Hamilton Anxiety Rating Scale; HAM-D: Hamilton Depression Rating Scale; SCRAS: Sheehan Clinical Rated Anxiety Scale.
raphobia: females with agoraphobia had the highest mean number of personality disorders for each patient (1.3 diagnoses), while males without agoraphobia had the lowest (0.7 diagnoses). The interaction was statistically significant also when we considered the mean number of cluster C diagnoses. The results of the ANOVA analysis are reported in table III. DISCUSSION Patients of both sexes did not differ in index age and age at onset. Female patients had a significantly higher educational level, but this result is difficult to interpret for its implications on the assessment of personality disorder diagnoses. According to literature data [6, 7, 21, 25, 26], mean scores on rating scales did not show any statistically significant difference in the severity of the disorder at the baseline evaluation between the two groups, while women had a higher rate of co-morbid agoraphobia. The prevalence of personality disorders observed in our sample (68.5%) is in agreement with those proposed by several literature studies focusing on PD (35–95%) [2, 4, 8, 12, 15, 24]. Interestingly, the pattern of personality diagnoses differs between males and females. The most common diagnoses of personality disorders belonged to the ‘anxious-fearful cluster’ and more than half of the female group had at least one cluster C diagnosis with a trend toward significance compared to the male group. In particular, females had significantly higher rates of dependent personality disorder. Cluster B diagnoses were more common in male patients with significantly higher percentages of borderline personality disorder. Moreover, among cluster B personality disorders, female patients seemed to be characterized by significantly higher percentages of histrionic personality disorder. Diagnoses belonging to Eur Psychiatry 2001 ; 16 : 173–9
the ‘odd cluster’ were less frequent in the sample, but they were significantly more common among males, and the most common disorder observed was schizoid personality disorder. Our results are in accordance with literature data on co-morbid Axis II disorders among PD patients that showed high co-morbidity rates with cluster C personality disorders (dependent and avoidant) and cluster B personality disorders (histrionic and borderline) [2, 4, 5, 8, 12, 15, 18, 24]. The findings of higher percentages of dependent and histrionic personality disorder among females is in accordance with literature data focusing on gender-related differences in the distribution of personality disorders [1, 10]. Our findings show evidence of a higher frequency of borderline personality disorder in male patients; data on borderline personality disorder and gender are controversial [11, 14, 19]. None of our patients met diagnostic criteria for antisocial personality disorder, although the presence of such a diagnosis was not an exclusion criteria. This finding can be related to the exclusion from the study of patients with actual co-morbid substance-related disorders and to the type of recruitment (outpatients referred to a specialist service for depressive and anxiety disorders). Our data also showed a relatively high percentage of co-morbidity with personality disorders belonging to the ‘odd cluster’, particularly schizoid personality disorder among males. Studies in the literature reported that schizoid personality disorder is more commonly observed in male patients. The observed differences in the pattern of co-morbidity with personality disorders according to gender in our sample of PD patients are in agreement with data reported among patients with other Axis I disorders and in the general population. This result suggests that men and women with PD had patterns of co-morbidity with personality disorders similar to men
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and women in the general population and that a diagnosis of PD on Axis I seems not to influence the distribution of personality disorders. Moreover, males and females did not differ either in rates of patients with at least one personality disorder nor in mean number of personality disorder diagnoses for each patient, but when we considered the interaction between gender and co-morbid agoraphobia we observed that women with PD and agoraphobia were characterized by a higher mean number of personality disorders, particularly cluster C personality disorders. According to literature data female patients with PD are characterized by higher co-morbidity with agoraphobia and by a more chronic course of illness [6, 7, 21, 25, 26]. Our results confirmed that women more commonly had PD with agoraphobia and suggested that panic-agoraphobic females commonly also had an underlying ‘anxiousfearful’ personality. In agreement with these observations it can be hypothesized that among women PD with agoraphobia represents a state anxiety disorder, which develops in subjects with traits characteristic of anxiety. Recently Langs et al. [16] suggested that the development of agoraphobic avoidance in panic patients is influenced by specific factors, such as earlier age at onset, fear of losing control and chills or hot flushes, and perhaps an increased ‘phobia proneness’. We can hypothesize that female sex and an underlying anxiousfearful personality contribute to the phobia proneness among PD patients. However, Latas and collegues [17] recently suggested that some of the cluster C personality disorders observed in patients with PD and agoraphobia may be a consequence of the long-lasting panicagoraphobic illness. Although the comparison of mean scores on rating scales for anxiety, depression and global assessment did not show any significant difference between the sexes, male patients seem to be characterized by the presence of more severe Axis II diagnoses: they had significantly higher percentages of borderline and schizoid personality disorder. This finding seems to confirm the hypothesis that PD not only represents a disorder in the sense of a psychiatric entity but that it may also be encountered as a syndrome in a variety of clinical pictures, which are more complex from a psychopathological point of view. Moreover, in these cases PD is less frequently complicated by the presence of co-morbid agoraphobia. In agreement with literature findings, lifetime co-morbidity with substance-related disorder characterized male PD patients; however, we considered actual co-morbidity with substance dependence/
abuse an exclusion criteria. We can hypothesize that the co-morbidity with substance-related disorders and the presence of severe personality disorders should have a clinically significant relationship in male patients, but we can’t perform this analysis and we need further studies to evaluate this association. In particular, while early studies reported alcoholism to be frequently a secondary superimposed condition with respect to PD, more recent reports showed interesting evidence that in some cases the onset of alcohol abuse precedes PD onset [20]. We may hypothesize that in some cases male patients with PD and substance-related disorder are characterized by an underlying personality disorder, particularly cluster B and A diagnoses. The complex relationship between panic, gender, and personality seems to show evidence of a possible heterogeneity among PD patients, with subgroups of subjects who specifically show different underlying personality characteristics. There are several limitations to the study. Firstly, the mode of recruitment: although we did not find any bias in the recruitment between male or female patients, our sample derives from a specialist service and may not be representative of the whole population of PD patients. Secondly, most subjects had Axis I co-morbidity, largely consisting of other anxiety disorders and mood disorders, which are commonly found in PD patients. The relatively high rate of Axis I co-morbidity observed in our sample is consistent with the high rate of co-morbid Axis I disorders reported in the literature. This should make our findings generalizable to many patients suffering from PD, but reduce the specificity of the results. For example, a relevant percentage of patients with PD also met diagnostic criteria for lifetime major depression, and recently authors reported that PD patients and patients with PD and co-morbid major depression differ in co-morbid Axis II conditions [4, 5, 15]. In our study a current diagnosis of major depression was considered exclusion criteria because the involvement of state depression on assessment of personality disorders is still a matter of controversy. Moreover, the lifetime co-morbidity with major depression that we observed among our PD patients did not show a different distribution according to gender. In conclusion, our data show that among women PD is frequently associated with co-morbid agoraphobia and that these Axis I disorders seems to develop on an underlying anxious-fearful personality. The presence of an anxious trait may explain other characteristics of PD in female patients, in particular the more chronic course Eur Psychiatry 2001 ; 16 : 173–9
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of illness. Among men PD is more commonly associated with a more severe personality psychopathology: PD may represent one of the possible syndromic manifestations of the underlying personality psychopathology. REFERENCES 1 Alnaes K, Torgersen S. DSM-III symptom disorders (Axis I) and personality disorders (Axis II) in an outpatient population. Acta Psychiatr Scand 1988 ; 78 : 348-55. 2 Alnaes K, Torgersen S. DSM-III personality disorders among patients with major depression, anxiety disorders, and mixed conditions. J Nerv Ment Dis 1990 ; 178 : 693-8. 3 American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th ed. Washington, DC: APA; 1994. 4 Ampollini P, Marchesi C, Signifredi R, Maggini C. Temperament and personality features in panic disorder with or without comorbid mood disorders. Acta Psychiatr Scand 1997 ; 95 : 420-3. 5 Ampollini P, Marchesi C, Signifredi R, Ghinaglia E, Scardovi F, Codeluppi S, et al. Temperament and personality features in patients with major depression, panic disorder and mixed conditions. J Affect Disord 1999 ; 52 : 203-7. 6 Bekker MHL. Agoraphobia and gender: a review. Clin Psychol Rev 1996 ; 16 : 129-46. 7 Cox BJ, Swinson RP, Shulman ID, Kuch K, Reichman JT. Gender effects and alcohol use in panic disorder with agoraphobia. Behav Res Ther 1993 ; 31 : 413-6. 8 Friedman CJ, Shear MK, Frances AF. DSM-III personality disorders in panic patients. J Pers Disord 1987 ; 1 : 132-5. 9 Golomb M, Fava M, Abraham M, Rosenbaum JF. Gender differences in personality disorders. Am J Psychiatry 1995 ; 152 : 579-82. 10 Grilo CM, Becker DF, Walker ML, Edell WS, McGlashan TH. Gender differences in personality disorders in psychiatrically hospitalized young adults. J Nerv and Ment Dis 1996 ; 184 : 754-7. 11 Grilo CM, Becker DF, Fehon DC, Walker ML, Edell WS, McGlashan TH. Gender differences in personality disorders in psychiatrically hospitalized adolescents. Am J Psychiatry 1996 ; 153 : 1089-91. 12 Hoffart A, Thornes K, Hedley LM, Strand J. DSM-III-R Axis I and Axis II disorders in agoraphobic patients with and without panic disorder. Acta Psychiatr Scand 1994 ; 89 : 186-91.
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13 Jackson HJ, Whiteside HL, Bates GW, Bell R, Rudd RP, Edwards J. Diagnosing personality disorders in psychiatric inpatients. Acta Psychiatr Scand 1991 ; 83 : 206-13. 14 Kroll J, Sines L, Martin K, Lari S, Pyle R, Zander J. Borderline personality disorder: construct validity of the concept. Arch Gen Psychiatry 1981 ; 38 : 1021-6. 15 Langs G, Quehenberger F, Fabisch K, Klug G, Fabisch H, Zapotoczky HG. Prevalence, patterns and role of personality disorders in panic disorder patients with and without comorbid (lifetime) major depression. Acta Psychiatr Scand 1998 ; 98 : 116-23. 16 Langs G, Quehenberger F, Fabisch K, Klug G, Fabisch H, Zapotoczky HG. The development of agoraphobia in panic disorder: a predictable process? J Affect Disord 2000 ; 58 : 43-50. 17 Latas M, Starcevic V, Trajkovic G, Bogojevic G. Predictors of comorbid personality disorders in patients with panic disorder with agoraphobia. Compr Psychiatry 2000 ; 41 : 28-34. 18 Mavissakalian MR, Hamman MS, Abou Haidar S, de Groot CM. DSM-III personality disorders in generalized anxiety, panic/agoraphobia, and obsessive-compulsive disorders. Compr Psychiatry 1993 ; 34 : 243-8. 19 Mc GI, shan TH. The Chestnut Lodge Follow-Up Study, III: long-term outcome of borderline personalities. Arch Gen Psychiatry 1986 ; 43 : 20-30. 20 Merikangas KR, Stevens DE, Fenton B, et al. Co-morbidity and familial aggregation of alcoholism and anxiety disorders. Psychol Med 1998 ; 28 : 773-88. 21 Oei TPS, Wanstall K, Evans L. Sex differences in panic disorder with agoraphobia. J Anxiety Disord 1990 ; 4 : 317-24. 22 Reich J. Sex distribution of DSM-III personality disorders in psychiatric outpatients. Am J Psychiatry 1987 ; 144 : 485-8. 23 Robins LN, Helzer JE, Weissman MM, Orvaschel H, Gruenberg E, Burke JD Jr, et al. Lifetime prevalence of specific psychiatric disorders in three sites. Arch Gen Psychiatry 1984 ; 41 : 949-58. 24 Sanderson WC, Wetzler S, Beck AT, Betz F. Prevalence of personality disorders among patients with anxiety disorders. Psychatry Res 1993 ; 51 : 167-74. 25 Starcevic V, Djordjevic A, Latas M, Bogojevic G. Characteristics of agoraphobia in women and men with PD with agoraphobia. Depress Anxiety 1998 ; 8 : 8-13. 26 Yonkers KA, Zlotnick C, Allsworth J, Warshaw M, Shea T, Keller MB. Is the course of panic disorder the same in women and men? Am J Psychiatry 1998 ; 155 : 596-602. 27 Zimmerman M, Coryell WH. DSM-III personality disorder dimensions. J Nerv Ment Dis 1990 ; 178 : 686-92.