واکنش سمپاتیکی در بیماران مبتلا آگروفوبیا با و بدون اختلال شخصیتی

Abstract Objective: To compare sympathetic activity in agoraphobic patients with and without personality disorders before and after 11 weeks inpatient treatment. Methods: Agoraphobic patients (n=38), 84% with panic disorder and 47% with personality disorders underwent cold pressure test (CPT), mental stress test (MST), and a specific anxiety test (SAT). Psychological assessments were done by the Bodily Sensations Questionnaire (BSQ), the Agoraphobic Cognitions Questionnaire (ACQ), Spielberger STAI-1 and -2, and a Stress Test Anxiety (STA) questionnaire. Sympathetic activity was measured by blood pressure, heart rate, epinephrine, and norepinephrine. Results: The sympathetic activity did not differ significantly between patient groups, and the reactivity to stress was very low. The sympathetic reactivity remained unchanged after treatment, whereas psychiatric symptoms decreased. Correlations between sympathetic activity and psychological distress were not significant. Conclusion: Interpretation of bodily signals seems to be more important than the actual sympathetic activity in agoraphobic patients

Introduction For more than a century, the sympathetic nervous system has been linked to the pathogenesis of panic disorder [1] and [2]. These patients are highly sensitive to bodily sensations that might be subject to catastrophic misinterpretation [3]. This can be illustrated by the finding that among patients referred for first time for outpatient cardiological examination, there were 38% with panic disorder and 16% with coronary heart disease [4]. Increased cardiovascular mortality has been reported in patients with panic disorder as well as in men with phobic anxiety [5], [6], [7] and [8]. It has been suggested that the increased mortality may be due to cardiovascular hyperreactivity to stress that may promote future cardiovascular events [9] and essential hypertension [10]. Alderman et al. [11] found that blood pressure reactivity to laboratory stressors might predict myocardial infarction among treated hypertensive subjects. According to the DSM-IV [12], agoraphobia is considered a further development of panic disorder, and therefore a more serious and chronic condition. However, studies on neurobiological factors have almost exclusively focused on panic disorder with or without agoraphobia. This may have followed from the experience that agents like sodium lactate, carbon dioxide, caffeine, isoproterenol, yohimbine, and cholecystokinin may provoke panic attacks. As these agents differ in their specific neurochemical mechanisms and effects, however, a final common pathway has not yet been found [13]. Palmero et al. [14] found that university students with the personality trait Type A behaviour pattern, characterized by time urgency, hostility, and competitive behaviour showed greater activation, reactivity, and slower recovery than those with Type B pattern when in a stressful laboratory situation. Although there might be an association between reactivity and some personality traits, this does not necessarily mean that we would find the same relationship in a clinical sample of patients with personality disorders. Many patients with personality disorders, however, have experienced difficult and stressful life events during life, which may have influenced their autonomic nervous system in a different way than patients without personality disorders. The prevalence of personality disorders (mostly cluster C) among panic disordered patients with and without agoraphobia has been reported as ranging from 27% to 58% in psychiatric samples [15] and [16]. To our knowledge, however, no studies have compared the reactivity in such patients with or without personality disorders. Neither are we aware of studies that have compared reactivity to stress before and after treatment for agoraphobia. We therefore decided to compare reactivity to stress in agoraphobic patients with and without personality disorder. The aims of the present study has been to investigate the following research questions: 1. Are there differences in sympathetic activity at rest in agoraphobic patients with and without personality disorders? 2. Is the sympathetic reactivity to stress different in these two groups? 3. Have the sympathetic responses to stress changed after treatment in the two groups? 4. What is the relationship between sympathetic activity and psychological factors in the two groups?

Results The sympathetic activity at rest in agoraphobic patients with and without personality disorder There were no significant differences at rest in agoraphobic patients with and without personality disorder with respect to the levels of heart rate, blood pressure, epinephrine, and norepinephrine either before or after treatment Table 1 and Table 2. Table 1. Sympathetic activity for agoraphobic patients with and without personality disorders before treatment (mean±S.E.) Test Before stress exposure Reactivity to stress P values a 0 1 0 1 0 1 CPT Heart rate (bpm) 65.3±2.8 69.4±2.6 1.8±2.2 4.2±2.4 NS NS Systolic blood pressure (mm Hg) 115.4±6.4 107.8±3.8 3.6±2.9 2.8±2.7 NS NS Epinephrine (pg/ml) 51.4±12.6 70.1±13.7 10.1±6.4 −6.9±7.2 NS NS MST Heart rate (bpm) 65.0±3.1 67.8±1.8 9.7±2.2 4.2±1.1* <.05 <.05 Systolic blood pressure (mm Hg) 126.4±5.0 117.2±4.9 3.8±3.6 5.9±2.5 NS NS Epinephrine (pg/ml) 50.8±8.0 58.4±7.0 28.4±14.1 −6.6±6.3* NS NS SAT Heart rate (bpm) 72.6±3.9 73.3±3.1 2.3±3.5 0.0±2.0 NS NS Systolic blood pressure (mm Hg) 120.3±5.5 120.3±5.9 3.9±3.2 −3.7±3.0 NS NS Epinephrine (pg/ml) 56.6±6.4 50.8±8.0 2.8±3.2 −3.7±3.0 NS NS a Baseline vs. stress test within groups. * P<.05 for differences between 0 (no personality disorder) and 1 (personality disorder). Table options Table 2. Sympathetic activity for agoraphobic patients with and without personality disorders after treatment (mean±S.E.) Test Before stress exposure Reactivity to stress P values a 0 1 0 1 0 1 CPT Heart rate (bpm) 63.3±2.3 66.1±2.5 4.4±2.7 2.9±1.1 NS <.05 Systolic blood pressure (mm Hg) 113.9±4.2 106.9±4.3 5.4±1.9 0.0±3.2* <.05 NS Epinephrine (pg/ml) 66.1±6.1 53.4±6.5 −9.9±4.0 11.7±8.1* <.05 NS MST Heart rate (bpm) 65.1±2.6 67.6±3.1 10.5±2.0 3.6±2.1 <.05 NS Systolic blood pressure (mm Hg) 120.0±3.1 112.2±4.2 7.2±1.7 7.4±4.6 <.05 NS Epinephrine (pg/ml) 61.0±10.0 55.4±4.9 16.1±6.7 23.9±12.5 <.05 NS SAT Heart rate (bpm) 67.3±3.1 68.6±3.1 2.8±1.6 −0.1±1.4 NS NS Systolic blood pressure (mm Hg) 122.0±3.5 110.9±4.8 2.3±3.1 −3.1±1.8 NS NS Epinephrine (pg/ml) 53.7±7.2 53.6±3.3 6.2±6.8 4.7±6.8 NS NS a Baseline vs. stress test within groups. * P<.05 for differences between 0 (no personality disorder) and 1 (personality disorder). Table options Sympathetic reactivity to stress Paired t tests gave only 2 out of 18 stress responses that were statistically significant before treatment. There were significantly increased heart rate responses during MST for both groups. After treatment, there were 6 out of 18 significant differences; 5 of these were among the patients without personality disorder: systolic blood pressure and epinephrine during CPT, heart rate, blood pressure, and epinephrine during MST. The only significant response in the other group was heart rate during CPT. Diastolic pressure and norepinephrine measurements gave no more significant responses. Before treatment, the reactivity to stress was generally low in both groups, 4 out of 18 responses even negative, although not statistically significant, adding 3 more when considering diastolic pressure and norepinephrine. There were only significant differences in the level of reactivity between nonpersonality disorder and personality disorder agoraphobic patients on 4 out of 15 variables, MST heart rate, epinephrine, and norepinephrine reactivity was greater among patients without personality disorders, whereas SAT norepinephrine was lower. After treatment, the reactivity was still low (3 out of 18 were negative) (Table 2) and 2 out of 15 of the responses were significantly different between patient groups, CPT systolic blood pressure was higher, and epinephrine lower among the participants without personality disorders than among those with personality disorders. The reactivity did not differ statistically after treatment compared to before, except for a lower reactivity post for CPT epinephrine among patients without personality disorders. Pooling the groups gave two significantly stress responses before treatment (heart rate during CPT and systolic blood pressure during MST), but otherwise no different results regarding either reactivity to stress or effect of treatment. Psychological variables As shown in Table 3, the participants with personality disorder had higher scores in all psychological tests than those without. Comparing the variables pre- and posttreatment, patients with personality disorders improved significantly on ACQ only, whereas those without personality disorder improved both in ACQ and BSQ. There was no significant improvement in anxiety measured by STAI-1 and -2. Table 3. Comparisons between psychological variables before and after treatment (mean±S.E.) Psychological test Personality disorder No personality disorder P values BSQ before 3.1±0.2 2.6±0.2 .054 BSQ after 2.9±0.2 2.2±0.2a .023 ACQ before 47.6±4.1 28.5±4.7 .004 ACQ after 38.9±4.9a 19.0±3.3a .002 P values reflect differences between treatment groups. a Significantly lower posttreatment. Table options Correlations between sympathetic activity and psychological variables At rest Correlation analyses among ACQ, BSQ, STAI-1, and -2 before treatment and levels of heart rate, systolic blood pressure, and epinephrine in the three stress situations at rest showed that 71 out of 72 correlations in the two patient groups were not statistically significant. During stress ACQ and BSQ for patients with personality disorder correlated negatively with most biological variables (13 out of 18), but only systolic blood pressure during SAT (r=−.51, P<.05) and heart rate during MST (r=−.70, P<.05) were statistically significant. The only significant correlations between BSQ and sympathetic reactivity (during stress−before stress) was systolic blood pressure during SAT (r=−.52, P<.05), epinephrine during SAT (r=−.52, P<.05) and STAI-1 and epinephrine during MST (r=−.62, P<.05). There were no significant differences for patients without personality disorder, either in absolute scores or for correlations between psychological variables and sympathetic reactivity. Correlations between STA and sympathetic reactivity The groups did not differ in subjectively reported anxiety either before or during the stress test. They reported significantly more anxiety during stress, the nonpersonality disorder patients increasing from 1.8±0.4 (mean±S.E.) to 4.6±0.6 during the SAT, while patients with personality disorder increased from 3.2±0.5 to 5.6±0.6. Differences in STA (STA during stress−STA before stress) were correlated with sympathetic reactivity for heart rate, systolic blood pressure, and epinephrine (during stress−before stress). Only one correlation was statistically significant both for participants with personality disorders and patients without personality disorders (Table 4). Table 4. Correlations between differences in STA (anxiety during stress−anxiety before stress) and sympathetic reactivity before and after treatment STAdiff HRdiff Sysdiff Epidiff Patients with personality disorders During CPT Before treatment .04 .23 .06 After treatment −.05 −.01 −.05 During MST Before treatment −.05 .26 .14 After treatment .10 .36 −.10 During SAT Before treatment .41* .26 .02 After treatment .18 −.03 .12 Patients without personality disorders During CPT Before treatment .16 .21 −.26 After treatment −.11 .06 .24 During MST Before treatment .03 .00 .25 After treatment −.21 .22 .12 During SAT Before treatment −.47* .35 −.05 After treatment −.26 .16 −.11 STAdiff=STA during stress−before stress; HRdiff=heart rate during stress−before stress; Sysdiff=systolic blood pressure during stress−before stress; Epidiff=epinehrine during stress−before stress. * P<.05.