Panic disorder history in the families of patients with angiographically normal coronary arteries.

OBJECTIVE: The authors evaluated the diagnostic validity of an interview-based panic disorder diagnosis in cardiology chest pain patients with angiographically normal coronary arteries. METHOD: Patient probands with normal coronary arteries (N = 65) were first contracted immediately after their normal angiogram and were given a structured diagnostic interview. On the basis of the results of the interview, probands were grouped as having panic disorder (N = 19), panic attacks that did not meet frequency criteria for panic disorder (N = 17), or no panic (N = 29). At a later time, patient probands were recontacted and given a structured family history interview that inquired about psychopathology in their first-degree biological relatives (N = 544). RESULTS: As predicted, panic disorder was significantly more prevalent among the first-degree relatives of probands with normal coronary arteries diagnosed with panic disorder or panic attacks than among the family members of probands with normal coronary arteries without panic (17.4% versus 15.7% versus 4.0%). Family members of probands with panic attacks were significantly more likely to be diagnosed with major depression than were the family members of probands with no panic; however, differences did not reach significance for family members of the panic disorder proband group. Groups did not differ significantly in familial alcoholism. CONCLUSIONS: These data support the construct validity of an interview-based panic disorder diagnosis among patients with chest pain and normal coronary arteries and suggest that these patients could benefit from treatment for panic disorder.     

Major depression and agoraphobia in patients with angiographically normal coronary arteries and panic disorder

Patients with panic disorder and/or agoraphobia appearing in psychiatric settings report rates for lifetime major depression between 24% and 91%. Between 40% and 90% of patients with panic disorder in psychiatric populations report concomitant agoraphobia. A recent study of panic disorder subjects appearing in an outpatient cardiology clinic confirmed the strong link between panic and depression but found only a weak association between panic disorder and agoraphobia. In order to test the reliability of these outpatient cardiology findings, the authors studied major depression and agoraphobia in patients with angiographically normal coronary arteries and panic disorder. Twelve of the 32 (37.5%) panic disorder subjects reported a lifetime history of major depression (nine current, three past only). Only two of the 32 (six percent) reported any phobic avoidance. This study confirms the previous findings which suggest that major depression is common in cardiology populations with panic disorder and that phobic avoidance is uncommon in this group.     

Platelet survival in patients with angiographically diseased and normal coronary arteries

Platelets may contribute to the pathogenesis of atherosclerosis and to the complications of coronary artery disease. Therefore, platelet kinetics were studied in 69 patients with angiographically documented coronary artery disease and in 16 patients with a normal coronary angiogram. Platelet survival time was calculated from the decay of radioactivity after injection of 51Cr-labeled autologous platelets. None of the mathematical models used was able to discriminate between the two patients groups. No correlation existed between survival time and extent of the arterial disease. Patients with a high serum cholesterol did not exhibit an enhanced platelet consumption. Thus, these studies do not support the idea that turnover is enhanced in patients with coronary artery disease as compared to those with normal coronary arteries.     

Response to 35% CO2 in patients with chest pain and angiographically normal coronary arteries.

OBJECTIVES: Several interview studies have suggested that panic disorder (PD) exists in patients with angiographically normal coronary arteries (NCA). Interview studies require corroboration by other studies in order to validate them. The purpose of this study is to test whether response to the inhalation of 35% CO2 reliably discriminates between PD and non-panic disorder patients in this population. METHOD: Three groups were studied: six with NCA and PD, five with NCA and no PD, and ten in the control group. All subjects breathed room air, then 35% CO2 in a single-blind fashion. Each completed the Acute Panic Inventory (API) before and during the procedure. RESULTS: The NCA-panic group scored significantly higher than the other two groups on the Acute Panic Inventory from baseline to post-inhalation. CONCLUSION: Despite several methodological limitations including a relatively small number people in each cells, 35% CO2 was shown to trigger more intense responses in panic patients, thus helping to validate the interview findings.     

Plasminogen activator inhibitor contributes to the coronary wall thickening in patients with angiographically normal coronary

INTRODUCTION: Angiographically normal coronary arteries have concealed intimal thickening that importantly contribute to coronary arterial disease activity. Increased plasma levels of plasminogen activator inhibitor (PAI) are associated with myocardial infarction and atherosclerosis. However, it remains unclear whether the PAI contributes to vascular wall thickening detected by intravascular ultrasound (IVUS) in normal coronary angiogram. The aim of this study was to evaluate if the PAI activity contributes to the extent of atherosclerotic changes in angiographically normal coronary arteries using IVUS technique. MATERIALS AND METHODS: We studied 33 consecutive patients with normal coronary angiograms. These patients were divided into a high level of plasma PAI activity group (H-PAI; n=12) and a normal range of PAI activity group (N-PAI; n=21), according to the plasma PAI activity levels. RESULTS: The average of "percent intima+media area (%I+M area)" and "maximal intima+media (I+M) thickness" were significantly greater in the H-PAI group as compared with those in the N-PAI group (p<0.05). Minimal lumen diameter and lumen area were comparable between these groups. The plasma PAI activity level was the independent predictor of increase in maximal I+M thickness, in multiple regression analysis with the traditional risk factors as covariates. CONCLUSIONS: Thickened intima+media of angiographically normal coronary arteries were associated with high plasma level of PAI activity, independently of other traditional risk factors. PAI may contribute to the pathogenesis of coronary intimal thickening that might increase coronary arterial tone.     

Panic disorder in patients with chronic heart failure

OBJECTIVE: Our objective was to assess the prevalence of panic disorder, its influence on quality of life (QoL), and the presence of further anxiety and depressive comorbid disorders in outpatients with chronic heart failure (CHF). METHODS: In a cross-sectional study, anxiety and depressive disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria in patients with CHF who were aged > or =18 years and had New York Heart Association (NYHA) Functional Classes I-IV, using the Patient Health Questionnaire. Health-related QoL was evaluated using the Short-Form 36 Health Survey (SF-36). RESULTS: Of the 258 participating patients, 24 (9.3%) fulfilled diagnostic criteria for panic disorder. Seven of these (29.2%) were diagnosed with comorbid anxiety disorders, 11 (47.3%) were diagnosed with comorbid depressive disorder, and 5 (20.8%) were diagnosed with other anxiety disorders and any depressive disorder. Female gender [odds ratio (OR)=3.1; 95% confidence interval (95% CI)=1.2-7.8; P=.02] and a lower level of education (OR=0.3; 95% CI=0.1-0.9; P=.04) were associated with the presence of panic disorder. In patients with panic disorder, QoL was significantly more restricted on all subscales of the SF-36 as compared to those without panic disorder, even when age, gender, and NYHA functional class were controlled for (P=.05 to <.01). CONCLUSION: Approximately 1 of 10 patients with CHF suffers from panic disorder, many of whom also have additional anxiety or depressive comorbid disorders. Female gender and a low level of education are positively associated with the presence of panic disorder. QoL is severely limited by the presence of panic disorder. Diagnosis of mental disorders and treatment offers for affected patients should be available in patient care.     

Panic and phobic disorders in patients with obsessive compulsive disorder

Obsessive compulsive disorder shares numerous clinical features with other anxiety disorders. To study the relationship between OCD and other anxiety disorders, the authors administered the Structured Clinical Interview for DSM-III to 36 OCD patients. Thirty-nine percent (14) of patients reported a lifetime history of panic attacks, and 14% (5) met DSM-III-R criteria for panic disorder at the time of interview. Fourteen percent (5) met criteria for social phobias, and 19% (7) met criteria for simple phobias. Eighteen patients were treated with clomipramine in doses of at least 100 mg/day for 3 months. Patients with a history of other anxiety disorders responded significantly better to clomipramine.     

Panic disorder and agoraphobia: Fear of fear or fear of the symptoms produced by hyperventilation?

Two versions of the fear-of-fear hypothesis of panic disorder are discussed. The fear-of-fear-somatic-effects-of-fear version, which is distinguished from the classical conditioning version, is compared with the hyperventilation theory of panic disorder and agoraphobia. The fear-of-the-somatic-effects-of-fear hypothesis is criticized on the basis of its inability to explain adequately (a) the initiation of panic attacks, (b) the growth in intensity of panic attacks, and (c) the termination of panic attacks. The tenability of the hyperventilation theory is supported by evidence from programs of treatment derived from the basic assumptions of the theory.     

Heart rate variability in coronary artery disease patients with and without panic disorder

Panic disorder (PD) and coronary artery disease (CAD) often co-occur, and CAD patients with comorbid PD suffer greater cardiovascular morbidity and mortality relative to CAD patients without PD. However, the mechanisms underlying these associations are still unknown. Reduced heart rate variability (HRV), a non-invasive measure of cardiac autonomic modulation, is an important predictor of adverse cardiac events. Interestingly, reduced HRV has been observed in patients with panic-like anxiety and PD, as well as in various CAD populations. However, the extent to which HRV is altered in patients with both PD and CAD is unknown. This study evaluated HRV in 42 CAD patients with (n=20) and without (n=22) PD. Patients underwent 48-h electrocardiographic monitoring. Power spectral analysis of HRV indicated that CAD patients with PD exhibited significantly lower LF/HF ratios, which may reflect lower sympathetic modulation, compared with non-PD patients. Additionally, total power in PD patients was made up of a significantly higher proportion of HF power and a significantly lower proportion of VLF power than in non-PD patients. No other significant differences in HRV indices were observed. Results suggest that contrary to what has been observed in the majority of PD-only and CAD-only populations; patients with both PD and CAD appear to exhibit lower sympathetic modulation during ordinary daily life conditions. Though preliminary, these findings suggest that changes in HRV may not be the mechanism underlying greater cardiovascular morbidity and mortality among CAD patients with PD.     

Angina pectoris with normal coronary arteries in Shy-Drager syndrome.

A patient with Shy-Drager syndrome who presented with severe angina pectoris is described. Special investigations of his autonomic nervous system showed sympathetic and parasympathetic dysfunction with supersensitive end-organ response. Sympathetic dysfunction manifested as labile hypertension, severe postural hypotension, and inadequate heart rate response to atropine and the Valsalva manoeuvre. These changes in blood pressure were accompanied by severe disabling angina pectoris. Selective coronary angiography showed normal coronary arteries. It is suggested that angina pectoris resulted from the inadequate circulatory response and is another clinical manifestation of the Shy-Drager syndrome.     

Panic disorder with and without agoraphobia: comorbidity within a half-year of the onset of panic disorder

The present study was performed to compare the clinical features of patients with panic disorder with and without agoraphobia. The subjects were 233 outpatients with panic disorder (99 males and 134 females) diagnosed according to DSM-IV criteria. Sixty-three patients met the criteria for panic disorder without agoraphobia, and 170 met the criteria for panic disorder with agoraphobia. Patients with agoraphobia showed a significantly longer duration of panic disorder and higher prevalence of generalized anxiety disorder. However, there were no significant differences in prevalence of major depressive episodes, in current severity of panic attacks, or in gender ratio between the two groups. The second aim of the present study was to investigate the effects of onset age and sex differences on the development of agoraphobia within a half-year. The subjects were divided into two groups according to their self-report: patients who did or did not develop agoraphobia within 24 weeks of onset of panic disorder. A total of 40.6% of the patients developed agoraphobia within 24 weeks of the onset of panic disorder, and onset age and sex differences had no robust effect on the development of agoraphobia within 24 weeks.     

Mitral valve prolapse and neuroticism in chest pain patients with normal and diseased coronary arteries

Patients with chest pain and normal coronary arteries (NCA) score higher on measures of neuroticism than patients with coronary artery disease (CAD). This relationship, coupled with findings linking mitral valve prolapse (MVP) and anxiety disorders, led us to examine prospectively the possibility that a greater incidence of MVP among NCA patients accounts for their elevated neuroticism scores. One-hundred-forty-four patients completed psychological tests and a structured interview prior to cardiac catheterization. Forty-one of the 144 patients (28%) had normal coronary arteries. Within the NCA group 29 percent had MVP; within the CAD group only 13 percent had MVP. Despite the significant difference between NCA and CAD groups on measures of neuroticism, there were no differences as a function of MVP status, nor was there an interaction of MVP and coronary arterial status. These findings support the case for an association between NCA and neuroticism independent of the presence or absence of MVP.     

Panic disorder in schizophrenia.

OBJECTIVE: To determine the frequency of panic attacks and panic disorder in patients with chronic schizophrenia or schizoaffective disorder. METHOD: Fifty-three male outpatients meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for chronic schizophrenia or schizoaffective disorder were administered sections of the Structured Clinical Interview for DSM-IV (SCID). If panic attacks were reported, patients were queried about treatment and about onset relative to psychotic symptoms. RESULTS: Forty-nine patients were sufficiently organized to participate in the evaluation. Twenty-one (43%) experienced panic attacks, and 16 (33%) had current or past panic disorder. Eight (50%) of the 16 with panic disorder had been treated for panic. Substance dependence was not associated with having panic attacks or current or past panic disorder. Patients with paranoid schizophrenia were more likely than patients with schizoaffective or undifferentiated schizophrenia to have experienced panic attacks (57% versus 20%, chi 2 = 6.0, P < 0.02) or panic disorder (47% versus 10%, chi 2 = 6.9, P < 0.01). CONCLUSION: Panic attacks and panic disorder are common in men with schizophrenia or schizoaffective disorder. Panic disorder may be an overlooked comorbid diagnosis in patients with schizophrenia.     

Panic response to lactate administration in alcoholic and nonalcoholic patients with panic disorder

The authors administered lactate to 12 abstinent alcoholics with panic disorder, 10 nonalcoholic patients with panic disorder, and eight control subjects. They found that the alcoholic patients had fewer panic attacks in response to lactate infusion than the nonalcoholic patients. This finding was not attributable to differences in baseline anxiety or the change in plasma chemical values brought about by sodium lactate administration. The authors suggest that there may be subgroups of patients with panic disorder who need further characterization to meaningfully elucidate the pathophysiology of the disorder.     

Panic disorder patients have reduced cyclic AMP in platelets.

Little is known about the intracellular mechanisms involved in the pathophysiology of panic disorder (PD). Abnormalities in the cyclic AMP system have been described in several psychiatric disorders but there are no studies in panic patients. We evaluated not only the levels of platelet cyclic AMP, but also cyclic GMP and nitric oxide synthase (NOS) activity in patients with PD at baseline and after treatment with clomipramine and in healthy volunteers. Platelet cyclic AMP was determined by enzymeimmunoassay, cyclic GMP by radioimmunoassay and NOS activity by the conversion of (3)H-arginine to (3)H-citruline in 17 PD patients before treatment with clomipramine, after remission of panic attacks and in 22 healthy volunteers. Average baseline cyclic AMP of PD patients was lower than after remission of panic attacks (P<0.005) and lower than in healthy volunteers (P<0.005). Average cyclic AMP after remission of panic attacks was not significantly different than in healthy volunteers. There were no significant differences in cyclic GMP and NOS analysis. Our results suggest that PD patients without treatment have lower platelets cyclic AMP levels than healthy volunteers and that this decrease may be corrected by clomipramine.     

Panic disorder patients at the time of air strikes

We assessed the impact of real danger on several aspects of the panic disorder (PD) patients' psychopathology and level of disability. At the time of the NATO air strikes on Belgrade, 84 PD patients who were in partial or complete remission were administered the Panic and Agoraphobia Scale (PAS). All had been treated previously, and the majority (58.3%) were taking antipanic medications. The PAS, which was used as part of the regular follow-up assessment battery for PD patients, measures the overall severity of PD and the severity of key aspects and components of PD. Compared to the PAS assessments made before the onset of air strikes, the PAS assessments made at the time of air strikes showed significant differences in terms of decreased overall severity of PD, fewer health concerns, decrease in the level of disability, and greater intensity and frequency of anticipatory anxiety. Differences on the measures of panic attacks and agoraphobic avoidance were negligible. These results suggest that there is no relationship between panic attacks and real danger and lend support to the notion that panic attacks and fear induced by real danger are different phenomena. Contrary to the expectations of many PD patients, the presence of real danger does not seem to be associated with deterioration in their functioning, and PD patients can be reassured that they are not likely to cope worse under conditions of danger.