Salivary alpha-amylase and cortisol responsiveness following electrical stimulation stress in panic disorder patients

Psychosocial stress-induced activation of salivary α-amylase (sAA) functions is as a marker of sympathoadrenal medullary system (SAM) activity. However, in contrast to salivary cortisol, sAA has been less extensively studied in panic disorder patients. The present study measured sAA and salivary cortisol levels in patients with panic disorder following electrical stimulation stress. The authors determined Profile of Mood State (POMS) scores and State-Trait anxiety Inventory (STAI) scores, heart rate variability (HRV), and levels of sAA and salivary cortisol in 34 patients with panic disorder and 41 healthy volunteers following the application of electrical stimulation stress. 34 alprazolam-treated patients with panic disorder were divided into non-responder and responder group. Vigor scores in patients with panic disorder were significantly decreased compared with healthy controls. Another score in POMS in patients with panic disorder were significantly increased compared with healthy controls. Trait and state anxiety of STAI in panic disorder patients were higher than healthy controls. There was no difference in either HRV or threshold of electrical stimulation applied between panic disorder patients and healthy controls. SAA levels in the responder group were significantly elevated compared with the non-responder group and controls both before and after electrical stimulation. In addition, there were no differences in salivary cortisol levels between responder and non-responder groups of patients with panic disorder and control. The sample may not be representative of the general population. These preliminary results suggest that sAA might be useful predictive biological markers of treatment responsiveness in patients with panic disorder.     

Characterological traits of recovered patients with panic disorder and agoraphobia.

Three self-rating personality inventories were administered to 33 patients who had recovered from panic disorder associated with agoraphobia and to 33 healthy subjects matched for sociodemographic variables. The personality inventories comprised the Tridimensional Personality Questionnaire (TPQ), which provides three major dimensions (novelty seeking, harm avoidance and reward dependence), the Anxiety Sensitivity Index (ASI) and the Emotional Inhibition Scale (EIS). Agoraphobic patients reported significantly more TPQ harm avoidance and anxiety sensitivity than controls. Although these findings might have been influenced by residual anxiety symptoms in panic-free patients and could also apply to patients with other anxiety disorders, they suggest that harm avoidance and anxiety sensitivity may be risk factors for developing agoraphobia and panic disorder. There may be overlap between this characterologic cluster and prodromal symptoms of panic disorder with agoraphobia, such as anxiety, phobias and hypochondriasis.     

The 35% carbon dioxide test in stress and panic research: overview of effects and integration of findings

The carbon dioxide test--a vital capacity breath of air containing 35% carbon dioxide (CO(2))--provokes panic attacks in many individuals with panic disorder (PD). It has thus been extensively used as an experimental model of panic and less frequently as a clinical method of provoking symptoms for interoceptive exposure treatment. Recently, stress researchers have suggested another use for the CO(2) test: that of an acute physiological stressor indexing the human stress response. The purpose of this review is to synthesize findings about the effects of the CO(2) test from both the panic and stress literatures in order to advance understanding about this increasingly popular test. Both panic and stress researchers have examined the fleeting effects of the CO(2) test, finding that the test engenders transient breathlessness, dizziness, and minor anxiety in most participants and panic attacks in those with or at risk for PD. Physiological measurements after the test indicate a brief homeostatic disruption in many bodily systems, including increased respiration, systolic blood pressure, and noradrenaline, and decreased heart rate. Most studies indicate increased cortisol. Possible benefits of integrating findings from the panic and stress research lines, given their common use of the CO(2) test, are discussed.     

Lactate infusion induces panic attacks in patients with premenstrual syndrome.

A sodium lactate test was performed during the premenstrual phase in 35 women suffering from prospectively confirmed premenstrual syndrome (PMS) and in 16 controls in order to assess whether these patients were sensitive to this test and whether this sensitivity was accounted for primarily by the presence of concomitant panic disorder. Patients with PMS also underwent the Structured Clinical Interview for the DSM-III-R (SCID) to determine the presence of co-morbid anxiety and/or mood disorders. Only 31% of the PMS patients were free from a depressive/anxiety disorder, while nine patients met criteria for panic disorder, and the remaining 15 subjects were diagnosed as having anxiety and/or mood disorders. Lactate infusion induced panic attacks in 22 subjects (62.9%) and two controls (12.5%). Panickers were equally distributed among PMS patients with or without a concurrent anxiety/mood disorder. Although cardiovascular responses to lactate were similar among PMS patients regardless of the presence of concomitant anxiety/mood disorders, both plasma cortisol levels and panic and mood scores were higher during the test in those patients with concomitant panic disorder. These results suggest that PMS patients display an increased sensitivity to lactate, which is not primarily accounted for by the presence of co-morbid panic disorder.     

Quality of life and treatment outcome in panic disorder: cognitive behavior group therapy effects in patients refractory to medication treatment

BACKGROUND: Improvements in quality of life (QoL) as well as symptomatic relief are important outcomes for the treatment of panic disorder (PD). The aim of this study is to assess the impact of brief cognitive behavior group therapy (CBGT) for panic disorder on QoL and to identify the clinical features associated with these changes. METHODS: Thirty-six patients with PD refractory to pharmacological treatment took part in a treatment protocol consisting of 12 sessions of CBGT. To evaluate the changes in QoL, the WHOQOL-bref was administered before and after treatment. RESULTS: Thirty-two patients completed the treatment. Significant improvement in all domains of QoL was observed (p< 0.001), which was associated with reductions in general and anticipatory anxiety (p = 0.018) and agoraphobic avoidance (p = 0.046). Consistent with previous findings, associations between QoL and panic-free status did not reach significance in this small study (p = 0.094). CONCLUSIONS: CBGT was efficacious in the treatment of PD; the symptoms of anticipatory anxiety and avoidance appear to be more important than episodic panic episodes in affecting QoL.     

Cardiovascular dystonia in recovered panic patients

Resting heart rate, heart rate variability and blood pressure; the heart rate and blood pressure response to standing; and the heart rate response to Valsalva's manoeuvre, have been measured in a group of 12 patients with panic disorder and a group of 12 age- and sex-matched normal subjects. The patients had undergone treatment for their panic attacks with cognitive therapy; all had responded and all had been panic-free for a minimum of 4 months (mean 7.6 months). Mood ratings (BDI, BAI and SSAI) were comparable with established norms. The patients nevertheless had a raised resting systolic blood pressure, a reduced resting heart rate and an abnormal orthostatic response.     

Relevance of assessment of cognitions during panic attacks in the treatment of panic disorder

BACKGROUND: In this paper the effects of cognitive therapy on the belief in causal catastrophic misinterpretations (CCMs) of bodily sensations in panic disorder patients were studied. METHODS: CCMs were formulated at the start of treatment and assessed at every treatment session for credibility during panic attacks and during that session. The relation between the belief in CCMs and other measures of panic was also studied. Sixty-six patients rated their belief in 1-3 CCMs during treatment with cognitive therapy. They also filled in questionnaires (ACQ and BSQ) at the start and end of treatment and kept a panic diary. RESULTS: The belief in CCMs diminished significantly in the course of treatment. A significant correlation between panic frequency and belief in CCMs during panic attacks, but not during treatment sessions, was found. Relations between improvement in panic frequency, ACQ- and BSQ-scores on the one hand and belief in CCMs on the other, also revealed significant correlations with belief ratings during panic attacks only. CONCLUSIONS: Especially ratings of belief during panic attacks are important in assessing the outcome of cognitive therapy in panic disorder. This measure can be considered as a severity measure. Belief in CCMs during treatment sessions seems to have little clinical significance.     

The relationship between agoraphobia symptoms and panic disorder in a non-clinical sample of adolescents

BACKGROUND: The purpose of this study was to evaluate the clinical correlates of agoraphobic fear and avoidance and panic disorder in a non-clinical sample of adolescents. METHOD: In a sample of 2365 high school students, combined data from a questionnaire and a structured clinical interview were used to classify subjects with agoraphobic fear and avoidance. Panic symptoms, major depression, childhood separation anxiety disorder, anxiety sensitivity and negative affectivity were also assessed. RESULTS: Fifteen subjects met study criteria for agoraphobic fear and avoidance in the past year. Only three (20%) of those with agoraphobia symptoms reported histories of panic attacks and there was no overlap between those with agoraphobic fear and avoidance and the 12 subjects who met DSM-III-R criteria for panic disorder. However, subjects with agoraphobia symptoms and those with panic disorder reported similar levels of anxiety sensitivity and negative affectivity. Childhood separation anxiety disorder was more common among those with agoraphobic fear and avoidance compared to those without. CONCLUSION: Agoraphobic avoidance is rare in non-clinical samples of adolescents and usually not associated with panic attacks. However, adolescents with agoraphobia symptoms and those with panic disorder have similar clinical correlates consistent with a panic/agoraphobia spectrum model.     

Psychopathology of panic attacks in panic disorder

PURPOSE: This study examined the relationships among certain subtypes of panic attacks (full vs. limited symptom; spontaneous vs. situational) and between these subtypes, panic disorder subtypes, and other characteristics of panic disorder, especially agoraphobia. METHOD: Data were drawn from a large (n = 1,168) treatment study of panic disorder in which panic attacks were carefully subtyped and counted using a diary. Relationships between variables at baseline were examined primarily using non-parametric methods, and the course of improvement for panic subtypes among completers was plotted. RESULTS: The median number of spontaneous panic attacks per week at baseline was similar among patients with panic disorder without agoraphobia (PD), limited phobic avoidance (PDL), and agoraphobia (PDA). The median number of situational attacks and the median agoraphobia ratings rose progressively across diagnostic subtypes. Anticipatory anxiety, HAM-A, HAM-D, and disability scores were higher in PDA than in PD. Full and limited symptom panic attacks were positively correlated. The proportion of total attacks that were limited rose during the first two weeks of treatment, suggesting conversion of full to limited symptom attacks before complete disappearance. Spontaneous and situational attacks were correlated minimally or not at all. Agoraphobia ratings were more positively correlated with situational than with spontaneous panic attacks. Few of the correlations among measures at baseline were high. CONCLUSIONS: Full and limited symptom panic attacks differ primarily in severity. Spontaneous and situational attacks are relatively independent, and situational attacks are more closely related to agoraphobia. These findings are consistent with previous work suggesting that spontaneous attacks reflect a biological component, whereas situational attacks reflect a cognitive component in the psychopathology-- and possibly the pathogenesis-- of panic disorder. This provides a rationale for the use of combined pharmacotherapy and psychotherapy in the treatment of panic disorder. Future investigations of panic disorder should carefully separate panic attack subtypes.     

Specificity of lactate response in panic disorder, panic with concurrent depression and major depression

Lactate infusions with 0.5 molar sodium lactate in a dose of 10 ml/kg within 20 min were given to patients with panic disorder (n = 6), panic attacks with concurrent major depression (n = 7) and major depression without panic (n = 5). Lactate-induced anxiety and symptom attacks without panic were seen more often in the groups with panic attacks, but a full-blown panic attack was provoked in only four subjects, all belonging to the groups with a history of panic attacks. The low incidence of lactate-induced panic attacks can be explained by differences in the procedure that aimed at reducing expectancy biases and baseline anxiety.     

Nocturnal sleep panic and depression: relationship to subjective sleep in panic disorder

BackgroundPatients with panic disorder (PD) often complain of sleep disturbances. PD patients have high co-morbid depression and almost 65–70% reports a history of nocturnal panic attacks. It is possible that both nocturnal-sleep panic attacks and depression contribute to sleep disturbances in PD patients. However, the individual and interactive effects of nocturnal-sleep panic attacks and lifetime depression on subjective sleep in PD are unknown.MethodsThe National Institute of Mental Health Panic Disorder Questionnaire (NIMH-PQ) was administered to 773 individuals who met DSM-IV criteria for PD. All of these subjects completed queries related to nocturnal-sleep panic attacks, lifetime depression, difficulty sleeping, and sleep duration.ResultsWe examined difficulty in sleeping and sleep duration in four subgroups [PD without nocturnal panic attacks or lifetime depression (NP?D?), PD with nocturnal panic attacks (NP+D?), PD with lifetime depression (NP?D+), and PD with both nocturnal panic attacks and lifetime depression (NP+D+)]. Significantly greater proportions of NP+D+ subjects reported difficulty sleeping compared to other three subgroups. In addition, the NP+D+ patients reported significantly decreased subjective sleep durations compared to the other three subgroups. Using ≤ 5h as a criteria for severe sleep restriction, approximately 20% of the NP+D+ patients, compared to 9.2%, 9.6%, and 2.5% in the NP+D?, NP?D+, NP?D? subgroups, respectively, reported sleeping 5h or less. 8.2% of panic disorder patients reported excessive sleeping per sleeping period.ConclusionsA high percentage of panic disorder individuals report subjective sleep disturbances. Not surprisingly, an unusually high prevalence of patients with nocturnal panic attacks or depression have sleep problems and 92.3% of patients with both nocturnal panic attacks and depression report striking extremes in sleep duration or insomnia. Thus, nocturnal-sleep panic attacks and depression are independently as well as interactively associated with increased sleep disturbances in panic disorder. Although these findings are expected, they underscore the importance of assessing sleep functions, including over-sleeping, in panic disorder patients.     

Alcoholism in 274 patients with panic disorder in Spain,one of the main producers of wine worldwide

BACKGROUND: Though panic disorder (PD) and alcoholism have been found in epidemiologic studies to often co-occur, the influence of cultural factors on the order of onset of the disorders has not been frequently addressed. METHODS: A sample of 274 patients with PD was assessed and compared according to the presence of alcohol use disorder (AUD) (alcohol abuse or dependence), employing several clinical scales. RESULTS: A total of 26 subjects were diagnosed from AUD. In 73.1% of patients, onset of alcohol use was previous to PD onset. PD subjects with AUD were found to have an earlier age at PD onset. They were more likely to be males, to have a family history of alcoholism, to abuse other drugs and to experience a more severe PD (more attacks in the last month, higher scores in anticipatory anxiety). CONCLUSIONS: Patients with PD and alcoholism may represent a distinct clinical subgroup. Our finding of an uncommon order of onset for both disorders may reflect cultural influences. CLINICAL IMPLICATIONS: (i)The study of panic disorder patients with comorbid alcoholism may help to better characterize this subgroup of patients. (ii) Patterns of alcohol use and the order of onset of both disorders may be influenced by cultural factors, with important practical implications. (iii) Patients with panic disorder and alcoholism may represent a distinct clinical subgroup, with an earlier age at panic disorder onset and greater clinical severity of anxiety. LIMITATIONS: (i) Our results refer to a clinical sample, which may not be representative of the general population. (ii) Alcoholic patients with a history of other drug abuse or dependence were not excluded. (iii) Owing to the small sample size, patients with alcohol dependence and with alcohol abuse were not separated.     

Relationship between alexithymia and panic disorder: a longitudinal study to answer an open question

BACKGROUND: In the present study, we evaluated whether patients with panic disorder (PD) in complete remission were more alexithymic than normal controls. METHODS: Fifty-two PD patients (both during the acute phase of the disorder and after at least 2 months of complete remission) and 52 age- and sex-matched normal subjects completed the Toronto Alexithymia Scale-20 and the Hamilton Rating Scales for Anxiety (Ham-A) and for Depression. RESULTS: A higher rate of alexithymia was found in PD patients than in controls (3.8%) both during the acute phase (44.2%; p < 0.001) and after remission of the disorder (21.2%; p = 0.008). During remission, PD patients showed: (1) Ham-A scores significantly higher than controls (p < 0.001); (2) only an elevation of the 'difficulty in identifying feeling' (DIF) dimension of alexithymia, and (3) a positive relationship between Ham-A scores and DIF levels (p < 0.001). CONCLUSION: After remission of panic attacks, phobic avoidance and anticipatory anxiety, PD patients are more alexithymic (even though the levels of alexithymia decreased after the resolution of the acute phase of PD) and anxious than controls. This finding might be explained by an overlap between cognitive aspects of PD and the DIF dimension of alexithymia, since alexithymic and anxious levels are positively related.     

Effects of parental anxiety disorders in children at high risk for panic disorder: a controlled study

BACKGROUND: To examine the association between anxiety disorders in parents and offspring in a sample of children at risk for panic disorder. We hypothesized that individual anxiety disorders will breed true in offspring. METHODS: Comparisons were made between offspring of parents with PD+MD (N=136), PD (N=27), MD (N=27), and Controls (N=103). All subjects were assessed with structured diagnostic interviews. Individual anxiety disorders in the offspring were used as dependent variables in logistic regression models where parental PD status, parental MD, and the same parental anxiety diagnosis were used as independent binary variables. RESULTS: Social phobia and separation anxiety disorder in the offspring were accounted for by the same disorders in the parent, whereas agoraphobia and OCD in the offspring were accounted for by parental panic disorder. CONCLUSIONS: These findings suggest that differing risk factors underlie the expression of individual anxiety disorders in children at risk for panic disorder.     

Anxiety and stress can predict pain perception following a cognitive stress

Hoeger Bement, M.K., A. Weyer, M. Keller, A. Harkins, and S.K. Hunter. Anxiety and stress can predict pain perception following a cognitive stressor. PHYSIOL BEHAV 000-000. The purpose of this study was to investigate the influence of a cognitive stressor on pain perception and determine individual characteristics that may predict the pain response. Twenty-five subjects participated in three sessions: one familiarization and two experimental. The experimental sessions involved measurement of pain perception before and after 1) mental math tasks (stressor session) and 2) quiet rest (control session). Pain threshold and ratings were assessed with a mechanical noxious stimulus. Changes in stress and anxiety were examined with self-reported and physiological measures including questionnaires, visual analogue scales, and salivary cortisol levels. During the control session, stress and anxiety decreased and pain reports remain unchanged. During the stressor session, stress and anxiety increased and pain reports were variable among subjects. Based on the pain response to mental math, subjects were divided into three groups (increase, decrease or no change in pain). The increase-pain group (n = 8) had lower baseline stress and anxiety, lower baseline pain reports, and large anxiety response following the mental math. In contrast, the decrease-pain group (n = 9) had higher baseline stress and anxiety levels, higher baseline pain reports, and a large increase in cortisol levels. Thus, the differential response in the changes in pain perception was related to anxiety and stress levels prior to and during the cognitive stressor, indicating that psychosocial characteristics can help determine the stress-induced pain response.     

A breath-holding challenge in panic disorder patients,their healthy first-degree relatives,and normal controls

Our aim was to observe the induction of panic attacks (PA) symptoms by a breath-hold test in panic disorder (PD) patients as the Diagnostic and Statistical Manual for Mental Disorders 4th edition (DSM-IV) and their healthy first-degree relatives. We randomly selected 26 PD patients, 28 healthy first-degree relatives of probands with PD and 25 normal volunteers with no family history of PD. They were induced to breath-hold for as long as possible four times with a two-min interval between them. Anxiety scales were applied before and after the test. Using specific PA criteria, 46.1% (n=12) PD patients, 7.1% (n=2) first-degree relatives and 4.0% (n=1) control subjects had a PA after the test (chi(2)=7.82, df=2, P=0.023). There was no heart rate, anxiety levels or breath-hold time differences among the groups. In this breath hold challenge test PD patients were more sensitive to breath-hold than first-degree relatives and normal volunteers.     

Hyperventilation is not diagnostically specific to panic patients.

It has been claimed that hyperventilation is a cause of panic attacks in patients suffering from panic disorder (PD), and various studies have, in fact, documented low resting CO2 in PD patients. However, most comparisons have been made using non-psychiatric controls. Since increased ventilation is a common concomitant of distress, the relevance of using healthy/non-anxious control groups may be questioned. Respiratory peculiarities of PD patients may actually just reflect background anxiety rather than a diagnostically specific feature. In order to explore the possible diagnostic specificity of hyperventilation, as well as increased respiratory rate and respiratory variability, to PD patients, capnographic patterns were analyzed from PD patients, non-panic disorder anxiety patients, and healthy controls. Capnographic data were obtained while subjects were resting, watching an exciting film, relaxing, and being exposed to idiosyncratically relevant fearful imagery. Findings were robust. As found in most studies, PD patients had lower resting CO2 than healthy controls; however, that of non-panic disorder anxiety patients was just as low as PD patients. The exciting film and fearful imagery produced consistent increases in distress and concomitant increases in respiratory rate, variability of end-tidal CO2, and decreases in end-tidal CO2. However, this was similar in all three groups. Data suggest that hyperventilation is not specific to PD patients.     

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.     

A comparison of patients with illness phobia and panic disorder.

Fourteen subjects with illness phobia, a subtype of hypochondriasis, were compared with an equal number of subjects with panic disorder who had been matched for age and sex. The illness phobic subjects differed from panic subjects in not having spontaneous panic attacks or agoraphobic symptoms, the characteristic features of panic disorder. The onset of illness phobia was related to experience with illness in half the subjects. Half of the illness phobic subjects also had family histories of anxiety disorders. The results suggest that illness phobia is distinct from panic disorder and that it is a disorder in which environmental and genetic factors are etiologically important.     

Association testing of panic disorder candidate genes using CCK-4 challenge in healthy volunteers

Despite continuing efforts to determine genetic vulnerability to panic disorder (PD), the studies of candidate genes in this disorder have produced inconsistent or negative, results. Laboratory panic induction may have a potential in testing genetic substrate of PD. In this study we aimed to explore the effects of several genetic polymorphisms previously implicated in PD on the susceptibility to cholecystokinin-tetrapeptide (CCK-4) challenge in healthy subjects. The study sample consisted of 110 healthy volunteers (47 males and 63 females, mean age 22.2 +/- 5.2) who participated in CCK-4 challenge test. Nine gene-candidates, including 5-HTTLPR, MAO-A VNTR, TPH2 rs1386494, 5-HTR1A -1019C-G, 5-HTR2A 102T-C, CCKR1 246G-A, CCKR2 -215C-A, DRD1 -94G-A and COMT Val158Met, were selected for genotyping based on previous positive findings from genetic association studies in PD. After CCK-4 challenge, 39 (35.5%) subjects experienced a panic attack, while 71 subjects were defined as non-panickers. We detected significant differences for both genotypic and allelic frequencies of 1386494A/G polymorphism in TPH2 gene between panic and non-panic groups with the frequencies of G/G genotype and G allele significantly higher in panickers. None of the other candidate loci were significantly associated with CCK-4-induced panic attacks in healthy subjects. In line with our previous association study in patients with PD, we detected a possible association between TPH2 rs1386494 polymorphism and susceptibility to panic attacks. Other polymorphisms previously associated with PD were unrelated to CCK-4-induced panic attacks, probably due to the differences between complex nature of PD and laboratory panic model.