Jeffrey C. Richards

Internet vs. paper and pencil administration of questionnaires commonly used in panic/agoraphobia research

The aim of this study was to investigate the psychometric properties of Internet administered questionnaires used in panic research. Included were 494 people who had registered for an Internet-based treatment program for panic disorder (PD). Participants were randomly assigned to fill in the questionnaires either on the Internet or the paper-and-pencil versions, and then to fill in the same questionnaires again the next day using the other format. The questionnaires were the body sensations questionnaire [BSQ; Chambless, D. L., Caputo, G. C., Bright, P., & Gallagher, R. (1984). Assessment of fear of fear in agoraphobics: the body sensations questionnaire and the agoraphobic cognitions questionnaire. Journal of Consulting and Clinical Psychology, 52, 1090-1097], agoraphobic cognitions questionnaire [ACQ; Chambless, D. L., Caputo, G. C., Bright, P., & Gallagher, R. (1984). Assessment of fear of fear in agoraphobics: the body sensations questionnaire and the agoraphobic cognitions questionnaire. Journal of Consulting and Clinical Psychology, 52, 1090-1097], mobility inventory [MI; Chambless, D. L., Caputo, G., Jasin, S., Gracely, E. J., & Williams, C. (1985). The mobility inventory for agoraphobia. Behaviour Research and Therapy, 23, 35-44], beck anxiety inventory [BAI; Beck, A. T., Epstein, N., Brown, G., & Steer, R. A. (1988). An inventory for measuring clinical anxiety: psychometric properties. Journal of Consulting and Clinical Psychology, 56, 893-897], beck depression inventory II [Beck, A. T., & Steer, R. A. (1996). Beck Depression Inventory. Manual, Svensk version (Swedish version). Fagernes, Norway: Psykologiforlaget, AB], quality of life inventory [QOLI; Frisch, M. B., Cornell, J., Villanueva, M., & Retzlaff, P. J. (1992). Clinical validation of the quality of life inventory. A measure of life satisfaction for use in treatment planning and outcome assessment. Psychological Assessment, 4, 92-101], and montgomery Asberg depression rating scale [MADRS; Svanborg, P., & Asberg, M. (1994). A new self-rating scale for depression and anxiety states based on the comprehensive psychopathological rating scale. ACTA Psychiatrica Scandinavica, 89, 21-28]. Results showed largely equivalent psychometric properties for the two administration formats (Cronbachs @a between 0.79 and 0.95). The results also showed high and significant correlations between the Internet and the paper-and-pencil versions. Analyses of order effects showed an interaction effect for the BSQ and the MI (subscale Accompanied), a main effect was identified for ACQ, MI-Alone, BAI and BDI II. However, in contrast to previous research, the Internet version did not consistently generate higher scores and effect sizes for the differences were generally low. Given the presence of an interaction effect, we recommend that the administration format should be stable in research across measurement points. Finally, the findings suggest that Internet versions of questionnaires used in PD research can be used with confidence.

Psychophysiological mechanisms in panic disorder: a correlative analysis of noradrenaline spillover, neuronal noradrenaline reuptake, power spectral analysis of heart rate variability, and psychological variables.

Background: The risk of adverse clinical cardiac events is increased in patients with panic disorder (PD). We evaluated possible mechanistic links between PD and heart disease. We estimated cardiac vagal activity from heart rate variability (HRV) measurements and quantified sympathetic nervous system (SNS) activity using plasma noradrenaline tracer kinetics methodology. Methods: Thirty-nine people with PD and 39 age- and gender-matched healthy volunteers were studied. In 19 participants with PD, both HRV and plasma noradrenaline kinetics were tested; in 20 with PD and 20 healthy volunteers, HRV measurements only were made, whereas in 19 healthy volunteers, noradrenaline kinetics only was tested. All panic disorder participants completed psychological measures of anxiety sensitivity and state and trait anxiety; healthy volunteers in whom HRV was measured also provided psychological measures. Results: Sympathetic nervous tone in the heart, based on rates of cardiac noradrenaline spillover, was normal in PD. Noradrenaline and adrenaline plasma clearance and plasma tritiated noradrenaline and adrenaline extraction in transit through the heart, all dependent on the noradrenaline transporter (NET), were reduced in PD. Psychometric testing linked inhibition of anger to this deficit in NET functioning. Anxiety sensitivity was specifically associated with impaired cardiac NET. High- and low-frequency heart rate spectral power was unrelated to all plasma noradrenaline kinetics measurements. Conclusion: Defective neuronal reuptake of noradrenaline, by augmenting the sympathetic neural signal in the heart, might have a dual effect, sensitizing the heart such as to lead to symptom development (and thus perhaps causing panic disorder) and, second, potentially contributing to adverse cardiac events in established PD. PD = panic disorder; CVD = cardiovascular disease; CAD = coronary artery disease; HRV = heart rate variability; LF = low frequency; ADIS-IV = Anxiety Disorders Interview Schedule for DSM-IV; ASP = Anxiety Sensitivity Profile; ASI = Anxiety Sensitivity Index; NET = noradrenaline transporter; SSRI = selective serotonin reuptake inhibiting; HF = high frequency; MAO = monoamine oxidase.

Extension and Replication of an Internet-Based Treatment Program for Panic Disorder

This study describes an internet-based intervention for people with panic disorder that consisted of a 5-module program. Participants accessed the program for 5-8 weeks and were then re-assessed 3 months later. Use of the program was associated with reductions in severity of panic disorder and in catastrophic misinterpretation of ambiguous panic body sensations in 9 people with this anxiety disorder. There were also non-significant trends for body vigilance to decrease over the course of the study. Further investigations of the efficacy of this medium for the treatment of panic disorder and the associated mechanisms of change are warranted.

Internet cognitive behavioural therapy for panic disorder: Does the inclusion of stress management information improve end-state functioning?

Previous research has established Internet-based cognitive behavioural therapy (CBT) for panic disorder (PD) as effective in reducing panic severity and frequency. There is evidence, however, that such programs are less effective at improving overall end-state functioning, defined by a PD clinician severity rating of ≤2 and panic free. In order to test the effect on end-state functioning of the incorporation of stress management material within a CBT program for PD, 32 people with PD were randomised to either Internet-based CBT (PO1), Internet-based CBT plus stress management (PO2) or an Internet-based information-only control condition (IC). Both CBT treatments were more effective at posttreatment assessment than the control condition in reducing PD severity, panic and agoraphobia-related cognition, negative affect and self-ratings of health. PO2 was more effective than PO1 at posttreatment assessment on PD severity and general anxiety, although at 3-month follow-up these differences were no longer apparent. This study provides further support for the efficacy of Internet-based CBT for PD and suggests that although the incorporation of stress management material confers short-term advantages over a standard program, it is not associated with any longer term improvements on panic severity and related cognitions, negative affect, general wellbeing and end-state functioning.

The neuronal noradrenaline transporter, anxiety and cardiovascular disease

Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses. The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients. Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic ‘co-morbidity’ perhaps underlies the clinical concordance. Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.

Internet-based treatment for panic disorder

Increasingly, the internet is being used as a source of mental health information as well as structured treatment programs for people with mental health concerns or problems. The present review focuses mainly on research conducted at the University of Ballarat in Australia, and Uppsala University in Sweden, on internet-based treatment for panic disorder, one of the more common and disabling anxiety disorders. Our studies suggest that internet-based cognitive behavioural therapy is an effective intervention for panic disorder, and that it is more effective than some other self-help therapies. We have found that this mode of intervention is associated with clinically significant change, improved psychological well-being and functioning, and low participant attrition, provided that timely, limited therapist assistance is also provided. This review also discusses treatment credibility and participant satisfaction, as well as assessment and crisis management issues. Although promising as a form of intervention, there is a need for more research on the efficacy of internet-based treatment for PD and on comparisons with evidence-based face-to-face therapies.

Serum Lipids and Their Relationships With Hostility and Angry Affect and Behaviors in Men

Research into the relationship between the Type A behavior pattern and coronary heart disease suggests that the anger-hostility-aggression (AHA!) syndrome is directly related to total serum cholesterol and low-density lipoproteins. The present study involved an investigation of the specific components of the AHA! syndrome related to blood lipid levels in 98 healthy men. The disposition to experience and express anger when frustrated, criticized, or treated unfairly (angry reaction, a component of trait anger) was related to total serum cholesterol and to low-density lipoprotein levels. Age and diet also predicted levels of these lipids, but each was unrelated to angry reaction. These results suggest that in healthy men, the experience of strong angry affect in reaction to perceived rejection, criticism, or unfair treatment may be health-toxic because of its relationship to elevated unfavorable serum lipids.

Interpretation of Ambiguous Interoceptive Stimuli in Panic Disorder and Nonclinical Panic

Cognitive bias in the misinterpretation of ambiguous interoceptive stimuli has been demonstrated in panic disorder. This study investigated whether this cognitive bias also occurs in people with nonclinical panic who are at risk of developing panic disorder. The responses of 25 people with nonclinical panic were compared to those of 20 people with panic disorder and 69 nonpanic controls on a measure of interpretive bias, the Brief Body Sensations Interpretation Questionnaire. There was evidence for interpretive cognitive bias for ambiguous interoceptive stimuli among the nonclinical panickers which did not differ from that of the people with panic disorder, but which differed from the nonpanic controls. High anxiety sensitivity predicted interpretive bias toward both interoceptive and external stimuli. Results therefore suggest that interpretive cognitive bias for ambiguous interoceptive stimuli may be a risk factor for the development of panic disorder.

Single-unit analysis of sympathetic nervous discharges in patients with panic disorder.

Patients with panic disorder are at increased cardiac risk. While the mechanisms responsible remain unknown, activation of the sympathetic nervous system may be implicated. Using isotope dilution methodology, investigations of whole‐body and regional sympathetic nervous activity have failed to show any differences between patients with panic disorder and healthy subjects. Using direct recording of single unit efferent sympathetic vasoconstrictor nerve activity by microneurography we examined sympathetic nervous function in patients with panic disorder more precisely than previously reported. The activity of multiunit and single unit vasoconstrictor sympathetic nerves was recorded at rest at the level of the peroneal nerve in 10 patients diagnosed with panic disorder and in nine matched healthy volunteers. Multiunit sympathetic activity was not different between the two groups (26 ± 3 bursts min−1 in patients with panic disorder and 28 ± 3 bursts min−1 in controls). The firing frequency of single unit vasoconstrictor neurones was also similar between the two groups (0.38 ± 0.09 versus 0.22 ± 0.03 Hz). However, the probability of firing during a sympathetic burst was higher in patients with panic disorder compared with healthy controls (45 ± 5%versus 32 ± 3%, P < 0.05). When only the neural bursts during which the vasoconstrictor neurone was active were considered, we found that in patients with panic disorder the neurones tended to fire more often in a ‘multiple spike’ pattern than in the controls (i.e. the probability of the neurone firing twice was 25 ± 3% in patients with panic disorder compared with 14 ± 3% in controls). Quantification from single vasoconstrictor unit recording provides evidence of a disturbed sympathetic firing pattern in patients with panic disorder.

Cardiac Sympathetic Nerve Biology and Brain Monoamine Turnover in Panic Disorder

Abstract: Panic disorder serves as a clinical model for testing whether mental stress can cause heart disease. Our own cardiologic management of panic disorder provides case material of recurrent emergency room attendances with angina and electrocardiogram ischemia, triggered arrhythmias (atrial fibrillation, ventricular fibrillation), and documented coronary artery spasm, in some cases with coronary spasm being complicated by coronary thrombosis. Application of radiotracer catecholamine kinetics and clinical microneurography methodology suggests there is a genetic predisposition to panic disorder that involves faulty neuronal norepinephrine uptake, possibly sensitizing the heart to symptom generation. During panic attacks there are large sympathetic bursts, recorded by clinical microneurography in the muscle sympathetic nerve neurogram, and large increases in cardiac norepinephrine spillover, accompanied by surges of adrenal medullary epinephrine secretion. In other conditions such as heart failure and presumably here also, a high level of sympathetic nervous activation can mediate increased cardiac risk. The sympathetic nerve cotransmitter, neuropeptide Y (NPY), is released from the cardiac sympathetics during panic attacks, an intriguing finding given that NPY can cause coronary artery spasm. There is ongoing, continuous release of epinephrine from the heart in panic sufferers, perhaps attributable to epinephrine loading of cardiac sympathetic nerves by uptake from plasma during panic attacks, or possibly to in situ synthesis of epinephrine through the action of intracardiac phenylethanolamine‐N‐methytransferase (PNMT) activated by repeated cortisol responses. We have used internal jugular venous sampling and measurement of overflowing lipophilic brain monoamine metabolites to quantify brain norepinephrine and serotonin turnover in untreated patients with panic disorder. We find normal norepinephrine turnover but a marked increase in brain serotonin turnover in patients with panic disorder, in the absence of a panic attack, which presumably represents an underlying neurotransmitter substrate for the condition.