Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor

Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain serotonin turnover most likely derived not from impaired serotonin reuptake, but from increased firing in serotonergic midbrain raphe neurons projecting to both subcortical brain regions and the cerebral cortex.     

Feared consequences of panic attacks in panic disorder: a qualitative and quantitative analysis

Cognitions are hypothesized to play a central role in panic disorder (PD). Previous studies have used questionnaires to assess cognitive content, focusing on prototypical cognitions associated with PD; however, few studies have qualitatively examined cognitions associated with the feared consequences of panic attacks. The purpose of this study was to conduct a qualitative and quantitative analysis of feared consequences of panic attacks. The initial, qualitative analysis resulted in the development of 32 categories of feared consequences. The categories were derived from participant responses to a standardized, semi-structured question (n = 207). Five expert-derived categories were then utilized to quantitatively examine the relationship between cognitions and indicators of PD severity. Cognitions did not predict PD severity; however, correlational analyses indicated some predictive validity to the expert-derived categories. The qualitative analysis identified additional areas of patient-reported concern not included in previous research that may be important in the assessment and treatment of PD.     

Heartbeat perception in panic disorder: a reanalysis

This article describes a reanalysis of seven studies on heart beat perception (HBP) in panic disorder. The pooled sample had 709 participants from eight diagnostic categories. Accurate HBP was uncommon, but more prevalent among panic disorder patients than among healthy controls, depressed patients, patients with palpitations and individuals with infrequent panic attacks. No differences were found between panic disorder patients and patients with other anxiety disorders. Accurate perceivers had higher anxiety sensitivity scores than inaccurate perceivers. The data remain inconclusive as to whether perceived heart rate is correlated with anxiety in inaccurate perceivers. Physical exercise, distraction, variations in instructions and treatment each influenced HBP. However, the influence was different than previously thought. Finally, it is suggested that HBP may be understood in terms of schema-guided information processing.     

Anxiety sensitivity and panic attacks in a nonclinical population

In the present study, we administered the Anxiety Sensitivity Index (ASI) and a modified version of the Panic Attack Questionnaire (PAQ) to 425 college students to determine whether high anxiety sensitivity ('fear of fear') occurs in the absence of a history of unpredictable ('spontaneous') panic attacks, or whether such attacks are a necessary precursor to high anxiety sensitivity. Based on their ASI scores, subjects were assigned to either the high, medium, or low anxiety sensitivity groups. High anxiety sensitivity subjects more frequently reported both a personal and family history of panic than did subjects in the other groups. Nevertheless, two-thirds of the high anxiety sensitivity subjects had never experienced an unpredictable panic attack. This suggests that the fear of anxiety can be acquired in ways other than through personal experience with panic.     

Rorschach-profile in panic disorder

The Rorschach test was applied to four groups: 41 Panic Disorder (PD), 14 Major Depression (MD), 11 Generalized Anxiety Disorder (GAD) and 18 normal subjects. The aims were to describe the test profile of PD patients and to discuss implications for cognitive processing ability and personality structure. A hypothesis of a borderline personality structure in PD patients, based on psychodynamic literature, was tested, but was not unambiguously supported. A "loose", borderline-like personality structure and disturbances in processing abilities, however, characterized PD-patients. The normal subjects surprisingly provided many Fabulized Combinations, a response type, considered suspect of borderline pathology, but also showed more signs of integrative and synthesizing abilities than the other groups.     

Oedipal dynamics in panic disorder

Both research and clinical work have revealed factors that can lead to the onset and persistence of panic disorder. Preoedipal conflicts intensify the danger of oedipal longings for panic patients. Competition with the same-sex parent is linked with angry preoedipal fantasies and associated fears of disruption in attachments. Fantasies or actual successes can thus trigger panic episodes. Regression to a helpless, dependent state such as panic defends against the danger of aggressive, competitive fantasies and actual achievements. However, the regressive state can also be experienced as dangerous, and can be linked with frightening homosexual fantasies. A reactive aggressive oedipal stance can sometimes result, triggering escalating turmoil. The panic episode serves a series of compromise formations in dealing with these conflicted wishes.     

Psychological approaches to panic disorder: a review

Panic disorder has been the subject of considerable research and controversy. Though biological conceptualizations have been predominant, psychological theorists have recently advanced conditioning, personality, and cognitive hypotheses to explain the etiology of panic disorder. The purpose of this article is to provide an empirical and conceptual analysis of these psychological hypotheses. This review covers variants of the "fear-of-fear" construal of panic disorder (i.e., Pavlovian interoceptive conditioning, catastrophic misinterpretation of bodily sensations, anxiety sensitivity), research on predictability (i.e., expectancies) and controllability, and research on information-processing biases believed to underlie the phenomenology of panic. Suggestions for future research are made.     

Attentional fixation in panic disorder

According to Beck's (1988) clinical observations, patients with panic disorder describe a fixation on their distressing physical and psychological symptoms and an inability to access corrective information during panic attacks. The present study sought to evaluate empirically the notion that attentional fixation is characteristic of these patients. A subset of panic patients participating in 3 cognitive therapy clinical trials completed the Attentional Fixation Questionnaire (AFQ) at intake, during treatment and at termination. The AFQ had adequate internal consistency at all time intervals, and it correlated positively with measures of depression, anxiety and distorted cognitive content. At termination, the AFQ total score and nearly all single items decreased significantly, and patients who continued to meet diagnostic criteria for panic disorder scored higher on most items than patients who no longer met diagnostic criteria for panic disorder. These preliminary data suggest that attentional fixation is an important dimension of cognition relevant to panic disorder.     

The reliability and validity of the panic disorder self-report: a new diagnostic screening measure of panic disorder

This study examined the Panic Disorder Self-Report (PDSR), a new self-report diagnostic measure of panic disorder based on the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994). PDSR diagnoses were compared with structured interview diagnoses of individuals with generalized anxiety disorder, social phobia, and panic disorder and nonanxious controls. Receiver operating characteristic analyses revealed that the PDSR showed 100% specificity and 89% sensitivity. The PDSR also demonstrated retest reliability, convergent and discriminant validity, and kappa agreement of .93 with a structured interview. Finally, the PDSR demonstrated clinical validity. Students who were identified as having panic disorder using the PDSR did not have significantly different scores on the Panic Disorder Severity Scale--Self-Report form (P. R. Houck, D. A. Speigel, M. K. Shear, & P. Rucci, 2002) than a panic disordered community sample. However, both groups had significantly higher scores than students identified as not meeting criteria for panic disorder.     

Reporting experiences of panic: Sex differences in a community survey

This report aims to look at whether the results of a community survey of the prevalence of panic attacks and panic disorder could be influenced by a possible sex difference in the willingness to return screening questionnaires and to acknowledge psychiatric symptoms. The results suggest that men are less likely to return questionnaires, and that this effect is more marked in the younger age groups. This could indicate that an important group of people is being under-represented in prevalence figures for panic and possibly other psychiatric diagnoses.     

Treatment-resistant panic disorder

A substantial number of patients with panic disorder and agoraphobia may remain symptomatic after standard treatment (including selective serotonin reuptake inhibitors, tricyclic antidepressants, benzodiazepines, or irreversible monamine oxidase inhibitors). In this review, recommendations for the treatment of patients with panic disorder and agoraphobia who do not respond to these drugs are provided. Nonresponse to drug treatment could be defined as a failure to achieve a 50% reduction on a standard rating scale after a minimum of 6 weeks of treatment in adequate dose. When initial treatments have failed, the medication should be changed to other standard treatments. In further attempts at treatment, drugs should be used that have shown promising results in preliminary studies, such as venlafaxine. Combination treatments may be used, such as the combination of an selective serotonin reuptake inhibitor and a benzodiazepine. Psychological treatments such as cognitive-behavioral therapy have to be considered in all patients, regardless whether they are nonresponders or not. According to existing studies, a combination of pharmacologic treatment with cognitive-behavioral therapy can be recommended.     

Avoidant coping in panic disorder: a yohimbine biological challenge study

Abstract

Few studies have addressed whether the use of avoidance-oriented coping strategies is related to the development of panic in patients with panic disorder(PD). Self-report, clinician-rated, and physiological data were collected from 42 individuals who participated in a yohimbine biological challenge study, performed under double-blind, placebo-controlled conditions. Participants included 20 healthy controls and 22 currently symptomatic patients who met DSM-IV-TR diagnostic criteria for PD. Consistent with prediction, patients with PD who had higher perceived efficacy of avoidance-oriented strategies in reducing anxiety-related thoughts reported increased severity in panic symptoms during the yohimbine challenge condition as compared to the placebo. Further, patients with PD who had more fear of cognitive dyscontrol, cardiovascular symptoms, and publicly observable anxiety also reported increased severity in panic symptoms during the challenge. Healthy controls who had more fear of cardiovascular symptoms similarly reported increased severity in panic symptoms during the challenge. No effects were found for heart rate response to the challenge agent. These results provide support for the role of avoidance-oriented coping strategies and fear of anxiety-related symptoms as risk and maintenance factors in the development of panic symptoms, particularly within a biological challenge model.