Background: The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG). Methods: Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test. Results: Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks. Conclusions: We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder.

The correct development and function of CNS is critical for brain health of the organism. Early or chronic stress causes prominent alterations in brain function, and affects the expression of neurotrophic factors in limbic brain regions involved in the regulation of mood and cognition. Recent evidences have opened the idea that in complex organisms, an altered expression of certain neurotrophins by stress could be involved in the onset and pathophysiology of most psychiatric disorders, such as depression, squizophrenia or anxiety disorders. It is hypothesized that altered levels of neurotrophic factors could contribute to the atrophy and cell death of these regions, including the hippocampus and prefrontal cortex, which would produce a malfunction in limbic-related areas, and as a consequence, a precipitation or worsening of psychiatric illnesses. We were interested in panic disorder pathophysiology, which is a stress-related disorder and is characterized by an altered cognitive processing of emotional information. Although little evidence has been found supporting a neurotrophic role in PD, recent data has revealed that NT-3/TrkC signaling might play a key role in limbic system morphology and function. Therefore, we suggest that NT-3/TrkC system is involved in PD pathogenesis. The main objective in the work of this doctoral thesis lie to determine the role of NTRK3 gene, that codifies for TrKC, in emotional cognition and stress response processes that underlies PD. To this end, we used a genetically modified mouse model of NTRK3 overexpression, which was validated as a model of PD. Here, it is characterized the effects produced by the increase of NTRK3 expression in the CNS, focusing in neural alterations that might influence changes in cognitive processes involved in coping strategies. Moreover, it is studied the mechanisms that underlie in these processes by different approaches, 1/physiologically, measuring the HPA axis response, 2/brain activation, analyzing the activation pattern to a stress stimulus, 3/cellular and gene expression profiling, characterizing key brain regions in cognitive processes, and 4/pharmacologically, studying neurotransmitters function.

Theoretischer Hintergrund: Die Rolle der Therapeutenbegleitung während Expositionsübungen bei Panikstörung mit Agoraphobie (P/A) ist bislang ungeklärt. Eine kürzlich durchgeführte klinische Studie (MAC-Studie) lieferte Hinweise auf ein günstigeres Behandlungsergebnis bei Therapeutenbegleitung. Fragestellung: Wie lassen sich Effekte therapeutenbegleiteter Exposition (T+) im Vergleich zu Exposition ohne Therapeutenbegleitung (T–) erklären? Methode: Daten von 301 Patienten, die eine expositionsbasierte KVT mit bzw. ohne Therapeutenbegleitung erhalten hatten, wurden analysiert. Untersucht wurden der Einfluss der initialen Störungsschwere, des Sicherheitsverhaltens sowie differenzielle Effekte der Bedingungen auf die Angst vor der Angst. Zusätzlich wurde überprüft, inwieweit die Übungshäufigkeit in den Behandlungsbedingungen variiert und einen Mediator des Behandlungserfolgs darstellt. Ergebnisse: Störungsschwere und Sicherheitsverhalten zeigten keine differenziellen Effekte zwischen den Bedingungen; die T+ Bedingung führte jedoch zu stärkeren Reduktionen der Angst vor der Angst im Angstsensitivitätsindex. Patienten der T+ Bedingung führten häufiger selbständig Expositionsübungen durch, während Patienten in T– im Durchschnitt länger übten. Die Übungshäufigkeit stellte dabei einen Mediator des Behandlungserfolgs dar. Schlussfolgerungen: Günstigere Effekte einer therapeutenbegleiteten Exposition gehen auf stärkere Reduktionen der Angst vor der Angst sowie auf eine höhere Übungshäufigkeit im Selbstmanagement zurück. / Theoretical background: There is a paucity of studies examining the role of therapist guidance during in-vivo exposure for panic disorder with agoraphobia (PD/AG). A recent study (MAC-study) suggested superior effects of therapist-guided exposure compared to programmed practice. Objectives: Examining potential mechanisms of therapist-guided exposure. Methods: Data from 301 patients with PD/AG who received either CBT with therapist guidance during in-vivo exposure (T+), or CBT with programmed exposure practice (T–) were analysed in regard to effects of initial symptom severity, subtle avoidance behaviours, reductions in fear of fear, and frequency of exposure homework. Results: There were no interaction effects between symptom severity or subtle avoidance and outcome. T+ was associated with higher reductions in fear of fear as well as with higher frequency of exposure homework. Frequency of exposure homework mediated the effect of group on outcome. Conclusion: Advantages of therapist-guided exposure as well as frequency of self-exposure might be attributed to higher reductions in fear of fear.

Panic Disorder (PD) has been associated with abnormalities in the respiratory system for a long time, and treatment programs aimed at reversing these abnormalities have been developed. Panicogenic effects of biological challenges have been shown to be altered after successful treatment. Furthermore, there is evidence that anxious non-PD patients show similar responses to these challenges and hence may benefit from some kind of breathing training (BT). To test these assumptions, we recruited 45 PD patients, 39 Episodic Anxiety (EA) patients who suffered from subclinical panic attacks, and 20 non-anxious controls (NAC). Patients were randomized to one of two versions of a 4-week therapy with BT, either lower or raise end-tidal pCO2, or a waiting list (WL). Before and after treatment, participants underwent in randomized order a Voluntary Hypoventilation (VHO) test and a Voluntary Hyperventilation (VHT) test in which they were asked to either lower or raise their pCO2 while psychophysiological measures were recorded. Each test consisted of 3 segments: 1 min baseline, 3 min paced breathing, and 8 min recovery. Before treatment, PD and EA patients were more anxious, distressed, tense, and worried than NAC, and felt more dizziness, chest pain, and nausea during the laboratory assessment. However, increases in psychological symptoms or physiological sensations from baseline to the paced breathing segments were not different between groups. The two tests produced similar changes except that anxiety and dizziness increased more during the VHT than VHO. We replicated baseline breathing abnormalities previously reported for PD patients, namely greater respiration rate, tidal volume instability, and number of sighs. However, analyses did not find that patients recovered slower to either challenge. After treatment, both therapies improved on the main outcome measure. Furthermore, BT affected baseline pCO2, resulting in lower levels in the hypocapnic groups and higher levels in the hypercapnic groups without affecting any other measures. We conclude that baseline respiratory abnormalities are specific to PD. However, data suggest that the manipulations might have been too weak to elicit other previously reported group differences. Breathing training was equally effective for the lower and raise BT. Hence, factors unrelated to modifying one’s pCO2 must have accounted for the symptomatic improvement. Breathing training should not be restricted to PD but be applied to all patients suffering from anxiety attacks.

No description available.

Thesis (Ph.D.) in Psychology--University of Maine, 2004. / Includes bibliographical references (leaves 136-169).

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Desde a síndrome do coração irritável, passando pelas diversas síndromes do fin de siècle e chegando ao triunfo das teorias neurocientíficas sobre a hipersensibilidade dos centros cerebrais de resposta ao alarme e sufocação, a Medicina buscou teorias para explicar a experiência de pavor. Investiga-se o modo como ocorreram, ao longo da história, as transformações da atenção médica sobre o medo e os estados mórbidos que o acompanham. Ao se buscar na literatura médica vestígios de análises científicas sobre o mal-estar intenso, do meio do século XIX ao fim do XX, não se pretendeu construir uma história triunfalista, de modo que as teorias atuais pudessem ganhar status de superioridade em relação às do passado. Evidenciou-se, sim, a importância cultural e a força histórica de cada uma delas, salientando as possíveis continuidades e rupturas de sentido que elas assumiram. / From irritable heart syndrome, through the various syndromes of the fin de siècle and the coming triumph of neuroscientific theories about the brain centers of the hypersensitivity response to the alarm and suffocation, Medicine sought for theories to explain the experience of terror. This essay examines the way it occurred throughout history the transformation of medical concern on fear and several emotional states that come with it. By searching the medical literature on scientific analysis traces of the intense discomfort related to fear, from the mid-nineteenth century to the end of the twentieth century, we did not intend to build a triumphalist history, so that current theories could gain status of superiority in relation to the previous ones. Instead of it, the cultural and historical force of each theory was evidenced, emphasizing the possible continuities and disruptions in the meanings that they assumed.

Syftet med föreliggande studie var att vidareutveckla en behandlingsspecifik följsamhetsskala för paniksyndrom vid internetförmedlad kognitiv beteendeterapi (IKBT). Studiens frågeställningar var 1) uppnår skalan tillräcklig interbedömarreliabilitet, 2) finns det ett samband mellan skalan och det tidigare använda följsamhetsmåttet antalet genomförda moduler, och 3) finns det ett samband mellan skalan och behandlingsutfallet. Interbedömarreliabiliteten mellan två bedömare testades genom två omgångar samskattning. 80 deltagare som behandlades med IKBT för paniksyndrom vid enheten för internetpsykiatri i Stockholm skattades sedan enligt den behandlingsspecifika följsamhetsskalan. Även antalet moduler deltagarna genomförde registrerades. Resultaten visade att skalan sammantaget hade en god interbedömarreliabilitet. Vidare korrelerade följsamhetsskalan positivt med både antalet genomförda moduler och behandlingsutfallet. Slutsats: Skattningsskalan vidareutvecklad i föreliggande studie visade indikationer på att vara ett tillförlitligt och användbart instrument för att mäta följsamheten till IKBT vid paniksyndrom. / The purpose of this study was to further develop a treatment-specific rating scale for adherence to internet-based cognitive behavioural therapy (ICBT) for panic disorder. The research questions for this study were 1) does the rating scale show satisfying inter-rater reliability, 2) is there an association between the rating scale and the commonly used measurement of adherence, module completion, and 3) is there an association between the rating scale and treatment outcome. The inter-rater reliability between two raters was assessed twice. 80 participants treated with ICBT for panic disorder at Internetpsykiatrin (the unit for internet-based cognitive behavioural therapy in Stockholm) were then assessed using the treatment-specific rating scale for adherence. Module completion was also registered. Results show that the rating scale had an overall satisfying inter-rater reliability. Furthermore, the rating scale correlated positively with both module completion and treatment outcome. Conclusion: The rating scale further developed in the present study showed indications of being a reliable and useful instrument for measuring adherence to ICBT for panic disorder.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Desde a síndrome do coração irritável, passando pelas diversas síndromes do fin de siècle e chegando ao triunfo das teorias neurocientíficas sobre a hipersensibilidade dos centros cerebrais de resposta ao alarme e sufocação, a Medicina buscou teorias para explicar a experiência de pavor. Investiga-se o modo como ocorreram, ao longo da história, as transformações da atenção médica sobre o medo e os estados mórbidos que o acompanham. Ao se buscar na literatura médica vestígios de análises científicas sobre o mal-estar intenso, do meio do século XIX ao fim do XX, não se pretendeu construir uma história triunfalista, de modo que as teorias atuais pudessem ganhar status de superioridade em relação às do passado. Evidenciou-se, sim, a importância cultural e a força histórica de cada uma delas, salientando as possíveis continuidades e rupturas de sentido que elas assumiram. / From irritable heart syndrome, through the various syndromes of the fin de siècle and the coming triumph of neuroscientific theories about the brain centers of the hypersensitivity response to the alarm and suffocation, Medicine sought for theories to explain the experience of terror. This essay examines the way it occurred throughout history the transformation of medical concern on fear and several emotional states that come with it. By searching the medical literature on scientific analysis traces of the intense discomfort related to fear, from the mid-nineteenth century to the end of the twentieth century, we did not intend to build a triumphalist history, so that current theories could gain status of superiority in relation to the previous ones. Instead of it, the cultural and historical force of each theory was evidenced, emphasizing the possible continuities and disruptions in the meanings that they assumed.

Background: The relationship of panic attacks (PA), panic disorder (PD) and agoraphobia (AG) is controversial. The aim of the current study is to prospectively examine the 10-year natural course of PA, PD and AG in the first three decades of life, their stability and their reciprocal transitions. Methods: DSM-IV syndromes were assessed via Composite International Diagnostic Interview – Munich version in a 10-year prospective-longitudinal community study of 3,021 subjects aged 14–24 years at baseline. Results: (1) Incidence patterns for PA (9.4%), PD (with and without AG: 3.4%) and AG (5.3%) revealed differences in age of onset, incidence risk and gender differentiation. (2) Temporally primary PA and PD revealed only a moderately increased risk for subsequent onset of AG, and primary AG had an even lower risk for subsequent PA and PD. (3) In strictly prospective analyses, all baseline groups (PA, PD, AG) had low remission rates (0–23%). Baseline PD with AG or AG with PA were more likely to have follow-up AG, PA and other anxiety disorders and more frequent complications (impairment, disability, help-seeking, comorbidity) as compared to PD without AG and AG without PA. Conclusions: Differences in incidence patterns, syndrome progression and outcome, and syndrome stability over time indicate that AG exists as a clinically significant phobic condition independent of PD. The majority of agoraphobic subjects in this community sample never experienced PA, calling into question the current pathogenic assumptions underlying the classification of AG as merely a consequence of panic. The findings point to the necessity of rethinking diagnostic concepts and DSM diagnostic hierarchies.