Smoking, physical activity and respiratory irregularities in patients with panic disorder.

BACKGROUND: In the past decades different evidences suggested a relationship between panic disorder (PD) and respiration, among which the presence of different respiratory irregularities at rest in PD patients. It has been hypothesized that PD could be characterized by a dysfunction of those areas involved in the central control of respiration. The aim of the present study was to elucidate possible differences in breath-by-breath respiratory function at rest between a sample of PD patients with agoraphobia and healthy controls (HC), with particular attention to smoking and physical activity as possible relevant factors in the understanding of respiratory dynamics in PD. METHODS: Respiratory physiology was assessed in 32 PD patients and 24 HC. Respiratory rate (RR), tidal volume (VT), minute ventilation (VE), and end-tidal CO2 (pCO2) have been assessed. RESULTS: A significant diagnosis-by-smoking interaction was found for mean RR and VT. Mean pCO2 was significantly higher in active than in sedentary patients. Anxiety state did not account for the results. CONCLUSIONS: Our findings suggest an abnormal regulation of the respiratory system as a key mechanism in PD. In future studies it should be useful t o stratify data taking into account level and intensity of physical activity and smoking behaviour, as well as to consider the cardiac profile and the effect of those variables able to modulate the homeostatic brain functioning. .

Association between anxiety and factors of coagulation and fibrinolysis.

BACKGROUND: Psychological stress and anxiety have been shown to produce an activation of coagulation and fibrinolysis. Resulting hypercoagulability is a risk factor for cardiovascular diseases, and could therefore contribute to an increased prevalence of coronary artery disease in anxiety patients. However, hemostasis function has not yet been studied in patients with clinically relevant anxiety disorders. METHODS: A group of anxiety patients (panic disorder with agoraphobia or social phobia) and a healthy control group (each n = 29) completed some questionnaires [SCL-K9 (a short form of the SCL-90-R), State Trait Anxiety Inventory, ADS (general depression scale)], and had blood drawn after a 15-min rest period. To assess the reaction of the hemostatic system by global entities, sum scores were computed from parameters of coagulation and fibrinolysis (fibrinogen, FVII, FVIII, vWF, F1 + 2, TAT, D-dimer, alpha(2)-AP, PAP, tPA, PAI-1). Interfering variables, such as age, gender, alcohol consumption and smoking status, were controlled. RESULTS: Anxiety patients scored higher in a composite hemostatic score and a sum score of fibrinolysis in comparison to the control group, with a predominant activation of inhibitors in fibrinolysis. However, the psychological variable with the closest association to hemostasis was not trait anxiety, but self-perceived worry about blood drawing before blood sampling was performed. CONCLUSIONS: The coagulation and fibrinolysis system is activated in the direction of a hypercoagulable state in patients with severe phobic anxiety, triggered by fear of blood drawing. This could be one mediating factor for the increased risk of cardiovascular diseases in this population. Acute situational phobic anxiety should be monitored closely when studying the association between anxiety and hemostasis.

Smoking modulates neuroendocrine responses to ipsapirone in patients with panic disorder.

Reduced 5-HT1A-receptor responsiveness has been reported in patients with panic disorder(PD) and/or agoraphobia (PDA). Although many of these patients are regular smokers, it has not been examined whether psychological or neurobiological effects induced by the selective 5-HT1A-receptor agonist, ipsapirone, are affected by the smoking status of the patients. In order to clarify this question neuroendocrine challenges with oral doses of ipsapirone (0.3 mg/kg) and placebo were performed in 39 patients with PDA, and results were compared between patients who smoked (>10 cigarettes per day, n = 17) and patients who had been non-smokers for at least two years (n = 22). Patients who were smokers (but did not smoke during the challenge procedure) had significantly reduced baseline concentrations of cortisol and a significantly lower body temperature. In comparison to placebo, administration of ipsapirone was associated with significant increases of various psychological symptoms and plasma cortisol concentrations. The subgroup of PD patients who were smokers showed significantly higher cortisol responses to ipsapirone than non-smokers. In conclusion, smoking status has to be taken into account when assessing the responsiveness of 5-HT1A receptors in patients with psychiatric disorders. The prevention of smoking during challenge sessions might not be the ideal approach in heavy smokers, since sudden abstinence from smoking is likely to affect neurobiological and possibly psychological responses to ipsapirone.

Fisiopatología del trastorno de ansiedad / The physiopathologyof anxiety disorders

En los últimos años se ha estudiado el trastorno de ansiedad, desde muy diversos enfoques. En el siguiente artículo revisaremos las teorías fisiopatológicas propuestas por los diferentes grupos de investigación en esta área. Abordaremos tres enfoques teóricos: neurobiológico, psicoanalítico asi como del aprendizaje-conductual

Pentagastrin infusions in patients with panic disorder. II. Neuroendocrinology.

Cholecystokinin (CCK) has well-documented anxiogenic effects in animals and normal people, and panicogenic effects in patients with panic disorder, but little is known about its neuroendocrine profile. We examined neuroendocrine responses to intravenous infusions of pentagastrin, a selective CCK-B receptor agonist, in 10 patients with panic disorder and 10 normal control subjects. Pentagastrin potently activated the hypothalamic-pituitary-adrenal (HPA) axis, but did not release growth hormone or any of several vasoactive peptides (neurokinin A, substance P, vasoactive intestinal peptide). The HPA axis response was unrelated to increases in symptoms. Panic patients did not differ from controls in neuroendocrine responses to the CCK agonist. Differential sensitivity to novelty stress accounted for the only patient-control differences in neuroendocrine profiles. The data suggest that CCK may help modulate normal HPA axis activity, but its anxiogenic effects are unrelated to its stimulatory effects on the HPA axis. Pentagastrin provides a safe and readily available probe for further study of CCK receptor systems in humans.

Autorotation test abnormalities of the horizontal and vertical vestibulo-ocular reflexes in panic disorder.

Patients with panic disorder often describe dizziness as a disturbing symptom, with more severe episodes reported than in other psychiatric populations. Nineteen patients diagnosed as having a panic disorder were tested for vestibulo-ocular (VOR) abnormalities with the Vestibular Autorotation Test (VAT), a computerized test of the high-frequency (2 to 6 Hz) VOR. The patients were unselected for the presence or absence of balance disorders. Results showed VOR abnormalities, relative to a normal population, in the horizontal and/or vertical VORs of all 19 patients. Vestibulo-ocular reflex asymmetries were commonly present. Because the VAT tested the VOR over a frequency range encountered during common daily activities, the observed abnormalities could result in a perceptually moving visual field (oscillopsia). We hypothesize that the resulting experience of a visual-vestibular disturbance--perhaps in a biologically or psychologically predisposed individual--is catastrophically misinterpreted, leading to more bodily symptoms and anxiety. These could then contribute to more misinterpretation in a positive feedback sense, ultimately leading to a panic attack.

Evidence that decreased function of lymphocyte beta adrenoreceptors reflects regulatory and adaptive processes in panic disorder with agoraphobia.

OBJECTIVE: This study was designed to clarify the nature of the reduced function of the peripheral beta adrenoceptor system observed in panic disorder with agoraphobia. The authors hypothesized that this phenomenon reflected a regulatory and adaptive process. METHODS: Lymphocyte beta adrenoreceptor density and affinity, basal lymphocyte cAMP level, and isoproterenol-stimulated cAMP generation were measured in 27 untreated outpatients with panic disorder with agoraphobia and 24 healthy comparison subjects. Lymphocyte beta receptor attributes were again assessed in patients after 4 weeks of double-blind treatment with adinazolam (slow-release form) or placebo. Panic frequency, agoraphobic symptoms, overall anxiety, and improvement with treatment were assessed with standard rating instruments. RESULTS: Multivariate statistics revealed significantly lower beta receptor density and isoproterenol-stimulated cAMP generation in patients than in comparison subjects. beta receptor density tended to normalize after adinazolam but not after placebo. Pretreatment beta receptor density was lower in treatment responders than nonresponders. Patients with mild agoraphobia had lower cAMP responsivity than patients with moderate or severe agoraphobia. CONCLUSIONS: Decreased function of lymphocyte beta receptors in panic disorder with agoraphobia is expressed as both decreased density and decreased cAMP responsivity. This pattern of changes, and the tendency for receptor density to normalize with treatment, is consistent with an active, regulatory process rather than a structural deficit in the beta receptor system. Preliminary clinical findings suggest that these changes may reflect adaptive processes associated with a favorable clinical course in panic disorder with agoraphobia.

Sintomas e sinais otoneurológicos na síndrome de pânico e na agorafobia / Otoneurological symptoms and signs in panic disorder and agoraphobia

Foram examinados 16 casos de Síndrome de Pânico e seis casos de Agorafobia com Crises de Pânico sob o ponto de vista otoneurológico. Foi observada grande incidência de sintomatologia auditiva (hipersensibilidade a sons intensos, tinnitus e hipoacusia) e vestibular (tonturas rotatórias e näo rotatórias náuseas). Ao exame audiológico nenhuma anormalidade auditiva foi encontrada. Ao exame vestibular, importantes alteraçöes pertinentes a pesquisa do nistagmo espontâneo, de posiçäo, per-rotatório e pós-calórico foram identificados, na maioria dos pacientes, em ambas as síndromes psiquiátricas. Esses achados justificam a indicaçäo sistemática do exame otoneurológico nessas síndrome psiquiátricas

Biological alterations in the primary affective disorders and other tricyclic-responsive disorders.

Noradrenergic function was studied in patients with primary affective disorder and other tricyclic-responsive disorders including obsessive-compulsive disorder, anorexia nervosa and panic attack/agoraphobia in medication-free states. Pre-synaptic noradrenergic activity was assessed by assaying plasma concentrations of norepinephrine (NE) and its metabolite 3-methoxy,4-hydroxyphenylglycol (MHPG). Noradrenergic receptor responsiveness was evaluated by measuring plasma growth hormone (GH), MHPG, and NE responses to clonidine. Binding of tritiated dihydroergocriptine (3H-DHE) and biochemical responsiveness of alpha 2-adrenergic receptors were measured in platelet preparations. These studies suggest that noradrenergic activity may be altered in several tricyclic-responsive disorders and are consistent with the possibility that tricyclic antidepressants may serve to stabilize a dysregulated noradrenergic system in patients from several diagnostic categories.