Cybele Garcia-Leal

Anxiety and salivary cortisol in symptomatic and nonsymptomatic panic patients and healthy volunteers performing simulated public speaking

Anxiety and salivary cortisol were measured in subjects performing simulated public speaking (SPS), a procedure that has been neurobiologically related to panic disorder. The subjects were divided into three groups: 18 symptomatic panic patients, 16 nonsymptomatic, drug-treated panic patients, and 17 healthy controls. In the experimental session, subjective anxiety (Visual Analogue Mood Scale) and the total score of the Bodily Symptom Scale (BSS) were higher in symptomatic patients than in controls, with nonsymptomatic patients in between. Measures of cortisol taken at home showed that the level was higher at 9:00 h than at 23:00 h in every group, indicating a normal circadian regulation of the hypothalamic-pituitary-adrenal (HPA) axis in panic patients. Also in every group, the level of cortisol was high at the beginning of the experimental session and decreased after 70 min. This fall parallels the decrease in anxiety and BSS ratings, and appears to reflect habituation of initial, anticipatory anxiety. Preparation and performance of speech raised anxiety and BSS scores to the initial levels, but failed to increase cortisol measured over 60 min, starting at the end of the speech. Therefore, SPS does not seem to activate the HPA axis, as reported in panic attacks.

Does the panic attack activate the hypothalamic-pituitary-adrenal axis?

A bibliographic search has been performed in MEDLINE using cortisol and panic as key-words, occurring in the title and/or in the abstract. Human studies were selected, with no time limit. The following publications were excluded: review articles, case reports, panic attacks in disorders other than panic disorder, and studies on changes that occurred in-between panic attacks. The results showed that real-life panic attacks as well as those induced by selective panicogenic agents such as lactate and carbon dioxide do not activate the hypothalamic-pituitary-adrenal (HPA) axis. Agonists of the colecystokinin receptor B, such as the colecystokinin-4 peptide and pentagastrin, increase stress hormones regardless of the occurrence of a panic attack and thus, seem to activate the HPA axis directly. The benzodiazepine antagonist flumazenil does not increase stress hormones, but this agent does not reliably induce panic attacks. Pharmacological agents that increased anxiety in both normal subjects and panic patients raised stress hormone levels; among them are the alpha2-adrenergic antagonist yohimbine, the serotonergic agents 1-(m-chlorophenyl) piperazine (mCPP) and fenfluramine, as well as the psychostimulant agent caffeine. Therefore, the panic attack does not seem to activate the HPAaxis, in contrast to anticipatory anxiety.

Subjective and neurovegetative changes in healthy volunteers and panic patients performing simulated public speaking

Drug-free symptomatic panic patients, drug-treated nonsymptomatic patients and healthy controls were submitted to simulated public speaking. Subjective anxiety, cognitive impairment and discomfort measured by the visual analog mood scale as well as skin conductance level were higher in symptomatic patients than in controls at the beginning of the experimental session, nonsymptomatic patients lying in between. Subjective sedation, spontaneous fluctuations of skin conductance, heart rate and blood pressure were similar in the three groups. Preparation and performance of speech decreased sedation while increasing anxiety, cognitive impairment, level and fluctuations of skin conductance, heart rate and blood pressure. Anxiety, cognitive impairment and conductance level were less increased in symptomatic patients than in controls. Electrodermal activity, but not cardiovascular measures of sympathetic arousal correlated with anticipatory anxiety. Chronic treatment with serotonin uptake inhibitors attenuated the differences between panic patients and controls, supporting the participation of serotonin in panic disorder.

Escitalopram prolonged fear induced by simulated public speaking and released hypothalamic-pituitary-adrenal axis activation

Simulated public speaking (SPS) test is sensitive to drugs that interfere with serotonin-mediated neurotransmission and is supposed to recruit neural systems involved in panic disorder. The study was aimed at evaluating the effects of escitalopram, the most selective serotonin-selective reuptake inhibitor available, in SPS. Healthy males received, in a double-blind, randomized design, placebo (n = 12), 10 (n = 17) or 20 (n = 14) mg of escitalopram 2 hours before the test. Behavioural, autonomic and neuroendocrine measures were assessed. Both doses of escitalopram did not produce any effect before or during the speech but prolonged the fear induced by SPS. The test itself did not significantly change cortisol and prolactin levels but under the higher dose of escitalopram, cortisol and prolactin increased immediately after SPS. This fear-enhancing effect of escitalopram agrees with previously reported results with less selective serotonin reuptake inhibitors and the receptor antagonist ritanserin, indicating that serotonin inhibits the fear of speaking in public.

Altered functioning of the HPA axis in depressed postpartum women.

BACKGROUND The present study aimed to evaluate the relationship between the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and major depressive episodes in the remote postpartum period. METHODS The sample (mean age, 28.0±5.3 years) consisted of 37 depressed postpartum women (DPP), 42 euthymic postpartum women (EPP) and 25 non-postpartum healthy women (HC). Salivary cortisol samples were collected immediately after awakening and 30min, 3 and 12h later, at approximately the sixth month postpartum (mean, 169.6±60.3 days). RESULTS Differences in cortisol levels were observed at awakening (DPPEPP=HC). The relative increment in the cortisol awakening response (CARi%) was significantly higher in HC (113.5±94.3) than in EPP (63.1±69.8) and DPP (32.2±49.6). The relative reduction in diurnal variation (DVr%) was lower in DPP (56.5±41.8) than in EPP (75.6±22.4) and HC (75.1±13.0). LIMITATIONS The main limitation was cortisol collection on a single day and without measurement at midnight. CONCLUSIONS Our findings suggest that the remote postpartum period involves attenuation of HPA axis reactivity; this dysregulation is more pronounced in the presence of DPP, which is associated with a reduction in cortisol diurnal variation. Abnormalities in the neuroendocrine system related to stress processing, present even several months after delivery, can represent vulnerability to mental disorders. Thus, improvements in the mental health care of postpartum women are needed.

The 5-HT1D/1B receptor agonist sumatriptan enhances fear of simulated speaking and reduces plasma levels of prolactin

This study measured the effects of the preferential 5-HT1D/1B receptor agonist sumatriptan in healthy volunteers who performed the Simulated Public Speaking Test (SPST), which recruits the neural network involved in panic disorder and social anxiety disorder. In a double-blind, randomised experiment, 36 males received placebo (12), 50 mg (12) or 100 mg (12) of sumatriptan 2 h before the SPST. Subjective, physiological and hormonal measures were taken before, during and after the test. The dose of 100 mg of sumatriptan increased speech-induced fear more than either a 50mg dose of the drug or placebo. The largest dose of sumatriptan also enhanced vigilance more than placebo, without any change in blood pressure, heart rate or electrical skin conductance. Sumatriptan decreased plasma levels of prolactin. A significant but moderate increase in plasma cortisol after SPST occurred, independent of treatment. Because sumatriptan decreases 5-HT release into the extracellular space, the potentiation of SPST-induced fear caused by the drug supports the hypothesis that 5-HT attenuates this emotional state. As acute administration of antidepressants has also been shown to enhance speaking fear and increase plasma prolactin, in contrast to sumatriptan, the 5-HT regulation of stress-hormone release is likely to be different from that of emotion.

Experimental public speaking: contributions to the understanding of the serotonergic modulation of fear.

Public speaking is widely used as a model of experimental fear and anxiety. This review aimed to evaluate the effects of pharmacological challenges on public speaking responses and their implications for the understanding of the neurobiology of normal and pathological anxiety, specifically panic disorder. We also describe methodological features of experimental paradigms using public speaking as an inducer of fear and stress. Public speaking is a potent stressor that can provoke significant subjective and physiological responses. However, variations in the manners in which public speaking is modelled can lead to different responses that need to be considered when interpreting the results. Results from pharmacological studies with healthy volunteers submitted to simulated public speaking tests have similarities with the pharmacological responses of panic patients observed in clinical practice and panic patients differ from controls in the response to the public speaking test. These data are compatible with the Deakin and Graeff hypothesis that serotonin inhibits fear, as accessed by public speaking tasks, and that this inhibition is likely related to the actions of serotonin in the dorsal periaqueductal grey matter.

The functioning of the hypothalamic-pituitary-adrenal (HPA) axis in postpartum depressive states: a systematic review

ABSTRACT Introduction: A large body of literature suggests the role of the hypothalamic-pituitary-adrenal (HPA) axis in postpartum depression (PPD). Nonetheless, these studies present discrepant methodology and results; thus, this hypothesis deserves further exploration. Areas covered: This review included studies investigating the HPA axis in PPD or postpartum blues published until November 2016. In total, 48 studies met the inclusion criteria. The HPA axis was mostly investigated in the immediate postpartum period (62.5%), and the majority of studies collected samples in the morning (43.8%), with one measure in a single day (43.8%), and blood was the fluid more often collected (58.4%). Seven out of 21 studies evaluating postpartum blues, and 15 out of 28 studies evaluating PPD detected abnormalities in the HPA axis functioning. Expert commentary: We found a significant heterogeneity in the methodology adopted by studies and consequently, in the results. Despite that, the majority of studies reported HPA changes in women with PPD during the remote period. Notably, reactivity tests pointed to attenuated HPA axis response. Ideally, future investigations should use validated reactivity tests, include larger sample sizes, consider many measures of cortisol throughout the day, and more than one day of collection. We also recommend that studies continue to use validated scales for mood assessment.