Nicotine effects on human affective functions: a systematic review of the literature on a controversial issue.

The observation that nicotine modulates negative affectivity and has a mood enhancing effect mainly derives from studies conducted in the general population and in clinical samples, mostly in nicotine-deprived subjects. It has been explained by the so called deprivation-reversal hypothesis (i.e., nicotine modulates affect because it alleviates withdrawal symptoms). However, experimental studies suggest that nicotine might modulate different affective functions (e.g., aggressiveness, anxiety) and exert a direct modulating effect on human affectivity. The present paper is a systematic review of the literature aiming at verifying this second hypothesis. A computerized search was carried out (PubMed/Medline 1960-2012). Inclusion criteria were: 1. English language papers published in peer-reviewed journals; 2. experimental/quasi experimental design studies; 3. no deprived adults; 4. inclusion of a control condition; 5. no additional Axis I or II psychiatric disorders. Twenty-one papers met our inclusion criteria. Nicotine was showed to alleviate depression both in smokers and non-smokers, especially if depressed or vulnerable to depression. This effect seemed related to the activation of the dopaminergic brain rewarding system. No clear effect on anxiety was found. Nicotine, thus, seems to exert a direct modulating effect on human mood. Possible limitations of the reviewed studies and future research directions are proposed.

The weight of cognitions in panic: the link between misinterpretations and panic attacks.

In cognitive theory it is hypothesized that panic attacks are provoked by catastrophic misinterpretations of bodily sensations. The aim of the present study was to investigate the ability of associated word pairs referring to catastrophic thinking (e.g. palpitations-heart attack) in producing panic attacks. Patients with PD (n = 20), patients with mixed anxiety disorders (n = 20), and a healthy control group (n = 30) participated in the present study. To enhance ecological validity we first conducted a stimulus validation experiment. Subsequently, nine suitable panic and neutral word pairs were presented in block to the participants. Anxiety levels were assessed before and after the presentation. PD patients were more anxious when reading these word pairs, compared to neutral word pairs. However, none of the participants experienced a panic attack upon reading the word pairs. From the present results it seems that catastrophic thinking is rather related to the anticipatory anxiety for panic attacks, but not necessarily with the occurrence of the panic attacks themselves.

Carbon dioxide inhalation as a human experimental model of panic: the relationship between emotions and cardiovascular physiology.

Inhaling carbon dioxide (CO2)-enriched air induces fear and panic symptoms resembling real-life panic attacks, the hallmark of panic disorder. The present study aimed to describe the emotional and cardiovascular effects evoked by inhaling CO2, taking shortcomings of previous studies into account. Healthy volunteers underwent a double inhalation of 0, 9, 17.5, and 35% CO2, according to a randomized, cross-over design. In addition to fear, discomfort, and panic symptom ratings, blood pressure and heart rate were continuously monitored. Results showed a dose-dependent increase in all self-reports. Systolic and diastolic blood pressure rose with increasing CO2 concentration, whereas heart rate results were less consistent. Diastolic blood pressure and heart rate variation correlated with fear and discomfort. Based on this relationship and the observation that the diastolic blood pressure most accurately mimicked the degree of self-reported emotions, it might serve as a putative biomarker to assess the CO2-reactivity in the future.

On the psychotropic effects of carbon dioxide.

It has been well established that the inhalation of Carbon Dioxide (CO2) can induce in humans an emotion closely replicating spontaneous panic attacks, as defined by current psychiatry nosology. The purpose of this review is to provide a critical summary of the data regarding CO2's psychopharmacological properties and underlying mechanisms. The authors review the literature on the human and animal response for the exposure of exogenous CO2 focusing on five points of interest: 1) the early history of the use of CO2 as an anesthetic and therapeutic agent, 2) the subjective effects of breathing CO2 at different concentrations in humans, 3) the use of CO2 in experimental psychiatric research as an experimental model of panic, 4) the pharmacological modulation of CO2-induced responses, and 5) the putative neurobiological mechanisms underlying the affective state induced by CO2. The authors conclude with an evolutionary-inspired notion that CO2 might act as an agent of a primal emotion serving a homeostatic function, in the control of respiration and acid-base balance.

35% CO2 sensitivity in social anxiety disorder.

The 35% carbon dioxide (CO(2)) challenge is a well-established model of panic. This study aimed to investigate 35% CO(2) sensitivity in patients with social anxiety disorder (SAD) compared with patients with panic disorder (PD) and normal controls. First, a 35% CO(2) challenge was conducted including 16 patients with generalized SAD, 16 with PD and 16 normal subjects. Outcome was assessed by a Visual Analogue Scale for Fear (VAS-F) and the Panic Symptom List (PSL). Second, meta-analyses of fear and panic scores were performed, including data from the present experiment and from previous 35% CO(2) challenge studies in patients with SAD. The present 35% CO(2) challenge found equal increases in VAS-F and PSL in patients with SAD compared with normal controls, whereas the CO(2) response in patients with PD was significantly stronger than in controls. The meta-analyses confirmed the experimental data from this study, and in addition showed an intermediate panic rate in SAD patients, in between that of normal controls and patients with PD. In conclusion, neither our experiment nor the meta-analyses found evidence for a similarly exaggerated 35% CO(2) sensitivity in SAD and PD, suggesting that the pathogenesis of SAD is different from PD, although patients with SAD may be slightly more sensitive than non-anxious controls.

Effects of tryptophan depletion and tryptophan loading on the affective response to high-dose CO2 challenge in healthy volunteers.

RATIONALE: It has been reported that in panic disorder (PD), tryptophan depletion enhances the vulnerability to experimentally induced panic, while the administration of serotonin precursors blunts the response to challenges. OBJECTIVES: Using a high-dose carbon dioxide (CO(2)) challenge, we aimed to investigate the effects of acute tryptophan depletion (ATD) and acute tryptophan loading (ATL) on CO(2)-induced panic response in healthy volunteers. METHODS: Eighteen healthy volunteers participated in a randomized, double-blind placebo-controlled study. Each subject received ATD, ATL, and a balanced condition (BAL) in separate days, and a double-breath 35% CO(2) inhalation 4.5 h after treatment. Tryptophan (Trp) manipulations were obtained adding 0 g (ATD), 1.21 g (BAL), and 5.15 g (ATL) of l-tryptophan to a protein mixture lacking Trp. Assessments consisted of a visual analogue scale for affect (VAAS) and panic symptom list. A separate analysis on a sample of 55 subjects with a separate-group design has also been performed to study the relationship between plasma amino acid levels and subjective response to CO(2). RESULTS: CO(2)-induced subjective distress and breathlessness were significantly lower after ATD compared to BAL and ATL (p < 0.05). In the separate-group analysis, ΔVAAS scores were positively correlated to the ratio Trp:ΣLNAA after treatment (r = 0.39; p < 0.05). CONCLUSIONS: The present results are in line with preclinical data indicating a role for the serotonergic system in promoting the aversive respiratory sensations to hypercapnic stimuli (Richerson, Nat Rev Neurosci 5(6):449-461, 2004). The differences observed in our study, compared to previous findings in PD patients, might depend on an altered serotonergic modulatory function in patients compared to healthy subjects.

Tradução e adaptação transcultural do Questionário de Atividade Física Habitual / Translation and cross-cultural adaptation of the Habitual Physical Activity Questionnaire

CONTEXTO: Atualmente há na literatura um crescente interesse na interface entre exercício físico e transtornos psiquiátricos. Apesar disso, ainda há uma deficiência de instrumentos de autorrelato para medir os níveis de atividade física dos pacientes. OBJETIVO: A tradução, a aferição da equivalência semântica e uma aplicação piloto (n = 30), sem pretensão psicométrica, do Questionário de Atividade Física Habitual, visando sua utilização na população brasileira de diferentes níveis de escolaridade. MÉTODOS: O processo envolveu duas traduções e retrotraduções realizadas por avaliadores independentes, avaliação das versões seguida da elaboração de uma versão síntese e pré-teste comentado. RESULTADOS: A maioria dos participantes (91 por cento) não apresentou dificuldades de compreensão com o questionário. Para cada item do instrumento, apresentam-se os resultados das quatro etapas. Mais estudos são necessários para determinar a adequação para populações de baixa escolaridade. Os autores recomendam que sujeitos menos instruídos sejam supervisionados ao preencher o questionário. CONCLUSÕES: A utilização de duas versões de tradução e retrotradução, a discussão sobre a versão síntese e a interlocução com a população-alvo proporcionam maior segurança ao processo de equivalência semântica.

BACKGROUND: There has been a growing scientific interest on the interface between exercise and psychiatric disorders. However, there is a lack of self-report instruments to assess levels of physical activity adapted to Brazilian Portuguese. OBJECTIVE: To translate, assess the semantic equivalence of the Habitual Physical Activity Questionnaire and perform a non-psychometric pre-test with subjects (n = 30) from the Brazilian population, with different educational backgrounds. METHODS: The cross-cultural adaptation process consisted of two translations and back translations performed by two independent evaluators; an evaluation of the versions and the development of a synthetic version; and a commented pretest of the questionnaire. RESULTS: For each item of the instrument, the results of the four stages are reported. Most of the participants (91 percent) did not present any difficulties comprehending the items of the instrument. Further studies should be addressed to determine the adequacy of using this instrument in the less-educated population. We recommend that less instructed subjects be supervised while responding the questionnaire. DISCUSSION: The use of two translations versions, their critical appraisal and the assessment of the target population conceives more safety to the process of semantic equivalence.

Cigarette smoking and 35% CO(2) induced panic in panic disorder patients.

BACKGROUND: A disproportionately large number of persons with panic disorder (PD) smoke cigarettes compared to people in the general population and individuals with other anxiety disorders. Clinical and epidemiological data suggest that cigarette smoking increases the risk for the development and maintenance of PD. The carbon dioxide (CO(2)) challenge is well established as experimental model for panic. The present study seeks to examine whether cigarette smoking has an influence on laboratory elicited panic in PD patients. METHODS: In total 92 subjects (46 smokers and 46 non-smokers) with PD, according to the DSM-IV criteria, were compared. All subjects received a baseline clinical assessment and underwent a 35% CO(2) challenge. Response to the challenge was evaluated via the Panic Symptom List and the Visual Analogue Fear Scale. RESULTS: The two samples did not differ on baseline anxiety level. Smokers had a significantly higher increase in panic symptoms in response to the challenge compared to non-smokers (p=0.04). LIMITATIONS: This type of study does not provide information concerning the underlying mechanisms of the link between smoking and panic. Study limitations include lack of formal assessment of personality and of inter-rater reliability. CONCLUSIONS: The present findings are consistent with the idea that smoking facilitates panic in PD subjects. This may have clinical implications, as quitting smoking could become one of the relevant steps in the treatment of PD patients.

Cigarette smoking and panic: a critical review of the literature.

OBJECTIVE: Cigarette smoking increases the risk of panic disorder with or without agoraphobia's emerging. Although the cause of this comorbidity remains controversial, the main explanations are that (1) cigarette smoking promotes panic by inducing respiratory abnormalities/lung disease or by increasing potentially fear-producing bodily sensations, (2) nicotine produces physiologic effects characteristic of panic by releasing norepinephrine, (3) panic disorder promotes cigarette smoking as self-medication, and (4) a shared vulnerability promotes both conditions. The aim of this review was to survey the literature in order to determine the validity of these explanatory models. DATA SOURCES: Studies were identified by searching English language articles published from 1960 to November 27, 2008, in MEDLINE using the key words: nicotine AND panic, tobacco AND panic, and smoking AND panic. STUDY SELECTION: Twenty-four studies were reviewed and selected according to the following criteria: panic disorder with or without agoraphobia and nicotine dependence, when used, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised, Fourth Edition, or Fourth Edition, Text Revision; no additional comorbidity or, if present, adjustment for it in the statistical analyses; use of adult or adolescent samples; comparison with a nonclinical control group or application of a crossover design. DATA EXTRACTION: Non-significant results or trends only were reported as no difference. Data on anxiety disorders or substance abuse in general were not included. DATA SYNTHESIS: Panic and cigarette smoking each appear to have the capacity to serve as a causal factor/facilitator in the development of the other. Although the temporal pattern and the pathogenetic explanations of such a co-occurrence are still being discussed, cigarette smoking tends to precede the onset of panic and to promote panic itself. CONCLUSIONS: Additional studies are strongly recommended.

Negative affectivity in smokers applying to smoking cessation clinics: a case-control study.

OBJECTIVE: The objective of this study was to assess whether subjects applying to smoking cessation clinics display a higher level of affective symptoms than smokers recruited from the general population. METHODS: The study was conducted according to a cross-sectional, case-control design. Cases were smokers applying to public smoking cessation clinics for the first time and controls were smokers recruited from the general population. Socio-demographic data and clinical information were collected. Self- (Hospital Anxiety Depression Scale, Beck Depression Inventory, State-Trait Anxiety Inventory) and hetero-administered (Montgomery Asberg Depression Rating Scale, Hamilton Anxiety scale) rating scales were used to assess anxious and depressive symptoms. Nicotine dependence was measured via a self-administered questionnaire (Fagerström Tolerance Questionnaire). RESULTS: Sixty-eight cases were recruited, individually matched, and compared to controls. Overall, cases had significantly higher scores than controls when the rating scales assessing anxious and depressive symptoms were evaluated. CONCLUSIONS: Smokers applying to smoking cessation clinics for the first time have a higher level of negative affectivity than smokers from the general population. An evaluation of the level of negative affectivity could be introduced into clinical practice to have a complete assessment of the patient. We propose adding psychological or pharmacological support to complement the smoking cessation program.

Objective and subjective measures in recovery from a 35% carbon dioxide challenge.

OBJECTIVES: Because hyperventilation, dyspnea, and a feeling of choking are often core features of a panic attack, respiration has been one of the most widely studied physiological parameters in panic disorder (PD) patients. A respiratory subgroup of PD, with distinct etiological pathways, has also been suggested. Investigation of the recovery phase following a respiratory challenge may be a reliable way to establish respiratory impairment in PD patients. The objective of the present study was to investigate the recovery phase from a 35% carbon dioxide challenge in PD patients and in healthy controls, and to test the hypothesis of a different respiratory pattern in patients, compared to control subjects. METHODS: Eleven nonmedicated PD patients with or without agoraphobia, 11 medicated PD patients, and 11 control subjects took part in a 35% carbon dioxide and 65% oxygen inhalation challenge. Respiratory rate, partial pressure of carbon dioxide, heart rate, and blood pressure were recorded during the baseline phase (10 minutes) and the recovery phase (10 minutes). Visual Analogue Scale of Anxiety and Panic Symptom List scores were collected pre- and post-challenge. RESULTS: Nonmedicated patients had increased variability in respiratory rate and partial pressure of carbon dioxide during recovery, compared with control subjects and medicated PD patients. Also, PD patients tended to have higher heart rates and to need more time to recover from the challenge than control subjects. CONCLUSIONS: Results suggest that PD patients have less effective homeostatic control after their physiological equilibrium has been disrupted by a respiratory stressor.

Carbon dioxide-induced emotion and respiratory symptoms in healthy volunteers.

A number of evidences have established that panic and respiration are closely related. Clinical studies indicated that respiratory sensations constitute a discrete cluster of panic symptoms and play a major role in the pathophysiology of panic. The aim of the present study was to explore the phenomenology of an experimental model of panic in healthy volunteers based on the hypothesis that: (1) we can isolate discrete clusters of panic symptoms, (2) respiratory symptoms represent a distinct cluster of panic symptoms, and (3) respiratory symptoms are the best predictor of the subjective feeling of panic, as defined in the DSM IV criteria.Sixty-four healthy volunteers received a double inhalation of four mixtures containing 0, 9, 17.5 and 35% CO(2,) respectively, in a double-blind, cross-over, random design. An electronic visual analog scale and the Panic Symptom List (PSL) were used to assess subjective 'fear/discomfort' and panic symptoms, respectively. Statistical analyses consisted of Spearman's correlations, a principal component factor analysis of the 13 PSL symptoms, and linear regressions analyses.The factor analysis extracted three clusters of panic symptoms: respiratory, cognitive, and neurovegetative (r(2)=0.65). Respiratory symptoms were highly related to subjective feeling of fear/discomfort specifically in the CO(2)-enriched condition. Moreover, the respiratory component was the most important predictor of the subjective feeling of 'fear/discomfort' (beta=0.54).The discrete clusters of symptoms observed in this study were similar to those elicited in panic attacks naturally occurring in patients affected by panic disorder. Consistent with the idea that respiration plays a crucial role in the pathophysiology of panic, we found that respiratory symptoms were the best predictors the subjective state defined in the DSM IV criteria for panic.

Effects of experimental panic on neuroimmunological functioning.

OBJECTIVE: Psychoimmunological research in panic disorder (PD) so far focussed on single time point evaluation in resting conditions. No robust evidence for changes in the immune system was found using this method. However, PD is characterized by the occurrence of unexpected panic attacks (PAs). The current research focuses on cytokine and acute phase protein (APP) levels and mitogen-induced cytokine secretion following 35% CO(2) inhalation-induced panic. METHODS: Eighteen PD patients and 18 matched healthy control subjects underwent both a placebo and a 35% CO(2) inhalation on separate days. Blood samples for cytokine and APP determination were taken before and after the inhalation. In addition to serum determination, whole blood samples were cultured and stimulated with mitogens for assessment of the functional capacity of the immune system. RESULTS: The 35% CO(2) inhalation induced significantly higher levels of anxiety in PD patients as compared to the control subjects, but no differences in immune parameters were found, either in basal conditions or after experimental panic induction. CONCLUSION: In our sample we do not find any changes in serum levels or functional capacity of several immunological parameters in the experimentally provoked PAs. Similar results have been found in social phobia, whereas in other affective disorders such as depression and posttraumatic stress disorder, immune changes are evident. Changes seem to coincide with alterations in hypothalamic-pituitary-adrenal (HPA) axis function. Therefore, the bidirectional communication pathway between the immune system and the HPA axis might play a role in some affective disorders, but it does not specifically seem to be involved in the etiology of PD.

Carbon dioxide inhalation induces dose-dependent and age-related negative affectivity.

BACKGROUND: Carbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO(2) in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001). This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05). CONCLUSIONS/SIGNIFICANCE: CO(2) induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO(2) may be part of a protective system triggered by suffocation and acute metabolic distress.

Amygdala hyperfunction in phobic fear normalizes after exposure.

BACKGROUND: The amygdala is implicated as a key brain structure in fear processing. Studies exploring this process using the paradigm of fear conditioning have implicated the amygdala in fear acquisition and in generating behavioral fear responses. As such, fear extinction could be expected to induce a reduction in amygdala activity. However, exposure in specific phobia has never been shown persistently to reduce amygdala activity. METHODS: By means of event-related functional magnetic resonance imaging, responses to phobia-related, general threat, and neutral pictures were measured before and 2 weeks after an intensive exposure session in 20 subjects with specific phobia for spiders and compared with healthy control subjects. RESULTS: Phobic subjects showed increased amygdala activity at baseline. This hyperactivity was significantly reduced 2 weeks after exposure therapy. Furthermore, a significant reduction of hyperactivity in anterior cingulate cortex and insula was found postexposure. CONCLUSIONS: To our knowledge, this is the first study demonstrating the effect of exposure on the amygdala in specific phobia. Our findings suggest that exposure therapy can have an effect on subcortical structures.

Alcohol use disorders and panic disorder: a review of the evidence of a direct relationship.

OBJECTIVE: It is generally agreed that alcohol use disorders and panic disorder with (PD[A]) or without agoraphobia (PD) tend to occur within the same individual. However, the cause of this comorbidity remains controversial. Three main explanations are that (1) PD(A) promotes pathologic alcohol use as self-medication, (2) chronic alcohol use and alcohol withdrawal induce changes in the neurochemical system that promote panic, and (3) a third factor, such as familial transmission, promotes both conditions. The aim of this review was to survey the literature in order to determine the validity of these explanatory models. DATA SOURCES: A review of epidemiologic, family, and laboratory studies was performed. Studies were identified using PubMed (English-language articles published from 1960 to 2006, using the search term alcohol and panic). STUDY SELECTION: Twenty studies were reviewed and selected according to the following criteria: PD(A) and alcohol abuse/dependence diagnosed according to the DSM, no additional comorbidity, use of adult samples, comparison with a nonclinical control group, or application of a crossover design. DATA EXTRACTION: Nonsignificant results or trends only were reported as "no difference." Data on "anxiety disorders" or "substance abuse" in general were not included. DATA SYNTHESIS: In PD(A), alcohol lessens anxious apprehension, thereby decreasing the likelihood of panic. In alcohol use disorders, alcohol increases CO2 sensitivity and may thereby promote panic. In both cases, a significant familial transmission contributes to the co-occurrence. CONCLUSION: Findings would seem to indicate that PD(A) and alcohol use disorders can both serve to initiate the other via independent mechanisms. Further studies are warranted.

CO2 challenge induced HPA axis activation in panic.

The hypothalamic-pituitary-adrenal axis (HPA axis) plays a critical role in stress management. Involvement of this physiological axis in the underlying mechanisms of panic disorder (PD) has been suggested. Studies using 35% CO(2) inhalation to provoke panic found no evidence for robust increases in cortisol levels in PD. However, cortisol levels alone may not be conclusive, as this hormone is merely the end product of a complex physiological axis. Sixteen PD patients and 16 healthy control subjects underwent a 35% CO(2) inhalation and a placebo inhalation on separate days according to a fixed order, double-blind design. Both serum and salivary cortisol, as well as adrenocorticotropic hormone (ACTH) were measured at regular time intervals. Cortisol and ACTH levels increased in the patient and control groups following 35% CO(2) inhalation. The magnitude of the increase was similar in patients and controls despite marked differences in anxiety. This study is the first to document a clear HPA response following 35% CO(2) inhalation in both PD patients and controls. This effect occurs independently of the specific panicogenic properties of the CO(2) challenge. It remains to be clarified whether panic is initially accompanied by major HPA axis activation or whether other stress-responsive systems underlie panic.

Effect of nicotine on 35% CO2-induced anxiety: A study in healthy volunteers.

Panic disorder and cigarette smoking co-occur at a rate that exceeds what would be expected by chance. Theoretically, cigarette smoking may (a) attenuate panicky symptoms via cognitive factors or pharmacological action, (b) contribute to the development of panic disorder, or (c) share an etiological vulnerability with panic. The present study was aimed at testing whether nicotine has a direct influence on laboratory-elicited panic. In a placebo-controlled, double-blind, randomized, cross-over study, 33 healthy nonsmokers underwent a 35% CO2 challenge after transdermal administration of a nicotine patch on one test day and a placebo patch on another test day. Physiological measures (blood pressure, heart rate) and rating scale scores (Panic Symptom List [PSL], Visual Analog Scale of Anxiety, State-Trait Anxiety Inventory) were assessed. Compared with the placebo condition, nicotine increased diastolic blood pressure (p < .1), heart rate (p < .001), and PSL scores (p < .005) prior to the CO2 challenge but did not affect responding to the CO2 challenge itself. Results are consistent with the notion that nicotine promotes autonomic activation. However, the present study did not provide direct evidence that nicotine elicits panic in healthy volunteers. Replication in a clinical sample is warranted.

Prevalence of respiratory disorders in first-degree relatives of panic disorder patients.

BACKGROUND: Panic Disorder (PD) patients often report a history of respiratory pathology, such as asthma. It is known that both PD and respiratory disorders, like asthma, run in families. A common diathesis for PD and some respiratory disorders may be present both in PD patients and their first-degree relatives. We examined whether the lifetime prevalence of respiratory disorders is higher in first-degree relatives of PD patients than in first-degree relatives of patients with other anxiety disorders. METHODS: The lifetime history of respiratory pathology was assessed in 379 first-degree relatives of patients with an anxiety disorder by means of a questionnaire. RESULTS: We found the first-degree relatives of PD patients to report more chronic obstructive pulmonary diseases (COPD) in general (24.8%) and asthma (10.5%) in particular than the comparison group (13.2% and 3.3%, respectively). LIMITATIONS: Our data rely on retrospective self-reports. CONCLUSIONS: Our findings are consistent with and extend previous studies suggesting a specific association between COPD, asthma in particular, and PD.

CO2 challenge results in hypothalamic-pituitary-adrenal activation in healthy volunteers.

The 35% CO(2) challenge is known to induce symptoms of a panic attack both in panic disorder (PD) patients and healthy volunteers. Although the challenge applies more to PD patients, studies in healthy volunteers provide the opportunity to isolate the physical symptoms from the disorder and to focus on the direct effect from the challenge on stress responsive systems. One of the main stress responsive systems is the hypothalamic-pituitary-adrenal (HPA) axis. It remains unclear whether panic symptoms are accompanied by HPA axis activation. Differences in design have hampered any comparison between studies. For example, both serum and salivary cortisol have been used to provide an index of HPA axis activation. Furthermore, indications for central HPA axis disturbance have been suggested. The current study aimed to study the HPA axis response following the induction of panic symptoms in healthy volunteers, both at the pituitary level and at the adrenal level. Furthermore, both serum and salivary cortisol levels were determined. Subjective feelings of anxiety and, correspondingly, cortisol and ACTH levels, were found to be significantly increased following the 35% CO(2) challenge. Cortisol and ACTH responses to CO(2) were also associated. A significant cortisol increase was observed in both serum and saliva samples, although these were more pronounced when considering the free fraction serum values. We conclude that the induction of panic symptoms results in HPA axis activation, both at the pituitary and adrenal level. The question remains as to whether positive responders to the 35% CO(2) inhalation (more specifically PD patients) show a more pronounced HPA axis response.