Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers

The study of carbon dioxide (CO2) inhalation in psychiatry has a long and varied history, with recent interest in using inhaled CO2 as an experimental tool to explore the neurobiology and treatment of panic disorder. As a consequence, many studies have examined the panic-like response to the gas either using the single or double breath 35% CO2 inhalation or 5-7% CO2 inhaled for 15-20 min, or rebreathing 5% CO2 for a shorter time. However, this lower dose regime produces little physiological or psychological effects in normal volunteers. For this reason we have studied the effects of a higher concentration of CO2, 7.5%, given over 20 min. Twenty healthy volunteers were recruited to a double blind, placebo-controlled study where air and 7.5% CO2 were inhaled for 20 min. Cardiovascular measures and subjective ratings were obtained. When compared to air, inhaling 7.5% CO2 for 20 min increases systolic blood pressure and heart rate, indicating increased autonomic arousal. It also increases ratings of anxiety and fear and other subjective symptoms associated with an anxiety state. The inhalation of 7.5% CO2 for 20 min is safe for use in healthy volunteers and produces robust subjective and objective effects. It seems promising as an anxiety provocation test that could be beneficial in the study of the effects of anxiety on sustained performance, the discovery of novel anxiolytic agents, and the study of brain circuits and mechanisms of anxiety.     

Effects of carbon dioxide-oxygen inhalations on subjective anxiety and some neurovegetative parameters

The immediate effects of double inhalations of a 35% CO₂-65% O₂ mixture were studied on 12 subjects, all of them undergraduate students. For placebo control double inhalations of compressed air were administered to the same experimental subjects. In comparison, CO₂/O₂ inhalations were found to provoke significantly stronger autonomic reactions, viz. drops in heart rate and diastolic blood pressure. Reduction in subjective feeling of anxiety was observed with both CO₂/O₂ and air intake. On this parameter of subjective feeling the order in which the treatments were received interacted with the gas variable, i.e. CO₂/O₂ and air.The occurrence of a carry-over effect was indicated: Subjects having taken the placebo before CO₂/O₂ showed lower SUD scores than did those treated reversely.     

The effect of focused attention and open monitoring meditation on attention network function in healthy volunteers

Mindfulness meditation techniques are increasingly popular both as a life-style choice and therapeutic adjunct for a range of mental and physical health conditions. However, little is known about the mechanisms through which mindfulness meditation and its constituent practices might produce positive change in cognition and emotion. Our study directly compared the effects of Focused Attention (FA) and Open-Monitoring (OM) meditation on alerting, orienting and executive attention network function in healthy individuals. Participants were randomized to three intervention groups: open-focused meditation, focused attention, and relaxation control. Participants completed an emotional variant of the Attention Network Test (ANT) at baseline and post-intervention. OM and FA practice improved executive attention, with no change observed in the relaxation control group. Improvements in executive attention occurred in the absence of change in subjective/self-report mood and cognitive function. Baseline levels of dispositional/trait mindfulness were positively correlated with executive control in the ANT at baseline. Our results suggest that mindfulness meditation might usefully target deficits in executive attention that characterise mood and anxiety disorders.     

Neuroendocrine and behavioural responses to CO2 inhalation in central versus peripheral autonomic failure

Abstract Multiple system atrophy (MSA) and pure autonomic failure (PAF) represent distinct pathological models of autonomic failure in humans. We have investigated the neuroendocrine, behavioural and autonomic cardiovascular responses to the 35% CO₂ challenge. Nine patients with MSA, nine with PAF and five control subjects received a single breath of 35% CO₂. Peripheral autonomic failure (i.e., PAF) was associated with significantly lower resting noradrenaline levels. All groups demonstrated a significant pressor response to CO₂. In controls, the mean pressor response was +60.2 mm Hg, which was significantly smaller in both the PAF (+26.8 mm Hg, P < 0.01) and MSA (+18.3 mm Hg, P < 0.001) patients. In addition, the onset of the response was significantly delayed in both MSA (140.2 s) and PAF (154.2 s) patients compared with controls (32.4 s, P = 0.04 and P = 0.03, respectively). Noradrenaline levels increased only in controls. Central autonomic impairment (i.e., MSA) was associated with lower cortisol release (+8.8% in MSA compared with +35.2% in control and +23.7% in PAF) and fewer somatic symptoms of emotional arousal. Both MSA and PAF exhibit marked sympathetic autonomic impairment, however, residual (albeit differing) sympathetic pathways can still maintain a partial cardiovascular response. A central autonomic lesion, however, also appears to be associated with blunting of both cortisol and emotional responses to this stress paradigm.     

Experiential,autonomic, and respiratory correlates of CO2 reactivity in individuals with high and low anxiety sensitivity

Psychometric studies indicate that anxiety sensitivity (AS) is a risk factor for anxiety disorders such as panic disorder (PD). To better understand the psychophysiological basis of AS and its relation to clinical anxiety, we examined whether high-AS individuals show similarly elevated reactivity to inhalations of carbon dioxide (CO₂) as previously reported for PD and social phobia in this task. Healthy individuals with high and low AS were exposed to eight standardized inhalations of 20% CO₂-enriched air, preceded and followed by inhalations of room air. Anxiety and dyspnea, in addition to autonomic and respiratory responses were measured every 15 s. Throughout the task, high AS participants showed a respiratory pattern of faster, shallower breathing and reduced inhalation of CO₂ indicative of anticipatory or contextual anxiety. In addition, they showed elevated dyspnea responses to the second set of air inhalations accompanied by elevated heart rate, which could be due to sensitization or conditioning. Respiratory abnormalities seem to be common to high AS individuals and PD patients when considering previous findings with this task. Similarly, sensitization or conditioning of anxious and dyspneic symptoms might be common to high AS and clinical anxiety. Respiratory conditionability deserves greater attention in anxiety disorder research.     

Anxiety sensitivity and subjective social status in relation to anxiety and depressive symptoms and disorders among Latinos in primary care

The present investigation examined the interactive effects of anxiety sensitivity and subjective social status in relation to anxiety and depressive symptoms and psychopathology among 143 Latinos (85.7% female; M_age = 39.0, SD = 10.9; 97.2% used Spanish as their first language) who attended a community-based primary healthcare clinic. Results indicated that the interaction between anxiety sensitivity and subjective social status was significantly associated with number of mood and anxiety disorders, panic, social anxiety, and depressive symptoms. The form of the significant interactions indicated that individuals reporting co-occurring higher levels of anxiety sensitivity and lower levels of subjective social status evidenced the greatest levels of psychopathology and panic, social anxiety, and depressive symptoms. The present findings suggest that there is merit in focusing further scientific attention on the interplay between anxiety sensitivity and subjective social status in regard to understanding, and thus, better intervening to reduce anxiety/depressive vulnerability among Latinos in primary care.     

Unexpected arousal, anxiety sensitivity, and their interaction on CO₂-induced panic: further evidence for the context-sensitivity vulnerability model

The present experiment tested several predictions derived from the context-sensitivity vulnerability model of panic. Participants (N = 79) scoring either high or low in anxiety sensitivity (AS) and with no history of unexpected panic were randomly assigned to one of two instructional sets: expected arousal (EA) or expected relaxation (ER). All participants were administered inhalation of room air and 35% CO₂ in a counterbalanced order. Consistent with theoretical predictions, High-AS participants who received ER instructions showed greater emotional responding compared to High-AS participants who received EA instructions, while instructional set did not affect responding among Low-AS participants. Panic attacks were observed in 52% of the High-AS-ER group compared to 17%, 5%, and 5% in the High-AS-EA, Low-AS-ER, and Low-AS-EA groups respectively. These findings are consistent with the theory's assertion that dispositional tendencies, such as anxiety sensitivity potentiate the panicogenic effects of threat-relevant context variables.     

Examining the Potential Influence of Diabetes on Depression and Anxiety Symptoms via Multiple Sample Confirmatory Factor Analysis

Background  

Assessing and diagnosing depression and anxiety in the presence of diabetes is complicated by overlapping symptoms that, therefore, are etiologically ambiguous (e.g., fatigue, appetite disturbance, autonomic arousal).     

Synergistic effects of pain intensity and anxiety sensitivity in relation to anxiety and depressive symptoms and disorders among economically disadvantaged latinos in a community-based primary care setting

The present investigation examined the interactive effects of anxiety sensitivity and pain intensity in relation to anxious arousal, social anxiety, and depressive symptoms and disorders among 203 Latino adults with an annual income of less than $30,000 (84.4% female; M_age = 38.9, SD = 11.3 and 98.6% used Spanish as their first language) who attended a community-based primary healthcare clinic. As expected, the interaction between anxiety sensitivity and pain intensity was significantly related to increased anxious arousal, social anxiety, and depressive symptoms as well as number of depressive/anxiety disorder diagnoses. The form of the significant interactions indicated that participants reporting co-occurring higher levels of anxiety sensitivity and pain intensity evinced the greatest levels of anxious arousal, social anxiety, and depressive symptoms as well as higher levels of depressive and anxiety disorders. These data provide novel empirical evidence suggesting that there is clinically-relevant interplay between anxiety sensitivity and pain intensity in regard to a relatively wide array of anxiety and depressive variables among Latinos in a primary care medical setting.     

The effect of peripheral beta-blockade on psychophysiologic responses in obsessional neurotics

Ithas been postulated that anxiety symptoms are mediated through peripheral mechanisms and that subjective feelings of anxiety are learned associations to bodily symptoms.¹ This hypothesis has been supported by findings indicating the beneficial effects of beta-adrenergic receptor blocking agents in psychiatric patients.^2,3 In anxiety states, particularly, mood changes have been reported even with beta-blockers that penetrate very slowly into the brain.^4–6 Therefore, the improvement in subjective anxiety would appear to be related to peripheral beta-blockade rather than central action.There is also evidence that obsessive-compulsive patients experience increased subjective discomfort, associated with increased autonomic reactivity, while they hold in fantasy ruminative thoughts, or when they touch “contaminating” objects, compared to neutral thoughts or objects.^7,8 The present work is an attempt to measure the psychophysiologic arousal during internal stimulation of such patients before and after beta-blockade with practolol¹ an agent lacking central effects. A decrease in autonomic reactivity accompanied by similar amelioration in subjective anxiety would support Breggin's hypothsis.¹ On the other hand, failure of the latter to accompany the physiologic modifications brought about by practolol would support the theoretical position that assigns fundamental importance to cognitive and situational factors in the genesis and maintenance of anxiety.⁹ This would be of interest with patients in which a specific type of cognitive activity and avoidance behavior dominate the clinical symptomatology.     

Cognitive complaints in women with fibromyalgia: Are they due to depression or to objective cognitive dysfunction?

Introduction: Cognitive complaints are common in fibromyalgia, but it is unclear whether they represent an objective cognitive dysfunction or whether they could be explained by depressive symptoms. Here, we aim to elucidate the frequency of subjective cognitive complaints in a sample of women with fibromyalgia, in addition to analyzing associations between these subjective complaints and objective measures linked to the attention and executive cognitive domains. Finally, we aim to investigate the ability of demographic, clinical, and psychological variables to explain the subjective complaints observed. Method: One hundred and five women aged 30–55 years diagnosed with fibromyalgia completed a neuropsychological assessment, which included measures of attention and executive functions. They also completed self-report inventories of subjective cognitive complaints, depression, anxiety, intensity of pain, sleep quality, everyday physical functioning, and quality of life. Results: Eighty-four percent of the patients reported subjective cognitive complaints. Depression scores, everyday physical functioning, and working memory performance were most strongly associated with subjective cognitive complaints. These three variables were significant predictors for subjective cognitive complaints with a final model explaining 32% of the variance. Conclusions: Cognitive complaints are very frequent in patients with fibromyalgia, and these are related to functional and cognitive impairment as well as to depressive symptoms.     

Autonomic correlates of the subjective anxiety scale

The subjective anxiety scale is an assessment tool commonly used in behavioral research and therapy to quantify verbal report to private events, usually states of fear. An investigation was undertaken to determine the extent of relationship between the subjective anxiety scale and two concurrent measures of autonomic arousal, peripheral vasoconstriction and heart rate. Measures were recorded during baseline, surgical film and second baseline phases for 20 subjects. The subjective and autonomic measures indicated increased anxiety during the film phase and significant correlations were found between subjective report of anxiety and the two physiological indices. The results support the continued use of the subjective anxiety scale as a clinical assessment tool. Practice and research implications are discussed.     

Influence of sympathetic autonomic arousal on tics: Implications for a therapeutic behavioral intervention for Tourette syndrome

ObjectivesThe pharmacological treatment of Tourette syndrome (TS) has improved due to the application of new medications and combinations of medications, coupled to greater phenomenological and neurobiological understanding of the condition. Nevertheless, for many individuals with TS, potentially troublesome tics persist despite optimized drug treatment. Anecdotally, a relationship is frequently described between tic frequency and states of bodily arousal and/or focused attention. The galvanic skin response (GSR) is an accessible and sensitive index of sympathetic nervous activity, reflecting centrally induced changes in peripheral autonomic arousal. Sympathetic nervous arousal, measured using GSR, has been shown to have an inverse relationship with an electroencephalographic index of cortical excitability (slow cortical potential), and GSR arousal biofeedback shows promise as an adjunctive therapy in management of treatment-resistant epilepsy.MethodWe examined how changes in sympathetic arousal, induced using GSR biofeedback, impact on tic frequency in individuals with TS. Two different physiological states (sympathetic arousal and relaxation) were induced using GSR biofeedback in 15 individuals with a diagnosis of TS. During both biofeedback sessions, participants were videotaped to monitor the occurrence of tics.ResultsWe observed significantly lower tics during relaxation biofeedback compared to arousal biofeedback, with tic frequency positively correlating with sympathetic arousal during the arousal session.ConclusionThese findings indicate that the conjunction of focused attention to task and reduced peripheral sympathetic tone inhibits tic expression and suggests a potential therapeutic role of biofeedback relaxation training for tic management in patients with TS.     

Premenstrual distress predicts panic-relevant responding to a CO2 challenge among young adult females

The current study examined the incremental validity of self-reported premenstrual distress in predicting panic responsivity (self-reported panic symptoms and skin conductance response frequency; SCR) following inhalation of 10% CO₂-enriched air. A community sample of young adult women (n = 46) completed questionnaires assessing substance use patterns, premenstrual symptoms and distress, and anxiety sensitivity and underwent a laboratory biological challenge procedure (4-min 10% CO₂-enriched air inhalation). As hypothesized, higher premenstrual distress scores significantly predicted greater self-reported panic symptoms following the CO₂ challenge above and beyond other theoretically relevant variables (anxiety sensitivity, cigarette use, and alcohol consumption). In predicting SCR, premenstrual distress exhibited only a trend towards statistical significance. These findings provide preliminary evidence that premenstrual symptoms may serve as a potential risk factor to experience more intense panic symptoms in response to perturbations in bodily sensations.     

Psychophysiological assessment of stress reactivity and recovery in anxiety disorders

The present study aimed to examine changes in psychophysiological arousal from baseline to a stressor phase (reactivity) and from the stressor phase to a second resting phase (recovery) in patients with anxiety disorders. Fifty adult patients with DSM-5 anxiety disorders (panic disorder, generalized anxiety disorder, or social anxiety disorder) and 28 healthy control (HC) participants underwent psychophysiological monitoring including electrocardiogram, respiration rate, electrodermal activity, gastrocnemius electromyograph, and end-tidal CO₂ for a 3-min resting phase, a 6-min mild stressor phase, and a 3-min recovery phase. Anxious patients then went on to receive naturalistic cognitive-behavioral therapy (CBT) in a specialty outpatient clinic. Results for the reactivity phase indicated that compared to HCs, patients with social anxiety disorder exhibited heightened psychophysiological reactivity while patients with panic disorder and generalized anxiety disorder exhibited attenuated reactivity. Results for physiological recovery (return to baseline after the stressor was withdrawn) were mixed, but provided some support for slower autonomic recovery in patients with generalized anxiety disorder and panic disorder compared to HCs. Participants with all anxiety disorders exhibited diminished change in high frequency heart rate variability compared to HCs. Generally, psychophysiological reactivity and recovery were not associated with CBT outcome, though exploratory analyses indicated that greater respiration rate reactivity and stronger respiration rate recovery were associated with better CBT outcomes in patients with panic disorder.     

Physiological reactivity to phobic stimuli in people with fear of flying

Objective

The nature of the relationship between physiological and subjective responses in phobic subjects remains unclear. Phobics have been thought to be characterized by a heightened physiological response (physiological perspective) or by a heightened perception of a normal physiological response (psychological perspective).

Method

In this study, we examined subjective measures of anxiety, heart rate (HR), and cardiac autonomic responses to flight-related stimuli in 127 people who applied for fear-of-flying therapy at a specialized treatment center and in 36 controls without aviophobia.

Results

In keeping with the psychological perspective, we found a large increase in subjective distress (η²=.43) during exposure to flight-related stimuli in the phobics and no change in subjective distress in the controls, whereas the physiological responses of both groups were indiscriminate. However, in keeping with the physiological perspective, we found that, within the group of phobics, increases in subjective fear during exposure were moderately strong coupled to HR (r=.208, P=.022) and cardiac vagal (r=.199, P=.028) reactivity. In contrast to predictions by the psychological perspective, anxiety sensitivity did not modulate this coupling.

Conclusion

We conclude that subjective fear responses and autonomic responses are only loosely coupled during mildly threatening exposure to flight-related stimuli. More ecologically valid exposure to phobic stimuli may be needed to test the predictions from the physiological and psychological perspectives.     

Influence of sympathetic autonomic arousal on tics: Implications for a therapeutic behavioral intervention for Tourette syndrome

Objectives

The pharmacological treatment of Tourette syndrome (TS) has improved due to the application of new medications and combinations of medications, coupled to greater phenomenological and neurobiological understanding of the condition. Nevertheless, for many individuals with TS, potentially troublesome tics persist despite optimized drug treatment. Anecdotally, a relationship is frequently described between tic frequency and states of bodily arousal and/or focused attention. The galvanic skin response (GSR) is an accessible and sensitive index of sympathetic nervous activity, reflecting centrally induced changes in peripheral autonomic arousal. Sympathetic nervous arousal, measured using GSR, has been shown to have an inverse relationship with an electroencephalographic index of cortical excitability (slow cortical potential), and GSR arousal biofeedback shows promise as an adjunctive therapy in management of treatment-resistant epilepsy.

Method

We examined how changes in sympathetic arousal, induced using GSR biofeedback, impact on tic frequency in individuals with TS. Two different physiological states (sympathetic arousal and relaxation) were induced using GSR biofeedback in 15 individuals with a diagnosis of TS. During both biofeedback sessions, participants were videotaped to monitor the occurrence of tics.

Results

We observed significantly lower tics during relaxation biofeedback compared to arousal biofeedback, with tic frequency positively correlating with sympathetic arousal during the arousal session.

Conclusion

These findings indicate that the conjunction of focused attention to task and reduced peripheral sympathetic tone inhibits tic expression and suggests a potential therapeutic role of biofeedback relaxation training for tic management in patients with TS.     

Speeches, strangers, and alcohol use: the role of context in social stress response dampening

According to the Stress Response Dampening model, problem drinking develops after learning that alcohol limits the stress response in anxiety-provoking situations. However, laboratory-based studies testing alcohol’s effects on social anxiety have yielded mixed results. The current study was the first to examine stress response dampening across two contexts: a performance-based (a speech) and an interaction-based (a conversation) social situation. Undergraduates (N = 62; M_age = 22.85; 31% women; 81% Caucasian) were randomly assigned to consume an alcoholic (target BAC = .08%; n = 22), placebo (n = 20), or nonalcoholic control (n = 20) beverage followed by the anxiety-inducing social tasks. Results revealed a 3 (alcohol condition) × 2 (social task condition) × 4 (measurement point) interaction, controlling for baseline subjective state anxiety and trait social anxiety. The pattern of scores over the course of the task varied across alcohol conditions for the speech, but not the conversation. Specifically, participants in the alcohol and placebo conditions evidenced increased subjective anxiety following the first measurement point prior to the speech and their anxiety remained elevated at all subsequent measurements. Participants in the nonalcoholic control condition evidenced stable subjective anxiety ratings for all speech measurement points. Results did not support stress response dampening for either type of social situation. Instead, the only between-group difference found was that the placebo group reported greater subjective anxiety than the nonalcoholic control group after the speech. Concerns about alcohol’s negative effects on one’s performance might have led to increased anxiety. Findings shed light on previous inconsistent findings and highlight the need to consider context and timing in understanding drinking to cope with social anxiety.     

Subjective deficits of attention,cognition and depression in patients with narcolepsy

ObjectivePatients with narcolepsy often complain about attention deficits in everyday situations. In comparison with these subjective complaints, deficits in objective testing are subtler. The present study assessed the relationships between subjective complaints, objectively measured cognitive performance, disease-related variables, and mood.Patients/MethodsA total of 51 patients with narcolepsy and 35 healthy controls responded to questionnaires regarding subjectively perceived attention deficits, sleepiness, anxiety and depression. Moreover, they performed an extensive neuropsychological assessment tapping into attention, executive functions, and memory.ResultsPatients rated their level of attention in everyday situations to be relatively poor. In an objective assessment of cognitive functioning, they showed only slight attention and executive function deficits. The subjective ratings of attention deficits significantly correlated with ratings of momentary sleepiness, anxiety, and depression, but not with objectively measured cognitive performance. Momentary sleepiness and depression predicted almost 39% of the variance in the ratings of subjectively perceived attention deficits.ConclusionThe present study showed that sleepiness and depression, more than objective cognitive deficits, might play a role in the subjectively perceived attention deficits of patients with narcolepsy. The results suggested that when counselling and treating patients with narcolepsy, clinicians should pay attention to potential depression because subjective cognitive complaints may not relate to objective cognitive impairments.