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ORIGINAL ARTICLES |
Department of Psychology (I.V.D., S.V., I.C., S.D.P., S.D., O.V.d.B.) and Department of Respiratory Medicine, University Hospital Gasthuisberg (K.P.V.d.W.), University of Leuven, Belgium.
Address correspondence and reprint requests to Ilse Van Diest, Research Group for Stress, Health and Well-Being, Department of Psychology, University of Leuven, Tiensestraat 102, B-3000 Leuven, Belgium. E-mail: Ilse.Vandiest{at}psy.kuleuven.ac.be
| ABSTRACT |
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MATERIALS AND METHODS: In the first study, 110 participants (83 women) completed the PANAS and a Checklist for Psychosomatic Symptoms in daily life. FetCO2 was measured noninvasively during 5 minutes via a nose cannula connected to a capnograph. In the second study, FetCO2 of high (N= 20, 10 men) and low (N= 20, 10 men) NA participants was sampled once with a nasal cannula and once while breathing through a mouthpiece for 6 minutes each during rest, completion of the NEO-PI-R questionnaire, and completion of a verbal knowledge test.
RESULTS: The first study found no association between trait NA and resting FetCO2 after partialling out the effects of gender, menstrual phase, and use of oral contraceptives. The second study showed that FetCO2 increased significantly in the high NA group only when the particpants filled out the questionnaires, regardless of its type.
CONCLUSIONS: Overall, no association between dispositional NA and cross-situational FetCO2 was observed. Apparently inconsistent findings may be caused by lack of control for hormonal status and mental load during testing.
Key Words: negative affectivity, neuroticism, carbon dioxide pressure, hyperventilation.
Abbreviations: NA = negative affectivity;; FetCO2 = fractional concentration of end-tidal carbon dioxide;; PANAS = positive and negative affect scales;; CPS = checklist for psychosomatic symptoms;; ASI = anxiety sensitivity index;; STAI = trait version of the state-trait anxiety inventory;; NEO-PI-R = revised NEO personality inventory.
| INTRODUCTION |
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The existence and direction of an association between FetCO2 and trait NA is clinically important for a number of topics in the field of psychosomatic medicine. First, a high resting FetCO2 has been found to be related to hypertension in women (30), suggesting that psychosocial interventions may be helpful in its treatment. Second, an association of trait NA with FetCO2 may help to clarify the hypothesized role of hyperventilation in quite a number of pathological conditions, such as panic disorder, somatization, chronic fatigue syndrome, chronic muscle pain, and multiple chemical sensitivity (3136). Third, chronically reduced PCO2 levels in the blood of high trait NA persons could partly explain the association between NA and symptom reports in nonclinical samples (3742).
Several explanations may account for the inconsistencies between the studies on resting FetCO2 and trait NA. First, the studied samples vary greatly in inclusion criteria, age, and gender. For example, the participants in the study of Stegen (23) were selected from the upper and lower quartiles of the NA distribution, which was not the case in other studies. Only men participated in the studies of Wientjes and Grossman (21) and Shershow (22), whereas other studies included both genders. Although gender was no significant predictor in the study of Dhokalia et al. (20), other studies report a significantly higher FetCO2 in men than in women (4345). The absence of a gender effect in the study of Dhokalia et al. (20) might be explained by yet another relevant, interacting variable: age. Convergent evidence shows that FetCO2 decreases with age in men (4647), whereas the picture is less clear for women. For example, Anderson, Parsons, and Scuteri (46) found a higher PetCO2 in older women than in older men, but no association of PetCO2 with age in women. Other authors report that in association with the menopause, FetCO2 of women increases and approximates values observed in similarly aged men (48). Extensive research by Han et al. (7) has revealed complex interactions between trait NA, age, and gender in the prediction of FetCO2. We argue that whenever a wide age-ranged sample is studied, such interaction terms should be introduced in the model predicting FetCO2.
Second, a methodological flaw in studies including female participants is the lack of control for hormonal influences on FetCO2. Higher progesterone levels are associated with a lower FetCO2 (49,50). Progesterone levels are typically increased during the luteal phase of the menstrual cycle, during pregnancy, and also when using oral contraceptives.
Third, another important difference between the reported studies concerns the invasiveness of the measurement devices. In the Stegen (2429) studies, participants wore a nose clip and breathed via a mouthpiece connected to a pneumotachograph. This technique measures respiration accurately (51) but affects spontaneous breathing quite strongly (52,53), particularly in anxious participants (7). Mouthpiece breathing may constitute a respiratory challenge rather than a resting condition, which may increase ventilation and, consequently, reduce FetCO2 levels more in high-NA than in low-NA persons.
The establishment of a true resting condition is problematic also in the study of Dhokalia et al. (20). In this study, FetCO2 was measured while the participants were filling out a neuroticism questionnaire, which may have affected breathing behavior differently in high- versus low-NA participants, either through influences on emotional or on attentional processes. Indeed, cognitive load is associated with a decreased ventilation (54), which could have led to an increased FetCO2.
The present investigation contains two studies that aimed to clarify the inconsistent findings reported. In the first study, we assessed trait NA in 110 students and measured FetCO2 for 5 minutes via a noninvasive nose cannula, controlling for progesterone related fluctuations in FetCO2 in women. The second study (N= 40, balanced for gender and trait NA) investigated the influence on FetCO2 of: (1) the mental load associated with completing questionnaires (rest, filling out the NEO-PI-R, and completing a verbal knowledge test) and (2) the invasiveness of the used measurement device (nasal cannula or a mouthpiece).
| MATERIALS AND METHOD |
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Materials
Self report measures. The following questionnaires (Dutch translations) were completed in a group session before the individual sessions.
The Positive and Negative Affect scale (PANAS) (55) consists of 20 positive and negative affect words for which the participants had to indicate to which extent they feel that way in general (trait version) or now (state version).
The Anxiety Sensitivity Index (ASI) (56) is a 16-item questionnaire that measures an individuals fear of the symptoms of anxiety.
The Checklist for Psychosomatic Symptoms (CPS) consists of 35 symptoms belonging to one of the following subsets: paresthesia, cerebral, cardiac, gastrointestinal, respiratory, anxiety, or unclassified symptoms. The CPS was originally developed to assess symptoms that frequently occur in association with hyperventilation (21). We added four sensations that are rarely associated with hyperventilation, further called "atypical symptoms" to this list: nasal congestion, joint pain, low back pain, and burning eyes. Participants had to rate the extent to which they had felt each symptom during the past year (never, rarely, regularly, often, very often, coded as 1, 2, 3, 4, and 5, respectively).
At the end of the individual sessions, participants completed the state version of the PANAS. Finally, women were asked to indicate the phase of their menstrual cycle and whether they were using oral contraceptives.
Apparatus and Physiological DRecordings
Fractional end-tidal CO2-concentration (FetCO2) was measured using a nasal CO2-sampling cannula connected to a nondispersive infrared CO2-monitor (model 1265; Novametrix, USA). Its memory retained maximum values of FetCO2 over 8 seconds. Incomplete and irregular expirations that did not reach a reliable end-tidal plateau and would result in an overall underestimation of FetCO2 were discarded. Novacom software extracted the data via a RS232 serial port communication.
Procedure
The participants sat in a comfortable chair in a room adjacent to the equipment room and were monitored by the experimenter through a video camera.
To avoid drawing the participants attention to their breathing, a cover story described the aim of the study as an investigation of the relationship between body temperature and temperament. It was told that the nose cannula sampled expired air to measure its temperature "far more accurately than a standard thermometer." The participants were asked to keep their eyes open, not to move and to relax during the measurement, which would last for 5 minutes. After the FetCO2 measurement, they completed the state version of the PANAS and the questions regarding menstrual cycle and the use of oral contraceptives (for women).
Data Analyses
In a first step, we analyzed our data in a similar way as Stegen (23): a two-way ANOVA on FetCO2 was performed using a NA category (lower/upper quartiles of trait NA scores) x gender (male/female) design.
A second step in our analyses aimed to account for the influence of menstrual cycle and the use of oral contraceptives on FetCO2 in women. To check for these effects, a two-way ANOVA on FetCO2 with menstrual phase (follicular/luteal) and the use of oral contraceptives (yes/no) as independent variables was performed on the female subgroup.
Subsequently, FetCO2 of men was predicted in a standard multiple regression analysis with trait and state NA, trait and state positive affectivity (PA), and the ASI scores3 as predictors. Menstrual phase and Use of oral contraceptives were additional predictors of FetCO2 for women. Our sample size of women (N= 77 women) provided a reasonable power (0.83) to detect effects of medium size of the variables of primary interest (trait NA, menstrual phase, and use of oral contraceptives) (58). This was not the case for our sample size of men (N= 27), which had a power of only 0.30 to detect a medium effect of trait NA. Therefore, the results for men will be reported only for explorative reasons and should be interpreted with great caution.
In a third analysis, correlations between trait NA and PA, ASI and FetCO2 with the symptom scores of the CPS were calculated to check whether our data replicated the negative correlation between symptom reports and FetCO2 (21) and the positive correlation of trait NA with symptom reports (3742). For the latter correlation, the anxiety symptoms of the CPS were discarded in the calculation of the total symptom score, because of content overlap with several NA items.
| RESULTS |
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Women using oral contraceptives and women in the luteal phase of their menstrual cycle had a lower resting FetCO2 than, respectively, women not using oral contraceptives and women who were in the follicular phase [main effects of use of oral contraceptives, F (1, 73) = 7.67, p< 0.01, and of menstrual phase, F (1, 73) = 5.98, p< .005]. There was no significant interaction between both variables: F (1, 73) = 0.25, not significant.
Table 2 summarizes the multiple regression analyses. R2s were 18.6% for women and 13% for men. Trait and state NA, trait and state PA, and the ASI scores did not significantly predict resting FetCO2 in women, nor in men. Only menstrual phase (power = 0.66) and the use of oral contraceptives (power = 0.75) emerged as significant predictors of FetCO2 in women.
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Participants were selected on the basis of their scores on two measures of trait NA and on the CPS (see procedure). All participants smoked less than 5 cigarettes per day and had no respiratory or other major diseases. Only women not using oral contraceptives could participate and they were all tested in the second week of their menstrual cycle (follicular phase). Participants did not eat anything or drink any sugared or caffeinated beverages 2 hours preceding the experiment. To minimize the influence of circadian changes on FetCO2, they were all tested between 1:00 and 4:00 PM.
Materials
Participants completed the PANAS (55), a validated Dutch version (59) of the trait version of the STAI (60) and the CPS (21). The STAI is a 20-item questionnaire measuring trait anxiety and is considered a good measure of NA (19).
During the experiment, they completed the scales of the Dutch NEO-PI-R4 (61) and the VAT69 (62). The VAT69 assesses knowledge of the grammatical function of words. For 40 pairs of sentences, participants indicated which word(s) in the second sentence fulfilled the same grammatical function as the word(s) underlined in the first sentence. This test served to control for the potential effect of the emotional content of the NEO-PI-R items on FetCO2.
Apparatus and Physiological Recordings
FetCO2 was measured during performance of each task. Depending on the condition, expired air was sampled close to the mouthpiece (side stream) or through a nasal cannula. In the mouthpiece condition, the setup used by Stegen (2329) was replicated: participants wore a nose clip and had to breathe via a mouthpiece that was connected to a pneumotachograph (Fleisch no. 2, Switzerland). Upstream from the latter device, a double one-way valve ensured separation of inspired and expired air.
Procedure
In a group session preceding the experiment, 439 students had completed the trait version of the PANAS (55), the STAI (59), and the CPS (21). From that pool, high- and low-NA participants were selected. The scores of the former were in the upper quartile of the STAI and above the medians of the PANAS (NA scale) and the CPS. The scores of the selected low-NA participants were in the lower quartile of the STAI and below the medians of the NA scale of the PANAS and the CPS.5
After completing an informed consent form, the experimenter explained the aim of the experiment using the same cover story as in study one. It was added that for the sake of reliability, the measurement would take place three times with each of two different methods. The FetCO2 of each participant was measured for 6 minutes in each of the six trials made up by crossing the device variable (cannula, mouthpiece) with the task variable (resting, completing the NEO-PI-R, completing the VAT69). The order of these six within-subject conditions was semi-randomized with the restriction that nasal sampling was always alternated with mouthpiece sampling. The participants of each of the four between groups (N= 10) were similarly distributed across these six different orders (2 participants of each group were assigned to the first 4 orders and 1 participant of each group to the remaining 2 orders). Each nasal cannula and mouthpiece trial was followed by, respectively, 120 and 240 seconds of recovery, during which the sampling tubes were cleaned. The recovery following mouthpiece breathing lasted longer to ensure that the breathing of the participant would be fully recovered. Participants who did not finish the first 140 items of the NEO-PI-R within the foreseen time window (2 x 6 min) were asked to complete the remaining part of the questionnaire after the experiment.
Data Analyses and Design
Mean FetCO26 for each 6-minute period was calculated and analyzed in a NA (low/high) x gender (female/male) x devices (nose cannula/mouthpiece) x task (rest/NEO-PI-R/VAT69) design. NA and gender were between-subject variables; devices and task were within subject variables. Greenhouse-Geisser corrections were used wherever the task factor was involved.
Results
Table 4 displays the mean scores of trait NA as measured by the PANAS, the STAI, and the neuroticism scale of the NEO-PI-R, the mean symptom scores and the mean FetCO2 for high- and low-NA men and women.
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= 0.65) interacted with NA [F(1, 36) = 3.97, p< 0.001,
= 0.65; power = 0.92) (58). As can be seen in Fig 1, FetCO2 of high NA participants during rest is significantly lower than during both conditions of mental load [F(1, 36) = 18.65, p< 0.001,
= 0.65). This was not true for the low NA group [F(1, 36) = 1.43, not significant,
= 0.65). FetCO2 of high- and low-NA participants were not different during rest, nor during completion of the NEO-PI-R or the VAT69 [simple main F(1, 36) were 0.84, 0.12, and 0.16, not significant, respectively].
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= 0.65; power = 0.70]. Figure 2 showed that this was the case in the VAT 69 condition [F(1, 36) = 21.20, p< 0.001), but not in the NEO-PI-R [F(1, 36) = 2.79, ns] or in the rest condition [F(1, 36) = 0.29, not significant].
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| DISCUSSION |
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Our data, however, do confirm the findings of Dhokalia et al. (20) in that NA is positively associated with FetCO2 during filling out questionnaires, which indicates that the latter may not be considered a proper resting condition. More generally, our results strongly suggest that NA is an important modulator of situational influences on FetCO2. The increase in FetCO2 in high NA participants during both the completion of the NEO-PI-R and the VAT69 shows that not the emotional content of the personality questionnaire but rather the associated cognitive load is critical for the observed effect.
Whereas a decrease in FetCO2 (or hyperventilation) is a well-known response to stress and anxiety, less attention has been paid to the opposite response, ie, FetCO2 increases. Exceptions to this are the studies of Anderson and colleagues (63,64), showing that an inhibited breathing pattern in animals is characteristic for states of vigilance. Fokkema (65) provided two explanations for such an inhibited (strained) breathing pattern: it may be functional in depressing the noise associated with breathing when a predator is present and in preventing the threatened organism from hyperventilating when no physical activity is needed (yet). In humans, inhibited breathing showed up more frequently in the workplace, when people were sedentary or in social situations (66,67). Scuteri, Parsons, Chesney, and Anderson (68) interestingly suggest that the inhibited breathing pattern may be characteristic for a typical "female" physiological response to stress, in which sympathetically mediated "fight or flight" responses are inhibited in favor of parasympathetically mediated increases in oxytocin and reproductive hormones that support self-protective behaviors (69). Another, temptative interpretation of FetCO2 increases under conditions of mental load may be that, through cerebrovascular dilatation (44,45,7072), pCO2 increases may be functional in an enhanced cognitive performance. In that case, FetCO2 responses would constitute a promising measure of interest in research on test anxiety and cognitive performance.
To summarize, both increases and decreases in FetCO2 may be viewed very likely as adaptive responses to stress. This is in line with studies on situational influences on FetCO2, since the occurrence of hyperventilation responses depends on the type of laboratory stressor used (73,74). For example, FetCO2 decreases in response to a cold pressor test, but not in response to a shock avoidance task (13). Because high-NA participants are thought to be more reactive to stressors than low-NA participants (19), one could expect both responses to be more frequently present in the former than in the latter. If this holds, it is not surprising that there is no habitual, cross-situational relationship between NA and FetCO2 in nonclinical participants. The lower levels of resting FetCO2 in panic patients (212) then suggest that such patients are more inclined to respond with decreases in FetCO2 to a wide variety of stressors, whereas nonclinical participants would be better in selecting the response which is most adaptive for a particular situation. Such a reduced flexibility in selecting the most appropriate response is a key feature of anxiety pathology following Thayer and Lanes (75) model of emotional (dys)regulation.
The negative association of trait NA with FetCO2 found by Stegen (23) remains somewhat puzzling. Beause there was no interaction of Devices with NA in study two, Stegens finding could not be explained by an enhanced responsiveness of high-NA participants to the invasive measurement technique. Neither did we replicate the effect of Stegen (23) when only extreme NA scorers were used for analyses (lowest/upper quartiles), similarly to his study.
In study one, we replicated both the moderate, positive correlation between trait NA and symptom reports (3742) and the low, negative association of FetCO2 with symptom reports as found by Wientjes and Grossman (21). Except for cardiac symptoms, the correlations of symptom scores with anxiety sensitivity tended to be lower than with trait NA. However, whereas the correlations of trait NA with the subset symptom scores yielded a rather undifferentiated pattern, the ASI seemed to differentiate better between prototypical and atypical hyperventilation symptoms. Despite this specificity, the ASI was not significantly related to resting FetCO2.
Our data clearly confirmed the influence of progesterone on FetCO2: the obtained values were lower for women using oral contraceptives and for women in the luteal phase of their menstrual cycle. Moreover, because the gender difference disappeared when testing only women not using oral contraceptives at a time of very low progesterone levels (second week of the menstrual cycle), our data suggest that there is no gender difference in FetCO2 that could not be related to circulating progesterone.
In study two, it was found that FetCO2 during mouthpiece sampling was higher than during nasal sampling, but this held only during the VAT69 condition (Figure 2). One possible explanation for this may be that a strained breathing pattern (that is, a shortened inspiratory time with a lengthened expiratory time) (65) may have been more prominent during the verbal ability test. In combination with the dead space of the mouthpiece and the pneumotachograph, this may have led to a more rapid and pronounced increase in FetCO2.
More generally, we argue that the use of a very homogeneous sample may be an advantage when ones goal is to detect a small effect of a psychological variable on a measure that is also strongly influenced by other, biological variables. Indeed, the association between NA and FetCO2 in a more heterogeneous sample would more likely be confounded with age-, sex-, and, perhaps, also disease-related influences on FetCO2.
To summarize, we found no cross-situational association between trait NA and FetCO2. Whereas Dhokalia et al. (20) suggest that their observed positive association of FetCO2 with trait NA reflects a habitual state of chronic vigilance in people scoring high on NA, our data suggest that the association is induced by the situation, ie, completing a questionnaire during the FetCO2 measurement.
| NOTES |
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2Negative affectivity, trait anxiety and neuroticism can be used interchangeably (19). ![]()
3PA and ASI were introduced in the model for explorative reasons. Because the PA construct refers to ones level of energy and activity, it might be related to resting FetCO2. The ASI has been found to be a risk factor for the occurrence of spontaneous panic attacks, which might be reflected in a lower resting FetCO2 (57). ![]()
4Because the participants had only two time windows of 6 minutes each available for completing the NEO-PI-R, it was impossible to complete all scales. The items were rearranged in such way that all items of the Neuroticism scale were situated in the first 140 items. ![]()
5The criterion regarding the level of reported hyperventilation symptoms in daily life (CPS) was added to maximize the chance to observe an association between NA and FetCO2. Using this additional selection criterion, 23.4% of the possible participants based on the NA-criterion only (high NA with low symptom scores and low NA with high symptom scores) were excluded from the study. ![]()
6Because (maximally 5) breaths not reaching an end-tidal plateau were discarded, the number of observation points ranged from 40 to 45. ![]()
Received for publication October 15, 2002.
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