Metabolic decoupling in daily life in patients with panic disorder and agoraphobia
Introduction
Numerous studies have assessed cognitive and physiological underpinnings of panic attacks (PAs) (Papp et al., 1993), but a clear understanding of panic disorder (PD) is still lacking. Moreover, it is questionable if laboratory findings can be generalized to patients' everyday life since PD patients are particularly sensitive to experimental contexts (Abelson et al., 2007). Therefore, some studies have investigated PD patients in their daily lives. These studies found subtle but significant precursors of naturally occurring PAs in heart rate and other physiological measures (Margraf et al., 1987, Meuret et al., 2011). A rarely studied question relates to PD patients' psychophysiological functioning in the absence of PAs. Specifically, do PD patients show elevated physiological responses to challenges of daily life? Such responses would parallel subjective complaints about persistently elevated anxiety and arousal (Taylor, 1995, Brown and McNiff, 2009). Furthermore, such background psychophysiological activation might provide a basis for PAs by lowering the threshold for acute panic (Clark, 1986, Ehlers et al., 1988). The present study was concerned with the assessment of such alterations.
One index of potential psychophysiological background activation in anxiety disorders is HR (Kreibig, 2010). HR is closely related to emotional processes: During intense anxiety, accelerations of up to 110 bpm have been observed (Wilhelm and Roth, 1998a). Laboratory studies demonstrated that HR elevations to acute threat are in excess of metabolic demand and beta-adrenergically mediated (Langer et al., 1979, Sherwood et al., 1986). Since much of HR variation across the day reflects movement related muscular activity, separation of metabolic and anxiety related contributions to HR is a challenge for ambulatory anxiety research. Thus, the concept of ‘additional HR’ was developed: sophisticated accelerometric measurements were used to index metabolic demand. HR acceleration in excess of these demands were considered anxiety related, additional HR (Myrtek et al., 1988). This approach has been expanded by measuring minute ventilation (Vm, the total amount of liters expired and inspired per minute) (Grossman et al., 2010; Wilhelm and Roth, 1998b). Here, we utilize both accelerometry and Vm to index metabolic contributions to HR.
In daily life, HR and Vm are strongly coupled to physical activity since muscular work and the associated increased metabolism require increased oxygen transport. Generally, at low to moderate levels of aerobic exercise, which correspond well with people's daily routines, both HR and Vm increase rather linearly to transport oxygen to muscles and organs (Delistraty et al., 1991). At these levels, Vm is a good proxy for oxygen consumption, a putative index of metabolic activity (Grossman et al., 2010). Compared to HR, Vm is less tightly coupled to emotional activation (Delistraty et al., 1991, Wilhelm et al., 2006). Nevertheless, anxiety and PD have been associated with respiratory alterations. For example, variability indices (Wilhelm et al., 2001a) and sigh rate (Wilhelm et al., 2001b) but also lowered end-tidal partial CO2 pressure were repeatedly found in PD (Papp et al., 1997, Hegel and Ferguson, 1997). However, in line with other studies showing that hyperventilation plays some, but not a major role in anxiety (Wilhelm and Roth, 1998a, Kreibig, 2010; Garssen et al., 1996), ambulatory recordings of respiratory pattern in PD found no evidence for trait-abnormalities in breathing – not in terms of respiratory timing and respiratory volume parameters and neither during minimal physical activity (Pfaltz et al., 2009) nor during different levels of physical activity (Pfaltz et al., 2010b). Vm might therefore be considered a relatively anxiety-independent index of metabolic demand, especially in ambulatory studies. In daily life of PD patients, elevated anxiety (outside PAs) should thus result in HR increases but also in decoupling between physical activity and HR, due to emotion related HR changes, occurring in excess of metabolically related HR alterations (Wilhelm and Roth, 1998b, Carroll et al., 1986). Conversely, coupling between physical activity and Vm should be relatively unaffected by anxiety, as Vm is strongly related to physical activity but only weakly to anxiety. Thus, elevated anxiety in PD should also reduce coupling between HR and Vm.
We assessed this anxiety-related decoupling between physical activity and HR and between Vm and HR in daily life of PD patients and healthy controls (HC). We assumed that assessment of metabolic coupling would reveal physiological alterations in PD that, with traditional methods, were only detectable in some (Martinez et al., 1986, Stein et al., 1995) but not in other ambulatory studies (Hoehn-Saric et al., 2004, Pfaltz et al., 2009, Pfaltz et al., 2010b). More specifically, we assumed that PD patients show elevated and more frequent phasic anxiety reactions to daily situations (Pfaltz et al., 2010a) that might be accompanied by HR fluctuations that are disproportional to metabolic demands. This would give rise to a) elevated HR and b) decoupling between HR and accelerometry and between HR and Vm. Second, we assumed that PD patients show elevated trait anxiety and anxiety sensitivity (McNally, 1999), resulting in elevated tonic emotional activation and associated trait-like, anxiety related physiological changes like persistent HR elevations (Hoehn-Saric et al., 1991, Martinez et al., 2010, Roth et al., 1986, Cohen et al., 2000). Such persistent changes might interfere with the fine tuning between organismic systems that are normally efficiently and rapidly coupled via feedback loops during periods of varying physical activity, further diminishing associations between HR and accelerometry and between HR and Vm. We thus assessed the hypotheses that 1) PD patients show diminished coupling between HR and accelerometry and between HR and Vm and that 2) In PD, HR-Acc coupling and HR-Vm coupling are inversely related to both phasic and tonic anxiety.
Section snippets
Participants
Participants were recruited as part of a larger study assessing anxiety symptoms (Pfaltz et al., 2010a, Pfaltz et al., 2013) and ambulatory respiratory measurements (Pfaltz et al., 2009, Pfaltz et al., 2010b). For the present analyses, we included 19 PD patients and 20 HC of the original sample (Pfaltz et al., 2009) who, in addition to undergoing physiological monitoring, completed electronic symptom diaries (Pfaltz et al., 2010a), providing information on anxiety and PAs. All PD patients were
Results
Groups did not differ in age, gender, or BMI but patients showed elevated tonic and phasic anxiety (Table 1).
Groups were comparable regarding mean Acc and Vm. PD patients had higher mean HR than HC (Table 2). When including Acc as covariate, this group difference was no longer significant (F (1,35) = 3.36, p = .075). For Vm, when including Acc as covariate, no significant group difference emerged (F(1,35) = 0.58, p = .45). Acc-HR and Vm-HR coupling was lower in PD than in HC. When using Acc and
Discussion
We used a novel approach to examine metabolic indices and emotional activation in PD patients in daily life. In line with our hypotheses, considering ventilation and accelerometry separately as metabolic activity markers reliably revealed reduced coupling of these indices with HR in PD relative to HC. When combining the two, the effect size for the group difference in metabolic coupling was even higher, suggesting that accelerometry and minute ventilation are both important, non-redundant
Role of the funding source
This research was supported by Grant 105311–105850 from the Swiss National Science Foundation (SNSF) to FHW and JM. The SNSF had no role in study design, data collection, analysis or interpretation, or in writing of the manuscript or decision to publish.
Contributors
Frank H. Wilhelm, Monique C. Pfaltz, Jens Blechert, Juergen Margraf, and Paul Grossman contributed to designing the study and drafting the manuscript. Data were analyzed by Monique C. Pfaltz and Vitaliy Kolodyazhniy. All authors approved the final version of the manuscript.
Conflicts of interest
None of the authors have any biomedical, financial, or other conflicts of interest.
Acknowledgments
We are thankful to Rebecca Dittmann, M.Sc. for her help with data collection and to Peter Peyk, Ph.D. for his help with data analyses.
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These two authors contributed equally to this paper.