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Psychophysiological Mechanisms in Panic Disorder: A Correlative Analysis of Noradrenaline Spillover, Neuronal Noradrenaline Reuptake, Power Spectral Analysis of Heart Rate Variability, and Psychological Variables
Abstract
Background: The risk of adverse clinical cardiac events is increased in patients with panic disorder (PD). We evaluated possible mechanistic links between PD and heart disease. We estimated cardiac vagal activity from heart rate variability (HRV) measurements and quantified sympathetic nervous system (SNS) activity using plasma noradrenaline tracer kinetics methodology. Methods: Thirty-nine people with PD and 39 age- and gender-matched healthy volunteers were studied. In 19 participants with PD, both HRV and plasma noradrenaline kinetics were tested; in 20 with PD and 20 healthy volunteers, HRV measurements only were made, whereas in 19 healthy volunteers, noradrenaline kinetics only was tested. All panic disorder participants completed psychological measures of anxiety sensitivity and state and trait anxiety; healthy volunteers in whom HRV was measured also provided psychological measures. Results: Sympathetic nervous tone in the heart, based on rates of cardiac noradrenaline spillover, was normal in PD. Noradrenaline and adrenaline plasma clearance and plasma tritiated noradrenaline and adrenaline extraction in transit through the heart, all dependent on the noradrenaline transporter (NET), were reduced in PD. Psychometric testing linked inhibition of anger to this deficit in NET functioning. Anxiety sensitivity was specifically associated with impaired cardiac NET. High- and low-frequency heart rate spectral power was unrelated to all plasma noradrenaline kinetics measurements. Conclusion: Defective neuronal reuptake of noradrenaline, by augmenting the sympathetic neural signal in the heart, might have a dual effect, sensitizing the heart such as to lead to symptom development (and thus perhaps causing panic disorder) and, second, potentially contributing to adverse cardiac events in established PD. PD = panic disorder; CVD = cardiovascular disease; CAD = coronary artery disease; HRV = heart rate variability; LF = low frequency; ADIS-IV = Anxiety Disorders Interview Schedule for DSM-IV; ASP = Anxiety Sensitivity Profile; ASI = Anxiety Sensitivity Index; NET = noradrenaline transporter; SSRI = selective serotonin reuptake inhibiting; HF = high frequency; MAO = monoamine oxidase.
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“Conversely, with the coexistence of impaired norepinephrine reuptake with firing salvos in normal-weight essential hypertension 31,[33][34][35][36] and in depressive illness 42,51,79 and panic disorder, 51,79,80 there is evidence of cardiac risk, 84 even in panic disorder.[85][86][87]”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [80]
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“It is perhaps noteworthy that this phenotype of impaired neuronal noradrenaline reuptake is also well documented in essential hypertension (48) and the postural tachycardia syndrome (49), both being conditions which commonly coexist with PD (41,49,50).”
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Metadata
- Authors
- Alvarenga, M. E., Richards, J. C., Lambert, G., & Esler, M. D.
- Affiliations
- Monash University (AU)
- Baker Heart and Diabetes Institute (AU)
- Corresponding author
- Alvarenga, Marlies E.
- Venue
- Psychosomatic Medicine
- Published
- 2006-01
- Volume
- 68
- Issue
- 1
- Pages
- 8-16
- ISSN
- 0033-3174 (ISSN-L)
- OpenAlex
- W2001789483
- Semantic Scholar
- 07b5239887e1b70bccb062e31e6ae8416096dd7e
- Cited by
- 136
- References
- 45
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 8 · 2019: 2 · 2018: 4 · 2017: 2 · 2016: 16 · 2015: 11 · 2014: 4 · 2013: 10 · 2012: 8
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Psychosomatic Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- panic disorder, noradrenaline spillover, norepinephrine transporter, heart rate variability, cardiac vagal activity, sympathetic nervous system, anxiety sensitivity, state-trait anxiety, cardiovascular risk, adverse cardiac events
- MeSH terms
- Adult, Autonomic Nervous System Diseases, Epinephrine, Female, Heart Diseases, Heart Rate, Humans, Male, Middle Aged, Neurons, Norepinephrine, Spectrum Analysis, Panic Disorder, Norepinephrine Plasma Membrane Transport Proteins
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