title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Faculty of Medicine, Monash University & Cardiovascular Neurosciences Division, Baker Heart Research Institute, Baker Heart Research Institute, Prahran, Victoria, Australia. Marlies.alvarenga@med.monash.edu.au
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Alvarenga
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Richards
authors.forename: Gavin
authors.initials: G
authors.lastname: Lambert
authors.forename: Murray D
authors.initials: MD
authors.lastname: Esler
mesh_terms: D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000502:physiology; D016584:Panic Disorder / Q000150:complications / Q000503:physiopathology*; D013057:Spectrum Analysis
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D009638:Norepinephrine; D004837:Epinephrine