The neuronal noradrenaline transporter, anxiety and cardiovascular disease

  title={The neuronal noradrenaline transporter, anxiety and cardiovascular disease},
  author={Murray Esler and Marlies Alvarenga and Ciaran Pier and Jeff Richards and Assam El-Osta and David Barton and Deepak Haikerwal and David M. Kaye and Markus P. Schlaich and Ling Guo and Garry L R Jennings and Flora Socratous and Gavin W. Lambert},
  journal={Journal of Psychopharmacology},
  pages={60 - 66}
Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses. The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype… 

Figures from this paper

Altered central catecholaminergic transmission and cardiovascular disease

Targeted long‐term modulation of specific noradrenergic cell groups in defined brain areas using viral gene transfer is helping to clarify the links between central catecholamines and cardiovascular control in health and disease.

Methylation of the SLC6a2 Gene Promoter in Major Depression and Panic Disorder

Overall the variation in DNA methylation between patients was small, and the significance of this variation remains equivocal, and further in-depth analysis of alternative mechanisms of transcriptional regulation of the SLC6a2 gene in human health and disease would be of value.

Sympathetic Neural Control in Humans with Anxiety-Related Disorders.

This article assesses behavioral and lifestyle modifications that have been shown to concurrently improve anxiety symptoms, as well as sympathetic control, and examines the link between anxiety and cardiovascular risk.

Possible Mechanisms Linking Panic Disorder and Cardiac Syndromes

The aim of this chapter is to present the various ways in which the scientific community has been investigating the relations of panic disorder with cardiac syndromes.

Functional Gene Variation in the Human Norepinephrine Transporter

Altered transcription of SLC6A2 may represent a novel risk factor for the development of ADHD and be associated with ADHD through a significant association of the −3081(T) variant with ADHD.

Investigation into the molecular mechanisms of the norepinephrine and serotonin transporters in Attention Deficit/Hyperactivity Disorder

The role of genetic influence of the NE system on NET binding to be pertubated in ADHD is supported, and symptoms of hyperactivity and impulsivity correlated with NET BPND in the cerebellum depending on genotype.

Methylation of the SLC 6 a 2 Gene Promoter in Major Depression and Panic Disorder

Patients with MDD or panic disorder were not found to differ significantly from healthy controls in the pattern of methylation of the SLC6a2 gene promotor, and no significant changes in SLC 6a2 promoter methylation were observed in response to antidepressant treatment.

Neurovisceral phenotypes in the expression of psychiatric symptoms

Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety.



Cardiac Sympathetic Nerve Biology and Brain Monoamine Turnover in Panic Disorder

Normal norepinephrine turnover but a marked increase in brain serotonin turnover in patients with panic disorder, in the absence of a panic attack, is found, which presumably represents an underlying neurotransmitter substrate for the condition.

Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks.

Whole-body and regional sympathetic nervous activity are not elevated at rest in patients with panic disorder, possibly due to loading of cardiac neuronal stores by uptake from plasma during surges of epinephrine secretion in panic attacks.

Psychophysiological Mechanisms in Panic Disorder: A Correlative Analysis of Noradrenaline Spillover, Neuronal Noradrenaline Reuptake, Power Spectral Analysis of Heart Rate Variability, and Psychological Variables

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.

Neuropeptide Y: a cardiac sympathetic cotransmitter?

  • M. Haass
  • Biology, Medicine
    Advances in pharmacology
  • 1998

Single‐unit analysis of sympathetic nervous discharges in patients with panic disorder

Quantification from single vasoconstrictor unit recording provides evidence of a disturbed sympathetic firing pattern in patients with panic disorder.

Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension

It is suggested that neuronal reuptake of NE is impaired in essential hypertension and through amplification of the neural signal, such a defect could constitute a neurogenic variant of essential hypertension.

Norepinephrine Kinetics in Essential Hypertension

A defect in neuronal uptake of norepinephrine, by exposing adrenergic receptors to high local nore Pinephrine concentration, may be important in the parhogenesis of blood pressure elevation in some patients with essential hypertension.

Cardiac sympathetic nerve function in congestive heart failure.

Decreased NE store size in the failing heart appears to result not from insufficient tyrosine hydroxylation but from chronically increased NE turnover and reduced efficiency of NE reuptake and storage.

Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency.

Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance, a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli.

Catecholamines : bridging basic science with clinical medicine

Mutations in the tyrosine hydroxylase gene cause various forms of L DOPA responsive dystonia, K. Bartholome, B. Ludecke New regulatory protein of catecholamine synthesizing-enzyme expression, T.