The neuronal noradrenaline transporter, anxiety and cardiovascular disease

Esler, Murray, Alvarenga, Marlies, Pier, Ciaran, Richards, Jeff, El-Osta, Assam, Barton, David, Haikerwal, Deepak, Kaye, David, Schlaich, Markus, Guo, Ling, Jennings, Garry, Socratous, Flora and Lambert, Gavin 2006, The neuronal noradrenaline transporter, anxiety and cardiovascular disease, Journal of psychopharmacology, vol. 20, no. 4, Supplement, pp. 60-66, doi: 10.1177/1359786806066055.

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Title The neuronal noradrenaline transporter, anxiety and cardiovascular disease
Author(s) Esler, Murray
Alvarenga, Marlies
Pier, Ciaran
Richards, Jeff
El-Osta, Assam
Barton, David
Haikerwal, Deepak
Kaye, David
Schlaich, Markus
Guo, Ling
Jennings, Garry
Socratous, Flora
Lambert, Gavin
Journal name Journal of psychopharmacology
Volume number 20
Issue number 4
Season Supplement
Start page 60
End page 66
Publisher Sage Publications Ltd
Place of publication London, England
Publication date 2006
ISSN 1461-7285
Keyword(s) NET gene
DNA methylation
panic disorder
postural tachycardia syndrome
Summary 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, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients.

Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic ‘co-morbidity’ perhaps underlies the clinical concordance.

Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.
Language eng
DOI 10.1177/1359786806066055
Field of Research 110901 Autonomic Nervous System
Socio Economic Objective 920111 Nervous System and Disorders
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2006, British Association for Psychopharmacology
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Document type: Journal Article
Collections: Faculty of Health
School of Psychology
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