This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Esler, M. Articles by Lambert, G. Search for Related Content PubMed PubMed Citation Articles by Esler, M. Articles by Lambert, G. Social Bookmarking                         What's this?

The neuronal noradrenaline transporter, anxiety and cardiovascular disease

Marlies Alvarenga

Baker Heart Research Institute, Melbourne, Australia

Ciaran Pier

Department of General Practice, Monash University, Melbourne, Australia

Jeff Richards

Assam El-Osta

David Barton

Baker Heart Research Institute, Melbourne, Australia

Deepak Haikerwal

Heart Centre, Alfred Hospital, Melbourne, Australia

David Kaye

Markus Schlaich

Ling Guo

Garry Jennings

Flora Socratous

Gavin Lambert

Baker Heart Research Institute, Melbourne, Australia

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.

Key Words: NET gene • epigenetics • DNA methylation • hypertension • panic disorder • postural tachycardia syndrome • noradrenaline • serotonin

Journal of Psychopharmacology, Vol. 20, No. 4 suppl, 60-66 (2006)
DOI: 10.1177/1359786806066055


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. Thorin and N. Thorin-Trescases Vascular endothelial ageing, heartbeat after heartbeat Cardiovasc Res, October 1, 2009; 84(1): 24 - 32. [Abstract] [Full Text] [PDF]

				V Raj, K L Haman, S R Raj, D Byrne, R D Blakely, I Biaggioni, D Robertson, and R C Shelton Psychiatric profile and attention deficits in postural tachycardia syndrome J. Neurol. Neurosurg. Psychiatry, March 1, 2009; 80(3): 339 - 344. [Abstract] [Full Text] [PDF]

				S. Kasparov and A. G. Teschemacher Altered central catecholaminergic transmission and cardiovascular disease Exp Physiol, June 1, 2008; 93(6): 725 - 740. [Abstract] [Full Text] [PDF]