Autonomic nervous system and its association with brain function in major depressive disorder

  • Dr Tye Dawood, Baker IDI Heart and Diabetes Institute, Australia
  • Dr David Barton, Baker IDI Heart and Diabetes Institute, Australia
  • Dr Elisabeth Lambert, Baker IDI Heart and Diabetes Institute, Australia
  • Mr Dominique Laude, INSERM UMRS 872, France
  • Prof Jean-Luc Elghozi, Necker Hospital, France
  • Ms Florentia Socratous, Baker IDI Heart and Diabetes Institute, Australia
  • Dr Sarah Hennebry, Baker IDI Heart and Diabetes Institute, Australia
  • Dr Gavin Lambert, Baker IDI Heart and Diabetes Institute, Australia

We recently demonstrated elevated brain serotonin turnover in untreated MDD, with over a 2-fold increase in turnover being associated with carriage of the s allele of the serotonin transporter (5-HTT) gene. Further, sympathetic nervous activity (SNA) followed a bimodal distribution, with some extraordinarily high values and some marginally lower than in healthy subjects. Therefore, we hypothesized that the bimodal distribution of SNA may be related to the 5-HTT genotype and hence, the degree of SNA in MDD may be dependent upon the level of brain serotonin turnover.

Twenty-five unmedicated patients with moderate-severe MDD were studied at rest and following 10 minutes mental arithmetic, before and approximately 12 weeks after SSRI treatment. Using arterial blood sampling with norepinephrine isotope dilution methodology, SNA levels were assessed. In parallel, cardiac baroreflex function and heart rate variability were used as indexes of parasympathetic/vagal activity, and 5-HTT genotype determined. Statistical analyses comprised 2 way repeated measures ANOVA.

Resting SNA was significantly higher in patients carrying the s allele (712±76 v 386±82ng/min). In response to mental stress, SNA and heart rate increased by a similar magnitude in the long and short genotype groups, whereas blood pressure was substantially increased in the s genotype group (P<0.001). Vagal activity decreased following stress but bore no association with the 5-HTT genotype. Therapy markedly decreased HamD and BDI-II, and resting heart rate and vagal activity (P=0.03 and 0.05, respectively). SNA was reduced (P<0.01) in the s genotype, 262±91ng/min (s allele) v 245±83ng/min (l allele). Interestingly, SSRI therapy was associated with dampening of the sympathetic, parasympathetic and associated hemodynamic responses to stress.

Elevated SNA is evident in MDD patients carrying the s allele of the 5-HTT gene. Given previous observations linking 5-HTT genotype and brain serotonin turnover, robust measures of SNA may provide an indirect marker of brain function in MDD.