Genetic influences on autonomic nervous system activity and the pro-inflammatory state: the moderating role of mental health status.

Repeated and prolonged sympathetic nervous system (SNS) activity coupled to
decreased parasympathetic nervous system (PNS) activity and the presence of
low-grade inflammation both lead to an increase in the risk for cardiovascular
disease.
Genetic association and family studies suggest that genetic factors are a
source of individual differences in pro-inflammatory status as well as
autonomic nervous system activity, although a large scale twin study on these
traits has not yet been undertaken. Based on theoretical notions, poor mental
health state has been cited as a second potential contributor to chronic
low-grade inflammation as well as to a shift towards higher sympathetic and
lower vagal cardiac control. To date the empirical evidence for this notion is
weak, and the observed association between mental health and sympathovagal
balance or inflammatory cytokines or acute phase reactants are modest at best.
Here we propose a new theoretical model that assumes that mental health status
interacts with the genetic factors influencing sympathovagal balance and the
pro-inflammatory state. We will use the twin-sibling design to determine the
genetic main effects and the gene-by-mental-health interaction effects on
individual differences in 1) pro-inflammatory cytokines and acute phase
proteins, and 2) 24-hour cardiac sympathovagal balance. We will further test
the hypothesis that sympathovagal balance and the pro-inflammatory state can
exert a mutual influence on each other.
Previous cross-sectuonal studies have already suggested an association between
these two sets of risk factors, but the causality of this association is
unclear. To test bidirectional causality we will combine existing data on the
sympathovagal balance at baseline in 1998-2003 and inflammation at a first
follow-up in 2004-2008 to a new round of data collection of sympathovagal
balance in a second follow-up in twins in 2010-2012. During the new study we
will collect:
1. 24-hour electrocardiogram and impedancecardiogram measurements by means of
the ambulatory VU-AMS device to assess heart rate variability (RSA) as a
measure of cardiac vagal control and the pre-ejection period (PEP) as a measure
of cardiac sympathetic control.
2. Mental health status using validated Dutch translations of the Spielberger
Trait Anxiety Inventory, the YASR anxious/depression subscale, the EPQ
neuroticism scale, the
Rosenberg Self-esteem questionnaire, the Happiness and
Satisfaction with Life scales.
3. A number of covariates including sex and age, socioeconomic status
(educational attainment, current profession), regular exercise behavior, major
life events, body mass index and waist-hip ratio, blood pressure, salivary
cortisol, current medication use, and sleep quality.

We will test a new theoretical model that assumes that mental health status
interacts with the genetic factors influencing sympathovagal balance and the
pro-inflammatory state. The results will be published in scientific magazines,
and/or presented at congresses, and can be of importance in the prevention of
depression and cardiovascular disease.

During the new study we will collect the following data in 160 MZ twins, 100 DZ
twins and 160 siblings:
1. 24-hour electrocardiogram and impedancecardiogram measurements by means of
the ambulatory VU-AMS device to assess heart rate variability (RSA) as a
measure of cardiac vagal control and the pre-ejection period (PEP) as a measure
of cardiac sympathetic control.
2. Mental health status using validated Dutch translations of the Spielberger
Trait Anxiety Inventory, the YASR anxious/depression subscale, the EPQ
neuroticism scale, the
Rosenberg Self-esteem questionnaire, the Happiness and
Satisfaction with Life scales.
3. A number of covariates including sex and age, socioeconomic status
(educational attainment, current profession), regular exercise behavior, major
life events, body mass index and waist-hip ratio, blood pressure, salivary
cortisol, current medication use, and sleep quality.

There are no familiar risks in measuring ECG or ICG with external electrodes.

The burden for the subjects is kept at a minimum by using nonivasive techniques
and a small measurement apparatus. In addition, the duration of the study is
being kept at a minimum because subjects are visited at home.