The Correlations Between Fluctuations in Anxiety Symptoms and Heart Rate Variability in Patients With Panic Disorder Combined With Agoraphobia: Application of Time Series Analysis in Individual Treatment

Panic disorder is a common psychiatric disorder. The lifetime prevalence is
2.1% and 12-months prevalence is 1.2%, women are 1.5 to 3 times more affected
then men, besides that panic disorders are responsible for 2,6% of all the
absence of work. There seems to be a bimodal distribution of prevalence with
age, one peak in late adolescence (15 - 19 years) and a second peak later in
life (35 - 50 years) 5. Patients that develop a panic disorder during
adolescence have an increased risk of acquiring a depressive disorder, other
psychiatric comorbidity and even suicide.
Patients with a panic disorder present themselves with episodes of
intense anxiety. These episodes are attended by physical symptoms such as chest
aches, sweating and shortness of breath. Because most patients believe that
these complaints are caused by heart failure (catastrophic cognitions), they
often visit the emergency room.
Patients have multiple panic attacks a week; this causes the patient to
worry about the future, when and where the next attack will occur. When this
leads to phobic avoidance behaviour for situations that could possible provoke
an attack, the patient has agoraphobia. Agoraphobia can lead to severe social
restriction, because patients sometimes are too afraid to use public transport
or even too afraid to leave the house3. This gives patients with agoraphobia
three kinds of fear. First there is the panic attack itself. Second there is
anticipation fear, in which the patients is afraid of a situation that is about
to come. And the third kind of fear is when the patient is exposed to what he*s
afraid of, called exposure. So on the one hand, there is the fear of a sudden
panic attack, and on the other hand there is fear for when the next attack will
be. This gives strong fluctuations in anxiety, with a lot of individual
differences in these fluctuations.
Knowledge about the underlying mechanisms for the fluctuations in anxiety
symptoms can contribute to the knowledge about the panic attack itself, but can
also provide the foundation for new, different kind of treatments. A possible
measure that has been related to both psychological as physical health
complaints in panic disorder is heart rate variability (HRV).
HRV refers to the fluctuations in the time intervals between
heartbeats. HRV is a common measure for vagal (main branch of the parasymathic
nervous system) innervation of the heart but is also a marker for the capacity
of emotional regulation. The ANS is subdivided in the sympathic (SNS) and
parasympathic nervous system (PNS). During physical or psychological stress the
activity of SNS becomes more dominant, producing a physiological arousal to
help adapting to the physical or emotional needs. During periods of stability,
the PNS takes over and maintains a lower degree of physiological arousal and
makes the heart beat at a slower pace. The ease with which an individual can
transition between different states of anxiety is dependent on the ability of
the ANS to rapidly vary heart rate.

HRV is an independent risk factor for several somatic diseases, but is also
related to psychiatric disorders, including panic disorder, agoraphobia and
anxiety symptoms. Previous research has shown that a low HRV has been
associated with high levels of stress, emotional tensions and an elevated state
of anxiety. One explanation may be that the lack of flexibility of the
autonomic nervous system may hinder an individual to produce an adequately
responding to an environment that is constantly changing. This could enhance
feelings of anxiety, and therefor may increase the risk for developing anxiety
problems later in life. The relation between HRV and anxiety symptoms is
bidirectional. Efferent output of the brain influences the cardiovascular
regulation, and afferent output of the heart influences the brain. So in
conclusion HRV serves as a marker for emotion regulation, and is regulated by
emotions itself.

A recent study has shown that in adolescent girls, HRV predicted anxiety levels
2 years later, in boys no association was found. Previous research has shown
that anxiety symptoms and HRV have the same anatomic basis, and genetic overlap
has been suggested as well. However not all studies found these association. A
possible explanation is that besides the fluctuations as described above, HRV
can fluctuate between and in patients as well. Whether HRV increases the state
of anxiety, or an increased state of anxiety decreases the HRV, or both are
possibilities. But the amount of research to these findings in studies with an
idiographic design is surprisingly low.

By achieving multiple measurements of ambulatory HRV and anxiety symptoms in
one individual agoraphobia patient during a standard treatment at the
University Center for Psychiatry (UCP), we will investigate how the
bidirectional causal relations between anxiety symptoms and HRV work. To
achieve this we use intensive ambulatory measurements during the patients daily
life
1. Will the daily reported anxiety symptoms decrease during the patients
treatment?
2. Will an increase of HRV decrease anxiety symptoms or will a decrease in
anxiety symptoms increase HRV?

The design of this study is idiographic, which means that instead of taking
measurements in a group, the focus in this study will be on a large amount of
measurements (>50) in one individual. Patients will be tracked while following
their treatment (8 weeks) for panic disorder during their daily life. The total
duration of the study is 10 weeks and will start one week prior to the
treatment, and will continue until one week after. In the weeks prior and after
the treatment an ECG-device is added. During the entire study patients must
wear an accelerometer and keep a diary, to document current anxiety symptoms
and self-esteem, which is supposed to be filled out several times a day.

Except the intensity of the study, there no health risks or what so ever. The
burdens consist out of, an inclusion interview (one hour), keeping a diary (x6
x 3x minutes a day prior and after treatment, during treatment x3 x 3x minutes
a day), wear an accelerometer and wear an ambulatory monitoring device for two
weeks in total: one week before, and one week after the treatment. The study
period is 10 weeks. Benefits for the patients include, more insight in the
patients pattern of anxiety symptoms, and person-specific factors that promote
a good mood.