Interoceptive fear conditioning and generalization to respiratory sensations in panic disorder patients and healthy controls

Interoceptive processes may play an important role in the pathogenesis of panic
and anxiety disorders, prominently through the principles of classical
conditioning. However, despite their clinical importance, they are largely
understudied. Further focus on interoceptive fear conditioning and
generalization for interoceptive stimuli is important for the research of
etiology and treatment of not only panic disorder but also other psychosomatic
disorders and anxiety in general. If interoceptive conditioning and
generalization indeed play an important role, a new perspective for future
treatment is offered.


The overall objective of this study is the investigation of interoceptive fear
conditioning and generalization in both healthy subjects and a group of panic
patients. For the conditioning procedure, we will make use of respiratory
stimuli that are not aversive and completely harmless (conditioned stimulus,
CS). As the aversive stimulus we use a short, inspiratory, occlusion (US). The
duration of the occlusion is determined for each individual subject, based on
how long they are able to hold their breath, after expiration. After the
acquisition phase, subjects will show a slight fear response with respect to
the CS that was coupled with the occlusion. During a subsequent generalization
test, we can then examine to what extent participants show a fear response to
other, similar, respiratory sensations. After completion of the generalization
test, we ensure that all conditioned fear responses are extinguished by using
an extinction procedure (CS-alone presentations). More specific, one of our
expectations is a stronger fear acquisition and generalization in panic
patients, compared to the healthy control group.

The overall aim of this study is to investigate interoceptive conditioning of
fear and it*s generalization in both panic/anxiety patients and healthy control
subjects. Therefore we have three specific objectives.
The first objective is to replicate findings in healthy persons on how
interoceptive fear can be learned in a novel paradigm (Pappens, Smets,
Vansteenwegen, Van den Bergh, & Van Diest, 2012). In addition, we will
investigate whether panic patients acquire such interoceptive fear more
easily. In this paradigm, a slight sensation of obstructed breathing (created
by a flow resistor, or, *load* of 20 cmH²O/l/s) serves as the interoceptive
conditioned stimulus (CS) whereas a short interruption of the airflow
(occlusion) serves as the unconditioned stimulus (US). When the sensation
created by the *load* becomes a predictor for the occlusion, participants
will acquire fear to this originally benign sensation.
The second aim is to investigate to what extent this acquired fear
generalizes to other, similar, sensations. Therefore we present different
intensities of the obstructed breathing sensations (range 5 - 30 cmH²O/l/s) to
verify if participants also show fear responses to these stimuli (generalized
stimulus, or GS*s) that were never presented before.
The third aim is to investigate individual difference variables in the
extent of generalization and the course of panic disorder. Variables of
interest include heart rate variability at rest, memory for specific learning
events (as measured by the Autobiographical Memory Test (AMT) and the Rey
Visual Learning Design Test (RVDLT).

The study involves a paired/unpaired design that will be run both in a group of
persons with panic disorder and a healthy control group.
A resistive load (CS) will be used as a predictor for a short occlusion of the
airflow (US), in the acquisition phase, the paired group receives paired
presentations of CS and US, whereas both stimuli are explicitly unpaired in the
unpaired group. During generalization, both groups receive partially reinforced
presentation of the original CS and unreinforced presentation of the other
load-intensities (GS*s)

There are no risks associated with this study and both medical and personal
information are treated according to privacy and confidentiality regulations.