A genotype-specific, randomized controlled behavioral intervention to improve the neuroemotional outcome of cardiac surgery: study protocol for a randomized controlled trial

Background: Cardiac surgery is one of the most commonly performed
surgical procedures worldwide with > 700,000 surgeries in 2006
in the US alone. Cardiac surgery results in a considerable exposure
to physical and emotional stress; stress-related disorders such as
depression or post-traumatic stress disorder are the most common
adverse outcomes of cardiac surgery, seen in up to 20% of patients.
Using information from a genome-wide association study to
characterize genetic effects on emotional memory, we recently
identified a single nucleotide polymorphism of the glucocorticoid
receptor gene (the Bcll single nucleotide polymorphism) as a
significant genetic risk factor for traumatic memories from cardiac
surgery and symptoms of post-traumaticstress disorder. The Bcll
high-risk genotype (Bcll GG) has a prevalence of 16.6% in patients
undergoing cardiac surgery and is associated with increased
glucocorticoid receptor signaling under stress. Concomitant animal
experiments have confirmed an essential role of glucocorticoid
receptor activation for traumatic memory formation during stressful
experiences. Early cognitive behavioral intervention has been shown
to prevent stress-related disorders after heart surgery.
Methods/Design: The proposed study protocol is based on the above
mentioned earlier findings from animal experiments and preclinical
studies in volunteers. Patients (n = 872) will be genotyped for the
Bcll single nucleotide polymorphism before surgery, which should
result in 120 homozygous high-risk carriers of the Bcll GG allele
and 240 randomly selected low-risk heterozygous or non-carriers of
the single nucleotide polymorphism. All patients will then undergo
randomization to either cognitive behavioral intervention or a
control intervention consisting of non-specific general information
about the role of stress in heart disease. The primary efficacy
endpoint will be post-traumatic stress levels at one year after
surgery as determined by a standardized questionnaire that has been
specifically validated in patients after critical illness.
Discussion: The proposed randomized controlled trial intends to
demonstrate that a preoperatively administered minimal cognitive
behavioral intervention targeted to homozygous carriers of the
Bc/l*G high-risk allele reduces traumatic memories and
post-traumatic stress disorder symptoms after heart surgery to a
level seen in non-carriers of the mutation, and thus improves the
neuroemotional outcome of cardiac surgery.