title: Idiopathic environmental intolerance: increased prevalence of panic disorder-associated cholecystokinin B receptor allele 7.
abstract: BACKGROUND
  A growing body of evidence suggests that idiopathic environmental intolerance (IEI) is a psychophysiologic disorder with prominent features of anxiety/panic and somatization, although proponents of a toxicogenic explanation claim, despite a lack of convincing evidence, that symptoms arise from exposure to otherwise nonnoxious environmental agents. Patient behaviour is characterized by strenuous avoidance of perceived triggers to the point of severe impairment of normal social and vocational functioning. IEI proponents claim that previous studies showing a high prevalence of psychopathology in patients with IEI and studies showing panic responses to known panicogenic challenges merely reflect the anxiety-producing result of living with IEI.
  
  
  OBJECTIVE
  We explored whether IEI and panic disorder, personality traits, or both shared an underlying neurogenetic basis that would predate the anxiety of IEI symptomatology. The DNA of patients with IEI was examined for the presence of known panic disorder-associated cholecystokinin B (CCK-B) receptor alleles and for personality trait-associated dopamine D4 receptor polymorphisms.
  
  
  METHODS
  Eleven patients with typical IEI symptoms were recruited and were individually matched to normal control subjects from an existing bank for age, sex, and ethnic background. Genomic DNA was extracted from peripheral blood samples. CCK-B and dopamine D4 receptor polymorphisms were examined by using standard PCR-based techniques.
  
  
  RESULTS
  There was a significantly higher prevalence of the panic disorder-associated CCK-B receptor allele 7 in subjects with IEI (9/22 [40.9%]) compared with control subjects (2/22 [9.1%], P =.037). There was no difference in personality trait-associated polymorphisms of the gene encoding dopamine D4 receptor between patients and control subjects.
  
  
  CONCLUSIONS
  These findings provide preliminary evidence that IEI and panic disorder share a common neurogenetic basis, which would predate the anxiety-producing effects of IEI symptoms. Further studies with larger samples are warranted, but these results support previous studies that suggest that panic disorder may account for much of the symptomatology in at least some cases of IEI and provide a basis for rational treatment strategies.
authors.affiliation: Gage Occupational and Environmental Health Unit, University of Toronto, Toronto, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Binkley
authors.forename: N
authors.initials: N
authors.lastname: King
authors.forename: N
authors.initials: N
authors.lastname: Poonai
authors.forename: P
authors.initials: P
authors.lastname: Seeman
authors.forename: C
authors.initials: C
authors.lastname: Ulpian
authors.forename: J
authors.initials: J
authors.lastname: Kennedy
mesh_terms: D000483:Alleles; D001362:Avoidance Learning / Q000502:physiology; D002766:Cholecystokinin / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018777:Multiple Chemical Sensitivity / Q000235:genetics*; D016584:Panic Disorder / Q000235:genetics*; D011110:Polymorphism, Genetic; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4
chemical_list: C493599:DRD4 protein, human; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D002766:Cholecystokinin; D004298:Dopamine