title: Association testing of panic disorder candidate genes using CCK-4 challenge in healthy volunteers.
abstract: Despite continuing efforts to determine genetic vulnerability to panic disorder (PD), the studies of candidate genes in this disorder have produced inconsistent or negative, results. Laboratory panic induction may have a potential in testing genetic substrate of PD. In this study we aimed to explore the effects of several genetic polymorphisms previously implicated in PD on the susceptibility to cholecystokinin-tetrapeptide (CCK-4) challenge in healthy subjects. The study sample consisted of 110 healthy volunteers (47 males and 63 females, mean age 22.2 +/- 5.2) who participated in CCK-4 challenge test. Nine gene-candidates, including 5-HTTLPR, MAO-A VNTR, TPH2 rs1386494, 5-HTR1A -1019C-G, 5-HTR2A 102T-C, CCKR1 246G-A, CCKR2 -215C-A, DRD1 -94G-A and COMT Val158Met, were selected for genotyping based on previous positive findings from genetic association studies in PD. After CCK-4 challenge, 39 (35.5%) subjects experienced a panic attack, while 71 subjects were defined as non-panickers. We detected significant differences for both genotypic and allelic frequencies of 1386494A/G polymorphism in TPH2 gene between panic and non-panic groups with the frequencies of G/G genotype and G allele significantly higher in panickers. None of the other candidate loci were significantly associated with CCK-4-induced panic attacks in healthy subjects. In line with our previous association study in patients with PD, we detected a possible association between TPH2 rs1386494 polymorphism and susceptibility to panic attacks. Other polymorphisms previously associated with PD were unrelated to CCK-4-induced panic attacks, probably due to the differences between complex nature of PD and laboratory panic model.
authors.affiliation: Department of Psychiatry, University of Tartu, Tartu, Estonia. Eduard.Maron@kliinikum.ee
authors.forename: Eduard
authors.initials: E
authors.lastname: Maron
authors.forename: Innar
authors.initials: I
authors.lastname: Tõru
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tasa
authors.forename: Anne
authors.initials: A
authors.lastname: Must
authors.forename: Egle
authors.initials: E
authors.lastname: Toover
authors.forename: Aavo
authors.initials: A
authors.lastname: Lang
authors.forename: Veiko
authors.initials: V
authors.lastname: Vasar
authors.forename: Jakov
authors.initials: J
authors.lastname: Shlik
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects / Q000235:genetics; D002395:Catecholamines / Q000096:biosynthesis; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D016584:Panic Disorder / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics*; D013758:Tetragastrin / Q000009:adverse effects; D014365:Tryptophan Hydroxylase / Q000235:genetics*; D055815:Young Adult
chemical_list: D002395:Catecholamines; D013758:Tetragastrin; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase