Association between Serotonin-related Genetic Polymorphisms and CCK-4-induced Panic Attacks with or without 5-hydroxytryptophan Pretreatment in Healthy Volunteers

• Published in: The world journal of biological psychiatry 2004-07, Vol.5 (3), p.149-154
• Main Authors: Maron, Eduard, Tasa, Gunnar, To˜ru, Innar, Lang, Aavo, Vasar, Veiko, Shlik, Jakov
• Format: Article
• Language: English
• Subjects: 5-Hydroxytryptophan - therapeutic use; Alleles; cholecystokinin; DNA Primers - genetics; Female; genetic polymorphism; Genotype; Humans; Male; Membrane Glycoproteins - genetics; Membrane Transport Proteins - genetics; Monoamine Oxidase - genetics; Nerve Net - metabolism; Nerve Tissue Proteins - genetics; panic attacks; Panic Disorder - drug therapy; Panic Disorder - genetics; Polymorphism, Genetic - genetics; Promoter Regions, Genetic - genetics; Receptors, Cholecystokinin - genetics; serotonin; Serotonin - genetics; Serotonin - metabolism; Serotonin Plasma Membrane Transport Proteins; Sex Factors; Up-Regulation - genetics
• ISSN: 1562-2975; 1814-1412
• DOI: 10.1080/15622970410029927

Summary Genetic regulation of the function of serotonin (5- HT) may be important for the neurobiology of panic disorder. In order to evaluate the influence of 5-HTrelated gene variants on the vulnerability to panic attacks, we genotyped 32 healthy volunteers who participated in the study of the effect of 5- hydroxytryptophan on panic attacks induced with cholecystokinin tetrapeptide (CCK-4). The polymorphisms of interest included those of 5-HT transporter (5-HTTLPR) and monoamine oxidase A (MAO-A promoter region) genes. The results showed significant associations between certain genotypes and panic rate in females but not in male volunteers. Specifically, there was a significantly lower rate of CCK-4-induced panic attacks in female subjects who had MAO-A longer alleles or 5- HTTLPR short allele gene variants. These data suggest that functional genetic polymorphisms of the 5-HT system may influence the vulnerability to panic attacks and add to the growing evidence of inhibitory function of 5-HT in the neuronal circuitry of panic.