Association between serotonin-related genetic polymorphisms and CCK-4-induced panic attacks with or without 5-hydroxytryptophan pretreatment in healthy volunteers.
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-HT-related 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.
Maron
Eduard
E
Department of Psychiatry, University of Tartu, Raja 31, Tartu 50417, Estonia. Eduard.Maron@kliinikum.ee
Tasa
Gunnar
G
Tõru
Innar
I
Lang
Aavo
A
Vasar
Veiko
V
Shlik
Jakov
J
D006916:5-Hydroxytryptophan / Q000627:therapeutic use*; D000483:Alleles; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics; D009415:Nerve Net / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics; D016584:Panic Disorder / Q000188:drug therapy / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011949:Receptors, Cholecystokinin / Q000235:genetics*; D012701:Serotonin / Q000235:genetics* / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D012737:Sex Factors; D015854:Up-Regulation / Q000235:genetics
D017931:DNA Primers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011949:Receptors, Cholecystokinin; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D006916:5-Hydroxytryptophan; D008995:Monoamine Oxidase