This COMT variant might increase the vulnerability to panic disorder by modulating dopaminergic tonus in relevant brain regions and thus altering neuronal processing of anxiety-related emotional cues.
Polymorphic markers at catechol O-methyltransferase (COMT), serotonin transporter (5-HTT), and tryptophan hydroxylase (TPH) genes were analyzed in a case-control association study of bipolar disorder patients with or without lifetime panic disorder.
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 COMTVal158Met, were selected for genotyping based on previous positive findings from genetic association studies in PD.
These results suggest that the L/L genotype of the COMT gene may be related to the development and treatment outcome of panic disorder in some patients.
The gender-specific effect of the COMT genotype suggests that the COMT Val/Met genotype may influence a personality trait, openness to experience, in males with panic disorder.
Only Val158Met polymorphism of the catechol-O-methyltransferase gene has been implicated in susceptibility to PD by several studies in independent samples and confirmed in a recent meta-analysis.
Recent association studies using persons with panic disorder described some association between polymorphisms in the genes encoding cholecystokinin and the cholecystokinin B-receptor and panic disorder.
In this age- and gender-matched case-control study involving 119 PD patients and 119 healthy controls, we examined the genotype distributions and allele frequencies of the serotonin transporter gene linked polymorphic region (5-HTTLPR), -1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (5-HT1A), and catechol-O-methyltransferase (COMT) gene polymorphism (rs4680) and their association with PD.
Our genetic dissection of the CCK system thus far suggests that the CCK-B receptor gene variation may contribute to the neurobiology of panic disorder.
However, given the relatively small number of case-control studies presently available, several more association studies, preferably including a larger number of family-based studies, are warranted for conclusive evaluation of the COMTval158met polymorphism as a vulnerability factor in panic disorder.
Genetic variation at the catechol-O-methyltransferase (COMT) gene has been significantly associated with risk for various neuropsychiatric conditions such as schizophrenia, panic disorder, bipolar disorders, anorexia nervosa and others.
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).
However, given the relatively small number of case-control studies presently available, several more association studies, preferably including a larger number of family-based studies, are warranted for conclusive evaluation of the COMT val158met polymorphism as a vulnerability factor in panic disorder.
We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36C>T) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls.
Together with the negative reports on association analyses using other polymorphisms of the CCKBR gene and Japanese samples, the present results exclude a major genetic contribution of the CCKBR gene to susceptibilities to panic disorder and schizophrenia in Japanese cohorts.
Our results suggest that the COMT L/L genotype is associated with PD and the genetic variant of the COMT enzyme may be related to the clinical severity and treatment response to paroxetine in PD.
We examined the promoter, exon, and exon-intron boundaries of the genes encoding CCK and its receptors (CCKAR and CCKBR) for variations in 187 patients with PD and 277 screened control individuals.
However, TBSS analysis showed increased fractional anisotropy (FA) in posterior thalamic radiation, posterior and superior corona radiata, superior longitudinal fasciculus, and sagittal stratum, all located in the right hemisphere in COMT AA/AG genotype group compared to GG genotype in panic disorder.
In the nuclear families, significant transmission disequilibrium for the valine allele was observed between the alleles of the Val158Met COMT polymorphism and panic disorder (p<0.01).
We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36C>T) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls.
We analyzed five genes, derived from pharmacological or translational mouse models, in a new case-control study of PD and SAD in European Americans: (1) the serotonin transporter (SLC6A4), (2) the serotonin receptor 1A, (3) catechol-O-methyltransferase, (4) a regulator of g-protein signaling and (5) the gastrin-releasing peptide receptor.