ABSTRACT
The aim of the study was to investigate whether polymorphisms in the preproghrelin gene are associated with anxiety disorders, such as panic disorder, in humans. Panic disorder is a severe anxiety disorder, characterized by sudden attacks of intense fear or anxiety in combination with somatic symptoms. The preproghrelin gene codes for two gut-derived circulating peptides that have been linked to anxiety-like behaviour in rodents: ghrelin (an orexigenic, pro-obesity hormone) and obestatin. In the present study, we genotyped three missense mutations in the preproghrelin gene in 215 patients suffering from panic disorder and in 451 controls. The A allele of the rs4684677 polymorphism was significantly associated with panic disorder, while there were no significant associations with the two other polymorphisms studied. We conclude that the rs4684677 (Gln90Leu) polymorphism in the preproghrelin gene may be associated with increased risk of panic disorder. It will be important to confirm these findings in additional panic disorder patient groups.
Subject(s)
Genetic Predisposition to Disease/genetics , Ghrelin/genetics , Panic Disorder/genetics , Polymorphism, Single Nucleotide/genetics , Adolescent , Adult , Aged , Female , Gene Frequency , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Mutation, Missense/genetics , Young AdultABSTRACT
BACKGROUND: Orexin A and B are neuropeptides influencing, for example, arousal and respiration. Although panic disorder is characterized by both enhanced proneness for arousal and by respiratory abnormalities, the possible influence of orexin-related genes on the risk of developing this disorder has not been studied until now. METHODS: We have analyzed the Ile408Val polymorphism in the hypocretin receptor 1 (HCRTR1) gene and the Val308Iso (G1246A) polymorphism in the hypocretin receptor 2 (HCRTR2) gene in a sample of 215 panic disorder patients and 454 controls. RESULTS: Although the polymorphism in the HCRTR1 did not differ between groups, the Iso allele of the HCRTR2 polymorphism was significantly more frequent in patients than in controls. After the population was divided according to sex, the association between the Iso allele of the Val308Iso polymorphism and panic disorder was observed only in female patients. CONCLUSION: Our results suggest that the HCRTR2 polymorphism may be of importance for the pathophysiology of panic disorder. The results should be regarded as preliminary until replicated in an independent sample. This indicates that further research on the possible role of orexin in panic disorder may prove rewarding.
Subject(s)
Amino Acid Substitution/genetics , Genetic Predisposition to Disease , Panic Disorder/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, G-Protein-Coupled/genetics , Receptors, Neuropeptide/genetics , Adult , Female , Gene Frequency/genetics , Humans , Male , Orexin ReceptorsABSTRACT
The association between the catechol-O-methyltransferase Val158Met polymorphism and panic disorder was studied in a Swedish sample of 211 patients and 452 controls. We found a significant excess of the Val allele in both male and female patients, the latter but not the former finding being in line with previous studies.
Subject(s)
Catechol O-Methyltransferase/genetics , Methionine/genetics , Panic Disorder/genetics , Polymorphism, Genetic , Valine/genetics , Adult , Female , Gene Frequency , Genetic Association Studies , Humans , Male , Middle Aged , SwedenSubject(s)
Anxiety Disorders/enzymology , Anxiety Disorders/genetics , Depression/enzymology , Depression/genetics , Polymorphism, Genetic , Tryptophan Hydroxylase/genetics , Adult , Amino Acid Substitution , Base Sequence , Case-Control Studies , DNA Primers/genetics , Female , Humans , Male , Middle AgedABSTRACT
Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.
Subject(s)
Genetic Predisposition to Disease , Panic Disorder/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Progesterone/genetics , Chromosomes, Human, Pair 11/genetics , Female , Gene Frequency , Humans , Male , Risk Factors , Sex FactorsABSTRACT
Enhanced respiratory variability and decreased heart rate variability have repeatedly been observed in patients with panic disorder. Prompted by the notion that angiotensin may be involved in the control of respiration, heart rate variability, and anxiety-like behavior, we investigated the putative association between polymorphisms in three angiotensin-related genes and panic disorder-angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II (ANG II) receptor type 1 (ATr1) in 72 patients with panic disorder and 504 controls. Allele and genotype distribution of the ATr1 A1166C allele and the AGT M235T did not differ between patients and controls. With respect to the ACE I/D polymorphism, the I allele was found to be more frequent in male (chi(2) = 8.042, df = 1, P = 0.005), but not female, panic disorder patients than in controls. The results of this investigation provide preliminary evidence for the suggestion that angiotensin-related genes may be associated with panic disorder in men.
Subject(s)
Angiotensinogen/genetics , Panic Disorder/genetics , Peptidyl-Dipeptidase A/genetics , Receptor, Angiotensin, Type 1/genetics , Alleles , DNA/chemistry , DNA/genetics , DNA Mutational Analysis , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Mutation, Missense , Panic Disorder/pathology , Polymorphism, GeneticABSTRACT
BACKGROUND: Panic disorder (PD) is generally regarded as a chronic condition with considerable variation in severity of symptoms. AIMS: To describe the long-term outcome of naturalistically treated PD. METHODS: Fifty-five outpatients with PD, who participated in a placebo-controlled drug trial of the efficacy of alprazolam and imipramine 15 years ago were reassessed with the same instruments used in the original study. RESULTS: Complete recovery (no panic attacks and no longer on medication during the last 10 years) was seen in 18% of patients, and an additional 13% recovered but were still on medication. Fifty-one percent experienced recurrent anxiety attacks whereas 18% still met diagnostic criteria for PD. The incidence of agoraphobia decreased from 69% to 20%. Patients with agoraphobia at admission tended to have a poorer long-term outcome according to daily functioning compared with patients without agoraphobia at admission, although both groups reported improved daily functioning at follow-up. Maintenance medication was common. No benzodiazepine abuse was reported. CONCLUSION: PD has a favourable outcome in a substantial proportion of patients. However, the illness is chronic and needs treatment. The short-term treatment given in the drug trial had no influence on the long-term outcome.
