What are the genetic factors that contribute to panic disorder?

Updated: Mar 21, 2018
  • Author: Mohammed A Memon, MD; Chief Editor: Randon S Welton, MD  more...
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Panic disorder is a common psychiatric disorder that affects 3-5% of the population. [61] Studies of the association between psychiatric illness in first-degree relatives revealed a heredity of approximately 43% for panic disorder. [42] Patients with panic disorder also have a high rate (80%) of having other psychiatric disorders, many of which also have an important genetic basis.

Although panic disorder is a disease with a significant genetic basis, the exact nature of the basis is unclear. The present understanding suggests that panic disorder is a multifactorial condition, with multiple genes creating susceptibility to the condition coupled with influences from the environment. [54] The genetics of panic disorder is poorly understood relative to many psychiatric disorders in which genome-wide association studies (GWAS) have isolated numerous loci associated with susceptibility to disease.

Nonetheless, there are several loci that have been implicated in families with a strong history of panic disorder. Locus 13q22-32 has been linked to panic disorder and bladder conditions in families although the association was not found in families who had isolated panic disorder. [43] A locus at 9q31 was found to be associated with panic disorder (and likely generalized anxiety disorder) for an Icelandic cohort. [44]

In a study that performed a genome scan looking for regions of interest for anxiety disorders broadly defined in 219 US subjects in 19 extended pedigrees, investigators found an association at marker D4S413 on chromosome 4q31-q34, which is located near the NPY1R gene. This gene encodes the neuropeptide Y 1 receptor, and in an animal model, manipulation of this receptor was associated with anxiolysis. [45] A large GWAS that looked mainly at bipolar disorder but also psychosis, panic disorder, and suicidal behavior found an associated locus for panic disorder on 7q21. [47, 52]

Further study has implicated a few genes as likely contributors to panic disorder. Because monoamine oxidase inhibitors (MAOIs) have been used effectively in the treatment of panic disorder, the MAOA (monoamine oxidase A) gene is a logical consideration for contribution to panic disorder. In a study of a German and Italian population, patients with a longer repeat polymorphism in the MAOA promoter region had a higher incidence of panic disorder. [59] In recent years, the use of MAOIs has been in large part supplanted by newer agents.

Persons who are homozygous for a polymorphism in the COMT gene (catechol-o-methyltransferase), in which a methionine substitutes for a valine at position 158, have been associated with a higher rate of panic disorder than persons who did not carry these polymorphisms. [46] Additionally, it has been suggested that people who were homozygous for this polymorphism also had a poorer response to treatment. [46] A different study of the same polymorphism found an increased benefit of exposure-based therapy for those who had the Val158Met polymorphism. [53]

More recently, studies have isolated additional genes of interest for panic disorder. A polymorphism on the HCRT (hypocretin) gene, in which isoleucine substitutes for valine at position 308 on 17q21.2, has been implicated in increased risk of panic disorder. [48] Additional GWAS have identified the neuropeptide S gene, the amiloride-sensitive cation channel gene, and the adenosine A(2A) genes as candidate genes. [49, 50, 51]

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