The Genetics of Panic Disorder

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A study published earlier this year in the American Journal of Medical Genetics suggests that lymphoblast gene expression may be used to identify biomarkers for panic disorder. Researchers at the University of Iowa evaluated gene expression profiles in lymphoblasts (immature white blood cells) cultured from patients with and without panic disorder and found specific disorder- and sex-related differences [1]. A blood test for panic disorder and other mental health conditions based on the study results is being developed. However, a commercial diagnostic test may be premature as the study results are far from conclusive.

Panic attacks and panic disorder

Panic attacks are episodes of acute, intense anxiety, characterized by a variety of physical symptoms that may include numbness in the hands and feet, shortness of breath, chest pain, heart palipitations, dizziness and a feeling of loss of control or dying. The onset of a panic attack is sudden and may have no obvious trigger. A panic attack is a response of the sympathetic nervous system, a branch of the autonomic nervous system that maintains homeostasis in the body, which becomes active during periods of stress.

Researchers aren’t sure what causes panic attacks. A variety of biological and pharmacological factors can trigger them, including stress, stimulants, hyperventilation, vitamin b deficiency and heredity. According to the American Psychological Association:

Many people experience occasional panic attacks, and if you have had one or two such attacks, there probably isn’t any reason to worry. The key symptom of panic disorder is the persistent fear of having future panic attacks. If you suffer from repeated (four or more) panic attacks, and especially if you have had a panic attack and are in continued fear of having another, these are signs that you should consider finding a mental health professional who specializes in panic or anxiety disorders.

Indeed, repeated attacks can become very debilitating. Increased phobias and anxiety can lead to the development of panic disorder, which affects about 6 million American adults [2] and is twice as common in women as in men [3]. Panic disorder is characterized as an anxiety disorder, which involves having recurrent, unexpected panic attacks followed by at least one month of persistent concern about having another attack, worry about the consequences of panic attacks and a change in behavior as a result of the attacks [4]. Patients with panic disorder have an increased risk of developing other psychiatric disorders. Panic disorder is further associated with other medical conditions such as migraines, fibromyalgia and irritable bowel syndrome [5].

Genetics

Studies of twins and families suggest that genetics plays a role in the development of panic disorder. First-degree biological relatives of people with panic disorder are 4 to 7 times more likely to develop panic disorder [4]. Children of parents who have panic disorder are up to 8 times more likely to develop the condition [4]. Additionally, children of parents who have either depression or bipolar disorder are also at a higher risk of developing panic disorder [6-7].

A large number of candidate gene studies and several genome-wide studies have been conducted to identify genetic factors associated with increased susceptibility to panic disorder. These studies have failed to clearly describe the biology of panic disorder. Indeed, the phenotypic and genetic complexity of panic disorder has made biological studies challenging [8]. Obstacles defining the molecular mechanisms involved in panic disorder arise, in part, from the inherent difficulties accessing brain tissue in quantities and qualities necessary for scientific study.

To overcome these issues, University of Iowa researchers recently used lymphocytes and their derived lymphoblast cell lines as an alternative tissue source, citing a number of studies that have demonstrated that gene expression differences found in either lymphoblasts or lymphoblast cell lines are predictive of complex “medical” illnesses including hyperlipidemia, hypertension and arthritis [9]. They suggest that peripheral blood cells could serve as a biosensor if environmental or gene-environmental interactions are important in the etiology of panic disorder, since nearly 82% of the genes expressed in the central nervous system are expressed in peripheral blood and the expression of genes in peripheral blood is affected by “environmental conditions.”

Cultured lymphoblast gene expression was compared from 16 patients with panic disorder and 17 without the disorder. Patients with panic disorder were found to have significantly different patterns of lymphoblast gene expression compared to patients without. Interestingly, almost 7 times more genes were found to be activated than repressed in patients with panic disorder. Researchers also identified a number of sex-specific differences in gene expression; that is, increased or decreased gene expression in cell lines from women with panic disorder as compared to female control lines, and from men with panic disorder as compared to male control lines. However, the study has a number of problems, some of which are troubling given that the data is being used to develop a costly predictive test [10].

First, although panic disorder is a disease of brain cells, the study evaluated the expression of genes from lymphoblasts. The principle assumption is that environmental or gene-environmental interactions are causal factors for panic disorder and gene expression differences in lymphoblasts will be predictive of panic disorder. However, this has yet to be shown. Second, all but 2 of the 16 patients with panic disorder were on psychiatric medications, which may confound the results. Third, there was discrepancies in the age of cell lines between patients with and without panic disorder. Fourth, only 5 genes were selected for confirmation by qRT-PCR, and only 3 of the 5 passed. Lastly, functional cluster analysis, which attempts to ascribe biological function to clusters of genes displaying similar expression patterns by identifying statistical over-representation of genes associated with biological pathways or processes, failed to identify any significant enrichment.

The researchers mention several calcium channel genes that were dysregulated in patients with panic disorder. The role of calcium in anxiety disorders has been proposed for decades. However, the limited analysis and failure to identify functional enrichment leaves little to be derived from the study. Nevertheless, the identification of lymphoblast gene expression differences in patients with and without panic disorder is promising for future investigation.

Treatment

There is no way to prevent panic disorder. However, if you have been diagnosed with panic disorder, avoiding caffeine, alcohol and some over-the-counter cold medications may help prevent panic attacks. Many people with anxiety disorder benefit from self-help and/or support groups.

A number of health-focused social networks that offer mental health support groups are listed in the Highlight HEALTH Web Directory – Health 2.0 – Patient Social Networks, including:

Additional information on “Panic Attacks” and “Panic Disorder” can be found at Organized Wisdom, iMedix and TauMed.

Effective treatment for panic attacks and panic disorder is available and may involve cognitive behavior therapy to better understand panic attacks, the triggers, and how to deal with them, as well as medications, including an antidepressant, such as sertraline (Zoloft), paroxetine (Paxil) or fluoxetine (Prozac, Sarafem), and a benzodiazepine, such as clonazepam (Klonopin) or alprazolam (Xanax). Anxiety disorders also include obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), social and specific phobias, and generalized anxiety disorder.

References

Blood Tests May Be Possible For Mental Health Conditions. University of Iowa News Services. 2007 Mar 6.
Kessler et al. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry, 2005 Jun;62(6):617-27.
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Psychiatric Disorders in America: the Epidemiologic Catchment Area Study. Robins LN and Regier DA, eds. New York: The Free Press, 1991.
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), Fourth Edition. Washington, DC: American Psychiatric Association, 2000.
Hudson et al. Comorbidity of fibromyalgia with medical and psychiatric disorders. Am J Med. 1992 Apr;92(4):363-7.
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MacKinnon et al. Comorbid bipolar disorder and panic disorder in families with a high prevalence of bipolar disorder. Am J Psychiatry. 2002 Jan;159(1):30-5.
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Biederman et al. Patterns of psychopathology and dysfunction in high-risk children of parents with panic disorder and major depression. Am J Psychiatry. 2001 Jan;158(1):49-57.
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Finn and Smoller. The genetics of panic disorder. Curr Psychiatry Rep. 2001 Apr;3(2):131-7.
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Philibert et al. Transcriptional profiling of lymphoblast lines from subjects with panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2007 Jul 5;144(5):674-82. DOI: 10.1002/ajmg.b.30502
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Panic Disorder Blood Test May Aid Treatment. ABC News. 2007 Sep 21.