This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison
Anxiety Disorders
Figure 1. Types of Anxiety Disorders.
Anxiety is a common human emotional state characterized by fear, worry, and restlessness. It is natural for everyone to experience anxiety as a response to stress, but prolonged, overwhelming anxiety can be classified as one of several anxiety disorders [1].
Anxiety Disorders affect about 40 million American adults age 18 years and older (about 18%) in a given year [2], and many cases are undiagnosed and untreated as it is difficult for an individual to differentiate between what is normal and what is excessive or debilitating worry. Anxiety occurs on a spectrum of severity, and each form of anxiety disorder exhibits varying symptoms and requires a different treatment approach. Details regarding the symptoms of each subtype of anxiety disorder can be found here.
There are often physical symptoms that occur due to the release of adrenaline when someone is subject to extreme or prolonged anxiety. These symptoms may be classified as a panic attack if the response is an episode described in Figure 1, or the symptoms may be chronic such as muscle tension, increased blood pressure, nausea, decreased sex drive, and irritability [3].
Anxiety Disorders affect about 40 million American adults age 18 years and older (about 18%) in a given year [2], and many cases are undiagnosed and untreated as it is difficult for an individual to differentiate between what is normal and what is excessive or debilitating worry. Anxiety occurs on a spectrum of severity, and each form of anxiety disorder exhibits varying symptoms and requires a different treatment approach. Details regarding the symptoms of each subtype of anxiety disorder can be found here.
There are often physical symptoms that occur due to the release of adrenaline when someone is subject to extreme or prolonged anxiety. These symptoms may be classified as a panic attack if the response is an episode described in Figure 1, or the symptoms may be chronic such as muscle tension, increased blood pressure, nausea, decreased sex drive, and irritability [3].
Treatment of Anxiety
Anxiety disorders are most commonly treated with a combination of medication and psychotherapy [1]. Treatment is individualized to the symptoms of the patient, the approach depending upon any coexisting conditions (anxiety disorders are often coupled with depression and substance abuse) and response to medication and therapy. Treating anxiety disorders is subsequently difficult as several attempts may be needed to find a successful remedy.
Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) will not cure anxiety disorders, but have been proven to considerably decrease anxiety symptoms by increasing serotonin levels in the brain (see Figure 2 [4]). Antidepressants generally take 4-6 weeks to take effect.
Antidepressants such as selective serotonin reuptake inhibitors (SSRIs) will not cure anxiety disorders, but have been proven to considerably decrease anxiety symptoms by increasing serotonin levels in the brain (see Figure 2 [4]). Antidepressants generally take 4-6 weeks to take effect.
Figure 2. Function of SSRIs on synapses.
Other anti-anxiety drugs such as benzodiazepines, which inhibit neuron activity in the central nervous system, act more immediately to decrease anxiety and do not have prolonged effects. Medications for anxiety are purely supplemental to therapy in terms of curing anxiety disorders.
The Role of Research
Environmental factors such as pollution, physical and psychological stress, and diet all impact anxiety. Treatment of anxiety disorders takes these factors into account, but genetic information is beginning to shed light on exactly why anxiety is more pronounced in some individuals more than others. Increased activity of a particular enzyme, glyoxalase 1 (GLO1), has recently been connected to anxious behavior, and could serve as a target for treatment of anxiety disorders.
Glo1: Possible Genetic Connection
Figure 3. Human chromosome 6. Glo1 is labeled at p21.2 by the red line [5].
The Glo1 gene encodes for the protein Glyoxalase 1 (GLO1), an enzyme that metabolizes cytotoxic alpha-oxoaldehydes, particularly methylglyoxal (MG) [6]. MG is a natural byproduct of the degradation of intermediates in cell metabolism, but in large concentrations, MG induces protein and nucleotide modification as well as triggering apoptosis (cell death). GLO1 is therefore necessary in clearing MG, converting it to a less toxic substance, L-lactate.
MG has been shown to directly decrease symptoms of anxiety in mice by binding and activating GABAA receptors. These ion channels hyperpolarize and inhibit the action potential of neurons in the central nervous system, regulating neuron excitability. Activating GABAA receptors reduces anxiety, like the action of benzodiazepenes, and more potently leads to anesthetic effects [7].
In effect, increased copies and expression of Glo1 lead to less active GABAA receptors and more anxiety.
MG has been shown to directly decrease symptoms of anxiety in mice by binding and activating GABAA receptors. These ion channels hyperpolarize and inhibit the action potential of neurons in the central nervous system, regulating neuron excitability. Activating GABAA receptors reduces anxiety, like the action of benzodiazepenes, and more potently leads to anesthetic effects [7].
In effect, increased copies and expression of Glo1 lead to less active GABAA receptors and more anxiety.
References
[1] "Types of Anxiety Disorders." Anxiety Treatment Hub. Retrieved February 5, 2013 from http://anxietytreatmenthub.com/types-of-anxiety-disorders/
[2] "Anxiety Disorders." National Institute of Mental Health. Retrieved February 5, 2013 from http://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml
[3] "Anxiety | Conditions and Diseases." RX Prescription Guide RSS. Retrieved February 5, 2013 from http://www.rxprescriptionguide.org/diseases/anxiety
[4] Lattimore, K. A., Donn, S. M., Kaciroti, N., Kemper, A. R., Neal, C. R., & Vazquez, D. M. (2005). Selective Serotonin Reuptake Inhibitor (SSRI) Use during Pregnancy and Effects on the Fetus and Newborn: A Meta-Analysis. Nature Publishing Group , 25 (9). Retrieved from: http://www.nature.com/jp/journal/v25/n9/full/7211352a.html
[5] "Glyoxalase 1." GeneCards. HGNC, 11 Oct. 2012. Web. 7 Feb. 2013. Retrieved from: http://www.genecards.org/cgi-bin/carddisp.pl?gene=GLO1
[6] Distler M. G., Plant L. D., Sokoloff G., Hawk A. J., Aneas I., Wuenschell G. E., et al. (2012). Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal. J. Clin. Invest. 122, 2306–2315. doi: 10.1172/JCI61319
[7] Distler, M. G., and A. A. Palmer. "Role of Glyoxalase 1 (Glo1) and Methylglyoxal (MG) in Behavior: Recent Advances and Mechanistic Insights." PubMed (2012): n. pag. NCBI. Web. 7 Feb. 2013. doi: 10.3389
[2] "Anxiety Disorders." National Institute of Mental Health. Retrieved February 5, 2013 from http://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml
[3] "Anxiety | Conditions and Diseases." RX Prescription Guide RSS. Retrieved February 5, 2013 from http://www.rxprescriptionguide.org/diseases/anxiety
[4] Lattimore, K. A., Donn, S. M., Kaciroti, N., Kemper, A. R., Neal, C. R., & Vazquez, D. M. (2005). Selective Serotonin Reuptake Inhibitor (SSRI) Use during Pregnancy and Effects on the Fetus and Newborn: A Meta-Analysis. Nature Publishing Group , 25 (9). Retrieved from: http://www.nature.com/jp/journal/v25/n9/full/7211352a.html
[5] "Glyoxalase 1." GeneCards. HGNC, 11 Oct. 2012. Web. 7 Feb. 2013. Retrieved from: http://www.genecards.org/cgi-bin/carddisp.pl?gene=GLO1
[6] Distler M. G., Plant L. D., Sokoloff G., Hawk A. J., Aneas I., Wuenschell G. E., et al. (2012). Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal. J. Clin. Invest. 122, 2306–2315. doi: 10.1172/JCI61319
[7] Distler, M. G., and A. A. Palmer. "Role of Glyoxalase 1 (Glo1) and Methylglyoxal (MG) in Behavior: Recent Advances and Mechanistic Insights." PubMed (2012): n. pag. NCBI. Web. 7 Feb. 2013. doi: 10.3389
Site created by: Emma Baar
Last updated: 5-14-2013
University of Wisconsin - Madison
Last updated: 5-14-2013
University of Wisconsin - Madison
