Generalized anxiety disorder (GAD) is an anxiety disorder characterized by excessive, uncontrollable and often irrational worry, that is, apprehensive expectation about events or activities.  This excessive worry often interferes with daily functioning, as individuals with GAD typically anticipate disaster, and are overly concerned about everyday matters such as health issues, money, death, family problems, friendship problems, interpersonal relationship problems, or work difficulties.  GAD is the most common cause of disability in the workplace in the United States.
Individuals often exhibit a variety of physical symptoms, including
- numbness in hands and feet
- muscle tension
- muscle aches
- difficulty swallowing
- excessive stomach acid buildup
- stomach pain, vomiting
- bouts of breathing difficulty
- difficulty concentrating
- hot flashes
- rashes, and
- inability to fully control the anxiety
(ICD-10). Especially the last point, the perceived inability and the sense of loss of control often leads into a vicious cycle of anxiety, anxiety begetting yet more anxiety.
Two percent of the adult population experience GAD in Europe and the US in a given year.   Globally about 4% are affected at some point in their life.  GAD is seen in women twice as much as men. GAD is also common in individuals with a history of substance abuse and a family history of the disorder.  Once GAD develops, it may become chronic, but can be managed or eliminated with proper treatment.
Where does it come from?
In most psychiatric conditions three factors are implicated, especially so in GAD:
- biology (e.g. genes)
- psychology (e.g. one’s experiences and strategies to deal with stressors)
- social environment
About a third of the variance for generalized anxiety disorder has been attributed to genes. Individuals with a genetic predisposition for GAD are more likely to develop GAD, especially in response to a life stressor. 
Antidpressants, especially the serotonin reuptaker inhibitors (SSRIs), are on the medication side the first line of treatment. Benzodiazepines, such as Alprazolam (Xanax®), can be of help in the short-run. However, long-term use of benzodiazepines can worsen underlying anxiety, with evidence that reduction of benzodiazepines can lead to a lessening of anxiety symptoms.  Similarly, long-term alcohol use is associated with anxiety disorders,  with evidence that prolonged abstinence can result in a disappearance of anxiety symptoms. Still, it can take up to two years for anxiety symptoms to return to baseline in about a quarter of people recovering from alcoholism. Sometimes anxiety pre-exists alcohol or benzodiazepine dependence, but the dependence acts to keep the anxiety disorders going and often progressively making them worse.
Tobacco smoking has also been established as a risk factor for developing anxiety disorders, as has excessive caffeine usage has been linked to anxiety. 
Generalized anxiety disorder has been linked to disrupted functional connectivity of the amygdala and its processing of fear and anxiety.  Sensory information enters the amygdala through the nuclei of the basolateral complex (consisting of lateral, basal and accessory basal nuclei). The basolateral complex processes the sensory-related fear memories and communicates their threat importance to memory and sensory processing elsewhere in the brain, such as the medial prefrontal cortex and sensory cortices. Another area, the adjacent central nucleus of the amygdala, controls species-specific fear responses in its connections to the brainstem, hypothalamus and cerebellum areas. In those with generalized anxiety disorder, these connections seem less functionally distinct, and there is greater gray matter in the central nucleus. Another difference is that the amygdala areas have decreased connectivity with the insula and cingulate areas that control general stimulus salience, while having greater connectivity with the parietal cortex and prefrontal cortex circuits that underlie executive functions. The latter suggests a compensation strategy for dysfunctional amygdala processing of anxiety. This is consistent with cognitive theories that suggest the use in this disorder of attempts to reduce the involvement of emotions with compensatory cognitive strategies.
- Association, American Psychiatric (2013). Diagnostic and statistical manual of mental disorders : DSM-5. (5th ed.). Washington, D.C.: American Psychiatric Association. p. 222. ISBN 978-0-89042-554-1.
- “What Is Generalized Anxiety Disorder?”, National Institute of Mental Health.
- Torpy, Janet M.; Burke, AE; Golub, RM (2011). “Generalized Anxiety Disorder”. JAMA. 305 (5): 522. doi:10.1001/jama.305.5.522. PMID 21285432.
- International Classification of Diseases) ICD-10
- Spitzer, Robert L.; Kroenke, K; Williams, JB; Löwe, B (2006). “A Brief Measure for Assessing Generalized Anxiety Disorder”. Archives of Internal Medicine. 166 (10): 1092–7. doi:10.1001/archinte.166.10.1092. PMID 16717171.
- Ballenger, JC; Davidson, JR; Lecrubier, Y; Nutt, DJ; Borkovec, TD; Rickels, K; Stein, DJ; Wittchen, HU (2001). “Consensus statement on generalized anxiety disorder from the International Consensus Group on Depression and Anxiety”. The Journal of Clinical Psychiatry. 62 Suppl 11: 53–8. PMID 11414552.
- “The Numbers Count”, National Institute of Mental Health. Accessed 28 May 2007.
- Lieb, Roselind; Becker, Eni; Altamura, Carlo (2005). “The epidemiology of generalized anxiety disorder in Europe”. European Neuropsychopharmacology. 15 (4): 445–52. doi:10.1016/j.euroneuro.2005.04.010. PMID 15951160.
- Craske, MG; Stein, MB (24 June 2016). “Anxiety.”. Lancet (London, England). PMID 27349358.
- “In The Clinic: Generalized Anxiety Disorder”. Annals Of Internal Medicine. 159 (11). 2013.
- Rickels, K; Schweizer, E (1990). “The clinical course and long-term management of generalized anxiety disorder”. Journal of Clinical Psychopharmacology. 10 (3 Suppl): 101S–110S. doi:10.1097/00004714-199006001-00017. PMID 1973934.
- Hettema, J. M.; Neale, MC; Kendler, KS (2001). “A Review and Meta-Analysis of the Genetic Epidemiology of Anxiety Disorders”. American Journal of Psychiatry. 158 (10): 1568–78. doi:10.1176/appi.ajp.158.10.1568. PMID 11578982.
- Donner, Jonas; Pirkola, Sami; Silander, Kaisa; Kananen, Laura; Terwilliger, Joseph D.; Lönnqvist, Jouko; Peltonen, Leena; Hovatta, Iiris (2008). “An Association Analysis of Murine Anxiety Genes in Humans Implicates Novel Candidate Genes for Anxiety Disorders”. Biological Psychiatry. 64 (8): 672–80. doi:10.1016/j.biopsych.2008.06.002. PMC 2682432. PMID 18639233.
- Galanter, Marc (1 July 2008). The American Psychiatric Publishing Textbook of Substance Abuse Treatment (American Psychiatric Press Textbook of Substance Abuse Treatment) (4 ed.). American Psychiatric Publishing, Inc. p. 197. ISBN 978-1-58562-276-4.
- Ashton, Heather (2005). “The diagnosis and management of benzodiazepine dependence”. Current Opinion in Psychiatry. 18 (3): 249–55. doi:10.1097/01.yco.0000165594.60434.84. PMID 16639148.
- Lindsay, S.J.E.; Powell, Graham E., eds. (28 July 1998). The Handbook of Clinical Adult Psychology (2nd ed.). Routledge. p. 173. ISBN 978-0-415-07215-1.
- Cargiulo, T. (2007). “Understanding the health impact of alcohol dependence”. American Journal of Health-System Pharmacy. 64 (5 Supplement 3): S5–11. doi:10.2146/ajhp060647. PMID 17322182.
- Wetterling, T; Junghanns, K (2000). “Psychopathology of alcoholics during withdrawal and early abstinence”. European Psychiatry. 15 (8): 483–8. doi:10.1016/S0924-9338(00)00519-8. PMID 11175926.
- Cohen, SI (1995). “Alcohol and benzodiazepines generate anxiety, panic and phobias”. Journal of the Royal Society of Medicine. 88 (2): 73–7. PMC 1295099. PMID 7769598.
- Morissette, Sandra Baker; Tull, Matthew T.; Gulliver, Suzy Bird; Kamholz, Barbara Wolfsdorf; Zimering, Rose T. (2007). “Anxiety, anxiety disorders, tobacco use, and nicotine: A critical review of interrelationships”. Psychological Bulletin. 133 (2): 245–72. doi:10.1037/0033-2909.133.2.245. PMID 17338599.
- Bruce M. S., Lader M.; Lader (2009). “Caffeine abstention in the management of anxiety disorders”. Psychological Medicine. 19 (1): 211–4. doi:10.1017/S003329170001117X. PMID 2727208.
- Etkin, Amit; Prater, Katherine E.; Schatzberg, Alan F.; Menon, Vinod; Greicius, Michael D. (2009). “Disrupted Amygdalar Subregion Functional Connectivity and Evidence of a Compensatory Network in Generalized Anxiety Disorder”. Archives of General Psychiatry. 66 (12): 1361–72. doi:10.1001/archgenpsychiatry.2009.104. PMID 19996041.
- Möller, Hans-Jürgen; Bandelow, Borwin; Bauer, Michael; Hampel, Harald; Herpertz, Sabine C.; Soyka, Michael; Barnikol, Utako B.; Lista, Simone; Severus, Emanuel; Maier, Wolfgang (26 August 2014). “DSM-5 reviewed from different angles: goal attainment, rationality, use of evidence, consequences—part 2: bipolar disorders, schizophrenia spectrum disorders, anxiety disorders, obsessive–compulsive disorders, trauma- and stressor-related disorders, personality disorders, substance-related and addictive disorders, neurocognitive disorders”. European Archives of Psychiatry and Clinical Neuroscience. 265: 87–106. doi:10.1007/s00406-014-0521-9.
© Dr Christian Jonathan Haverkampf. All rights reserved.
Psychotherapy & Counselling, Communication, Medicine (Psychiatry); Dublin, Ireland
This article is solely a basis for academic discussion and no medical advice can be given in this article, nor should anything herein be construed as advice. Always consult a professional if you believe you might suffer from a physical or mental health condition.
Trademarks belong to their respective owners. They have not been checked.
Potentially helpful links: