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Anxiety Disorders

  • Author: William R Yates, MD, MS; Chief Editor: David Bienenfeld, MD  more...
 
Updated: Apr 18, 2016
 

Background

Anxiety disorders are common psychiatric disorders. Many patients with anxiety disorders experience physical symptoms related to anxiety and subsequently visit their primary care providers. Despite the high prevalence rates of these anxiety disorders, they often are underrecognized and undertreated clinical problems.

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),[1] anxiety disorders include disorders that share features of excessive fear and anxiety and related behavioral disturbances. Some of these disorders include separation anxiety disorder, selective mutism, social anxiety disorder, panic disorder, and agoraphobia. Obsessive-compulsive disorder and posttraumatic stress disorder are no longer considered anxiety disorders as they were in the previous version of the DSM.

Anxiety disorders appear to be caused by an interaction of biopsychosocial factors, including genetic vulnerability, which interact with situations, stress, or trauma to produce clinically significant syndromes. (See Pathophysiology and Etiology.)

Symptoms vary depending on the specific anxiety disorder. (See Clinical Presentation.)

Treatment usually consists of a combination of pharmacotherapy (see Medication) and/or psychotherapy. (See Treatment Strategies and Management.)

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Anatomy

The brain circuits and regions associated with anxiety disorders are beginning to be understood with the development of functional and structural imaging. The brain amygdala appears key in modulating fear and anxiety. Patients with anxiety disorders often show heightened amygdala response to anxiety cues. The amygdala and other limbic system structures are connected to prefrontal cortex regions. Hyperresponsiveness of the amygdala may relate to reduced activation thresholds when responding to perceived social threat.[2, 3] Prefrontal-limbic activation abnormalities have been shown to reverse with clinical response to psychologic or pharmacologic interventions.

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Pathophysiology

In the central nervous system (CNS), the major mediators of the symptoms of anxiety disorders appear to be norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA). Other neurotransmitters and peptides, such as corticotropin-releasing factor, may be involved. Peripherally, the autonomic nervous system, especially the sympathetic nervous system, mediates many of the symptoms.[4]

Positron emission tomography (PET) scanning has demonstrated increased flow in the right parahippocampal region and reduced serotonin type 1A receptor binding in the anterior and posterior cingulate and raphe of patients with panic disorder.[5] MRI has demonstrated smaller temporal lobe volume despite normal hippocampal volume in these patients.[6] The CSF in studies in humans shows elevated levels of orexin, also known as hypocretin, which is thought to play an important role in the pathogenesis of panic in rat models.[7]

 

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Etiology

Anxiety disorders in general

The first consideration is the possibility that anxiety is due to a known or unrecognized medical condition. Substance-induced anxiety disorder (over-the-counter medications, herbal medications, substances of abuse) is a diagnosis that often is missed.

Genetic factors significantly influence risk for many anxiety disorders. Environmental factors such as early childhood trauma can also contribute to risk for later anxiety disorders. The debate whether gene or environment is primary in anxiety disorders has evolved to a better understanding of the important role of the interaction between genes and environment.[13] Some individuals appear resilient to stress, while others are vulnerable to stress, which precipitates an anxiety disorder.

Most presenting anxiety disorders are functional psychiatric disorders. Psychological theories range from explaining anxiety as a displacement of an intrapsychic conflict (psychodynamic models) to conditioning (learned) paradigms (cognitive-behavioral models). Many of these theories capture portions of the disorder.

The psychodynamic theory has explained anxiety as a conflict between the id and ego. Aggressive and impulsive drives may be experienced as unacceptable resulting in repression. These repressed drives may break through repression, producing automatic anxiety. The treatment uses exploration with the goal of understanding the underlying conflict. Cognitive theory has explained anxiety as the tendency to overestimate the potential for danger. Patients with anxiety disorder tend to imagine the worst possible scenario and avoid situations they think are dangerous, such as crowds, heights, or social interaction.

Panic disorder

Panic disorder appears to be a genetically inherited neurochemical dysfunction that may involve autonomic imbalance; decreased GABA-ergic tone[14] ; allelic polymorphism of the catechol-O-methyltransferase (COMT) gene; increased adenosine receptor function; increased cortisol[15] ; diminished benzodiazepine receptor function; and disturbances in serotonin,[16] serotonin transporter (5-HTTLPR)[17] and promoter (SLC6A4) genes,[18] norepinephrine, dopamine, cholecystokinin, and interleukin-1-beta.[19] Some theorize that panic disorder may represent a state of chronic hyperventilation and carbon dioxide receptor hypersensitivity.[8] Some epileptic patients have panic as a manifestation of their seizures. Genetic studies suggest that the chromosomal regions 13q, 14q, 22q, 4q31-q34, and probably 9q31 may be associated with the heritability of panic disorder phenotype.[20]

The cognitive theory regarding panic is that patients with panic disorder have a heightened sensitivity to internal autonomic cues (eg, tachycardia). Triggers of panic can include the following:

  • Injury (eg, accidents, surgery)
  • Illness
  • Interpersonal conflict or loss
  • Use of cannabis (can be associated with panic attacks, perhaps because of breath-holding) [21]
  • Use of stimulants, such as caffeine, decongestants, cocaine, and sympathomimetics (eg, amphetamine, MDMA ["ecstasy"]) [22]
  • Certain settings, such as stores and public transportation (especially in patients with agoraphobia)
  • Sertraline can induce panic in previously asymptomatic patients. [23]
  • The SSRI discontinuation syndrome can induce symptoms similar to those experienced by panic patients.

In experimental settings, symptoms can be elicited in people with panic disorder by hyperventilation, inhalation of carbon dioxide, caffeine consumption, or intravenous infusions of hypertonic sodium lactate or hypertonic saline,[24] cholecystokinin, isoproterenol, flumazenil,[25] or naltrexone.[26] The carbon dioxide inhalation challenge is especially provocative of panic symptoms in smokers.[27]

Social anxiety disorder (social phobia)

Genetic factors seem to play a role in social phobia. Based on family and twin studies, the risk for social phobia appears to be moderately heritable.[28, 29]

Social phobia can be initiated by traumatic social experience (eg, embarrassment) or by social skills deficits that produce recurring negative experiences. A hypersensitivity to rejection, perhaps related to serotonergic or dopaminergic dysfunction, is present. Current thought is that social phobia appears to be an interaction between biological and genetic factors and environmental events.

A psychoanalyst would likely conceptualize social anxiety as a symptom of a deeper conflict-for instance, low self-esteem or unresolved conflicts with internal objects. A behaviorist would see phobia as a learned, conditioned response resulting from a past association with a situation with negative emotional valence at the time of association (eg, social situations are avoided because intense anxiety was originally experienced in that setting). Even if no danger is posed in most social encounters, an avoidance response has been linked to these situations. Treatment from this perspective aims to weaken and eventually separate the specific response from the stimulus.

Specific phobia

Genetic factors seem to play a role in specific phobia as well (eg, in blood-injury phobia), and the risk for such phobias also seems to be moderately heritable.[28] In addition, specific phobia can be acquired by conditioning, modeling, or traumatic experience.

Agoraphobia may be the result of repeat, unexpected panic attacks, which, in turn, may be linked to cognitive distortions, conditioned responses, and/or abnormalities in noradrenergic, serotonergic, or GABA-related neurotransmission.

 

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Epidemiology

United States statistics

Social anxiety disorder (social phobia) is the most common anxiety disorder; it has an early age of onset—by age 11 years in about 50% and by age 20 years in about 80% of individuals that have the diagnosis—and it is a risk factor for subsequent depressive illness and substance abuse.[40]  The 12-month prevalance estimate of social anxiety disorder for the United States is approximately 7%.[1]

According to 2 major studies in the United States—the Epidemiological Catchment Area (ECA) study[41] and the National Comorbidity Survey (NCS) study[42] —in conjunction with other studies, the estimated lifetime prevalence rates for individual anxiety disorders are 2.3-2.7% for panic disorder, 4.1-6.6% for generalized anxiety disorder, and 2.6-13.3% for social phobia.

Further, the NCS reported the following lifetime (and 30-day) prevalence estimates: 6.7% (and 2.3%) for agoraphobia, 11.3% (and 5.5%) for simple (ie, specific) phobia, and 13.3% (and 4.5%) for social phobia.[43, 44]

International statistics

The prevalence of specific anxiety disorders appears to vary between countries and cultures. A cross-national study of the prevalence of panic disorder found lifetime prevalence rates ranging from 0.4% in Taiwan to 2.9% in Italy. The median prevalance of social anxiety disorder in Europe is 2.3%.[1]

In some Far East cultures, individuals with social anxiety disorder may develop fears of being offensive to others rather than fears of being embarrassed. In Japan and Korea, this syndrome is referred to as taijin kyofusho.[1]

Prevalence of anxiety disorders by race

The ECA study found no difference in rates of panic disorder among white, African American, or Hispanic populations in the United States.

Sex ratio for anxiety disorders

The female-to-male ratio for any lifetime anxiety disorder is 3:2 (see the image below).

Anxiety. Chart showing the female-to-male sex rati Anxiety. Chart showing the female-to-male sex ratio for anxiety disorders. Adapted from Kessler et al, 1994.

Age distribution for anxiety disorders

Most anxiety disorders begin in childhood, adolescence, and early adulthood (see the image below). Separation anxiety is an anxiety disorder of childhood that often includes anxiety related to going to school. This disorder may be a precursor for adult anxiety disorders.

Anxiety. Age of onset for anxiety disorders based Anxiety. Age of onset for anxiety disorders based on specific anxiety disorder type.

Panic disorder demonstrates a bimodal age of onset in the NCS study in the age groups of 15-24 years and 45-54 years. The age of onset for OCD appears to be in the mid 20s to early 30s.

Most social phobias begin before age 20 years (median age at illness onset, 16 years[43] ).

Agoraphobia usually begins in late adolescence to early adulthood (median age at illness onset, 29 years[43] ).

In general, specific phobia appears earlier than social phobia or agoraphobia. The age of onset depends on the particular phobia. For example, animal phobia is most common at the elementary school level and appears at a mean age of 7 years; blood phobia appears at a mean age of 9 years; dental phobia appears at a mean age of 12 years; and claustrophobia appears at a mean age of 20 years. Most simple (specific) phobias develop during childhood (median age at illness onset, 15 years).[43] and eventually disappear. Those that persist into adulthood rarely go away without treatment.

New-onset anxiety symptoms in older adults should prompt a search for an unrecognized general medical condition, a substance abuse disorder, or major depression with secondary anxiety symptoms.

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Prognosis

Anxiety disorders have high rates of comorbidity with major depression and alcohol and drug abuse. Some of the increased morbidity and mortality associated with anxiety disorders may be related to this high rate of comorbidity. Anxiety disorders may contribute to morbidity and mortality through neuroendocrine and neuroimmune mechanisms or by direct neural stimulation, (eg, hypertension or cardiac arrhythmia). Chronic anxiety may be associated with increased risk for cardiovascular morbidity and mortality.

Considerable evidence shows that social phobia (social anxiety disorder) results in significant functional impairment and decreased quality of life.[45, 46]

Severe anxiety disorders may be complicated by suicide, with or without secondary mood disorders (eg, depression). The Epidemiological Catchment Area study found that panic disorder was associated with suicide attempts (odds ratio = 18 compared with populations without psychiatric disorders). How much of the association of panic disorder with suicide is mediated through the association of panic disorder with mood and substance abuse disorders is unclear. Acute stress may play a role in producing suicidal behavior. The presence of any anxiety disorder, phobias included, in combination with a mood disorder appears to increase likelihood of suicide attempts compared with a mood disorder alone.[47] Suicide attempts can be precipitated by adverse life events such as divorce or financial disaster. The effects of acute stress in producing suicidal behavior are increased in those with underlying mood, anxiety, and substance abuse problems.

Phobias are highly comorbid. Most comorbid simple (specific) and social phobias are temporally primary, while most comorbid agoraphobia is temporally secondary. Comorbid phobias are generally more severe than pure phobias. Social phobia is also frequently comorbid with major depressive disorder and atypical depression, which results in increased disability.[46, 48] Despite evidence of impairment, only a minority of individuals with simple (specific) phobia ever seek professional treatment.

Interestingly, in clinical samples, over 95% of the patients reporting agoraphobia also present with panic disorder, while in epidemiologic samples, simple agoraphobia appears to be more prevalent than panic disorder with agoraphobia.[49]

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Patient Education

Education can be obtained through books, newsletters, support groups, and the Internet. Some useful Web sites are as follows:

Family members should receive information about the effect of anxiety disorders on mood, behavior, and relationships. Family members can assist in care by reinforcing the need for medical treatment and supervision. Family members may also assist by providing a collaborative resource for monitoring the severity of the patient’s anxiety symptoms and response to treatment interventions.

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Contributor Information and Disclosures
Author

William R Yates, MD, MS Research Psychiatrist, Laureate Institute for Brain Research; Professor of Research, Department of Psychiatry, University of Oklahoma College of Medicine at Tulsa

William R Yates, MD, MS is a member of the following medical societies: American Academy of Family Physicians

Disclosure: Nothing to disclose.

Chief Editor

David Bienenfeld, MD Professor, Departments of Psychiatry and Geriatric Medicine, Wright State University, Boonshoft School of Medicine

David Bienenfeld, MD is a member of the following medical societies: American Medical Association, American Psychiatric Association, Association for Academic Psychiatry

Disclosure: Nothing to disclose.

Acknowledgements

Edward Bessman, MD Chairman, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University School of Medicine

Edward Bessman, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences,and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Colin Y Daniels, MD Consulting Staff, Department of Psychiatry, Madigan Army Medical Center

Colin Y Daniels, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Marilyn T Erickson, PhD Professor Emeritus, Department of Psychology, Virginia Commonwealth University

Disclosure: Nothing to disclose.

Sandra L Friedman, MD, MPH Assistant Professor of Pediatrics, Harvard University Medical School; Director of Pediatrics, LEND/UCEDD, Department of Medicine, Division of General Pediatrics, Children's Hospital of Boston

Sandra L Friedman, MD, MPH is a member of the following medical societies: American Academy of Pediatrics and American Medical Directors Association

Disclosure: Nothing to disclose.

Robert Harwood, MD, MPH, FACEP, FAAEM Senior Physcian, Department of Emergency Medicine, Advocate Christ Medical Center; Assistant Professor, Department of Emergency Medicine, University of Illinois at Chicago College of Medicine

Robert Harwood, MD, MPH, FACEP, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Council of Emergency Medicine Residency Directors, Phi Beta Kappa, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Samuel M Keim, MD Associate Professor, Department of Emergency Medicine, University of Arizona College of Medicine

Samuel M Keim, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Public Health Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Michael C Plewa, MD Research Coordinator, Consulting Staff, Department of Emergency Medicine, Lucas County Emergency Physicians, Inc, and Mercy Saint Vincent Medical Center

Michael C Plewa, MD, is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Physicians for Social Responsibility, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Lemeneh Tefera, MD, FAAEM Attending Physician, Department of Emergency Medicine, Beth Israel Medical Center

Lemeneh Tefera, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine

Disclosure: Nothing to disclose.

Lauren Claire Tomao, MD, JD Resident, Department of Emergency Medicine, Albert Einstein College of Medicine, Beth Israel Medical Center

Lauren Claire Tomao, MD, JD is a member of the following medical societies: American Bar Association

Disclosure: Nothing to disclose.

References
  1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: APA Press; 2013.

  2. Martinez RC, Ribeiro de Oliveira A, Brandão ML. Serotonergic mechanisms in the basolateral amygdala differentially regulate the conditioned and unconditioned fear organized in the periaqueductal gray. Eur Neuropsychopharmacol. 2007 Nov. 17(11):717-24. [Medline]. [Full Text].

  3. Keeton CP, Kolos AC, Walkup JT. Pediatric generalized anxiety disorder: epidemiology, diagnosis, and management. Paediatr Drugs. 2009. 11(3):171-83. [Medline].

  4. Freitas-Ferrari MC, Hallak JE, Trzesniak C, Filho AS, Machado-de-Sousa JP, Chagas MH. Neuroimaging in social anxiety disorder: a systematic review of the literature. Prog Neuropsychopharmacol Biol Psychiatry. 2010 May 30. 34(4):565-80. [Medline].

  5. Katerndahl DA, Talamantes M. A comparison of persons with early-versus late-onset panic attacks. J Clin Psychiatry. 2000 Jun. 61(6):422-7. [Medline].

  6. Vythilingam M, Anderson ER, Goddard A, Woods SW, Staib LH, Charney DS. Temporal lobe volume in panic disorder--a quantitative magnetic resonance imaging study. Psychiatry Res. 2000 Aug 28. 99(2):75-82. [Medline].

  7. Johnson PL, Truitt W, Fitz SD, Minick PE, Dietrich A, Sanghani S. A key role for orexin in panic anxiety. Nat Med. 2010 Jan. 16(1):111-5. [Medline]. [Full Text].

  8. Greist JH, Jefferson JW, Kobak KA, Katzelnick DJ, Serlin RC. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. A meta-analysis. Arch Gen Psychiatry. 1995 Jan. 52(1):53-60. [Medline].

  9. Kobak KA, Greist JH, Jefferson JW, Katzelnick DJ, Henk HJ. Behavioral versus pharmacological treatments of obsessive compulsive disorder: a meta-analysis. Psychopharmacology (Berl). 1998 Apr. 136(3):205-16. [Medline].

  10. Bloch MH, Landeros-Weisenberger A, Kelmendi B, Coric V, Bracken MB, Leckman JF. A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder. Mol Psychiatry. 2006 Jul. 11(7):622-32. [Medline].

  11. Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992 Sep. 49(9):681-9. [Medline].

  12. Pittenger C, Krystal JH, Coric V. Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder. NeuroRx. 2006 Jan. 3(1):69-81. [Medline].

  13. Tambs K, Czajkowsky N, Røysamb E, Neale MC, Reichborn-Kjennerud T, Aggen SH. Structure of genetic and environmental risk factors for dimensional representations of DSM-IV anxiety disorders. Br J Psychiatry. 2009 Oct. 195(4):301-7. [Medline].

  14. Zwanzger P, Eser D, Nothdurfter C, Baghai TC, Möller HJ, Padberg F, et al. Effects of the GABA-reuptake inhibitor tiagabine on panic and anxiety in patients with panic disorder. Pharmacopsychiatry. 2009 Nov. 42(6):266-9. [Medline].

  15. Wedekind D, Bandelow B, Broocks A, Hajak G, Rüther E. Salivary, total plasma and plasma free cortisol in panic disorder. J Neural Transm. 2000. 107(7):831-7. [Medline].

  16. Neumeister A, Bain E, Nugent AC, Carson RE, Bonne O, Luckenbaugh DA. Reduced serotonin type 1A receptor binding in panic disorder. J Neurosci. 2004 Jan 21. 24(3):589-91. [Medline].

  17. Lonsdorf TB, Rück C, Bergström J, Andersson G, Ohman A, Schalling M, et al. The symptomatic profile of panic disorder is shaped by the 5-HTTLPR polymorphism. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Nov 13. 33(8):1479-83. [Medline].

  18. Strug LJ, Suresh R, Fyer AJ, Talati A, Adams PB, Li W, et al. Panic disorder is associated with the serotonin transporter gene (SLC6A4) but not the promoter region (5-HTTLPR). Mol Psychiatry. 2010 Feb. 15(2):166-76. [Medline]. [Full Text].

  19. Johnson MR, Lydiard RB, Ballenger JC. Panic disorder. Pathophysiology and drug treatment. Drugs. 1995 Mar. 49(3):328-44. [Medline].

  20. Maron E, Hettema JM, Shlik J. Advances in molecular genetics of panic disorder. Mol Psychiatry. 2010 Jul. 15(7):681-701. [Medline].

  21. Dannon PN, Lowengrub K, Amiaz R, Grunhaus L, Kotler M. Comorbid cannabis use and panic disorder: short term and long term follow-up study. Hum Psychopharmacol. 2004 Mar. 19(2):97-101. [Medline].

  22. Schifano F, Di Furia L, Forza G, et al. MDMA (‘‘ecstasy’’) consumption in the context of polydrug abuse: a report on 150 patients. Drug Alcohol Depend. Sep.

  23. González-Berríos N. Sertraline-induced panic attack. Bol Asoc Med P R. 2009 Jan-Mar. 101(1):59-60. [Medline].

  24. Molosh AI, Johnson PL, Fitz SD, Dimicco JA, Herman JP, Shekhar A. Changes in central sodium and not osmolarity or lactate induce panic-like responses in a model of panic disorder. Neuropsychopharmacology. 2010 May. 35(6):1333-47. [Medline].

  25. Dratcu L. Panic, hyperventilation and perpetuation of anxiety. Prog Neuropsychopharmacol Biol Psychiatry. 2000 Oct. 24(7):1069-89. [Medline].

  26. Esquivel G, Fernández-Torre O, Schruers KR, Wijnhoven LL, Griez EJ. The effects of opioid receptor blockade on experimental panic provocation with CO2. J Psychopharmacol. 2009 Nov. 23(8):975-8. [Medline].

  27. Knuts IJ, Cosci F, Esquivel G, Goossens L, van Duinen M, Bareman M, et al. Cigarette smoking and 35% CO(2) induced panic in panic disorder patients. J Affect Disord. 2010 Jul. 124(1-2):215-8. [Medline].

  28. Kendler KS, Karkowski LM, Prescott CA. Fears and phobias: reliability and heritability. Psychol Med. 1999 May. 29(3):539-53. [Medline].

  29. Fyer AJ, Mannuzza S, Chapman TF, Liebowitz MR, Klein DF. A direct interview family study of social phobia. Arch Gen Psychiatry. 1993 Apr. 50(4):286-93. [Medline]. [Full Text].

  30. van Grootheest DS, Cath DC, Beekman AT, Boomsma DI. Twin studies on obsessive-compulsive disorder: a review. Twin Res Hum Genet. 2005 Oct. 8(5):450-8. [Medline].

  31. Carey G, Gottesman I. Twin and family studies of anxiety, phobic, and obsessive disorders. In: Klein DF, Rabkin JG. Anxiety: New Research and Changing Concepts. New York: Raven Press; 2000.

  32. Lochner C, Mogotsi M, du Toit PL, Kaminer D, Niehaus DJ, Stein DJ. Quality of life in anxiety disorders: a comparison of obsessive-compulsive disorder, social anxiety disorder, and panic disorder. Psychopathology. 2003 Sep-Oct. 36(5):255-62. [Medline].

  33. Arnold PD, Sicard T, Burroughs E, Richter MA, Kennedy JL. Glutamate transporter gene SLC1A1 associated with obsessive-compulsive disorder. Arch Gen Psychiatry. 2006 Jul. 63(7):769-76. [Medline].

  34. Denys D, Van Nieuwerburgh F, Deforce D, Westenberg H. Association between the dopamine D2 receptor TaqI A2 allele and low activity COMT allele with obsessive-compulsive disorder in males. Eur Neuropsychopharmacol. 2006 Aug. 16(6):446-50. [Medline].

  35. Dickel DE, Veenstra-VanderWeele J, Cox NJ, Wu X, Fischer DJ, Van Etten-Lee M. Association testing of the positional and functional candidate gene SLC1A1/EAAC1 in early-onset obsessive-compulsive disorder. Arch Gen Psychiatry. 2006 Jul. 63(7):778-85. [Medline].

  36. Lin PY. Meta-analysis of the association of serotonin transporter gene polymorphism with obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13. 31(3):683-9. [Medline].

  37. Deykin EY. Posttraumatic Stress Disorder in Childhood and Adolescence: A Review. Medscape Mental Health [online]. 1999. [Full Text].

  38. Marshall RD, Pierce D. Implications of recent findings in posttraumatic stress disorder and the role of pharmacotherapy. Harv Rev Psychiatry. 2000 Jan-Feb. 7(5):247-56. [Medline].

  39. Milad MR, Orr SP, Lasko NB, Chang Y, Rauch SL, Pitman RK. Presence and acquired origin of reduced recall for fear extinction in PTSD: results of a twin study. J Psychiatr Res. 2008 Jun. 42(7):515-20. [Medline].

  40. Stein MB, Stein DJ. Social anxiety disorder. Lancet. 2008 Mar 29. 371(9618):1115-25. [Medline].

  41. Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry. 1988 Dec. 45(12):1094-9. [Medline].

  42. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry. 1994 Jan. 51(1):8-19. [Medline].

  43. Magee WJ, Eaton WW, Wittchen HU, McGonagle KA, Kessler RC. Agoraphobia, simple phobia, and social phobia in the National Comorbidity Survey. Arch Gen Psychiatry. 1996 Feb. 53(2):159-68. [Medline].

  44. Wittchen HU, Fehm L. Epidemiology, patterns of comorbidity, and associated disabilities of social phobia. Psychiatr Clin North Am. 2001 Dec. 24(4):617-41. [Medline].

  45. Schneier FR, Heckelman LR, Garfinkel R, Campeas R, Fallon BA, Gitow A. Functional impairment in social phobia. J Clin Psychiatry. 1994 Aug. 55(8):322-31. [Medline].

  46. Lochner C, Mogotsi M, du Toit PL, Kaminer D, Niehaus DJ, Stein DJ. Quality of life in anxiety disorders: a comparison of obsessive-compulsive disorder, social anxiety disorder, and panic disorder. Psychopathology. 2003 Sep-Oct. 36(5):255-62. [Medline].

  47. Sareen J, Cox BJ, Afifi TO, de Graaf R, Asmundson GJ, ten Have M. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch Gen Psychiatry. 2005 Nov. 62(11):1249-57. [Medline]. [Full Text].

  48. Matza LS, Revicki DA, Davidson JR, Stewart JW. Depression with atypical features in the National Comorbidity Survey: classification, description, and consequences. Arch Gen Psychiatry. 2003 Aug. 60(8):817-26. [Full Text].

  49. American Psychiatric Association. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fourth Edition, Text Revision (DSM-IV-TR). Washington, DC: American Psychiatric Association Press; 2000.

  50. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989 Nov. 46(11):1006-11. [Medline].

  51. First MB, Spitzer RL, Gibbon M, Williams JBW. Structured Clinical Interview for DSM-IV-TR Axis I Disorders. Patient Edition (SCID-I/P, 11/2002 revision). New York: Biometrics Research Department, New York State Psychiatric Institute; November 2002.

  52. Helping Children and Adolescents Cope with Violence and Disasters. National Institute of Mental Health. NIH Publication No. 01-3518. Bethesda, Md: National Institute of Mental Health; 2001.

  53. Dickie EW, Brunet A, Akerib V, Armony JL. An fMRI investigation of memory encoding in PTSD: influence of symptom severity. Neuropsychologia. 2008 Apr. 46(5):1522-31. [Medline].

  54. Kluge M, Schüssler P, Steiger A. Persistent generalized anxiety after brief exposure to the dopamine antagonist metoclopramide. Psychiatry Clin Neurosci. 2007 Apr. 61(2):193-5. [Medline].

  55. Cha C, Nock M. Emotional intelligence is a protective factor for suicidal behavior. J Am Acad Child Adolesc Psychiatry. 2009 Apr. 48(4):422-30. [Medline].

  56. Nitschke JB, Sarinopoulos I, Oathes DJ, Johnstone T, Whalen PJ, Davidson RJ. Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. Am J Psychiatry. 2009 Mar. 166(3):302-10. [Medline].

  57. Germain A, Shear MK, Hall M, Buysse DJ. Effects of a brief behavioral treatment for PTSD-related sleep disturbances: a pilot study. Behav Res Ther. 2007 Mar. 45(3):627-32. [Medline].

  58. Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007 Apr 15. 61(8):928-34. [Medline].

  59. de Beurs E, van Balkom AJ, Van Dyck R, Lange A. Long-term outcome of pharmacological and psychological treatment for panic disorder with agoraphobia: a 2-year naturalistic follow-up. Acta Psychiatr Scand. 1999 Jan. 99(1):59-67. [Medline].

  60. Shear MK, Beidel DC. Psychotherapy in the overall management strategy for social anxiety disorder. J Clin Psychiatry. 1998. 59 Suppl 17:39-46. [Medline].

  61. [Guideline] Mayor S. NICE advocates computerised CBT. BMJ. 2006 Mar 4. 332(7540):504. [Medline].

  62. Hunot V, Churchill R, Silva de Lima M, Teixeira V. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev. 2007. (1):CD001848. [Medline].

  63. Ipser JC, Carey P, Dhansay Y, Fakier N, Seedat S, Stein DJ. Pharmacotherapy augmentation strategies in treatment-resistant anxiety disorders. Cochrane Database Syst Rev. 2006 Oct 18. CD005473. [Medline].

  64. Walkup J, Labellarte M, Riddle MA, Pine DS, Greenhill L, Fairbanks J, et al. Treatment of pediatric anxiety disorders: an open-label extension of the research units on pediatric psychopharmacology anxiety study. J Child Adolesc Psychopharmacol. 2002 Fall. 12(3):175-88. [Medline].

  65. Toneatto T, Nguyen L. Does mindfulness meditation improve anxiety and mood symptoms? A review of the controlled research. Can J Psychiatry. 2007 Apr. 52(4):260-6. [Medline].

  66. [Guideline] American Psychiatric Association (APA). Practice guideline for the treatment of patients with panic disorder. 2nd ed. Washington (DC): American Psychiatric Association (APA); 2009 Jan. Available from the PsychiatryOnline website. Available at http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1680635. Accessed: June 15, 2011.

  67. Celexa (citalopram hydrobromide) [package insert]. St. Louis, Missouri: Forest Pharmaceuticals, Inc. August, 2011. Available at [Full Text].

  68. US Food and Drug Administration. Celexa (citalopram hydrobromide): Drug safety communication – abnormal heart rhythms associated with high doses. [Full Text].

  69. Croom KF, Perry CM, Plosker GL. Mirtazapine: a review of its use in major depression and other psychiatric disorders. CNS Drugs. 2009. 23(5):427-52. [Medline].

  70. Kim JE, Yoon SJ, Kim J, Jung JY, Jeong HS, Cho HB, et al. Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial. Int J Clin Pract. 2011 Mar. 65(3):323-9. [Medline].

  71. Sinclair LI, Christmas DM, Hood SD, Potokar JP, Robertson A, Isaac A. Antidepressant-induced jitteriness/anxiety syndrome: systematic review. Br J Psychiatry. 2009 Jun. 194(6):483-90. [Medline].

  72. Rodriguez BF, Weisberg RB, Pagano ME, Machan JT, Culpepper L, Keller MB. Mental health treatment received by primary care patients with posttraumatic stress disorder. J Clin Psychiatry. 2003 Oct. 64(10):1230-6. [Medline].

  73. Högberg G, Pagani M, Sundin O, Soares J, Aberg-Wistedt A, Tärnell B. Treatment of post-traumatic stress disorder with eye movement desensitization and reprocessing: outcome is stable in 35-month follow-up. Psychiatry Res. 2008 May 30. 159(1-2):101-8. [Medline].

  74. Ponniah K, Hollon SD. Empirically supported psychological treatments for adult acute stress disorder and posttraumatic stress disorder: a review. Depress Anxiety. 2009. 26(12):1086-109. [Medline].

  75. Litz BT, Engel CC, Bryant RA, Papa A. A randomized, controlled proof-of-concept trial of an Internet-based, therapist-assisted self-management treatment for posttraumatic stress disorder. Am J Psychiatry. 2007 Nov. 164(11):1676-83. [Medline].

  76. Foa EB, Wilson R. Stop Obsessing!: How to Overcome Your Obsessions and Compulsions. Revis ed. New York: Bantam Dell; 2001.

  77. Coric V, Taskiran S, Pittenger C, Wasylink S, Mathalon DH, Valentine G, et al. Riluzole augmentation in treatment-resistant obsessive-compulsive disorder: an open-label trial. Biol Psychiatry. 2005 Sep 1. 58(5):424-8. [Medline].

  78. Greenberg WM, Benedict MM, Doerfer J, Perrin M, Panek L, Cleveland WL. Adjunctive glycine in the treatment of obsessive-compulsive disorder in adults. J Psychiatr Res. 2009 Mar. 43(6):664-70. [Medline].

  79. Grayson J. Freedom From Obsessive Compulsive Disorder: A Personalized Recovery Program for Living With Uncertainty. New York: Berkley Publishing Group; 2004.

  80. Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007 Jul. 164(7 Suppl):5-53. [Medline]. [Full Text].

  81. Jung HH, Kim CH, Chang JH, Park YG, Chung SS, Chang JW. Bilateral anterior cingulotomy for refractory obsessive-compulsive disorder: Long-term follow-up results. Stereotact Funct Neurosurg. 2006. 84(4):184-9. [Medline].

  82. Greenberg BD, Malone DA, Friehs GM, Rezai AR, Kubu CS, Malloy PF. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006 Nov. 31(11):2384-93. [Medline].

  83. Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008 Nov 13. 359(20):2121-34. [Medline].

  84. Barlow JH, Ellard DR, Hainsworth JM, Jones FR, Fisher A. A review of self-management interventions for panic disorders, phobias and obsessive-compulsive disorders. Acta Psychiatr Scand. 2005 Apr. 111(4):272-85. [Medline].

  85. Lewis C, Pearce J, Bisson JI. Efficacy, cost-effectiveness and acceptability of self-help interventions for anxiety disorders: systematic review. Br J Psychiatry. 2012 Jan. 200:15-21. [Medline].

  86. Lydiard RB. The role of drug therapy in social phobia. J Affect Disord. 1998 Sep. 50 Suppl 1:S35-9. [Medline].

  87. Van Ameringen M, Allgulander C, Bandelow B, Greist JH, Hollander E, Montgomery SA, et al. WCA recommendations for the long-term treatment of social phobia. CNS Spectr. 2003 Aug. 8(8 Suppl 1):40-52. [Medline].

  88. Heimberg RG, Liebowitz MR, Hope DA, Schneier FR, Holt CS, Welkowitz LA, et al. Cognitive behavioral group therapy vs phenelzine therapy for social phobia: 12-week outcome. Arch Gen Psychiatry. 1998 Dec. 55(12):1133-41. [Medline]. [Full Text].

  89. Allgulander C. Paroxetine in social anxiety disorder: a randomized placebo-controlled study. Acta Psychiatr Scand. 1999 Sep. 100(3):193-8. [Medline].

  90. Stein MB, Fyer AJ, Davidson JR, Pollack MH, Wiita B. Fluvoxamine treatment of social phobia (social anxiety disorder): a double-blind, placebo-controlled study. Am J Psychiatry. 1999 May. 156(5):756-60. [Medline].

  91. Furukawa TA, Watanabe N, Churchill R. Psychotherapy plus antidepressant for panic disorder with or without agoraphobia: systematic review. Br J Psychiatry. 2006 Apr. 188:305-12. [Medline].

  92. Ayala ES, Meuret AE, Ritz T. Treatments for blood-injury-injection phobia: a critical review of current evidence. J Psychiatr Res. 2009 Oct. 43(15):1235-42. [Medline].

  93. Rothbaum BO, Anderson P, Zimand E, Hodges L, Lang D, Wilson J. Virtual reality exposure therapy and standard (in vivo) exposure therapy in the treatment of fear of flying. Behav Ther. 2006 Mar. 37(1):80-90. [Medline]. [Full Text].

  94. Practice guideline for the treatment of patients with panic disorder. Work Group on Panic Disorder. American Psychiatric Association. Am J Psychiatry. 1998 May. 155(5 Suppl):1-34. [Medline].

  95. Pohl RB, Wolkow RM, Clary CM. Sertraline in the treatment of panic disorder: a double-blind multicenter trial. Am J Psychiatry. 1998 Sep. 155(9):1189-95. [Medline]. [Full Text].

  96. Michelson D, Lydiard RB, Pollack MH, Tamura RN, Hoog SL, Tepner R, et al. Outcome assessment and clinical improvement in panic disorder: evidence from a randomized controlled trial of fluoxetine and placebo. The Fluoxetine Panic Disorder Study Group. Am J Psychiatry. 1998 Nov. 155(11):1570-7. [Medline].

  97. Uhlenhuth EH, Balter MB, Ban TA, Yang K. International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications: VI. Trends in recommendations for the pharmacotherapy of anxiety disorders, 1992-1997. Depress Anxiety. 1999. 9(3):107-16. [Medline].

  98. Herrera-Arellano A, Jiménez-Ferrer E, Zamilpa A, Morales-Valdéz M, García-Valencia CE, Tortoriello J. Efficacy and tolerability of a standardized herbal product from Galphimia glauca on generalized anxiety disorder. A randomized, double-blind clinical trial controlled with lorazepam. Planta Med. 2007 Jul. 73(8):713-7. [Medline].

  99. Komossa K, Depping AM, Meyer M, Kissling W, Leucht S. Second-generation antipsychotics for obsessive compulsive disorder. Cochrane Database Syst Rev. 2010 Dec 8. 12:CD008141. [Medline].

  100. Advisory Committee FDA. SEROQUEL XR for the Treatment of Patients with either Major Depressive Disorder or Generalized Anxiety Disorder. FDA. Available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/PsychopharmacologicDrugsAdvisoryCommittee/UCM161963.pdf.

  101. Cuijpers P, Donker T, Weissman MM, Ravitz P, Cristea IA. Interpersonal Psychotherapy for Mental Health Problems: A Comprehensive Meta-Analysis. Am J Psychiatry. 2016 Apr 1. appiajp201515091141. [Medline].

 
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Anxiety. Chart showing the female-to-male sex ratio for anxiety disorders. Adapted from Kessler et al, 1994.
Anxiety. Age of onset for anxiety disorders based on specific anxiety disorder type.
Brain structures involved in dealing with fear and stress.
 
 
 
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