Generalized anxiety disorder in adults: Epidemiology, pathogenesis, clinical manifestations, course, assessment, and diagnosis
- David Baldwin, DM FRCPsych
David Baldwin, DM FRCPsych
- Professor of Psychiatry and Head of Mental Health Group
- University of Southampton Faculty of Medicine
Generalized anxiety disorder (GAD) is characterized by excessive and persistent worrying that is hard to control, causes significant distress or impairment, and occurs on more days than not for at least six months. Other features include psychological symptoms of anxiety, such as apprehensiveness and irritability, and physical (or somatic) symptoms of anxiety, such as increased fatigue and muscular tension.
Effective treatments for generalized anxiety disorder include psychological interventions such as cognitive-behavioral therapy and applied relaxation, and medications including selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors.
This topic addresses the epidemiology, pathogenesis, clinical manifestations, and diagnosis of generalized anxiety disorder. Pharmacotherapy and psychotherapy for generalized anxiety disorder are discussed separately. (See "Pharmacotherapy for generalized anxiety disorder in adults" and "Psychotherapy for generalized anxiety disorder in adults".)
Generalized anxiety disorder (GAD) is common in both community and clinical settings. Epidemiologic studies of nationally representative samples in the United States have found a lifetime prevalence of GAD of 5.1 percent [1,2] to 11.9 percent . A review of epidemiological studies in Europe found a 12-month prevalence of 1.7 to 3.4 percent , and a lifetime prevalence of 4.3 to 5.9 percent .
GAD is one of the most common mental disorders in primary care settings and is associated with increased use of health services . In a study of adult primary care patients in four Nordic countries, the rates of GAD were 4.1 to 6.0 percent among men, and 3.7 to 7.1 percent among women .
- Wittchen HU, Zhao S, Kessler RC, Eaton WW. DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1994; 51:355.
- Kessler RC, Berglund P, Demler O, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62:593.
- Kessler RC, Gruber M, Hettema JM, et al. Co-morbid major depression and generalized anxiety disorders in the National Comorbidity Survey follow-up. Psychol Med 2008; 38:365.
- Wittchen HU, Jacobi F, Rehm J, et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011; 21:655.
- Wittchen HU, Jacobi F. Size and burden of mental disorders in Europe--a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005; 15:357.
- Wittchen HU, Kessler RC, Beesdo K, et al. Generalized anxiety and depression in primary care: prevalence, recognition, and management. J Clin Psychiatry 2002; 63 Suppl 8:24.
- Munk-Jørgensen P, Allgulander C, Dahl AA, et al. Prevalence of generalized anxiety disorder in general practice in Denmark, Finland, Norway, and Sweden. Psychiatr Serv 2006; 57:1738.
- Lenze EJ. Anxiety disorders in the elderly. In: Textbook of Anxiety Disorders, 2nd ed, Stein DJ, Hollander E, Rothbaum BO. (Eds), American Psychiatric Publishing, Inc, Washington, DC 2010. p.651.
- Brawman-Mintzer O, Lydiard RB, Emmanuel N, et al. Psychiatric comorbidity in patients with generalized anxiety disorder. Am J Psychiatry 1993; 150:1216.
- Tyrer P, Seivewright H, Johnson T. The Nottingham Study of Neurotic Disorder: predictors of 12-year outcome of dysthymic, panic and generalized anxiety disorder. Psychol Med 2004; 34:1385.
- Beesdo K, Hoyer J, Jacobi F, et al. Association between generalized anxiety levels and pain in a community sample: evidence for diagnostic specificity. J Anxiety Disord 2009; 23:684.
- Allgulander C. Morbid anxiety as a risk factor in patients with somatic diseases: A review of recent findings. Mind Brain 2010.
- Kendler KS. Major depression and generalised anxiety disorder. Same genes, (partly)different environments--revisited. Br J Psychiatry Suppl 1996; :68.
- Hettema JM, Prescott CA, Kendler KS. Genetic and environmental sources of covariation between generalized anxiety disorder and neuroticism. Am J Psychiatry 2004; 161:1581.
- Mackintosh MA, Gatz M, Wetherell JL, Pedersen NL. A twin study of lifetime Generalized Anxiety Disorder (GAD) in older adults: genetic and environmental influences shared by neuroticism and GAD. Twin Res Hum Genet 2006; 9:30.
- You JS, Hu SY, Chen B, Zhang HG. Serotonin transporter and tryptophan hydroxylase gene polymorphisms in Chinese patients with generalized anxiety disorder. Psychiatr Genet 2005; 15:7.
- Donner J, Sipilä T, Ripatti S, et al. Support for involvement of glutamate decarboxylase 1 and neuropeptide Y in anxiety susceptibility. Am J Med Genet B Neuropsychiatr Genet 2012; 159B:316.
- Unschuld PG, Ising M, Specht M, et al. Polymorphisms in the GAD2 gene-region are associated with susceptibility for unipolar depression and with a risk factor for anxiety disorders. Am J Med Genet B Neuropsychiatr Genet 2009; 150B:1100.
- Sevy S, Papadimitriou GN, Surmont DW, et al. Noradrenergic function in generalized anxiety disorder, major depressive disorder, and healthy subjects. Biol Psychiatry 1989; 25:141.
- Garvey MJ, Noyes R Jr, Woodman C, Laukes C. The association of urinary 5-hydroxyindoleacetic acid and vanillylmandelic acid in patients with generalized anxiety. Neuropsychobiology 1995; 31:6.
- Abelson JL, Glitz D, Cameron OG, et al. Blunted growth hormone response to clonidine in patients with generalized anxiety disorder. Arch Gen Psychiatry 1991; 48:157.
- Weizman R, Tanne Z, Granek M, et al. Peripheral benzodiazepine binding sites on platelet membranes are increased during diazepam treatment of anxious patients. Eur J Pharmacol 1987; 138:289.
- Ferrarese C, Appollonio I, Frigo M, et al. Decreased density of benzodiazepine receptors in lymphocytes of anxious patients: reversal after chronic diazepam treatment. Acta Psychiatr Scand 1990; 82:169.
- Wemmie JA, Taugher RJ, Kreple CJ. Acid-sensing ion channels in pain and disease. Nat Rev Neurosci 2013; 14:461.
- Wu JC, Buchsbaum MS, Hershey TG, et al. PET in generalized anxiety disorder. Biol Psychiatry 1991; 29:1181.
- Nitschke JB, Sarinopoulos I, Oathes DJ, et al. Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response. Am J Psychiatry 2009; 166:302.
- Hirsch CR, Meeten F, Krahé C, Reeder C. Resolving Ambiguity in Emotional Disorders: The Nature and Role of Interpretation Biases. Annu Rev Clin Psychol 2016; 12:281.
- MacLeod C, Mathews A, Tata P. Attentional bias in emotional disorders. J Abnorm Psychol 1986; 95:15.
- Mathews A, Richards A, Eysenck M. Interpretation of homophones related to threat in anxiety states. J Abnorm Psychol 1989; 98:31.
- Mogg K, Bradley BP, Millar N, White J. A follow-up study of cognitive bias in generalized anxiety disorder. Behav Res Ther 1995; 33:927.
- Mogg K, Baldwin DS, Brodrick P, Bradley BP. Effect of short-term SSRI treatment on cognitive bias in generalised anxiety disorder. Psychopharmacology (Berl) 2004; 176:466.
- Safren SA, Gershuny BS, Marzol P, et al. History of childhood abuse in panic disorder, social phobia, and generalized anxiety disorder. J Nerv Ment Dis 2002; 190:453.
- Rosenbaum JF, Biederman J, Bolduc-Murphy EA, et al. Behavioral inhibition in childhood: a risk factor for anxiety disorders. Harv Rev Psychiatry 1993; 1:2.
- Tyrer P, Seivewright H, Johnson T. The core elements of neurosis: mixed anxiety-depression (cothymia) and personality disorder. J Pers Disord 2003; 17:129.
- Khan AA, Jacobson KC, Gardner CO, et al. Personality and comorbidity of common psychiatric disorders. Br J Psychiatry 2005; 186:190.
- Beck AT, Emery G, Greenberg RL. Anxiety Disorders and Phobias: A Cognitive Perspective, Basic Books, New York 1985.
- Barlow DH. Anxiety and Its Disorders: The Nature and Treatment of Anxiety and Panic, Guilford Press, New York 1988.
- Borkovec TD, Alcaine O, Behar E. Avoidance theory of worry and generalized anxiety disorder. In: Generalized Anxiety Disorder: Advances in Research and Parctice, Heimberg RG, Turk CL, Mennin DS. (Eds), Guilford Press, New York 2004. p.77.
- Dugas MJ, Marchand A, Ladouceur R. Further validation of a cognitive-behavioral model of generalized anxiety disorder: diagnostic and symptom specificity. J Anxiety Disord 2005; 19:329.
- Wells A, King P. Metacognitive therapy for generalized anxiety disorder: an open trial. J Behav Ther Exp Psychiatry 2006; 37:206.
- Roemer L, Molina S, Borkovec TD. An investigation of worry content among generally anxious individuals. J Nerv Ment Dis 1997; 185:314.
- Brown TA, O’Leary TA, Barlow DH. Generalized anxiety disorder. In: Clinical Handbook of Psychological Disorders, 2nd ed, Barlow DH. (Ed), Guilford Press, New York 1993. p.137.
- Bruce SE, Yonkers KA, Otto MW, et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Am J Psychiatry 2005; 162:1179.
- Ramsawh HJ, Raffa SD, Edelen MO, et al. Anxiety in middle adulthood: effects of age and time on the 14-year course of panic disorder, social phobia and generalized anxiety disorder. Psychol Med 2009; 39:615.
- Beesdo K, Knappe S, Pine DS. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am 2009; 32:483.
- Angst J, Gamma A, Baldwin DS, et al. The generalized anxiety spectrum: prevalence, onset, course and outcome. Eur Arch Psychiatry Clin Neurosci 2009; 259:37.
- Shores MM, Glubin T, Cowley DS, et al. The relationship between anxiety and depression: a clinical comparison of generalized anxiety disorder, dysthymic disorder, panic disorder, and major depressive disorder. Compr Psychiatry 1992; 33:237.
- Hoehn-Saric R, Hazlett RL, McLeod DR. Generalized anxiety disorder with early and late onset of anxiety symptoms. Compr Psychiatry 1993; 34:291.
- Zhang X, Norton J, Carrière I, et al. Risk factors for late-onset generalized anxiety disorder: results from a 12-year prospective cohort (the ESPRIT study). Transl Psychiatry 2015; 5:e536.
- Kessler RC, DuPont RL, Berglund P, Wittchen HU. Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. Am J Psychiatry 1999; 156:1915.
- Wittchen HU, Carter RM, Pfister H, et al. Disabilities and quality of life in pure and comorbid generalized anxiety disorder and major depression in a national survey. Int Clin Psychopharmacol 2000; 15:319.
- Tully PJ, Cosh SM, Baune BT. A review of the affects of worry and generalized anxiety disorder upon cardiovascular health and coronary heart disease. Psychol Health Med 2013; 18:627.
- Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med 2006; 166:1092.
- Kertz S, Bigda-Peyton J, Bjorgvinsson T. Validity of the Generalized Anxiety Disorder-7 scale in an acute psychiatric sample. Clin Psychol Psychother 2013; 20:456.
- Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res 2002; 52:69.
- Dear BF, Titov N, Sunderland M, et al. Psychometric comparison of the generalized anxiety disorder scale-7 and the Penn State Worry Questionnaire for measuring response during treatment of generalised anxiety disorder. Cogn Behav Ther 2011; 40:216.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
- Biological factors
- Neuropsychological factors
- Developmental and personality factors
- Cognitive origins of excessive worrying
- CLINICAL MANIFESTATIONS
- Screening instrument
- Symptom severity assessment instrument
- Differential diagnosis
- - Depression
- - Hypochondriasis
- - Panic disorder
- - Adjustment disorder
- Obsessive compulsive disorder
- SUMMARY AND RECOMMENDATIONS