Anxiety Disorders

doi:10.1017/9781009067287.019

Chapter 18 - Anxiety Disorders

Published online by Cambridge University Press: 01 February 2024

Laura Celebre and

Edited by

Peter Falkai and

Andrea Fiorillo: Affiliation:
University of Campania “L. Vanvitelli”, Naples
Peter Falkai: Affiliation:
Ludwig-Maximilians-Universität München
Philip Gorwood: Affiliation:
Sainte-Anne Hospital, Paris

Book contents

Get access

Summary

Anxiety Disorders (ADs) are the most prevalent mental disorders worldwide and are characterized by a wide variety of psychological and somatic symptoms, which are often misinterpreted as symptoms of a medical condition. ADs carry a large disease burden that impacts negatively on patients’ health-related quality of life and global life satisfaction and disrupts important activities of daily living. In this chapter we analyze the epidemiology and clinical presentation of ADs, highlighting recent innovations and changes in the classification of anxiety disorders in DSM-5 and ICD-11. Main available pharmacological and nonpharmacological therapies for the treatment of ADs, based on the most recent clinical evidence and updated literature, are presented as well. Lastly, we focus the attention on future perspectives about ADs, examining clinical correlations of peripheral biomarkers, neuroimaging, genetics, epigenetics, and microbiota data. These features may be useful to achieve further insight in terms of physiopathology, to support early diagnosis, and to facilitate the prediction of illness susceptibility and treatment response, in order to support clinicians’ practice and to develop personalized treatment strategies.

Keywords

anxiety disorders panic disorder generalized anxiety disorder social anxiety disorder genetics neuroimaging psychopharmacology

Information

Type: Chapter
Information: Mental Health Research and Practice
From Evidence to Experience
, pp. 317 - 340

DOI: https://doi.org/10.1017/9781009067287.019 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2024

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

American Psychiatric Association/DSM-5 Task Force. Diagnostic and statistical manual of mental disorders: DSM-5. 5th ed. American Psychiatric Association; 2013. www.worldcat.org/title/diagnostic-and-statistical-manual-of-mental-disorders-dsm-5/oclc/830807378.Google Scholar

Penninx, BW, Pine, DS, Holmes, EA, Reif, A. Anxiety disorders. Lancet 2021;397(10277):914–27. www.thelancet.com/article/S0140673621003597/fulltext.CrossRef Google Scholar PubMed

Park, SC, Kim, YK. Anxiety disorders in the DSM-5: Changes, controversies, and future directions. Adv Exp Med Biol 2020;1191:187–96.CrossRef Google Scholar PubMed

Asmundson, GJG, Taylor, S, Smits, JAJ. Panic disorder and agoraphobia: An overview and commentary on DSM-5 changes. Depress Anxiety 2014;31(6):480–6.CrossRef Google Scholar PubMed

World Health Organization. ICD-11 – Mortality and Morbidity Statistics 2019. https://icd.who.int/browse11/l-m/en#/http://id.who.int/icd/entity/831337417.Google Scholar

World Health Organization. ICD-10 online versions. 2019; https://icd.who.int/browse10/2019/en.Google Scholar

Gaebel, W, Kerst, A. ICD-11 Mental, behavioural or neurodevelopmental disorders: Innovations and managing implementation. Arch Psychiatry Psychother 2019;21(3):7–12.CrossRef Google Scholar

Reed, GM, First, MB, Kogan, CS, et al. Innovations and changes in the ICD-11 classification of mental, behavioural and neurodevelopmental disorders. World Psychiatry 2019;18(1):3–19.CrossRef Google Scholar PubMed

Kogan, CS, Stein, DJ, Maj, M, et al. The classification of anxiety and fear-related disorders in the ICD-11. Depression and Anxiety 2016;33(12):1141–54.CrossRef Google Scholar PubMed

Remes, O, Brayne, C, van der Linde, R, Lafortune, L. A systematic review of reviews on the prevalence of anxiety disorders in adult populations. Brain Behav 2016;6(7):e00497. https://doi.org/10.1002/brb3.497. PMID: 27458547; PMCID: PMC4951626.CrossRef Google Scholar PubMed

Baxter, AJ, Scott, KM, Ferrari, AJ, et al. Challenging the myth of an “epidemic” of common mental disorders: Trends in the global prevalence of anxiety and depression between 1990 and 2010. Depress Anxiety 2014;31(6):506–16.CrossRef Google Scholar PubMed

OECD. Health at a Glance: Europe 2018 OECD (Health at a Glance: Europe); 2018. www.oecd-ilibrary.org/social-issues-migration-health/health-at-a-glance-europe-2018_health_glance_eur-2018-en Google Scholar

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(9):655–79.CrossRef Google Scholar PubMed

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(6):593–602. https://doi.org/10.1001/archpsyc.62.6.593. Erratum in: Arch Gen Psychiatry 2005;62(7):768. Merikangas, KR [added]. PMID: 15939837.CrossRef Google Scholar PubMed

Winkler, P, Formanek, T, Mlada, K, et al. Increase in prevalence of current mental disorders in the context of COVID-19: Analysis of repeated nationwide cross-sectional surveys. Epidemiol Psychiatr Sci 2020;29:e173.CrossRef Google Scholar PubMed

Czeisler, M, Lane, RI, Wiley, JF, et al. Follow-up survey of US adult reports of mental health, substance use, and suicidal ideation during the COVID-19 pandemic, September 2020. JAMA Netw Open 2021;4(2):e2037665–e2037665.CrossRef Google Scholar PubMed

Wang, Y, Shi, L, Que, J, et al. The impact of quarantine on mental health status among general population in China during the COVID-19 pandemic. Mol Psychiatry 2021; 26: 1–10.CrossRef Google Scholar

Huang, Y, Zhao, N. Generalized anxiety disorder, depressive symptoms and sleep quality during COVID-19 outbreak in China: a web-based cross-sectional survey. Psychiatry Res 2020;288.CrossRef Google Scholar

Compton, MT, West, JC, Olfson, M. Prolonged duration of untreated psychosis in nonaffective first-episode psychotic disorders compared to other psychoses. Int J Psychiatry Clin Pract 2006;10(4):265–8. https://pubmed.ncbi.nlm.nih.gov/24941145/.CrossRef Google Scholar PubMed

Dell’Osso, B, Camuri, G, Benatti, B, Buoli, M, Altamura, AC. Differences in latency to first pharmacological treatment (duration of untreated illness) in anxiety disorders: A study on patients with panic disorder, generalized anxiety disorder and obsessive-compulsive disorder. Early Interv Psychiatry 2013;7(4):374–80.Google Scholar

Dell’Osso, B, Altamura, AC. Duration of untreated psychosis and duration of untreated illness: New vistas, CNS Spectrums 2010;15(4):238–46. https://pubmed.ncbi.nlm.nih.gov/20414173/.Google Scholar PubMed

Altamura, AC, Dell’Osso, B, Mundo, E, Dell’Osso, L. Duration of untreated illness in major depressive disorder: A naturalistic study. Int J Clin Pract 2007;61(10):1697–700. https://pubmed.ncbi.nlm.nih.gov/17877655/.CrossRef Google Scholar PubMed

Altamura, AC, Dell’Osso, B, Vismara, S, Mundo, E. May duration of untreated illness influence the long-term course of major depressive disorder? Eur Psychiatry 2008;23(2):92–6. https://pubmed.ncbi.nlm.nih.gov/18248964/.CrossRef Google Scholar PubMed

Dell’Osso, B, Cremaschi, L, Grancini, B, et al. Italian patients with more recent onset of Major Depressive Disorder have a shorter duration of untreated illness. Int J Clin Pract 2017;71(2). https://pubmed.ncbi.nlm.nih.gov/28090727/.Google Scholar PubMed

Galimberti, C, Bosi, MF, Volontè, M, et al. Duration of untreated illness and depression severity are associated with cognitive impairment in mood disorders. Int J Psychiatry Clin Pract 2020;24(3):227–35. https://pubmed.ncbi.nlm.nih.gov/32338553/.CrossRef Google Scholar PubMed

Buoli, M, Cesana, BM, Fagiolini, A, et al. Which factors delay treatment in bipolar disorder? A nationwide study focussed on duration of untreated illness. Early Interv Psychiatry 2020;15(5):1136–45. https://pubmed.ncbi.nlm.nih.gov/33058435/.Google Scholar PubMed

Altamura, AC, Buoli, M, Albano, A, Dell’Osso, B. Age at onset and latency to treatment (duration of untreated illness) in patients with mood and anxiety disorders: A naturalistic study. Int Clin Psychopharmacol 2010;25(3):172–9. https://pubmed.ncbi.nlm.nih.gov/20305566/.CrossRef Google Scholar PubMed

Dell’Osso, B, Benatti, B, Grancini, B, et al. Investigating duration of illness and duration of untreated illness in obsessive compulsive disorder reveals patients remain at length pharmacologically untreated. Int J Psychiatry Clin Pract 2019;23(4):311–13. https://pubmed.ncbi.nlm.nih.gov/31144538/.CrossRef Google Scholar PubMed

Matsumoto, Y, Nakamae, T, Abe, Y, Watanabe, A, Narumoto, J. Duration of untreated illness of patients with obsessive–compulsive disorder in Japan. Early Interv Psychiatry 2020;15(6):1644–9. https://pubmed.ncbi.nlm.nih.gov/33372398/.Google Scholar PubMed

Herzog, A, Shedden-Mora, MC, Jordan, P, Löwe, B. Duration of untreated illness in patients with somatoform disorders. J Psychosom Res 2018;107:1–6. https://pubmed.ncbi.nlm.nih.gov/29502757/.CrossRef Google Scholar PubMed

Neubauer, K, Weigel, A, Daubmann, A, et al. Paths to first treatment and duration of untreated illness in anorexia nervosa: Are there differences according to age of onset? Eur Eat Disord Rev 2014;22(4):292–8. https://pubmed.ncbi.nlm.nih.gov/24888519/.CrossRef Google Scholar PubMed

Buoli, M, Dell’Osso, B, Zaytseva, Y, et al. Duration of untreated illness (DUI) and schizophrenia sub-types: A collaborative study between the universities of Milan and Moscow. Int J Soc Psychiatry 2013;59(8):765–70. https://pubmed.ncbi.nlm.nih.gov/23034286/.CrossRef Google Scholar PubMed

Dell’Osso, B, Glick, ID, Baldwin, DS, Altamura, AC. Can long-term outcomes be improved by shortening the duration of untreated illness in psychiatric Disorders? a conceptual framework. Psychopathology; 2012;46(1):14–21. https://pubmed.ncbi.nlm.nih.gov/22890286/.CrossRef Google Scholar PubMed

Bukh, JD, Bock, C, Vinberg, M, Kessing, LV. The effect of prolonged duration of untreated depression on antidepressant treatment outcome. J Affect Disord 2013;145(1):42–8. https://pubmed.ncbi.nlm.nih.gov/22854096/.CrossRef Google Scholar PubMed

Palazzo, MC, Arici, C, Dell’osso, B, et al. Access and latency to first antipsychotic treatment in Italian patients with schizophrenia and other schizophrenic spectrum disorders across different epochs. Hum Psychopharmacol 2016;31(2):113–20. https://pubmed.ncbi.nlm.nih.gov/26948428/.CrossRef Google Scholar PubMed

Dell’Osso, B, Oldani, L, Camuri, G, et al. Reduced duration of untreated illness over time in patients with schizophrenia spectrum, mood and anxiety disorders. Psychiatry Clin Neurosci 2016;70(5):202–10. https://pubmed.ncbi.nlm.nih.gov/26821781/.Google Scholar PubMed

Vigne, P, Fortes, P, Dias, RV, et al. Duration of untreated illness in a cross-diagnostic sample of obsessive-compulsive disorder, panic disorder, and social anxiety disorder. CNS Spectr 2019;24(5):526–32. https://pubmed.ncbi.nlm.nih.gov/30419984/.CrossRef Google Scholar

Benatti, B, Camuri, G, Dell’Osso, B, et al. Which factors influence onset and latency to treatment in generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder? Int Clin Psychopharmacol 2016;31(6):347–52. https://pubmed.ncbi.nlm.nih.gov/27384739/.CrossRef Google Scholar PubMed

Altamura, AC, Santini, A, Salvadori, D, Mundo, E. Duration of untreated illness in panic disorder: a poor outcome risk factor? Neuropsychiatr Dis Treat 2005;1(4):345–7. http://www.ncbi.nlm.nih.gov/pubmed/18568114.Google Scholar PubMed

Wagner, R, Silove, D, Marnane, C, Rouen, D. Delays in referral of patients with social phobia, panic disorder and generalized anxiety disorder attending a specialist anxiety clinic. J Anxiety Disord. 2006;20(3):363–71.CrossRef Google Scholar PubMed

Kroenke, K, Spitzer, RL, Williams, JBW, Monahan, PO, Löwe, B. Anxiety disorders in primary care: Prevalence, impairment, comorbidity, and detection. Ann Intern Med. 2007;146(5):317–25.CrossRef Google Scholar PubMed

Martin-Merino, E, Ruigomez, A, Wallander, M-A, Johansson, S, Garcia-Rodriguez, LA. Prevalence, incidence, morbidity and treatment patterns in a cohort of patients diagnosed with anxiety in UK primary care. Fam Pract. 2010;27(1):9–16.CrossRef Google Scholar

Strawn, JR, Welge, JA, Wehry, AM, Keeshin, B, Rynn, MA. Efficacy and tolerability of antidepressants in pediatric anxiety disorders: a systematic review and meta-analysis. Depress Anxiety. 2015;32(3):149–57.CrossRef Google Scholar PubMed

Katzman, MA, Bleau, P, Blier, P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry 2014;14(1):S1. https://pubmed.ncbi.nlm.nih.gov/25081580/.CrossRef Google Scholar PubMed

Bandelow, B, Scott, M, Wedekind, D. Treatment of anxiety disorders. Dialogues Clin Neurosci 2017;19(2):93–107. https://pubmed.ncbi.nlm.nih.gov/28867934/.CrossRef Google Scholar PubMed

Bruce, SE, Vasile, RG, Goisman, RM, et al. Are benzodiazepines still the medication of choice for patients with panic disorder with or without agoraphobia? Am J Psychiatry 2003;160(8):1432–8. https://pubmed.ncbi.nlm.nih.gov/12900305/.CrossRef Google Scholar PubMed

Kessler, RC, Wai, TC, Jin, R, et al. The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2006;63(4):415–24.CrossRef Google Scholar PubMed

Grancini, B, De Carlo, V, Palazzo, M, et al. Does initial use of benzodiazepines delay an adequate pharmacological treatment? A multicentre analysis in patients with psychotic and affective disorders. Int Clin Psychopharmacol 2018;33(3):140–6. https://pubmed.ncbi.nlm.nih.gov/29461302/.CrossRef Google Scholar PubMed

De Carlo, V, Grancini, B, Vismara, M, et al. Exploring characteristics associated with first benzodiazepine prescription in patients with affective disorders and related diagnoses. Hum Psychopharmacol 2019;34(3):e2695. https://pubmed.ncbi.nlm.nih.gov/31044486/.CrossRef Google Scholar PubMed

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (3rd ed.). American Psychiatric Association; 1980.Google Scholar

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised). American Psychiatric Association; 1987.Google Scholar

American Psychiatric Association., Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders: DSM-IV. American Psychiatric Association; 1994. 886 p.Google Scholar

Shear, MK, Maser, JD. Standardized assessment for panic disorder research: A conference report. Arch Gen Psychiatry 1994;51(5):346–54. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/496590.CrossRef Google Scholar PubMed

Marchesi, C, Cantoni, A, Fontò, S, Giannelli, M, Maggini, C. Predictors of symptom resolution in panic disorder after one year of pharmacological treatment: A naturalistic study. Pharmacopsychiatry 2006;39(2):60–5. https://pubmed.ncbi.nlm.nih.gov/16555166/.CrossRef Google Scholar PubMed

Breier, A, Charney, DS, Heninger, GR. Agoraphobia with panic attacks: Development, diagnostic stability, and course of illness. Arch Gen Psychiatry 1986;43(11):1029–36. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/493912.CrossRef Google Scholar PubMed

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.). American Psychiatric Association. 2000. https://doi.org/10.1176/appi.books.9780890425596.Google Scholar

World Health Organization(WHO). The ICD-10 classification of mental and behavioural disorders. 1993. https://apps.who.int/iris/handle/10665/37108.Google Scholar

Marks, I. Agoraphobia, panic disorder and related conditions in the DSM-IIIR and ICD-10. J Psychopharmacol. 1987;1(1):6–12. https://doi.org/10.1177/026988118700100103.CrossRef Google Scholar PubMed

Wittchen, H, Gloster, A, Beesdo-Baum, K, Fava, G, Craske, M. Agoraphobia: A review of the diagnostic classificatory position and criteria. Depress Anxiety 2010;27(2):113–33. https://pubmed.ncbi.nlm.nih.gov/20143426/.CrossRef Google Scholar PubMed

Bystritsky, A, Kerwin, L, Niv, N, et al. Clinical and subthreshold panic disorder. Depress Anxiety 2010;27(4):381.CrossRef Google Scholar PubMed

Chou, K-L. Panic disorder in older adults: Evidence from the national epidemiologic survey on alcohol and related conditions. Int J Geriatr Psychiatry 2010;25(8):822–32. https://onlinelibrary.wiley.com/doi/full/10.1002/gps.2424.CrossRef Google Scholar PubMed

Horenstein, A, Heimberg, R. Anxiety disorders and healthcare utilization: A systematic review. Clin Psychol Rev 2020;81:101894. https://pubmed.ncbi.nlm.nih.gov/32818687/.CrossRef Google Scholar PubMed

Otto, MW, Tuby, KS, Gould, RA, McLean, RYS, Pollack, MH. An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. Am J Psychiatry. 2001;158(12):1989–92.CrossRef Google Scholar PubMed

Bakker, A, Balkom AJLM, Van, Spinhoven, P. SSRIs vs. TCAs in the treatment of panic disorder: a meta-analysis. Acta Psychiatr Scand. 2002;106(3):163–7.CrossRef Google Scholar PubMed

Moylan, S, Staples, J, Ward, SA, et al. The efficacy and safety of alprazolam versus other benzodiazepines in the treatment of panic disorder. J Clin Psychopharmacol. 2011;31(5):647–52.CrossRef Google Scholar PubMed

Nardi, AE, Valença, AM, Freire, RC, et al. Psychopharmacotherapy of panic disorder: 8-week randomized trial with clonazepam and paroxetine. Brazilian J Med Biol Res. 2011;44(4):366–73.CrossRef Google Scholar PubMed

Schweizer, E, Pohl, R, Balon, R, et al. Alprazolam in the treatment of panic disorder. Pharmacopsychiatry. 1990;23(02):229–33.CrossRef Google Scholar PubMed

Noyes, R, Burrows, GD, Reich, JH, et al. Diazepam versus alprazolam for the treatment of panic disorder. J Clin Psychiatry 1996;57(8):349–55. http://europepmc.org/abstract/MED/8752017.Google Scholar PubMed

Galynker, I, Khan, A, Grebchenko, Y, et al. Low-dose risperidone and quetiapine as monotherapy for comorbid anxiety and depression. J Clin Psychiatry 2005;66(04):544.CrossRef Google Scholar PubMed

Hollifield, M, Thompson, PM, Ruiz, JE, Uhlenhuth, EH. Potential effectiveness and safety of olanzapine in refractory panic disorder. Depress Anxiety. 2005;21(1):33–40.CrossRef Google Scholar PubMed

Simon, NM, Hoge, EA, Fischmann, D, et al. An open-label trial of risperidone augmentation for refractory anxiety disorders. J Clin Psychiatry 2006;67(03):381–5.CrossRef Google Scholar PubMed

Prosser, JM, Yard, S, Steele, A, Cohen, LJ, Galynker, II. A comparison of low-dose risperidone to paroxetine in the treatment of panic attacks: a randomized, single-blind study. BMC Psychiatry 2009;9(1):25.CrossRef Google Scholar PubMed

Perna, G, Caldirola, D. Management of treatment-resistant panic disorder. Curr Treat Options Psychiatry 2017;4(4):371–86. https://link.springer.com/article/10.1007/s40501-017-0128-7.Google Scholar PubMed

Hofmann, SG, Smits, JAJ. Cognitive-behavioral therapy for adult anxiety disorders: A meta-analysis of randomized placebo-controlled trials. J Clin Psychiatry 2008;69(4):621–32. https://pubmed.ncbi.nlm.nih.gov/18363421/.Google Scholar PubMed

Sánchez-Meca, J, Rosa-Alcázar, AI, Marín-Martínez, F, Gómez-Conesa, A. Psychological treatment of panic disorder with or without agoraphobia: A meta-analysis. Clin Psychol Rev 2010;30(1):37–50.CrossRef Google Scholar PubMed

Muris, P, van Brakel AML, , Arntz, A, Schouten, E. Behavioral inhibition as a risk factor for the development of childhood anxiety disorders: A longitudinal study. J Child Fam Stud 2011;20(2):157–70.CrossRef Google Scholar PubMed

Furukawa, TA, Watanabe, N, Churchill, R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev 2007;1:CD004364.Google Scholar

Crocq, M. The history of generalized anxiety disorder as a diagnostic category. Dialogues Clin Neurosci 2017;19(2):107–16. https://pubmed.ncbi.nlm.nih.gov/28867935/.CrossRef Google Scholar PubMed

Berger, A, Dukes, E, Wittchen, H-U, et al. Patterns of healthcare utilization in patients with generalized anxiety disorder in general practice in Germany. Eur J Psychiatry 2009;23(2).CrossRef Google Scholar

Wittchen, H-U. Generalized anxiety disorder: Prevalence, burden, and cost to society. Depress Anxiety 2002;16(4):162–71. https://onlinelibrary.wiley.com/doi/full/10.1002/da.10065.CrossRef Google Scholar PubMed

Sanderson, WC, Barlow, DH. A description of patients diagnosed with DSM-III-R generalized anxiety disorder. J Nerv Ment Dis 1990;178(9):588–91.CrossRef Google Scholar PubMed

Starcevic, V. Anxiety states: A review of conceptual and treatment issues. Curr Opin Psychiatry 2006;19(1):79–83. https://pubmed.ncbi.nlm.nih.gov/16612184/.CrossRef Google Scholar

Yonkers, K, Bruce, S, Dyck, I, Keller, M. Chronicity, relapse, and illness–course of panic disorder, social phobia, and generalized anxiety disorder: Findings in men and women from 8 years of follow-up. Depress Anxiety 2003;17(3):173–9. https://pubmed.ncbi.nlm.nih.gov/12768651/.CrossRef Google Scholar PubMed

Ravindran, LN, Stein, MB. Anxiety disorders: Somatic treatment. In Sadock, BJ, Sadock, VA, Ruiz, P (Eds.) Kaplan & Sadock Comprehensive Textbook of Psychiatry. Wolters Kluwer; 2009. pp. 1906–14.Google Scholar

Reinhold, JA, Rickels, K. Pharmacological treatment for generalized anxiety disorder in adults: an update. Expert Opin Pharmacother 2015;16(11):1669–81.CrossRef Google Scholar PubMed

Kapczinski, F, dos Santos Souza, JJ, Batista Miralha da Cunha, AA, Schmitt, RR. Antidepressants for generalised anxiety disorder (GAD). In Kapczinski, F (Ed.). Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2003.Google Scholar

Taylor, WD. Depression in the Elderly. N Engl J Med 2014;371(13):1228–36. https://doi.org/10.1056/NEJMcp1402180.CrossRef Google Scholar PubMed

Gommoll, C, Durgam, S, Mathews, M, et al. A double-blind, randomized, placebo-controlled, fixed dose phase III study of Vilazodone in patients with Generalized Anxiety Disorder. Depress Anxiety 2015;32(6):451–9.CrossRef Google Scholar PubMed

Chessick, CA, Allen, MH, Thase, ME, et al. Azapirones for generalized anxiety disorder. Cochrane Database Syst Rev 2006;3:CD006115.Google Scholar

Baldwin, DS, den Boer, JA, Lyndon, G, et al. Efficacy and safety of pregabalin in generalised anxiety disorder: A critical review of the literature. J Psychopharmacol 2015;29(10):1047–60.CrossRef Google Scholar PubMed

Kreys, T-JM, Phan, S V. A literature review of quetiapine for generalized anxiety disorder. Pharmacother J Hum Pharmacol Drug Ther 2015;35(2):175–88.CrossRef Google Scholar PubMed

Ravindran, LN, Stein, MB. The pharmacologic treatment of anxiety disorders. J Clin Psychiatry 2010;71(7):839–54.CrossRef Google Scholar PubMed

Billioti de Gage, S, Pariente, A, Bégaud, B. Is there really a link between benzodiazepine use and the risk of dementia? Expert Opin Drug Saf 2015;14(5):733–47.CrossRef Google Scholar PubMed

Cuijpers, P, van Straten, A. Improving outcomes in social anxiety disorder. The Lancet Psychiatry. 2014;1(5):324–6. https://pubmed.ncbi.nlm.nih.gov/26360985/.CrossRef Google Scholar PubMed

Janet, P, Raymond, F. Les obsessions et la psychasthénie. Paris: Alcan; 1903. www.worldcat.org/title/obsessions-et-la-psychasthenie/oclc/5949962.Google Scholar

Rose, GM, Tadi, P. Social anxiety disorder. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2021. Available from: www.ncbi.nlm.nih.gov/books/NBK555890/.Google Scholar

Scaini, S, Belotti, R, Ogliari, A. Genetic and environmental contributions to social anxiety across different ages: A meta-analytic approach to twin data. J Anxiety Disord 2014;28(7):650–6. https://pubmed.ncbi.nlm.nih.gov/25118017/.CrossRef Google Scholar

Leichsenring, F, Leweke, F. Social anxiety disorder. N Engl J Med 2017;376(23):2255–64. www.nejm.org/doi/10.1056/NEJMcp1614701.CrossRef Google Scholar PubMed

Hyett, MP, McEvoy, PM. Social anxiety disorder: Looking back and moving forward. Psychol Med 2018;48(12):1937–44. https://pubmed.ncbi.nlm.nih.gov/29321077/.CrossRef Google Scholar PubMed

Heimberg, RG, Hofmann, SG, Liebowitz, MR, et al. Social anxiety disorder in DSM-5. Depress Anxiety 2014;31(6):472–9. https://pubmed.ncbi.nlm.nih.gov/24395386/.CrossRef Google Scholar PubMed

Bögels, SM, Alden, L, Beidel, DC, et al. Social anxiety disorder: Questions and answers for the DSM-V. Depress Anxiety 2010;27(2):168–89. https://pubmed.ncbi.nlm.nih.gov/20143427/.CrossRef Google Scholar PubMed

Beidel, DC, Turner, SM, Sallee, FR, et al. SET-C versus fluoxetine in the treatment of childhood social phobia. J Am Acad Child Adolesc Psychiatry 2007;46(12):1622–32. https://pubmed.ncbi.nlm.nih.gov/18030084/.CrossRef Google Scholar PubMed

Stein, MB, Stein, DJ. Social anxiety disorder. The Lancet 2008;371(9618):1115–25. https://pubmed.ncbi.nlm.nih.gov/18374843/.CrossRef Google Scholar PubMed

Steinert, C, Hofmann, M, Leichsenring, F, Kruse, J. What do we know today about the prospective long-term course of social anxiety disorder? A systematic literature review. J Anxiety Disord 2013;27(7):692–702. https://pubmed.ncbi.nlm.nih.gov/24176803/.CrossRef Google Scholar PubMed

Kashdan, T, Hofmann, S. The high-novelty-seeking, impulsive subtype of generalized social anxiety disorder. Depress Anxiety 2008;25(6):535–41. https://pubmed.ncbi.nlm.nih.gov/17935217/.CrossRef Google Scholar PubMed

D’Avanzato, C, Dalrymple, K. Recent Insight Into the Subtypes of Social Anxiety Disorder. Curr Psychiatry Rep 2016;18(5):50. https://pubmed.ncbi.nlm.nih.gov/27017831/.CrossRef Google Scholar PubMed

Nagata, T, Suzuki, F, Teo, AR. Generalized social anxiety disorder: A still-neglected anxiety disorder 3 decades since Liebowitz’s review. Psych Clin Neurosci 2015;69(12):724–40. https://pubmed.ncbi.nlm.nih.gov/26121185/.CrossRef Google Scholar

Ruscio, AM, Brown, TA, Chiu, WT, et al. Social fears and social phobia in the USA: Results from the National Comorbidity Survey Replication. Psychol Med 2008;38 (1):15–28. https://pubmed.ncbi.nlm.nih.gov/17976249/.CrossRef Google Scholar PubMed

Koyuncu, A, İnce, E, Ertekin, E, Tükel, R. Comorbidity in social anxiety disorder: Diagnostic and therapeutic challenges. Drugs in Context 2019;8:212573. https://pubmed.ncbi.nlm.nih.gov/30988687/CrossRef Google Scholar PubMed

Kessler, RC. The impairments caused by social phobia in the general population: Implications for intervention. Acta Psych Scand, Suppl 2003;417:19–27. https://pubmed.ncbi.nlm.nih.gov/12950433/.CrossRef Google Scholar

Mayo-Wilson, E, Dias, S, Mavranezouli, I, et al. Psychological and pharmacological interventions for social anxiety disorder in adults: A systematic review and network meta-analysis. The Lancet Psychiatry 2014;1(5):368–76. https://pubmed.ncbi.nlm.nih.gov/26361000/.CrossRef Google Scholar PubMed

Fedoroff, IC, Taylor, S. Psychological and pharmacological treatments of social phobia: A meta-analysis. J Clin Psychopharmacol 2001;21(3):311–24. https://pubmed.ncbi.nlm.nih.gov/11386495/.CrossRef Google Scholar PubMed

Canton, J, Scott, KM, Glue, P. Optimal treatment of social phobia: Systematic review and meta-analysis. Neuropsychiatr Dis Treat 2012;8:203–15. https://pubmed.ncbi.nlm.nih.gov/22665997/.Google Scholar PubMed

Lader, M, Stender, K, Bürger, V, Nil, R. Efficacy and tolerability of escitalopram in 12- and 24-week treatment of social anxiety disorder: Randomised, double-blind, placebo-controlled, fixed-dose study. Depress Anxiety 2004;19(4:241–8.CrossRef Google Scholar PubMed

Kasper, S, Stein, DJ, Loft, H, Nil, R. Escitalopram in the treatment of social anxiety disorder. Br J Psychiatry 2005;186(3):222–6.CrossRef Google Scholar PubMed

Van Ameringen, MA, Lane, RM, et al. Sertraline treatment of generalized social phobia: A 20-week, double-blind, placebo-controlled study. Am J Psychiatry 2001;158(2):275–81.CrossRef Google Scholar PubMed

Liebowitz, MR, DeMartinis, NA, Weihs, K, et al. Efficacy of sertraline in severe generalized social anxiety disorder. J Clin Psychiatry 2003;64(7):785–92.CrossRef Google Scholar PubMed

Allgulander, C, Mangano, R, Zhang, J, et al. Efficacy of Venlafaxine ER in patients with social anxiety disorder: A double-blind, placebo-controlled, parallel-group comparison with paroxetine. Hum Psychopharmacol Clin Exp. 2004;19(6):387–96.CrossRef Google Scholar

Stein, MB, Pollack, MH, Bystritsky, A, et al. Efficacy of low and higher dose extended-release venlafaxine in generalized social anxiety disorder: A 6-month randomized controlled trial. Psychopharmacology (Berl). 2005;177(3):280–8.CrossRef Google Scholar PubMed

Feltner, DE, Liu-Dumaw, M, Schweizer, E, Bielski, R. Efficacy of pregabalin in generalized social anxiety disorder. Int Clin Psychopharmacol. 2011;26(4):213–20.CrossRef Google Scholar PubMed

Worthington, EL, vanOyen Witvliet, C, Lerner, AJ, Scherer, M. Forgiveness in health research and medical practice. Explor J Sci Heal 2005;1(3):169–76. https://pubmed.ncbi.nlm.nih.gov/16781526/.Google Scholar PubMed

Sepede, G, De Berardis, D, Gambi, F, et al. Olanzapine augmentation in treatment-resistant panic disorder: A 12-week, fixed-dose, open-label trial. J Clin Psychopharmacol 2006;26(1):45–9. https://pubmed.ncbi.nlm.nih.gov/16415705/.CrossRef Google Scholar PubMed

Van Ameringen, M, Mancini, C, Wilson, C. Buspirone augmentation of selective serotonin reuptake inhibitors (SSRIs) in social phobia. J Affect Disord 1996;39(2):115–21. https://pubmed.ncbi.nlm.nih.gov/8827420/.CrossRef Google Scholar PubMed

Taylor, S. Meta-analysis of cognitive-behavioral treatments for social phobia. J Behav Ther Exp Psychiatry 1996;27(1):1–9.CrossRef Google Scholar PubMed

Stangier, U, Heidenreich, T, Peitz, M, Lauterbach, W, Clark, DM. Cognitive therapy for social phobia: Individual versus group treatment. Behav Res Ther 2003;41(9):991–1007. https://pubmed.ncbi.nlm.nih.gov/12914803/.CrossRef Google Scholar PubMed

Mörtberg, E, Clark, DM, Sundin, Ö, Åberg Wistedt, A. Intensive group cognitive treatment and individual cognitive therapy vs. treatment as usual in social phobia: A randomized controlled trial. Acta Psychiatr Scand 2007;115(2):142–54. https://pubmed.ncbi.nlm.nih.gov/17244178/.CrossRef Google Scholar PubMed

Acarturk, C, Cuijpers, P, Van Straten, A, De Graaf, R. Psychological treatment of social anxiety disorder: A meta-analysis. Psychol Med 2009;39(2):241–54. https://pubmed.ncbi.nlm.nih.gov/18507874/.CrossRef Google Scholar PubMed

Titov, N, Andrews, G, Schwencke, G, Drobny, J, Einstein, D. Shyness 1: Distance treatment of social phobia over the internet. Aust New Zeal J Psychiatry 2008;42(7):585–94.Google Scholar

Berger, T, Hohl, E, Caspar, F. Internet-based treatment for social phobia: A randomized controlled trial. J Clin Psychol 2009;65(10):1021–35.CrossRef Google Scholar PubMed

Furmark, T. Neurobiological aspects of social anxiety disorder. Isr J Psychiatry Relat Sci 2009;46(1):5–12. https://pubmed.ncbi.nlm.nih.gov/19728568/.Google Scholar PubMed

Andrews, G, Davies, M, Titov, N. Effectiveness randomized controlled trial of face to face versus internet cognitive behaviour therapy for social phobia. Aust New Zeal J Psychiatry 2011;45(4):337–40.Google Scholar PubMed

Hedman, E, Furmark, T, Carlbring, P, et al. A 5-year follow-up of internet-based cognitive behavior therapy for social anxiety disorder. J Med Internet Res 2011;13(2):e39. https://pubmed.ncbi.nlm.nih.gov/21676694/.CrossRef Google Scholar PubMed

Otto, MW, Pollack, MH, Gould, RA, et al. A comparison of the efficacy of clonazepam and cognitive-behavioral group therapy for the treatment of social phobia. J Anxiety Disord 2000;14(4):345–58. https://pubmed.ncbi.nlm.nih.gov/11043885/.CrossRef Google Scholar PubMed

Clark, DM, Ehlers, A, McManus, F, et al. Cognitive therapy versus fluoxetine in generalized social phobia: A randomized placebo-controlled trial. J Consult Clin Psychol 2003;71(6):1058–67. https://pubmed.ncbi.nlm.nih.gov/14622081/.CrossRef Google Scholar PubMed

Davidson, JRT, Foa, EB, Huppert, JD, et al. Fluoxetine, comprehensive cognitive behavioral therapy, and placeboin generalized social phobia. Arch Gen Psychiatry 2004;61(10):1005–13.CrossRef Google Scholar

Gomez, AF, Barthel, AL, Hofmann, SG. Comparing the efficacy of benzodiazepines and serotonergic anti-depressants for adults with generalized anxiety disorder: A meta-analytic review. Expert Opin Pharmacother 2018;19(8):883–94. https://pubmed.ncbi.nlm.nih.gov/29806492/CrossRef Google Scholar PubMed

Maron, E, Nutt, D. Biological predictors of pharmacological therapy in anxiety disorders. Dialogues Clin Neurosci 2015;17(3):305–17. https://pubmed.ncbi.nlm.nih.gov/26487811/.CrossRef Google Scholar PubMed

Koen, N, Stein, DJ. Pharmacotherapy of anxiety disorders: A critical review. Dialogues Clin Neurosci 2011;13(4):423–37. https://pubmed.ncbi.nlm.nih.gov/22275848/.CrossRef Google Scholar PubMed

Dell’Osso, B, Buoli, M, Baldwin, DS, Altamura, AC. Serotonin norepinephrine reuptake inhibitors (SNRIs) in anxiety disorders: A comprehensive review of their clinical efficacy. Hum Psychopharmacol 2010;25(1):17–29. https://pubmed.ncbi.nlm.nih.gov/20041476/.CrossRef Google Scholar PubMed

Prendes-Alvarez, S, Nemeroff, CB. Personalized medicine: Prediction of disease vulnerability in mood disorders. Neurosci Lett 2018;669:10–13. https://pubmed.ncbi.nlm.nih.gov/27746310/.CrossRef Google Scholar PubMed

Vismara, M, Girone, N, Cirnigliaro, G, et al. Peripheral biomarkers in DSM-5 anxiety disorders: An updated overview. Brain Sciences 2020;10(8):564.CrossRef Google Scholar

Kim, Y-K. (Ed.) Anxiety Disorders. Springer Singapore; 2020. http://link.springer.com/10.1007/978-981-32-9705-0.CrossRef Google Scholar PubMed

Bandelow, B, Baldwin, D, Abelli, M, et al. Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition. World J Biol Psychiatry 2017;18(3):162–214. https://pubmed.ncbi.nlm.nih.gov/27419272/.CrossRef Google Scholar PubMed

Niculescu, AB, Levey, D, Le-Niculescu, H, et al. Psychiatric blood biomarkers: Avoiding jumping to premature negative or positive conclusions. Mol Psychiatry 2015;20(3):286–8. https://pubmed.ncbi.nlm.nih.gov/25582618/.CrossRef Google Scholar PubMed

Quevedo, J, Yatham, LN. Biomarkers in mood disorders: Are we there yet? Vol. 233, J Affect Disord 2018;233:1–2. https://pubmed.ncbi.nlm.nih.gov/29395259/.CrossRef Google Scholar PubMed

Massaro, AR, Scivoletto, G, Tonali, P. Cerebrospinal fluid markers in neurological disorders. Ital J Neurol Sci 1990;11(6):537–47. https://pubmed.ncbi.nlm.nih.gov/1707039/.CrossRef Google Scholar PubMed

Juruena, MF, Eror, F, Cleare, AJ, Young, AH. The role of early life stress in HPA axis and anxiety. Adv Exp Med Biol 2020;1191:141–53.CrossRef Google Scholar PubMed

Faravelli, C, Lo Sauro, C, Lelli, L, et al. The Role of Life Events and HPA Axis in Anxiety Disorders: A Review. Curr Pharm Des 2012;18(35):5663–74.CrossRef Google Scholar PubMed

Gould, TD, Gottesman, II. Psychiatric endophenotypes and the development of valid animal models. Genes Brain Behav 2006;5(2):113–19. https://pubmed.ncbi.nlm.nih.gov/16507002/.CrossRef Google Scholar PubMed

Gottesman, II, Gould, TD. The endophenotype concept in psychiatry: Etymology and strategic intentions. Am J Psychiatry 2003;160(4):636–45. https://pubmed.ncbi.nlm.nih.gov/12668349/.CrossRef Google Scholar PubMed

Perna, G, Cocchi, S, Bertani, A, Arancio, C, Bellodi, L. Sensitivity to 35% CO₂ in healthy first-degree relatives of patients with panic disorder. Am J Psychiatry 1995;152(4):623–5. https://pubmed.ncbi.nlm.nih.gov/7694916/.Google Scholar PubMed

Battaglia, M, Perna, G. The 35% CO₂ challenge in panic disorder: Optimization by receiver operating characteristic (ROC) analysis. J Psychiatr Res. 1995;29(2):111–19.CrossRef Google Scholar PubMed

do Amaral, JMX, Spadaro, PTM, Pereira, VM, et al. The carbon dioxide challenge test in panic disorder: A systematic review of preclinical and clinical research. Revista Brasileira de Psiquiatria 2013;35(3):318–31.Google Scholar

Perna, G, Bussi, R, Allevi, L, Bellodi, L. Sensitivity to 35% carbon dioxide in patients with generalized anxiety disorder. J Clin Psychiatry. 1999;60(6):379–84.CrossRef Google Scholar PubMed

Verburg, K, Griez, E, Meijer, J, Pols, H. Discrimination between panic disorder and generalized anxiety disorder by 35% carbon dioxide challenge. Am J Psychiatry 1995;152(7):1081–3. https://pubmed.ncbi.nlm.nih.gov/7793449/.Google Scholar PubMed

Bertani, A, Caldirola, D, Bussi, R, Bellodi, L, Perna, G. The 35% CO₂ hyperreactivity and clinical symptomatology in patients with panic disorder after 1 week of treatment with citalopram: An open study. J Clin Psychopharmacol 2001;21(3):262–7. https://pubmed.ncbi.nlm.nih.gov/11386488/.CrossRef Google Scholar PubMed

Perna, G, Bertani, A, Caldirola, D, et al. Antipanic drug modulation of 35% CO₂ hyperreactivity and short-term treatment outcome. J Clin Psychopharmacol. 2002;22(3):300–8.CrossRef Google Scholar PubMed

Perna, G, Bertani, A, Gabriele, A, Politi, E, Bellodi, L. Modification of 35% carbon dioxide hypersensitivity across one week of treatment with clomipramine and fluvoxamine: A double-blind, randomized, placebo-controlled study. J Clin Psychopharmacol 1997;17(3):173–8. https://pubmed.ncbi.nlm.nih.gov/9169961/.CrossRef Google Scholar PubMed

Perna, G, Bertani, A, Caldirola, D, et al. Modulation of hyperreactivity to 35% CO₂ after one week of treatment with paroxetine and reboxetine: A double-blind, randomized study. J Clin Psychopharmacol 2004;24(3):277–82. https://pubmed.ncbi.nlm.nih.gov/15118481/.CrossRef Google Scholar PubMed

Eriksson, E, Westberg, P, Alling, C, Thuresson, K, Modigh, K. Cerebrospinal fluid levels of monoamine metabolites in panic disorder. Psychiatry Res 1991;36(3):243–51. https://pubmed.ncbi.nlm.nih.gov/1712114/.CrossRef Google Scholar PubMed

Cosci, F, Mansueto, G. Biological and clinical markers in panic disorder. Psychiat Investigation 2019;16(1):27–36. https://pubmed.ncbi.nlm.nih.gov/30184613/.CrossRef Google Scholar PubMed

Bhad, R. Editorial: Red blood cell and platelet indices: A potential biomarker for panic disorder. J Neurosci Rural Pract 2017;8(2):164. https://pubmed.ncbi.nlm.nih.gov/28479785/.Google Scholar PubMed

Quagliato, LA, Nardi, AE. Cytokine alterations in panic disorder: A systematic review. J Affect Disord. 2018;228:91–6. https://pubmed.ncbi.nlm.nih.gov/29241050/.CrossRef Google Scholar PubMed

Iny, LJ, Pecknold, J, Suranyi-Cadotte, BE, et al. Studies of a neurochemical link between depression, anxiety, and stress from [3 H]imipramine and [3 H]paroxetine binding on human platelets. Biol Psychiatry 1994;36(5):251–91. https://pubmed.ncbi.nlm.nih.gov/7993954/.CrossRef Google Scholar PubMed

Hernández, E, Lastra, S, Urbina, M, Carreira, I, Lima, L. Serotonin, 5-hydroxyindoleacetic acid and serotonin transporter in blood peripheral lymphocytes of patients with generalized anxiety disorder. Int Immunopharmacol 2002;2(7):893–900. https://pubmed.ncbi.nlm.nih.gov/12188031/.CrossRef Google Scholar PubMed

Phillips, AC, Batty, GD, Gale, CR, et al. Major depressive disorder, generalised anxiety disorder, and their comorbidity: Associations with cortisol in the Vietnam Experience Study. Psychoneuroendocrinology 2011;36(5):682–90. https://pubmed.ncbi.nlm.nih.gov/20952132/.CrossRef Google Scholar PubMed

Molendijk, ML, Bus, BAA, Spinhoven, P, et al. Gender specific associations of serum levels of brain-derived neurotrophic factor in anxiety. World J Biol Psychiatry 2012;13(7):535–43. https://pubmed.ncbi.nlm.nih.gov/21888560/.CrossRef Google Scholar PubMed

Bankier, B, Barajas, J, Martinez-Rumayor, A, Januzzi, JL. Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients. Eur Heart J 2008;29(18):2212–17. https://pubmed.ncbi.nlm.nih.gov/18603621/.CrossRef Google Scholar PubMed

Copeland, WE, Shanahan, L, Worthman, C, Angold, A, Costello, EJ. Generalized anxiety and C-reactive protein levels: A prospective, longitudinal analysis. Psychol Med 2012;42(12):2641–50. https://pubmed.ncbi.nlm.nih.gov/22716910/CrossRef Google Scholar

Marazziti, D, Abelli, M, Baroni, S, et al. Neurobiological correlates of social anxiety disorder: An update. CNS Spectrums 2015;20(2):100–11. https://pubmed.ncbi.nlm.nih.gov/24571962/.CrossRef Google Scholar PubMed

van Honk, J, Bos, PA, Terburg, D, Heany, S, Stein, DJ. Neuroendocrine models of social anxiety disorder. Dialogues Clin Neurosci 2015;17(3):287–93. https://pubmed.ncbi.nlm.nih.gov/26487809/.CrossRef Google Scholar PubMed

Jones, C, Barrera, I, Brothers, S, Ring, R, Wahlestedt, C. Oxytocin and social functioning. Dialogues Clin Neurosci 2017;19(2):193–201. https://pubmed.ncbi.nlm.nih.gov/28867943/.CrossRef Google Scholar PubMed

Giltay, EJ, Enter, D, Zitman, FG, et al. Salivary testosterone: Associations with depression, anxiety disorders, and antidepressant use in a large cohort study. J Psychosom Res 2012;72(3):205–13. https://pubmed.ncbi.nlm.nih.gov/22325700/.CrossRef Google Scholar

Hoge, EA, Lawson, EA, Metcalf, CA, et al. Plasma oxytocin immunoreactive products and response to trust in patients with social anxiety disorder. Depress Anxiety 2012;29(11):924–30. https://pubmed.ncbi.nlm.nih.gov/22807189/.CrossRef Google Scholar PubMed

Ressler, KJ, Nemeroff, CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety 2000;12:2–19.3.0.CO;2-4>CrossRef Google Scholar PubMed

Johnson, MR, Lydiard, RB. The neurobiology of anxiety disorders. Psychiatric Clinics of North America 1995; 18: 681–725.CrossRef Google Scholar PubMed

McNaughton, N, Corr, PJ. A two-dimensional neuropsychology of defense: Fear/anxiety and defensive distance. Neurosci Biobehav Rev 2004; 28:285–305. https://pubmed.ncbi.nlm.nih.gov/15225972/.CrossRef Google Scholar PubMed

Moreira, FP, Fabião, JD, Bittencourt, G, et al. The Met allele of BDNF Val66 Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder. Psychiatr Genet 2015;25(5):201–17. https://pubmed.ncbi.nlm.nih.gov/26110341/.CrossRef Google Scholar

Lin, M, Zhu, J, Yuan, Y, et al. Association analysis of the brain-derived neurotrophic factor gene val66 met polymorphism and gender with efficacy of antidepressants in the Chinese Han population with generalized anxiety disorder. Genet Test Mol Biomarkers 2018;22(3):199–206. https://pubmed.ncbi.nlm.nih.gov/29446659/.CrossRef Google Scholar

Maron, E, Tõru, I, Must, A, et al. Association study of tryptophan hydroxylase 2 gene polymorphisms in panic disorder. Neurosci Lett 2007;411(3):180–4. https://pubmed.ncbi.nlm.nih.gov/17123728/.CrossRef Google Scholar PubMed

Domschke, K, Deckert, J, O’Donovan, MC, Glatt, SJ. Meta-analysis of COMT val158 met in panic disorder: Ethnic heterogeneity and gender specificity. Am J Med Genet Part B Neuropsychiatr Genet 2007;144(5):667–73. https://pubmed.ncbi.nlm.nih.gov/17357147/.Google Scholar

Spence, SH, Rapee, RM. The etiology of social anxiety disorder: An evidence-based model. Behaviour Research and Therapy. 2016;86: 50–67. https://pubmed.ncbi.nlm.nih.gov/27406470/.CrossRef Google Scholar PubMed

Bergman, O, Åhs, F, Furmark, T, et al. Association between amygdala reactivity and a dopamine transporter gene polymorphism. Transl Psychiatry 2014;4(8). https://pubmed.ncbi.nlm.nih.gov/25093598/.CrossRef Google Scholar

Domschke, K, Stevens, S, Beck, B, et al. Blushing propensity in social anxiety disorder: Influence of serotonin transporter gene variation. J Neural Transm 2009;116(6):663–6. https://pubmed.ncbi.nlm.nih.gov/18629430/.CrossRef Google Scholar PubMed

Perna, G, Favaron, E, Di Bella, D, Bussi, R, Bellodi, L. Antipanic efficacy of paroxetine and polymorphism within the promoter of the serotonin transporter gene. Neuropsychopharmacology 2005;30(12):2230–5. https://pubmed.ncbi.nlm.nih.gov/16034444/.CrossRef Google Scholar PubMed

Schiele, MA, Domschke, K. Epigenetics at the crossroads between genes, environment and resilience in anxiety disorders. Genes Brain Behav 2018;17(3):e12423. https://pubmed.ncbi.nlm.nih.gov/28873274/.CrossRef Google Scholar PubMed

Schartner, C, Ziegler, C, Schiele, MA, et al. CRHR1 promoter hypomethylation: An epigenetic readout of panic disorder? Eur Neuropsychopharmacol 2017;27(4):360–71. https://pubmed.ncbi.nlm.nih.gov/28233670/.CrossRef Google Scholar PubMed

Domschke, K, Tidow, N, Schrempf, M, et al. Epigenetic signature of panic disorder: A role of glutamate decarboxylase 1 (GAD1) DNA hypomethylation? Prog Neuro-Psychopharmacology Biol Psychiatry 2013;46:189–96. https://pubmed.ncbi.nlm.nih.gov/23906988/.CrossRef Google Scholar PubMed

Ziegler, C, Dannlowski, U, Bräuer, D, et al. Oxytocin receptor gene methylation: Converging multilevel evidence for a role in social anxiety. Neuropsychopharmacology 2015;40(6):1528–38. https://pubmed.ncbi.nlm.nih.gov/25563749/.CrossRef Google Scholar PubMed

Won, E, Kim, YK. Neuroinflammation‐associated alterations of the brain as potential neural biomarkers in anxiety disorders. Int J Mol Sci 2020;21(18):1–19. https://pubmed.ncbi.nlm.nih.gov/32906843/.CrossRef Google Scholar PubMed

Bas-Hoogendam, JM, Groenewold, NA, Aghajani, M, et al. ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders Human Brain Mapping 2020;43(1):83–112. https://pubmed.ncbi.nlm.nih.gov/32618421/.CrossRef Google Scholar

Gorman, JM, Kent, JM, Sullivan, GM, Coplan, JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 2000;157:493–505. https://pubmed.ncbi.nlm.nih.gov/10739407/.CrossRef Google Scholar PubMed

Engel, KR, Obst, K, Bandelow, B, et al. Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls. Eur Arch Psychiatry Clin Neurosci 2016;266(6):557–66. https://pubmed.ncbi.nlm.nih.gov/26585457/.CrossRef Google Scholar PubMed

Sobanski, T, Wagner, G. Functional neuroanatomy in panic disorder: Status quo of the research. World J Psychiatry 2017;7(1):12. https://pubmed.ncbi.nlm.nih.gov/28401046/.CrossRef Google Scholar PubMed

Perna, G, Guerriero, G, Brambilla, P, Caldirola, D. Panic and the brainstem: Clues from neuroimaging studies. CNS Neurol Disord – Drug Targets 2014;13(6):1049–56. https://pubmed.ncbi.nlm.nih.gov/24923341/.CrossRef Google Scholar PubMed

Shin, LM, Davis, F, VanElzakker, MB, Dahlgren, MK, Dubois, SJ. Neuroimaging predictors of treatment response in anxiety disorders. Biol Mood Anxiety Disord 2013;3(1):15. https://pubmed.ncbi.nlm.nih.gov/23915782/.CrossRef Google Scholar PubMed

Santos, VA, Carvalho, DD, Van Ameringen, M, Nardi, AE, Freire, RC. Neuroimaging findings as predictors of treatment outcome of psychotherapy in anxiety disorders. Prog Neuro-Psychopharmacol Biol Psychiatry 2019;91:60–71. https://pubmed.ncbi.nlm.nih.gov/29627509/.CrossRef Google Scholar PubMed

Etkin, A, Prater, KE, Schatzberg, AF, Menon, V, Greicius, MD. Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch Gen Psychiatry 2009;66(12):1361–72. https://pubmed.ncbi.nlm.nih.gov/19996041/.CrossRef Google Scholar PubMed

Liao, M, Yang, F, Zhang, Y, et al. Childhood maltreatment is associated with larger left thalamic gray matter volume in adolescents with generalized anxiety disorder. PLoS One 2013;8(8):e71898. https://pubmed.ncbi.nlm.nih.gov/23951265/.CrossRef Google Scholar PubMed

Hilbert, K, Pine, DS, Muehlhan, M, et al. Gray and white matter volume abnormalities in generalized anxiety disorder by categorical and dimensional characterization. Psychiatry Res – Neuroimaging 2015;234(3):314–20. https://pubmed.ncbi.nlm.nih.gov/26490569/.CrossRef Google Scholar PubMed

Makovac, E, Meeten, F, Watson, DR, et al. Neurostructural abnormalities associated with axes of emotion dysregulation in generalized anxiety. NeuroImage Clin 2016;10:172–81. https://pubmed.ncbi.nlm.nih.gov/26759791/.CrossRef Google Scholar PubMed

Schienle, A, Ebner, F, Schäfer, A. Localized gray matter volume abnormalities in generalized anxiety disorder. Eur Arch Psychiatry Clin Neurosci 2011;261(4):303–7. https://pubmed.ncbi.nlm.nih.gov/20820793/.CrossRef Google Scholar PubMed

Whalen, PJ, Johnstone, T, Somerville, LH, et al. A functional magnetic resonance imaging predictor of treatment response to venlafaxine in generalized anxiety disorder. Biol Psychiatry 2008;63(9):858–63. https://pubmed.ncbi.nlm.nih.gov/17964548/.CrossRef Google Scholar PubMed

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(3):302–10. https://pubmed.ncbi.nlm.nih.gov/19122007/.CrossRef Google Scholar PubMed

Ball, TM, Stein, MB, Ramsawh, HJ, et al. Single-subject anxiety treatment outcome prediction using functional neuroimaging. Neuropsychopharmacology 2014;39(5):1254–61. https://pubmed.ncbi.nlm.nih.gov/24270731/.CrossRef Google Scholar PubMed

Cremers, HR, Roelofs, K. Social anxiety disorder: A critical overview of neurocognitive research. Wiley Interdiscip Rev Cogn Sci 2016 ;7(4):218–32. https://pubmed.ncbi.nlm.nih.gov/27240280/.CrossRef Google Scholar PubMed

Klumpp, H, Fitzgerald, JM. Neuroimaging predictors and mechanisms of treatment response in social anxiety disorder: An overview of the amygdala. Curr Psychiatry Rep 2018;20(10):89. https://pubmed.ncbi.nlm.nih.gov/30155657/.CrossRef Google Scholar PubMed

Liu, S, Li, E, Sun, Z, et al. Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrum disorder. Sci Rep 2019;9(1):287. https://pubmed.ncbi.nlm.nih.gov/30670726/.CrossRef Google Scholar PubMed

Jiang, H, Ling, Z, Zhang, Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun 2015;48:186–94. https://pubmed.ncbi.nlm.nih.gov/25882912/.CrossRef Google Scholar PubMed

Schwarz, E, Maukonen, J, Hyytiäinen, T, et al. Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response. Schizophr Res 2018;192:398–403. https://pubmed.ncbi.nlm.nih.gov/28442250/.CrossRef Google Scholar PubMed

Evans, S, Bassis, C, Hein, R, et al. The gut microbiome composition associates with bipolar disorder and illness severity. J Psychiatr Res 2017;87:23–9. https://pubmed.ncbi.nlm.nih.gov/27988330/.CrossRef Google Scholar PubMed

Keller, J, Gomez, R, Williams, G, et al. HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition. Mol Psychiatry 2017;22(4):527–36. https://pubmed.ncbi.nlm.nih.gov/27528460/.CrossRef Google Scholar PubMed

Winter, G, Hart, R, Charlesworth, R, Sharpley, C. Gut microbiome and depression: What we know and what we need to know. Rev Neurosci 2018;29(6):629–43. https://pubmed.ncbi.nlm.nih.gov/29397391/.CrossRef Google Scholar PubMed

Mayer, E, K T, Gupta, A. Gut/brain axis and the microbiota. J Clin Invest 2015;125(3):926–38. https://pubmed.ncbi.nlm.nih.gov/25689247/.CrossRef Google Scholar PubMed

Mayer, E, Knight, R, Mazmanian, S, Cryan, J, Tillisch, K. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci 2014;34(46):15490–6. https://pubmed.ncbi.nlm.nih.gov/25392516/.CrossRef Google Scholar PubMed

Chen, Y, Bai, J, Wu, D, et al. Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response. J Affect Disord 2019;259:56–66. https://pubmed.ncbi.nlm.nih.gov/31437702/.CrossRef Google Scholar PubMed

Bangsgaard Bendtsen, K, Krych, L, Sørensen, D, et al. Gut microbiota composition is correlated to grid floor induced stress and behavior in the BALB/c mouse. PLoS One 2012;7(10). https://pubmed.ncbi.nlm.nih.gov/23056268/.CrossRef Google Scholar PubMed

Vemuri, R, Sylvia, K, Klein, S, et al. The microgenderome revealed: sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility. Semin Immunopathol 2019;41(2):265–75. https://pubmed.ncbi.nlm.nih.gov/30298433/.CrossRef Google Scholar PubMed

Gibson-Smith, D, Bot, M, Brouwer, I, Visser, M, Penninx, B. Diet quality in persons with and without depressive and anxiety disorders. J Psychiatr Res 2018;106:1–7. https://pubmed.ncbi.nlm.nih.gov/30240962/.CrossRef Google Scholar PubMed

Simpson, C, Schwartz, O, Simmons, J. The human gut microbiota and depression: widely reviewed, yet poorly understood. J Affect Disord 2020;274:73–5. https://pubmed.ncbi.nlm.nih.gov/32469834/.CrossRef Google Scholar PubMed

Mörkl, S, Butler, M, Holl, A, Cryan, J, Dinan, T. Probiotics and the microbiota-gut-brain axis: Focus on psychiatry. Curr Nutr Rep 2020;9(3):171–82. https://pubmed.ncbi.nlm.nih.gov/32406013/.Google Scholar PubMed

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the HTML of this chapter is currently unknown and may be updated in the future.