Abstract
In adults, anxious depression has been identified as a more severe form of major depressive disorder (MDD), associated with higher depression severity, more suicidal ideation and worse treatment outcome. Research in pediatric depression, however, has been sparse. 126 children and adolescents aged 8–18 years with a primary diagnosis of MDD were categorized into a MDD-only group and an anxious depression group based on clinically elevated scores on the Beck Anxiety Inventory. One-third of the sample was classified as having anxious depression with females being overrepresented in the anxious depressed compared to the MDD-only group. 42.2% of the anxious depressed youth met diagnostic criteria for a comorbid anxiety disorder. Anxious depressed youth were more likely to suffer recurrent depressive episodes, showed higher depression severity and a unique pattern of depressive symptoms characterized by more severe sleep problems, more somatic complaints, more severely depressed mood and more frequent suicidal ideations. Scores on a suicidal ideation scale were increased even when controlling for overall depression severity. However, when comparing depressed patients with and without comorbid anxiety disorders, no differences in depression severity, symptom patterns or suicidal ideations were observed. The results indicate that high anxiety levels in depressed youth are clinically relevant, and given the increase in suicidal ideation, anxiety symptoms during depressive episodes should routinely be screened in clinical practice even in the absence of a fully formed comorbid anxiety disorder.
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References
American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders. American Psychiatric Association, Washington, DC
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Publishing, Arlington
Andreescu C, Butters M, Lenze EJ, Venkatraman VK, Nable M, Reynolds CF et al (2009) fMRI activation in late-life anxious depression: a potential biomarker. Int J Geriatr Psychiatry 24(8):820–828. https://doi.org/10.1002/gps.2327
Antypa N, Souery D, Tomasini M, Albani D, Fusco F, Mendlewicz J et al (2016) Clinical and genetic factors associated with suicide in mood disorder patients. Eur Arch Psychiatry Clin Neurosci 266(2):181–193. https://doi.org/10.1007/s00406-015-0658-1
Bardhoshi G, Duncan K, Erford BT (2016) Psychometric meta-analysis of the English version of the Beck Anxiety Inventory. J Couns Dev 94(3):356–373. https://doi.org/10.1002/jcad.12090
Beck AT, Epstein N, Brown G, Steer RA (1988a) An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 56(6):893–897
Beck AT, Steer RA, Garbin MA (1988b) Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev 8:77–100
Beesdo K, Knappe S, Pine DS (2009) Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin N Am 32(3):483–524. https://doi.org/10.1016/j.psc.2009.06.002
Blom EH, Larsson JO, Serlachius E, Ingvar M (2010) The differentiation between depressive and anxious adolescent females and controls by behavioural self-rating scales. J Affect Disord 122(3):232–240. https://doi.org/10.1016/j.jad.2009.07.006
Clayton PJ, Grove WM, Coryell W, Keller M, Hirschfeld R, Fawcett J (1991) Follow-up and family study of anxious depression. Am J Psychiatry 148(11):1512–1517 (<Go to ISI>://WOS:A1991GM20200008)
Coryell W, Fiedorowicz JG, Solomon D, Leon AC, Rice JP, Keller MB (2012) Effects of anxiety on the long-term course of depressive disorders. Br J Psychiatry 200(3):210–215. https://doi.org/10.1192/bjp.bp.110.081992
Costello EJ, Mustillo S, Erkanli A, Keeler G, Angold A (2003) Prevalence and development of psychiatric disorders in childhood and adolescence. Arch Gen Psychiatry 60(8):837–844. https://doi.org/10.1001/archpsyc.60.8.837
Costello EJ, He JP, Sampson NA, Kessler RC, Merikangas KR (2014) Services for adolescents with psychiatric disorders: 12-month data from the National Comorbidity Survey-Adolescent. Psychiatr Serv 65(3):359–366. https://doi.org/10.1176/appi.ps.201100518
Curry J, Rohde P, Simons A, Silva S, Vitiello B, Kratochvil C et al (2006) Predictors and moderators of acute outcome in the Treatment for Adolescents with Depression Study (TADS). J Am Acad Child Adolesc Psychiatry 45(12):1427–1439. https://doi.org/10.1097/01.chi.0000240838.78984.e2
Delaparte L, Yeh FC, Adams P, Malchow A, Trivedi MH, Oquendo MA et al (2017) A comparison of structural connectivity in anxious depression versus non-anxious depression. J Psychiatr Res 89:38–47. https://doi.org/10.1016/j.jpsychires.2017.01.012
Essau CA (2008) Comorbidity of depressive disorders among adolescents in community and clinical settings. Psychiatry Res 158(1):35–42. https://doi.org/10.1016/j.psychres.2007.09.007
Farabaugh AH, Bitran S, Witte J, Alpert J, Chuzi S, Clain AJ et al (2010) Anxious depression and early changes in the HAMD-17 anxiety-somatization factor items and antidepressant treatment outcome. Int Clin Psychopharmacol 25(4):214–217. https://doi.org/10.1097/YIC.0b013e328339fbbd
Farabaugh A, Alpert J, Wisniewski SR, Otto MW, Fava M, Baer L et al (2012) Cognitive therapy for anxious depression in STAR*D: what have we learned? J Affect Disord 142(1–3):213–218. https://doi.org/10.1016/j.jad.2012.04.029
Fava M, Alpert JE, Carmin CN, Wisniewski SR, Trivedi MH, Biggs MM et al (2004) Clinical correlates and symptom patterns of anxious depression among patients with major depressive disorder in STAR*D. Psychol Med 34(7):1299–1308
Fava M, Rush AJ, Alpert JE, Carmin CN, Balasubramani GK, Wisniewski SR et al (2006) What clinical and symptom features and comorbid disorders characterize outpatients with anxious major depressive disorder: a replication and extension. Can J Psychiatry 51(13):823–835. https://doi.org/10.1177/070674370605101304
Fava M, Rush AJ, Alpert JE, Balasubramani GK, Wisniewski SR, Carmin CN et al (2008) Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 165(3):342–351. https://doi.org/10.1176/appi.ajp.2007.06111868
Foley DL, Goldston DB, Costello EJ, Angold A (2006) Proximal psychiatric risk factors for suicidality in youth: the Great Smoky Mountains Study. Arch Gen Psychiatry 63(9):1017–1024. https://doi.org/10.1001/archpsyc.63.9.1017
Franco X, Saavedra LM, Silverman WK (2007) External validation of comorbid patterns of anxiety disorders in children and adolescents. J Anxiety Disord 21(5):717–729. https://doi.org/10.1016/j.janxdis.2006.10.002
Gaspersz R, Lamers F, Kent JM, Beekman ATF, Smit JH, van Hemert AM et al (2017) Anxious distress predicts subsequent treatment outcome and side effects in depressed patients starting antidepressant treatment. J Psychiatr Res 84:41–48. https://doi.org/10.1016/j.jpsychires.2016.09.018
Gaspersz R, Nawijn L, Lamers F, Penninx B (2018) Patients with anxious depression: overview of prevalence, pathophysiology and impact on course and treatment outcome. Curr Opin Psychiatry 31(1):17–25. https://doi.org/10.1097/YCO.0000000000000376
Geissner E, Huetteroth A (2018) Beck Anxiety Inventory German Version: a reliable, valid, patient-friendly instrument for measuring clinical anxiety. Psychother Psychosom Med Psychol 68(3–4):118–125. https://doi.org/10.1055/s-0043-122941
Goldberg D, Fawcett J (2012) The importance of anxiety in both major depression and bipolar disorder. Depress Anxiety 29(6):471–478. https://doi.org/10.1002/da.21939
Goldberg DP, Wittchen HU, Zimmermann P, Pfister H, Beesdo-Baum K (2014) Anxious and non-anxious forms of major depression: familial, personality and symptom characteristics. Psychol Med 44(6):1223–1234. https://doi.org/10.1017/S0033291713001827
Guberman C, Manassis K (2011) Symptomatology and family functioning in children and adolescents with comorbid anxiety and depression. J Can Acad Child Adolesc Psychiatry 20(3):186–195
Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32(1):50–55
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62. https://doi.org/10.1136/jnnp.23.1.56
Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6(4):278–296
Ionescu DF, Niciu M, Henter ID, Zarate CA (2013) Defining anxious depression: a review of the literature. CNS Spectr 18(5):252–260. https://doi.org/10.1017/S1092852913000114
Jolly JB, Aruffo JF, Wherry JN, Livingston R (1993) The utility of the Beck Anxiety Inventory with inpatient adolescents. J Anxiety Disord 7(2):95–106. https://doi.org/10.1016/0887-6185(93)90008-9
Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P et al (1997) Schedule for Affective Disorders and Schizophrenia for School-Age Children Present and Lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36(7):980–988. https://doi.org/10.1097/00004583-199707000-00021
Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU (2012) Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 21(3):169–184. https://doi.org/10.1002/mpr.1359
Kessler RC, Sampson NA, Berglund P, Gruber MJ, Al-Hamzawi A, Andrade L et al (2015) Anxious and non-anxious major depressive disorder in the World Health Organization World Mental Health Surveys. Epidemiol Psychiatr Sci 24(3):210–226. https://doi.org/10.1017/S2045796015000189
Lauth B, Arnkelsson GB, Magnusson P, Skarphedinsson GA, Ferrari P, Petursson H (2010) Validity of K-SADS-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) depression diagnoses in an adolescent clinical population. Nord J Psychiatry 64(6):409–420. https://doi.org/10.3109/08039481003777484
Lewinsohn PM, Shankman SA, Gau JM, Klein DN (2004) The prevalence and co-morbidity of subthreshold psychiatric conditions. Psychol Med 34(4):613–622. https://doi.org/10.1017/S0033291703001466
Lin CH, Wang FC, Lin SC, Chen CC, Huang CJ (2014) A comparison of inpatients with anxious depression to those with nonanxious depression. Psychiatry Res 220(3):855–860. https://doi.org/10.1016/j.psychres.2014.08.048
Malhi GS, Parker GB, Gladstone G, Wilhelm K, Mitchell PB (2002) Recognizing the anxious face of depression. J Nerv Ment Dis 190(6):366–373
Maneeton N, Suttajit S, Maneeton B, Likhitsathian S, Eurviyanukul K, Udomratn P et al (2017) Clinical and socio-demographic correlates of anxious distress in Asian outpatients with major depressive disorder. Nord J Psychiatry 71(7):503–508. https://doi.org/10.1080/08039488.2017.1335344
Margraf J, Ehlers A (2007) Beck Angst-Inventar—BAI. Manual Deutsche Bearbeitung. Harcourt Test Services GmbH, Frankfurt am Main
Mayes TL, Bernstein IH, Haley CL, Kennard BD, Emslie GJ (2010) Psychometric properties of the Children’s Depression Rating Scale-Revised in adolescents. J Child Adolesc Psychopharmacol 20(6):513–516. https://doi.org/10.1089/cap.2010.0063
Melton TH, Croarkin PE, Strawn JR, McClintock SM (2016) Comorbid anxiety and depressive symptoms in children and adolescents: a systematic review and analysis. J Psychiatr Pract 22(2):84–98. https://doi.org/10.1097/PRA.0000000000000132
Nelson JC (2010) Anxiety does not predict response to duloxetine in major depression: results of a pooled analysis of individual patient data from 11 placebo-controlled trials. Depress Anxiety 27(1):12–18. https://doi.org/10.1002/da.20632
Newman TB (2004) A black-box warning for antidepressants in children? N Engl J Med 351(16):1595–1598. https://doi.org/10.1056/NEJMp048279
Nock MK, Hwang I, Sampson N, Kessler RC, Angermeyer M, Beautrais A et al (2009) Cross-national analysis of the associations among mental disorders and suicidal behavior: findings from the WHO World Mental Health Surveys. PLoS Med 6(8):e1000123. https://doi.org/10.1371/journal.pmed.1000123
Nock MK, Hwang I, Sampson NA, Kessler RC (2010) Mental disorders, comorbidity and suicidal behavior: results from the National Comorbidity Survey Replication. Mol Psychiatry 15(8):868–876. https://doi.org/10.1038/mp.2009.29
Osman A, Hoffman J, Barrios FX, Kopper BA, Breitenstein JL, Hahn SK (2002) Factor structure, reliability, and validity of the Beck Anxiety Inventory in adolescent psychiatric inpatients. J Clin Psychol 58(4):443–456. https://doi.org/10.1002/jclp.1154
Pinto A, Whisman MA, McCoy KJM (1997) Suicidal ideation in adolescents: psychometric properties of the suicidal ideation questionnaire in a clinical sample. Psychol Assess 9(1):63–66 (<Go to ISI>://WOS:A1997WN06500008)
Poznanski E, Mokros H (1996) Children’s Depression Rating Scale-Revised (CDRS-R). WPS, Los Angeles
Reynolds, W. M. (1988). Suicidal Ideation Questionnaire: Professional Manual. Psychological Assessment Resources
Reynolds WM, Mazza JJ (1999) Assessment of suicidal ideation in inner-city children and young adolescents: Reliability and validity of the suicidal ideation questionnaire-JR. School Psychology Review 28(1):17–30 (<Go to ISI>://WOS:000079675200003)
Rohde P, Clarke GN, Lewinsohn PM, Seeley JR, Kaufman NK (2001) Impact of comorbidity on a cognitive-behavioral group treatment for adolescent depression. J Am Acad Child Adolesc Psychiatry 40(7):795–802. https://doi.org/10.1097/00004583-200107000-00014
Rosellini AJ, Bourgeois ML, Correa J, Tung ES, Goncharenko S, Brown TA (2018) Anxious distress in depressed outpatients: prevalence, comorbidity, and incremental validity. J Psychiatr Res 103:54–60. https://doi.org/10.1016/j.jpsychires.2018.05.006
Seo HJ, Jung YE, Kim TS, Kim JB, Lee MS, Kim JM et al (2011) Distinctive clinical characteristics and suicidal tendencies of patients with anxious depression. J Nerv Ment Dis 199(1):42–48. https://doi.org/10.1097/NMD.0b013e3182043b60
Sharma T, Guski LS, Freund N, Gotzsche PC (2016) Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ 352:i65. https://doi.org/10.1136/bmj.i65
Smits JAJ, Minhajuddin A, Thase ME, Jarrett RB (2012) Outcomes of acute phase cognitive therapy in outpatients with anxious versus nonanxious depression. Psychother Psychosom 81(3):153–160. https://doi.org/10.1159/000334909
Stein MB, Fuetsch M, Muller N, Hofler M, Lieb R, Wittchen HU (2001) Social anxiety disorder and the risk of depression—a prospective community study of adolescents and young adults. Arch Gen Psychiatry 58(3):251–256. https://doi.org/10.1001/archpsyc.58.3.251
van Bronswijk SC, Lemmens LHJM, Huibers MJH, Arntz A, Peeters FPML (2018) The influence of comorbid anxiety on the effectiveness of cognitive therapy and interpersonal psychotherapy for major depressive disorder. J Affect Disord 232:52–60. https://doi.org/10.1016/j.jad.2018.02.003
Weeks M, Ooi LL, Coplan RJ (2016) Cognitive biases and the link between shyness and social anxiety in early adolescence. J Early Adolesc 36(8):1095–1117. https://doi.org/10.1177/0272431615593175
Wehry AM, McNamara RK, Adler CM, Eliassen JC, Croarkin P, Cerullo MA et al (2015) Neurostructural impact of co-occurring anxiety in pediatric patients with major depressive disorder: a voxel-based morphometry study. J Affect Disord 171:54–59. https://doi.org/10.1016/j.jad.2014.09.004
Weissman MM, Wolk S, Goldstein RB, Moreau D, Adams P, Greenwald S et al (1999) Depressed adolescents grown up. JAMA 281(18):1707–1713. https://doi.org/10.1001/jama.281.18.1707
WHO (2016) Global health estimates. World Health Organization. https://www.who.int/maternal_child_adolescent/data/causes-death-adolescents/en/. Accessed 28 May 2019
Wiethoff K, Bauer M, Baghai TC, Moller HJ, Fisher R, Hollinde D et al (2010) Prevalence and treatment outcome in anxious versus nonanxious depression: results from the German Algorithm Project. J Clin Psychiatry 71(8):1047–1054. https://doi.org/10.4088/JCP.09m05650blu
World Health Organization (2018) International statistical classification of diseases and related health problems (11th revision)
Wu Z, Chen J, Yuan C, Hong W, Peng D, Zhang C et al (2013) Difference in remission in a Chinese population with anxious versus nonanxious treatment-resistant depression: a report of OPERATION study. J Affect Disord 150(3):834–839. https://doi.org/10.1016/j.jad.2013.03.012
Xia W, Zhou R, Zhao G, Wang F, Mao R, Peng D et al (2018) Abnormal white matter integrity in Chinese young adults with first-episode medication-free anxious depression: a possible neurological biomarker of subtype major depressive disorder. Neuropsychiatr Dis Treat 14:2017–2026. https://doi.org/10.2147/NDT.S169583
Zhang Y, Yip PSF, Fu KW (2014) Validation of the Chinese version of the Reynolds’ suicidal ideation questionnaire: psychometric properties and its short version. Health and Quality of Life Outcomes. https://doi.org/10.1186/1477-7525-12-33
Zhao K, Liu H, Yan R, Hua L, Chen Y, Shi J et al (2017) Cortical thickness and subcortical structure volume abnormalities in patients with major depression with and without anxious symptoms. Brain Behav 7(8):e00754. https://doi.org/10.1002/brb3.754
Ziebold C, Mari JJ, Goldberg DP, Minhas F, Razzaque B, Fortes S et al (2019) Diagnostic consequences of a new category of anxious depression and a reduced duration requirement for anxiety symptoms in the ICD-11 PHC. J Affect Disord 245:120–125. https://doi.org/10.1016/j.jad.2018.10.082
Zimmerman M, Martin J, Clark H, McGonigal P, Harris L, Holst CG (2017) Measuring anxiety in depressed patients: a comparison of the Hamilton anxiety rating scale and the DSM-5 Anxious Distress Specifier Interview. J Psychiatr Res 93:59–63. https://doi.org/10.1016/j.jpsychires.2017.05.014
Zimmerman M, Kerr S, Kiefer R, Balling C, Dalrymple K (2019a) What is anxious depression? Overlap and agreement between different definitions. J Psychiatr Res 109:133–138. https://doi.org/10.1016/j.jpsychires.2018.11.028
Zimmerman M, Martin J, McGonigal P, Harris L, Kerr S, Balling C et al (2019b) Validity of the DSM-5 anxious distress specifier for major depressive disorder. Depress Anxiety 36(1):31–38. https://doi.org/10.1002/da.22837
Zisook S, Lesser I, Stewart JW, Wisniewski SR, Balasubramani GK, Fava M et al (2007) Effect of age at onset on the course of major depressive disorder. Am J Psychiatry 164(10):1539–1546. https://doi.org/10.1176/appi.ajp.2007.06101757
Acknowledgements
We would like to thank all members of the Omega-3 Study team, especially all members of the clinical sites for their help in recruiting patients, namely Oliver Pick and Alain Di Gallo from the Department of Child and Adolescent Psychiatry, Psychiatric University Hospitals Basel; Stefan Müller from the Child and Adolescent Psychiatric Services Baselland; Simone Heitzer and Maria Dokianaki from the Clienia Littenheid; Amir Yamini from the Child and Adolescent Psychiatric Services Thurgau; Michael Schmid from the Child and Adolescent Psychiatric Services St. Gallen; Ioannis Christodoulakis from the Klinik Sonnenhof. We also thank all our patients and their families for participating in the trial.
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This research was funded as an investigator initiated clinical trial by the Swiss National Foundation (SNF Grant 33IC30_166826). Furthermore, the Thalmann Foundation (University of Basel) and the Ebnet Foundation support additional PhD projects. The Research Department of Child and Adolescent Psychiatry, University Hospital of Psychiatry Zurich of the University of Zurich provides infrastructure and administrative staff support. Burgerstein, Antistress AG, and Rapperswil-Jona (SG, Switzerland) provided the study medication for the clinical trial with no restrictions regarding data analysis or publication rights. No additional industrial funding was provided throughout the study.
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All authors contributed to the study conception, design, recruitment and data collection. IH ran the analysis. The manuscript was written by IH, GB and SW. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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S.W. has received in the last 5 years royalties from Thieme Hogrefe, Kohlhammer, Springer, Beltz. S.W. received lecture honoraria from Opopharma in the last 5 years. Her work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diff. EU FP7 s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann Fonds. Outside professional activities and interests are declared under the link of the University of Zurich www.uzh.ch/prof/ssl-dir/interessenbindungen/client/web/. In the last 5 years KS has received royalties from Springer, Hogrefe and Schattauer. Since 2014, KS received no honoraria from pharmaceutical or other industrial companies. His work was supported in the last 5 years by the Swiss National Science Foundation (SNF), Swiss Ministry of Justice, University of St. Gallen, Botnar Foundation and Gertrud Thalmann Fonds. Gregor Berger was supported by the Swiss National Science Foundation, the Stanley Foundation, the Gertrud Thalmann Fonds, and the Ebnet Foundation and has received lecture honoraria from Lundbeck, Opopharma, Antistress AG (Burgerstein) in the last 5 years. The other authors declare no conflict of interest.
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Häberling, I., Baumgartner, N., Emery, S. et al. Anxious depression as a clinically relevant subtype of pediatric major depressive disorder. J Neural Transm 126, 1217–1230 (2019). https://doi.org/10.1007/s00702-019-02069-x
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DOI: https://doi.org/10.1007/s00702-019-02069-x