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Open Access 01-12-2020 | Magnetic Resonance Imaging | Study protocol

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder

Authors: J. Santiago, E. Akeman, N. Kirlic, A. N. Clausen, K. T. Cosgrove, T. J. McDermott, B. Mathis, M. Paulus, M. G. Craske, J. Abelson, C. Martell, K. Wolitzky-Taylor, J. Bodurka, W. K. Thompson, Robin L. Aupperle

Published in: Trials | Issue 1/2020

Abstract

Background

Only 40–60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of “personalized medicine.” Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder.

Methods/design

We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder–7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods.

Discussion

This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome.

Trial registration

The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results.

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Kessler RC. The costs of depression. Psychiatr Clin North Am. 2012;35(1):1–14. https://doi.org/10.1016/j.psc.2011.11.005.CrossRefPubMed

Wittchen HU. Generalized anxiety disorder: prevalence, burden, and cost to society. Depress Anxiety. 2002;16(4):162–71. https://doi.org/10.1002/da.10065.CrossRefPubMed

Hoffman DL, Dukes EM, Wittchen HU. Human and economic burden of generalized anxiety disorder. Depress Anxiety. 2008;25(1):72–90. https://doi.org/10.1002/da.20257.CrossRefPubMed

Penninx BW, Nolen WA, Lamers F, Zitman FG, Smit JH, Spinhoven P, et al. Two-year course of depressive and anxiety disorders: results from the Netherlands Study of Depression and Anxiety (NESDA). J Affect Disord. 2011;133(1–2):76–85. https://doi.org/10.1016/j.jad.2011.03.027.CrossRefPubMed

Moffitt TE, Harrington H, Caspi A, Kim-Cohen J, Goldberg D, Gregory AM, et al. Depression and generalized anxiety disorder: cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years. Arch Gen Psychiatry. 2007;64(6):651–60. https://doi.org/10.1001/archpsyc.64.6.651.CrossRefPubMed

Sherbourne CD, Wells KB. Course of depression in patients with comorbid anxiety disorders. J Affect Disord. 1997;43(3):245–50. https://doi.org/10.1016/s0165-0327(97)01442-0.CrossRefPubMed

Hidalgo RB, Tupler LA, Davidson JR. An effect-size analysis of pharmacologic treatments for generalized anxiety disorder. J Psychopharmacol. 2007;21(8):864–72. https://doi.org/10.1177/0269881107076996.CrossRefPubMed

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://doi.org/10.4088/jcp.v69n0415.CrossRefPubMedPubMedCentral

Hollon SD, Stewart MO, Strunk D. Enduring effects for cognitive behavior therapy in the treatment of depression and anxiety. Annu Rev Psychol. 2006;57:285–315. https://doi.org/10.1146/annurev.psych.57.102904.190044.CrossRefPubMed

10.

Cuijpers P, Sijbrandij M, Koole S, Huibers M, Berking M, Andersson G. Psychological treatment of generalized anxiety disorder: a meta-analysis. Clin Psychol Rev. 2014;34(2):130–40. https://doi.org/10.1016/j.cpr.2014.01.002.CrossRefPubMed

11.

Marciniak MD, Lage MJ, Dunayevich E, Russell JM, Bowman L, Landbloom RP, et al. The cost of treating anxiety: the medical and demographic correlates that impact total medical costs. Depress Anxiety. 2005;21(4):178–84.CrossRefPubMed

12.

Sanislow CA, Pine DS, Quinn KJ, Kozak MJ, Garvey MA, Heinssen RK, et al. Developing constructs for psychopathology research: research domain criteria. J Abnorm Psychol. 2010;119(4):631–9. https://doi.org/10.1037/a0020909.CrossRefPubMed

13.

Craske MG. Honoring the past, envisioning the future: ABCT’s 50th anniversary presidential address. Behav Ther. 2018;49(2):151–64. https://doi.org/10.1016/j.beth.2017.05.003.CrossRefPubMed

14.

Fernandes BS, Williams LM, Steiner J, Leboyer M, Carvalho AF, Berk M. The new field of ‘precision psychiatry’. BMC Med. 2017;15:80.CrossRefPubMedPubMedCentral

15.

Altamura AC, Dell’osso B, D’Urso N, Russo M, Fumagalli S, Mundo E. Duration of untreated illness as a predictor of treatment response and clinical course in generalized anxiety disorder. CNS Spectr. 2008;13(5):415–22.CrossRefPubMed

16.

Blair KS, Blair R. A cognitive neuroscience approach to generalized anxiety disorder and social phobia. Emot Rev. 2012;4(2):133–8. https://doi.org/10.1177/1754073911430251.CrossRef

17.

Santos VA, Carvalho DD, Van Ameringen M, Nardi AE, Freire RC. Neuroimaging findings as predictors of treatment outcome of psychotherapy in anxiety disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2019;91:60–71. https://doi.org/10.1016/j.pnpbp.2018.04.001.CrossRefPubMed

18.

Ball TM, Stein MB, Ramsawh HJ, Campbell-Sills L, Paulus MP. Single-subject anxiety treatment outcome prediction using functional neuroimaging. Neuropsychopharmacology. 2014;39(5):1254–61. https://doi.org/10.1038/npp.2013.328.CrossRefPubMedPubMedCentral

19.

Behar E, DiMarco ID, Hekler EB, Mohlman J, Staples AM. Current theoretical models of generalized anxiety disorder (GAD): conceptual review and treatment implications. J Anxiety Disord. 2009;23(8):1011–23. https://doi.org/10.1016/j.janxdis.2009.07.006.CrossRefPubMed

20.

Aupperle RL, Paulus MP. Neural systems underlying approach and avoidance in anxiety disorders. Dialogues Clin Neurosci. 2010;12(4):517–31.PubMed

21.

Millan MJ. The neurobiology and control of anxious states. Prog Neurobiol. 2003;70(2):83–244.CrossRefPubMed

22.

Kirlic N, Young J, Aupperle RL. Animal to human translational paradigms relevant for approach avoidance conflict decision making. Behav Res Ther. 2017;96:14–29. https://doi.org/10.1016/j.brat.2017.04.010.CrossRefPubMedPubMedCentral

23.

Aupperle RL, Melrose AJ, Francisco A, Paulus MP, Stein MB. Neural substrates of approach-avoidance conflict decision-making. Hum Brain Mapp. 2015;36(2):449–62. https://doi.org/10.1002/hbm.22639.CrossRefPubMed

24.

Aupperle RL, Sullivan S, Melrose AJ, Paulus MP, Stein MB. A reverse translational approach to quantify approach-avoidance conflict in humans. Behav Brain Res. 2011;225(2):455–63. https://doi.org/10.1016/j.bbr.2011.08.003.CrossRefPubMedPubMedCentral

25.

Craske MG, Barlow DH. Mastery of your anxiety and worry. 2nd ed. San Antonio: Psychological Corp.; 2006.CrossRef

26.

Dillon DG, Rosso IM, Pechtel P, Killgore WD, Rauch SL, Pizzagalli DA. Peril and pleasure: an RDOC-inspired examination of threat responses and reward processing in anxiety and depression. Depress Anxiety. 2014;31(3):233–49. https://doi.org/10.1002/da.22202.CrossRefPubMed

27.

Cuijpers P, van Straten A, Warmerdam L. Behavioral activation treatments of depression: a meta-analysis. Clin Psychol Rev. 2007;27(3):318–26. https://doi.org/10.1016/j.cpr.2006.11.001.CrossRefPubMed

28.

Craske MG, Roy-Byrne PP, Stein MB, Sullivan G, Sherbourne C, Bystritsky A. Treatment for anxiety disorders: efficacy to effectiveness to implementation. Behav Res Ther. 2009;47(11):931–7. https://doi.org/10.1016/j.brat.2009.07.012.CrossRefPubMedPubMedCentral

29.

Martell CR, Dimidjian S, Herman-Dunn R. Behavioral activation for depression: a clinician’s guide. New York: Guilford Press; 2013.

30.

Sheehan DV, Harnett-Sheehan K, Raj BA. The measurement of disability. Int Clin Psychopharmacol. 1996;11 Suppl 3:89–95.CrossRefPubMed

31.

Schalet BD, Pilkonis PA, Yu L, Dodds N, Johnston KL, Yount S, et al. Clinical validity of PROMIS depression, anxiety, and anger across diverse clinical samples. J Clin Epidemiol. 2016;73:119–27. https://doi.org/10.1016/j.jclinepi.2015.08.036.CrossRefPubMedPubMedCentral

32.

Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories-IA and -II in psychiatric outpatients. J Pers Assess. 1996;67(3):588–97. https://doi.org/10.1207/s15327752jpa6703_13.CrossRefPubMed

33.

Meyer TJ, Miller ML, Metzger RL, Borkovec TD. Development and validation of the Penn State Worry Questionnaire. Behav Res Ther. 1990;28(6):487–95. https://doi.org/10.1016/0005-7967(90)90135-6.CrossRefPubMed

34.

American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®). 5th ed. Washington, DC: American Psychiatric Publishing; 2013.CrossRef

35.

Norman SB, Hami Cissell S, Means-Christensen AJ, Stein MB. Development and validation of an overall anxiety severity and impairment scale (OASIS). Depress Anxiety. 2006;23(4):245–9.CrossRefPubMed

36.

Dimidjian S, Hollon SD, Dobson KS, Schmaling KB, Kohlenberg RJ, Addis ME, et al. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression. J Consult Clin Psychol. 2006;74(4):658–70. https://doi.org/10.1037/0022-006X.74.4.658.CrossRefPubMed

37.

Arch JJ, Ayers CR, Baker A, Almklov E, Dean DJ, Craske MG. Randomized clinical trial of adapted mindfulness-based stress reduction versus group cognitive behavioral therapy for heterogeneous anxiety disorders. Behav Res Ther. 2013;51(4–5):185–96. https://doi.org/10.1016/j.brat.2013.01.003.CrossRefPubMed

38.

Craske MG, Treanor M, Conway CC, Zbozinek T, Vervliet B. Maximizing exposure therapy: an inhibitory learning approach. Behav Res Ther. 2014;58:10–23. https://doi.org/10.1016/j.brat.2014.04.006.CrossRefPubMedPubMedCentral

39.

Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research Electronic Data Capture (REDCap) – a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377–81. https://doi.org/10.1016/j.jbi.2008.08.010.CrossRefPubMed

40.

Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): development and validation of a structured diagnostic psychiatric interview. J Clin Psychiatry. 1998;59 Suppl 20:22–33.PubMed

41.

Pedrelli P, Blais MA, Alpert JE, Shelton RC, Walker RS, Fava M. Reliability and validity of the Symptoms of Depression Questionnaire (SDQ). CNS Spectr. 2014;19(6):535–46. https://doi.org/10.1017/S1092852914000406.CrossRefPubMedPubMedCentral

42.

Spielberger C. State-Trait Anxiety Inventory (Form Y) manual. Palo Alto: Mind Garden; 1983.

43.

Taylor S, Koch WJ, McNally RJ, Crockett DJ. Conceptualizations of anxiety sensitivity. Psychol Assess. 1992;4(2):245.CrossRef

44.

Spitzer RL, Kroenke K, Williams JB, Lowe B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092–7. https://doi.org/10.1001/archinte.166.10.1092.CrossRefPubMed

45.

Buhr K, Dugas MJ. The intolerance of uncertainty scale: psychometric properties of the English version. Behav Res Ther. 2002;40(8):931–45. https://doi.org/10.1016/s0005-7967(01)00092-4.CrossRefPubMed

46.

Baker SL, Heinrichs N, Kim HJ, Hofmann SG. The Liebowitz social anxiety scale as a self-report instrument: a preliminary psychometric analysis. Behav Res Ther. 2002;40(6):701–15.CrossRefPubMed

47.

Shear MK, Rucci P, Williams J, Frank E, Grochocinski V, Vander Bilt J, et al. Reliability and validity of the Panic Disorder Severity Scale: replication and extension. J Psychiatr Res. 2001;35(5):293–6. https://doi.org/10.1016/s0022-3956(01)00028-0.CrossRefPubMed

48.

Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16(9):606–13. https://doi.org/10.1046/j.1525-1497.2001.016009606.x.CrossRefPubMedPubMedCentral

49.

Kanter JW, Mulick PS, Busch AM, Berlin KS, Martell CR. The Behavioral Activation for Depression Scale (BADS): psychometric properties and factor structure. J Psychopathol Behav. 2007;29(3):191. https://doi.org/10.1007/s10862-006-9038-5.CrossRef

50.

Brown SA, Myers MG, Lippke L, Tapert SF, Stewart DG, Vik PW. Psychometric evaluation of the Customary Drinking and Drug Use Record (CDDR): a measure of adolescent alcohol and drug involvement. J Stud Alcohol. 1998;59(4):427–38. https://doi.org/10.15288/jsa.1998.59.427.CrossRefPubMed

51.

Vrana S, Lauterbach D. Prevalence of traumatic events and post-traumatic psychological symptoms in a nonclinical sample of college students. J Trauma Stress. 1994;7(2):289–302.CrossRefPubMed

52.

Bernstein DP, Fink L, Handelsman L, Foote J, Lovejoy M, Wenzel K, et al. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry. 1994;151(8):1132. https://doi.org/10.1176/ajp.151.8.1132.CrossRefPubMed

53.

Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988;54(6):1063–70. https://doi.org/10.1037//0022-3514.54.6.1063.CrossRefPubMed

54.

Carver CS, White TL. Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J Pers Soc Psychol. 1994;67(2):319.CrossRef

55.

Burns GL, Keortge SG, Formea GM, Sternberger LG. Revision of the Padua Inventory of obsessive compulsive disorder symptoms: distinctions between worry, obsessions, and compulsions. Behav Res Ther. 1996;34(2):163–73.CrossRefPubMed

56.

John OP, Srivastava S. The Big Five trait taxonomy: history, measurement, and theoretical perspectives. Handbook of personality: Theory and research. 1999;2(1999):102–38.

57.

Mehling WE, Price C, Daubenmier JJ, Acree M, Bartmess E, Stewart A. The Multidimensional Assessment of Interoceptive Awareness (MAIA). PLoS One. 2012;7(11):e48230. https://doi.org/10.1371/journal.pone.0048230.CrossRefPubMedPubMedCentral

58.

Carpenter JS, Andrykowski MA. Psychometric evaluation of the Pittsburgh Sleep Quality Index. J Psychosom Res. 1998;45(1):5–13. https://doi.org/10.1016/s0022-3999(97)00298-5.CrossRefPubMed

59.

Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al. International Physical Activity Questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381–95. https://doi.org/10.1249/01.MSS.0000078924.61453.FB.CrossRefPubMed

60.

Devilly GJ, Borkovec TD. Psychometric properties of the credibility/expectancy questionnaire. J Behav Ther Exp Psychiatry. 2000;31(2):73–86.CrossRefPubMed

61.

Kazantzis N, Deane FP, Ronan KR. Assessing compliance with homework assignments: review and recommendations for clinical practice. J Clin Psychol. 2004;60(6):627–41. https://doi.org/10.1002/jclp.10239.CrossRefPubMed

62.

Hatcher RL, Gillaspy JA. Development and validation of a revised short version of the Working Alliance Inventory. Psychother Res. 2006;16(1):12–25. https://doi.org/10.1080/10503300500352500.CrossRef

63.

Kaida K, Takahashi M, Åkerstedt T, Nakata A, Otsuka Y, Haratani T, et al. Validation of the Karolinska Sleepiness Scale against performance and EEG variables. Clin Neurophysiol. 2006;117(7):1574–81. https://doi.org/10.1016/j.clinph.2006.03.011.CrossRefPubMed

64.

Broderick JE, DeWitt EM, Rothrock N, Crane PK, Forrest CB. Advances in patient-reported outcomes: the NIH PROMIS® measures. EGEMS. 2013;1(1):2015. https://doi.org/10.13063/2327-9214.CrossRef

65.

Salsman JM, Butt Z, Pilkonis PA, Cyranowski JM, Zill N, Hendrie HC, et al. Emotion assessment using the NIH Toolbox. Neurology. 2013;80(11 Supplement 3):S76–86. https://doi.org/10.1212/WNL.0b013e3182872e11.CrossRefPubMedPubMedCentral

66.

Matsumoto D, Ekman P. Japanese and Caucasian facial expressions of emotion (JACFEE). San Francisco: Intercultural and Emotion Research Laboratory, Department of Psychology, San Francisco State University; 1988.

67.

Wilkinson GS, Robertson GJ. Wide Range Achievement Test 4 professional manual. Lutz: Psychological Assessment Resources; 2006.

68.

Delis DC, Kaplan E. Delis-Kaplan Executive Function battery. San Antonio: Psychological Corpor.; 2001.

69.

Wechsler D, Coalson DL, Raiford SE. WAIS-IV technical and interpretive manual. San Antonio: Psychological Corp.; 2008.

70.

Delis DC, Kramer JH, Kaplan E, Ober BA. The California Verbal Learning Test. Second ed. San Antonio: The Psychological Corp.; 2000.

71.

Heuer K, Rinck M, Becker ES. Avoidance of emotional facial expressions in social anxiety: the approach-avoidance task. Behav Res Ther. 2007;45(12):2990–3001. https://doi.org/10.1016/j.brat.2007.08.010.CrossRefPubMed

72.

Lang PJ, Bradley MM, Cuthbert BN. International Affective Picture System (IAPS): affective ratings of pictures and instruction manual. Technical Report A-8. Gainesville: University of Florida; 2008.

73.

Bradley MM, Lang PJ. International Affective Digitized Sounds (IADS): stimuli, instruction manual, and affective ratings. Tech. Rep. No. B-2. Gainesville: Center for Research in Psychophysiology, University of Florida; 1999.

74.

Cox RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res. 1996;29(3):162–73. https://doi.org/10.1006/cbmr.1996.0014.CrossRefPubMed

75.

Tibshirani R. Regression shrinkage and selection via the lasso. J R Stat Soc Series B Stat Methodol. 1996;58(1):267–88.

76.

Ramsay J, Silverman BW. Functional data analysis. New York: Springer Science + Business; 2005.CrossRef

77.

MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V. A comparison of methods to test mediation and other intervening variable effects. Psychol Methods. 2002;7(1):83–104.CrossRefPubMedPubMedCentral

78.

Bureau A, Dupuis J, Falls K, Lunetta KL, Hayward B, Keith TP, et al. Identifying SNPs predictive of phenotype using random forests. Genet Epidemiol. 2005;28(2):171–82.CrossRefPubMed

79.

Arch JJ, Ayers CR. Which treatment worked better for whom? Moderators of group cognitive behavioral therapy versus adapted mindfulness based stress reduction for anxiety disorders. Behav Res Ther. 2013;51(8):434–42. https://doi.org/10.1016/j.brat.2013.04.004.CrossRefPubMed

80.

Nitschke JB, Sarinopoulos I, Oathes DJ, Johnstone T, Whalen PJ, Davidson RJ, 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://doi.org/10.1176/appi.ajp.2008.07101682.CrossRefPubMedPubMedCentral

81.

Farchione TJ, Fairholme CP, Ellard KK, Boisseau CL, Thompson-Hollands J, Carl JR, et al. Unified protocol for transdiagnostic treatment of emotional disorders: a randomized controlled trial. Behav Ther. 2012;43(3):666–78. https://doi.org/10.1016/j.beth.2012.01.001.CrossRefPubMedPubMedCentral

82.

Czajkowski SM, Powell LH, Adler N, Naar-King S, Reynolds KD, Hunter CM, et al. From ideas to efficacy: the ORBIT model for developing behavioral treatments for chronic diseases. Health Psychol. 2015;34(10):971. https://doi.org/10.1037/hea0000161.CrossRefPubMedPubMedCentral

83.

Young KD, Zotev V, Phillips R, Misaki M, Drevets WC, Bodurka J. Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: a review. Psychiatry Clin Neurosci. 2018;72(7):466–81. https://doi.org/10.1111/pcn.12665.CrossRefPubMedPubMedCentral

84.

Clausen AN, Thelen J, Francisco AJ, Bruce J, Martin L, McDowd J, et al. Computer-based executive function training for combat veterans with PTSD: a pilot clinical trial assessing feasibility and predictors of dropout. Front Psychiatry. 2019;10:62. https://doi.org/10.3389/fpsyt.2019.00062.CrossRefPubMedPubMedCentral

85.

Amir N, Beard C, Burns M, Bomyea J. Attention modification program in individuals with generalized anxiety disorder. J Abnorm Psychol. 2009;118(1):28–33. https://doi.org/10.1037/a0012589.CrossRefPubMedPubMedCentral

86.

Choi DC, Rothbaum BO, Gerardi M, Ressler KJ. Pharmacological enhancement of behavioral therapy: focus on posttraumatic stress disorder. In: Stein M, Steckler T, editors. Behavioral neurobiology of anxiety and its treatment. Vol. 2. Berlin: Springer; 2009. p. 279–99.CrossRef

Title: Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder
Authors: J. Santiago
E. Akeman
N. Kirlic
A. N. Clausen
K. T. Cosgrove
T. J. McDermott
B. Mathis
M. Paulus
M. G. Craske
J. Abelson
C. Martell
K. Wolitzky-Taylor
J. Bodurka
W. K. Thompson
Robin L. Aupperle
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Affective Disorder
Generalized Anxiety Disorder
Affective Disorder
Anxiety
Published in: Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-019-3802-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder

Abstract

Background

Methods/design

Discussion

Trial registration

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods/design

Discussion

Trial registration

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