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Negative symptoms, anxiety, and depression as mechanisms of change of a 12-month trial of assertive community treatment as part of integrated care in patients with first- and multi-episode schizophrenia spectrum disorders (ACCESS I trial)

  • Stefanie J. Schmidt
  • Matthias Lange
  • Daniel Schöttle
  • Anne Karow
  • Benno G. Schimmelmann
  • Martin Lambert
Original Paper

Abstract

Assertive community treatment (ACT) has shown to be effective in improving both functional deficits and quality of life (QoL) in patients with severe mental illness. However, the mechanisms of this beneficial effect remained unclear. We examined mechanisms of change by testing potential mediators including two subdomains of negative symptoms, i.e. social amotivation as well as expressive negative symptoms, anxiety, and depression within a therapeutic ACT model (ACCESS I trial) in a sample of 120 first- and multi-episode patients with a schizophrenia spectrum disorder (DSM-IV). Path modelling served to test the postulated relationship between the respective treatment condition, i.e. 12-month ACT as part of integrated care versus standard care, and changes in functioning and QoL. The final path model resulted in 3 differential pathways that were all significant. Treatment-induced changes in social amotivation served as a starting point for all pathways, and had a direct beneficial effect on functioning and an additional indirect effect on it through changes in anxiety. Expressive negative symptoms were not related to functioning but served as a mediator between changes in social amotivation and depressive symptoms, which subsequently resulted in improvements in QoL. Our results suggest that social amotivation, expressive negative symptoms, depression, and anxiety functioned as mechanisms of change of ACCESS. An integrated and sequential treatment focusing on these mediators may optimise the generalisation effects on functioning as well as on QoL by targeting the most powerful mechanism of change that fits best to the individual patient.

Keywords

Mediation Amotivation Quality of life Functioning Negative symptoms Psychosis 

Notes

Compliance with ethical standards

Financial support

This study was supported by Astra Zeneca. The sponsor was not involved in designing and conducting the study, analysing as well as interpreting the data or writing up the manuscript.

Conflict of interest

Dr Schmidt and Dr Lange have no conflict of interest to declare. Dr Schöttle has received honoraria from Astra Zeneca. Dr Karow has received honoraria from and serves on speakers boards of Astra Zeneca. Dr Schimmelmann has served as paid speaker for Eli Lilly and Shire. Dr Lambert has received grant/research support from and served on speakers or advisory boards of Astra Zeneca and has received honoraria from Astra Zeneca, Eli Lilly, Janssen-Cilag, and Bristol-Myers Squibb.

Ethical standards

The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional guides on the care and use of laboratory animals.

References

  1. 1.
    Simonsen C, Sundet K, Vaskinn A, Ueland T, Romm KL, Hellvin T, Andreassen OA (2010) Psychosocial function in schizophrenia and bipolar disorder: relationship to neurocognition and clinical symptoms. J Int Neuropsychol Soc 16(5):771–783CrossRefPubMedGoogle Scholar
  2. 2.
    Bechdolf A, Pukrop R, Köhn D, Tschinkel S, Veith V, Schultze-Lutter F, Klosterkötter J (2005) Subjective quality of life in subjects at risk for a first episode of psychosis: a comparison with first episode schizophrenia patients and healthy controls. Schizophr Res 79(1):137–143CrossRefPubMedGoogle Scholar
  3. 3.
    Chugh PK, Rehan HS, Unni KE, Sah RK (2013) Predictive value of symptoms for quality of life in first-episode schizophrenia. Nord J Psychiatry 67(3):153–158CrossRefPubMedGoogle Scholar
  4. 4.
    Meesters PD, Comijs HC, de Haan L, Smit JH, Eikelenboom P, Beekman ATF, Stek ML (2013) Subjective quality of life and its determinants in a catchment area based population of elderly schizophrenia patients. Schizophr Res 147(2–3):275–280. doi: 10.1016/j.schres.2013.04.030 CrossRefPubMedGoogle Scholar
  5. 5.
    Álvarez-Jiménez M, Gleeson JF, Henry LP, Harrigan SM, Harris MG, Killackey E, Bendall S, Amminger GP, Yung AR, Herrman H, Jackson HJ, McGorry PD (2012) Road to full recovery: longitudinal relationship between symptomatic remission and psychosocial recovery in first-episode psychosis over 7.5 years. Psychol Med 42(3):595–606CrossRefPubMedGoogle Scholar
  6. 6.
    Álvarez-Jimenez M, Gleeson JF, Henry LP, Harrigan SM, Harris MG, Amminger GP, Killackey E, Yung AR, Herrman H, Jackson HJ, McGorry PD (2011) Prediction of a single psychotic episode: a 7.5-year, prospective study in first-episode psychosis. Schizophr Res 125(2–3):236–246CrossRefPubMedGoogle Scholar
  7. 7.
    Burns T (2010) The rise and fall of assertive community treatment? Int Rev Psychiatry 22(2):130–137CrossRefPubMedGoogle Scholar
  8. 8.
    Armijo J, Méndez E, Morales R, Schilling S, Castro A, Alvarado R, Rojas G (2013) Efficacy of community treatments for schizophrenia and other psychotic disorders: a literature review. Front Psychiatry 4:116CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Kerkemeyer L, Mostardt S, Biermann J, Wasem J, Neumann A, Walendzik A, Jahn R, Bartels C, Falkai P, Brannath W, Breunig-Lyriti V, Mester B, Timm J, Wobrock T (2015) Evaluation of an integrated care program for schizophrenia: concept and study design. Eur Arch Psychiatry Clin Neurosci 265(2):155–162CrossRefPubMedGoogle Scholar
  10. 10.
    Karow A, Reimer J, König HH, Heider D, Bock T, Huber C, Lambert M (2012) Cost-effectiveness of 12-month therapeutic assertive community treatment as part of integrated care versus standard care in patients with schizophrenia treated with quetiapine immediate release (ACCESS trial). J Clin Psychiatry 73(3):402–408CrossRefGoogle Scholar
  11. 11.
    Lambert M, Bock T, Schöttle D, Golks D, Meister K, Rietschel L, Schimmelmann BG (2010) Assertive community treatment as part of integrated care versus standard care: a 12-month trial in patients with first- and multiple-episode schizophrenia spectrum disorders treated with quetiapine immediate release (ACCESS trial). J Clin Psychiatry 71(10):1313–1323CrossRefPubMedGoogle Scholar
  12. 12.
    Frazier PA, Trix AP, Barron KE (2004) Testing moderator and mediator effects in counseling psychology research. J Couns Psychol 51(1):115–134CrossRefGoogle Scholar
  13. 13.
    Baron RM, Kenny DA (1986) The moderator—mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol 51(6):1173–1182CrossRefPubMedGoogle Scholar
  14. 14.
    Bowie CR, Depp C, McGrath JA, Wolyniec P, Mausbach BT, Thornquist MG, Pulver AE (2010) Prediction of real-world functional disability in chronic mental disorders: a comparison of schizophrenia and bipolar disorder. Am J Psychiatry 167(9):1116–1124CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Chudleigh C, Naismith SL, Blaszczynski A, Hermens DF, Hodge M, Hickie IB (2011) How does social functioning in the early stages of psychosis relate to depression and social anxiety? Early Interv Psychiatry 5(3):224–232CrossRefPubMedGoogle Scholar
  16. 16.
    Hayhurst KP, Drake RJ, Massie JA, Dunn G, Barnes TR, Jones PB, Lewis SW (2014) Improved quality of life over one year is associated with improved adherence in patients with schizophrenia. Eur Psychiatry 29(3):191–196CrossRefPubMedGoogle Scholar
  17. 17.
    Margariti M, Ploumpidis D, Economou M, Christodoulou GN, Papadimitriou GN (2015) Quality of life in schizophrenia spectrum disorders: associations with insight and psychopathology. Psychiatry Res 225(3):695–701CrossRefPubMedGoogle Scholar
  18. 18.
    Liemburg E, Castelein S, Stewart R, van der Gaag M, Aleman A, Knegtering H (2013) Two subdomains of negative symptoms in psychotic disorders: established and confirmed in two large cohorts. J Psychiatry Res 47(6):718–725CrossRefGoogle Scholar
  19. 19.
    Galderisi S, Merlotti E, Mucci A (2015) Neurobiological background of negative symptoms. Eur Arch Psychiatry Clin Neurosci 265(7):543–558CrossRefPubMedGoogle Scholar
  20. 20.
    Boyette LL, Korver-Nieberg N, Meijer C, de Haan L (2014) Quality of life in patients with psychotic disorders: impact of symptoms, personality, and attachment. J Nerv Ment Dis 202(1):64–69CrossRefPubMedGoogle Scholar
  21. 21.
    Gade K, Malzahn D, Anderson-Schmidt H, Strohmaier J, Meier S, Frank J, Schulze TG (2015) Functional outcome in major psychiatric disorders and associated clinical and psychosocial variables: a potential cross-diagnostic phenotype for further genetic investigations? World J Biol Psychiatry 16(4):237–248CrossRefPubMedGoogle Scholar
  22. 22.
    Blanchard JJ, Cohen AS (2006) The structure of negative symptoms within schizophrenia: implications for assessment. Schizophr Bull 32(2):238–245CrossRefPubMedGoogle Scholar
  23. 23.
    Chiappelli J, Nugent KL, Thangavelu K, Searcy K, Hong LE (2013) Assessment of trait and state aspects of depression in schizophrenia. Schizophr Bull 40(1):132–142CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kirkpatrick B, Galderisi S (2008) Deficit schizophrenia: an update. World Psychiatry 7(3):143–147CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    An der Heiden W, Leber A, Häfner H (2016) Negative symptoms and their association with depressive symptoms in the long-term course of schizophrenia. Eur Arch Psychiatry Clin Neurosci 266(5):387–396CrossRefPubMedGoogle Scholar
  26. 26.
    Schmidt SJ, Schimmelmann BG (2015) Mechanisms of change in psychotherapy for children and adolescents: current state, clinical implications, and methodological and conceptual recommendations for mediation analysis. Eur Child Adolesc Psychiatry 24(3):249–253CrossRefPubMedGoogle Scholar
  27. 27.
    Ventura J, Liberman RP, Green MF, Shaner A, Mintz J (1998) Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-I/P). Psychiatry Res 79(2):163–173CrossRefPubMedGoogle Scholar
  28. 28.
    McGorry PD, Edwards J, Mihalopoulos C, Harrigan SM, Jackson HJ (1996) EPPIC: an evolving system of early detection and optimal management. Schizophr Bull 22(2):305–326CrossRefPubMedGoogle Scholar
  29. 29.
    Ritsner MS, Kurs R, Gibel A (2005) Validity of an abbreviated quality of life enjoyment and satisfaction questionnaire (Q-LES-Q-18) for schizophrenia, schizoaffective, and mood disorder patients. Qual Life Res 14(7):1693–1703CrossRefPubMedGoogle Scholar
  30. 30.
    Kay SR, Falzbein A, Opfer LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13(2):261–276CrossRefPubMedGoogle Scholar
  31. 31.
    Sass H, Wittchen HU, Zaudig M, Houben I (2003) Diagnostische kriterien des diagnostischen und statistischen manuals psychischer störungen. DSM-IV-TR. Hogrefe, GöttingenGoogle Scholar
  32. 32.
    Hayes AF (2013) Introduction to mediation, moderation, and conditional process analysis: a regression-based approach. The Guilford Press, New YorkGoogle Scholar
  33. 33.
    Tucker LR, Lewis C (1973) A reliability coefficient for maximum likelihood factor analysis. Psychometrika 38(1):1–10CrossRefGoogle Scholar
  34. 34.
    Bentler PM (1990) Comparative fit indexes in structural models. Psychol Bull 107(2):238–246CrossRefPubMedGoogle Scholar
  35. 35.
    Steiger JH (1990) Structural model evaluation and modification: an interval estimation approach. Multivariate Behav Res 25(2):173–180CrossRefPubMedGoogle Scholar
  36. 36.
    Bentler PM (1992) On the fit of models to covariances and methodology to the Bulletin. Psychol Bull 112(3):400–404CrossRefPubMedGoogle Scholar
  37. 37.
    Preacher KJ, Hayes A (2004) SPSS and SAS procedures for estimating indirect effects in simple mediation models. Behav Res Methods Instrum Comput 36(4):717–731CrossRefPubMedGoogle Scholar
  38. 38.
    Brown TA (2006) Confirmatory factor analysis for applied research. The Guilford Press, New YorkGoogle Scholar
  39. 39.
    Spratt M, Carpenter J, Sterne JA, Carlin JB, Heron J, Henderson J, Tilling K (2010) Strategies for multiple imputation in longitudinal studies. Am J Epidemiol 172:478–487CrossRefPubMedGoogle Scholar
  40. 40.
    Green MF, Hellemann G, Horan WP, Lee J, Wynn JK (2012) From perception to functional outcome in schizophrenia: modelling the role of ability and motivation. Arch Gen Psychiatry 69(12):1216–1224CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Kring AM, Gur RE, Blanchard JJ, Horan WP, Reise SP (2013) The clinical assessment interview for negative symptoms (CAINS): final development and validation. Am J Psychiatry 170(2):165–172CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Quinlan T, Roesch S, Granholm E (2014) The role of dysfunctional attitudes in models of negative symptoms and functioning in schizophrenia. Schizophr Res 157(1–3):182–189CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Chang WC, Kwong VW, Hui CL, Chan SK, Lee EH, Chen EY (2016) Relationship of amotivation to neurocognition, self-efficacy and functioning in first-episode psychosis: a structural equation modeling approach. Psychol Med 47(4):755–765CrossRefPubMedGoogle Scholar
  44. 44.
    Strauss GP, Gold JM (2012) A new perspective on anhedonia in schizophrenia. Am J Psychiatry 169(4):364–373CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Engel M, Fritzsche A, Lincoln TM (2016) Anticipation and experience of emotions in patients with schizophrenia and negative symptoms. An experimental study in a social context. Schizophr Res 170(1):191–197CrossRefPubMedGoogle Scholar
  46. 46.
    Barch DM, Treadway MT, Schoen N (2014) Effort, anhedonia, and function in schizophrenia: reduced effort allocation predicts amotivation and functional impairment. J Abnorm Psychol 123(2):387–397CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Strauss GP, Whearty KM, Morra LF, Sullivan SK, Ossenfort KL, Frost KH (2016) Avolition in schizophrenia is associated with reduced willingness to expend effort for reward on a progressive ratio task. Schizophr Res 170(1):198–204CrossRefPubMedGoogle Scholar
  48. 48.
    Buck B, Lysaker PH (2013) Consummatory and anticipatory anhedonia in schizophrenia: stability, and associations with emotional distress and social function over six months. Psychiatry Res 205(1–2):30–35CrossRefPubMedGoogle Scholar
  49. 49.
    Grant PM, Beck AT (2009) Defeatist beliefs as a mediator of cognitive impairment, negative symptoms, and functioning in schizophrenia. Schizophr Bull 35(4):798–806CrossRefPubMedGoogle Scholar
  50. 50.
    Wolf DH, Satterthwaite TD, Kantrowitz JJ, Katchmar N, Vandekar L, Elliott MA, Ruparel K (2014) Amotivation in schizophrenia: integrated assessment with behavioural, clinical, and imaging measures. Schizophr Bull 40(6):1328–1337CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Del-Monte J, Raffard S, Salesse RN, Marin L, Schmidt RC, Varlet M, Bardy BG, Philippe Boulenger J, Christine Gély-Nargeot M, Capdevielle D (2013) Nonverbal expressive behaviour in schizophrenia and social phobia. Psychiatry Res 210(1):29–35CrossRefPubMedGoogle Scholar
  52. 52.
    Krauss RM, Chen Y, Chawla P (1996) Nonverbal behavior and nonverbal communication: what do conversational hand gestures tell us? Adv Exp Soc Psychol 28:389–450CrossRefGoogle Scholar
  53. 53.
    Bell M, Tsang HW, Greig TC, Bryson GJ (2009) Neurocognition, social cognition, perceived social discomfort, and vocational outcomes in schizophrenia. Schizophr Bull 35(4):738–747CrossRefPubMedGoogle Scholar
  54. 54.
    Brekke JS, Hoe M, Long J, Green MF (2007) How neurocognition and social cognition influence functional change during community-based psychosocial rehabilitation for individuals with schizophrenia. Schizophr Bull 33(5):1247–1256CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Kaiser SL, Snyder JA, Corcoran R, Drake RJ (2006) The relationships among insight, social support, and depression in psychosis. J Nerv Ment Dis 194(12):905–908CrossRefPubMedGoogle Scholar
  56. 56.
    Alessandrini M, Lançon C, Fond G, Faget-Agius C, Richieri R, Faugere M, Metairie E, Boucekine M, Llorca PM, Auquier P, Boyer L (2016) A structural equation modelling approach to explore the determinants of quality of life in schizophrenia. Schizophr Res 171(1–3):27–34CrossRefPubMedGoogle Scholar
  57. 57.
    Urben S, Baier V, Mantzouranis G, Pigois E, Graap C, Dutoit F, Cherix-Parchet M, Henz C, Faucherand A, Senent E, Holzer L (2015) Predictors and moderators of clinical outcomes in adolescents with severe mental disorders after an assertive community treatment. Child Psychiatry Hum Dev 46(6):997–1005CrossRefPubMedGoogle Scholar
  58. 58.
    Schmidt SJ, Mueller DR, Roder V (2011) Social cognition as a mediator variable between neurocognition and functional outcome in schizophrenia: empirical review and new results by structural equation modelling. Schizophr Bull 37(Suppl. 2):41–54CrossRefGoogle Scholar
  59. 59.
    Hayduk LA, Littvay L (2012) Should researchers use single indicators, best indicators, or multiple indicators in structural equation models? BMC Med Res Methodol 12:159CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Stefanie J. Schmidt
    • 1
    • 2
  • Matthias Lange
    • 3
  • Daniel Schöttle
    • 3
  • Anne Karow
    • 3
  • Benno G. Schimmelmann
    • 1
    • 4
  • Martin Lambert
    • 3
  1. 1.University Hospital of Child and Adolescent Psychiatry and PsychotherapyUniversity of BernBernSwitzerland
  2. 2.Department of Psychiatry and PsychotherapyUniversity of CologneCologneGermany
  3. 3.Department for Psychiatry and Psychotherapy, Psychosis Centre, Centre for Psychosocial MedicineUniversity Medical Centre Hamburg-EppendorfHamburgGermany
  4. 4.University Hospital of Child and Adolescent Psychiatry, Centre for Psychosocial MedicineUniversity Medical Centre Hamburg-EppendorfHamburgGermany

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