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Course of clinical high-risk states for psychosis beyond conversion

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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Background

The main focus of research on clinical high-risk states for psychosis (CHR) has been the development of algorithms to predict psychosis. Consequently, other outcomes have been neglected, and little is known about the long-term diagnostic and functional outcome among those not converting to psychosis.

Methods

In a naturalistic study, incidence, persistence, and remission rates of CHR states according to symptomatic ultra-high risk or cognitive disturbances criteria were investigated in 160 of 246 outpatients of an early detection of psychoses service (21.1% CHR negative and 78.9% CHR positive at baseline) who had not converted to psychosis within follow-up (median 53.7 months, range 13.9–123.7 months).

Results

Remission rate of CHR status was 43.3% of all 194 CHR-positive cases, including converters, or 72.4% if only the 116 non-converters were considered, persistence rate was 27.6%, and new occurrence rate in initially CHR-negative patients was 9.1%. At follow-up, 54.5% of the non-converters met criteria of at least one Axis-I diagnosis, mainly affective and anxiety disorders, and had functional problems. The severity of risk at baseline was not associated with a higher presence of Axis-I diagnosis at follow-up.

Conclusions

During follow-up, CHR symptoms remitted in one-third of initially CHR-positive patients, while almost 10% met CHR criteria newly in CHR-negative adults presenting at early detection services. The presence of CHR criteria seems to maintain the risk for lower functioning and mental disorders, particularly for affective disorders. Thus, therapeutic efforts targeting CHR patients should also focus on the current mental disorders as well as social and role functions to improve the long-term outcome.

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References

  1. Schultze-Lutter F, Michel C, Schmidt SJ, Schimmelmann BG, Maric NP, Salokangas RK, Riecher-Rössler A, van der Gaag M, Nordentoft M, Raballo A, Meneghelli A, Marshall M, Morrison A, Ruhrmann S, Klosterkötter J (2015) EPA guidance on the early detection of clinical high risk states of psychoses. Eur Psychiatry 30(3):405–416

    Article  CAS  PubMed  Google Scholar 

  2. Yung AR, Yuen HP, McGorry PD, Phillips LJ, Kelly D, Dell’Olio M, Francey SM, Cosgrave EM, Killackey E, Stanford C, Godfrey K, Buckby J (2005) Mapping the onset of psychosis: the comprehensive assessment of at-risk mental states. Aust N Z J Psychiatry 39(11–12):964–971

    Article  PubMed  Google Scholar 

  3. McGlashan TH, Walsh BC, Woods SW (2010) The Psychosis-risk syndrome: handbook for diagnosis and follow-up. Oxford University Press, New York

    Google Scholar 

  4. Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rössler A, Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman LJ, Valmaggia L, Cannon T, Velthorst E, De Haan L, Cornblatt B, Bonoldi I, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkötter J, McGuire P, Yung A (2013) The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry 70(1):107–120

    Article  PubMed  PubMed Central  Google Scholar 

  5. Schultze-Lutter F, Ruhrmann S, Fusar-Poli P, Bechdolf A, Schimmelmann BG, Klosterkötter J (2012) Basic symptoms and the prediction of first-episode psychosis. Curr Pharm Des 18(4):351–357

    Article  CAS  PubMed  Google Scholar 

  6. Miller TJ, McGlashan TH, Rosen JL, Somjee L, Markovich PJ, Stein K, Woods SW (2002) Prospective diagnosis of the initial prodrome for schizophrenia based on the Structured Interview for Prodromal Syndromes: preliminary evidence of interrater reliability and predictive validity. Am J Psychiatry 159(5):863–865

    Article  PubMed  Google Scholar 

  7. Yung AR, Phillips LJ, Yuen HP, Francey SM, McFarlane CA, Hallgren M, McGorry PD (2003) Psychosis prediction: 12-month follow up of a high-risk (“prodromal”) group. Schizophr Res 60(1):21–32

    Article  PubMed  Google Scholar 

  8. Ruhrmann S, Schultze-Lutter F, Salokangas RK, Heinimaa M, Linszen D, Dingemans P, Birchwood M, Patterson P, Juckel G, Heinz A, Morrison A, Lewis S, von Reventlow HG, Klosterkötter J (2010) Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study. Arch Gen Psychiatry 67(3):241–251

    Article  PubMed  Google Scholar 

  9. Schultze-Lutter F, Klosterkötter J, Ruhrmann S (2014) Improving the clinical prediction of psychosis by combining ultra-high risk criteria and cognitive basic symptoms. Schizophr Res 154(1–3):100–106

    Article  PubMed  Google Scholar 

  10. Ruhrmann S, Schultze-Lutter F, Klosterkötter J (2010) Sub-threshold states of psychosis – a challenge to diagnosis and treatment. Clin Neuropsychiatr 7(2):72–87

    Google Scholar 

  11. Ruhrmann S, Schultze-Lutter F, Schmidt SJ, Kaiser N, Klosterkotter J (2014) Prediction and prevention of psychosis: current progress and future tasks. Eur Arch Psychiatry Clin Neurosci 264(Suppl 1):S9–S16

    Article  PubMed  Google Scholar 

  12. Schultze-Lutter F, Ruhrmann S, Berning J, Maier W, Klosterkötter J (2010) Basic symptoms and ultrahigh risk criteria: symptom development in the initial prodromal state. Schizophr Bull 36(1):182–191

    Article  PubMed  Google Scholar 

  13. Lemos-Giráldez S, Vallina-Fernández O, Fernández-Iglesias P, Vallejo-Seco G, Fonseca-Pedrero E, Paíno-Piñeiro M, Sierra-Baigrie S, García-Pelayo P, Pedrejón-Molino C, Alonso-Bada S, Gutiérrez-Pérez A, Ortega-Ferrández JA (2009) Symptomatic and functional outcome in youth at ultra-high risk for psychosis: a longitudinal study. Schizophr Res 115(2–3):121–129

    Article  PubMed  Google Scholar 

  14. Velthorst E, Nieman DH, Klaassen RM, Becker HE, Dingemans PM, Linszen DH, De Haan (2011) Three-year course of clinical symptomatology in young people at ultra high risk for transition to psychosis. Acta Psychiatr Scand 123(1):36–42

    Article  CAS  PubMed  Google Scholar 

  15. Velthorst E, Nelson B, Wiltink S, de Haan L, Wood SJ, Lin A, Yung AR (2013) Transition to first episode psychosis in ultra high risk populations: does baseline functioning hold the key? Schizophr Res 143(1):132–137

    Article  PubMed  Google Scholar 

  16. Carrión RE, McLaughlin D, Goldberg TE, Auther AM, Olsen RH, Olvet DM, Correll CU, Cornblatt BA (2013) Prediction of functional outcome in individuals at clinical high risk for psychosis. JAMA Psychiatry 70(11):1133–1142

    Article  PubMed  PubMed Central  Google Scholar 

  17. de Wit S, Schothorst PF, Oranje B, Ziermans TB, Durston S, Kahn RS (2014) Adolescents at ultra-high risk for psychosis: long-term outcome of individuals who recover from their at-risk state. Eur Neuropsychopharmacol 24(6):865–873

    Article  PubMed  Google Scholar 

  18. Ziermans T, de Wit S, Schothorst P, Sprong M, van Engeland H, Kahn R, Durston S (2014) Neurocognitive and clinical predictors of long-term outcome in adolescents at ultra-high risk for psychosis: a 6-year follow-up. PLoS One 9(4):e93994

    Article  PubMed  PubMed Central  Google Scholar 

  19. Simon AE, Borgwardt S, Riecher-Rössler A, Velthorst E, de Haan L, Fusar-Poli P (2013) Moving beyond transition outcomes: meta-analysis of remission rates in individuals at high clinical risk for psychosis. Psychiatry Res 209(3):266–272

    Article  PubMed  Google Scholar 

  20. American Psychiatric Association (APA) (1994) Diagnostic and statistical manual of mental disorders, fourth edition (DSM-IV). American Psychiatric. Press, Washington, DC

    Google Scholar 

  21. Hall RC (1995) Global assessment of functioning. A modified scale. Psychosomatics 36(3):267–275

    Article  CAS  PubMed  Google Scholar 

  22. McGlashan TH, Miller TJ, Woods SW, Rosen JL, Hoffman RE, Davidson L (2001) Structured interview for prodromal syndromes (version 3.0). Yale School of Medicine, PRIME Research Clinic, New Haven

    Google Scholar 

  23. Haroun N, Dunn L, Haroun A, Cadenhead KS (2006) Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. Schizophr Bull 32(1):166–178

    Article  PubMed  Google Scholar 

  24. Addington J, Cornblatt BA, Cadenhead KS, Cannon TD, McGlashan TH, Perkins DO, Seidman LJ, Tsuang MT, Walker EF, Woods SW, Heinssen R (2011) At clinical high risk for psychosis: outcome for nonconverters. Am J Psychiatry 168(8):800–805

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ziermans TB, Schothorst PF, Sprong M, van Engeland H (2011) Transition and remission in adolescents at ultra-high risk for psychosis. Schizophr Res 126(1–3):58–64

    Article  PubMed  Google Scholar 

  26. Schlosser DA, Jacobson S, Chen Q, Sugar CA, Niendam TA, Li G, Bearden CE, Cannon TD (2012) Recovery from an at-risk state: clinical and functional outcomes of putatively prodromal youth who do not develop psychosis. Schizophr Bull 38(6):1225–1233

    Article  PubMed  Google Scholar 

  27. Simon AE, Grädel M, Cattapan-Ludewig K, Gruber K, Ballinari P, Roth B, Umbricht D (2012) Cognitive functioning in at-risk mental states for psychosis and 2-year clinical outcome. Schizophr Res 142(1–3):108–115

    Article  PubMed  Google Scholar 

  28. Lee TY, Kim SN, Correll CU, Byun MS, Kim E, Jang JH, Kang DH, Yun JY, Kwon JS (2014) Symptomatic and functional remission of subjects at clinical high risk for psychosis: a 2-year naturalistic observational study. Schizophr Res 156(2–3):266–271

    Article  PubMed  Google Scholar 

  29. Woods SW, Walsh BC, Addington J, Cadenhead KS, Cannon TD, Cornblatt BA, Heinssen R, Perkins DO, Seidman LJ, Tarbox SI, Tsuang MT, Walker EF, McGlashan TH (2014) Current status specifiers for patients at clinical high risk for psychosis. Schizophr Res 158(1–3):69–75

    Article  PubMed  PubMed Central  Google Scholar 

  30. Eslami A, Jahshan C, Cadenhead KS (2011) Disorganized symptoms and executive functioning predict impaired social functioning in subjects at risk for psychosis. J Neuropsychiatr Clin Neurosci 23(4):457–460

    Article  Google Scholar 

  31. Correll CU, Smith CW, Auther AM, McLaughlin D, Shah M, Foley C, Olsen R, Lencz T, Kane JM, Cornblatt BA (2008) Predictors of remission, schizophrenia, and bipolar disorder in adolescents with brief psychotic disorder or psychotic disorder not otherwise specified considered at very high risk for schizophrenia. J Child Adolesc Psychopharmacol 18(5):475–490

    Article  PubMed  PubMed Central  Google Scholar 

  32. Armando M, Pontillo M, De Crescenzo F, Mazzone L, Monducci E, Lo Cascio N, Santonastaso O, Pucciarini ML, Vicari S, Schimmelmann BG, Schultze-Lutter F (2015) Twelve-month psychosis-predictive value of the ultra-high risk criteria in children and adolescents. Schizophr Res 169(1–3):186–192

    Article  PubMed  Google Scholar 

  33. Schultze-Lutter F, Ruhrmann S, Klosterkötter J (2009) Early detection of psychosis—establishing a service for persons at risk. Eur Psychiatry 24(1):1–10

    Article  PubMed  Google Scholar 

  34. Yung AR, Phillips LJ, McGorry PD, McFarlane CA, Francey S, Harrigan S, Patton GC, Jackson HJ (1998) Prediction of psychosis. A step towards indicated prevention of schizophrenia. Br J Psychiatry Suppl 172(33):14–20

    CAS  PubMed  Google Scholar 

  35. Gross G, Huber G, Klosterkötter J, Linz M (1987) Bonner Skala für die Beurteilung von Basissymptomen [BSABS; Bonn Scale for the Assessment of Basic Symptoms]. Springer, Berlin

    Google Scholar 

  36. Schultze-Lutter F, Addington J, Ruhrmann S, Klosterkötter J (2007) Schizophrenia proneness instrument, adult version (SPI-A). Giovanni Fioriti Editore s.l.r., Rome

  37. Miller TJ, McGlashan TH, Woods SW, Stein K, Driesen N, Corcoran CM, Hoffman RE, Davidson L (1999) Symptom assessment in schizophrenic prodromal states. Psychiatr Q 70(4):273–287

    Article  CAS  PubMed  Google Scholar 

  38. Michel C, Schimmelmann BG, Kupferschmid S, Siegwart M, Schultze-Lutter F (2014) Reliability of telephone assessments of at-risk criteria of psychosis: a comparison to face-to-face interviews. Schizophr Res 153(1–3):251–253

    Article  PubMed  Google Scholar 

  39. Wittchen HU, Zaudig M, Fydrich T (1997) SKID - Strukturiertes klinisches Interview für DSM-IV, Achse I und II. Hogrefe, Göttingen

    Google Scholar 

  40. Schultze-Lutter F, Schimmelmann BG, Klosterkötter J, Ruhrmann S (2012) Comparing the prodrome of schizophrenia-spectrum psychoses and affective disorders with and without psychotic features. Schizophr Res 138(2–3):218–222

    Article  PubMed  Google Scholar 

  41. Lin A, Wood SJ, Nelson B, Beavan A, McGorry P, Yung AR (2015) Outcomes of nontransitioned cases in a sample at ultra-high risk for psychosis. Am J Psychiatry 172(3):249–258

    Article  PubMed  Google Scholar 

  42. Schultze-Lutter F (2009) Subjective symptoms of schizophrenia in research and the clinic: the basic symptom concept. Schizophr Bull 35(1):5–8

    Article  PubMed  PubMed Central  Google Scholar 

  43. Salokangas RKR, Ruhrmann S, von Reventlow HG, Heinimaa M, Svirskis T, From T, Luutonen S, Juckel G, Linszen D, Dingemans P, Birchwood M, Patterson P, Schultze-Lutter F, Klosterkötter J (2012) Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: prospective follow-up of 245 clinical high-risk outpatients in four countries. Schizophr Res 138(2–3):192–197

    Article  PubMed  Google Scholar 

  44. Hui C, Morcillo C, Russo DA, Stochl J, Shelley GF, Painter M, Jones PB, Perez J (2013) Psychiatric morbidity, functioning and quality of life in young people at clinical high risk for psychosis. Schizophr Res 148(1–3):175–180

    Article  PubMed  PubMed Central  Google Scholar 

  45. Fusar-Poli P, Nelson B, Valmaggia L, Yung AR, McGuire PK (2014) Comorbid depressive and anxiety disorders in 509 individuals with an at-risk mental state: impact on psychopathology and transition to psychosis. Schizophr Bull 40(1):120–131

    Article  PubMed  Google Scholar 

  46. Schultze-Lutter F, Michel C, Ruhrmann S, Schimmelmann BG (2014) Prevalence and clinical significance of DSM-5-attenuated psychosis syndrome in adolescents and young adults in the general population: the Bern epidemiological at-risk (BEAR) study. Schizophr Bull 40(6):1499–1508

    Article  PubMed  Google Scholar 

  47. Nelson B, Yuen HP, Wood SJ, Lin A, Spiliotacopoulos D, Bruxner A, Broussard C, Simmons M, Foley DL, Brewer WJ, Francey SM, Amminger GP, Thompson A, McGorry PD, Yung AR (2013) Long-term follow-up of a group at ultra high risk (“prodromal”) for psychosis: the PACE 400 study. JAMA. Psychiatry 70(8):793–802

    Google Scholar 

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Authors and Affiliations

  1. Research Department, University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bolligenstrasse 111, Haus A, 3000, Bern 60, Switzerland

    Chantal Michel, Benno G. Schimmelmann & Frauke Schultze-Lutter

  2. Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany

    Stephan Ruhrmann & Joachim Klosterkötter

Authors
  1. Chantal Michel
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  2. Stephan Ruhrmann
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  3. Benno G. Schimmelmann
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  4. Joachim Klosterkötter
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  5. Frauke Schultze-Lutter
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Correspondence to Chantal Michel.

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Financial support

This work was supported by a grant from the Koeln Fortune Program / Faculty of Medicine, University of Cologne [Grant Numbers 8/2005, 27/2006] to Dr. Schultze-Lutter. The study’s sponsor had no role in study design, data collection, or analysis, or in interpretation, writing, or submission of the report.

Conflict of interest

Drs Michel and Schultze-Lutter declare that there are no conflicts of interest in relation to the subject of this study. Professor Ruhrmann received speaker’s honoraria from AstraZeneca, Bristol-Myers Squibb, Essex, and Janssen-Cilag; travel support from Servier; and consultancy honoraria from Roche. Professor Klosterkötter received speaker’s honoraria from AstraZeneca, Bristol-Myers Squibb, and Janssen-Cilag; a research grant from Bristol-Myers Squibb; and is a former member of the expert advisory board of Janssen-Cilag Germany. Professor Schimmelmann has been a consultant and/or advisor to or has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and Shire.

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C. Michel and S. Ruhrmann shared first authorship.

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Michel, C., Ruhrmann, S., Schimmelmann, B.G. et al. Course of clinical high-risk states for psychosis beyond conversion. Eur Arch Psychiatry Clin Neurosci 268, 39–48 (2018). https://doi.org/10.1007/s00406-016-0764-8

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  • DOI: https://doi.org/10.1007/s00406-016-0764-8

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