Hostname: page-component-cd9895bd7-jn8rn Total loading time: 0 Render date: 2024-12-26T17:27:16.409Z Has data issue: false hasContentIssue false
  • English
  • Français

Research in young people at ultra-high risk for psychosis: a review of the current evidence

Published online by Cambridge University Press:  19 March 2013

K. O'Connor
K. O'Connor*
Affiliation:
Department of Psychiatry, Tallaght Hospital, Tallaght, Dublin, Ireland
*
*Address for correspondence: K. O'Connor, Department of Psychiatry, Tallaght Hospital, Tallaght, Dublin 24, Ireland. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

The past 15 years have seen a growing interest in early intervention and detection of psychosis before the onset of the first episode. Recent proposals to include a psychosis risk syndrome (PRS) in DSM 5 have focused attention on the evidence base achieved to date in this field.

Aims

This article aims to (1) review the underlying principles of early identification and intervention during the pre-psychotic phase, (2) summarise the naturalistic follow-up studies conducted to date in this ‘at-risk’ population, (3) discuss the identified clinical risk factors for transition to psychosis, (4) summarise the interventional studies both psychological and pharmacological completed to date and (5) briefly discuss the controversy around the proposed inclusion of the PRS in DSM 5.

Methods

Electronic databases EmBase, MedLine and PsychInfo were searched using the keywords ultra-high risk/at-risk mental state/risk syndrome/pre-psychotic/prodrome/prodromal and psychosis/schizophrenia.

Results

The evidence suggests that it is possible to identify individuals who may be at risk of developing psychosis. Results from intervention studies, mostly involving second-generation antipsychotics and cognitive behavioural therapy, are currently insufficient to make treatment recommendations for this group. The emerging research with regard to possible neuroprotective factors such as omega fatty acids is promising, but will require replication in larger cohorts before it can be recommended.

Keywords

Pre-psychoticprodromepsychosisschizophreniaultra-high risk
Type
Review Article
Information
Irish Journal of Psychological Medicine , Volume 30 , Issue 1 , March 2013 , pp. 77 - 89
Copyright
Copyright © College of Psychiatrists of Ireland 2013

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.)

References

Addington, J, Epstein, I, Liu, L, French, P, Boydell, KM, Zipursky, RB (2011). A randomized controlled trial of cognitive behavioral therapy for individuals at clinical high risk of psychosis. Schizophrenia Research 125, 54–61.CrossRefGoogle ScholarPubMed
Amminger, PG, Schafer, MR, Papageorgiou, K, Klier, CM, Cotton, SM, Harrigan, SM, Mackinnon, A, McGorry, PD, Berger, GE (2010). Long chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomised placebo-controlled trial. Archives of General Psychiatry 67, 146–154.CrossRefGoogle Scholar
Auther, AMetal. (2008). Presented at the 63rd Annual Meeting of the Society of Biological Psychiatry, Washington, DC, May 2008.Google Scholar
Bechdolf, A, Pukrop, R, Kohn, D, Tschinkel, S, Veith, V, Schultze-Lutter, F, Ruhrmann, S, Geyer, C, Pohlmann, B, Klosterkotter, J (2005). Subjective quality of life in subjects at risk of psychosis in Germany: concept and recruitment. Schizophrenia Research 79, 137–143.CrossRefGoogle Scholar
Bechdolf, A, Wagner, M, Ruhrmann, S, Harrigan, S, Putzfeld, V, Pukrop, R, Brockhaus-Dumke, A, Berning, J, Janssen, B, Decker, P, Bottlender, R, Maurer, K, Möller, HJ, Gaebel, W, Häfner, H, Maier, W, Klosterkötter, J (2012). Preventing progression to first-episode psychosis in early initial prodromal states. British Journal of Psychiatry 200, 22–29.CrossRefGoogle ScholarPubMed
Bertelsen, M, Jeppesen, P, Petersen, L, Thorup, A, Øhlenschlaeger, J, le Quach, P, Christensen, TØ, Krarup, G, Jørgensen, P, Nordentoft, M (2008). Five-year follow-up of a randomized multicenter trial of intensive early intervention vs standard treatment for patients with a first episode of psychotic illness: the OPUS trial. Archives of General Psychiatry 65, 762–771.CrossRefGoogle ScholarPubMed
Binbay, T, Drukker, M, Elbi, H, Tanık, FA, Özkinay, F, Onay, H, Zaǧli, N, van Os, J, Alptekin, L (2011). Testing the psychosis continuum: differential impact of genetic and nongenetic risk factors and comorbid psychopathology across the entire spectrum of psychosis. Schizophrenia Bulletin. epub ahead of print (doi:10.1093/schbul/sbr003).Google ScholarPubMed
Birchwood, M, Trower, P (2006). The future of cognitive-behavioural therapy for psychosis: not a quasi-neuroleptic. British Journal of Psychiatry 188, 107–108.CrossRefGoogle Scholar
Birchwood, M, Smith, J, Macmillan, F (1989). Cognitive therapy for the prevention of psychosis in people at ultra high risk for psychosis: randomised system using patients and families as observers. Psychological Medicine 19, 649–656.CrossRefGoogle Scholar
Bowers, MB (1965). The onset of psychosis – a diary account. Psychiatry 28, 346–358.CrossRefGoogle ScholarPubMed
Cannon, TD, Cadenhead, K, Cornblatt, B, Woods, SW, Addington, J, Walker, E, Seidman, LJ, Perkins, D, Tsuang, M, McGlashan, T, Heinssen, R (2008). Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America. Archives of General Psychiatry 65, 28–37.CrossRefGoogle ScholarPubMed
Clarke, M, Whitty, P, Browne, S, McTigue, O, Kamali, M, Gervin, M, Kinsella, A, Waddington, JL, Larkin, C, O'Callaghan, E (2006). Untreated illness and outcome of psychosis. British Journal of Psychiatry 189, 235–240.CrossRefGoogle ScholarPubMed
Corcoran, CM, First, MB, Cornblatt, B (2010). The psychosis risk syndrome and its proposed inclusion in the DSM-V: a risk–benefit analysis. Schizophrenia Research 120, 16–22.CrossRefGoogle ScholarPubMed
Crumlish, N, Whitty, P, Clarke, M, Browne, S, Kamali, M, Gervin, Metal. (2009). Beyond the critical period: longitudinal study of 8-year outcome in first-episode non-affective psychosis. British Journal of Psychiatry 194, 18–24.CrossRefGoogle ScholarPubMed
Dominguez, MD, Wichers, M, Lieb, R, Wittchen, HU, van Os, J (2011). Evidence that onset of clinical psychosis is an outcome of progressively more persistent subclinical psychotic experiences: an 8-year cohort study. Schizophrenia Bulletin 37, 84–93.CrossRefGoogle ScholarPubMed
DSM Task Force (2012). American Psychiatric Association. (http://www.dsm5.org/about/Pages/DSMVOverview.aspx). Accessed 12 April 2012.Google Scholar
DSM Task Force (2012). American Pschiatric Association. (http://www.dsm5.org/proposedRevisions/Pages/proposedrevision.aspx?rid=412). Accessed 1 July 2012.Google Scholar
Foley, D, Morley, K (2011). Systematic review of early cardiometabolic outcomes of the first treated episode of psychosis. Archives of General Psychiatry 68, 609–616.CrossRefGoogle ScholarPubMed
Fornito, A, Yung, AR, Wood, SJ, Phillips, LJ, Nelson, B, Cotton, S, Velakoulis, D, McGorry, PD, Pantelis, C, Yücel, M (2008). Anatomic abnormalities of the anterior cingulate cortex before psychosis onset: an MRI study of ultra-high-risk individuals. Biological Psychiatry 64, 758–765.CrossRefGoogle ScholarPubMed
Fusar-Poli, P, Bonoldi, I, Yung, AR, Borgwardt, S, Kempton, MJ, Valmaggia, L, Barale, F, Caverzasi, E, McGuire, P (2012). Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Archives of General Psychiatry 69, 220–229.CrossRefGoogle ScholarPubMed
Giuliano, AJ, Li, H, Mesholam-Gately, RI, Sorenson, SM, Woodberry, KA, Seidman, LJ (2012). Neurocognition in the psychosis risk syndrome: a quantitative and qualitative review. Current Pharmaceutical Design 18, 399–415.CrossRefGoogle ScholarPubMed
Gross, G, Huber, G, Klosterkötter, J, Linz, M (1987). BSABS, Bonner Skala für die Beurteilung von Basissymptomen, Bonn Scale for the Assessment of Basic Symptoms. Springer: Berlin, Heidelberg, New York.Google Scholar
Gumley, AI, O'Grady, M, McNay, L, Reilly, J, Power, K, Norrie, J (2003). Early intervention for relapse in schizophrenia: results of a 12-month randomised controlled trial of cognitive behaviour therapy. Psychological Medicine 33, 419–431.CrossRefGoogle Scholar
Hafner, H, Maurer, K, Loffler, W, Bustamante, S, an der Heiden, W, Riecher-Rossler, A, Nowotny, B (1995). Onset and early course of schizophrenia. In Search for the Cause of Schizophrenia, Vol. 3 (ed. H. G. W. Hafner), pp. 43–66. Springer-Verlag: Berlin.CrossRefGoogle Scholar
Haroun, N, Dunn, L, Haroun, A, Cadenhead, KS (2006). Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. Schizophrenia Bulletin 32, 166–178.CrossRefGoogle ScholarPubMed
Hegarty, JD, Baldessarini, RJ, Tohen, M, Waternaux, C, Oepen, G (1994). One hundred years of schizophrenia: a meta analysis of the outcome literature. American Journal of Psychiatry 151, 1409–1416.Google ScholarPubMed
Henry, LP, Amminger, GP, Harris, MG, Yuen, HP, Harrigan, SM, Prosser, ALetal. (2010). The EPPIC follow-up study of first-episode psychosis: longer-term clinical and functional outcome 7 years after index admission. The Journal of Clinical Psychiatry 71, 716–728.CrossRefGoogle ScholarPubMed
Kelleher, I, Connor, D, Clarke, MC, Devlin, N, Harley, M, Cannon, M (2012 a). Prevalence of psychotic symptoms in childhood and adolescence: a systematic review and meta-analysis of population-based studies. Psychological Medicine. ePub ahead of print (doi:10.1017/S0033291711002960).CrossRefGoogle ScholarPubMed
Kelleher, I, Keeley, H, Corcoran, P, Lynch, F, Fitzpatrick, C, Devlin, N, Molloy, C, Roddy, S, Clarke, MC, Harley, M, Arseneault, L, Wasserman, C, Carli, V, Sarchiapone, M, Hoven, C, Wasserman, D, Cannon, M (2012 b). Clinicopathological significance of psychotic experiences in non-psychotic young people: evidence from four population-based studies. British Journal of Psychiatry. ePub ahead of print (doi: 10.1192/bjp.bp.111.101543).CrossRefGoogle ScholarPubMed
Klosterkotter, J, Hellmich, M, Steinmyer, E (2001). Diagnosing schizophrenia in the initial prodromal phase. Archives of General Psychiatry 58, 158–164.CrossRefGoogle ScholarPubMed
Larsen, TK, Johannssem, JO, Opjordsmoen, S (1998). First-episode schizophrenia with long duration of untreated psychosis. Pathways to care. British Journal of Psychiatry 172, 45–52.CrossRefGoogle ScholarPubMed
Marshall, M, Rathbone, J (2011). Early intervention for psychosis. Cochrane Database of Systematic Reviews, Issue 6. Art. No.: CD004718. (doi: 10.1002/14651858.CD004718.pub3).CrossRefGoogle ScholarPubMed
McGlashan, TH, Johannessen, JO (1996). Early detection and intervention with schizophrenia: rationale. Schizophrenia Bulletin 22, 201–222.CrossRefGoogle ScholarPubMed
McGlashan, TH, Zipursky, RB, Perkins, D, Addington, J, Miller, T, Woods, SW, Hawkins, KA, Hoffman, RE, Preda, A, Epstein, I, Addington, D, Lindborg, S, Trzaskoma, Q, Tohen, M, Breier, A (2006). Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. Am J Psychiatry 163, 790–799.CrossRefGoogle ScholarPubMed
McGorry, PD, Yung, AR, Philips, LJ, Yuen, HP, Francey, S, Cosgrave, EM, Germano, D, Bravin, J, McDonald, T, Blair, A, Adlard, S, Jackson, H (2002). Randomised controlled trial of interventions designed to reduce the risk of progression to first episode psychosis in a clinical sample with sub-threshold symptoms. Archives of General Psychiatry 59, 921–928.CrossRefGoogle Scholar
McGorry, PD, Nelson, B, Amminger, GP, Bechdolf, A, Francey, S, Berger, G, Riecher-Rössler, A, Klosterkötter, J, Ruhrmann, S, Schultze-Lutter, F, Nordentoft, M, Hickie, I, McGuire, P, Berk, M, Chen, EY, Keshavan, MS, Yung, AR (2009). Intervention in individuals at ultra high risk for psychosis: a review and future directions. The Journal of Clinical Psychiatry 70, 1206–1212.CrossRefGoogle ScholarPubMed
Meares, A (1959). The diagnosis of pre-psychotic schizophrenia. Lancet 10, 55–58.CrossRefGoogle Scholar
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. American Journal of Psychiatry 159, 863–865.CrossRefGoogle ScholarPubMed
Morrison, AP, French, P, Parker, S (2007). Three-year follow-up of a randomized controlled trial of cognitive therapy for the prevention of psychosis in people at ultrahigh risk. Schizophrenia Bulletin 33, 682–687.CrossRefGoogle ScholarPubMed
Morrison, A, French, P, Parker, S, Roberts, M, Stevens, H, Bentall, RP, Lewis, SW (2007). Three-year follow-up of a randomized controlled trial of cognitive therapy for the prevention of psychosis in people at ultra high risk. Schizophrenia Bulletin 33, 682–687.CrossRefGoogle Scholar
Morrison, AP, French, P, Walford, L, Lewis, SW, Kilcommons, A, Green, J, Parker, S, Bentall, RP (2004). Cognitive therapy for the prevention of psychosis in people at ultra high risk for psychosis: randomised control trial. British Journal of Psychiatry 185, 291–297.CrossRefGoogle Scholar
Morrison, AP, French, P, Stewart, S, Birchwood, M, Fowler, D, Gumley, AI, Jones, PB, Bentall, RP, Lewis, SW, Murray, GK, Patterson, P, Brunet, K, Conroy, J, Parker, S, Reilly, T, Byrne, R, Davies, LM, Dunn, G (2012). Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial. BMJ, Apr 5;344:e2233. (DOI: 10.1136/bmj.e2233).CrossRefGoogle ScholarPubMed
Olsen, KA, Rosenbaum, B (2006). Prospective investigations of the prodromal state of schizophrenia: review of studies. Acta Psychiatrica Scandinavica 113, 247–272.CrossRefGoogle ScholarPubMed
Pantelis, C, Velakoulis, D, McGorry, PD, Wood, SJ, Suckling, J, Philips, LJetal. (2003). Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison. Lancet 25, 281–288.CrossRefGoogle Scholar
Philips, LJ, Yung, AR, McGorry, PD (2000). Identification of young people at risk of psychosis: validation of Personal Assessment and Crisis Evaluation Clinic intake criteria. Australian and New Zealand Journal of Psychiatry 34, 5164–5169.CrossRefGoogle Scholar
Phillips, LJ, Curry, C, Yung, AR, Yuen, HP, Adlard, S, McGorry, PD (2002). Cannabis use is not associated with the development of psychosis in an ‘ultra’ high-risk group. Australian and New Zealand Journal of Psychiatry 36, 800–806.CrossRefGoogle ScholarPubMed
Phillips, LJ, McGorry, PD, Yuen, HP, Ward, J, Donovan, K, Kelly, D, Francey, SM, Yung, AR (2007). Medium term follow-up of a randomized controlled trial of interventions for young people at ultra high risk of psychosis. Schizophrenia Research 96, 25–33.CrossRefGoogle ScholarPubMed
Raven, M, Stuart, GW, Jureidini, J (2012). ‘Prodromal’ diagnosis of psychosis: ethical problems in research and clinical practice. Australian and New Zealand Journal of Psychiatry 46, 64–65.CrossRefGoogle ScholarPubMed
Ruhrmann, S, Bechdolf, A, Kühn, KU, Wagner, M, Schultze-Lutter, F, Janssen, B, Maurer, K, Häfner, H, Gaebel, W, Möller, HJ, Maier, W, Klosterkötter, J (2007). Acute effects of treatment for prodromal symptoms for people putatively in a late initial prodromal state of psychosis. British Journal of Psychiatry 191, S88–S95.CrossRefGoogle Scholar
Ruhrmann, S, Schultze-Lutter, F, Salokangangas, RK, Heinmaa, 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. Archives of General Psychiatry 67, 241–251.CrossRefGoogle Scholar
Schaffner, K, McGorry, PD (2001). Preventing severe mental illnesses – new prospects and ethical challenges. Schizophrenia Research 51, 3–15.CrossRefGoogle ScholarPubMed
Schultze-Lutter, F (2009). Subjective symptoms of schizophrenia in research and the clinic: the basic symptoms concept. Schizophrenia Bulletin 35, 5–8.CrossRefGoogle ScholarPubMed
Schultze-Lutter, F, Ruhrmann, S, Picker, H, Klosterkotter, J (2007). The Schizophrenia Proneness Instrument (SPI-A) – a tool for the assessment of basic symptoms. European Psychiatry 21, s27.Google Scholar
Schultze-Lutter, F, Ruhrmann, S, Hoyer, C, Klosterkotter, J, Leweke, FM (2007). The initial prodrome of schizophrenia: different duration, different underlying deficits? Comprehensive Psychiatry 48, 479–488.CrossRefGoogle ScholarPubMed
Sullivan, HS (1927). The onset of schizophrenia. American Journal of Psychiatry 151, 135–139.Google Scholar
Tandon, R, Nasrallah, HA, Keshavan, MS (2009). Schizophrenia, ‘just the facts’ 4. Clinical features and conceptualization. Schizophrenia Research 110, 1–23.CrossRefGoogle ScholarPubMed
van Os, J, Linscott, RJ, Myin-Germeys, I, Delespaul, P, Krabbendam, L (2009). A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychological Medicine 39, 179–195.CrossRefGoogle ScholarPubMed
Velakoulis, D, Wood, SJ, Wong, MT, McGorry, PD, Yung, A, Phillips, L, Smith, D, Brewer, W, Proffitt, T, Desmond, P, Pantelis, C (2006). Hippocampal and amygdala volumes according to psychosis stage and diagnosis: a magnetic resonance imaging study of chronic schizophrenia, first-episode psychosis, and ultra-high-risk individuals. Archives of General Psychiatry 63, 139–149.CrossRefGoogle ScholarPubMed
Walker, EF, Cornblatt, BA, Addington, J, Cadenhead, KS, Cannon, TD, McGlashan, TH, Perkins, DO, Seidman, LJ, Tsuang, MT, Woods, SW, Heinssen, R (2009). The relation of antipsychotic and antidepressant medication with baseline symptoms and symptoms progression: a naturalistic study of the North American prodrome longitudinal sample. Schizophrenia Research 115, 50–57.CrossRefGoogle ScholarPubMed
Warner, R (2002). Limitations of the Bonn Scale for the assessment of basic symptoms as a screening measure. Archives of General Psychiatry 59, 470–471.CrossRefGoogle ScholarPubMed
Woodberry, KA, Seidman, LJ, Giuliano, AJ, Verdi, MB, Cook, WL, McFarlane, WR (2010). Neuropsychological profiles in individuals at clinical high risk for psychosis: relationship to psychosis and intelligence. Schizophrenia Research 123, 188–198.CrossRefGoogle ScholarPubMed
Woods, SW, Walsh, BC, Saksa, JR, McGlashan, TH (2010). The case for including Attenuated Psychotic Symptoms Syndrome in DSM-5 as a psychosis risk syndrome. Schizophrenia Research 123, 199–207.CrossRefGoogle ScholarPubMed
Woods, SW, Breier, A, Zipursky, RB, Perkins, DO, Addington, J, Miller, TJ, Hawkins, KA, Marquez, E, Lindborg, SR, Tohen, M, McGlashan, TH (2003). Randomised trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome. Biological Psychiatry 54, 453–464.CrossRefGoogle ScholarPubMed
Woods, SW, Addington, J, Cadenhead, KS, Cannon, TD, Cornblatt, BA, Heinssen, Retal. (2009). Validity of the prodromal risk syndrome for psychosis: findings from the North American Prodrome Longitudinal Study. Schizophrenia Bulletin 35, 894–908.CrossRefGoogle ScholarPubMed
Wyatt, R, Henter, I (2001). Rationale for the study of early intervention. Schizophrenia Research 51, 69–76.CrossRefGoogle Scholar
Yung, AR, McGorry, PD (1996). The prodromal phase of first episode psychosis: past and current conceptualisations. Schizophrenia Bulletin 22, 353–370.CrossRefGoogle Scholar
Yung, AR, Nelson, B (2011). Young people at ultra high risk for psychosis: a research update. Early Intervention in Psychiatry 5, 52–57.CrossRefGoogle ScholarPubMed
Yung, AR, Philips, LJ, Yuen, HP, Francey, SM, McFarlane, CA, Hallgren, M, McGorry, PD (2000). Psychosis prediction: 12 month follow up of a high risk (‘prodromal’) group. Schizophrenia Research 60, 21–32.CrossRefGoogle Scholar
Yung, AR, Philips, LJ, Yuen, HP, McGorry, PD (2004). Risk factors for psychosis in an ultra high risk group: psychopathology and clinical features. Schizophrenia Research 67, 131–142.CrossRefGoogle Scholar
Yung, AR, Phillips, LJ, Yuen, HP (2004). Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features. Schizophrenia Research 67, 131–142.CrossRefGoogle Scholar
Yung, A, Nelson, B, Thompson, A, Wood, SJ (2010). The psychosis threshold in ultra high risk (prodromal) research: is it valid? Schizophrenia Research 120, 1–3.CrossRefGoogle ScholarPubMed
Yung, AR, Nelson, B, Thompson, AD, Wood, SJ (2010). Should a ‘Risk Syndrome for Psychosis’ be included in the DSMV? Schizophrenia Research 120, 7–15.CrossRefGoogle ScholarPubMed
Yung, AR, Yuen, HP, McGorry, PD, Phillips, LJ, Kelly, D, Dell-Olio, Metal. (2005). Mapping the onset of psychosis: The Comprehensive Assessment of At Risk Mental States (CAARMS). Australian and New Zealand Journal of Psychiatry 39, 964–971.CrossRefGoogle Scholar
Yung, AR, Yuen, HP, Berger, G, Francey, S, Hung, T, Nelson, Betal. (2007). Declining transition rate in ultra high risk (prodromal) services: dilution or redirection of risk? Schizophrenia Bulletin 33, 673–681.CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, Nelson, B, Francey, SM, PanYuen, H, Simmons, MBet al. (2011). Randomized controlled trial of interventions for young people at ultra high risk for psychosis: 6-month analysis. Journal of Clinical Psychiatry 72, 430–440.CrossRefGoogle ScholarPubMed