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Research to Improve the Care of Persons at Clinical High Risk for Psychotic Disorders


Robert K. Heinssen, Ph.D., A.B.P.P.
Director, Division of Services and Intervention Research


The goals of this initiative are to (1) test the effectiveness of interventions that target symptomatic and functional difficulties associated with clinical risk states for psychosis; (2) create an evidence base to inform stepped-care models of early psychosis treatment; and, (3) determine the feasibility for implementing such approaches in community treatment settings within the United States.


Approximately 100,000 young people in the United States experience a first episode of psychosis every year (calculated from McGrath et al., 2008).1 During the same interval, over one million children and adolescents may experience problems in thinking, mood, and social functioning suggestive of a pre-psychosis risk state (estimated from Kelleher et al., 2012).2 Given the highly disruptive and disabling nature of psychotic disorders, early intervention has been recommended as a means of preventing the onset of psychosis among at-risk individuals, as well as averting other adverse mental health outcomes associated with psychosis risk states, such as mood syndromes, substance abuse disorders, and functional decline.3

Eleven randomized controlled trials (RCTs) have been conducted over the past decade that test the efficacy of psychological, pharmacological, nutritional, and multi-component psychosocial interventions for preventing the onset of psychosis among help-seeking individuals who meet clinical high-risk criteria. In these studies, ascertainment of an individual’s risk state is based on defined criteria involving attenuated psychotic symptoms, transient psychotic symptoms, or genetic risk combined with functional deterioration. In a recent meta-analysis, the authors concluded that cognitive-behavioral therapy exerts a moderate effect on transition to psychosis 12 months later, and that multi-component treatment also delays or reduces transition to psychotic illness over a one-year period.4 Although no clear evidence supports pharmacological interventions for persons at high clinical risk, one study suggests a potentially beneficial effect for nutritional supplementation (i.e., omega-3 fatty acids).5

Additional RCTs are required to expand knowledge regarding effective interventions during the clinical high-risk period, and to build an evidence base to support high-quality community care. Clinical staging or stepped-care models could serve as a framework for future effectiveness studies, with RCTs comparing treatments that address clinical issues apparent at various stages of psychosis risk.4,6,7 Overall, this initiative aims to support research that will inform a step-wise approach to care that features lower intensity/lower risk treatments as first-line interventions, with decisions regarding discharge, maintenance therapy, or step-up to more intensive care based on a priori definitions of recovery, stabilization, and worsening. Anticipated outcomes from this program of research include, but are not limited to:

  • Interventions of varying complexity, intensity, and duration that address symptoms, problems, and functional impairments that characterize different clinical high-risk states;
  • Empirical data regarding the effectiveness, risks, and benefits of various forms of stage-specific treatment; and,
  • Information regarding the feasibility of implementing promising therapies in community treatment settings in the United States.

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 1 McGrath J, Saha S, Chant D, Welham J. (2008). Schizophrenia: a concise overview of incidence, prevalence, and mortality. Epidemiologic Reviews, 30:67-76.

 2 Kelleher I, Murtagh A, Molloy C, Roddy S, Clarke MC, Harley M, Cannon M. (2012). Identification and characterization of prodromal risk syndromes in young adolescents in the community: A population-based clinical interview study. Schizophrenia Bulletin, 38(2):239-246.

 3 McGorry PD, Killackey E, Yung A. (2008). Early intervention in psychosis: Concepts, evidence, and future directions. World Psychiatry; 7:148-156.

 4 Stafford MR, Jackson H, Mayo-Wilson E, Morrison AP, Kendall T. (2013). Early interventions to prevent psychosis: Systematic review and meta-analysis. British Medical Journal, 346:f185.

 5 Amminger GP, Schafer MR, Papageorgiou K, Klier CM, Cotton SM et al. (2010). Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Archives of General Psychiatry, 67(2):146-54

 6 McGorry PD. (2010). Risk syndromes, clinical staging and DSM V: New diagnostic infrastructure for early intervention in psychiatry. Schizophrenia Research, 120:49-53.

 7 Van Os J; Murray RM. (2013). Can we identify and treat “schizophrenia light” to prevent true psychotic illness? British Medical Journal, 346:f304.