Early interventions in risk groups for schizophrenia: what are we waiting for?

Abstract

Intervention strategies in adolescents at ultra high-risk (UHR) for psychosis are promising for reducing conversion to overt illness, but have only limited impact on functional outcome. Recent studies suggest that cognition does not further decline during the UHR stage. As social and cognitive impairments typically develop before the first psychotic episode and even years before the UHR stage, prevention should also start much earlier in the groups at risk for schizophrenia and other psychiatric disorders. Early intervention strategies could aim to improve stress resilience, optimize brain maturation, and prevent or alleviate adverse environmental circumstances. These strategies should urgently be tested for efficacy: the prevalence of ~1% implies that yearly ~22 in every 100,000 people develop overt symptoms of this illness, despite the fact that for many of them-e.g., children with an affected first-degree family member or carriers of specific genetic variants-increased risk was already identifiable early in life. Our current ability to recognize several risk groups at an early age not only provides an opportunity, but also implies a clinical imperative to act. Time is pressing to investigate preventive interventions in high-risk children to mitigate or prevent the development of schizophrenia and related psychiatric disorders.

Figure 1

Hypothesized typical course of schizophrenia. (a) shows the clinical course of the disease. (b) shows the hypothesized course of the underlying molecular mechanisms.

Figure 2

(a–c) Economical feasibility of early-intervention strategies. This figure indicates the total cost (in €) of any intervention strategy (x axis) to prevent the development of schizophrenia in one individual (y axis). (a–c) represent three scenarios based on different prevention rates of the intervention (5%, 10%, and 25% respectively). For reference, the black dotted line represents the estimated economic burden of one individual who develops a psychotic disorder calculated for a time span of 10 years. The area under the dotted line indicates an economic benefit since the costs of the preventive strategy to prevent one transition to schizophrenia outweighs the economic burden of one affected individual. Several factors influence whether a preventive intervention is cost-effective, including (i) the costs of the intervention (x axis). (ii) lifetime risk for a psychotic disorder in the target population (different line colors) with lower risks resulting in a reduced cost-effectiveness. The blue line refers to the risk for schizophrenia in the general population (1%), the red line applies to the selected population of 22q11DS individuals with a 25% lifetime incidence of schizophrenia and (iii) the effectiveness of the intervention; that is, in what proportion of individuals can the development of a psychotic disorder be averted as a result of the intervention?