Toward a world consensus on prevention of schizophrenia

Abstract

Screening for preschizophrenia in the general population with the aim of preventing transition to full-blown illness is an epidemiological impossibility because a rare disease cannot be predicted. The lack of specificity resulting in abundance of false-positives can be remedied in part by using much more restrictive screening criteria that combine several indicators of risk for transition to schizophrenia. Raising the specificity (reducing the false-positives), however, can only be done at the expense of sensitivity (increasing the false-negatives). The most commonly used strategy to raise specificity is the sample enrichment strategy. This involves the creation of samples enriched with schizophrenia risk by selectively filtering at-risk people out over a range of consecutive referral processes starting in the general population, through to general practioners, mental health services, and the early detection clinic. However, improvements in specificity obtained by the sample enrichment strategy should not be attributed to the use of some predictive instrument that supposedly identifies high-risk individuals. The epidemiologically and ethically most viable way for screening and early detection is to selectively increase the permeability of the filters on the pathway to mental health care. This will occasion samples of help-seekers enriched with schizophrenia risk at the level of mental health services (thus reducing false-positives), while at the same time making an attempt to "attract" as many detectable schizophrenia prodromes as possible through the filters along the pathway to mental health care (thus reducing false-negatives). Early psychosis research has yielded some useful suggestions in that it is becoming increasingly clear that it is not just psychosis itself, but rather the clinical context of the psychotic experience that determines risk for transition to schizophrenia. Thus, risk for transition to full-blown psychotic disorder is to a large degree determined by size of psychosis "load," comorbid distress and depression, cannabis use, cognitive ability, and subjective reports of impairment and coping. Making a diagnosis of psychotic disorder is not an exact science: it involves an arbitrary cutoff imposed on dimensional variation of psychopathology and need for care over time. Gaining insight into the cognitive and biological factors that drive the dimensional variation, including therapeutic interventions, is arguably more useful than sterile dichotomous prediction models.

Figure 1.. Prepsychotic expression of illness.

Figure 2.. Prevention of full-blown psychotic disorder.

Figure 3.. Course of subclinical psychosis. Person c has a stable low level and person d a stable higher level of subclinical psychosis. Persons a and b have unstable levels, but person a never crosses the clinical threshold, whereas person b does. Person e has unstable levels, develops an attenuated psychotic experience that initially resolves, but later results in full-blown psychotic disorder. The psychotic disorder of person e could possibly have been prevented by intervening in the attenuated stage. BLIPS, brief limited intermittent psychotic symptoms.

Figure 4.. Making schizophrenia more predictable (but for fewer patients), Predictor A is the presence of subclinical psychotic experiences, which previous research has shown increased the 1 -year risk of schizophrenia by 4%. As the majority of patients with schizophrenia (around 90%) displayed such subclinical experiences as part of the prodrome, 90% of all schizophrenia should theoretically be predictable if this criterion were used. However, if a family history of schiozphrenia were used (predictor B), only 20% of all schizophrenia would be predictable, given that only 20% of patients have a family history, Therefore, although the application of predictor C (the combination of subclinical psychosis and a positive family history) greatly increased the 1-year predictive value, only a small proportion of all schizophrenia would be predictable with the criterion.

Figure 5.. Figure 5. Filter model of psychotic symptoms and psychotic disorder. GP, general practitioner. Reproduced from reference 69: Goldberg D, Huxley P. Mental Illness in the Community. London, UK: Tavistock Publications; 1980. Copyright © Tavistock Publications, 1980.