The Closein Strategy

The development of an alternative high-risk strategy with a higher rate of transition to psychosis, a lower false positive rate and shorter follow-up period than the traditional genetic studies has been central to progress in very early preventive interventions for psychosis. Bell proposed that

Table 2.3 Obstacles to prepsychotic intervention

• False positive rate for early psychosis remains substantial. Are falsely identified individuals helped or harmed by involvement in clinical strategies? Receiving treatment at this time may heighten stigma or personal anxiety about developing psychosis or schizophrenia. If exposed to drug therapies, especially antipsychotic medications, adverse reactions may occur without benefit in false positive cases.

• If the false positive rate is improved, then the accurate detection rate may conversely decrease. This is a mathematical feature of the screening process, even when this is based on encouraging help-seeking for this group. Even with enrichment or successful screening, most of the "cases" will still emerge from the low-risk group. The solution may be two- or three-step sequential screens with a continuous entry mechanism. Even if there is a ceiling for the proportion of cases that can be detected and engaged at this phase, there will still be some advantages.

• We are unable to distinguish between false positives and false false positives (in the latter case a true vulnerability exists though it has not yet been fully expressed) [10].

• Lessons from early intervention in cancer, coronary heart disease and stroke have not yet been translated to psychosis and schizophrenia.

''multiple-gate screening'' and ''close-in'' follow-up of cohorts selected as being at risk of developing a psychosis would minimize false positive rates [23]. Multiple-gate screening is a form of sequential screening that involves putting in place a number of different screening measures to concentrate the level of risk in the selected sample. In other words, an individual must meet a number of conditions to be included in the high-risk sample, rather than just one, as in the traditional studies. Close-in follow-up involves shortening the period of follow-up necessary to observe the transition to psychosis by commencing the follow-up period close to the age of maximum incidence of psychotic disorders. In order to improve the accuracy of identifying the high-risk cohort further, Bell also recommended using signs of behavioural difficulties in adolescence as selection criteria. This also allows the approach to become more clinical, to move away from traditional screening paradigms and to focus on help-seeking troubled young people, who are therefore highly ''incipient'' and frankly symptomatic. To maximize the predictive power as well as enabling the engagement of the patient to be well justified on immediate clinical grounds, the timing is critical. Patients should really be as ''incipient'' as possible, yet this is difficult to measure and consistently sustain. Transition rates in samples may therefore vary on this basis and also because of variation in the underlying proportions of true and false positives who enter the sample. It should be emphasized that young people involved in this strategy have clinical problems and help is being sought either directly by them or on their behalf by concerned relatives.

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