There is a consensus among clinicians that psychotic disorders can be conceptualised using stress vulnerability models, which suggest that inherited vulnerabilities interact with environmental factors to produce psychosis (Reference Zubin and SpringZubin & Spring, 1977; Reference Neuchterlein and DawsonNeuchterlein & Dawson, 1984). These models are consistent with Strauss's (Reference Strauss1969) hypothesis that psychotic phenomena lie on a continuum with normal processes. Consistent with this viewpoint, epidemiological studies suggest a higher incidence of psychotic phenomena in the general population than expected from studies of psychiatric admissions. For example approximately 5% of the population experience auditory hallucinations (Reference TienTien, 1991; Reference van Os, Hanssen and Bijlvan Os et al, 2000); and about 9% hold delusional beliefs (Reference van Os, Hanssen and Bijlvan Os et al, 2000). There is also evidence that psychotic phenomena can be detected in apparently mentally healthy primary care patients by means of self-report questionnaires. Verdoux et al (Reference Verdoux, Maurice-Tison and Gay1998) found that 16% of a large sample (n=462) of primary care patients experienced verbal hallucinations and 26% believed that there was a conspiracy against them. Yung et al (1996, Reference Yung, Phillips and McGorry1998) used a combination of state and trait indicators to identify a high-risk sample of whom 40% became psychotic after just 6 months. These findings raise the possibility that individuals prone to psychosis might be detected before they become engaged with traditional psychiatric services and offered treatment to prevent the emergence of a full-blown psychotic illness. However, five of the eight patients who made the transition in their study did so in the first month, suggesting a potential criticism that some patients were already psychotic at initial assessment, but were too suspicious or worried to disclose this. Exclusion of these patients would have reduced their transition rate to 15%.

The Early Detection and Intervention Evaluation (EDIE) trial is the focus of this initial report. The aims of the trial are to identify an indicated high-risk group using Yung et al's criteria and randomly allocate participants to a psychological intervention (cognitive therapy), or a monthly monitoring condition.

We hypothesise that it will be possible to identify indicators of risk that accurately predict transition to psychosis, that a cognitive—behavioural intervention will reduce the rate of transition to psychosis and that the identification of at-risk individuals and subsequent monitoring will reduce the duration of untreated psychosis (DUP). The current report has two aims. First, we wish to establish whether operationally defined at-risk individuals can be ascertained in British health care settings and recruited into a randomised treatment trial, which has not been shown before. Second, it is important to validate the approach by showing that individuals so identified differ from normal controls in psychological characteristics thought to be relevant to the development of psychosis; and also that a significant proportion will go on to develop full psychosis over a follow-up period.

METHOD

The report describes preliminary data from the EDIE trial.

RESULTS

Rate of transition to psychosis

An analysis of the rate of transition to psychosis is shown in Fig. 1. This shows the survival curve (up to 6 months) of those high-risk patients who have been followed up for at least 6 months (n=23) using the criteria for transition to psychosis reported by Yung et al (Reference Yung, Phillips and McGorry1998). This analysis includes patients allocated to both conditions, and treatment group is not used as a factor in the analysis in order to maintain the blind until the study is completed. At the time of writing, five of the 23 patients (22%) had made the transition to psychosis, but one patient's transition is not indicated in the figure because it occurred at month 12.

Fig. 1 Survival curve showing patients making transition to psychosis during 12-month follow-up period.

All of the five patients who have made transition (excluding those in month 1) were recruited via the attenuated symptom sub-group. Vignettes describing the symptomatology and history of those patients who made the transition to psychosis were rated by an experienced clinician (S.W.L), blind to treatment allocation and referral data, in order to determine the likely DSM—IV diagnoses. Two patients were given a diagnosis of schizophrenia, two were given a diagnosis of schizophreniform disorder and one was given a diagnosis of schizoaffective disorder.

Group comparisons on psychological measures

In this paper we report preliminary data from the patients on some of the psychological measures administered. In order to investigate differences between the high-risk group and normals on the psychological measures, comparisons were made between the scores of the present sample and data available from previous studies conducted with healthy individuals. Normal data for the OLIFE were available from a study conducted by O'Reilly et al (Reference O'Reilly, Dunbar and Bentall2001), who administered the questionnaire to 45 male and 55 female undergraduates with a mean age of 22.32 years (s.d.=3.08). No significant difference was observed between the mean age of this sample and that of the EDIE participants (t=0.06, P=0.98, 2-tailed). Data from the current sample, and also from the sample studied by O'Reilly et al (Reference O'Reilly, Dunbar and Bentall2001) are shown in Table 1. The results of t-tests revealed that the high-risk participants scored highly on all four sub-scales and that these differences remained significant even after correcting for type-1 errors by means of the Bonferroni correction (maximum acceptable P=0.0125).

Table 1 Group comparisons for Oxford—Liverpool Inventory of Feelings and Experiences sub-scales

Sub-scale	High-risk sample mean (s.d.)	Non-patients mean (s.d.)	t	P (I-tailed)
Unusual experiences	38.57 (39.32)	15.81 (6.69)	5.56	<0.001*
Cognitive disorganisation	41.07 (37.64)	14.22 (4.83)	7.00	<0.001*
Introverted anhedonia	36.04 (40.95)	4.96 (4.21)	7.52	<0.001*
Asocial behaviour	36.18 (40.61)	12.68 (3.32)	5.78	<0.001*

Comparison data for the MCQ and the SAS were available from a sample of 8 males and 42 females (undergraduate students and warehouse staff living in the same geographical area as the high-risk sample); no significant difference was observed between the mean age of this group (21.7 years, s.d.=7.71) and that of the high risk-sample (t=0.94, P=0.35, 2-tailed). In order to investigate differences between the high-risk group and the non-patients on the personality dimensions and metacognitive beliefs, a series of t-tests was conducted. It can be seen from Table 2 that high-risk patients had significantly higher scores on all dimensions of meta-cognition, except positive beliefs about worry, and scored significantly higher on fear of rejection and criticism, in comparison with non-patients. All of these comparisons survive correction for type-1 errors by the Bonnferoni method (maximum acceptable P=0.007).

Table 2 Group comparisons for Meta-Cognitions Questionnaire (MCQ) and Sociotropy—Autonomy Scale (SAS) sub-scales

Variable	High-risk sample mean (s.d.)	Non-patients mean (s.d.)	t	P (I-tailed)
MCQ
Positive beliefs about worry	36.40 (9.12)	35.85 (9.98)	0.2	n.s.
Worry about controllability	48.06 (9.68)	31.90 (8.65)	6.58	<0.001*
Cognitive confidence	24.22 (6.03)	18.51 (5.44)	3.69	<0.001*
Negative beliefs about thoughts	31.12 (7.19)	21.34 (4.93)	6.14	<0.001*
Cognitive self-consciousness	20.67 (4.99)	17.24 (4.23)	2.71	0.004*
SAS
Fear of rejection and criticism	67.02 (21.47)	53.55 (17.42)	2.79	0.004*
Need for independent goal attainment	54.20 (20.87)	60.05 (18.86)	1.21	n.s.

DISCUSSION

The present findings confirm that Yung and colleagues' approach is a viable procedure for detecting individuals who are likely to develop a psychotic illness in the very near future. Twenty-two per cent of the high-risk sample in the present study who had been followed-up for at least 6 months had made the transition to psychosis (operationally defined using the PANSS). The rate of transition in the present study is lower than that obtained by Yung et al (Reference Yung, Phillips and McGorry1998), but compares favourably with that study if those making transition in the first month are excluded.

These findings are consistent with the emerging evidence that risk indicators can predict psychotic episodes (Yung et al, 1996, Reference Yung, Phillips and McGorry1998; Reference Falloon, Kydd and CoverdaleFalloon et al, 1996; Reference Olin and MednickOlin & Mednick, 1996; Reference Miller, Lawrie and HodgesMiller et al, 2001). Risk factors identified to date have included adolescent and childhood problems, schizotypal personality (Reference Yung, Phillips and McGorryYung et al, 1998) and a family history of schizophrenia-spectrum disorders (Reference AsarnowAsarnow, 1988; Reference Miller, Lawrie and HodgesMiller et al, 2001). Recent studies have shown that the median duration of untreated psychosis is at least 12 weeks (Reference Drake, Haley and AkhtarDrake et al, 2000; Reference Ho and AndreasenHo & Andreasen, 2001), although the DUI, which includes the initial prodromal phase, is often much longer (Reference Larsen, McGlashen and MoeLarsen et al, 1996). It has also been suggested that early psychosis may represent a critical period (Reference Birchwood, McGorry and JacksonBirchwood et al, 1997), and that psychological interventions targeted at this period might reduce subsequent long-term impairment (Reference Drury, Birchwood and CochraneDrury et al, 1996; Reference Haddock, Morrison and HopkinsHaddock et al, 1998). Given the high social and economic costs of psychotic disorders, the early detection of psychosis-prone individuals in primary care, together with protocols to reduce DUP/DUI and effective early interventions, could have substantial benefits for individuals and for society (Reference Falloon, Coverdale and LaidlawFalloon et al, 1998; Reference Johannessen, Friis and VaglumJohannessen et al, 1999). The results of this study suggest that early detection of people who are likely to develop a psychotic illness in the very near future is feasible, and it is likely that regular monitoring of such individuals could reduce the DUP.

Most studies of potential indicators have used either prospective or retrospective research designs. The former include the genetic high-risk studies, which have identified children of parents with an existing disorder and followed them up over time, limiting the number of cases available for study and ignoring those people who become psychotic in the absence of a family history. Although the retrospective design enables a more representative sample of patients to be studied, research of this sort relies on the accuracy of memory or records. Yung et al's (1996, Reference Yung, Phillips and McGorry1998) method of identifying an indicated high-risk group and studying them prospectively, developed at the PACE clinic in Melbourne, Australia, represents a new approach to this problem. This study validates the adoption of such an approach in a British population. A similar but more long-term approach been described by Klosterkötter et al (Reference Klosterkötter, Hellmich and Steinmeyer2001), who reported that 70% of a clinic sample of 110 subjects who had endorsed one or more items on the Bonn Scale for Assessment of Basic Symptoms (Reference Gross, Huber and KlosterkötterGross et al, 1987) had developed DSM—IV schizophrenia at 9.6-year follow-up.

The approach taken to measuring indicators of psychosis in the present study has differed from that taken in most previous investigations, which have nearly always employed neurocognitive measures. The high scores of the present sample on the OLIFE are consistent with the hypothesis, developed by personality theorists such as Claridge (Reference Claridge1985), that disposition to psychosis is best considered a dimension. Chapman et al (Reference Chapman, Chapman and Kwapil1994) found that students scoring highly on similar measures of schizotypal traits had a relatively high risk of becoming psychotic over a 10-year follow-up period compared with normal controls. Together with the present findings, these data suggest that questionnaire measures of schizotypy may be useful screening instruments for identifying people at risk. However, an approach based on questionnaires alone is likely to suffer from a high rate of false positives, which the indicated high-risk strategy partially avoids.

Recent research suggests that neurocognitive measures may be poorly associated with positive symptoms (Reference GreenGreen, 1999). Other studies suggest that positive symptoms may be associated with meta-cognitive (Reference Baker and MorrisonBaker & Morrison, 1998; Reference Morrison and WellsMorrison & Wells, 2000), attributional and self-schema abnormalities (Reference Bentall, Corcoran and HowardBentall et al, 2001), which have not previously been assessed in high-risk paradigms. The present findings need to be treated with some caution, given the non-matched comparison samples available to us. However, the high scores obtained on the meta-cognition questionnaire sub-scales are consistent with Morrison's proposal that these kinds of beliefs play a significant role in the development of hallucinations and delusions, and the high scores on the fear of rejection and criticism component of the SAS (SAS—RCS) are consistent with current conceptualisations of the development of paranoid ideation (Reference Bentall, Corcoran and HowardBentall et al, 2001). The present findings therefore suggest that these and related variables are worthy of further investigation as potential high-risk indicators.

This improved ability to accurately define high risk achieved by Yung et al (1996, Reference Yung, Phillips and McGorry1998) and confirmed in this study has led some researchers to attempt illness prevention with atypical antipsychotic medication (Reference McGorry, Phillips and YungMcGorry et al, 1999; Reference Miller and McGlashenMiller & McGlashen, 2000). In these studies, atypical antipsychotic medications (risperidone and olanzapine, respectively) are being evaluated in randomised controlled trials in an attempt to reduce transition to psychosis. However, all treatment studies in this population have potential problems. First, treatments shown to be effective in psychotic disorders may have a different effectiveness profile in prodromal/high-risk states. Second, the specificity of prodromal/high-risk states in the prediction of later psychosis will be less than 100%, meaning that some cases, the false positives, will have been exposed to the risks of treatment unnecessarily. These limitations apply, with different emphases, both to drug and psychosocial interventions. In the existing pharmacological studies, the majority of people (the false positives) in receipt of a medication may be expected to tolerate relatively common side-effects such as pronounced weight gain and sexual dysfunction without any benefit to themselves; given the typical concerns of people in the age range at greatest risk (approximately 16-30 years), this seems highly undesirable. Less common, but more severe, side-effects (including potentially fatal problems such as neuroleptic malignant syndrome) make the use of antipsychotic medication with individuals who may never develop psychosis a highly contentious, possibly unethical, practice.

Given that the risks associated with using pharmacological interventions with false positive cases are considerable, the logical alternative would seem to be the use of psychosocial interventions. Cognitive therapy, perhaps the best researched and most widely recognised treatment of this sort, would pose little risk to the false positive group; indeed the problem-oriented nature of this intervention would mean that it is likely to be of benefit to these individuals (all people in Yung et al's group and in the present study have some level of past or current psychotic symptoms or a deterioration in functioning). Cognitive therapy is collaborative, educational and time-limited, and involves the patient and therapist working together on an agreed problem list which may prioritise problems unrelated to psychosis, such as family relationships, occupational concerns, social anxiety and depression.

Several arguments can be adduced to suggest that cognitive therapy may be particularly beneficial to high-risk groups. First, the psychological processes typically targeted during cognitive therapy include meta-cognitions and self-schemas, factors that we have argued may play a role in conferring risk of illness. Second, it has been shown in patients with established psychosis that cognitive—behavioural monitoring of prodromal signs can facilitate early intervention and relapse prevention or amelioration (Reference Birchwood, Smith and MacmillanBirchwood et al, 1989). Similarly there are a number of randomised controlled trials that have indicated the efficacy of cognitive—behavioural interventions for acute and chronic psychotic symptoms in patients with schizophrenia-spectrum diagnoses (Reference Drury, Birchwood and CochraneDrury et al, 1996; Reference Kuipers, Garety and FowlerKuipers et al, 1997; Reference Tarrier, Yusupoff and KinneyTarrier et al, 1998; Reference Sensky, Turkington and KingdonSensky et al, 2000). A final compelling rationale for the provision of cognitive—behavioural therapy to people at high risk of developing psychosis is the predominance of mood-related symptoms in psychotic prodromal states (Reference Birchwood, Haddock and SladeBirchwood, 1996). Cognitive—behavioural therapy is an effective treatment for both anxiety disorders (Reference ClarkClark, 1999) and depression (Reference Hollon, DeRubeis, Evans and SalkovskisHollon et al, 1996). When considered together, these arguments suggest that cognitive—behavioural therapy may be uniquely suitable for preventing transition to psychosis in a way that is acceptable to patients and their carers.

The EDIE project is the first study to attempt this type of intervention in a randomised clinical trial. Although it remains too early to determine whether this intervention will be effective in reducing the rate of transition as we hypothesise, it is probable that regular monitoring of this population will result in a reduction of the DUP or DUI, which on its own should be a benefit. However, a final conclusion about the effectiveness of these interventions must await the completion of the study.

CLINICAL IMPLICATIONS

1. ▪ It is possible to identify people at high risk of developing psychosis in a British population.

2. ▪ Cognitive therapy appears well suited as an intervention for such patients.

3. ▪ Clinicians should consider assessment of metacognitive beliefs and self-schemas.

LIMITATIONS

1. ▪ Data regarding the efficacy of interventions with high-risk patients are currently unavailable.

2. ▪ It is too early to determine whether psychological factors predict transition to psychosis.

3. ▪ The study is conducted in an urban population.