Psychotic-like experiences and multimorbid psychopathology: The relationship between the 16-item prodromal questionnaire and DSM-IV classifications in a help-seeking population.

AIM: Identifying multimorbid psychopathology is necessary to offer more adequate treatment and ultimately reduce the prevalence of persistent mental illnesses. Psychotic symptoms are increasingly seen as a transdiagnostic indicator of multimorbidity, severity and complexity of non-psychotic psychopathology. This study aims to investigate whether psychotic-like experiences and subclinical psychotic symptoms as measured by the 16-item Prodromal Questionnaire are also associated with multimorbid psychopathology. METHODS: Participants were help-seeking individuals from outpatient mental healthcare settings and intensive home-treatment teams, aged 17-35. Assessment included the 16-item Prodromal Questionnaire to measure psychotic-like experiences, the Structured Clinical Interview for DSM-IV Axis I, and three sections of the Structured Clinical Interview for DSM-IV Axis II Disorders to determine DSM-IV-TR classifications. The final sample comprised of 160 participants who scored above a cutoff of 6 items on the 16-item Prodromal Questionnaire (HIGH-score) and 60 participants who scored below cutoff (LOW-score). A Poisson Regression was executed to determine the association between the PQ-16 and DSM-IV-TR classifications. RESULTS: The HIGH-score group had a mean of 2.76 multimorbid disorders (range 0-7), while the LOW-score group had a mean of 1.45 disorders (range 0-3). Participants with four to seven disorders scored high on the 16-item Prodromal Questionnaire. CONCLUSIONS: Our results suggest that psychotic-like experiences are associated with multimorbidity and severity of psychopathology. Screening for psychotic-like experiences via the PQ-16 in a help-seeking population may help prevent under-diagnosis and under-treatment of comorbid psychopathology.

The association between migrant status and transition in an ultra-high risk for psychosis population.

PURPOSE: Migrant status is one of the most replicated and robust risk factors for developing a psychotic disorder. This study aimed to determine whether migrant status in people identified as Ultra-High Risk for Psychosis (UHR) was associated with risk of transitioning to a full-threshold psychotic disorder. METHODS: Hazard ratios for the risk of transition were calculated from five large UHR cohorts (n = 2166) and were used to conduct a meta-analysis using the generic inverse-variance method using a random-effects model. RESULTS: 2166 UHR young people, with a mean age of 19.1 years (SD ± 4.5) were included, of whom 221 (10.7%) were first-generation migrants. A total of 357 young people transitioned to psychosis over a median follow-up time of 417 days (I.Q.R.147-756 days), representing 17.0% of the cohort. The risk of transition to a full-threshold disorder was not increased for first-generation migrants, (HR = 1.08, 95% CI 0.62-1.89); however, there was a high level of heterogeneity between studies The hazard ratio for second-generation migrants to transition to a full-threshold psychotic disorder compared to the remainder of the native-born population was 1.03 (95% CI 0.70-1.51). CONCLUSIONS: This meta-analysis did not find a statistically significant association between migrant status and an increased risk for transition to a full-threshold psychotic disorder; however, several methodological issues could explain this finding. Further research should focus on examining the risk of specific migrant groups and also ensuring that migrant populations are adequately represented within UHR clinics.

Cost-Effectiveness of Virtual Reality Cognitive Behavioral Therapy for Psychosis: Health-Economic Evaluation Within a Randomized Controlled Trial.

BACKGROUND: Evidence was found for the effectiveness of virtual reality-based cognitive behavioral therapy (VR-CBT) for treating paranoia in psychosis, but health-economic evaluations are lacking. OBJECTIVE: This study aimed to determine the short-term cost-effectiveness of VR-CBT. METHODS: The health-economic evaluation was embedded in a randomized controlled trial evaluating VR-CBT in 116 patients with a psychotic disorder suffering from paranoid ideation. The control group (n=58) received treatment as usual (TAU) for psychotic disorders in accordance with the clinical guidelines. The experimental group (n=58) received TAU complemented with add-on VR-CBT to reduce paranoid ideation and social avoidance. Data were collected at baseline and at 3 and 6 months postbaseline. Treatment response was defined as a pre-post improvement of symptoms of at least 20% in social participation measures. Change in quality-adjusted life years (QALYs) was estimated by using Sanderson et al's conversion factor to map a change in the standardized mean difference of Green's Paranoid Thoughts Scale score on a corresponding change in utility. The incremental cost-effectiveness ratios were calculated using 5000 bootstraps of seemingly unrelated regression equations of costs and effects. The cost-effectiveness acceptability curves were graphed for the costs per treatment responder gained and per QALY gained. RESULTS: The average mean incremental costs for a treatment responder on social participation ranged between €8079 and €19,525, with 90.74%-99.74% showing improvement. The average incremental cost per QALY was €48,868 over the 6 months of follow-up, with 99.98% showing improved QALYs. Sensitivity analyses show costs to be lower when relevant baseline differences were included in the analysis. Average costs per treatment responder now ranged between €6800 and €16,597, while the average cost per QALY gained was €42,030. CONCLUSIONS: This study demonstrates that offering VR-CBT to patients with paranoid delusions is an economically viable approach toward improving patients' health in a cost-effective manner. Long-term effects need further research. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 12929657; http://www.isrctn.com/ISRCTN12929657.

Designing and Testing of a Health-Economic Markov Model for Prevention and Treatment of Early Psychosis.

BACKGROUND: This study aims to report on the design of a model to determine the cost-effectiveness of prevention and treatment of early psychosis (PsyMod) and to estimate ten-year cost-effectiveness and budget impact of interventions targeting individuals with ultra-high risk (UHR) of developing psychosis or with first episode psychosis (FEP). METHODS: PsyMod was built in parallel with the development of a new standard of care for treatment of early psychosis in the Netherlands. PsyMod is a state-transition cohort simulation model and considers six health states, namely ultra-high risk of psychosis (UHR), FEP, post-FEP, no-UHR, recovery/remission, and death. Results are expressed as total healthcare costs, QALYs, incremental cost-effectiveness ratio (ICER), and budget impact. RESULTS: PsyMod was used to extrapolate budget impact and cost-effectiveness of cognitive behavioural therapy for preventing FEP for individuals at UHR of psychosis (CBTuhr) compared to care as usual. CBTuhr resulted in a per-patient increase of 0.06 QALYs and a per patient cost reduction of €654 (dominant ICER) with a reduction in 5-year healthcare costs of €1,002,166. CONCLUSIONS: PsyMod can be used to examine cost-effectiveness and budget impact of interventions targeting prevention and treatment of FEP and is freely available for academic purposes upon request by the authors.

Individualized Prediction of Transition to Psychosis in 1,676 Individuals at Clinical High Risk: Development and Validation of a Multivariable Prediction Model Based on Individual Patient Data Meta-Analysis.

Background: The Clinical High Risk state for Psychosis (CHR-P) has become the cornerstone of modern preventive psychiatry. The next stage of clinical advancements rests on the ability to formulate a more accurate prognostic estimate at the individual subject level. Individual Participant Data Meta-Analyses (IPD-MA) are robust evidence synthesis methods that can also offer powerful approaches to the development and validation of personalized prognostic models. The aim of the study was to develop and validate an individualized, clinically based prognostic model for forecasting transition to psychosis from a CHR-P stage. Methods: A literature search was performed between January 30, 2016, and February 6, 2016, consulting PubMed, Psychinfo, Picarta, Embase, and ISI Web of Science, using search terms ("ultra high risk" OR "clinical high risk" OR "at risk mental state") AND [(conver* OR transition* OR onset OR emerg* OR develop*) AND psychosis] for both longitudinal and intervention CHR-P studies. Clinical knowledge was used to a priori select predictors: age, gender, CHR-P subgroup, the severity of attenuated positive psychotic symptoms, the severity of attenuated negative psychotic symptoms, and level of functioning at baseline. The model, thus, developed was validated with an extended form of internal validation. Results: Fifteen of the 43 studies identified agreed to share IPD, for a total sample size of 1,676. There was a high level of heterogeneity between the CHR-P studies with regard to inclusion criteria, type of assessment instruments, transition criteria, preventive treatment offered. The internally validated prognostic performance of the model was higher than chance but only moderate [Harrell's C-statistic 0.655, 95% confidence interval (CIs), 0.627-0.682]. Conclusion: This is the first IPD-MA conducted in the largest samples of CHR-P ever collected to date. An individualized prognostic model based on clinical predictors available in clinical routine was developed and internally validated, reaching only moderate prognostic performance. Although personalized risk prediction is of great value in the clinical practice, future developments are essential, including the refinement of the prognostic model and its external validation. However, because of the current high diagnostic, prognostic, and therapeutic heterogeneity of CHR-P studies, IPD-MAs in this population may have an limited intrinsic power to deliver robust prognostic models.

CBT in the prevention of psychosis and other severe mental disorders in patients with an at risk mental state: A review and proposed next steps.

Patients with an 'At risk mental state' (ARMS) for developing psychosis can be treated successfully with CBT to postpone and prevent the transition to a first psychotic episode. A characteristic of individuals that meet ARMS criteria is that they are still open for multiple explanations for extraordinary experiences. CBT aims to normalize extraordinary experiences with education and to prevent delusional explanations. The treatment is not only effective, but also cost-saving in averting psychosis as well as in reducing disability adjusted life years at 18- and 48-month follow-up. Profiling within the ARMS group results in a personalized treatment. The screening and early treatment for ARMS fulfills all the criteria of the World Health Organization and is ready to be routine screening and treatment in mental health care. At the same time, ARMS patients are complex patients with multi-morbid disorders. Especially childhood trauma is associated to ARMS status, together with co-morbid PTSD, depression, substance abuse and anxiety disorders. Psychotic symptoms appear to be severity markers in other non-psychotic disorders. Preventing psychosis in ARMS patients should be broadened to also address other disorders and aim to reduce chronicity of psychopathology and improve social functioning in general. Several mechanisms play a part in psychopathology in ARMS patients such as stress sensitivity as a result of adverse experiences, dopamine sensitivity that is associated with salience and aggravates several cognitive biases, dissociation mediating between trauma and hallucinations, and low self-esteem and self-stigma. New avenues to treat the complexity of ARMS patients will be proposed.

Ultrahigh risk for developing psychosis and psychotic personality organization.

AIMS: Childhood adversities combined with unsafe parenting may disturb personality development. This study investigated whether psychotic personality organization as defined by Kernberg and assessed with de Dutch Short Form of the MMPI (DSFM) is more prevalent in ultrahigh risk (UHR) for psychosis compared with non-psychotic psychiatric control patients (NPPC). METHODS: A total of 73 UHR and 119 NPPC patients were assessed with the DSFM and the Comprehensive Assessment of at Risk Mental States (CAARMS). RESULTS: The results showed that the psychotic personality organization (PPO) was not associated to UHR status. The UHR group showed more severe symptoms, particularly higher scores on DSFM subscales negativism (negative affect) and somatization (vague somatic complaints) and severe psychopathology (psychotic symptoms and dissociation). CONCLUSION: The PPO profile is not associated to the risk of developing psychosis.

Four-Year Cost-effectiveness of Cognitive Behavior Therapy for Preventing First-episode Psychosis: The Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial.

Background: This study aims to evaluate the long-term cost-effectiveness of add-on cognitive behavior therapy (CBT) for the prevention of psychosis for individuals at ultrahigh risk (UHR) of psychosis. Method: The Dutch Early Detection and Intervention randomized controlled trial was used, comparing routine care (RC; n = 101) with routine care plus CBT for UHR (here called CBTuhr; n = 95). A cost-effectiveness analysis was conducted with treatment response (defined as proportion of averted transitions to psychosis) as an outcome and a cost-utility analysis with quality-adjusted life years (QALYs) gained as a secondary outcome. Results: The proportion of averted transitions to psychosis was significantly higher in the CBTuhr condition (with a risk difference of 0.122; b = 1.324, SEb = 0.017, z = 7.99, P < 0.001). CBTuhr showed an 83% probability of being more effective and less costly than RC by -US$ 5777 (savings) per participant. In addition, over the 4-year follow-up period, cumulative QALY health gains were marginally (but not significantly) higher in CBTuhr than for RC (2.63 vs. 2.46) and the CBTuhr intervention had a 75% probability of being the superior treatment (more QALY gains at lower costs) and a 92% probability of being cost-effective compared with RC at the Dutch threshold value (US$ 24 560; €20 000 per QALY). Conclusions: Add-on preventive CBTuhr had a high likelihood (83%) of resulting in more averted transitions to psychosis and lower costs as compared with RC. In addition, the intervention had a high likelihood (75%) of resulting in more QALY gains and lower costs as compared to RC.

The effect of childhood adversity on 4-year outcome in individuals at ultra high risk for psychosis in the Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial.

Childhood adversity is associated with a range of mental disorders, functional impairment and higher health care costs in adulthood. In this study we evaluated if childhood adversity was predictive of adverse clinical and functional outcomes and health care costs in a sample of patients at ultra-high risk (UHR) for developing a psychosis. Structural Equation Modeling was used to examine the effect of childhood adversity on depression, anxiety, transition to psychosis and overall functioning at 4-year follow-up. In addition, we evaluated economic costs of childhood adversity in terms of health care use and productivity loss. Data pertain to 105 UHR participants of the Dutch Early Detection and Intervention Evaluation (EDIE-NL). Physical abuse was associated with higher depression rates (b=0.381, p=0.012) and lower social functional outcome (b=-0.219, p=0.017) at 4-year follow-up. In addition, emotional neglect was negatively associated with social functioning (b=-0.313, p=0.018). We did not find evidence that childhood adversity was associated with transition to psychosis, but the experience of childhood adversity was associated with excess health care costs at follow-up. The data indicate long-term negative effects of childhood adversity on depression, social functioning and health care costs at follow-up in a sample of UHR patients.

The Prodromal Questionnaire: a case for IRT-based adaptive testing of psychotic experiences?

Computerized adaptive tests (CATs) for positive and negative psychotic experiences were developed and tested in N = 5705 help-seeking, non-psychotic young individuals. Instead of presenting all items, CATs choose a varying number of different items during test administration depending on respondents' previous answers, reducing the average number of items while still obtaining accurate person estimates. We assessed the appropriateness of two-parameter logistic models to positive and negative symptoms of the Prodromal Questionnaire (PQ), computed measurement precision of all items and resulting adaptive tests along psychotic dimensions by Real Data Simulations (RDS), and computed indices for criterion and predictive validities of the CATs. For all items, mean absolute differences between observed and expected response probabilities were smaller than 0.02. CAT-POS predicted transition to psychosis and duration of hospitalization in individuals at-risk for psychosis, and CAT-NEG was suggestively related to later functioning. Regarding psychosis risk classifications of help-seeking individuals, CAT-POS performed less than the PQ-16. Adaptive testing based on self-reported positive and negative symptoms in individuals at-risk for psychosis is a feasible method to select patients for further risk classification. These promising findings need to be replicated prospectively in a non-selective sample that also includes non-at-risk individuals. Copyright © 2016 John Wiley & Sons, Ltd.

Exposing therapists to trauma-focused treatment in psychosis: effects on credibility, expected burden, and harm expectancies.

BACKGROUND: Despite robust empirical support for the efficacy of trauma-focused treatments, the dissemination proves difficult, especially in relation to patients with comorbid psychosis. Many therapists endorse negative beliefs about the credibility, burden, and harm of such treatment. OBJECTIVE: This feasibility study explores the impact of specialized training on therapists' beliefs about trauma-focused treatment within a randomized controlled trial. METHOD: Therapist-rated (n=16) credibility, expected burden, and harm expectancies of trauma-focused treatment were assessed at baseline, post-theoretical training, post-technical training, post-supervised practical training, and at 2-year follow-up. Credibility and burden beliefs of therapists concerning the treatment of every specific patient in the trial were also assessed. RESULTS: Over time, therapist-rated credibility of trauma-focused treatment showed a significant increase, whereas therapists' expected burden and harm expectancies decreased significantly. In treating posttraumatic stress disorder (PTSD) in patients with psychotic disorders (n=79), pre-treatment symptom severity was not associated with therapist-rated credibility or expected burden of that specific treatment. Treatment outcome had no influence on patient-specific credibility or burden expectancies of therapists. CONCLUSIONS: These findings support the notion that specialized training, including practical training with supervision, has long-term positive effects on therapists' credibility, burden, and harm beliefs concerning trauma-focused treatment.

Predicting trauma-focused treatment outcome in psychosis.

OBJECTIVE: Although TF treatments are effective in patients with psychosis, it is unknown whether specific psychosis-related obstacles limit the effects, and what determines good outcome. METHODS: Baseline posttraumatic stress disorder (PTSD) symptom severity and seven psychosis-specific variables were tested as predictors in patients with a psychotic disorder and PTSD (n=108), who received eight sessions of TF treatment (Prolonged Exposure, or Eye Movement Desensitization and Reprocessing therapy) in a single-blind randomized controlled trial. Multiple regression analyses were performed. RESULTS: Baseline PTSD symptom severity was significantly associated with posttreatment PTSD symptom severity, explaining 11.4% of the variance. Additionally, more severe PTSD at baseline was also significantly associated with greater PTSD symptom improvement during treatment. After correction for baseline PTSD symptom severity, the model with the seven baseline variables did not significantly explain the variance in posttreatment PTSD outcome. Within this non-significant model, the presence of auditory verbal hallucinations contributed uniquely to posttreatment outcome but explained little variance (5.4%). Treatment completers and dropouts showed no significant difference on any of the psychosis-related variables. CONCLUSIONS: Given the low predictive utility of baseline psychosis-related factors, we conclude that there is no evidence-based reason to exclude patients with psychotic disorders from TF treatments. Also, we speculate that patients with psychosis and severe baseline PTSD might derive more benefit if given more than eight sessions. Trial registration current controlled-trials.com | Identifier: ISRCTN79584912 | http://www.isrctn.com/ISRCTN79584912.

COMT Val(158)Met genotype and cannabis use in people with an At Risk Mental State for psychosis: Exploring Gene x Environment interactions.

BACKGROUND: Epidemiological and retrospective studies suggest a cannabis x catechol-O-methyltransferase (COMT) Val(158)Met interaction effect on development of psychosis. The aim of this study was to examine this interaction and its association with severity of subclinical symptoms in people with an At Risk Mental State (ARMS) for psychosis. METHODS: Severity of symptoms, cannabis use and genotype were assessed at baseline in 147 help-seeking young adults who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. RESULTS: Cannabis use and COMT Val-allele showed an interaction effect in ARMS subjects. Subjects who were weekly cannabis users at some point prior to entering the study showed more severe positive symptoms. This effect increased if they were carriers of the COMT Val-allele and even more so if they were homozygous for the Val-allele. CONCLUSIONS: Our results suggest that the COMT Val(158)Met polymorphism moderates the effect of regular cannabis use on severity of subclinical psychotic symptoms.

Four-Year Follow-up of Cognitive Behavioral Therapy in Persons at Ultra-High Risk for Developing Psychosis: The Dutch Early Detection Intervention Evaluation (EDIE-NL) Trial.

BACKGROUND: Previously, we demonstrated that cognitive behavior therapy for ultra-high risk (called CBTuhr) halved the incidence of psychosis over an 18-month period. Follow-up data from the same study are used to evaluate the longer-term effects at 4 years post-baseline. METHOD: The Dutch Early Detection and Intervention Evaluation study was a randomized controlled trial of 196 UHR patients comparing CBTuhr with treatment-as-usual (TAU) for comorbid disorders with TAU only. Of the original 196 patients, 113 consented to a 4-year follow-up (57.7%; CBTuhr = 56 vs TAU = 57). Over the study period, psychosis incidence, remission from UHR status, and the effects of transition to psychosis were evaluated. RESULTS: The number of participants in the CBTuhr group making the transition to psychosis increased from 10 at 18-month follow-up to 12 at 4-year follow-up whereas it did not change in the TAU group (n = 22); this still represents a clinically important (incidence rate ratio [IRR] = 12/22 = 0.55) and significant effect (F(1,5) = 8.09, P = .03), favoring CBTuhr. The odds ratio of CBTuhr compared to TAU was 0.44 (95% CI: 0.24-0.82) and the number needed to treat was 8. Moreover, significantly more patients remitted from their UHR status in the CBTuhr group (76.3%) compared with the TAU group (58.7%) [t(120) = 2.08, P = .04]. Importantly, transition to psychosis was associated with more severe psychopathology and social functioning at 4-year follow-up. CONCLUSIONS: CBTuhr to prevent a first episode of psychosis in persons at UHR of developing psychosis is still effective at 4-year follow-up. Our data also show that individuals meeting the formal criteria of a psychotic disorder have worse functional and social outcomes compared with non-transitioned cases. TRIAL REGISTRATION: The trial is registered at Current Controlled Trials as trial number ISRCTN21353122 (http://controlled-trials.com/ISRCTN21353122/gaag).

The distribution of self-reported psychotic-like experiences in non-psychotic help-seeking mental health patients in the general population; a factor mixture analysis.

PURPOSE: Factor mixture analysis (FMA) and item response mixture models in the general population have shown that the psychosis phenotype has four classes. This study attempted to replicate this finding in help-seeking people accessing mental health services for symptoms of non-psychotic mental disorders. METHODS: All patients (18-35 years old) referred for non-psychotic mental health problems to the secondary mental healthcare service in The Hague between February 2008 to February 2010 (N = 3,694), were included. Patients completed the Prodromal Questionnaire (PQ). Hybrid latent class analysis was applied to explore the number, size and symptom profiles of the classes. RESULTS: The FMA resulted in four classes. Class 1 (N = 1,039, 28.1%) scored high on conceptual disorganization, inattention and mood disorder. Patients in Class 2 (N = 619, 16.8%) endorsed almost all PQ-items, were more often screened as being psychotic or at high risk of developing psychosis, without care takers noticing. In Class 3 (N = 1,747, 47.3%) perplexity, paranoia and negative symptoms were more prevalent. Patients were more often at high risk of developing psychosis. Class 4 (N = 286, 7.7%) represented the 'normative' group with low probabilities for all items. DISCUSSION: The results support the hypothesis that a representation in four classes of psychotic-like experiences can also be applied in a help-seeking population.

Depression and social anxiety in help-seeking patients with an ultra-high risk for developing psychosis.

Knowledge on associations between ultra-high risk (UHR) for developing psychosis and on non-psychotic psychopathology in help-seeking populations is limited with respect to differences between male and female patients. The present study tests the hypothesis that both social anxiety and depression are highly prevalent in an UHR population, particularly among women. From February 2008 to February 2010 baseline data were collected from help-seeking subjects (14-35 years) who were included in the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial. Two recruiting strategies were used: a two-stage screening strategy in a population of consecutive help-seeking and distressed subjects of secondary mental health services, and a referral strategy. This study included 201 patients with a mean age of 22.7 years. Of these, 102 (51%) were female, 58% of the patients met the criteria for clinical depression on the Beck Depression Inventory and 42% met the criteria for clinical social phobia on the Social Interaction Anxiety Scale. Women showed more depression and social anxiety than men. The results support the hypothesis that UHR is associated with depression and social anxiety, particularly in women. Screening a help-seeking population with depression and anxiety may be effective in detecting patients at UHR for developing psychosis.

Cognitive behavioral therapy for subjects at ultrahigh risk for developing psychosis: a randomized controlled clinical trial.

BACKGROUND: Evidence for the effectiveness of treatments for subjects at ultrahigh risk (UHR) for developing psychosis remains inconclusive. OBJECTIVE: A new cognitive behavioral intervention specifically targeted at cognitive biases (ie, Cognitive Behavioral Therapy [CBT] for UHR patients plus treatment as usual [TAU] called CBTuhr) is compared with TAU in a group of young help-seeking UHR subjects. METHODS: A total of 201 patients were recruited at 4 sites and randomized. In most cases, CBTuhr was an add-on therapy because most people were seeking help for a comorbid disorder. The CBT was provided for 6 months, and the follow-up period was 18 months. RESULTS: In the CBTuhr condition, 10 patients transitioned to psychosis compared with 22 in the TAU condition (χ(2) (1) = 5.575, P = .03). The number needed to treat (NNT) was 9 (95% confidence interval [CI]: 4.7-89.9). At 18-month follow-up the CBTuhr group was significantly more often remitted from an at-risk mental state, with a NNT of 7 (95% CI: 3.7-71.2). Intention-to-treat analysis, including 5 violations against exclusion criteria, showed a statistical tendency (χ(2) (1) = 3.338, P = .06). CONCLUSIONS: Compared with TAU, this new CBT (focusing on normalization and awareness of cognitive biases) showed a favorable effect on the transition to psychosis and reduction of subclinical psychotic symptoms in subjects at UHR to develop psychosis.

The validity of the 16-item version of the Prodromal Questionnaire (PQ-16) to screen for ultra high risk of developing psychosis in the general help-seeking population.

In order to bring about implementation of routine screening for psychosis risk, a brief version of the Prodromal Questionnaire (PQ; Loewy et al., 2005) was developed and tested in a general help-seeking population. We assessed a consecutive patient sample of 3533 young adults who were help-seeking for nonpsychotic disorders at the secondary mental health services in The Hague with the PQ. We performed logistic regression analyses and CHi-squared Automatic Interaction Detector decision tree analysis to shorten the original 92 items. Receiver operating characteristic curves were used to examine the psychometric properties of the PQ-16. In the general help-seeking population, a cutoff score of 6 or more positively answered items on the 16-item version of the PQ produced correct classification of Comprehensive Assessment of At-Risk Mental State (Yung et al., 2005) psychosis risk/clinical psychosis in 44% of the cases, distinguishing Comprehensive Assessment of At-Risk Mental States (CAARMS) diagnosis from no CAARMS diagnosis with high sensitivity (87%) and specificity (87%). These results were comparable to the PQ-92. The PQ-16 is a good self-report screen for use in secondary mental health care services to select subjects for interviewing for psychosis risk. The low number of items makes it quite appropriate for screening large help-seeking populations, thus enhancing the feasibility of detection and treatment of ultra high-risk patients in routine mental health services.

A single blind randomized controlled trial of cognitive behavioural therapy in a help-seeking population with an At Risk Mental State for psychosis: the Dutch Early Detection and Intervention Evaluation (EDIE-NL) trial.

BACKGROUND: Psychotic disorders are a serious mental health problem. Intervention before the onset of psychosis might result in delaying the onset, reducing the impact or even preventing the first episode of psychosis. This study explores the effectiveness of cognitive behavioural therapy (CBT) in targeting cognitive biases that are involved in the formation of delusions in persons with an ultra-high risk for developing psychosis. A single blind randomised controlled trial compares CBT with treatment as usual in preventing or delaying the onset of psychosis. METHOD/DESIGN: All help seeking patients aged 14 to 35 years referred to the mental health services in three regions in the Netherlands are pre-screened with the Prodromal Questionnaire during a period of two years. Patients with a score of 18 or more on the sub-clinical positive symptoms items (45 items in total) will be assessed with the Comprehensive Assessment of At Risk Mental State (CAARMS). In a different pathway to care model all referrals from the mental health services in Amsterdam to the specialized psychosis clinic of the Academic Medical Centre in Amsterdam are also assessed with the CAARMS. The primary outcome is the transition rate to psychosis according to the CAARMS-criteria. Group differences will be analysed with chi-square tests and survival analyses. DISCUSSION: CBT is a highly tolerated treatment. The psycho-educational CBT approach may prove to be a successful strategy since most people with an At Risk Mental State (ARMS) are distressed by odd disturbing experiences. Giving explanations for and normalising these experiences may reduce the arousal (distress) and therefore may prevent people from developing a catastrophic delusional explanation for their odd experiences and thus prevent them from developing psychosis.Screening the entire help-seeking population referred to community mental health services with a two-stage strategy, as compared with traditional referral to a specialist clinical psychosis centre, might detect more ultra-high-risk (UHR) patients. This type of screening could be implemented in mental health care as routine screening. The trial is registered at Current Controlled trials as trial number ISRCTN21353122.