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.

Age of onset of cannabis use is associated with age of onset of high-risk symptoms for psychosis.

OBJECTIVE: Increasing interest in the prodromal stage of schizophrenia over the past decade led us to perform our study to monitor people at high risk for developing a psychosis. We hypothesized that cannabis use or a cannabis use disorder at a younger age relates to high-risk symptoms at a younger age. METHOD: People referred to the Academic Medical Centre in Amsterdam, the Netherlands, with an ultra-high risk (UHR) for psychosis were interviewed with the Composite International Diagnostic Interview to assess their cannabis consumption. The Interview for the Retrospective Assessment of the Onset of Schizophrenia was used to collect data about age of onset of high-risk or prodromal symptoms. Nine high-risk symptoms were selected and clustered because of their known relation with cannabis use. RESULTS: Among the 68 included participants, 35 had used cannabis (51.5%), of whom 15 had used recently. Twenty-two participants had been cannabis abusers or cannabis-dependent (32.4%) in the past. Younger age at onset of cannabis use was related to younger age of onset of the cluster of symptoms (rho = 0.48, P = 0.003) and also to 6 symptoms individually (rho = 0.47 to 0.90, P < 0.001 to 0.04). Younger age at onset of a cannabis use disorder was related to younger age of onset of the cluster of symptoms (rho = 0.67, P = 0.001) and also to 6 symptoms individually (rho = 0.50 to 0.93, P = 0.007 to 0.03). CONCLUSION: Cannabis use or a cannabis use disorder at a younger age in a group with an UHR for transition to psychosis is related to onset of high-risk symptoms for psychosis at a younger age.

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.

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).

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.

Psychosis prediction: stratification of risk estimation with information-processing and premorbid functioning variables.

BACKGROUND: The period preceding the first psychotic episode is regarded as a promising period for intervention. We aimed to develop an optimized prediction model of a first psychosis, considering different sources of information. The outcome of this model may be used for individualized risk estimation. METHODS: Sixty-one subjects clinically at high risk (CHR), participating in the Dutch Prediction of Psychosis Study, were assessed at baseline with instruments yielding data on neuropsychology, symptomatology, environmental factors, premorbid adjustment, and neurophysiology. The follow-up period was 36 months. RESULTS: At 36 months, 18 participants (29.5%) had made a transition to psychosis. Premorbid adjustment (P = .001, hazard ratio [HR] = 2.13, 95% CI = 1.39/3.28) and parietal P300 amplitude (P = .004, HR = 1.27, 95% CI = 1.08/1.45) remained as predictors in the Cox proportional hazard model. The resulting prognostic score (PS) showed a sensitivity of 88.9% and a specificity of 82.5%. The area under the curve of the PS was 0.91 (95% CI = 0.83-0.98, cross-validation: 0.86), indicating an outstanding ability of the model to discriminate between transition and nontransition. The PS was further stratified into 3 risk classes establishing a prognostic index. In the class with the worst social-personal adjustment and lowest P300 amplitudes, 74% of the subjects made a transition to psychosis. Furthermore, transition emerged on average more than 17 months earlier than in the lowest risk class. CONCLUSIONS: Our results suggest that predicting a first psychotic episode in CHR subjects could be improved with a model including premorbid adjustment and information-processing variables in a multistep algorithm combining risk detection and stratification.

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.

Environmental factors and social adjustment as predictors of a first psychosis in subjects at ultra high risk.

BACKGROUND: The onset of schizophrenia is associated with genetic, symptomatic, social and environmental risk factors. The aim of the present study was to determine which environmental factors may contribute to a prediction of a first psychotic episode in subjects at Ultra High Risk (UHR) for developing psychosis. METHOD: We included 72 UHR subjects and followed them over a period of 36 months, of whom nineteen (26.4%) made a transition to psychosis. We applied survival analyses to determine associations between a transition to psychosis and environmental factors and social adjustment. To determine which items are the best predictors of transition to a first psychotic episode, Cox Regression analyses were applied. RESULTS: Urbanicity, receiving state benefits and poor premorbid adjustment (PMA) significantly influenced the transition to psychosis. Urbanicity (Wald=10.096, p=.001, HR=30.97), social-sexual aspects (Wald=8.795, p=.003, HR=1.91) and social-personal adjustment (Wald=10.794, p=.001, HR=4.26) appeared to be predictors for developing psychosis in our UHR group. CONCLUSIONS: Environmental characteristics and social adjustment are predictive of transition to a psychosis in subjects at UHR. These characteristics should be implemented in a model for prediction of psychosis. Such a model would be more specific than current models and may lead to patient-specific preventive interventions.

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.