Changing vistas of psychosis and antipsychotic drug dosing toward personalized management of antipsychotics in clinical practice.

OBJECTIVE: To discuss current evidence on tapering antipsychotic drugs in view of changing vistas of psychosis, suggesting a provisional framework for safely tapering antipsychotic drugs to an optimal low dose, in collaboration with patients and their relatives, to promote functional recovery while preventing relapse. METHODS: Paradigm shifts during recent years regarding the nature of psychotic disorders and the role of the dopamine system are discussed, including the positive effects of dopamine blockade in acute psychosis and the limitations and drawbacks of dopamine blockade regarding negative and cognitive symptoms after remission of positive symptoms. Recent advances in tapering strategies and upcoming ways to solve the dilemma between the need to prevent relapses with antipsychotics on the one hand and the need to minimize side effects by tapering these drugs on the other are presented. RESULTS: Modern tapering strategies appear to reduce relapse risk to acceptable levels and offer a feasible personalized option to find the least effective dose to treat and prevent positive symptoms without redundant side effects and functional incapacity. These findings need replication, and several trials that might provide more certainty are on their way. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Preliminary evidence and clinical experience indicate that personalized dose reduction of antipsychotics is feasible and safe if carried out in close collaboration with patients and their relatives, according to a provisionally suggested framework presented here. These preliminary directions still must be confirmed, revised, and adjusted according to upcoming trial results. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Five-year outcome of clinical recovery and subjective well-being in older Dutch patients with schizophrenia.

Outcome of schizophrenia in later life can be evaluated from different perspectives. The recovery concept has moved forward this evaluation, discerning clinical-based and patient-based definitions. Longitudinal data on measures of recovery in older individuals with schizophrenia are scant. This study evaluated the five-year outcome of clinical recovery and subjective well-being in a sample of 73 older Dutch schizophrenia patients (mean age 65.9 years; SD 5.4), employing a catchment-area based design that included both community living and institutionalized patients regardless of the age of onset of their disorder. At baseline (T1), 5.5% of participants qualified for clinical recovery, while at five-year follow-up (T2), this rate was 12.3% (p = 0.18; exact McNemar's test). Subjective well-being was reported by 20.5% of participants at T1 and by 27.4% at T2 (p = 0.27; exact McNemar's test). Concurrence of clinical recovery and subjective well-being was exceptional, being present in only one participant (1.4%) at T1 and in two participants (2.7%) at T2. Clinical recovery and subjective well-being were not correlated neither at T1 (p = 0.82; phi = 0.027) nor at T2 (p = 0.71; phi = -0.044). There was no significant correlation over time between clinical recovery at T1 and subjective well-being at T2 (p = 0.30; phi = 0.122) nor between subjective well-being at T1 and clinical recovery at T2 (p = 0.45; phi = -0.088). These results indicate that while reaching clinical recovery is relatively rare in older individuals with schizophrenia, it is not a prerequisite to experience subjective well-being.

Reprint of: Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy.

BACKGROUND: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. METHODS: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. OUTCOMES: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. INTERPRETATION: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.

Onset and transition of and recovery from adverse development: Study methodology.

AIM: Early intervention programs for first-episode psychosis have led to the awareness that the period before onset of a first episode is important in light of early intervention. This has induced a focus on the so-called 'at risk mental state' (ARMS). Individuals with ARMS are at increased risk for later psychotic disorder, but also for other psychiatric disorders as well as poor psychosocial functioning. Thus, adequate detection and treatment of ARMS is essential. METHODS: Since 2018, screening for and treatment of ARMS is recommended standard care in the Netherlands. Implementation is still ongoing. We initiated a naturalistic long-term cohort study of ARMS individuals, the onset and transition of and recovery from adverse development (OnTheROAD) study, with the aim to monitor course and outcome of symptoms and psychosocial functioning over time, as well as patterns of comorbidity and associations with factors of risk and resilience. To this end, participants complete a broad battery of instruments at baseline and yearly follow-up assessments up to 3 years. Outcome is defined in terms of symptom severity level, functioning and quality of life. In particular, we aim to investigate the impact of negative symptoms as part of the ARMS concept. Results from this study can aid in refining the existing ARMS criteria, understanding the developmental course of ARMS and investigating the hypothesized pluripotentiality in outcome of ARMS. New knowledge may inform the further development of specialized early interventions. RESULTS AND CONCLUSIONS: In this article, we describe the rationale, outline and set-up of OnTheROAD.

Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy.

BACKGROUND: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. METHODS: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. OUTCOMES: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. INTERPRETATION: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients.

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.

Course and predictors of symptomatic remission in late-life schizophrenia: A 5-year follow-up study in a Dutch psychiatric catchment area.

BACKGROUND: The number of older schizophrenia patients is growing, the majority being treated in outpatient settings. Reported symptomatic remission rates in younger cohorts vary largely. Further insight into course trajectories and putative predictors of remission in older persons with schizophrenia is needed. METHODS: 5-year follow-up course trajectories of symptomatic remission were examined in a catchment area-based group of 77 older Dutch patients (mean age 66.0 years) with schizophrenia or schizoaffective disorder. A modified version of the 'Remission in Schizophrenia Working Group' criteria was used to determine remission status. In individuals who did not fulfil remission criteria at baseline (n = 56), predictors of conversion to remission status at 5-year follow-up were analysed using multivariable regression analyses. RESULTS: A substantial increase in remission rate at 5-year follow-up (27.3% at baseline (T1), 49.4% at follow-up (T2)) was found. Of all participants, 23.4% was in remission at both assessments and 46.8% was in non-remission at both assessments. 26.0% of the participants converted from non-remission at T1 to remission at T2, while 3.9% fell back from remission at T1 to non-remission at T2. Two significant baseline predictors of conversion to remission at follow-up were found: lower score on the PANSS positive symptom subscale, and having a partner. CONCLUSION: Symptomatic remission was as an attainable goal for almost half of all older patients with schizophrenia or schizoaffective disorder at 5-year follow-up. With a lower PANSS positive symptom subscale score, and having a partner emerging as the only predictors of conversion to remission, there remains a need to search for modifiable predictors.

Personalizing antipsychotic treatment: evidence and thoughts on individualized tailoring of antipsychotic dosage in the treatment of psychotic disorders.

Effectiveness of relapse prevention with antipsychotic drugs has been robustly demonstrated. However, the drawbacks of antipsychotic maintenance treatment have prompted alternative strategies to reduce antipsychotic load. A prominent drawback of antipsychotics is their negative impact on subjective well-being, initiative, and drive related to dopamine D2 blockade. This might compromise functional capacity. First-episode studies from 1980 to 2018, including relevant reviews and meta-analyses, are evaluated, showing a lack of functional outcome data. In addition to relapse rates, which is the primary outcome in the great majority of studies, long-term functional outcome is pivotal, because these two outcome domains may point in opposite directions. The trade-off between relapse rates and functional outcome is discussed by our 2013 dose-reduction study. We conclude that divergent outcomes and various individual risk-profiles preclude the construction of a generic outcome measure. The relationship of relapse and functional outcome is considered, as well as the conceivable role of negative symptoms and some related issues. Future profiling of individual risk/benefit characteristics combined with personal preferences may offer better guidance in antipsychotic pharmacotherapy. More studies are needed to elucidate individual risk profiles, predictive of functional capacity and relapse rates, to draw differential conclusions on long-term risks and benefits of antipsychotics across the spectrum of psychosis.

Searching for the optimal number of response alternatives for the distress scale of the four-dimensional symptom questionnaire.

BACKGROUND: The Four-Dimensional Symptom Questionnaire (4DSQ) is a self-report questionnaire designed to measure distress, depression, anxiety, and somatization. Prior to computing scale scores from the item scores, the three highest response alternatives ('Regularly', 'Often', and 'Very often or constantly present') are usually collapsed into one category to reduce the influence of extreme responding on item- and scale scores. In this study, we evaluate the usefulness of this transformation for the distress scale based on a variety of criteria. METHODS: Specifically, by using the Graded Response Model, we investigated the effect of this transformation on model fit, local measurement precision, and various indicators of the scale's validity to get an indication on whether the current practice of recoding should be advocated or not. In particular, the effect on the convergent- (operationalized by the General Health Questionnaire and the Maastricht Questionnaire), divergent- (operationalized by the Neuroticism scale of the NEO-FFI), and predictive validity (operationalized as obtrusion with daily chores and activities, the Biographical Problem list and the Utrecht Burnout Scale) of the distress scale was investigated. RESULTS: Results indicate that recoding leads to (i) better model fit as indicated by lower mean probabilities of exact test statistics assessing item fit, (ii) small (<.02) losses in the sizes of various validity coefficients, and (iii) a decrease (DIFF (SE's) = .10-.25) in measurement precision for medium and high levels of distress. CONCLUSIONS: For clinical applications and applications in longitudinal research, the current practice of recoding should be avoided because recoding decreases measurement precision for medium and high levels of distress. It would be interesting to see whether this advice also holds for the three other domains of the 4DSQ.

Can antipsychotic dose reduction lead to better functional recovery in first-episode psychosis? A randomized controlled-trial of antipsychotic dose reduction. The reduce trial: Study protocol.

Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. AIM: The primary aim of the study is, in a population of young people with first-episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence-based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24-months follow-up. METHODS: Our single-blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2-year period in 180 remitted first-episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow-up. RESULTS: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. CONCLUSION: This study will provide evidence as to whether an antipsychotic dose-reduction recovery treatment leads to improved functioning and safer outcomes in first-episode psychosis patients. In addition, it will be the first-controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population.

Functional recovery of individuals with serious mental illnesses: Development and testing of a new short instrument for routine outcome monitoring.

OBJECTIVE: This article describes the development and testing of the Functional Recovery tool (FR tool), a short instrument for assessing functional recovery during routine outcome monitoring of people living with serious mental illnesses. METHODS: To assess functional recovery, mental health professionals conducted semistructured interviews with people living with serious mental illnesses on three areas of social functioning: daily living and self-care, work and study, and social contacts. Functioning in each of these areas over the past 6 months was rated on a 3-point scale: 0 (independent), 1 (partially independent), and 2 (dependent). The dichotomous overall outcome of the tool is defined as independent functioning in all areas. We analyzed interrater and test-retest reliability, sensitivity to change, and correlations with constructs that are assumed to be similar to the FR tool (quality of life in daily living, work, and social contacts) or divergent from it (symptomatic functioning). RESULTS: The FR tool was administered to 840 individuals with serious mental illnesses in Dutch mental health care services, 523 of whom were followed up for 1 year (response rate 62%). The tool was easy to complete and was appropriate for policy evaluation and practice. However, when it was combined with more elaborate instruments, it added little extra clinical information. Interrater and test-retest reliability, convergent and discriminant validity, and sensitivity to change were rated sufficient to good. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The FR tool could be a useful measure of functional recovery in addition to current measures of symptomatic remission and personal recovery in routine outcome monitoring. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Self-monitoring and personalized feedback based on the experiencing sampling method as a tool to boost depression treatment: a protocol of a pragmatic randomized controlled trial (ZELF-i).

BACKGROUND: Depression is a leading cause of disability worldwide. To reduce the societal burden and improve quality of life for individual patients, treatments for depression need to be optimized. There is a particular need for person-tailored interventions that reinforce self-management of patients. Systematic self-monitoring and personalized feedback through the Experience Sampling Method (ESM) could provide such a person-tailored, empowering intervention that enhances treatment outcomes. The primary aim of this study is to investigate the efficacy of self-monitoring and personalized feedback as an add-on tool in the treatment of depressive complaints in a natural setting. METHODS: The ZELF-i study is a pragmatic multi-site randomized controlled trial (RCT). We aim to recruit 150 individuals with depressive symptoms aged between 18 and 65 years, who have an intake for outpatient basic or specialized treatment at a mental health care organization in the North of the Netherlands. After the intake, participants will be randomly allocated to one of three study arms: two experimental groups engaging in 28 days of systematic self-monitoring (5 times per day) and receiving weekly personalized feedback on positive affect and activities ("Do"-module) or on negative affect and thinking patterns ("Think"-module), and a control group receiving no additional intervention. Self-report inventories of depressive symptoms, psychosocial functioning and feelings of empowerment will be administered before and after the intervention period, and at follow-up measurements at 1, 2, 3 and 6 months. The patient-experienced utility of the intervention will be investigated by a combination of quantitative and qualitative research methods. DISCUSSION: The present study is the first to examine the effects of add-on self-monitoring and personalized feedback on depressive complaints in clinical practice. It is also the first to evaluate two different ESM modules targeted at both of depression's core symptoms. Lastly, it is the first study that uses a combination of qualitative and quantitative methods to evaluate the patient-experienced utility of ESM with personalized feedback as an intervention for depression. Results of the present study may improve treatment for depression, if the intervention is found to be effective. TRIAL REGISTRATION: Dutch Trial Register, NTR5707 , registered prospectively 1 February 2016.

A Smart Screening Device for Patients with Mental Health Problems in Primary Health Care: Development and Pilot Study.

BACKGROUND: Adequate recognition of mental health problems is a prerequisite for successful treatment. Although most people tend to consult their general practitioner (GP) when they first experience mental health problems, GPs are not very well equipped to screen for various forms of psychopathology to help them determine clients' need for treatment. OBJECTIVE: In this paper, the development and characteristics of CATja, a computerized adaptive test battery built to facilitate triage in primary care settings, are described, and first results of its implementation are reported. METHODS: CATja was developed in close collaboration with GPs and mental health assistants (MHAs). During implementation, MHAs were requested to appraise clients' rankings (N=91) on the domains to be tested and to indicate the treatment level they deemed most appropriate for clients before test administration. We compared the agreement between domain score appraisals and domain score computed by CATja and the agreement between initial (before test administration) treatment level advice and final treatment level advice. RESULTS: Agreements (Cohen kappas) between MHAs' appraisals of clients' scores and clients' scores computed by CATja were mostly between .40 and .50 (Cohen kappas=.10-.20), and the agreement between "initial" treatment levels and the final treatment level advised was .65 (Cohen kappa=.55). CONCLUSIONS: Using CATja, caregivers can efficiently generate summaries of their clients' mental well-being on which decisions about treatment type and care level may be based. Further validation research is needed.

Towards a comprehensive routine outcome monitoring program for people with psychotic disorders: The Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS).

BACKGROUND: Patients with psychotic disorders are at risk of developing mental health and social problems, and physical disorders. To monitor and treat these problems when indicated, an annual routine outcome monitoring program, Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS), was developed. This paper presents the background and content of PHAMOUS, implementation of PHAMOUS, characteristics of the patients screened in 2015, and the outcome of patients with three annual screenings between 2011 and 2015. METHODS: PHAMOUS was implemented in four mental health institutions in the Northern Netherlands in 2006. During the PHAMOUS screening, patients are assessed on socio-demographics, psychiatric symptoms, medication, physical parameters, lifestyle, (psycho)social functioning and quality of life, using internationally validated instruments. RESULTS: In 2015, 1955 patients with psychotic disorders were enrolled in the PHAMOUS screening. The majority (72%) was receiving mental healthcare for ten years or longer. A small group was hospitalized (10%) in the past year. Half of the patients were in symptomatic remission. Less than 10% had a paid job. More than half of the patients fulfilled the criteria for metabolic syndrome (54%). The subsample with three annual screenings from 2011 to 2015 (N = 1230) was stable, except the increasing prevalence of high glucose levels and satisfaction with social relationships (Cochran's Q = 16.33, p = .001 resp. Q = 14.79, p = .001). CONCLUSION: The annual PHAMOUS screening enables to follow the mental, physical and social health problems of patients, which offers a good basis for shared-decision making with regard to updating the annual treatment plan, next to a wealth of data for scientific research.

Study protocol for a prospective cohort study examining the predictive potential of dynamic symptom networks for the onset and progression of psychosis: the Mapping Individual Routes of Risk and Resilience (Mirorr) study.

INTRODUCTION: Our current ability to predict the course and outcome of early psychotic symptoms is limited, hampering timely treatment. To improve our understanding of the development of psychosis, a different approach to psychopathology may be productive. We propose to reconceptualise psychopathology from a network perspective, according to which symptoms act as a dynamic, interconnected system, impacting on each other over time and across diagnostic boundaries to form symptom networks. Adopting this network approach, the Mapping Individual Routes of Risk and Resilience study aims to determine whether characteristics of symptom networks can predict illness course and outcome of early psychotic symptoms. METHODS AND ANALYSIS: The sample consists of n=100 participants aged 18-35 years, divided into four subgroups (n=4×25) with increasing levels of severity of psychopathology, representing successive stages of clinical progression. Individuals representing the initial stage have a relatively low expression of psychotic experiences (general population), whereas individuals representing the end stage are help seeking and display a psychometric expression of psychosis, putting them at ultra-high risk for transition to psychotic disorder. At baseline and 1-year follow-up, participants report their symptoms, affective states and experiences for three consecutive months in short, daily questionnaires on their smartphone, which will be used to map individual networks. Network parameters, including the strength and directionality of symptom connections and centrality indices, will be estimated and associated to individual differences in and within-individual progression through stages of clinical severity and functioning over the next 3 years. ETHICS AND DISSEMINATION: The study has been approved by the local medical ethical committee (ABR no. NL52974.042.15). The results of the study will be published in (inter)national peer-reviewed journals, presented at research, clinical and general public conferences. The results will assist in improving and fine-tuning dynamic models of psychopathology, stimulating both clinical and scientific progress. TRIAL REGISTRATION NUMBER: NTR6205 ; Pre-results.

Identifying levels of general distress in first line mental health services: can GP- and eHealth clients' scores be meaningfully compared?

BACKGROUND: The Four-Dimensional Symptom Questionnaire (4DSQ) (Huisarts Wetenschap 39: 538-47, 1996) is a self-report questionnaire developed in the Netherlands to distinguish non-specific general distress from depression, anxiety, and somatization. This questionnaire is often used in different populations and settings and there is a paper-and-pencil and computerized version. METHODS: We used item response theory to investigate whether the 4DSQ measures the same construct (structural equivalence) in the same way (scalar equivalence) in two samples comprised of primary mental health care attendees: (i) clients who visited their General Practitioner responded to the 4DSQ paper-and-pencil version, and (ii) eHealth clients responded to the 4DSQ computerized version. Specifically, we investigated whether the distress items functioned differently in eHealth clients compared to General Practitioners' clients and whether these differences lead to substantial differences at scale level. RESULTS: Results showed that in general structural equivalence holds for the distress scale. This means that the distress scale measures the same construct in both General Practitioners' clients and eHealth clients. Furthermore, although eHealth clients have higher observed distress scores than General Practitioners' clients, application of a multiple group generalized partial credit response model suggests that scalar equivalence holds. CONCLUSIONS: The same cutoff scores can be used for classifying respondents as having low, moderate and high levels of distress in both settings.