A naturalistic cohort study of first-episode schizophrenia spectrum disorder: A description of the early phase of illness in the PSYSCAN cohort

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Introduction
Psychotic disorders constitute one of the highest disease burdens globally, affecting approximately 1-2 % of the population (Gustavsson et al., 2011;Wittchen et al., 2011).Following the first presentation of a psychotic episode, outcomes vary from patients making a good recovery to cases suffering multiple relapses (Lehman et al., 2004;ten Velden Hegelstad et al., 2013).Given that symptom patterns within the first two years of treatment are associated with outcomes over the long term (Alvarez-Jimenez et al., 2012;Cesková et al., 2007;Harrison et al., 2001;Lally et al., 2017;Rund et al., 2015;Santesteban-Echarri et al., 2017;ten Velden Hegelstad et al., 2013), the initial stage of illness has been a central theme in psychosis research.
The research field of first episode psychosis (FEP) has predominantly concentrated on the remission of psychotic symptoms.Varying symptom trajectories have been observed among patients; a substantial proportion of FEP patients (82-88 %) show a gradual improvement in symptoms over a 2-year period while a small subgroup (7-16 %) present with a persistently poor or relapsing pattern (Abdin et al., 2017;Meneghelli et al., 2020).Such heterogeneity is not only observed in the longitudinal pattern of symptoms, but also in the course of social-occupational functioning, with 48-66 % exhibiting a deterioration in functioning over 3 years of follow-up (Abdin et al., 2017;Chang et al., 2018).Accumulating evidence suggests that patients with negative symptoms, comorbid depressive symptoms, suicidal ideation, a history of suicide attempt, sustained substance use, a lower level of cognitive and intellectual functioning, male gender and an ethnic minority status are at risk of an unfavorable course (Amoretti et al., 2021;Austin et al., 2013;Bucci et al., 2020;Conus et al., 2017;de Nijs et al., 2021;Díaz-Caneja et al., 2015;Galderisi et al., 2013;M.-H. Hall et al., 2019;Santesteban-Echarri et al., 2017;Suvisaari et al., 2018).Hence, differences in demographic and clinical characteristics of the various research samples have likely affected the disorder trajectories reported in the literature to date, highlighting the need to study the illness course in FEP from a broader perspective.
Although the existing literature recognizes that these factors play a part in determining the general wellbeing of these individuals (Chang et al., 2016;Santesteban-Echarri et al., 2017;Suvisaari et al., 2018;Watson et al., 2018), methodological limitations have prevented past studies from taking such a broad approach.In addition to symptomatic improvement, it may be important to gain greater insight into other aspects of the early course of psychosis, including but not limited to psychiatric hospitalizations, suicidality, pharmacological and psychotherapeutic treatment, comorbid disorders such as depression or substance abuse, and a general quality of life (Díaz-Caneja et al., 2015;Hall et al., 2019;Koutsouleris et al., 2016;Phahladira et al., 2020;Stouten et al., 2014).The present study aims to address this knowledge gap by painting a comprehensive picture of the early course of illness in a large, international cohort of FEP patients within a naturalistic one-year follow-up design.It serves as a basis for future work focusing on explaining and predicting the observed variation in illness course.Since it is well-established that FEP patients diagnosed with schizophrenia have a relatively poor prognosis, compared to other psychotic diagnoses (Bowtell et al., 2018;Bozzatello et al., 2019), the current sample is restricted to FEP patients with a schizophrenia spectrum disorder (broadly defined as first-episode schizophrenia spectrum disorder; FES).

Setting and participants
PSYSCAN is an international, longitudinal, multicenter study examining the early stages of psychosis (HEALTH.2013.2.2.1-2-FEP).A detailed description of the study design and procedures has been provided elsewhere (Tognin et al., 2020).The present work used data from the first-episode psychosis cohort.Participants were recruited at 16 institutions across Europe, Israel and Australia, which are highly experienced in providing healthcare for psychotic illness (i.e., with an established FEP service) and have excellent research facilities.Participants could be either in-or outpatients and were recruited between July 2016 and March 2019 at the participating sites.
Patients were eligible for participation if they were 16-40 years of age, capable of providing informed consent (or assent in case of a minor) and had a first episode of psychosis as defined by a DSM-IV diagnosis of schizophrenia, schizoaffective disorder (depressive type) or schizophreniform disorder (Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text rev.) (American Psychiatric Association, 2000).Subjects meeting any of the following criteria were not eligible to participate: 1) a time interval between psychosis onset and study entry exceeding three years; onset of psychosis was defined as the initiation of treatment for psychosis (date of hospital admission or acceptance at healthcare service for psychosis), 2) any previous neurosurgery or neurological disorder, including epilepsy, 3) a history of head injury resulting in unconsciousness lasting at least 1 h, 4) pregnancy, 5) any contraindications for MRI, 6) refusing to undergo blood draws and/or MRI sessions, 7) unable to fully comprehend the purpose of the study or to make a rational decision on whether or not to participate.
All participants, or their legal representatives, provided written informed consent.The study was approved by the ethics committees of all participating centers and conducted in compliance with the Declaration of Helsinki ( 2013) and the International Committee on the Harmonization of Good Clinical Practice, if applicable according to local laws and regulations.The study was monitored by the University Medical Center Utrecht, the Netherlands.The last study visit took place on August 12, 2020, as some final visits were delayed due to COVID-19 lockdown restrictions.

Study design
Participants were followed up in a one-year, naturalistic, prospective design.At baseline, a semi-structured interview was performed to obtain data on sociodemographic variables, medical history, current medication use, recent psychiatric history and present treatment setting.Diagnoses were confirmed using the Structured Clinical Interview for DSM-IV Disorders (SCID-I) (First et al., 2002).Duration of untreated psychosis (DUP) was defined as the time interval from the onset of frank psychosis (delusions, hallucinations, clear-cut disorder of speech/ thinking, or disorganized, bizarre or markedly inappropriate behavior) to the initiation of treatment (defined as the date of first acceptance at healthcare service for psychosis; this could be either inpatient or outpatient, depending on the setting to which the individual first presented for psychosis), as reported by the participant.Eleven participants had started treatment before the onset of frank psychosis.Premorbid functioning was determined using the Premorbid Adjustment Scale (PAS; short version validated by Van Mastrigt & Addington) (Cannon-Spoor et al., 1982;van Mastrigt and Addington, 2002).IQ was estimated using an abbreviated version of the Wechsler's Adult Intelligence Scale (Third Edition, Short Form) (Blyler et al., 2000;Wechsler, 1997).Psychopathology was assessed with the Positive And Negative Syndrome Scale (PANSS) (Kay et al., 1987) and the 17-item Hamilton Rating Scale for Depression (HAM-D) (Hamilton, 1960).Severity of illness was determined with the Clinical Global Impression scale (CGI) (Guy, 1976).Psychosocial and occupational functioning were examined with the Global Assessment of Functioning scale (GAF) (Hall, 1995), Global Functioning Social (GF-S) (Piskulic et al., 2011), Global Functioning Role (GF-R) (Piskulic et al., 2011), and the Social and Occupational Functioning Assessment Scale (SOFAS) (Goldman et al., 1992), reflecting the current level of functioning.The World Health Organization Assist 3.0 questionnaire was used to asses drug and alcohol use (WHO ASSIST Working Group, 2002).
To explore the illness course in detail, patients were assessed at two, six and twelve months after study entry.Treatment characteristics (treatment setting, use of psychotropic medication and psychotherapeutic treatment), psychiatric hospitalizations, psychopathology, illness severity and psychosocial and occupational functioning were determined at all visits.Follow-up assessment of drug and alcohol use occurred at the 6-and 12-month time points.

Operational definitions
Symptomatic remission was assessed utilizing a modification of the criteria described by Andreasen and colleagues (Andreasen et al., 2005); a patient meets remission criteria if eight specific symptoms of schizophrenia as measured with the PANSS (P1, P2, P3, N1, N4, N6, G5 and G9) are absent, minimal or mildly present (maximum rating of 3 on all eight items).This definition of remission is widely used in clinical trials and shows good clinical validity as it has been associated with outcomes such as quality of life, social-occupational functioning, and subjective wellbeing (Emsley et al., 2007;van Os et al., 2006).The study design did not allow for the application of the minimum 6-month duration criterion; symptomatic remission status was based on the evaluation of symptoms over the past week.
Functional remission was defined as a SOFAS score >60.This reflects a situation in which the individual may have some difficulty in social, occupational, or school functioning, but is generally functioning pretty well.This definition is in line with previously reported criteria for functional remission (Chang et al., 2016;Menezes et al., 2009;Phahladira et al., 2020;Whitehorn et al., 2002).

Statistical analysis
Analyses were performed in SPSS version 27.0 (IBM Corp., 2020).All statistical tests were two-sided.The significance level was 0.05.First, descriptive statistics of baseline characteristics were carried out for the entire cohort.Subgroups of interest were created (study completers vs. dropouts, remitters vs. non-remitters) and differences in baseline characteristics were compared using independent sample t-tests or Mann-Whitney U tests (depending on variable distribution), and Pearson chisquare tests.Study completers were defined as those subjects who completed at least the baseline visit and the 12-month follow-up visit.Symptomatic remission status, functional remission status, psychiatric hospitalizations, treatment characteristics and substance use were determined as frequencies and percentages.To assess whether proportions of category membership changed over time, generalized linear mixed models were performed using a binomial distribution and a Logit link function.Pairwise comparisons were corrected for multiple comparisons using a Bonferroni adjustment.Continuous endpoints (PANSS, HAM-D, CGI, GAF, SOFAS, GF-S, GF-R) were analyzed using linear mixed models.Time point was included as a repeated fixed factor, assuming a Spatial Power covariance structure and with baseline as the reference category.For the CGI improvement, SOFAS, GAF, GF-S, GF-R, the HAM-D subgroup analysis (patients with or without a depressive episode at baseline), as well as the frequencies of participants receiving inpatient treatment and frequencies readmitted to hospital, a simpler covariance structure was more appropriate (a diagonal structure).Subject was included as a random effect, selecting a Scaled Identity covariance structure.Results of all pairwise comparisons between individual time points are summarized in the Supplements (Supplementary Tables 3-5).To assess the impact of missing data on the remission rates, an additional, 'Intention-To-Treat' analysis was performed.Results of these analyses as well as exploratory analyses on betweencountry differences are included in the Supplements (Supplementary Figs.1-2 and Supplementary Tables 11-16).

Results
A total of 325 patients were screened for eligibility, of whom 304 were included in the study (93.5 %).Reasons for exclusion are provided in Supplementary Table 17.Two hundred twenty-seven patients (74.7 %) completed the one-year follow-up assessment (Fig. 1).Baseline sociodemographic and clinical characteristics are provided in Table 1.At study entry, the sample presented with relatively mild psychotic symptoms (46.5 % in symptomatic remission).Importantly, some patients had been treated for a while before being enrolled to the study (i.e., a subgroup which may be more clinically stabilized), while others had started treatment for psychosis only a couple of weeks ago (median = 5.8 months, IQR = 13.0).Sociodemographic and baseline clinical characteristics were comparable between study completers and those who were lost to follow-up (see Supplementary Table 1) but differed noticeably between countries (Supplementary Table 11).

Treatment characteristics
Changes in psychotherapeutic treatment and psychotropic medication use are summarized in Table 2.A total of 31.1 % (68 out of 219 completers) had been (re)admitted to hospital for psychiatric reasons at some point after baseline (i.e., 22.4 % of the total cohort).A proportion of 20.9 % (46 out of 220 completers) reported being admitted to the hospital due to exacerbation of psychotic symptoms specifically (i.e., 15.1 % of the total cohort).The number of patients admitted to hospital since the last visit due to exacerbation of psychotic symptoms, and the number of patients admitted to hospital since the last visit for psychiatric reasons in general, did not differ between follow-up time points, F(2, 535) = 2.281, p = .103,and F(2, 545) = 2.817, p = .061,respectively (see Supplementary Table 6).

Symptom severity and functional outcome
Mixed-effects models revealed an effect of time on the PANSS total (F (3, 475.47) = 23.1, p < .001),PANSS positive (F(3, 575.29) = 23.0,p < .001),PANSS negative (F(3, 326.47) = 12.4,p < .001) as well as the PANSS general subscale (F(3, 538.16) = 13.8, p < .001).Several pairwise contrasts were significant (see Fig. 2A).The CGI-severity showed a significant decrease in the severity of psychotic illness, as judged by the clinician (F(3, 733.266) = 11.91,p < .001).CGI-improvement scores did not differ over time, p = .258(see Fig. 2B).Results of the linear mixed models on social, occupational and global functioning revealed a significant increase in GAF (F(3, 305.420) = 31.36,p < .001),SOFAS (F(3, 318.229) = 45.14, p < .001),GF-S (F(3, 304.468) = 13.12,p < .001)and GF-R scores (F(3, 281.008) = 28.44,p < .001)throughout the study (see Fig. 2C and D).Depressive symptoms, measured using the HAM-D, were in most cases absent to mildly present and remained stable over time (F (3, 443.087) = 1.84, p = .140).However, in the subgroup of patients meeting criteria for a depressive episode at baseline, depressive symptoms slightly decreased from moderate symptoms at baseline to mild depressive symptoms one year later (F(3, 22.628) = 3.37, p = .036;see Supplementary Fig. 3).were in symptomatic remission, compared to 140 out of 301 patients (46.5 %) at baseline.However, the patients who were in symptomatic remission at baseline were not necessarily those who were in remission at one-year follow-up (see Fig. 3).Nineteen patients (6.3 %) were initially in remission of psychotic symptoms, but did not remain in symptomatic remission one year later.Thirty patients (10.0 %) demonstrated a stable one-year trajectory of non-remission of psychotic symptoms.Patients who were not in remission twelve months postbaseline were more severely ill (CGI -S), presented with more severe psychotic symptoms (PANSS) and depressive symptoms (HAM -D), and had lower general and social-occupational functioning at baseline (GAF, SOFAS, GF-S, GF-R), p < .001(Supplementary Table 10).At one-year follow-up, 133 out of 217 patients (61.3 %) were in functional remission.Eight patients (2.7 %) were in functional remission at study entry, but did not maintain this status one year later.Fifty-three patients (17.6 %) did not achieve remission of functioning at any point during the oneyear follow-up period (i.e., consistent pattern of non-remission of functioning).Approximately half of the sample (102 out of 207 patients, 49.3 %) were in both symptomatic and functional remission after one year.Interestingly, when a stricter definition for symptomatic and functional remission was adopted (i.e., adding the absence of psychiatric hospitalizations or inpatient treatment since the previous visit as an additional criterion for remission), similar results were found (see Supplementary Tables 18-19).

Substance use
The number and proportion of patients using a substance at least once in the past three months relative to the assessment point, were determined per time point and substance category.Alcohol and tobacco were the most commonly used substances, with percentages ranging from 72.9 to 75.6 % (daily users ranged between 4.5-7.8%) and 69.1-72.1 % (daily users ranged between 56.1 and 57.9 %), respectively.The proportion of patients using cannabis ranged from 31.2 to 35.1 % over time (daily users ranged between 8.5 and 11.3 %).The proportion of daily tobacco, alcohol and cannabis users did not differ between the group who was in symptomatic remission after a year and the group of non-remitters.Details are provided in the Supplements (Supplementary Tables 7-9).

Discussion
The aim of this study was to provide a comprehensive overview of the early phase of illness after the onset of the first psychotic episode in a large group of patients with a schizophrenia-spectrum disorder.At study entry, patients had a median treatment duration of 5.8 months and had relatively mild psychotic symptoms.Although the majority were in remission of psychotic symptoms and in functional remission at one-year follow-up, there was a striking degree of inter-individual variability in the trajectories of remission.A total of 31 % had been readmitted to hospital for psychiatric reasons after a year, of whom two thirds were admitted due to psychosis.The vast majority were treated with antipsychotics throughout the study.The number of patients receiving psychological treatment decreased somewhat from baseline to the oneyear assessment.Depressive symptoms were absent to mildly present and remained stable over time in the sample in general, but slightly improved in the subgroup of patients who met criteria for a depressive episode at baseline.
The remission rate that we observed (67 % over 12 months) is partially consistent with previous naturalistic studies of FEP patients.For example, two studies using a similar definition of remission, reported comparable remission rates of 67 % (Korea) (Kang et al., 2021) and 74 % (Canada) (Menezes et al., 2009) one year after baseline.A oneyear remission rate of 66 % was reported by Simonsen et al. (Simonsen et al., 2007), who used a slightly different operationalization (PANSS scores below 4 on positive subscale items 1, 3, 5 and 6 and general subscale item 9 for at least one week).Other studies have reported lower remission rates at one-year follow-up, ranging from 19 to 41 % (Benoit et al., 2014;Fountoulakis et al., 2020;Renwick et al., 2015;Simonsen et al., 2017;Ventura et al., 2011).A review and meta-analysis from Catalan et al. (Catalan et al., 2021) reported that only around half of the pooled FEP sample reached symptomatic remission four years after a first psychotic episode.The variation in remission rates may be partly due to differences in the operationalization of the concept of remission.Inclusion of a duration component (Benoit et al., 2014;Simonsen et al., 2017;Ventura et al., 2011) results in more stringent remission criteria, acceptance at healthcare service for psychosis; discrepancy in the mean and median DUP is due to the influence of several outliers.PAS = Premorbid Adjustment Scale (range = 0-1, lower scores indicating better functioning).WAIS-III SF = Wechsler Adult Intelligence Scale, Third Edition, Short Form.Note.Data are n (%), or n/N (%), unless otherwise indicated.Denominators change because of incomplete data.F-statistic is derived from Generalized Linear Mixed Model analyses.
making it more difficult to achieve.The lower remission rates could also be explained by differences in demographic and clinical characteristics of the sample, such as differences in exposure to antipsychotic treatment (Fountoulakis et al., 2020), duration of illness at study entry (Altamura et al., 2015), or the proportion of males versus females (Chang et al., 2016;Suvisaari et al., 2018;Ventura et al., 2011).In this context, the diversity in the time span from treatment initiation to study entry in our sample (ranging up to three years) in combination with the relatively short period of follow-up (one year) is important to note.Alternatively, considering that the course of illness is generally observed to be different in affective (Ramain et al., 2022) and substance-induced psychoses (Dawe et al., 2011;Drake et al., 2011) compared to schizophrenia spectrum diagnoses, contradictory remission rates may also be related to the heterogeneity in diagnostic inclusion criteria of FEP studies.
Our results revealed an increase in social-occupational functioning over the course of follow-up.The one-year rate of functional remission (61 %) in our study is higher compared to previously reported rates in FEP samples with treatment as usual (Fountoulakis et al., 2020;Kang et al., 2021;Menezes et al., 2009;Simonsen et al., 2017;Ventura et al., 2011;Whitehorn et al., 2002), which may be caused by a different operationalization of the concept of functional remission.Indeed, studies using the same criteria (SOFAS >60) have more comparable rates of functional remission (50-51 %) than those using slightly different criteria, where functional remission rates tend to be lower (ranging around 3-26 %).Most studies reporting lower rates adopted more specific criteria on social interaction or occupational functioning, which may be more difficult to attain, e.g.requiring patients to be engaged in >50 % of full-time employment or study, or to meet specific expectations on the frequency of social contact.This once again emphasizes the importance of taking into account operational differences as well as the need for a more homogeneous definition of functional remission.Changes in healthcare organization in the field of early psychosis, including a shift towards deinstitutionalization as well as the increased interest in and availability of early intervention services (EIS) and specialized treatment programs for FEP, further complicate a comparison of the reported functional remission rates over the past decades (Huxley et al., 2021).Recent findings indicating that EIS are more effective than treatment as usual corroborate this hypothesis (Alvarez-Jimenez et al., 2011;Bird et al., 2010;Correll et al., 2018).The superiority of EIS is possibly mediated by a shorter duration of untreated psychosis (DUP), which has consistently shown to be predictive of better functional outcomes (Santesteban-Echarri et al., 2017).In the present study, a notable difference was observed between the median and mean DUP (4 versus 25 weeks).Moreover, the DUP varied substantially between countries, ranging from a few weeks (e.g., Israel) to six months or more (e.g., Italy and the Netherlands).Clinical characteristics at baseline such as the severity of psychotic symptoms, treatment setting and the level of functioning differed markedly between countries as well.Future studies should take these regional differences into consideration and should recognize that the present results may not translate to other countries, e.g. in the United States and Canada, where the DUP is generally longer (Marshall et al., 2005).It should also be acknowledged that, due to differences in the number of included participants, any between-country differences reported here are only provided as context, and do not reflect characteristics of representative subgroups of patients in specific countries.
Despite the overall improvement in psychotic symptoms and psychosocial and occupational functioning, around 33 % of the patients did not meet criteria for symptomatic remission and 40 % were not in functional remission after one year.Moreover, a total of 31 % were readmitted to hospital for psychiatric reasons at some time during follow-up.This is similar to previously reported levels of rehospitalization (36.1 % in Sile et al. (Sile et al., 2021) and 37.3 % in Menezes et al. (Menezes et al., 2006)).The proportion of rehospitalization in the current study may be optimistic as these are based on study completers only, but could also be an effect of specialized early intervention treatment, which has been linked to a reduced hospitalization risk (Bird et al., 2010;Correll et al., 2018).Future research could further examine which factors are predictive of relapse, such as cannabis use (Levi et al., 2023).In line with current antipsychotic treatment guidelines (Bowtell et al., 2018;Leucht et al., 2012), twelve months after baseline still nearly 80 % of FEP patients reported antipsychotic medication use.The proportion of patients receiving psychological treatment slightly decreased from baseline to 12 months.The majority still received some sort of psychological intervention, which is in accordance with international clinical practice guidelines for early psychosis (International Early Psychosis Association Writing Group, 2005), which recommend that pharmacological treatment is combined with psychosocial approaches, especially up to five years after a first psychotic episode.
A few limitations of our study need to be acknowledged.First, incomplete data at follow-up has possibly introduced attrition bias.Although no differences in demographic and clinical characteristics between dropouts and completers were observed at baseline, the results may be biased towards patients who are more eager to complete a noninterventional study with limited anticipated personal benefit.A second point of attention is the absence of a duration requirement in our definition of symptomatic and functional remission.These outcomes should therefore be considered a reflection of a single time point and not Fig. 3. Sankey diagram displaying the trajectories of symptomatic remission throughout the study (Bogart, 2022).Numbers represent patient counts.
representative of sustained remission.Third, the study design did not allow us to include more specific measures of functioning in the definition of functional remission, such as occupational status.Fourth, as our sample is restricted to patients with psychosis as part of a schizophrenia-spectrum diagnosis, the results may be less generalizable to FEP patients including a wider range of psychotic diagnoses.
Notwithstanding these limitations, studying a naturalistic FES cohort minimizes the potential confounding effects of chronicity of psychotic illness, such as long-term use of antipsychotic medication (Hall et al., 2019).The main strength of this specific study is the ecological validity and wide geographical coverage.Moreover, at present, only few studies have addressed changes in psychological treatment, medication use and treatment setting in a naturalistic cohort over time (Fountoulakis et al., 2020;Simonsen et al., 2017;Simonsen et al., 2007).
Taken together, the present study is one of the largest international, naturalistic FES cohorts providing valuable insight in the general course of a broad range of clinical and functional characteristics over a one-year period in FES patients treated as usual in routine clinical practice.An extensive overview of the early phase of psychotic illness is not only useful for treating physicians and therapists but also informative for patients and families.Future analyses on the rich dataset of the current study, including sociodemographic and clinical data, as well as blood biomarkers, cognition and neuroimaging, will provide more insight into a broad array of potential moderators and predictors of symptomatic and functional remission.Moreover, by combining the data from the three cohorts (first-episode psychosis, clinical high risk and healthy control subjects), future work can further elaborate on the prediction of the illness course both longitudinally and cross-sectionally.In order to move this area of research forward, it is recommended to create more consensus in the operational definition of outcomes like functional remission, as this will enhance comparability between studies (Huxley et al., 2021).Future research would benefit from obtaining more objective measures of social-occupational functioning over time, such as information on living conditions and employment status, which are more sensitive to small changes and easier to compare between studies.Esther Setien-Suero 5, 28

Fig. 1 .
Fig. 1.CONSORT flow diagram displaying the progress of participants through the study.Note.Twelve participants missed the 6-month assessment but did complete the final study visit.The number of participants therefore increased from 215 patients completing the 6-month follow-up to 227 patients completing the 12-month follow-up.The total number of dropouts from baseline to 12-month follow-up was 77.
Note.Data are mean (SD), n (%), or n/N (%), unless otherwise indicated.Denominators change because of incomplete data.* Years of education = years in school and college/university (excluding kindergarten/nursery).** Treatment initiation is defined as the date of first acceptance at healthcare service for psychosis (this could be either inpatient or outpatient, depending on the setting to which the individual first presented for psychosis).*** Duration of untreated psychosis (DUP) is defined as the time interval between first onset of frank psychotic symptoms and the date of first

Table 2
Psychotherapeutic treatment and psychotropic medication use.