Professional Documents
Culture Documents
Fusar Poli2016
Fusar Poli2016
Editorial
IMPORTANCE The prognostic significance of competing constructs and operationalizations Supplemental content at
for brief psychotic episodes (acute and transient psychotic disorder [ATPD], brief psychotic jamapsychiatry.com
disorder [BPD], brief intermittent psychotic symptoms [BIPS], and brief limited intermittent
psychotic symptoms [BLIPS]) is unknown.
DATA SOURCES The Web of Knowledge and Scopus databases were searched up to May 18,
2015; the articles identified were reviewed as well as citations of previous publications and
results of a manual search of the reference lists of retrieved articles.
STUDY SELECTION We included original articles that reported the risk of psychotic recurrence
at follow-up for patients in remission from first-episode ATPD, BPD, BLIPS, BIPS, and FES.
MAIN OUTCOMES AND MEASURES Proportion of patients with baseline ATPD, BPD, BLIPS, and
BIPS who had any psychotic recurrence at 6, 12, 24, and 36 or more months of follow-up.
(Reprinted) E1
A
s psychotic disorders of “dramatic symptomatology”2
Meaning: Current data may influence the diagnostic practice and
but remitting course, brief psychotic episodes repre- clinical services in the management of early psychosis.
sent one of the most intriguing paradoxes in psychia-
try. In 1863, Kahlbaum first distinguished the typical progres-
sive nature of psychotic forms (vesania typica) from a separate have been repeatedly reconceptualized and operationalized
group of disorders (dysphrenia) that appeared in an acute and without finding a widely accepted nosographic cataloguing as
severe form but then remitted with a full recovery “without bouffée délirante,5 cycloid psychoses,6 reactive psychoses,7
leaving a lasting alteration in the elements that serve its emotional psychoses,8 atypical psychoses,9 or schizophreni-
expression.”3(p67) Kahlbaum’s classification did not become form state10 (Figure 15,6,8,10-27).
popular. Instead, the nosography of Kraepelin dominated psy- The nosographic nomadism of brief psychotic episodes
chiatry and shaped today’s diagnostic system.2 Brief psy- continues today. The World Health Organization has brought
chotic episodes have been difficult to accommodate as a “third the above clinical concepts into the International Statistical
psychosis” in the Kraepelinian dichotomy of dementia prae- Classification of Diseases, 10th Revision (ICD-10) diagnostic cat-
cox and manic-depressive insanity.4 Brief psychotic episodes egory of acute and transient psychotic disorders (ATPDs), with
Figure 1. Historical Genealogy of Current Competing Diagnostic Constructs for Brief Psychotic Episodes
Cycloid psychoses
Bouffée délirante Kleist 1924
des dégénérés
Mangan 1885
Psychogenic psychoses Metabolic psychosis
Wimmer 1916 Paul Schröder 1926
Bouffée délirante
Ey 1954 Cycloid psychoses
(3 bipolar types)
Leonhard 1957
Schizophrenia-like
Transient ischemic attacks emotional psychoses
Kistler 1991 Staehelin 1946
Information available in multiple publications.5,6,8,10-27 Adapted from Marneros Assessment of At-risk Mental State; ICD-10, International Statistical
and Pillmann.14 ATPD indicates acute and transient psychotic disorder; Classification of Diseases, 10th Revision; SIPS, Structured Interview for
BIPS, brief intermittent psychotic symptoms; BLIPS, brief limited intermittent Prodromal Syndromes; TIA, transient ischemic attack.
psychotic symptom; BPD, brief psychotic disorder; CAARMS, Comprehensive
6 subtypes, stating that an ATPD is a short, remitting episode tend to suggest that patients with ATPD and BPD may fare bet-
of psychosis that may last up to 3 months.1 Similarly, in the ter overall compared with patients with schizophrenia,31 but
DSM-5, the American Psychiatric Association has introduced the recurrence of subsequent psychotic episodes in ATPD and
the diagnostic category of brief psychotic disorder (BPD), de- BPD may be as frequent as in schizophrenia.32 To our knowl-
scribing brief psychotic episodes with a duration of less than edge, we provide here the first meta-analysis of these stud-
1 month and with full recovery to the premorbid status.28 Al- ies. The current meta-analytical approach is of particular rel-
though ATPD and BPD address similar constructs, major op- evance given that operationalization differences may affect
erationalization differences exist in terms of their sympto- their prognostic concordance,33 and the diagnostic stability of
matic features, symptom duration (3 months in ATPD vs 1 brief psychosis is questionable.34
month in BPD), and subtypes (schizophreniform-like disor- One further complication is that, during the past 2
ders are included in ATPD) (Table 1). Previous investigations decades, brief psychotic episodes have been reclassified
attenuated psychosis symptoms subgroups only; (5) FES reporting bias in meta-analyses,59 and with the Egger test60
studies with samples who had not experienced full remis- using the metabias61 function of Stata. Supplementary analy-
sion from their first episode; and (6) studies with samples of ses are detailed in eMethods in the Supplement.
multi-episode or chronic psychosis. In the case of multiple
publications derived from the same study population, we
selected articles reporting the largest and most recent data
set. The literature search was summarized according to the
Results
PRISMA guidelines.52 Database
The literature search (Figure 2) identified 82 independent ar-
Recorded Variables ticles, with some contributing more than 1 sample. We iden-
Data extraction was independently performed by 2 investiga- tified a total of 93 independent samples: 27 ATPD, 22 BPD, 13
tors (M.C. and G.R.). To estimate the primary outcome vari- BLIPS, 10 BIPS, and 21 FES. The numbers of patients at base-
able, we extracted the baseline sample size and the number line and at each follow-up time point are reported in Table 2.
of patients with any psychotic recurrence at follow-up. To es- Age, sex, diagnostic instrument used to assign the baseline and
timate the secondary outcome, we collected the number of pa- follow-up diagnoses, duration of follow-up, and exposure to
tients who developed schizophrenia or affective psychoses at antipsychotics for each included sample are detailed in eTable
follow-up. We collected additional moderators as indicated in 2a and eTable 2b, and the list of excluded articles is detailed
the Statistical Analysis section and performed quality assess- in eTable 3 in the Supplement.
ment as detailed in eMethods in the Supplement.
Meta-analytical Prognosis of Brief Psychotic Episodes
Statistical Analysis The 93 independent samples reported primary outcome data
The outcome measure was the risk of psychotic recurrence in at different follow-up time points (Table 2). Across all time
patients who experienced remission from their first episode points, no significant differences were found in the risk of psy-
of ATPD, BPD, BLIPS, or BIPS (primary outcome) and FES (sec- chotic recurrence between ATPD, BPD, BLIPS, and BIPS
ondary outcome). This risk was calculated as the proportion (Figure 3 and Table 2), with all P > .03 (Table 2).
of baseline patients who had any psychotic recurrence at 6, 12,
24, or 36 or more months follow-up. Meta-analysis was con- Comparison With Remitted Schizophrenia
ducted with the metaprop package53 of Stata, version 13.1. This We found a significantly higher risk of psychotic recurrence
package is specifically developed for pooling proportions in a in the FES group compared with the other 4 groups at 24
meta-analysis of multiple studies. The 95% CIs are based on (P < .02) and 36 or more (P < .001) months (Figure 3 and
score (Wilson).54 Because proportions were often expected to Table 2). Subgroup analyses (eFigure 1A-C in the Supple-
be small, we used the Freeman-Tukey double arcsine ment) identified a modulating effect of antipsychotic treatment
transformation55 to stabilize the variances and then perform in the short term (ie, 6 and 12 months) but found no effect for
a random-effects meta-analysis implementing the Der Simo- remission criteria and study design.
nian-Laird method.56 The influence of moderators was tested
using subgroup (type of antipsychotic treatment, study de- Meta-regression, Publication Bias, and Sensitivity Analysis
sign, and remission criteria in FES groups) and meta- Meta-regressions investigating year of publication, mean age,
regression (publication year, mean age, proportion of proportion of females, exposure to antipsychotics from base-
females, exposure to antipsychotics from baseline to follow- line to follow-up, diagnostic criteria used to assess the brief
up, diagnostic criteria used to assess the psychotic episodes psychotic episode at follow-up, and quality assessment are re-
at follow-up, and quality assessment) analyses. The slope of ported in eTable 4 in the Supplement. At an uncorrected thresh-
the meta-regression line (β coefficient: direct [+] or inverse old for multiple comparisons, there was a significant effect for
[−]) indicates the strength of an association between mod- sex (12 [P = .03] and 24 [P = .02] months) and antipsychotic ex-
erator and outcome. The meta-regressions were Bonferroni posure (6 [P = .02], 12 [P = .002], and 24 [P = .004] months).
corrected for multiple testing. Between-study heterogeneity Sensitivity analyses (eResults in the Supplement) confirmed the
was assessed using Q statistics with the proportion of the robustness of the findings. There was no evidence of publica-
total variability in the effect size estimates being evaluated tion bias as indicated by visual inspection of the funnel plots
with the I2 index,57 which does not depend on the number (eFigure 2A-C in the Supplement) and by the Egger test for small-
of studies included. Because meta-analysis of observational study effects (P > .05 at all time points).
studies is supposed to be characterized by significant hetero-
geneity, random-effect models were used. In addition, sensi- Supplementary Analyses
tivity analyses were conducted to investigate the influence of No meta-analytical differences in the risk of developing
each study on the overall risk estimate by omitting one study schizophrenia at 24 months were observed between the
at a time using Stata’s user-written function (metaninf).58 A ATPD, BPD, BLIPS, and BIPS groups (eFigure 3A and B in the
study was considered to be influential if the pooled mean es- Supplement). No meta-analytical differences in the risk of
timate without it was not within the 95% CIs of the overall mean. developing affective psychoses were detected between the
Publication bias was assessed with the metafunnel function of ATPD, BPD, BLIPS, BIPS, and FES groups (eFigure 4 in the
Stata, which produced funnel plots for assessing small-study Supplement).
Follow-up, mo
Characteristic 6 12 24 ≥36
No. of samples 25 46 35 42
No. of patients analyzeda 1311 1883 1669 11 133
Risk of psychotic recurrence,
mean (95% CI)b
BLIPS 0.08 (0.00-0.23) 0.28 (0.08-0.52) 0.32 (0.11-0.57) 0.30 (0.12-0.52)
BIPS 0.22 (0.09-0.36) 0.35 (0.23-0.48) 0.43 (0.26-0.61) 0.46 (0.32-0.61)
ATPD 0.13 (0.09-0.18) 0.30 (0.19-0.42) 0.38 (0.27-0.48) 0.54 (0.41-0.66)
BPD 0.20 (0.08-0.36) 0.31 (0.12-0.52) 0.46 (0.31-0.60) 0.53 (0.34-0.72)
FES 0.30 (0.15-0.48) 0.42 (0.30-0.54) 0.78 (0.58-0.93) 0.84 (0.70-0.94)
BLIPS vs BIPS vs ATPD vs BPD test 4.71 0.90 1.20 3.65
for between-group heterogeneity (Q)
P value .19 .83 .75 .30
BLIPS vs BIPSvs ATPD vs BPD vs FES test 7.63 2.36 11.97 16.97
for between-group heterogeneity (Q)
P value .11 .67 .02 <.001
Abbreviations: ATPD, acute and transient psychotic disorder; BIPS, brief remission of the first episode of BLIPS, BIPS, ATPD, BPD, and FES. Details on
intermittent psychotic symptoms; BLIPS, brief limited intermittent psychotic the definition of the index episode are appended in eDiscussion 4 in the
symptoms; BPD, brief psychotic disorder; FES, remitted first-episode Supplement.
schizophrenia. b
The overall risk of psychotic recurrence across BLIPS, BIPS, ATPD, and BPD
a
The number of patients in each ATPD, BPD, BLIPS, BIPS group depends on the combined: 6 months, 0.12 (95% CI, 0.07-0.17); 12 months, 0.30 (95% CI,
follow-up time. At baseline, the numbers were BLIPS, 168; BIPS, 125; 0.22-0.39); 24 months, 0.39 (95% CI, 0.32-0.47); and 36 or more months,
BPD, 308; ATPD, 10 645; and FES, 1250. The index episode is defined at the 0.51 (95% CI, 0.41-0.61).
1.0
a b
0.9 BLIPS
Risk of Psychotic Recurrence, Mean
BIPS
0.8
ATPD
0.7
BPD
0.6 FES
0.5 ATPD indicates acute and transient
psychotic disorder; BIPS, brief
0.4 intermittent psychotic symptoms;
0.3 BLIPS, brief limited intermittent
psychotic symptoms; BPD, brief
0.2 psychotic disorder; and FES, remitted
0.1 first-episode schizophrenia.
a
P < .05 compared with BLIPS, BIPS,
0
6 12 24 ≥36 ATPD, and BPD.
b
Follow-up Time, mo P < .001 compared with BLIPS,
BIPS, ATPD, and BPD.
pothesis, the risk of psychotic recurrence in the long term (24 their comparable risks of psychotic recurrence over time, fur-
and ≥36 months) was significantly higher in the FES group com- ther suggesting a need for some psychometric standardiza-
pared with the other 4 groups. tion across the 2 competing definitions.66
This novel study has provided combined, robust meta- In addition, our meta-analysis suggests that BLIPS and BIPS
analytical evidence from 11 133 patients with first-episode, brief are prognostically overlapping with ATPD and BPD (Table 2),
psychotic episodes in contrast to single studies, in which the which challenges both the validity of BLIPS and BIPS as
sample size of brief psychotic episodes is relatively small. Our high-risk states for psychosis onset and the arbitrary use67 of
primary findings of no meta-analytical prognostic differ- psychosis severity thresholds in this field to discriminate be-
ences in the risk of psychotic recurrence between ATPD and tween high-risk states and frank psychotic disorders.65 The
BPD are in line with original data indicating good concor- overlap is confirmed by our supplementary analysis showing
dance between the 2 constructs, further supporting the claim a similar risk of brief psychotic episodes developing into schizo-
that there is no “clinical, practical, theoretical reason to sepa- phrenia in BLIPS and BIPS (21%) and in ATPD and BPD (15%)
rate them.14(p15) An earlier study33 in 42 patients with ATPD by 24 months (eFigure 3B in the Supplement). The speed of
found that 62% also fulfilled the BPD criteria. A follow-up progression to psychotic recurrence is also similar, with a mean
study62 in 343 patients with their first psychiatric hospitaliza- time to diagnosis of less than 2 years for both BLIPS and BIPS68
tion showed that the diagnoses were ATPD in 29% and BPD in and ATPD. 69 Although the founders of the BIPS concept
25%, for an overall κ score of 0.71. Other studies conducted in acknowledged that “patients whose fully psychotic experi-
500 patients63 and 403 patients64 with a first brief psychotic ence is of sufficient short duration to meet DSM criteria for brief
episode confirmed similar 2-year63 and 10-year64 prospective psychotic disorder could potentially meet prodromal
consistency across ATPD and BPD. Despite this consistency, criteria,” 13(p707) our meta-analysis is the first convincing
some notable differences between DSM-5 and ICD-10 remain evidence supporting this notion. Our prognostic overlap is
(Table 1). For example, schizophreniform features are coded further corroborated by converging evidence indicating
within the ATPD (subtype acute schizophrenia-like psychotic that BLIPS and BIPS present distinctive diagnostic, 4 0
disorder), although they are coded as an independent schizo- psychopathological,35 prognostic,39 and therapeutic needs70
phreniform disorder in the DSM-5. Some of these controver- when compared with the other high-risk groups.39 The level
sies will be addressed by the diagnostic revision planned in the of risk of BLIPS and BIPS is comparable to that of ATPD and
next ICD manual (ICD-11),34 in which only the subtype poly- BPD (current finding) and significantly higher than that of at-
morphic psychotic disorder without symptoms of schizophre- tenuated psychosis symptoms and genetic risk and deterio-
nia (F23.0) will be retained as ATPD (eDiscussion 1 in the ration syndrome.39 Therefore, the mixture of BLIPS and BIPS
Supplement). and attenuated psychotic symptoms seems unjustified as a ho-
The absence of a meta-analytical prognostic difference be- mogeneous group expressing a unitary level of risk for psy-
tween BLIPS and BIPS calls into question the strict 7-day du- chosis onset. In addition, because indicated prevention
ration of BLIPS. The psychosis threshold is higher in the BIPS strategies71,72 target people at high risk who do not meet the
than in the BLIPS construct (psychotic symptoms may last for diagnostic criteria for a disorder73 (ie, with attenuated psy-
>7 days to 3 months); at the same time, the psychosis thresh- chosis symptoms), it is problematic that BLIPS and BIPS fall
old is lower in the BIPS than in the BLIPS since the BIPS symp- outside this framework qualifying as prevention of psychotic
toms should not have urgency features65 (“urgency is any posi- recurrence73 (eDiscussion 2 in the Supplement).
tive psychotic symptom that is seriously disorganizing or One possible option would be to drop BLIPS and BIPS from
dangerous no matter what the duration”29(p15)). These 2 dif- the clinical high-risk rubric. This deletion would mirror the ap-
ferences may counterbalance each other and hence explain proach of excluding BLIPS and BIPS in the recent DSM-5 cat-
egory of attenuated psychosis syndrome.74 However, adopt- tions on psychotic recurrence (eFigure 1A in the Supple-
ing only the attenuated psychosis symptoms subgroup would ment), although there were no effects for the type of antipsy-
prevent research in individuals with BLIPS and BIPS, who have chotic discontinuation (eFigure 1B in the Supplement) or the
a particularly high risk of psychosis. Furthermore, exclusion criteria used to define remission (eFigure 1C in the Supple-
of the BLIPS and BIPS may cause a further significant drop in ment). Nevertheless, these findings should be interpreted cau-
transition risks.75 Innovative strategies combining homoge- tiously because this study was not primarily designed to test
neous high-risk samples with attenuated psychotic symp- the effect of antipsychotic treatment on prevention of psy-
toms only and neurodevelopmental deficits may yield a clini- chotic recurrence.80-82 Overall, the reduced risk of psychotic
cally significant risk enrichment (3-year risk of psychosis of recurrence among brief psychotic episodes is in line with ear-
28%).76 A more complex option would be to accept the no- lier claims (in 199783) and later findings indicating an overall
tion that BLIPS and BIPS represent a distinct and separate group more favorable outcome in the domains of social disability, psy-
at higher risk of psychotic recurrence than the attenuated psy- chological impairment, and general functioning84 compared
chotic group39 that prognostically overlaps with ATPD and BPD, with patients in the schizophrenia spectrum. Because our find-
in the hope of harmonizing the 4 competing constructs. This ings are robust and not affected by publication bias, they may
overlap would better fit the notion of different levels of risk serve as reliable predictive validators46 for the delineation of
purported by the clinical staging model.77 However, it would brief psychotic episodes from remitted first-episode schizo-
also require redefining the psychotic threshold to be used in phrenia (eDiscussion 3 in the Supplement). Data from this study
this clinical staging model. For instance, a duration of psy- could also be useful for future designation of early interven-
chotic symptoms from 1 day to 1 month could be used to de- tion programs and for the development of specific treatment
marcate brief psychotic episodes from attenuated psychotic guidelines or clinical services addressing the specific needs of
symptoms and from persisting psychotic disorders. Compro- these patients. For example, our risk estimates at different time
mising on the 1-month duration for brief psychotic disorders points are clinically useful, allowing health care profession-
would also align BLIPS and BIPS with ATPD in ICD-11 and BPD als to inform patients and caregivers about the likely risks at a
in DSM-5. Such a cross-diagnostic approach would fit with the particular time after their index episode (eDiscussion 4 in the
DSM-5—which uses the level, number, and duration of psy- Supplement).
chotic signs and symptoms to demarcate psychotic disorders There are some limitations to this study. Evidence of
from each other78—together with the new Clinician-Rated Di- absence is not absence of evidence.85 However, our meta-
mensions of Psychosis Symptom Severity79 scale. ATPD and analysis included a large data set with up to 11 133 patients
BPD frequently represent up to 6% of all first-episode when some statistically significant findings were obtained.
psychoses,64 with an incidence of approximately 4 per 100 000 Furthermore, we did not investigate outcomes other than
per year.69 Therefore, a conceptual model encompassing 2 dis- psychotic recurrence. There is some evidence that a substan-
tinct clinical stages of attenuated psychotic symptoms and brief tial proportion of patients with ATPD may show nonpsy-
psychotic episodes may significantly increase the clinical abil- chotic affective episodes during follow-up.84 In addition, we
ity to predict later development of persisting (ie, lasting more did not include affective psychoses as an additional compari-
than 1 month) psychotic disorders. Indeed, early accounts have son group. For example, the association between brief psy-
suggested that diagnostic instability and reported that change chotic episodes and bipolar affective disorders has been
in ATPD and BPD is evident in approximately half of the questioned. 86 However, pilot literature searches did not
patients.69 Given the lack of data to guide evidence-based treat- uncover enough data for a quantitative meta-analysis of the 2
ment recommendations and clinical management of BPDs, the points above. Finally, the actual proportion of baseline diag-
combined model may also facilitate future research and the nostic overlap between BLIPS and BIPS versus ATPD and BPD
development of tailored guidelines to prevent persisting remains unknown.
psychotic disorders.
To provide a clinical benchmark, we used a comparison
group of patients with remitted FES as a secondary outcome.
We showed that brief psychotic episodes have a better long-
Conclusions
term outcome than remitted FES after 24 months. The lower We found meta-analytical evidence for a better long-term prog-
risk of psychotic recurrence was remarkable at 36 or more nosis of brief psychotic episodes compared with remitted first-
months, when most patients with FES who had previous re- episode schizophrenia but no prognostic differences be-
mission had developed another psychotic episode compared tween ATPD, BPD, BLIPS, and BIPS. Achieving diagnostic
with only half of those with an initial brief psychotic episode consensus across competing diagnostic constructs will greatly
(defined as ATPD, BPD, BLIPS, and BIPS). Supplementary analy- assist future attempts to identify the most effective ways to
ses showing no significant differences at 6 and 12 months may prevent psychotic recurrence after initial brief psychotic
suggest a possible protective effect of antipsychotic medica- episodes.
ARTICLE INFORMATION Published Online: January 13, 2016. Psychiatry, London, England (Fusar-Poli,
Submitted for Publication: June 9, 2015; final doi:10.1001/jamapsychiatry.2015.2313. Cappucciati, Bonoldi, Rutigliano, McGuire); OASIS
revision received October 1, 2015; accepted Author Affiliations: Department of Psychosis Service, South London and the Maudsley National
October 2, 2015. Studies, King’s College London, Institute of Health Service Foundation Trust, London, England
(Fusar-Poli); Department of Brain and Behavioral 8. Störring GE, Suchenwirth R, Völkel H. 28. American Psychiatric Association. Diagnostic
Sciences, University of Pavia, Pavia, Italy Emotionalität und cycloide Psychosen. Psychiatr and Statistical Manual of Mental Disorders. 5th ed.
(Fusar-Poli, Cappucciati, Bonoldi, Politi); Neurol Med Psychol (Leipz). 1962;14:85-97. Arlington, VA: American Psychiatric Association; 2013.
Department of Psychiatry, University of Hong Kong, 9. Mitsuda H. The concept of “atypical psychoses” 29. McGlashan TH, Walsh B, Wood SJ. The
Hong Kong SAR, China (Hui); Department of from the aspect of clinical genetics. Acta Psychiatr Psychosis-Risk Syndrome: Handbook for Diagnosis
Biostatistics, King's College London, Institute of Scand. 1965;41(3):372-377. and Follow-up. New York, NY: Oxford University Press;
Psychiatry, London, England (Stahl); Department of 2010.
Psychiatry, University of Basel Psychiatric Clinics, 10. Langfeldt G. The Schizophreniform States.
Basel, Switzerland (Borgwardt); Department of Copenhagen, Denmark: E Munksgaard; 1939. 30. Yung AR, Phillips LJ, Yuen HP, McGorry PD.
Clinical Psychology, Chicago School of Professional 11. Yung AR, McGorry PD, McFarlane CA, Jackson Comprehensive Assessment of At-Risk Mental State.
Psychology, Southern California Campus, HJ, Patton GC, Rakkar A. Monitoring and care of Parkville, Australia: PACE Clinic, ORYGEN Research
Los Angeles, California (Mishara); Division of young people at incipient risk of psychosis. Centre, Dept of Psychiatry, University of Melbourne;
Psychiatry, University of Edinburgh, Edinburgh, Schizophr Bull. 1996;22(2):283-303. 2006.
Scotland (Lawrie); Maryland Psychiatric Research 12. Kistler JP, Ropper AA, Martin JB. 31. Pillmann F, Marneros A. Longitudinal follow-up
Center, University of Maryland School of Medicine, Cerebrovascular diseases. In: Wilson JD, Braunwald in acute and transient psychotic disorders and
Baltimore (Carpenter); Veterans Affairs Capitol E, Isselbacher KJ, et al, eds. Harrison’s Principles of schizophrenia. Br J Psychiatry. 2005;187:286-287.
Health Care Network, Mental Illness Research, Internal Medicine. New York, NY: McGraw-Hill; 1991: 32. Pillmann F, Haring A, Balzuweit S, Marneros A.
Education, and Clinical Center, Veterans Integrated 1977-2002. A comparison of DSM-IV brief psychotic disorder
Service Network, Baltimore, Maryland (Carpenter). with “positive” schizophrenia and healthy controls.
13. Miller TJ, McGlashan TH, Rosen JL, et al.
Author Contributions: Dr Fusar-Poli had full access Prodromal assessment with the Structured Compr Psychiatry. 2002;43(5):385-392.
to all the data in the study and takes responsibility Interview for Prodromal Syndromes and the Scale 33. Pillmann F, Haring A, Balzuweit S, Blöink R,
for the integrity of the data and the accuracy of the of Prodromal Symptoms: predictive validity, Marneros A. The concordance of ICD-10 acute and
data analysis. interrater reliability, and training to reliability. transient psychosis and DSM-IV brief psychotic
Study concept and design: Fusar-Poli, Cappucciati, Schizophr Bull. 2003;29(4):703-715. disorder. Psychol Med. 2002;32(3):525-533.
Politi, Mishara, Carpenter, McGuire.
Acquisition, analysis, or interpretation of data: 14. Marneros A, Pillmann P. Acute and Transient 34. Castagnini A, Foldager L. Epidemiology, course
Fusar-Poli, Cappucciati, Bonoldi, Hui, Rutigliano, Psychoses. Cambridge, England: Cambridge and outcome of acute polymorphic psychotic
Stahl, Borgwardt, Lawrie, Carpenter, McGuire. University Press; 2004. disorder: implications for ICD-11. Psychopathology.
Drafting of the manuscript: Fusar-Poli, Cappucciati. 15. Morel BA. Traité des dégénérescences de 2014;47(3):202-206.
Critical revision of the manuscript for important l’espèce humaine. Paris, France: Chez Bailliere; 1857. 35. Fusar-Poli P, Borgwardt S, Bechdolf A, et al. The
intellectual content: All authors. 16. Ey H. Bouffées délirantes’ et psychoses psychosis high-risk state: a comprehensive
Statistical analysis: Fusar-Poli, Cappucciati, Stahl. hallucinatoires aiguës: etudes psychiatriques. In: state-of-the-art review. JAMA Psychiatry. 2013;70
Obtained funding: McGuire. Structure des Psychoses Aigues et Déstructuration (1):107-120.
Administrative, technical, or material support: de la Conscience. Vol 3. Paris, France: Desclée de 36. Yung AR, Yuen HP, McGorry PD, et al. Mapping
Fusar-Poli, Bonoldi, Hui, McGuire. Brower; 1954:203-324. the onset of psychosis: the Comprehensive
Study supervision: Fusar-Poli, Borgwardt, Politi, Assessment of At-Risk Mental States. Aust N Z J
Lawrie, McGuire. 17. Pichot P. The concept of bouffée délirante with
special reference to the Scandinavian concept of Psychiatry. 2005;39(11-12):964-971.
Conflict of Interest Disclosures: None reported. reactive psychosis. Psychopathology. 1986;19(1-2): 37. Wolf ME, Held VE, Hennerici MG. Risk scores
Funding/Support: This study was supported in 35-43. for transient ischemic attack. Front Neurol Neurosci.
part by a 2014 Young Investigator Award from the 18. Mitsuda H. Klinisch-erbbiologische 2014;33:41-68.
Brain and Behaviour Research Foundation (Dr Untersuchung der Schizophrenie [in Japanese with 38. Yung AR, Phillips LJ, Yuen HP, McGorry PD. Risk
Fusar-Poli). German abstract]. Psychiatr Neurol (Basel). 1942; factors for psychosis in an ultra high-risk group:
Role of the Funder/Sponsor: The funding 46:298-362. psychopathology and clinical features. Schizophr Res.
organization had no role in the design and conduct 19. Jaspers K. Allgemeine Psychopathologie. Berlin, 2004;67(2-3):131-142.
of the study; collection, management, analysis, and Germany: Springer; 1913. 39. Fusar-Poli P, Cappucciati M, Borgwardt S, et al.
interpretation of the data; preparation, review, or Heterogeneity of psychosis risk within individuals at
approval of the manuscript; and decision to submit 20. Wimmer A. Psykogene sindssygdomsformer.
In: Wimmer A, ed. Jubilee Publication, St. Hans clinical high risk: a meta-analytical stratification
the manuscript for publication. [published online December 30, 2015]. JAMA
Hospital 1816-1916. Copenhagen, Denmark: Gad;
1916:85-216. Psychiatry. doi:10.1001/jamapsychiatry.2015.2324.
REFERENCES
21. Strömgren E. Psychogene Psychosen. Nervenarzt. 40. Winton-Brown TT, Harvey SB, McGuire PK. The
1. World Health Organization. International diagnostic significance of BLIPS (brief limited
Statistical Classification of Diseases, 10th Revision. 1986;57:88-95.
intermittent psychotic symptoms) in psychosis.
Geneva, Switzerland: World Health Organization; 22. Faergeman P. Psychogenic Psychoses. London, Schizophr Res. 2011;131(1-3):256-257.
1992. England: Butterworth; 1963.
41. Schultze-Lutter F, Schimmelmann BG,
2. Pillmann F, Marneros A. Brief and acute 23. Wernicke C. Grundriss der Psychiatrie in Ruhrmann S. The near Babylonian speech confusion
psychoses: the development of concepts. Hist klinischen Vorlesungen. Leipzig, Germany: Thieme; in early detection of psychosis. Schizophr Bull. 2011;
Psychiatry. 2003;14(54, pt 2):161-177. 1900. 37(4):653-655.
3. Kahlbaum L. Die Gruppirung psychischer 24. Kleist K. Über die gegenwärtigen Strömungen 42. Zhang JP, Gallego JA, Robinson DG, Malhotra
Krankheiten. Danzig, Germany: Kafemann; 1863. in der klinischen Psychiatrie. Allegemeine Zeitschrift AK, Kane JM, Correll CU. Efficacy and safety of
4. Kraepelin E. Psychiatrie: Ein Lehrbuch für für Psychiatrie. 1924;81:389-393. individual second-generation vs first-generation
Studirende und Aerzte: 5, vollständig umgearbeitete 25. Schröder P. Über Degenerationspsychosen antipsychotics in first-episode psychosis:
Auflage. Leipzig, Germany: Barth; 1896. (Metabolische Erkrankungen). Z Gesamte Neurol a systematic review and meta-analysis. Int J
5. Magnan V, Legrain M. Les Dégénérés: Etat Psychiatr. 1926;105:539-547. Neuropsychopharmacol. 2013;16(6):1205-1218.
Mental et Syndromes Épisodiques. Paris, France: Rueff 26. Perris C, Brockington IF. Cycloid psychosis and 43. Fusar-Poli P, Yung AR, McGorry P, van Os J.
et Cie; 1895. their relation to the major psychosis. In: Perris C, Lessons learned from the psychosis high-risk state:
6. Leonhard K. Die Aufteilung der endogenen Struwe D, Janson B, eds. Biological Psychiatry. towards a general staging model of prodromal
Psychosen: 1. Berlin, Germany: Akademie-Verlag; 1957. Amsterdam, the Netherlands: Elsevier; 1981:447-450. intervention. Psychol Med. 2014;44(1):17-24.
7. Jaspers K. General Psychopathology. Chicago, IL: 27. Staehelin JE. Zur Frage der Emotionspsy- 44. Stafford MR, Jackson H, Mayo-Wilson E,
University of Chicago Press; 1963. chosen. Bull Schweiz Akad Med Wiss. 1946;2:121-130. Morrison AP, Kendall T. Early interventions to
prevent psychosis: systematic review and 59. Sterne JA, Egger M, Smith GD. Systematic Options. Geneva, Switzerland: Dept of Mental Health
meta-analysis. BMJ. 2013;346:f185. reviews in health care: investigating and dealing and Substance Abuse, WHO; 2004.
45. Kapur S, Phillips AG, Insel TR. Why has it taken with publication and other biases in meta-analysis. 74. Fusar-Poli P, Carpenter W, Wood S, McGlashan
so long for biological psychiatry to develop clinical BMJ. 2001;323(7304):101-105. T. Attenuated psychosis syndrome: ready for
tests and what to do about it? Mol Psychiatry. 2012; 60. Egger M, Davey Smith G, Schneider M, Minder DSM-5.1? Annu Rev Clin Psychol. 2014;10:155-192.
17(12):1174-1179. C. Bias in meta-analysis detected by a simple, 75. Simon AE, Umbricht D, Lang UE, Borgwardt S.
46. Kendell R, Jablensky A. Distinguishing between graphical test. BMJ. 1997;315(7109):629-634. Declining transition rates to psychosis: the role of
the validity and utility of psychiatric diagnoses. Am 61. Harbord R, Harris R, Sterne A. Updated tests for diagnostic spectra and symptom overlaps in
J Psychiatry. 2003;160(1):4-12. small-study effects in meta-analyses. Stata J. individuals with attenuated psychosis syndrome.
47. Stroup DF, Berlin JA, Morton SC, et al. 2009;9(2):197-210. Schizophr Res. 2014;159(2-3):292-298.
Meta-analysis of observational studies in 62. Möller HJ, Jäger M, Riedel M, Obermeier M, 76. Cornblatt BA, Carrion RE, Auther A, et al.
epidemiology: a proposal for reporting: Strauss A, Bottlender R. The Munich 15-year Psychosis prevention: a modified clinical high risk
Meta-analysis Observational Studies in follow-up study (MUFUSSAD) on first-hospitalized perspective from the Recognition and Prevention
Epidemiology (MOOSE) group. JAMA. 2000;283 patients with schizophrenic or affective disorders: (RAP) Program. Am J Psychiatry. 2015;172(10):986-
(15):2008-2012. assessing courses, types and time stability of 994.
48. Riecher-Rössler A, Aston J, Ventura J, et al. The diagnostic classification. Eur Psychiatry. 2011;26(4): 77. McGorry PD. Early clinical phenotypes, clinical
Basel Screening Instrument for Psychosis (BSIP): 231-243. staging, and strategic biomarker research: building
development, structure, reliability and validity [in 63. Salvatore P, Baldessarini RJ, Tohen M, et al. blocks for personalized psychiatry. Biol Psychiatry.
German]. Fortschr Neurol Psychiatr. 2008;76(4): McLean-Harvard International First-Episode 2013;74(6):394-395.
207-216. Project: two-year stability of ICD-10 diagnoses in 78. Heckers S, Barch DM, Bustillo J, et al. Structure
49. Castagnini A, Berrios GE. Acute and transient 500 first-episode psychotic disorder patients. J Clin of the psychotic disorders classification in DSM-5.
psychotic disorders (ICD-10 F23): a review from a Psychiatry. 2011;72(2):183-193. Schizophr Res. 2013;150(1):11-14.
European perspective. Eur Arch Psychiatry Clin 64. Heslin M, Lomas B, Lappin JM, et al. Diagnostic 79. Tandon R, Gaebel W, Barch DM, et al. Definition
Neurosci. 2009;259(8):433-443. change 10 years after a first episode of psychosis. and description of schizophrenia in the DSM-5.
50. Correll CU, Smith CW, Auther AM, et al. Psychol Med. 2015;45(13):2757-2769. Schizophr Res. 2013;150(1):3-10.
Predictors of remission, schizophrenia, and bipolar 65. Fusar-Poli P, Van Os J. Lost in transition: setting 80. Kishimoto T, Agarwal V, Kishi T, Leucht S, Kane
disorder in adolescents with brief psychotic psychosis threshold in prodromal research. Acta JM, Correll CU. Relapse prevention in
disorder or psychotic disorder not otherwise Psychiatr Scand. 2013;127(3):248-252. schizophrenia: a systematic review and
specified considered at very high risk for 66. Fusar-Poli P, Cappucciati M, Rutigliano G, et al. meta-analysis of second-generation antipsychotics
schizophrenia. J Child Adolesc Psychopharmacol. At risk or not at risk? meta-analysis of the versus first-generation antipsychotics. Mol Psychiatry.
2008;18(5):475-490. prognostic accuracy of psychometric interviews for 2013;18(1):53-66.
51. Memon MA. Brief psychotic disorder treatment psychosis prediction. World Psychiatry. 2015;14(3): 81. Leucht S, Barnes TR, Kissling W, Engel RR,
& management. Medscape News & Perspective 322-332. Correll C, Kane JM. Relapse prevention in
website. http://emedicine.medscape.com/article 67. Yung AR, Nelson B, Thompson A, Wood SJ. The schizophrenia with new-generation antipsychotics:
/294416-treatment#d1. Published September 3, psychosis threshold in ultra high risk (prodromal) a systematic review and exploratory meta-analysis
2013. Accessed October 30, 2015. research: is it valid? Schizophr Res. 2010;120(1-3):1- of randomized, controlled trials. Am J Psychiatry.
52. Moher D, Liberati A, Tetzlaff J, Altman DG; 6. 2003;160(7):1209-1222.
PRISMA Group. Preferred reporting items for 68. Kempton MJ, Bonoldi I, Valmaggia L, McGuire 82. Leucht S, Tardy M, Komossa K, et al.
systematic reviews and meta-analyses: the PRISMA P, Fusar-Poli P. Speed of psychosis progression in Antipsychotic drugs versus placebo for relapse
statement. BMJ. 2009;339:b2535. people at ultra-high clinical risk: a complementary prevention in schizophrenia: a systematic review
53. Nyaga VN, Arbyn M, Aerts M. Metaprop: a Stata meta-analysis. JAMA Psychiatry. 2015;72(6):622-623. and meta-analysis. Lancet. 2012;379(9831):2063-
command to perform meta-analysis of binomial 69. Queirazza F, Semple DM, Lawrie SM. Transition 2071.
data. Arch Public Health. 2014;72(1):39. to schizophrenia in acute and transient psychotic 83. Jørgensen P, Bennedsen B, Christensen J,
54. Newcombe RG. Two-sided confidence intervals disorders. Br J Psychiatry. 2014;204:299-305. Hyllested A. Acute and transient psychotic disorder:
for the single proportion: comparison of seven 70. Fusar-Poli P, Frascarelli M, Valmaggia L, et al. a 1-year follow-up study. Acta Psychiatr Scand.
methods. Stat Med. 1998;17(8):857-872. Antidepressant, antipsychotic and psychological 1997;96(2):150-154.
55. Freeman MF, Tukey JW. Transformations interventions in subjects at high clinical risk for 84. Marneros A, Pillmann F, Haring A, Balzuweit S,
related to the angular and the square root. Ann psychosis: OASIS 6-year naturalistic study. Psychol Blöink R. What is schizophrenic in acute and
Math Stat. 1950;21:607-611. Med. 2015;45(6):1327-1339. transient psychotic disorder? Schizophr Bull. 2003;
56. DerSimonian R, Laird N. Meta-analysis in 71. Mrazek P, Haggerty R. Reducing Risks for Mental 29(2):311-323.
clinical trials. Control Clin Trials. 1986;7(3):177-188. Disorders: Frontiers for Preventive Intervention 85. Altman DG, Bland JM. Absence of evidence is
57. Lipsey M, Wilson D. Practical Meta-analysis. Research. Washington, DC: National Academy Press; not evidence of absence. BMJ. 1995;311(7003):485.
Thousand Oaks, CA: Sage Publications; 2000. 1994. 86. Marneros A, Pillmann F, Haring A, Balzuweit S,
58. Steichen T. METANINF: Stata Module to 72. Gordon RS Jr. An operational classification of Blöink R. The relation of “acute and transient
Evaluate Influence of a Single Study in Meta-analysis disease prevention. Public Health Rep. 1983;98(2): psychotic disorder” (ICD-10 F23) to bipolar
Estimation, Statistical Software Components 107-109. schizoaffective disorder. J Psychiatr Res. 2002;36
S419201. Boston, MA: Dept of Economics, Boston 73. World Health Organization. Prevention of (3):165-171.
College; 2001. Mental Disorders: Effective Interventions and Policy
E10 JAMA Psychiatry Published online January 13, 2016 (Reprinted) jamapsychiatry.com