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The ability of praecox-feeling to identify and predict
transition to schizophrenia in help-seeking individuals:
a systematic review
Juliana Fortes Lindau, Barnaby Nelson, Gennaro Catone, Paolo Fiori Nastro, Paolo Girardi, Andrea Cipriani, Belinda Lennox, Matthew Broome
Protocol
(Version 2.2 – August 2014) Juliana Fortes Lindau, M.D. Honorary Researcher, University Department of Psychiatry, Warneford Hospital Oxford OX3 7JX, UK NESMOS Department (Neurosciences, Mental Health and Sensory Functions), School of Medicine and Psychology, Sapienza University, Rome, Unit of Psychiatry, Sant’Andrea Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy Tel. +39-0633775951; +39-0633775342; e-mail: [email protected] Sources of support None
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Background
Schizophrenia is one of the most disabling and severe disorders in mental health
(Whiteford et al., 2013), with an incidence rate of around 15 cases per 100,000
(McGrath et al., 2004) and a prevalence that ranges from 4 to 7 per 1,000
persons, depending on the type of prevalence estimate used (Saha, Chant,
Welham, & McGrath, 2005). According to the Word Heath Organization (WHO)
schizophrenia affects around 24 million people worldwide, mostly in the age
group 15-35 years (World Health Organization., 2014). The first episode of
schizophrenia typically occurs in the late teenage years or the early 20s (Hafner
& Nowotny, 1995). However, the illness can remain undetected for about 2-3
years after the onset of clearly diagnosable symptoms (Loebel et al., 1992). Early
recognition is hindered by the often insidious nature of the onset of
schizophrenia, which occurs against a background of premorbid problems in
language, cognitive ability and behaviour (Frangou & Byrne, 2000).
Notwithstanding recent developments towards a better understanding of the
neurobiology, aetiology and pathophysiology of the disorder (van Os & Kapur,
2009), among clinicians and researchers the debate regarding the diagnosis of
schizophrenia is still open. No consensus has been reached so far whether to
focus mainly on the clinical presentation of the disorder and its symptoms (as all
the most important international operationalized diagnostic systems do), or to
look deeper at the “core” of schizophrenia (i.e. autism, lack of affectivity,
ambivalence, avolition, disturbance of self-consciousness) as originally described
in classical psychopathology and most of all by phenomenologist authors (Hojaij,
2000; Parnas, Bovet, & Zahavi, 2002). According to the latter perspective, the
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diagnostic intuition of the psychiatrist based on personal feelings, intuition,
thoughts and perceptions during the encounter with the patient (also called
clinician’s clinical impression) can play an important role (Kernberg, 1965;
Minkowski, 1970; Pallagrosi, Fonzi, Picardi, & Biondi, 2014).
Currently, one of the most important issues in the debate about the diagnosis of
schizophrenia is the delay of operationalized systems in detecting patients at
risk of developing psychosis (Parnas et al., 2012; F. Schultze-Lutter &
Schimmelmann, 2014). For many years, experts in the field of preventive
psychiatry have been focusing their attention to capture subjects in the pre-
psychotic phase of schizophrenia, because the earlier the recognition and the
intervention, the better the prognosis (better general and social functioning)
(Cechnicki et al., 2014), the better the treatment outcomes (lower number of re-
hospitalizations) (Helgason, 1990) and the lower the economic burden in terms
of costs for the health system (Valmaggia et al., 2009). Initially, this pre-
psychotic phase of schizophrenia was investigated retrospectively in patients
with full-blown symptoms, in order to collect specific information about the
prodromal phase of the disease. Some predisposing factors for psychosis were
identified (e.g. bizarre thinking, sleep disturbances, a schizotypal disorder,
recent deterioration in functioning) (Ruhrmann et al., 2010) and researchers
started to focus their attention on individuals at risk to become psychotic, like
help-seeking adolescents and young adults with subthreshold symptoms. The
prospective assessment of this new group of people, called ultra-high risk (UHR),
has generated new enthusiasm in the field of preventive psychiatry. Recent
estimates suggests that the risk of transition to psychosis in UHR subjects ranges
from 18% at 6 months to up to 32% by 3 years (Fusar-Poli et al., 2012).
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However, within this group, the existing criteria are neither sufficiently sensitive
nor specific to distinguish those at risk of schizophrenia from those at risk of
other psychotic disorders (Fusar-Poli & Borgwardt, 2007).
Among the different ways of coding clinician’s clinical impression, “Praecox
feeling” (PF) is the first one and probably one of the most important and
frequently quoted in the literature. The term was coined by Rümke more than 70
years ago to describe the intuitive and unique way psychiatrists can feel patients
with schizophrenia. In particular, the PF was used to indicate that detailed
experience that a psychiatrist feels as “inability to empathize” and “establish
contact” with the patient due to a breakdown of “the affective exchange”,
normally present in the relationship between two people. Even though it was
initially used to describe “this undefinable attribute that surrounds all the
observed symptoms”, its potential value for identifying patients with
schizophrenia was acknowledged by the author himself (Rümke, 1942). Over the
past 50 years, the diagnostic reliability of PF as has been investigated in many
studies (Irle, 1962; Sagi & Schwartz, 1989) but, interestingly, three recent
studies have reported conflicting results (Grube, 2006; Nelson & Yung, 2010;
Ungvari, Xiang, Hong, Leung, & Chiu, 2010). Two of these studies recruited
severely ill, psychotic patients and compared the ability of PF with the
international diagnostic classification systems (the Diagnostic and Statistical
Manual of Mental Disorders, 4th Edition (DSM IV) (American Psychiatric
Association., 1994) and the International statistical classification of diseases and
health-related problems, 10th Edition (ICD-10) (World Health Organization.,
1992) in identifying schizophrenic patients. The first study (Grube, 2006)
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included 67 patients with paranoid hallucinatory syndrome; aged between 18
and 49 years old (mean age 31.3 years). Compared to the standardised
diagnostic classifications, the precision of PF was remarkably high with a
sensitivity of about 0.85, specificity of about 0.80, a positive predictive power of
about 0.90 and a negative predictive power of about 0.65. By contrast, the
second study conducted in an heterogeneous sample of 102 consecutively
admitted patients showed low reliability of PF with poor results in terms of
sensibility, specificity and positive predictive value (less than 0.40) (Ungvari et
al., 2010). The contrasting findings between these two studies may be due to
some methodological flaws in Ungvari study’s design (for instance, the non-ideal
setting for the face-to-face interview or the selected questions used to
operationalize the PF), but also to their difference in terms of socio-
demographic variables, such as the clinical characteristics of the sample
population or the ways of expressing emotions, which can be country-specific.
The third study was the only one that was carried out to specifically investigate
the predictive value of “clinical impression” in UHR individuals (Nelson & Yung,
2010). This study was conducted in Australia and found no association between
clinical impression and risk of developing full-blown psychosis. Notwithstanding
the relatively large sample size, this study has some limitations: the participants
enrolled were non-consecutive patients attending their specialised clinic for
young people at risk of psychosis, all were taking active treatment and some of
them were involved in randomised controlled studies carried out in the same
clinic. Furthermore, in this study researchers looked at the ability of clinical
impression to predict transition to psychosis and did not specifically investigate
whether clinical impression can be a valid tool in predicting transition to
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schizophrenia specifically.
Considering the uncertainty about the diagnostic potential of PF, we will carry
out a systematic review of all the available evidence about the use and the ability
of PF in predicting future onset of schizophrenia in a population of help-seeking
and UHR people.
Objectives
1. To assess the use of PF in prodromal phase of schizophrenia
2. To assess, if any, the ability of PF in predicting first episode of psychosis
and transition to schizophrenia in two samples: help-seeking and UHR
population.
Methods
Types of studies and participants
We will include all observational studies that will report on the use of PF in a
clinical setting. Study participants will be of either sex, aged between 15 and 35
years old (World Health Organization., 2014), seeking assistance for
psychological distress or other problems, recruited in secondary care settings.
Substance abuse or dependence (including alcohol) will not be an exclusion
criterion. We will include both help-seeking and UHR individuals, as defined
below:
1. help-seeking: the behaviour of actively seeking help in terms of
understanding, advice, information, treatment, and general support in
response to a problem or distressing experience (Rickwood, Deane,
Wilson, & Ciarrochi, 2005);
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2. UHR: people with an imminent risk of conversion to a first episode of
psychosis usually defined by one or more of the following 3 groups,
according to either Comprehensive Assessment of At Risk Mental State
(CAARMS) (Yung et al., 2005) or Structured Interview for Prodromal
Symptoms (SIPS)/Scale of Prodromal Symptoms (SOPS) (Miller et al.,
2003):
i) Attenuated psychotic symptoms (APS): sub-threshold, attenuated
positive psychotic symptoms during the past year;
ii) Brief limited intermittent psychotic symptoms (BLIPS): hallucinations,
delusions or formal thought disorders resolving spontaneously within
1 week;
iii) Trait vulnerability plus a marked decline in psychosocial functioning
(Genetic Risk and Deterioration Syndrome: GRD): a first-degree
relative with a psychotic disorder or a DSM-IV schizotypal personality
disorder of the index person, combined with a significant decrease in
functioning during the past year.
Included and excluded studies will be collected following the Preferred
Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow
diagram (Moher, Liberati, Tetzlaff, Altman, & Group, 2009). Additionally, if there
is enough information to perform a meta-analysis, we will follow the Meta-
analysis Of Observational Studies in Epidemiology (MOOSE) guidelines (Stroup
et al., 2000).
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Definition of PF (or clinical impression)
Starting from the description of PF made by Rumke (Rümke, 1942) (that
experience that psychiatrists perceive as ‘inability to empathize’ and ‘establish
contact’ with the patients due to a breakdown of the ‘affective exchange’,
normally present in the relationship between two people), we will include any
study authors’ definition of PF, if recorded by:
1) Specific question asked by the clinician
2) General impression of the clinician
3) Any other tool (standardised or not standardised) used to describe
the PF
Definition of prodromal phase of schizophrenia
Prodromal phase can be divided into early and late prodromal phase (Fusar-Poli
et al., 2013).
To describe/diagnose the early prodromal phase we will consider the following
interview measure (Fusar-Poli et al., 2013):
1) The Basic Symptoms criteria (presence of at least any 1 of the 10 Cognitive-
Perceptive Symptoms (COPER) with a score ≥ 3 within the last three months
and first occurrence ≥ 12 months ago and/or presence of at least any 2 of 9
Cognitive Disturbances (COGDIS) score ≥ 3 within the last three months with
The Schizophrenia Proneness Instrument, Adult Version (SPI-A) for
individuals with more than 18 years (Frauke Schultze-Lutter, Addington,
Ruhrmann, & Klosterkötter, 2007) and with the Schizophrenia Proneness
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Instrument, Child and Youth Version (SPI-CY) for individuals with less than
18 years old) (Frauke Schultze-Lutter & Koch, 2010).
To describe/diagnose the late prodromal phase we will consider presence of one
or more of three alternative criteria (also known as “ultra” or “clinical” High-Risk
criteria) (Fusar-Poli et al., 2013):
i) APS group for CAARMS; presence of ≥ 1 of the subthreshold
attenuated positive symptoms (e.g. Ideas of reference, “magical”
thinking, perceptual disturbance, paranoid ideation, odd thinking and
speech) at least several time a week, present within the past year and
present for ≥ 1 week and ≤ 5 years AND decline in functioning ( Social
and Occupational Functioning Assessment Scale (SOFA) score at least
30% below the previous level, occurring within the last year) OR
sustained low functioning (SOFAS score of 50 or less for the past 12
months or longer).
APS group for SIPS/SOPS; presence of ≥ 1 of the subthreshold
attenuated positive symptoms (e.g. Unusual ideas,
paranoia/suspiciousness, grandiosity, perceptual disturbance,
conceptual disorganization); without psychotic-level conviction;
present within the past year and present for ≥ 1 week in the past
month.
ii) BLIPS for CAARMS; presence of ≥ 1 of the Transient psychotic
symptoms (symptoms in the subscales of unusual thought content,
non-bizarre ideas, perceptual abnormalities, disorganized speech);
duration of the episode ≤1 week; spontaneous remission; symptoms
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occurred within the past 12 month; AND decline in functioning OR
sustained low functioning by SOFAS criteria. BLIPS for SIPS/SOPS
Transient psychotic symptoms in the realm of delusions,
hallucinations, disorganization; intermittently for at least several
minutes per day at least once per month, but < 1 h/d, < 4 d/week over
1 month. Onset in past 3 month. Symptoms are not seriously
disorganizing or dangerous.
iii) GRD for CAARMS; Family history of psychosis OR an individual with
schizotypal personality disorder AND a decline in functioning OR
sustained low functioning by SOFAS criteria.
GRD for SIPS/SOPS; First-degree relative with a psychotic disorder OR
an individual with schizotypal personality disorder AND a significant
decrease in functioning in the past month compared with 1 year ago
(30% decrease in Global Assessment of Functioning Scale score for
premorbid baseline).
In order to be comprehensive in the assessment of prodromal phase of
schizophrenia, we will also include Basic Self-Disturbance by the Examination of
Anomalous Self-Experience (EASE) instrument (Parnas et al., 2005). Even if the
scale cannot be used alone as a diagnostic instrument, however, recently it has
been studied the utility of self-disorders for predicting later schizophrenia-
spectrum disturbance (Nelson, Thompson, & Yung, 2012). The EASE is a
symptom checklist for semi-structured phenomenological exploration of
subjective anomalies representative of basic self-disturbance. It consists of 57
items in 5 domains, which are not mutually exclusive: (a) cognition and stream
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of consciousness (17 items), (b) self-awareness and presence (18 items), (c)
bodily experiences (9 items), (d) demarcation/transitivism (5 items), and (e)
existential reorientation (8 items). Symptoms can be rated both dichotomously,
(i.e., present or absent), or continuously (on a 5-point severity/frequency scale).
Definition of first episode of psychosis
We will define the first episode of psychosis (FEP) as follows: (i) more than 1
week of psychotic symptoms according to CAARMS, (ii) presence of psychotic
symptoms for more than 1 hour/day for more than 4 days/week during 1 month
according to SIPS/SOPS, OR (iii) seriously disorganizing and dangerous
psychotic symptoms according to SIPS/SOPS.
Definition of schizophrenia
We will define “schizophrenia” according to the major international diagnostic
classification systems, as follows:
1. DSM IV-TR (American Psychiatric Association., 2000) or previous
editions. DSM-III (American Psychiatric Association., 1980), DSM-III-R
(American Psychiatric Association., 1987), DSM-IV (American Psychiatric
Association., 1994)
2. ICD-10 (World Health Organization., 1992) or previous editions ICD-8
(World Health Organization., 1974), ICD-9 (Commission on Professional
and Hospital Activities. & World Health Organization., 1978)
3. The Research Diagnostic Criteria (RDC) (Spitzer, Endicott, & Robins,
1975)
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4. Bleuler’s schizophrenia (Bleuler, 1950)
5. Mayer-Gross's schizophrenia (Mayer-Gross & Moore, 1944)
6. Schneider's first-rank criteria (Schneider, 1959)
7. The Feighner criteria (Feighner et al., 1972)
Operational diagnostic criteria essentially similar to the above will be included.
Types of outcome measures
Primary outcomes:
(i) Number of studies reporting the use of PF in the prodromal phase of
schizophrenia, together with the description of the socio-demographic and
clinical characteristics of the sample population (age, sex, education,
information about admission, treatment, comorbid diagnosis, etc.).
(ii) Description of the main characteristics of PF and how it was measured.
Secondary outcomes:
(i) Number of UHR or help seeking patients developing first episode
schizophrenia. For this outcome, we will consider only observational with a
follow up period of at least 6 months (Fusar-Poli et al., 2012).
Search Strategy and Data Extraction
Electronic searches
Relevant studies will be located by searching MEDLINE, PubMed, EMBASE,
PsychINFO using the terms:
(psychotic$ or psychos$ or schizo$).ti,ab,hw.
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AND
(((incipient or imminent) adj2 (psychos$ or risk$)) or pre?psychotic or
prodrom$ or (psychotic adj2 symptom$) or ((at risk or (high adj2 risk$)) adj4
psychos$) or future psychosis or psychosis risk syndrome or (sub?threshold adj
(syndrom$ or symptom$)) or (risk$ adj3 (develop$ or future or progress$) adj3
psychos$) or ultra high risk).ti,ab,hw.
OR
(help?seek$ or ((search$ or seek$) adj4 (care or assistance or counsel$ or
healthcare or help$ or support$ or therap$ or treat$))).ti,ab. or (help?seek$ or
health care seek$).hw.
AND
((clinical adj (decision making or judgement or prediction)) or impression or
intuitive or intuition or praecox$).ti,ab.
OR
((detect$ or diagnos$ or identif$ or predict$ or recogni$) and risk$).ti,ab,hw.
‘adolescent*’, ‘young adult*’, ‘help-seeking’, ‘Youth mental health’, ‘ultra hight
risk’, ‘at hight risk’, ‘uhr’ AND ‘praecox-feeling’ AND ‘prodrome’ ‘psychosis risk
syndrome’, ‘schizophrenia’, ‘psychotic*episode’, ‘schizophrenia spectrum
disorder*’, ‘transition’, ‘conversion’.
No language restriction will be applied. Reference lists of relevant papers and
previous review articles will hand searched for other relevant studies.
Study selection, data extraction and assessment of risk of bias
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Two review authors (JFL and GC) will independently screen title and abstract for
inclusion of all the potential studies we identify as a result of the search and code
them as “retrieve” (eligible or potentially eligible/unclear) or “do not retrieve”.
We will retrieve the full-text study reports/publication and two review authors
(JFL, GC) will independently screen the full-text and identify studies for
inclusion, and identify and record reasons for exclusion of the ineligible studies.
We will resolve any disagreement through discussion or, if required, we will
consult a third person (MB or BL). We will identify and exclude duplicate records
and we will collate multiple reports that relate to the same study so that each
study rather than each report is the unit of interest in the review.
We will use a data collection form to extract study characteristics and outcome
data. Two review authors (JFL, GC) will extract study characteristics and
outcome data from included studies. We will extract the following study
characteristics:
(i)Participant characteristics (age, sex, diagnosis, study setting);
(ii) measurements details (measurements of PF, measurements prodromal
phase and UHR, measurements outcomes of schizophrenia);
(iii) outcome measures of interest from the included studies.
Two authors (JFL and GC) will assess the risk of bias independently. Since all the
included studies will be non-randomized with a cohort or case–control design,
the Newcastle–Ottawa Scale (NOS) will be used to judge study quality, as
recommended by the Cochrane Collaboration (J. P. T. Higgins, Green, & Cochrane
Collaboration., 2008). This scale uses a star system to assess the quality of a
study in three domains: selection, comparability, and outcome (cohort studies)
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or exposure (case–control studies). The NOS assigns a maximum of four stars for
selection, two stars for comparability, and three stars for exposure/ outcome.
Therefore, nine stars reflect the highest quality. Any discrepancies will be
addressed by a joint revaluation of the original article with a third author (AC).
We will record the review authors’ judgments about the three NOS domains
(selection, comparability and exposure or outcome) in the Risk of Bias tool of the
Review Manager software of the Cochrane Collaboration. This tool allows us to
keep a record of the background reasons for each judgment, and will be
additionally used to produce a graphical representation of quality ratings similar
to that produced by Cochrane reviews for randomized studies, as suggested by
Wells (Wells et al., 2013).
Data Synthesis
Depending on the information retrieved from the systematic review, we will try
to merge the outcome data and carry out a meta-analysis using summary odds
ratios (ORs). When possible, we will pool adjusted relative risks or ORs or hazard
ratios, with their 95 % confidence interval (CI), with the assumption that these
are comparable measures of association; otherwise we will use raw data to
compute unadjusted ORs (Canonico, Plu-Bureau, Lowe, & Scarabin, 2008). Visual
inspection of graphs will be used to investigate the possibility of statistical
heterogeneity. This will be supplemented using, primarily, the I-squared (I2)
statistic. This provides an estimate of the percentage of variability due to
heterogeneity rather than chance alone. According to Higgins and Thompson (J.
P. Higgins & Thompson, 2002), a rough guide to interpretation is as follows: I2
around 25% represents low heterogeneity; I2 around 50% represents medium
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heterogeneity; I2 around 75% represents high heterogeneity. The results of
studies will be pooled and an overall estimate of OR will be obtained from a
random effects model, as this takes into account any differences between studies
even if there is no statistically significant heterogeneity.
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