St George's Hospital Medical School, London
Department of Psychiatry, University of Oxford
Trafford General Hospital, Manchester
Department of Psychiatry, University of Cambridge
Division of Psychiatry, University of Bristol, UK
Correspondence: Dr Swaran P. Singh, Department of Mental Health, Jenner Wing, St George's Hospital Medical School, London SW17 0RE, UK. Tel: +44 208 725 3390; fax: +44 208 725 3538; e-mail: s.singh{at}sghms.ac.ac.uk
Funding detailed in Acknowledgements.
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ABSTRACT |
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Aims To validate the nosological distinctiveness of ICD10 ATPDs by following up an inception cohort with first-episode psychosis.
Method All patients with first-episode psychosis identified in Nottingham between 1992 and 1994 and diagnosed using ICD10 criteria were reassessed 3 years later. ATPD outcomes were compared with schizophrenia and affective psychosis. Multivariate analyses were conducted to determine whether acute onset and early remission predicted favourable 3-year outcome in first-episode psychosis.
Results Of 168 cases of first-episode psychosis, 32 (19%) received an intake diagnosis of ATPD. The diagnosis of ATPD was stable in women over 3 years, but not in men. Outcomes in ATPD were better than in schizophrenia and similar to affective psychosis. In non-affective psychoses, favourable outcomes were a function of gender and premorbid functioning rather than acute onset and early remission.
Conclusions The ICD10 criteria for ATPDs identify a diagnostically unstable group of disorders. Acute onset and early remission do not independently predict favourable outcome over 3 years in first-episode psychosis.
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INTRODUCTION |
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In this study we aimed to:
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METHOD |
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Sample
The study sample was an intake cohort comprising all instances of
first-onset psychosis in patients aged 1664 years identified in
Nottingham between 1 June 1992 and 31 May 1994. The total population of
Nottingham in this age band in 1991 was 397 048
(Office of Population Censuses and
Surveys, 1992). The cohort was identified by screening all people
making their first-ever contact with psychiatric services for potential
psychosis. Patients with an organic mental illness or with severe learning
disabilities were excluded.
Follow-up study
The follow-up assessments were conducted between 1 June 1995 and 31 May
1997 and occurred in chronological order of the patient's initial contact with
psychiatric services, as close as possible to 3 years after the initial
contact. The following measures were used; see Singh et al
(2000) for details:
Family history and premorbid functioning
The patients' family histories and premorbid functioning were rated on
OPCRIT and Family HistoryResearch Diagnostic Criteria
(Endicott et al, 1975)
using all available sources of information, including case-note scrutiny and
direct interviews with carers. Family history of mental illness was recorded
for first-degree relatives of the patients, including parents, siblings and
children. OPCRIT categories were used for categorising premorbid
dysfunction.
Life events
At follow-up, life events information was collected for the 3 months
preceding the onset of the psychotic illness from all available sources,
including direct patient interview, information from family and carers, and
medical records on stressful life events. Events were categorised as
bereavement, major loss or separation, trauma or hospitalisation for a
non-psychiatric condition, social change including major changes in
employment, housing, marital status, migration, and post-partum events.
Definitions
Onset. Onset was defined as the period between the first reported
symptom or noticeable behavioural change and the emergence of psychotic
symptoms.
Duration of initial psychotic episode. Duration of initial psychotic episode was defined as the period between the emergence of clear psychotic symptoms and remission.
Remission. Remission was defined as the point in time when the patient is virtually symptom free and shows his or her usual premorbid personality (Jablensky et al, 1992).
Relapse. Relapse was defined as emergence of symptoms after a 4-week period of return to premorbid functioning.
Outcome. Favourable cross-sectional outcome was defined as no or minimal symptoms in the previous 4 weeks. Favourable longitudinal outcome (i.e. episodic rather than chronic course) was defined as a single psychotic episode with complete remission, or multiple episodes with inter-episodic remission.
Data collection
Information on onset, remission and relapse was gathered from all sources
of information, including psychiatric notes, general practitioner's notes,
patient interview and carer interview. In patients who had continuing residual
symptoms (negative or non-psychotic) following cessation of positive psychotic
symptoms, a judgement was made whether these symptoms were part of the initial
psychotic episode or represented a new or distinct episode. Where no complete
remission and return to premorbid status had been attained, the residual
symptoms were considered to be part of the initial episode. This allowed fewer
false-positive ratings of remission and also ensured that duration of episode
was not restricted to positive psychotic symptoms only.
Diagnostic process
The authors S.P.S. and S.A. presented the follow-up data and assessments to
a senior member of the research team (a consultant psychiatrist), with
everyone involved in the diagnostic process masked to the original consensus
diagnosis. All clinical information available over the 3-year follow-up period
was used to determine a longitudinal diagnosis based on ICD10 criteria
for all participants, including those who were currently well,
i.e. whose psychotic episode had ended before the follow-up assessment.
Diagnostic decision tree
A diagnostic decision tree was created as follows.
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RESULTS |
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Follow-up
Over the follow-up period, one patient was found to have an organic
psychosis and was excluded, and another refused to participate in the study,
leaving 166 individuals to be followed up. We traced 164 individuals (99%) to
their residence, obtained face-to-face interviews with 135 (81%) and another 8
(5%) were interviewed by telephone. Two people had died, one by suicide. For
139 participants (97% of those interviewed), assessments were conducted
3537 months from inclusion, thus ensuring homogeneity of time elapsed
since contact with services. We collected collateral information (from
treating psychiatry teams, carers known to the service and general
practitioners) on all cases, including those in which the person was not
interviewed. We therefore had complete follow-up data for 86% of participants
and partial data for the others, including all those who had not been directly
interviewed.
The socio-demographic profile of the total cohort and the ATPD subgroup,
subdivided by gender, is presented in Table
1. Diagnoses in the 166 cases were 112 (67.5%) non-affective
psychosis (F2029), 56 (33.7%) schizophrenia (F20), 41 (24.7%) affective
psychosis (F3033), 13 (7.8%) substance-induced psychosis (F1x)
and 32 (19%) acute and transient psychotic disorder (F23). In the ATPD group,
12 patients (37.5%) had acute delusional disorder (F23.3), 10 (31%) had acute
polymorphic disorder without symptoms of schizophrenia (F23.0), 7 (22%) had
acute schizophrenia-like psychosis (F23.2) and 3 (9%) had acute polymorphic
disorder with symptoms of schizophrenia (F23.1). Although there was no
statistically significant difference between men and women in this group in
mean age at first contact with psychiatric services (t=0.416,
P=0.68), there was a trend for women to be older than men; the means
were skewed by two outlying cases of men who had an age at first contact of
over 50 years. Dichotomising data into those below and above age 30 years
still did not lead to a statistical difference between the genders on age at
onset (2=1.347, P=0.28). Men with ATPDs were
significantly more likely to have been unemployed than women
(
2= 5.45, P=0.03). There was no excess of ethnic
minority patients in the ATPD group.
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Diagnostic certainty of ATPD
At the time of initial assessment there had been uncertainty about
acuteness of onset in a proportion of ATPD cases in which the possibility of
previous symptoms, prior to the acute emergence of psychosis, could not be
completely ruled out. Onset had been unequivocally acute in 9 of 11 women,
with two women having an alternative diagnosis of bipolar affective disorder,
current episode mixed (F31.6) and severe depressive episode with psychotic
symptoms. In more than half of the men (11 out of 21) there was uncertainty
regarding the acuteness of onset, with alternative diagnoses assigned in seven
cases as follows: one case each of cannabis-related psychosis (F12.5),
stimulant-induced psychosis (F15.53), psychotic mania (F30.2) and psychotic
depression (F32.3) and three cases of multiple drug use psychosis
(F19.53).
Diagnostic stability
After 3 years the longitudinal diagnosis remained unchanged in 8 out of 11
women (73%) but in only 3 out of 21 men (14%) with an intake diagnosis of
ATPD. In 9 men (43%) with an intake diagnosis of ATPD the longitudinal
diagnosis was changed to schizophrenia or delusional disorder and in 5 men
(24%) it was changed to affective psychosis. The corresponding figures for
women were 18% (2/11) and 9% (1/11) respectively. In none of the women, but in
3 men (14%), the intake diagnosis of ATPD was changed to substance-related
psychosis.
Reasons for diagnostic change
The most common reason for a change in diagnosis (in half of the 32 cases)
was that subsequent episodes met criteria for a non-ATPD diagnosis such as
schizophrenia or affective psychosis (Fig.
1). In 5 cases (16%) the diagnosis was changed because when the
duration of the initial episode was reassessed at follow-up, it was thought to
have been longer than the duration criteria for ATPDs. What appeared to have
been a complete remission during the intake diagnostic meeting was, at
follow-up assessment, considered to have been only a brief remission of
positive psychotic symptoms, with symptoms re-emerging without the patient
having achieved a return to premorbid level of functioning. No case given a
non-ATPD diagnosis at onset subsequently satisfied ICD10 criteria for
ATPDs at follow-up. This validated our a priori decision-tree
assumption that change in ATPD diagnosis would always be from ATPD to a
non-ATPD category. Comparing schizophrenia-like and non-schizophrenia
subgroups of ATPDs revealed that the diagnosis was stable in 6 of 22 (27.3%)
cases in the non-schizophrenia categories (F23.0 and F23.3) and in 5 of 10
(50%) cases of schizophrenia-like categories (F23.1 and F23.2). However, this
difference did not reach statistical significance (2=1.56,
d.f.=1, P=0.25), although the small number of cases has a low power
to detect any potential difference.
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Epidemiology of ATPDs
The incidence rates and gender ratios given here are age- and
gender-standardised for the population of England and Wales, 1991 census.
Based on the intake consensus diagnosis, the annual incidence rate of ATPDs
was 3.90 per 100 000 population (95% CI 2.55 to 5.26). The rate in men was
almost double that in women (5.08 v. 2.72) with a male/female ratio
of 1.87 (95% CI 0.90 to 3.88). The overall annual incidence rate for the
true 3-year diagnosis of ATPDs was much lower (1.36 per 100 000,
95% CI 0.56 to 2.17) with a female preponderance (men: 0.74 per 100 000, 95%
CI 70.09 to 1.58; women: 1.99 per 100 000, 95% CI 0.61 to 3.38; male/female
ratio 0.037, 95% CI 0.02 to 0.08).
Family history and premorbid functioning
Table 2 summarises premorbid
functioning and family history of patients with ATPDs (diagnosed at both
intake and 3-year assessments), schizophrenia and affective psychosis,
subdivided by gender. In the ATPD group diagnosed at intake, men were more
likely than women to have a positive family history of a psychiatric disorder
or of premorbid dysfunction. None of this group had a family history of
schizophrenia. In the 3-year true ATPD subgroup, no one had a
positive family history of any psychiatric disorder, and one man and one woman
had a history of premorbid dysfunction. The small numbers did not permit
further statistical analysis.
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Three-year course and outcome
Table 3 shows a range of
outcomes, comparing ATPDs with schizophrenia and affective psychosis. Compared
with the schizophrenia group, patients with ATPDs were significantly more
likely to have had an episodic course with full remission between episodes,
although the two groups did not differ on total number of admissions, days
spent in hospital or the proportion detained under the Mental Health Act 1983.
The social, occupational and symptomatic outcomes of the ATPD group in the
year preceding follow-up assessment were also significantly better than those
of the schizophrenia group. Cross-sectionally, patients with ATPDs had a
significantly better outcome in terms of disability and symptoms, including
negative symptoms, than patients with schizophrenia. Compared with the group
with affective psychosis, patients with ATPDs had similar longitudinal and
cross-sectional outcomes in every domain.
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Acute onset and early remission in first-episode non-affective psychoses
Of the 112 cases of non-affective psychoses (56 schizophrenia, 32 ATPDs, 13
delusional disorder, 5 schizoaffective psychosis, 1 induced delusional
disorder and 5 other or unspecified psychosis), 42 patients (38%) were female,
22 (20%) had an acute onset (reassessed onset at follow-up assessment), 34
(30%) had experienced a stressful life event prior to the emergence of
psychosis, 71 (63%) had a duration of psychotic episode of less than 6 months,
and 56 (50%) had a favourable, episodic course.
Figure 2 shows the distribution
of duration of initial psychotic episodes in participants with acute,
non-affective psychotic disorder. Eighteen (82%) had an initial episode
lasting less than 32 weeks; in the majority (15/22, 73%) its duration was less
than 6 months, and three patients (14%) had an episode longer than 1 year
(data missing in one case). It appears, therefore, that people with
acute-onset non-affective psychosis either tend to recover within about 6
months, or are ill for more than a year.
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There was no ethnic difference in acute onset (White v. non-White:
2=0.03, P= 0.53; White v.
AfricanCaribbean:
2=0.04, P=0.55) or a
duration of initial episode <6 months (White v. non-White:
2=0.384, P=0.65; White v.
AfricanCaribbean
2=1.28, P=0.33). An earlier
study from our data-set had found that course and outcome did not differ
between White patients and AfricanCaribbean patients with first-episode
psychosis (Harrison et al,
1999). Ethnicity was therefore not included as an independent
variable in subsequent analyses.
Multivariate analysis: predictors of favourable outcome
To test the independent effects of acute onset and brief duration of
initial psychotic episode and good outcome, logistic regression was conducted
with good cross-sectional and longitudinal outcome as the dependent variable
and gender, age at first contact, acute onset, brief initial duration of
psychotic episode, life event prior to first episode, premorbid functioning
and family history as independent variables.
Table 4 displays the results of the logistic regression showing adjusted odds ratios for variables predicting favourable cross-sectional and longitudinal outcome. Only female gender and favourable premorbid social functioning predicted favourable symptomatic outcome, and female gender and good premorbid occupational functioning predicted good longitudinal outcome. Acute onset, duration of initial psychotic episode, age at first contact, life event, premorbid personality dysfunction or a positive family history did not have an independent effect on either cross-sectional or longitudinal outcome. We repeated the analyses using different definitions of acute onset (less than 1 month) and early remission (episode duration less than 3 months) and on all first-episode psychoses, including affective psychoses. However, in each of these analyses, the only consistent predictors of good outcomes were female gender and good premorbid functioning in social and occupational domains.
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DISCUSSION |
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Limitations of the study
The most significant limitations of the study are the small sample size and
the limited follow-up period. This partly reflects the rarity of ATPDs,
especially in the developed world, and limits the power of the study to detect
small but potentially important differences in course and outcome. Second,
this is a study of treated outcomes of first-episode psychosis. The
true natural history of psychotic disorders cannot be determined
from studies of treated populations
(Waddington et al,
1997). In a secondary care setting such as the one in which this
study was conducted, it is unlikely that patients with psychosis would be
antipsychotic-free. Hence, comparisons between historical outcomes with those
in current mental health care settings have to be made cautiously. Finally,
cultural differences in the incidence and presentation of ATPDs suggest
caution in generalising our findings to other cultural settings.
Epidemiology, diagnostic stability and outcome of ATPDs
The ICD10 recognises that there is little empirical information on
ATPDs, and the limited data and clinical traditions that must therefore
be used instead do not give rise to concepts that can be clearly defined and
separated from each other (World
Health Organization, 1992a: p. 99). Our data suggest that
ICD10 criteria identify a diagnostically unstable group of disorders
comprising good-outcome schizophrenia, affective psychosis and a small group
of non-affective, non-schizophrenic psychoses with an acute onset and benign
3-year course. Diagnostic stability is not associated with any particular
subgroup of ICD10 ATPDs. Jørgensen et al
(1997) have also questioned
the value of having subgroups of ATPDs because the small numbers virtually
preclude empirical validation.
The male preponderance at intake in this study is at striking variance with most previous reports, which report female preponderance in all forms of ATPD (Leonhard, 1975; Cutting et al, 1978; Lindvall et al, 1986; Jørgensen et al, 1996, 1997; Pillmann et al, 2002; Marneros et al, 2003). Our follow-up suggests that men especially men with schizophrenia were more likely to have been assigned a false-positive diagnosis of ATPD at intake. This might also partly explain why in a greater proportion of patients the change in diagnosis was to schizophrenia rather than to affective psychosis, contrary to earlier reports (Jørgensen et al, 1997; Sajith et al, 2002). However, the gender ratio based on the 3-year longitudinal diagnoses is similar to that of the World Health Organization's Determinants of Outcome of Serious Mental Disorders (DOSMED) study, although the total incidence is twice that of the DOSMED rates for developed countries (Susser & Wanderling, 1994). Our 3-year incidence rate and gender ratio for ATPDs are possibly close to the true incidence of ATPDs in the developed world.
Even though the diagnosis changes over time, the overall outcome for ATPDs over 3 years is better than that in schizophrenia and similar to affective psychosis, confirming the good outcome of acute psychoses (Stephens et al, 1982; Susser et al, 1995a,b; Johnstone et al, 1996). Our results suggest that true ATPDs are not linked genetically to either schizophrenia or affective psychosis. The lack of a positive family history in diagnostically stable ATPDs points to environmental aetiological factors which may not have been elucidated by the relatively crude life events measure of this study. An environmental cause of ATPDs is also suggested by the absence of premorbid dysfunction in this and in a previous study (Pillman et al, 2003), since premorbid dysfunction is a measure of developmental deviance, usually associated with schizophrenia (van Os et al, 1995).
Acute onset and early remission in non-affective psychoses
We confirmed the finding by Susser et al
(1995a) that acute
non-affective psychoses tend either to resolve within 6 months or to have an
initial episode longer than 1 year. Susser et al suggested that such
a bimodal distribution confirms the existence of a group of
ATPDs distinct from schizophrenia. We did not feel that a conclusion regarding
bimodality was warranted in our data and we did not statistically test for
bimodality. Bimodality, in a strictly mathematical or statistical sense, can
be tested only when there is an underlying assumption of two normal
distributions. The term bimodal in this context may thus be
misleading, since those who have an initial psychotic episode longer than 52
weeks might not have a single mode at all. However, our findings support the
notion that the ICD10 duration criterion for ATPDs may be too brief and
restrictive (Susser et al,
1995b).
A third psychosis?
In our study, favourable outcomes in non-affective psychoses were
associated with female gender and good premorbid functioning rather than with
acute onset and a brief initial psychotic episode. This challenges the notion
of a third psychosis, distinct from schizophrenia and affective
psychosis, which can be identified solely on onset and duration criteria. The
ICD10 criteria for ATPDs have attempted to bring together overlapping
but discrete clinical constructs some based on aetiological notions,
others on psychodynamic concepts and some based on differences in clinical
presentation. In the absence of empirical evidence that might convert such
constructs into diagnostic criteria, ICD10 has selected the two shared
aspects that lend themselves to measurement: acute onset and early remission.
It is not surprising, therefore, that ICD10 ATPDs are (diagnostically
at least) a heterogeneous group of disorders. Both ICD and DSM systems are
based on symptoms and discount the non-empirical aspects of
diagnosis, which may constitute the phenomenological essence of
a psychotic disorder (Kendler,
1990). This conflict between logical empiricism and
phenomenological understanding of the disorder is reflected in the debates
about reliability v. validity of diagnostic categories.
Extra-clinical aspects of validity, such as positive family
history and premorbid dysfunction, could be included in future systems, but
developing reliable criteria for these is likely to be
problematic.
Implications for ICD11 and DSMV
Given our findings that neither acute onset nor early remission are
independently associated with good outcome, should a separate category of
ATPDs, defined by these two criteria, be maintained in diagnostic systems? The
answer at this stage of our understanding is probably yes, for
the following reasons. First, the significant cross-cultural differences in
the incidence rates and outcome of ATPDs
(Sartorius et al,
1978; Susser & Wanderling,
1994) cannot be discounted on the basis of a small study from a
part of the world where ATPDs are rare. Further cross-cultural research may
shed light on the reasons behind these cultural differences. Meanwhile, it is
important that international classification systems reflect international
variations in psychiatric disorders. Second, the ability to identify a
distinct group of acute and transient disorders among first-episode psychoses
confers important clinical advantages such as predicting course and devising
long-term treatment strategies. The criteria for identifying such a group need
to be refined rather than the category abandoned. Finally, having a category
of ATPDs draws attention to the spurious certainty about the boundaries
between schizophrenia and affective psychosis and emphasises the limitations
of the Kraepelinian dichotomy. It also highlights the shortcomings of the
current emphasis on reliability rather than validity of diagnostic
criteria.
We support the recommendation that ICD11 and DSMV should include a category of acute non-affective psychoses (Susser et al, 1996; Mojtabai et al, 2000). However, we propose that a specific criterion-based definition of onset be included. The definition of onset used in this study the time between the first reported or observed change in mental state or behaviour and the development of psychotic symptoms is promising. This definition includes both the beginning of onset (i.e. first change, including prodromal symptoms) and its termination (i.e. the point when any psychotic symptoms emerge and reach a diagnostic threshold).
Implications for future research
Our findings highlight the need for further research in two important
areas. First, onset in psychosis is not only poorly researched, it is also
poorly conceptualised. The ICD10 defines onset as a change from
a state without psychotic features to a clearly abnormal psychotic
state (World Health Organization,
1992a: p. 99). The Diagnostic Criteria for Research
define onset as the time interval between the first appearance of any
psychotic symptoms and the presentation of the fully developed disorder
(World Health Organization,
1994: p. 108). Although the former definition might include
prodromal symptoms, the latter excludes them, but fails to explain what the
phrase fully developed disorder means. There has been
practically no research into the chronology and components of the onset of
psychosis, and some of the uncertainty probably resides in the nebulous nature
of the phenomenon itself. However, if onset is to be a diagnostic criterion,
it needs a clearer definition, and some empirical validation of the chronology
of onset. Second, the relationship between life events, stress and psychosis
is still poorly understood. Identifying a group of psychotic disorders that
are precipitated by stress and have a favourable outcome would enhance our
understanding of the biological and psychosocial variables influencing the
course and outcome of psychosis. Many current debates and controversies, such
as the excess of schizophrenia in immigrant groups, the role of psychological
v. pharmacological treatments, and early detection and intervention
in high-risk groups might be illuminated by a greater understanding of the
nature of acute and transient psychotic disorder.
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Clinical Implications and Limitations |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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Received for publication January 27, 2004. Revision received June 1, 2004. Accepted for publication June 26, 2004.