University of Cologne, Department of Psychiatry and Psychotherapy, Early Recognition and Intervention Centre for Mental Crises (FETZ), Cologne, Germany
University of Cologne, Department of Psychiatry and Psychotherapy, Cologne, Germany
Correspondence: Dr Frauke Schultze-Lutter, University of Cologne, Department of Psychiatry and Psychotherapy, Early Recognition and Intervention Centre for Mental Crises (FETZ), 50924 Cologne, Germany, Tel: +49 221 478 6098; fax: +49 221 478 3624; email: frauke.schultze-lutter{at}uk-koeln.de
Declaration of interest None. Funding detailed in Acknowledgements.
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Aims To examine whether basic symptoms, i.e. subtle subjective deficits, differ between participants suffering from a potential prodrome (n=146), first-episode schizophrenia (n=153) and non-psychotic depression (n=115).
Method Basic symptoms were assessed with the Schizophrenia Proneness Instrument.
Results The prodrome and schizophrenia groups did not differ in level of basic symptoms but both had higher levels than the depression group. DSM–IV depression was frequent in those suffering from a potential prodrome (38%) and first-episode schizophrenia (21%). In both groups, participants with and without depression did not differ in basic symptoms. In multivariate analyses, consideration of current depression generally facilitated correct group classification, except for participants suffering from both a potential prodrome and depression.
Conclusions Cognitive basic symptoms distinguished well between all three groups. However, identification of persons suffering from a potential prodrome might be enhanced by considering current affective status.
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Basic symptoms, especially subtle, subjective disturbances of thought, speech and perception, as assessed with the Bonn Scale for the Assessment of Basic Symptoms (BSABS; Gross et al, 1987; Huber & Gross, 1989), were shown to be predictive of later schizophrenia (Klosterkötter et al, 2001) and to distinguish between non-psychotic affective disorders and schizophrenia (Klosterkötter et al, 1996). However, a direct comparison between patients with non-psychotic unipolar depressive disorder, those with potential prodrome and those suffering from a first-episode schizophrenia has not been studied.
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Inclusion criterion for the schizophrenia group was a first episode of schizophrenia according to DSM–IV criteria (American Psychiatric Association, 1994), and for the depression group an episode of major depressive disorder, dysthymic disorder or depressive disorder not otherwise specified according to DSM–IV without psychotic features for which help was sought for the first time.
General exclusion criteria were: (a) diagnosis of delirium, dementia, amnestic or other cognitive disorders, mental retardation, psychiatric disorders due to a somatic factor or related to psychotropic substances according to DSM–IV, (b) alcohol or drug abuse within the past 3 months according to DSM–IV and (c) diseases of the central nervous system (inflammatory, traumatic, epilepsy). In addition, current or past diagnosis of any psychotic disorder according to DSM–IV criteria served as an exclusion criterion in the prodromal and depression group. In the schizophrenia group, the latter was restricted to a past diagnosis of a psychotic disorder. An exception to this in the prodromal and schizophrenia group was psychosis not otherwise specified, when rated due to the presence of brief limited intermittent psychotic symptoms as defined by the ultra-high risk criteria (Phillips et al, 2000). The presence of attenuated or brief limited intermittent psychotic symptoms according to the ultra-high risk criteria was a further exclusion criterion in the depression group. In the matter of basic symptoms in the depression group, only the 10 cognitive–perceptive basic symptoms relevant for inclusion into the prodromal group were limited to not exceeding an occurrence of once in a month within the past 3 months, i.e. a maximum rating of 2 on the Schizophrenia Proneness Instrument.
Participants
Of the 414 participants included in the study, 146 were suffering from a
potential prodrome, 153 from first-episode schizophrenia (70% paranoid, 20%
undifferentiated, 9% disorganised and 1% catatonic subtype) and 115 from
depression (84% major depressive disorder, with 73% melancholic, 16% atypical
and 11% no melancholic, atypical or catatonic features; 2% dysthymic
disorders, equally with and without major depressive episode; and 14%
depressive disorders not otherwise specified, with 69% recurrent brief
depressive disorder and 31% minor depressive disorder). All gave written
informed consent to the study between June 2000 and December 2005, with
recruitment of participants suffering from a potential prodrome ending in
December 2003. The majority of them had sought help at the Cologne Early
Recognition and Intervention Centre for mental crisis (FETZ); others,
especially those with first-episode schizophrenia, were in-patients of the
Department of Psychiatry and Psychotherapy of the University of Cologne. In
addition to the inclusion criteria, 80% of participants suffering from a
potential prodrome reported attenuated psychotic symptoms, and only 1 person
(0.7%) supplementary brief limited intermittent psychotic symptoms. Group
differences for all socio-demographic characteristics are presented in
Table 1.
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View this table: [in a new window] | Table 1 Characteristics of sample |
Age was significantly correlated with graduation (Spearmans rS=0.316, P=0.000), vocational education (rS=0.456, P=0.000) and partnership (rS=0.232, P=0.000), which was also positively correlated with female gender (rS=0.397, P=0.000). Graduation and vocational education were weakly associated to each other (rS=0.197, P=0.000) and to current occupation (rS=0.208/0.188, each P=0.000).
Instruments
The subtle, self-experienced, self-reported deficits that often remain
solely in the self-perception of the patient and do not show in behaviour,
i.e. basic symptoms, were assessed with the Schizophrenia Proneness
Instrument, Adult version (SPI–A;
Schultze-Lutter et al,
2007). The 34-item SPI–A was derived from BSABS data on 79
individuals with a true prodrome and 346 with remitted schizophrenia, by
cluster and confirmatory facet analyses for use by experienced and trained
clinicians. Being a semi-structured interview, the SPI–A was designed to
be applied together with the Structured Interview for Prodromal Syndromes
(SIPS; Miller et al,
2002), assessing attenuated and brief limited intermittent
psychotic symptoms, and the Positive And Negative Syndrome Scale (PANSS;
Kay et al, 1987) to
cover the whole range from early prodromal basic symptoms via attenuated and
brief limited intermittent to frank psychotic symptoms. The SPI–A
comprises 6 sub-scales of 5 to 6 items each:
For the quantitative rating, a 7-point severity scale was introduced with maximum frequency of occurrence within the past 3 months as the guiding criterion; i.e. from 0=symptom absent to 6=present daily. The overall concordance rate of the four SPI–A interviewers with an expert rating (F.S.-L.) was 91%.
The Structured Clinical Interview for DSM–IV (SKID–I, German version; Wittchen et al, 1997) was conducted to rule out past or present psychotic disorders and confirm diagnoses in the schizophrenia and depression group as well as to assess comorbidity with affective disorders in the schizophrenia and potential prodrome group.
Data analysis
SPI–A sub-scale totals at baseline were compared between groups by
two-tailed Mann–Whitney tests and adjusted for multiple testing across
both, the pairwise group comparisons and sub-scales (18 pairwise tests in
all), according to the sequential method for ordinal data by Holm
(1979).
Despite the socio-demographic group differences, no covariance analyses were carried out, as nonparametric correlation analyses of the whole sample had only revealed weak, negligible associations between the socio-demographic and psychopathological data, these being highest for age and affective–dynamic disturbances (rS=0.142, P=0.004) followed by associations between age and perception disturbances (rS=0.108, P=0.028) and gender and affective–dynamic disturbances (rS=0.108, P=0.029).
For evaluation of the combined ability of the SPI–A sub-scales to discriminate participants with depression from those suffering from a potential prodrome as well as from first-episode schizophrenia and the influence of the main socio-demographic characteristics, age and gender, as well as the presence and kind of current depressive episode, stepwise logistic models (Wald-method, forward selection, without inclusion of a constant term) were used on the depression and potential prodrome group (a) with intake of current depressive disorder and (b) without its consideration. To assess the predictive accuracy of the derived model in an unbiased manner, data-sets of the depression and potential prodrome group were randomly split into a model generation sample (MG; n=132) and a model validation sample (MV; n=129) with participants with schizophrenia taken into account as a further validation group expected to be classified as prodromal.
To estimate the impact of a possible selection bias affecting the comparison between participants suffering from a potential prodrome and those with depression, additional subgroup comparisons were made. Such a selection bias might have been introduced by the inclusion criteria, of which about half of the items of cognitive disturbances (3 of 6 items), of disturbances in experiencing self and surroundings (3 of 5 items) and of perception disturbances (3 of 6 items) were – at a severity of at least 3 – part of the inclusion criteria of the prodrome. To assume that such a selection bias had not influenced the results, the following conditions, which centre on the schizophrenia group as the group included independently from any prerequisite regarding basic symptoms had to be met. If participants with schizophrenia but without current depression do not differ from either participants suffering from a potential prodrome without or with depression, and both potential prodrome subgroups do not differ from each other, then it can be concluded that the performance on the SPI–A of participants suffering from a potential prodrome is independent from the presence of current depression and not solely due to inclusion criteria, in which case it would be expected to exceed that of participants with schizophrenia but no depression. Furthermore, if schizophrenia subgroups with and without current depression show equal SPI–A subscale totals and the schizophrenia subgroup with depression outperforms the depression group but not the prodrome subgroup with depression (which again is assumed not to differ from the prodrome subgroup without depression) do not, then higher sub-scale totals of those suffering from a potential prodrome and depression as well as participants suffering from a potential prodrome but no depression in comparison to participants with depression alone can be assumed to reflect not solely the inclusion criteria but also true group differences. Comparisons of subgroups were carried out by two-tailed Mann–Whitney tests and adjusted for multiple testing across sub-scales (6 pairwise tests each), according to Holms method (Holm, 1979).
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![]() View larger version (31K): [in a new window] [as a PowerPoint slide] |
Fig. 1 Comparison of group means of the SPI–A sub-scale totals between
participants suffering from a potential prodrome,
and non-psychotic depression patients,
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2-test, d.f.=2, P=0.046). Furthermore, the two
subgroups did not differ in the percentage of persons with attenuated or brief
limited intermittent psychotic symptoms.
Of the participants with first-episode schizophrenia, 32 (21%) fulfilled
criteria of a depressive disorder not otherwise specified: 47% of a recurrent
brief depressive disorder, 31% of a major depressive disorder in addition to a
psychotic disorder and 22% of a post-psychotic depressive disorder. They
showed no difference in mean age to those with no current depression. There
was a higher proportion of female subjects in the schizophrenia with
depression group (41% v. 22%, 2x2
2-test,
d.f.=1, P=0.027). Despite no difference in graduation and vocational
education, participants with both schizophrenia and depression more frequently
had a regular occupation than those with solely schizophrenia (81% v.
54%, 2x4
2-test, d.f.=3, P=0.019). The greatest
difference between participants with schizophrenia with and without depression
was in the distribution of schizophrenia subtypes (2x4
2-test, d.f.=3, P=0.014): participants with
schizophrenia and depression were more frequently of the undifferentiated (42%
v. 14%) and less frequently of the paranoid subtype (52% v.
75%).
Considering all six SPI–A sub-scales, age, gender and current
depressive episode (i.e. major depressive, dysthymic or other depressive
episode), a model, reg1 (
2=117.5, d.f.=4, P=0.000),
was generated, which included cognitive disturbances (ß=0.203, s.e=0.069,
exp(ß)=1.225 with 95% CI (1.070/1.403)), disturbances in experiencing
self and surroundings (ß=0.170, s.e.=0.082, exp(ß)=1.186 with 95% CI
(1.009/1.394)), current major depressive episode (ß=–4.579,
s.e.=0.782, exp(ß)=0.010 with 95% CI (0.002/0.048)) and current episode
of depression not otherwise specified (ß=–2.003, s.e.=0.714,
exp(ß)=0.135 with 95% CI (0.003/0.547)), classifying 89.4% of the
participants with depression and those suffering from a potential prodrome of
the model generation (MG) group, 93.8% of the depression–potential
prodrome model validation (MV) group and 96.1% of the participants with
schizophrenia correctly (Table
2). In both, the potential prodrome and schizophrenia groups,
misclassifications were due solely to subjects with current depression, thus
leading to lower correct classification rates (76.8 and 81.3%) in these
respective subgroups (Table
2).
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View this table: [in a new window] | Table 2 Classification results in groups of stepwise logistic regression equations generated with (reg1) or without (reg2) consideration of current depressive disorders |
Taking current depression from the equation, a model, reg2
(
2=84.9, d.f.=5, P=0.000), including five parameters
was developed: cognitive–attentional impediments (ß=–0.134,
s.e.=0.057, exp(ß)=0.875 with 95% CI (0.782/0.979)), cognitive
disturbances (ß=0.322, s.e.=0.075, exp(ß)=1.381 with 95% CI
(1.191/1.600)), disturbances in experiencing self and surroundings
(ß=0.233, s.e.=0.076, exp(ß)=1.263 with 95% CI (1.089/1.465)), age
(ß=–0.069, s.e.=0.023, exp(ß)=0.933 with 95% CI (0.893/0.975))
and gender (ß=–1.411, s.e.=0.549, exp(ß)=0.244 with 95% CI
(0.083/0.715)), correctly classifying 80.3% of the MG sample, 83.7% of the MV
sample and 78.4% of participants with schizophrenia as well as 82.1% of the
potential prodrome subgroup with depression and 75.0% of the schizophrenia
subgroup with depression (Table
2).
Group comparisons, evaluation of the impact of a selection bias
Participants with schizophrenia but no depression did not differ from those
suffering from a potential prodrome and depression but did differ from those
suffering from a potential prodrome but no depression on
affective–dynamic disturbances (Padjusted=0.0009)
and disturbances in experiencing self and surroundings
(Padjusted=0.0033; Fig.
2). Thereby, participants with schizophrenia but no depression had
higher mean totals than those suffering from a potential prodrome but no
depression, which was mainly due to higher mean ratings on the 3 items of a
reduced stress tolerance in affective-dynamic disturbances (all
Padjusted<0.0001) and on unstable ideas of reference
(Padjusted <0.00001) and an increased emotional
reactivity in response to routine social interactions
(Padjusted<0.05).
![]() View larger version (34K): [in a new window] [as a PowerPoint slide] |
Fig. 2 Group means of the SPI–A sub-scale totals in subgroups.
, schizophrenia+depression (n=32);
, potential prodrome+depression
(n=56);
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0.014;
Fig. 2). Furthermore,
participants suffering from a potential prodrome and depression as well as
those not additionally suffering from depression had highly significant higher
means on each SPI–A sub-scale (Padjusted
0.0056),
except on affective–dynamic disturbances that did not differ between
participants suffering from a potential prodrome but not depression and those
with depression alone (Padjusted=0.179). Here, only the
impaired tolerance to certain everyday stressors was more severe in
participants suffering from a potential prodrome but not depression
(Padjusted<0.05); all the other four items did not
differ between the prodrome subgroup without depression and the unipolar
depression group.
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Conceptualised originally as primary psychopathological disturbances underlying psychotic symptoms in schizophrenia (Huber & Gross, 1989; Gross & Huber, 2005), basic symptoms have already been studied in affective disorders. These studies found that especially the cognitive–perceptive disturbances distinguish schizophrenia from non-psychotic affective disorder (Klosterkötter et al, 1996; Bechdolf et al, 2002) and possibly even psychotic bipolar illness (Parnas et al, 2003). Furthermore, basic symptoms, especially self-experienced cognitive disturbances, have been shown to be highly promising predictors of subsequent first-episode psychosis (Klosterkötter et al, 2001; Lam et al, 2004; Yung et al, 2005) and have reportedly aggregated significantly in schizophrenia (Parnas et al, 2003). These cognitive disturbances, in addition, support a more sensitive and narrow definition of a homogeneous group of at-risk subjects compared to other approaches (Simon et al, 2006). We found comparable expressions of basic symptoms in participants with first-episode schizophrenia and those suffering from a potential prodrome for all sub-scales of the SPI–A, which were decidedly more severe than in non-psychotic depressive subjects, even as regards the more depressive-like complaints subsumed in affective–dynamic disturbances. This gives support to the notion that basic symptoms are indeed a phenomenology specific to the schizophrenia spectrum. This notion is further delineated by the lack of differences within the potential prodrome and schizophrenia groups whether or not they have a diagnosis of a current depressive episode according to DSM–IV. Although groups differed significantly in socio-demographic data, the association between socio-demographic data and basic symptoms was negligibly low in correlation analyses, thus not indicating presence of a socio-demographic sample bias.
As in previous studies (Klosterkötter et al, 1996; Bechdolf et al, 2002; Parnas et al, 2003) and at highly significant adjusted P-levels, the differences between the potential prodrome and schizophrenia, respectively, and the depression group were most pronounced in the SPI–A sub-scales cognitive disturbances and disturbances in experiencing self and surroundings. The fact that about half of the items of cognitive disturbances (3 of 6 items) and disturbances in experiencing self and surroundings (3 of 5 items) were (at a severity of at least 3) part of the inclusion criteria of the prodrome is certainly prone to introduce a selection bias into the findings, which might lead to a tautology regarding the comparison of potential prodrome and non-psychotic depressive disorders. While the definition of the putatively prodromal as well as of the participants with nonpsychotic depression was at least partly dependent on SPI–A items, the schizophrenia subjects were a group included completely independently from their performance on the SPI–A. Thus, certain conditions focusing on the performance of these participants with schizophrenia were formulated and tested to estimate the amount to which the results might be influenced by the selection bias. Only three single comparisons did not follow the hypothesised directions: affective–dynamic disturbances and disturbances in self and surroundings were significantly more frequent in participants with schizophrenia but no depression than in those suffering from a potential prodrome but not depression, a result that gives even more support to the view that the high performance of those who are putatively prodromal is not only induced by the inclusion criterion for the prodrome than the hypothesised absence of a group difference. The third comparison that did not show the expected group difference between participants suffering from a nondepressive prodrome and participants with depression alone involved affective–dynamic disturbances was a sub-scale with none of its items being part of the prodromal inclusion criterion. Thus, with only one single comparison truly differing from the initial hypotheses, it seems fair to deduce that the selection bias had no major impact on the results. However, only follow-up of subjects will conclusively show whether the higher totals of cognitive disturbances and of disturbances in experiencing self and surroundings are truly associated with a conversion to psychosis in the comorbid potential prodrome group.
The prior notion of the importance of cognitive disturbances in the identification of persons symptomatically at an increased risk of psychosis is also supported by the results of the stepwise logistic regression analyses, which at a psychopathological level included mainly cognitive disturbances. This led to high rates of correct classifications of around 80% in the model validation groups including individuals with schizophrenia. When age and gender as the main socio-demographic variables accounting for group differences were considered along with current depressive disorders, classification rates improved by about a further 10%, thereby selecting current major depressive disorder and current depressive disorder not otherwise specified over age and gender. With a positive impact of psychopathology and a negative impact of current depression, the resulting equation led to a perfect classification of potential prodrome and schizophrenia subgroups without depression and to only few misclassifications of those participants with depression. Yet, the misclassification rates of prodrome and schizophrenia subgroups with current depression were around 20%. Future studies on larger samples and additional assessment of variables that are potentially relevant to depression, such as dysfunctional beliefs, will have to show if the introduction of a second-step classification algorithm especially generated to distinguish depressive subjects with regard to a potential prodrome of psychosis might significantly increase the number of right classifications in this group. Studies on other samples with different (comorbid) psychiatric conditions are needed to decide if such a two-step procedure might be reasonable for other potentially comorbid conditions such as anxiety disorders within the psychotic prodrome.
Thus, basic symptoms, and especially cognitive basic symptoms, seem to be a good tool to distinguish (pre-)psychotic from affective disorders. Furthermore, especially in those individuals suffering from a potential prodrome and a comorbid depressive disorder, a reliable early identification might require a second-step assessment to account for the comorbid condition.
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