Acute and transient psychotic disorders versus persistent delusional disorders: A comparative longitudinal study
Frank Pillmann, MD, Klinik und Poliklinik für Psychiatrie, Psychotherapie und Psychosomatik, Martin-Luther-Universität Halle-Wittenberg, 06097 Halle, Germany. Email: email@example.com
Aim: The aim of this work is to investigate differences between two non-schizophrenic, non-organic psychotic disorders, namely persistent delusional disorders (PDD) and acute and transient psychotic disorders (ATPD) according to ICD-10.
Method: In a prospective and longitudinal study, we compared all 43 inpatients with PDD who were treated at Halle-Wittenberg University Hospital during a 14-year period to a previously investigated cohort of 41 patients with ATPD in regard to demography, long-term symptomatic outcome, and social consequences. Sociobiographical data were collected using a semi-structured interview. Follow-up investigations were performed at a mean of 10–12 years after the onset of the disorder using standardized instruments.
Results: With the exception of the duration of the psychotic symptoms, the PDD patients were significantly different from the ATPD patients on various levels, such as sex ratio (female predominance only in ATPD), age at onset (older in PDD), the number of preceding stressful life-events in the index hospitalization (more frequent in ATPD), richness and variety of symptoms (higher in ATPD), and persistence of positive psychotic symptoms (in PDD). Patients with PDD had significantly less re-hospitalizations during the course of their illness. Long-term outcome was marked by chronicity of delusional symptoms and lower global functioning in PDD than in ATPD, while negative symptoms and loss of independence were infrequent in both conditions.
Conclusions: PDD differs from ATPD not only in the duration of the psychotic symptoms, but also in a variety of significant variables. They appear to be two separate entities within a psychotic spectrum.
PERSISTENT DELUSIONAL DISORDERS (PDD) and acute and transient psychotic disorders (ATPD) are two psychotic disorders that are supposedly distinct from schizophrenia in terms of their symptoms, pathogenesis, and prognosis.1–3 For both PDD and ATPD, however, the nosological status is disputed, and empirical data on both disorders are scarce because of their low frequency and a focus of research on patients with schizophrenia.4
According to ICD-10, PDD (F22.0) is a psychotic condition in which delusions constitute the most conspicuous or the only clinical characteristic, and must be present for at least 3 months. Subtypes of PDD may be specified as the persecutory type, the litigious type, the self-referential type, the grandiose type, the hypochondriacal (somatic) type, the jealous type, and the erotomanic type.5 In the DSM-IV, the diagnosis of delusional disorder (DD) (DSM-IV: 297.1) is operationalized in a largely analogous way.6
The creation of the concept of acute and transient psychotic disorders (ATPD) by the World Health Organization (WHO) is another consequence of the fact that some psychotic disorders could not be allocated to either of the two broad dichotomous groups: dementia praecox (later named schizophrenia) and manic-depressive insanity (later named affective disorder).7,8 The diagnosis of ATPD requires an acute (within 2 weeks) onset of psychotic symptoms and remission within 3 months (or within 4 weeks when schizophrenic symptoms are present). Several subtypes are defined according to the presence or absence of typical ‘polymorphic features’ and schizophrenic first-rank symptoms.9 The benign long-term course of ATPD has been confirmed in a follow-up study that was conducted by our group.9–11
PDD and ATPD have in common the development of psychotic symptoms in the absence of severe other psychopathological abnormalities. The nosological status of both disorders is disputed. Since a detailed knowledge of their long-term course is crucial for understanding these disorders and to establish their clinical validity, the principal aim of the present study was to conduct a longitudinal comparison of patients with either PDD or ATPD. To this end, we combined data from a long-term follow up of a cohort of patients with PDD with data of a group of patients with ATPD. Both groups of patients were diagnosed and treated as inpatients in the same institution, and then investigated and followed up using identical methodologies. We set out to determine common features as well as differences in sociodemographic variables, aspects of the acute episode, and long-term course and outcome of the two disorders. We hypothesized that both disorders have a favorable outcome, yet each displays a distinct pattern in terms of its demography, the long-term symptomatic outcome, and the social consequences.
The study was approved by the local ethics committee, and was carried out according to the Declaration of Helsinki. All subjects gave their written informed consent after the nature of the procedures had been fully explained.
Patients with PDD
The Halle Delusional Syndromes Study (HADES-Study) was initiated and designed by the senior author (A.M.). In the first phase of the study, we identified all consecutive cases of PDD among the 9969 patients who were treated as inpatients at the Department of Psychiatry, Psychotherapy and Psychosomatics of the Martin Luther University of Halle-Wittenberg, Halle, Germany between 1994 and 2008. The hospital serves a large municipal and suburban catchment area, and has a non-selective admission policy. Patients with a clinical discharge diagnosis of either DD or PDD were considered for inclusion in the study. All diagnoses were reviewed independently by the authors using a checklist that consisted of the ICD-10 research criteria for PDD (F22.0) and the DSM-IV criteria for DD (297.1). Only subjects who fulfilled either set of diagnostic criteria were included. During this procedure, we found that all patients who fulfilled the DSM-IV criteria for DD also fulfilled the ICD-10 criteria for PDD. Of the initial 61 patients with a discharge diagnosis of DD, 43 patients fulfilled these criteria during the 14-year period.
Follow-up investigations took place at 10.8 (SD 4.7) years after onset of the disorder or 6.6 (SD 3.8) years after the index hospitalization. At follow up, the patients were approached, and, after obtaining their informed consent, they were investigated with various psychiatric and psychological assessment instruments. Of the original 43 patients, three had died (one of them presumably by suicide), seven refused to give their consent, and the remaining 33 patients (82.5% of the 40 surviving patients) were personally interviewed.
Patients with ATPD
The second study group comprised 41 inpatients with ATPD, who were treated at the same hospital department between 1993 and 1997. This sample and the details of recruitment and data acquisition have been described previously.10,12 The ATPD group originally comprised 42 patients. One patient of the original group did not display delusions during the index hospitalization; this subject was excluded from the control group. The ATPD patients were investigated in three waves of follow-up investigations at predetermined times, namely 2.5 (SD 1.3) years, 4.9 (SD 1.4) years and 7.0 (SD 1.5) years after the index episode, or 8.6 (SD 7.8) years, 10.5 (SD 7.3) years and 12.4 (SD 7.3) years after the first episode. Data from at least one of the follow-up examinations could be obtained from 92.9% of the original sample. For the present comparison, data from the last available follow-up investigation for each subject were used if more than one dataset was available for a given patient.
We systematically recorded the demographic, sociobiological, and clinical features of each patient in the two study groups.3 Information was gathered using a semi-structured interview that had already been used in earlier studies.13 Clinical and clinical laboratory findings, as well as information that was gathered from the patients and their relatives or from other suitable sources during admission and treatment were recorded. The DSM-IV diagnoses for the index hospitalization and lifetime diagnoses were assessed using the structured clinical interview for DSM-IV (SCID).14 The ICD-10 diagnoses were assessed with checklists according to the ICD-10 research criteria.5 For the evaluation of psychopathological parameters on index hospitalization, a symptom list that was derived from the Brief Psychiatric Rating Scale15 and the assessment and documentation of psychopathology (AMDP) system16 were used. Items were scored as being either ‘present’ or ‘absent’.
Psychiatric re-hospitalizations and relapses were recorded. Relapse was defined as the occurrence of a major affective syndrome or of psychotic symptoms that led to either hospitalization or outpatient treatment, which included psychiatric medication and a disruption of daily activities. In most patients with PDD the delusional symptoms persisted more or less during the whole follow-up period. For such patients, hospitalizations during follow up did not necessarily mean a dramatic exacerbation of symptoms or deterioration, but were very frequently a result of the social conditions.
Psychopathological symptoms at the follow-up investigations were determined using the positive and negative syndrome scale (PANSS).17 The level of general functioning was assessed using the global assessment of functioning (GAF) scale,6 which is a widely used rating scale for evaluating the overall functioning of a subject on a continuum that ranges from a state of severe psychiatric illness to a state of health. The reliability and validity of the GAF scale are well documented.18 Social disability was measured using the German version of the WHO disability assessment schedule (DAS).19
All interviewers were physicians and staff members of the Psychiatric Department of the Martin Luther University Halle-Wittenberg, who had been extensively trained in the use of the instruments by a senior consultant (FP). Inter-rater reliability on the use of the instruments by members of our group has been previously determined, and the scores were found to be between good and excellent.11
The data were analyzed by a computerized statistical software program (spss V17.0, spss Inc., Chicago, IL, USA). Student's t-tests were used to analyze bivariate continuous data. The χ2-test or Fisher's exact test for 2 × 2 contingency tables were used to analyze categorical data, where appropriate. Student's t-tests or Mann–Whitney U-tests were used to compare quantitative data, where appropriate. Statistical significance was set at 5% (two-tailed tests).
Sociobiographical and non-symptomatological features of the disorders
About 79% of the APTD patients were female. This higher prevalence of the disorder in women than in men is characteristic of ATPD, and was not present in the patients with PDD, where no sex difference was found (Table 1).
Table 1. Relevant sociobiographical data
|Sex|| || || || || || |
| Female||21||(48.8)||32||(78.0)||7.691 (1)||0.006†|
| Male||22||(51.2)||9||(22.0)|| || |
|Birth complications||4||(9.3)||7||(17.1)||1.114 (1)||0.291†|
|Developmental disturbance||4||(9.3)||2||(4.9)|| ||0.676‡|
|‘Broken home’ environment||14||(32.6)||17||(41.5)||0.715 (1)||0.398†|
|Mental illness in a first-degree relative (any disorder)||10||(23.3)||14||(34.1)||1.120 (1)||0.269†|
|Mental illness in a first-degree relative (only psychotic or major affective disorders)||5||(11.6)||6||(14.6)||0.167 (1)||0.683†|
|Mental illness in a first-degree relative (major affective disorder)||4||(9.3)||2||(4.9)|| ||0.676‡|
|Mental illness in a first-degree relative (schizophrenia)||1||(2.3)||2||(4.9)|| ||0.611‡|
|Educational level|| || || || ||838.5||0.687§|
| Very low||3||(7.0)||5||(12.2)|| || |
| Low||18||(41.9)||11||(26.8)|| || |
| Medium||12||(27.9)||15||(36.6)|| || |
| High||10||(23.3)||10||(24.4)|| || |
Birth complications of any kind, such as prolonged labor, were more frequent in the ATPD patients, and developmental disturbances in childhood (defined by retardation in motor or speech development, as reported by the patient) were somewhat more frequent in the PDD patients. However, these differences were not statistically significant (Table 1).
A ‘broken home’ environment was defined as a disruption in the continuity of caregiving in the patient's family before the age of 15, when one of the following criteria was met: death of one or both parents, divorce or separation of the parents, the caregiver was not the parent, and severe substance abuse of one or both parents.20 The frequencies of a broken home environment in both patient groups were found to be very similar (Table 1).
A detailed family history was obtained for all subjects. Data did not allow a differentiation between different psychotic and major affective disorders, but an attempt was made to differentiate non-organic psychotic and affective disorders from other mental disorders, such as alcohol dependency. There was no statistically significant difference between the two groups in the number of study patients with a history of mental illness in a first-degree relative (Table 1).
Educational level was considered ‘very low’ for study patients with less than 8 years of schooling or who received special education, ‘low’ for study patients with 8 or 9 years of schooling, ‘medium’ for study patients with 10 or 11 years of schooling and ‘high’ for study patients with 12 or more years of schooling. The educational levels of the PDD patients were not significantly different from those of the ATPD patients (Table 1).
The non-symptomatological features of the index hospitalization of the two patient groups are presented in Table 2. The patients with PDD were 10 years older at the onset time of their disorder than the patients with ATPD, and this significant age difference is still reflected in the age difference at the index admission. At the time of the index admission, the patients with PDD have significantly fewer previous hospitalizations than the patients with ATPD (Table 2).
Table 2. Non-symptomatological characteristics of the index hospitalization
|Age at onset in years||46.9 ± 13.2||35.9 ± 11.2||3.998 (82)||<0.001†|
|Number of previous hospitalizations||0.47 ± 1.6||1.5 ± 3.0||615.5||0.003§|
|Age at index admission (years)||51.8 ± 12.6||41.4 ± 12.6||3.771 (82)||<0.001†|
|Duration of index hospitalization (days)||38.7 ± 27.6||34.3 ± 24.0||0.766 (82)||0.446†|
|Involuntary admission||8 (18.6)||9 (22.0%)||0.146 (1)||0.703‡|
|Discharge against medical advice||9 (20.9)||4 (9.8%)||2.003 (1)||0.157‡|
|Life events before the index hospitalization||9 (20.9)||18 (43.9%)||5.078 (1)||0.024‡|
|Life events before onset of disorder||19 (44.2)||19 (46.3)||0.039 (1)||0.843‡|
Otherwise, the differences between the two patient groups were small. The durations of hospitalizations were only minimally longer in the PDD patients than in the ATPD patients, and involuntary admission occurred in about 20% of the index hospitalizations in both groups. PDD patients discharged themselves against medical advice twice as often as ATPD patients, but this difference was not statistically significant.
Compared to the ATPD patients, a significantly smaller proportion of PDD patients experienced a stressful event during the 6 months before the index hospitalization. Interestingly, the frequency of stressful events that preceded the first hospitalization was similar in PDD patients and ATPD patients.
Symptomatological features of the disorders
Table 3 summarizes the symptoms that were displayed by PDD and ATPD patients during the index hospitalization. Some of the differences in symptoms reflect the diagnostic criteria. While almost all patients had delusions, hallucinations occurred in more than 75% of the ATPD patients, but only in a small number of the PDD patients. These PDD patients suffered from hallucinations in the background, which were derivable from delusional content. Anxiety was less frequent in the PDD patients than in the ATPD patients, while depressive symptoms were present in more than 50% of the study patients in both groups. Rapidly changing delusional topics and rapid changes of mood are the hallmarks of a ‘polymorphic’ psychotic syndrome, and these polymorphic symptoms were seen exclusively in the ATPD group.
Table 3. Symptomatology of the index hospitalization
|Depressed mood||24||(55.8)||30||(73.2)||2.754 (1)||0.730|
|First-rank symptoms||0||(0.0)||30||(73.2)||48.943 (1)||<0.001|
|Rapidly changing mood||0||(0.0)||28||(68.3)||44.049 (1)||<0.001|
|Delusions of being influenced||0||(0.0)||20||(48.8)||29.366 (1)||<0.001|
|Rapidly changing delusions||0||(0.0)||20||(48.8)||27.530 (1)||<0.001|
Course and outcome
During the follow-up period, six patients with PDD at index hospitalization met the DSM-IV criteria of schizophrenia, and one patient developed a schizoaffective disorder, manic type (Table 4). These seven patients were excluded from the various analyses of the outcome measures. Five patients with ATPD met the criteria of schizophrenia during follow up. One of these and an additional four patients with ATPD experienced schizoaffective episodes. To assure comparability between the two groups of study patients, these nine patients with ATPD were also excluded from the various analyses of the outcome measures. Therefore, the results of the analyses of the outcome measures refer to ‘pure’ PDD and ATPD patients. The proportion of ‘pure’ or ‘diagnostically stable’ forms was almost identical in both disorders (79% for PDD patients and 76% for ATPD patients).
Table 4. Diagnostic stability in persistent delusional disorders and acute and transient psychotic disorders
|Lost to follow up¶||10 (23.3)||3 (7.3)||4.076||0.043†|
|Completed follow up||33 (76.7)||38 (92.7)|| || |
| Schizophrenic episode during follow up§||6 (18.2)||5 (13.2)||0.320 (1)||0.560†|
| Schizoaffective episode during follow up§||1 (3.0)||5 (13.2)||2.342 (1)||0.206‡|
| Diagnostically stable§||26 (78.8)||29 (76.3)||0.804 (1)||0.804†|
With a mean age of 59 years, patients with PDD were about 10 years older at follow up compared to ATPD patients (Table 5). During the follow-up period, the number of re-hospitalizations of PDD patients was less than half of that of the ATPD group. Specifically, we found that most patients with PDD were not re-hospitalized, whereas only 28% of the ATPD patients were not re-hospitalized during the follow-up period. All these differences were statistically significant (Table 5). The finding of a reduced number of re-hospitalizations among the PDD patients should not be interpreted as an absence of symptoms, because delusions usually persisted in the PDD patients.
Table 5. Outcome: Re-hospitalizations and status at follow up (only ‘pure’ persistent delusional disorder and acute and transient psychotic disorder patients)
|Age at follow up||58.7 ± 11.8||48.3 ± 13.0||3.109 (53)||0.003†|
|Number of hospitalizations during follow-up period/year||0.11 ± 0.23||0.28 ± 0.27‡||203.5||0.002‡|
|Without re-hospitalization||19 (73.1)||8 (27.6)||11.352 (1)||0.001§|
|Early retirement||9 (34.6)||12 (41.4)||0.266 (1)||0.606§|
|Stable relationship||12 (46.2)||18 (62.1)||1.401 (1)||0.237§|
|On psychiatric medication||14 (53.8)||14 (48.3)||0.170 (1)||0.680§|
|Antipsychotic at follow up||13 (39.4)||12 (41.4)||0.266 (1)||0.606§|
|Antidepressant at follow up||9 (34.6)||4 (13.8)||3.293 (1)||0.070§|
|Living independently (autarkic)||23 (88.5)||27 (93.1)|| ||0.659¶|
|Disability Assessment Schedule|| || || || |
| Global score‡‡||1.04 ± 0.99||0.48 ± 0.83||2.253 (53)||0.028†|
|Positive and Negative Syndrome Scale§§|| || || || |
| Positive symptoms||11.0 ± 3.2||7.5 ± 1.5||5.155 (51)||<0.001†|
| Negative symptoms||8.6 ± 3.1||9.5 ± 5.7||–0.718 (51)||0.476†|
| General symptoms||21.6 ± 4.5||19.2 ± 4.7||1.906 (51)||0.062†|
| Total score||41.2 ± 8.5||36.2 ± 10.9||1.880 (51)||0.066†|
|Global Assessment of Functioning Score¶¶||62.7 ± 16.5||85.9 ± 9.7||–6.465 (53)||<0.001†|
| GAF score >70||8 (30.8)||26 (89.7)||20.104 (1)||<0.001§|
The psychosocial status at follow up of the two patient groups is also given in Table 5. Although the PDD patients were slightly less often in a stable partnership than the ATPD patients, this difference did not reach statistical significance. There also were no significant differences between the two study groups with regard to early retirement, autarky (i.e. capability of independent living with or without giving support to other family members), or the proportion on psychiatric medication. The use of antidepressant medications tended to be more frequent in the PDD patients than in the ATPD patients.
The lower part of Table 5 summarizes the various outcome measures for the PDD and ATPD patients in the domains of social disability, psychopathological symptoms, and general functioning. There were significant differences between the two patient groups in most measures. Generally, the outcome tended to be less favorable for the PDD patients than for the ATPD patients. Social impairment was significantly more pronounced in the PDD patients than in the ATPD patients, although the overall level of social impairment was rather low for both groups. PDD patients suffered from more positive symptoms at follow up, and had slightly higher total PANSS scores than the ATPD patients, but negative symptom scores were minimal for both groups. There was a marked difference in global functioning, and only a small number of PDD patients obtained scores greater than 70.
Subtypes of ATPD
In the present sample there were 28 patients with the polymorphic subtype of ATPD (ICD-10 F23.0 or F23.1), 11 with the subtype of ‘schizophreniform’ disorder (ICD-10 F23.2) and two patients belonging to residual categories. When all analyses were repeated with the ATPD sample restricted to the polymorphic subtype, the difference in the disability assessment schedule was reduced to trend level (P = 0.083). All other reported relationships remained unchanged.
PDD and ATPD are psychotic disorders that both differ in their course and outcome from schizophrenia and whose nosologies are disputed.3,8 Although positive psychotic symptoms, namely delusions, are characteristic of both disorders, afflicted patients do not generally develop progressive negative symptoms.3,9 It is unclear why repeated or persistent delusional symptoms occur in patients with PDD or ATPD without the severe deterioration that occurs in patients with schizophrenia.
To the best of our knowledge, a comparative study of the two psychiatric disorders has only been reported by Jørgensen21 in a sample of 88 inpatients with delusions of different origin. The strength of the present study is that this investigation was a comparative longitudinal study of two infrequently occurring psychotic disorders whose study patients were recruited from the same institution, and then assessed using identical standardized instruments. The main limitation of the study is the rather small number of study patients, even though we included all patients with PDD admitted over a considerable period of time. This limitation is inherent to most investigations of infrequent psychiatric conditions. Some of the results reflect differences in the diagnostic concepts of PDD and ATPD. The core findings, however, are not trivial because they either relate to features not included in the operational diagnostic criteria or verify supposed characteristics of the disorders by prospective longitudinal observations. To obtain samples as homogenous as possible, patients with a diagnostic change to schizophrenia or schizoaffective disorder were excluded from the longitudinal analyses. We cannot exclude that a small number of patients would undergo diagnostic shift at a still later time.
The results of the present investigation highlight several interesting differences between PDD and ATPD that persisted when analysis was restricted to the polymorphic subtype of ATPD. PDD has a later onset than ATPD, and has the same prevalence in men and women, whereas ATPD occurs much more frequently in women than it does in men.9 Interestingly, the duration of inpatient treatment for PDD is not markedly longer than that of ATPD. Although we did not detect a statistically significant effect in our sample, it is noteworthy that the number of patients with PDD who discharged themselves from hospital against medical advice was twice as high as the number of patients with ATPD. This pattern is consistent with the experience that many patients with PDD are delusional for long periods, and do not seek medical assistance.3 Precipitating factors that were associated with onset of the disorder were found in 44% of the patients with PDD, and this number was not significantly different from that found in the patients with ATPD (46%). This finding is in agreement with the finding of Opjordsmoen et al.,22 who studied the influence of preceding life events in delusional disorders. However, subsequent hospitalizations in PDD patients seem to be less often preceded by a stressful life-event than subsequent episodes of ATPD, as suggested by the finding of a significant difference in the number of stressful life-events that preceded the index hospitalization (which is not identical with the onset of the disorder).
In the evaluation of relapses (or re-hospitalizations), one has to bear in mind that the delusional symptoms in most patients with PDD persisted continuously during the follow-up period. For these patients, hospitalizations during follow up did not necessarily mean a dramatic deterioration of their symptoms. In contrast, a relapse in the ATPD patients always involved the sudden re-appearance of de novo psychotic symptoms while they were in a state of remission. In other words, while almost all relapses led to a hospitalization in the ATPD patients, PDD patients may be chronically symptomatic without being re-hospitalized. This difference in the acuteness of symptoms explains why re-hospitalizations were significantly less frequent in the PDD patients than in the ATPD patients. This holds true whether one examines the number of study patients who were hospitalization-free or the mean number of hospitalizations per year that occurred during the follow-up period.
The outcomes of the two diagnostic groups differed in some, but not all domains. The present study confirms the absence of clinically relevant negative symptoms in both disorders over a follow-up period of more than 10 years. However, the persistence of positive symptoms, namely delusions, prevailed in the PDD patients, and this persistence of delusions is also reflected by markedly lower GAF scores in these patients at follow up when compared with the ATPD patients. This result is in agreement with the study of Jørgensen21 who found similar differences in global functioning in his 8-year follow-up study of 88 PDD and ATPD patients with delusional beliefs. With respect to social outcome, PDD patients have a slightly less favorable course than ATPD patients as indicated by the DAS scores. However, the PDD subjects remained independent, had a stable partnership, and stayed in treatment almost as often as the ATPD patients, and their rates of early retirement did not exceed those of the ATPD patients. The findings of our study thus confirm Winokur's23 suggestion that a delusional disorder does not destroy the ability of the individual to function socially, but does create problems in daily living because of interpersonal conflicts.
In conclusion, the results of the present investigation show that, in contrast to ATPD, the delusional symptoms in PDD are highly preserved and tend to remain stable over many years. They can still be found at long-term follow up, and they affect the general functioning and, to a lesser degree, social adaptation. Both disorders share a relative absence of negative symptoms and the preservation of independence over the long term. Why psychotic symptoms remit in ATPD, but persist in PDD, remains unclear. The dissimilarities in sex ratio and the age at the time of onset of the two disorders may indicate nosological differences. These differences could be explored in future studies that embrace neuropsychological and neurobiological aspects of the two disorders.