Non-affective acute psychoses: Uncertainties on the way to DSM-V and ICD-11

Abstract

Since the early 20th century, a group of non-affective psychoses with acute onset and brief duration have been described in different countries and under various names, including cycloid psychosis, bouffée délirante, and reactive psychosis. These psychoses share a number of characteristics, including benign course, greater prevalence in women than men and in developing countries than industrialized countries, and high prevalence of premorbid psychological and physiological stressors. However, the variations in names and minute details of symptomatology have overshadowed the basic similarities across these various descriptions. Confusion in classification persists in the two contemporary diagnostic systems, the DSM-IV and the ICD-10. We believe that most cases of these psychoses could be captured under a broad, unified category of non-affective psychosis with acute onset and brief duration, and urge the authors of the upcoming revisions of the DSM and ICD to create such a category. A unified diagnostic category for these disorders would reduce unnecessary fragmentation in the diagnostic systems and assist in the progress of research on these rare conditions.

Introduction

A group of non-affective psychoses with brief duration and acute onset have been described since early 1900s [1]. These psychoses have been named differently in different countries, including cycloid psychosis in German-speaking countries, bouffée délirante in French-speaking countries, and reactive or psychogenic psychosis in Scandinavian countries [2]. These psychoses are also classified very differently in the two common classification systems, the American Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) [3] and the International Classification of Disease (ICD-10) [4].

The variations in classification systems are often confusing to novice clinicians and make generalization of research findings difficult. Yet the similarities among different descriptions are more striking than the differences and point to a common condition.

In this paper we present an overview of the current status of knowledge regarding these non-affective acute psychoses. We discuss recent findings regarding the phenomenology, epidemiology, correlates, course and treatment of these conditions as well as future directions for research. We use the term non-affective acute psychosis as an umbrella term for all cases of non-affective psychosis with an acute onset and brief duration.

Classification of non-affective acute psychoses

The DSM-IV and ICD-10 differences with regard to classification of non-affective acute psychoses are among the most striking differences between the two systems. The DSM-IV classifies these disorders under brief psychotic disorder, schizophreniform disorder and psychotic disorder not otherwise specified (NOS). Brief psychotic disorder is characterized as an episode with at least one psychotic symptom, lasting at least one day but less than one month, with a complete return to premorbid functioning [3,5]. Schizophreniform disorder is characterized as a psychotic episode with two or more classic symptoms of schizophrenia that lasts at least 1 month but less than 6 months. While acute onset is not a diagnostic criterion for either disorder, the manual describes brief psychotic disorder as a psychotic episode with sudden onset in the text of the manual and schizophreniform disorder diagnosis includes acute onset (within 4 weeks) as a good prognostic feature. The DSM-IV category of psychotic disorder NOS includes presentations of psychotic symptoms for which there are inadequate information to make a specific diagnosis or symptoms that do not meet full criteria for a specific psychotic disorder [3].

The ICD-10 classifies non-affective acute psychoses under the category of “acute and transient psychotic disorders” (ATPD), incorporating four specific disorders and two non-specific disorders. All ATPD share the common features of acute onset within two weeks, and presence of typical psychotic symptoms. Duration must not exceed 1 month in the subtypes involving schizophrenia-like symptoms, and 3 months in the other subtypes [4,5]. The ATPD category includes subcategories of acute polymorphic psychotic disorder, in which symptoms vary in type and intensity over a short period of time [5], and acute delusional psychotic disorder, in which persons exhibit relatively stable delusions and/or hallucinations. The description of ATPDs was influenced by the concepts of cycloid psychosis, bouffée délirante and reactive psychosis.

While not recognized as diagnoses in either the ICD or DSM, cycloid psychosis, bouffée délirante, reactive psychosis, and non-affective acute remitting psychosis are terms that also refer to syndromes characterized by acute onset psychosis. Karl Kleist coined the term cycloid psychosis in 1924, and later Karl Leonhard identified three categories of these psychoses: the anxiety-happiness psychosis, the excited-inhibited confusion psychosis, and the hyperkinetic-akinetic motility psychosis. Perris & Brockington defined these disorders to have a sudden onset and found the symptom presentation to often be mixed, including symptoms of confusion, anxiety, mood symptoms, motility disturbances and hallucinations [6]. Patients with cycloid psychosis have a normal premorbid personality and a good prognosis with either a single episode or recurrent episodes with complete remission in between [7,8].

The French concept of bouffée délirante refers to conditions with a sudden onset marked by prominent delusions with hallucinations, confusion, anxiety and affective symptoms. Symptoms vary rapidly, perhaps even by the hour, and there is a rapid return to the premorbid state of health [9]. A very similar syndrome of acute delusional psychosis has also been described by French psychiatrists [10].

Previously a frequently utilized diagnosis in Scandinavia, reactive psychosis referred to a psychotic episode precipitated by a traumatic experience that remitted when the cause was removed. This diagnosis has rarely been used since the introduction of the ICD-10 [11]. However, DSM-III and DSM-III-R paid homage to the concept by introducing the brief reactive psychosis diagnosis, defined as a psychotic episode lasting less than one month that was preceded by a marked stressor [12]. Presence of marked stressors as a specifier was maintained in the description of brief psychotic disorder in DSM-IV and discussed as a common feature in the description of ICD-10 ATPDs.

More recently, Susser and Wanderling introduced the term non-affective acute remitting psychosis (NARP) in their work on the World Health Organization Determinants of Outcome of Severe Mental Disorders (DOSMeD) study [13]. Patients were designated as cases of NARP if they experienced a non-affective psychotic episode with acute onset. Duration of NARP episodes can extend up to 6 months and episodes do not need to meet specific symptom criteria as long as they include psychotic symptoms and do not meet the criteria for a mood disorder episode. NARP also requires a remitting course, defined as either a single episode followed by complete remission or multiple episodes with complete remission between episodes [13]. NARP was introduced as a broad category that could accommodate most cases meeting the criteria of the classic syndromes as well as ATPD.

These varied descriptions share a number of common features. Almost all are characterized by acute onset, usually within 2 weeks or even a shorter period, brief duration and generally good prognosis. Many, but not all descriptions include confusion as a prominent symptom and some cases are characterized by rapidly changing symptoms. Nevertheless, the diagnoses do not overlap in practice. For example, despite the common features of cycloid psychosis, bouffée délirante, and reactive psychosis with the ICD-10 ATPD, a majority of cases with these older diagnoses cannot be classified as ATPD cases [14,15]. This is partly due to differences in symptom presentation or duration over 1-3 months which precludes an ATPD diagnoses.

Both similarities and differences in terms of symptomology have been found comparing non-affective acute psychoses to schizophrenia and bipolar disorder. A study in the Republic of Congo found no differences in cognitive functioning between patients with brief psychotic disorder, schizophreniform or schizophrenia [16]. In a Portuguese study, NARP patients were found to have shorter DUP and better premorbid adjustment as compared to patients with first episode schizophrenia [17]. First episode NARP patients in the U.S. and Iran had negative and positive symptom profiles more similar to patients with affective psychosis than schizophrenia [18,19]. The presence of affective symptoms and the remitting course in some cases of cycloid psychosis has led some researchers to conclude that these psychoses are more appropriately classified as affective disorders [20,21]. However, as currently characterized, the cycloid psychoses may include a heterogeneous group of psychoses including cases with affective symptoms [22].

Epidemiology

Non-affective acute psychoses are rare in industrialized countries. In Nottingham, UK, the age- and gender-standardized incidence rate of “true” ATPD (determined after 3 years of follow-up) was 1.36 per 100,000 [23]. The incidence of ATPD in Denmark was somewhat higher at 9.6 per 100,000, although in about 60% of these cases, the diagnosis was changed at a subsequent admission (most to schizophrenia or affective disorders) [24]. In Sweden, the incidence of cycloid psychosis was reported to be 0.043 per 1000 residents between 15 and 50 years of age in 1983 [25], and 0.016 per 100 person-years among women between 1947 and 1972 [26]. A more recent population survey in Finland reported lifetime prevalences of 0.05% for brief psychotic disorder, 0.07% for schizophreniform disorder, and 0.45% for psychotic disorder NOS [27].

It is not clear, however, whether between-country variations in incidence and prevalence reflect true variations in rates or differences in diagnostic practices. Furthermore, use of different diagnostic systems makes comparison across studies difficult. Researchers have repeatedly noted the higher incidence of non-affective acute psychoses in developing compared to industrialized countries [28,29]. To our knowledge, Susser and Wanderling’s 1994 report is the only study that directly compared incidence rates between industrialized and developing countries using standardized instruments [13]. These authors found a 10-fold higher incidence of NARP in developing as compared to industrialized countries.

In contrast to schizophrenia which has a slightly higher incidence rate in males [30,31], rates of non-affective acute psychosis are commonly reported to be higher in females. In the Nottingham sample, the annual incidence of true ATPD per 100,000 was 0.74 in men and 1.99 in women [23]. Susser and Wanderling reported male-female ratios of NARP of 0.96 in the developing countries and 0.44 in industrialized settings [13]. The incidence of cycloid psychosis in Sweden was also reported to be higher in women (.05 per 1000) than in men (.036 per 1000) [25]. In contrast, in the Danish registry sample, incidence rates were only slightly higher in females (9.8 vs. 9.4 per 100,000). However, gender-specific rates among those who retained their ATPD diagnoses were not reported [14].

Age of onset of non-affective psychoses varies considerably across studies. In the WHO DOSMeD, the mean age of onset of NARP was 22.4 years for both sexes in developing countries and 25.5 years for men and 24.9 years for women in industrialized countries [13]. Similar results have been reported from studies in Iran [18], however the mean age of onset of NARP in an incidence cohort from New York [19] and in a cohort of ATPD patients in Germany, was in mid-30s [32]. In Denmark, the age of onset of ATPD was also higher, and differed between men and women (46.2 for females vs. 37.8 for males) [24].

Overall, there are some consistencies among the few epidemiological studies of non-affective acute psychoses. First, these conditions appear to be more common in females than males, distinguishing this syndrome from schizophrenia. Second, the non-affective acute psychoses appear to be more common in developing country settings than industrialized settings [13,18,33]. Finally, the average age of onset of these psychoses is later than the age of onset of schizophrenia, although reported ages of onset vary widely.

Stress as a risk factor

A number of studies have examined biological and psycho-social risk factors for non-affective acute psychoses [17,18,34-36]. Stressful live events in the period immediately preceding onset have been a defining or common characteristic of these diagnoses across time and world region and are highlighted in the description of these syndromes in the DSM-IV and ICD-10. Stressful events are frequently found in patients with NARP [37]. A first episode study in Iran found that two-thirds of NARP patients had experienced a significant life event in the 4 weeks preceding the onset of their symptoms [18]. A first-episode study in India similarly reported stress within two weeks before onset in 69% of patients with a subtype of ATPD [38]. In a study from Chandigarh, India, recent life events (characterized as job distress for men and leaving or returning to parental village for women) were more common among the brief psychotic cases with acute onset than those with non-acute onset [39]. In a Danish sample, psychosocial stressors were reported within the two weeks prior to first psychotic symptoms for 53% of patients, and those with preceding stressors were more likely to experience an abrupt onset [40].

The role of stress may vary by gender and frequency of episodes. A study in India found that stressful events were more commonly reported among female than male patients with non-affective acute psychosis [41]. In a study of cycloid psychoses, 1/3 of first episode cases were precipitated by somatic or psychic stressors, but the impact of stress decreased in subsequent episodes [8]. The postpartum period might be an especially stressful period for women both physically and psychologically. Many cases of psychosis in the postpartum period can be characterized as cases of non-affective acute psychoses. In a sample of consecutively-admitted women with postpartum psychosis, 21% of the patients met the diagnostic criteria of acute and transient polymorphous psychotic disorders, and 54% met the criteria for cycloid psychosis [42]. As a sign of the recognition of this association, the DSM-IV brief psychotic disorder allows of a “with postpartum onset” specifier.

There is some evidence of increased rates of non-affective acute psychosis in immigrants. In a Portuguese sample, black immigrants were more likely than non-immigrant white patients to receive a diagnosis of schizophrenia or ATPD [35]. Although a lack of cultural competence on the part of psychiatrists might explain the increased rates, immigrant status and racial discrimination may play a role [35]. In a study of foreign domestic workers admitted to a psychiatric hospital in Hong Kong, 63% received a diagnosis of ATPD [43]. West African and Caribbean immigrants living in Britain have been reported to experience an increased frequency of acute psychotic reactions, although increased rates of schizophrenia have also been reported in this patient population as well [44]. Furthermore, non-affective acute psychoses are likely more common in the home countries of these immigrant populations [13,45]. To our knowledge, no studies have directly compared the rates of non-affective acute psychoses in immigrant populations with the rates in countries of origin.

Family history

There is some limited evidence for the role of hereditary factors in non-affective acute psychoses. Das and colleagues [46] reported a three-fold higher risk of ATPD in first degree relatives of index patients with ATPD compared to schizophrenia. In another study, the proportion of first-degree relatives with any mental disorder was higher in a group of ATPD patients (20.3%) compared to controls without mental disorders (3.6%) [32]. Increased risk of cycloid psychoses in family members of patients with cycloid psychoses has also been noted [8]. However, a twin study of patients with cycloid psychosis found little evidence supporting heritability [47].

Das et al. [34] also found that patients with ATPD who had a family history of psychiatric disorder among first-degree relatives reported fewer stressors in the two-week period prior to illness onset, compared to those without a family history [34]. This observation lends support to the stress-vulnerability hypothesis in the etiology of acute psychoses.

Biological correlates

There are few studies of the biological correlates of non-affective acute psychoses. In a study of first-episode psychosis in Barcelona, NARP patients had significantly fewer 5-HT2A receptors compared to patients with paranoid schizophrenia and to healthy controls [17]. This pattern was also distinct from affective disorders, lending support to the validity of NARP as distinct from affective psychosis and schizophrenia. An imaging study from Germany comparing the diagnoses of psychiatric patients with ventricular abnormalities and patients without such abnormalities found a higher prevalence of cycloid psychosis in the first group [36].

Fever preceding the onset of psychosis has been associated with NARP in comparison to other forms of acute and sub-acute psychosis in the Life Events sub-study of the WHO DOSMeD study [24,39,48]. In a study from Germany, Stöber and colleagues found an increased prevalence of first-trimester respiratory infection in offspring with cycloid psychoses compared to offspring with bipolar disorder or schizophrenia [49]. The association was especially prominent in cycloid psychosis cases with an early age of onset.

Overall, there are few replicated findings across the range of psychosocial and biological risk factors and correlates reported for non-affective acute psychoses. Among these, the experience of marked physiological or psychological stress in the period preceding the onset of psychosis appears to be most consistent.

Premorbid adjustment

A high rate (63%) of personality disorders was observed among an inpatient sample of ATPD patients in Denmark shortly after recovery from symptoms [40]. However, this rate decreased at one-year follow-up, to 46% using ICD-10 criteria and 29% using DSM-IV criteria [50]. In the Halle study, ATPD inpatients were no different on any of the 5 NEO-FFI personality subscales when compared to hospital-based controls [51].

A comparison of consecutively-admitted ATPD inpatients to a hospital in Germany with hospital-based controls found no differences in education level, or history of marriage/stable relationship [32]. However, ATPD patients were more likely than controls to have experienced a discontinuity in parental care giving before age 15.

Course

By definition, non-affective acute psychoses have a benign course. All of the patients with a first episode NARP diagnosis in an Iranian sample experienced remission from their index episode within 3 months, and two-thirds remained relapse free by the two year follow-up [18]. The modal duration of NARP in the WHO DOSMeD study was 2-4 months, often extending beyond the 1 or 3 month duration specified in the ICD-10 ATPD criteria [52].

Recurrence of psychotic episodes is common in this group of psychoses, yet not as common as in schizophrenia or bipolar disorder. Over 15 years of follow-up, 30% of ATPD patients experienced a single episode, 50% had an episodic-remitting course, and 20% had a chronic course [53]. Perris reported that patients with cycloid psychosis have, on average, around 5 episodes throughout their lifetime [8]. Throughout two years of follow-up, 48% of patients with NARP remained in full remission, as compared to 14% of patients with other types of remitting psychoses (i.e. schizophrenia, delusional disorder) [19]. The course of non-affective acute psychoses might be even more benign in developing countries. In the Chandigarh site of the DOSMeD study, only one (6%) out of 17 patients followed-up to 12 years had remaining symptoms of illness at follow-up [54].

Diagnostic stability is a contested issue, and differs widely by diagnosis and length of follow-up. A small study of first-episode psychotic patients in Iran found that 100% of those diagnosed with ICD-10 ATPD and DSM-IV brief psychotic disorder maintained the same diagnosis over 12 months of follow-up [55]. However, in a 15-year follow-up of 197 patients diagnosed using both the ICD-10 and DSM-IV, the diagnoses of ATPD, schizophreniform and brief psychotic disorder were quite unstable over time, with the majority of patients transitioning to diagnoses of schizophrenia or affective disorders [53]. A Danish study covering 15 years of register data found a 39% stability rate of ATPD, with 60% of the total ATPD sample developing another psychiatric disorder by their third admission [24]. Similarly, diagnostic stability over five years in a first episode psychotic sample in China was 35% for those diagnosed with ATPD, with 29% of ATPD patients transitioning to schizophrenia [56]. In the group of ATPD patients that were later reclassified, all of those developing schizophrenia had a “non-polymorphic” subtype at baseline, whereas patients with a “polymorphic” subtype at baseline were re-diagnosed with bipolar disorder [56]. In a small study of 16 cases with acute polymorphic disorder without symptoms of schizophrenia in Japan, five developed schizophrenia over the 12 year follow-up period [57]. In the only study that reported the stability of NARP in an industrialized country setting, 6% of the NARP patients from a New York sample changed to schizophrenia or schizoaffective diagnosis by the two year follow-up, whereas the majority (77%) of persons with other remitting psychosis at baseline transitioned to a schizophrenia or schizoaffective diagnosis [38].

Predictors of diagnostic stability and favorable outcome include sudden onset, female sex, duration less than one month, and good premorbid functioning [38]. Examining a small group of persons with ATPD, 40% of whom later developed schizophrenia, Suda found no significant differences in severity or duration of psychotic symptoms during the initial hospitalization, whereas acute insomnia was predictive of a single episode of ATPD [58]. Confusion and perplexity are listed among the good prognostic indicators of schizophreniform disorder in the DSM-IV [3], however, there is little recent empirical data on the predictive validity of this feature. In a review of 13 follow-up studies of ATPD, Castagnini and Berrios noted that studies in developing settings tend to show higher diagnostic stability and lower rates of relapse than studies in western settings [14].

While the outcome of non-affective acute psychoses is generally favorable when compared to schizophrenia, many individuals with non-affective acute psychoses experience adverse outcomes. An analysis of the Danish psychiatric case register data reported an overall standardized mortality ratio (SMR) of 2.9 for ATPD patients compared to the general population [59]. The SMR for unnatural causes was higher and varied by gender (11.1 for males and 9.1 for females), and was particularly high for suicide (30.9). In the Halle study, the rate of suicidal behavior during the course of ATPD was 35.7%, and was comparable to the rate found in schizophrenia (40.5%) [60].

Treatment

There is little data regarding the treatment of non-affective acute psychoses as a distinct entity, and, to our knowledge, no randomized clinical trials that deal with these disorders exclusively. In the Halle Study of brief and acute psychoses, 95% received an antipsychotic, 21% an antidepressant, and 7% lithium during the initial episode [5]. Compared to patients with schizophrenia or bipolar schizoaffective disorder, a smaller proportion of ATPD patients were still taking psychotropic medications over the follow-up period, and the authors reported good levels of functioning in all patients who were no longer taking medication [5]. NARP patients in an Iran first episode study were found to have received fewer months of antipsychotic medication than patients with other non-affective psychotic disorders [18], which likely reflects faster remission of these psychoses compared to other first admission psychotic disorders. An older, small study by Perris found that patients with cycloid psychosis on continuous lithium treatment had fewer repeat episodes [8].

General treatment recommendations for patients presenting with their first episode of psychosis, including psychotic disorders with acute onset, call for a comprehensive assessment to evaluate comorbidities and rule-out organic and substance induced causes [61]. Atypical antipsychotics, often at low initial doses, are recommended as the first line of medication treatment [61], with continuation of treatment for a year [62]. Coordination with the patients family and/or friends is recommended to help ensure treatment adherence and to educate them about the disorder [61].

Conclusion & Future Directions

Non-affective acute psychoses are admittedly rare, especially in industrialized settings. However, they are associated with suffering and adverse outcomes for the patients and their families. Furthermore, with ever-larger waves of immigration from developing to industrialized countries, more and more cases of non-affective acute psychosis are likely to seek treatment from mental health providers in the host countries. A better understanding of these conditions would help clinicians to more effectively assess and treat these patients.

Perhaps because of the rarity of these conditions in industrialized countries, where most of psychiatric research activity occurs, there is a paucity of research data on these conditions based on large and representative samples. Research on non-affective acute psychoses also remains hampered by differences across diagnostic systems. The ICD-10 and DSM-IV classify these conditions very differently, and despite calls to harmonize the two diagnostic systems [19,63,64], there is no evidence of major change to the relevant diagnostic categories in the recently publicized draft version of DSM-V. While there is some evidence that the majority of the cases of ICD-10 ATPD can be categorized into the brief psychotic disorder or schizophreniform disorder DSM-IV categories [50,65], it is not clear if the majority of these DSM-IV cases of are also captured by the ICD-10 ATPD diagnoses. Furthermore, many cases of non-affective acute psychosis do not meet either the ICD-10 ATPD or the DSM-IV brief psychotic or schizophreniform disorder criteria and are relegated to the non-specific and heterogeneous category of psychotic disorder NOS in DSM-IV.

The current nosological state of non-affective acute psychoses resembles the nosological state of schizophrenia before the landmark US-UK study [66] and before the introduction of DSM-III, when different diagnostic traditions characterized schizophrenia and affective disorder differently based on national psychiatric traditions. The WHO collaborative studies on acute psychoses [29] and the introduction of the ICD-10 ATPDs aimed to resolve these differences. However, a satisfactory resolution of the nosological status of these psychoses eludes us to this day.

Although the past research on non-affective acute psychoses cannot provide solid guidelines, it does provide information that can help authors of the future editions of the two diagnostic systems. First, there appear to be few symptomatic features at baseline that consistently distinguish non-affective acute psychoses from other psychotic conditions or to distinguish true positive from false positive cases (i.e., cases that receive other diagnoses in later assessment). Furthermore, symptom profiles distinguishing the different ATPD subtypes do not provide reliable prognostic indicators. Confusion and polymorphous symptomatology have been highlighted in some classic and modern descriptions of non-affective acute psychoses. However, ascertainment of these symptoms may not be easy for non-psychiatrist clinicians working in resource-poor settings.

An acute mode of onset, presence of any psychotic symptoms and brief duration of psychosis are easier to assess and will likely provide greater inter-rater reliability than specific symptom clusters. Susser and colleagues’ concept of NARP was introduced in an attempt to provide such criteria and thus capture all the cases of ICD-10 ATPD and DSM-IV brief psychotic disorder and schizophreniform disorder in addition to cases of acute psychosis that may be left out of these categories. Progress in research on the nature and etiology of non-affective acute psychotic disorders may ultimately depend on the development of a similar category of psychotic disorder to be used in both the ICD-11 and DSM-V.