Abstract
The study of first-episode psychosis affords many opportunities for early intervention [1–6] and investigations into the biological basis of psychotic disorders without potential confounds of prior treatment and illness chronicity [7]. Individuals with first-episode schizophrenia are particularly responsive to pharmacotherapy [8]. There is also a possible link between longer duration of untreated psychosis and poorer outcome [2,9–11] although this was not replicated in some studies [12–14] and remains an area requiring more research [15].
First-episode psychosis often follows a prodrome. This is a period of disturbance or deviation from the patient's previous experience and behaviour that occurs before the development of florid psychotic features [16]. Identifying the prodrome in an individual may provide the opportunity for early intervention and prevention [17].
Classical descriptions of the psychotic prodrome are rich in phenomenological descriptions [18–22]. However, they are mainly anecdotal in nature. Recent conceptualisations such as DSM-III-R have less breath and depth, and describe the schizophrenia prodrome in terms of mainly behavioural characteristics [23]. More recent retrospective studies by Yung and McGorry [24], however, used a combination of unstructured and semistructured techniques to describe a wide variety of prodromal phenomena, including a mixture of attenuated psychotic symptoms, neurotic and mood-related symptoms and behaviour changes.
All male Singaporeans aged between 17 and 23 are registered for National Service. Prior to enlistment, a minority are exempted on psychiatric grounds for psychotic conditions or severe neuroses. Of those enlisted, most tolerate the structure and demands of the military well. A small group, however, develop psychological disorders and is referred to the Psychological Care Centre for evaluation and management. Although most of these are stress-related adjustment problems [25], some suffer from first-episode psychiatric illness, including firstepisode psychosis.
To our knowledge, there is little local published data about prodromal symptoms of psychotic patients. We have thus aimed to retrospectively describe the prodromal symptoms of first-episode psychosis patients diagnosed at our Centre, and have also compared this with symptoms of patients with first-episode non-psychotic disorders.
Method
We selected consecutive military servicemen presenting with firstepisode psychosis between 1 August 1997 and 1 August 1999 to the Psychological Care Centre (PCC), a psychiatric facility for military servicemen with psychological problems. Exclusion criteria were clear-cut organic aetiology for psychotic symptoms (five subjects), patients with attenuated or questionable psychotic symptoms for which a firm diagnosis could not be made (five subjects). Thirty subjects with first-episode psychosis were studied.
Another 34 servicemen were randomly selected out of 123 servicemen presenting to PCC between 1 August 1997 and 1 August 1999 with first-episode non-psychotic and non-organic psychiatric conditions.
All the patients in this study were well known to the authors, who were the primary psychiatric caregivers. Most of the first-episode psychosis patients (26/30, 87%) were admitted to our Centre one or more times (mean = 1.6, SD = 1.2, range = 0–5), staying for a medianof 23 days (SD = 24, range = 2–120), during which they were reviewed daily. Of the remainder, two were first admitted to the state psychiatric hospital and later treated as outpatients at our Centre, while the other two were not hospitalized and received outpatient treatment at our Centre. The non-psychotic patients were admitted a mean of 1.2 times (SD = 2.3, range = 0–4), and stayed a median of 5 days (SD = 17, range = 1–60). The mean follow-up period for first-episode psychosis patients was 7.8 months (SD = 5.1, range = 1–23) while that for nonpsychotic patients was 6.8 months (SD = 6.3, range = 1–20).
A combination of unstructured and semistructured interviews of patients and informants were used to describe the symptoms and signs of first-episode psychosis patients and non-psychotic patients. A DSMIV diagnosis [26] was assigned for each patient.
The psychotic prodrome was defined as the period from first noticeable symptoms to the onset of psychotic symptoms [2]. Further information about symptoms experienced during the psychotic illness and the prodrome was also obtained to delineate the type, severity and duration of the symptoms. The patient's ability to function at school, work and at a social level while asymptomatic, during the prodrome and during psychosis was also assessed. At least one family member was interviewed to obtain corroborative accounts of symptoms and signs. Other relatives, friends, colleagues and superiors were interviewed, when available, to clarify ambiguous symptoms. Deterioration in scholastic studies was verified by inspecting school records, in addition to accounts of subjective decline in school performance reported by patient and informants. Detailed process-notes of each interview were kept using a computerized medical record system.
Symptoms and signs were tabulated under categories described previously by Yung and McGorry [24], namely neurotic symptoms; moodrelated symptoms; changes in volition; cognitive changes; physical symptoms; speech abnormalities; perceptual abnormalities; change in sense of self, others or the world; suspiciousness; change in motility; change in affect; and behavioural changes.
Statistical methods
Two-tailed tests of significance were used throughout. The t-test for independent variables was used to compare means of ages, number of years of education and Hollingshead parental social class [27] between the psychotic and the non-psychotic groups of patients. The χ2 test was used to test association of the various signs and symptoms with the psychotic prodrome. The Fisher's Exact Probability Test was used instead when the expected value in a cell was less than 5. SPSS (SPSS, Chicago, IL, USA) was used in the data analysis.
Results
Demographics
The majority of the 30 patients with first-episode psychosis (23/30, 77%) had schizophrenia-like syndromes (22 with schizophrenia and one with schizophreniform disorder), while seven patients had other psychotic syndromes (three with schizoaffective disorder, two with delusional disorder, one with major depression with psychotic features and one with brief psychotic disorder). The most common diagnoses of the 34 comparison patients were adjustment disorder (12/34, 35%) and personality disorders (10/34, 29%). The others suffered from anxiety disorders (5/34, 15%), depressive disorders (4/34, 12%) and obsessive– compulsive disorder (3/34, 9%). Their distribution was similar to that of the cohort of 123 first-episode non-psychotic patients followed up at our Centre during the study period. The 30 patients with first-episode psychosis and the 34 with non-psychotic illnesses were mostly young men in their early 20s, who were similar in age, race, educational exposure and parental social class (Table 1).
Age, racial demographics, number of years of education and parental social class of the patients with first-episode psychosis and non-psychotic illnesses
Prodromal symptoms and signs
Two first-episode psychosis patients presented without any prodromal symptoms while the remaining 28 had had prodromal symptoms lasting a median of 22 months (SD = 16.6, range = 6–84 months). The onset of prodromal symptoms occurred prior to enlistment inall 28 patients (median = 12, SD = 8.1, range = 3–60 months prior to enlistment). The onset of psychosis was distributed throughoutthe 24–30-month period of military service (median 12, SD = 5.2, range = 1–26 months after enlistment).
Overall, the most common prodromal symptoms were social withdrawal (83%); anxiety (77%); sleep disturbance (77%); disturbance in attention, concentration or memory (73%); deterioration in studies in school (70%); depressed mood (63%); odd behaviour (53%); and anger or irritability (53%) (Table 2). The 23 with schizophrenia-like syndromes (schizophrenia and schizophreniform disorder) had similar common prodromal symptoms: social withdrawal (87%); disturbance in attention, concentration or memory (87%); anxiety (74%); sleep disturbance (74%); school deterioration (70%); and depressed mood (52%) (Table 2). The common prodromal symptoms of the remaining seven patients with other psychotic syndromes (schizoaffective disorder, delusional disorder, major depression with psychotic features and brief psychotic disorder) were depressed mood (100%), anxiety (86%), social withdrawal (71%), and school deterioration (71%) (Table 2).
Signs and symptoms of prodromal symptoms of first-episode psychosis patients
Common symptoms of non-psychotic patients were sleep disturbance (97%), anxiety (88%), depressed mood (88%), poor appetite (82%), anger or irritability (62%) and suicidal ideation (53%) (Table 3). Common symptoms found in first-episode psychosis and non-psychotic patients included sleep disturbance, anxiety, depressed mood and anger or irritability.
Comparison of psychotic and non-psychotic patients
Common symptoms that were associated with the psychotic prodrome but not with the first episode of a non-psychotic disorder were social withdrawal (p < 0.001); deterioration in school results (p < 0.001); and disturbance in attention, concentration or memory (p < 0.001). The psychotic prodrome was also associated with apathy (p < 0.001), odd behaviour (p < 0.001), doing nothing (p = 0.004) and thought blocking (p = 0.04) (Table 3).
Cross-tabulation of these symptoms with the other prodromal symptoms showed that social withdrawal was associated with odd behaviour (p = 0.01); school deterioration with disturbances in attention, concentration or memory (p = 0.03); apathy with doing nothing (p < 0.001) and fatigue (p = 0.03); odd behaviour with impulsivity (p = 0.04) and self-neglect (p = 0.02); and doing nothing with self-neglect (p = 0.05).
Discussion
Methodological issues
Our study had a relatively small sample size of 30 firstepisode psychosis patients and 34 non-psychotic patients. All were well known to the authors, who were the primary psychiatric caregivers. This allowed the large amount of qualitative data available in the process-notes to be managed.
Our study was conducted within the military context on mainly National Servicemen in their early 20 s. Given the compulsory nature of National Service for Singaporean males, and medical screening prior to enlistment, our setting as the military psychiatry institution in Singapore allows us to access and treat an unbiased group of young male patients with no previous psychiatric diagnosis, who have subsequently developed psychosis.
The rigors and structured nature of the military organization often brings symptomatic individuals to medical attention early, accounting for some of the clinically significant, yet relatively mild and early cases of firstepisode psychosis in our study. Motivational and personality factors can sometimes complicate the presenting symptoms and signs [25], thus detailed data gathering from all patients and corroborative accounts from colleagues, superiors, friends and family were required in our assessments. Nevertheless, data on interrater reliability of our observations is absent and raters were not blinded to the diagnosis. We did not use formally validated instruments to assess the prodromal symptoms. In any case, none have been validated in Asian populations. However, although empirical, we believe the in-depth, detailed and consistent manner in which symptomatology was explored and corroborated have enabled subjects’ assessment to be valid and reliable. Further work would need to be done to construct validated instruments to gather this information more efficiently.
Results
Yung and McGorry did a retrospective descriptive study of prodromal symptoms in first-episode psychosis in 1996 [24], with which our data can be compared, although several differences need to be taken into account. They studied 21 civilian patients of both sexes who were older (mean = 23.1 years vs 20.6 years) who were referred to a frontline mental health service serving the suburbs of Melbourne. Although the majority of their patients had schizophrenia-spectrum disorders as well, they had seven patients with manic features while we had none. Corroborative accounts were also obtained from informants, but Yung and McGorry et al . used the Multidimensional Assessment of Psychotic Prodrome, an unstructured and semistructured interview instrument they developed [28, 29]. We did not use this instrument, but relied mainly on clinical observations from detailed interviews with patients and informants. These methodological differences, and some cultural differences, may account for some differences in the rate of prodromal symptoms observed. The Australians had more physical symptoms such as somatic symptoms (48% vs 7% p = 0.002), loss of weight (57% vs 7%, p < 0.001), sleep disturbance (100% vs 77%, p = 0.03) and speech abnormalities (57% vs 13%, p < 0.001). They also had more who reported perceptual abnormalities (62% vs 9% p = 0.02), subjective changes in sense of self, others or the world (62% vs 13%, p < 0.001), suspiciousness (72% vs 37%, p = 0.02), change in motility (62% vs 13%, p = 0.003) and fatigue (62% vs 23%, p = 0.006). Conversely, our patients had more with odd behaviour (53% vs 10%, p = 0.001) (Table 4).
Comparison of prodromal symptoms with Yung and McGorry [24]
Prodromal symptoms occurring frequently in both studies included anxiety (77% vs 86%, p = 0.5); disturbance of attention, concentration and memory problems (73% vs 71%, p = 0.9); deterioration in role or school functioning (70% vs 76%, p = 0.6) and social withdrawal (83% vs 72%, p = 0.3) (Table 4).
Comparison with non-psychotic patients
The comparison between psychotic and non-psychotic patients allowed symptoms that were associated with the psychotic prodrome to be identified. Some of the first presentations of non-psychotic disorders may develop into psychosis (that is these non-psychotic disorders may be manifestations of a psychotic prodrome themselves) [30]; hence, these associations may be tentative pending more data on prospective follow up. Our finding that the psychotic prodrome comprised neurotic symptoms, cognitive disturbances and attenuated negative symptoms is consistent with other studies reviewed by Yung and McGorry [17]. Nonetheless, in our study, while neurotic symptoms such as anxiety, depressed mood, anger or irritability and sleep disturbances were common in the psychotic prodrome, they were similarly common in non-psychotic patients. Symptoms such as social withdrawal, apathy, doing nothing and thought block; and cognitive symptoms such as disturbance in attention, concentration or memory, and school deterioration, were, however, more specific to the psychotic prodrome.
The cognitive disturbance is consistent with current conceptualizations of schizophrenia in which disturbances in learning, attention, speed of processing and executive functions are core characteristics [31–36]. Cognitive disturbance within the prodrome had also been described [30, 37, 38]. Interestingly, many of our firstepisode psychosis patients and informants described distinct deterioration in school functioning a few years before the onset of psychosis (mean age 16 years, median 15 years, SD = 1.8 years). Deterioration in studies at these times may warrant further study. The onset of other prodromal symptoms also occurred before enlistment in the 28 cases who experienced a prodrome. Further exploration into how they impacted the patient's performance in aptitude and psychological tests conducted during military training may provide more insight into the prodromal phenomenon.
Conclusion
Our setting as a military psychiatry institution in Singapore allows us to access and treat a number of young patients with early first-episode psychosis. Observations of the prodromal symptoms revealed a combination of neurotic symptoms, cognitive disturbances and attenuated negative symptoms, of which the latter two appear to be more specific to the psychotic prodrome. Further work needs to elaborate their qualitative aspects, particularly the finding that a number of patients with first-episode psychosis had deteriorated in their studies some time prior to developing psychotic symptoms. Further prospective research will also be required to study the predictive value of these prodromal symptoms.
Footnotes
Acknowledgements
The authors would like to thank Patrick D. McGorry, Director, Youth Program (incorporating EPPIC), Mental Health Services for Kids and Youth (MHSKY), Professor, Department of Psychiatry, University of Melbourne; and Chee Kuan Tsee, Senior Consultant Psychiatrist, Woodbridge Hospital, for their helpful comments on earlier versions of this manuscript.