Initial Prodrome Description in Recent Onset Schizophrenia

Amr El-Shribiny et al. Initial Prodrome Description in Recent Onset Schizophrenia Amr M M El-Shribiny, Salwa M. Rabie, Hanaa S. Soliman, Refaat Mahfouz Department of Neurology and Psychiatry, El-Minia University ABSTRACT Initial prodromal phase is gaining increasing significance for early detection, management and prognosis of recent onset psychosis. The present work aimed to assess and describe the prodromal phase in subjects with recent onset schizophrenia. 43 cases of recent onset schizophrenia were collected on outpatient basis and diagnosed according to ICD-10 DRC (WHO, 1993). A prodrome questionnaire to subject and informant was used to assess prodromal phase retrospectively. Results showed that 30 cases (69.9 %) had prodrome reported either by subject only (3 cases 7%), informant only (13 cases 30.2%) or by both subject and informant (14 cases, 32.6%). The duration of the prodrome reported by subjects ranged from 30-1825 days (5 years) (mean = 475.6 days, SD = ±495.1). The duration of the prodrome reported by informants ranged from 30-1095 days (3 years) (mean =361.1 days, SD = ±356.7). Prodromal symptoms, most commonly reported by subjects, were: Suspiciousness and Social withdrawal, followed by Ideas of references and Insomnia. Prodromal symptoms, most commonly reported by informants, were: Social withdrawal, Impaired functioning, followed by Somatic symptoms, Anxiety and Decreased appetite. Conclusions: recent onset schizophrenic patients experienced an initial prodromal phase that may vary from weeks to many years in duration. Prodrome can present with negative prodromal signs, positive symptoms and/or non-specific symptoms. The more prolonged prodromes are associated with more insidious onset and more impairment of functioning. (Egypt J. Neurol. Psychiat. Neurosurg., 2008, 45(2): 331-338) INTRODUCTION In medicine, a prodrome refers to the early symptoms and signs that herald the appearance of the complete clinical picture of an illness 1. The prodromal phase is gaining increasing significance for many causes. First, the prodromal phase study is crucial for early detection and management of recent onset psychosis. Furthermore, accurate assessment of the prodromal phase could have prognostic significance for psychosis 1,2. Prodromal symptoms of first episode psychosis are variable, protean and nonspecific 2,3,4. The basic prodromal symptoms are usually subtle, mostly subjectively experienced. Some authors 5,6 proposed that attenuated psychotic symptoms like attentional or perceptual distortions may increase the low specificity of the prodromal signs and symptoms. Yung et al. 7 suggested that the long duration of a pre-psychotic reduction in functioning and long duration of prodrome had a good predictive power and comparable sensitivity. The duration of the prodromal phase varies in different studies from a very brief period to several years 7. In general, research findings suggest that the prodrome before the first episode of psychosis in schizophrenia is often prolonged often lasting many months and up to several years 1. Lastly, Cornblatt et al. 8 concluded that a great deal of basic research is necessary to begin to shed light on this newly identified clinical entity. The present work aimed to assess and describe the prodromal phase in subjects with recent onset schizophrenia. SUBJECTS AND METHODS The subjects are 43 cases of recently diagnosed first episode schizophrenia (20 females &23 males) collected from El-Minia university outpatient Correspondence to Salwa M. Rabie, E-mail: salwarabie4@yahoo.com. Contact number: 0163392711 331

Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 psychiatry clinic diagnosed according to ICD-10 DRC 9. Demographic data and data related to Age of onset and Type of onset were collected by semistructured interview. Three types of onset were defined. Acute onset was considered, if it occurred within a week. Subacute onset occurred within 4 weeks. Gradual type of onset was defined to occur in more than month duration. Exclusion Criteria: 1- Past history of psychotic illness. 2- Mental retardation. 3- Evidence of organic brain disorder. Tools: The following tools were used: Prodrome Questionnaire 10. Positive and Negative Syndrome Scale (PANSS) 11. Global assessment of functioning Scale (GAF) 12. RESULTS Table (1) shows the sociodemographic characteristics of the sample. Table (2) illustrates clinical types of schizophrenia, type of onset, age at onset and positive and negative scales scores in the sample. Table (3) shows the distribution of patients regarding the presence of prodrome. It illustrates that 30 cases (69.9 %) had prodrome reported either by subject only (3 cases 7%), informant only (13 cases 30.2%) or by both subject and informant (14 cases, 32.6%). No prodrome was reported in 4 cases (9.3%). In 9 cases (20.9%) no valid information was available. The duration of the prodromal period is given in table (4). The duration of the prodrome reported by subjects ranged from 30-1825 days (5 years) (mean = 475.6 days, SD = ±495.1). The duration of the prodrome reported by informants ranged from 30-1095 days (3 years) (mean =361.1 days, SD = ±356.7). No statistically significant difference was found between groups. Table (5) ranks the 10 most frequent prodromal symptoms reported by subjects. Suspiciousness and Social withdrawal were the most common symptoms. Whereas, Social withdrawal, Impaired functioning, and Somatic symptoms were the most common symptoms reported by informants (Table 6). No statistically significant difference was found between males and females in the most common prodromal symptoms reported by informants (Table 7). Table (8) shows correlation between duration of prodrome reported by informant and other variables Figure (1) shows the significant positive correlation (r = 0.54, P = 0.001) between the duration of prodrome and type of onset: the longer the duration of prodrome is the more gradual the onset. Figure 2 shows the significant negative correlation (r = -0.49, P = 0.01) between the duration of the prodrome and GAF: the longer the duration of the prodrome is the lesser the functioning of the patients during the prodrome. Table 1. Sociodemographic description of the sample (N=43). Gender Male Female Marital status Single Married Divorced Education Illiterate Literate 332 Variables N % 23 20 33 9 1 53.5% 46.5% 76.7% 20.9% 2.3% 18 25 41.91% 58.1% Variable Min Max Mean±SD Age 15 40 22.3±6.8

Amr El-Shribiny et al. Table 2. Clinical description of the sample (N=43). Type of Schizophrenia N % Paranoid Undifferentiated Catatonic Hebephrenic 13 19 3 8 30.2% 40.2% 7% 18.6% Type of onset N % Acute Subacute Insidious 1 19 23 2.3% 44.2% 53.5% Variable Min Max Mean±SD Age at onset 14 40 20.3±6.9 GAF 35 75 62.7±10.3 Positive Scale 10 34 22.8±6.2 Negative Scale 15 45 28.1±8.7 Table 3: Distribution of patients regarding the presence or absence of prodrome. Reports of prodromes N % Reported prodrome by subject only 3 7% Reported prodrome by informant only 13 30.2% Reported prodrome by both subject and informant 14 32.2% Total subjects with prodrome 30 69.9% No prodrome reported 4 9.3% No valid information available 9 20.9% Total 43 100% Table 4: Duration of Prodrome reported by subjects and informants in days. Reported duration Min Max Mean±SD P Reported duration by subjects (N=17) 30 1825 475.6±495.1 P=0.3 Reported duration by informants (N=27) 30 1095 361.1±356.7 Difference between males/females in Duration from informants Males (N=17) Mean±SD Females (N=10) Mean±SD 834.3±1691.9 213.5±239.1 P=0.3 333

Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 Table 5. Ranking the 10 most frequent prodromal symptoms reported by subjects (N=17). Symptom Frequency (n/%) Suspiciousness 9 52.9% Social withdrawal 9 52.9% Ideas of references 7 41.2% Insomnia 6 35.3% Depressed mood 5 29.4% Impaired functioning 5 29.4% Decreased appetite 4 23.5% Somatic symptoms 4 23.5% Anxiety 4 23.5% Decreased weight 3 17.6% Table 6. Ranking the 10 most frequent prodromal symptoms reported by informants (n= 27). Symptom Frequency (n/%) Social withdrawal 15 55.6% Impaired functioning 14 51.9% Decreased appetite 8 29.6% Somatic symptoms 8 29.6% Anxiety 8 29.6% Decreased amount of speech 7 25.9% Suspiciousness 7 25.9% Decreased activity 7 25.9% Depressed mood 6 22.2% Decreased content of speech 6 22.2% Table 7. Comparison between males and females in the most common prodromal symptoms reported by informants. Symptom Males (n=17) Females (N=10) P N % N % Social withdrawal 10 55.6% 5 50%.9 Impaired functioning 10 51.9% 4 40%.2 Decreased appetite 4 23.5% 4 40%.4 Somatic symptoms 4 23.5% 4 40%.4 Anxiety 3 17.6% 5 50%.6 Table 8. Correlation between Duration of Prodrome reported by informant and other variables. Variable Duration of prodrome (r/p) Age at onset -.24.24 GAF -.49.01* Type of onset.54.001* Positive scale score -.22.3 Negative scale score -.1.5 *Correlation is significant at the level of 0.01 (2-tailed) 334

Type of onset Amr El-Shribiny et al. 0 900 800 700 600 500 400 300 200 100 1200 1100 1000 r=.54 p=.001 duration of prodrome by informant in days Fig. (1): Shows the correlation between the type of onset and the duration of prodrome. 80 75 70 65 60 55 50 45 40 35 30 25 20 0 100 200 300 400 500 600 700 800 900 100011001200 r=-.49 p=.01 duration in days Fig. (2): Correlation between the GAF and the duration of the prodrome. DISCUSSION Prodrome questionnaire 10 was used to detect if there is a prodrome before the first psychotic episode, its duration and the presenting symptoms. This tool does not necessarily provide complete assessment of the prodrome. However, it was attempted at a comprehensive assessment by including DSM-III-R prodromal symptoms of schizophrenia 13 and other nonspecific symptoms reported by many studies to occur in the prodromal phase of psychotic disorders 14. 335

Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 The results of the present study demonstrate that 69.9% had prodrome reported either by subject only, informant only or by both subject and informant. This is consistent with previous reports 15,16,17. In the current study subjects focused on subjective prodromal experiences where as informants focused on observable signs. In addition, 30% of subjects missed their own prodromal symptoms. This finding highlights the importance of taking seriously the complaints of family members who describe nonspecific changes of their relatives in the prepsychotic prodromal stage. The prodrome duration in the present study is variable in length (0 to 5-years). The finding that individuals with schizophrenia have variable prodromal periods was reported in previous studies 18,6. Although prodromal symptoms were observed in 69.9% of cases yet many years were spent with out active intervention until the onset of psychotic symptoms. This might reflect the insidious characteristic of schizophrenia and this is further supported, in the current study, by the positive correlation between prodromal duration and the type of onset. In the current study no significant difference was found between males and females either in the reported duration or the symptoms of the prodromal period, this finding has been reported by others 19,20. Thus, although gender differences in many aspects of schizophrenia has been reported, this apparently does not include prodromes. In the present study, the most frequent prodromal symptoms reported by the subjects were suspiciousness, social withdrawal, ideas of reference and insomnia. Less common symptoms were depressed mood, and impaired functioning. The most frequent symptoms reported by the informants were social withdrawal and impaired functioning followed by anxiety, decreased appetite and somatic symptoms. The apparent difference between subject report and informant report may be due to the subject concern with the most distressing symptoms, while the informant concern with the most observable symptoms. Similar results have been reported in previous studies 15,21. The results of the present study demonstrate that the longer the duration of prodrome is the more gradual the onset and the lesser the functioning. This finding is consistent with McGorry et al. 22 and Chovil 23 statements that most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. To conclude, 1st episode schizophrenic patients experienced a prodromal phase that can be very long reaching many years. Initial prodrome presents with nonspecific symptoms, negative symptoms and/or positive symptoms. The apparent difference between subject report and informant report in prodromal symptoms may be due to the subject concerns with the most distressing symptoms, while the informant concerns with the most observable symptoms. The more prolonged prodromes are associated with more insidious onset and more impairment of functioning. REEFRENCES 1. Yung, A.R. and McGorry, P.D. (1996): The Prodromal Phase of First-episode Psychosis: Past and Current Conceptualizations. Schizophrenia Bulletin, 22: 353-370. 2. Simon, A.E.; Ferrero, F.P. and Merlo, M.C.G. (2001): Prodromes of First-Episode psychosis: How Can We Challenge Nonspecificity? Comprehensive Psychiatry, 42: 382-392. 3. Rosen, J.L.; Woods, S.; Miller, T. and McGlashan, T. (2002): Prospective Observation of Emerging Psychosis. The Journal of Nervous and Mental Disease, 190: 133-141. 4. White, T., Anjum, A., and Schulz, S.C. (2006): The Schizophrenia Prodrome Am J Psychiatry 163: 376-380. 5. Yung, A.R.; McGorry, P.D.; McFarlane, C.A.; Jackson, H.J.; Patton, G.C. et al (1996): Monitoring and care of young people at incipient risk of psychosis. Schizophrenia Bulletin, 22: 283-303. 6. Yung, A. R.; Phillips, L.J.; McGorry, P.D.; McFarlane, C.A.; Francey, S. et al (1998): Prediction of psychosis: A step towards indicated prevention of schizophrenia [Verging On Reality]. The British Journal of Psychiatry, 172: 14-20. 7. Yung, A.R.; Lisa J. Phillips, L.J.; Yuen, H.P.; Francey, S.M. et al. (2003): Psychosis prediction: 12-month follow up of a high-risk ("prodromal") group. Schizophrenia Research, 60: 21-32. 336

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Egypt J. Neurol. Psychiat. Neurosurg. Vol. 45 (2) July 2008 ICD-10) 43 (PANSS) (GAF) 70 (DSM-IV) 338