The relationship of DUP, DUI, negative symptom severity and functional outcome among people with psychosis in Hong Kong. Title.

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1 Title The relationship of DUP, DUI, negative symptom severity and functional outcome among people with psychosis in Hong Kong Author(s) Cheung, Sze-ki; 張 斯 琪 Citation Issued Date 2013 URL Rights The author retains all proprietary rights, (such as patent rights) and the right to use in future works.

2 Abstract of thesis entitled The relationship of DUP, DUI, negative symptom severity and functional outcome among people with psychosis in Hong Kong. Submitted by Cheung Sze Ki For Master of Psychological Medicine At The University of Hong Kong In August, 2013 Empirical studies had demonstrated inconsistencies between duration of untreated psychosis (DUP) and outcome measures including negative symptoms severity and functional outcome. Therefore, this study aimed to investigate how either the construct of duration of untreated psychosis (DUP) or duration of untreated illness (DUI) acted on associating and predicting negative symptoms, its sub-domains and functional outcome among psychotic population in Hong Kong. Totally three hundred and forty five subjects were recruited from in-patient and out-patient setting in hospitals under hospital authority. DUP and DUI were assessed by semi-interviewed with subjects, their family members and other significant others. And the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) were adopted as assessment tools to measure negative symptoms severity and functioning of individual respectively. Regression models were used to analyse how DUI and DUP differed in associating and predicting different variables. Results showed that DUI took a more significant role in associating and predicting negative symptoms and functional outcome in which it demonstrated stronger positive correlation with negative symptoms and stronger negative correlation with functional outcome. DUI was also

3 found to act as a potential predictor for both negative symptom severity and functional outcome. At the same time, among all sub-domains, anhedonia showed mild positive correlation with both DUI and DUP while other four didn t show similar association. The results provided increased insight that DUI might play a more significant role in determining the development of negative symptoms and functional outcome than DUP. Yet, limitations on various aspects had been addressed in this study such as the high level of heterogeneity of our sample and potential confounders which partially correlated with the outcome parameter. Also, no causal relationship had been yield between DUI / DUP and outcome variables. Further investigation was suggested on dividing the sample into sub-group to draw information regarding the characteristics of associations. Meanwhile, better control on potential confounding variables might help generating clearer picture on how independent variables associated with each other.

4 Declaration I declare that this thesis represents my own work, except where due acknowledgement is made, and that it has not been previously included in a thesis, dissertation or report submitted to this University or to any other institution for a degree, diploma or other. i

5 Acknowledgement I would like to show my gratitude to my thesis supervisor, Dr. Edwin Lee, for his continuous support and opinions in my way to explore and complete the research work. This dissertation would not be able to complete without the guidance and the valuable assistance of Dr. Lee throughout the preparation and completion of the study. ii

6 Table of content Declaration..i Acknowledgement ii Table on contents.iii Lists of Tables...iv Chapter one Introduction Significance duration of untreated psychosis and duration of untreated illness.. 1 Construct of DUI prior to DUP DUI/DUP and negative symptoms severity. 2-3 DUI /DUP and sub-domains of negative symptoms DUI /DUP and functional outcome. 4-5 Hypothesis of study. 5 Chapter two Methodology and procedures Subject characteristics and recruitment procedures 6 Ethical approval.. 7 Assessments 7-8 Statistical models.8-9 Chapter three Results Clinical characteristics Correlation of DUI and DUP with overall negative symptoms sub-domains of negative symptoms and functional outcome. 14 DUI and DUP as predictors for negative symptoms severity and functional outcome Chapter four Discussion Chapter five DUI or DUP with negative symptoms severity and functional outcome Methodology limitations Further directions.21 Conclusion. 22 Reference iii

7 Lists of Tables Table 1 Demographic and clinical characteristics of the samples..12 Table 2 Correlation matrix of DUP / DUI with gender, age of onset, negative symptoms and SOFAS. 14 Table 3 Linear regression model of DUI / DUP as a predictor for negative symptom severity (SANS). 16 Table 4 Multiple regression model of DUI / DUP and negative symptoms as predictors for functional outcome (SOFAS).. 16 iv

8 Chapter 1 Introduction 1.1 Significance duration of untreated psychosis and duration of untreated illness Long-term course of psychosis has been largely investigated in recent year with clinicians increasing interest to explore factors associating with the development and prognosis of the illness. Among factors being identified, the significance of duration of untreated psychosis had gained increased attention in recent decades. According to Birchwood et al. (1998), early years of psychosis was defined as critical period and early intervention during this phase could lead to a better long-term prognosis. This hypothesis has then further promoted the development of early intervention towards people with early psychosis among different countries. The establishment of early intervention services for the population with early psychosis has become one of the key developments in psychiatric services in Hong Kong as well. With the phase-specific prognostic characteristics of first episode psychosis, clinicians had nowadays attempted to intervene in an earlier phase so as to shorten the duration of untreated psychosis. (Hui, 2012).Yet, the best time in which early detections and interventions towards psychosis might be implemented was still remaining inconclusive. Despite the growing body of research yielded on the construct of DUP on range of outcome variables, the association between DUP and the outcome variable was still not convincingly demonstrated. Therefore, this gave rise to the importance to further explore the effect of duration of untreated psychosis as a prognostic factor among psychotic population in Hong Kong. 1.2 Construct of DUI prior to DUP Duration of untreated psychosis (DUP) was generally defined as the period between onset of 1

9 psychotic experience and the accessibility of intervention service contact. (Wiersma et al., 1998, Bottlender, et al., 2002) In recent decades, there was growing body of research regarding the significance of duration of untreated psychosis (DUP) as a prognostic factor for people with early psychosis. However, despite increasing body of empirical evidences yielded, there was still lack of conclusion in respect to association of DUP and some outcome variables, such as negative symptoms and functional outcome. So some research has speculated that changes in certain outcome variables might have happened before the DUP, which led to the rising interest on another similar construct called duration of untreated illness (DUI). Generally, duration of untreated illness (DUI) had been adopted as a term to refer the untreated period comprising of both DUP and prodromal period. This construct has attracted increasing interest of researchers since it was found that DUP showed inconsistent association with negative symptoms and certain domains of functioning such as social ad occupational functioning. Meanwhile, there was still limited body of research focusing on how DUI interacted with potential outcome variables being yielded. This increased the importance to provide more evidences of how DUI appeared to be associated with and predicting potential outcomes measures. 1.3 DUI/DUP and negative symptoms severity Positive and negative symptoms had been projected as the core manifestation of schizophrenic syndrome. In view of symptom severity as an outcome measure, evidences suggesting the correlation of DUP and outcome on positive symptoms appeared to be relatively robust in which longer DUP would largely predict worse positive symptoms severity and future prognosis (Marshell et al., 2005, Perkins et al., 2005). Yet, it appeared that greater inconsistent findings had been existed in view of association between the length of DUP and severity of negative symptoms. While reviewing previous research investigating the construct of negative symptoms with DUP, some studies had found significant correlation of DUP and negative symptoms (Edward et al., 2002, Harrigan et al., 2003, Oosthuizen et al., 2005). However, there 2

10 were number of studies which did not demonstrate such a significant association. (Craig et al., 2000, Black et al., 2001, N. Schimitz et al., 2007). To explore the possible reasons of the phenomenon, some researchers suggested that the inconsistency across the studies might be attributed to the heterogeneity nature of psychotic patients (N. Schmitz et al., 2007). Another suggestion was that there was possibility in which the emergence of negative symptoms appeared before DUP, which might already been happened during the prodromal period (Chang et al., 2012). According Hafner et al. (1999), their research also suggested that the change of negative symptoms might have emerged before the DUP and deteriorated more significantly during the prodromal period. And this might probably help accounting for the inconsistency among researches in view of correlation between DUP and negative symptoms severity. Meantime, there was also speculation that negative symptoms might be a relatively persistent outcome during the DUP so that the changes appeared to be less obvious (Buchanan, 2007). With the consideration of the above comments from previous studies, this study attempted to shift the focus of research to an earlier phase which included the length of prodromal period as well. And this might probably help accounting for the inconsistency among researches in view of correlation between DUP and negative symptoms severity. In order to provide more insight of the importance of DUI in predicting outcome of people with early psychosis, our study would also attempt to yield more information regarding how DUI and DUP acted differently on accounting for variances. Thus, with the hypothesis of DUI and DUP as possible predictors for negative symptoms as an outcome, analysis would be conducted on how DUI and DUP took a role to correlate and predict negative symptoms severity for people with psychosis in Hong Kong DUI /DUP and sub-domains of negative symptoms Additionally, across empirical studies regarding correlation between DUI and negative symptoms, most studies tended to adopt negative symptoms as a single construct rather than further elaborating it into sub-domains while investigating the nature of association. Thus, there 3

11 was still limited information regarding the variation of how much each single domain contributed in related with DUP or DUI itself. It might be likely that different sub-domains attributed different degree in related to the length of DUI or DUP. Despite limited body of research investigating negative symptoms with sub-domain perspective, Malla et al., (2002) had demonstrated significant differences in the strength of correlation among different sub-constructs of negative symptoms with the length of DUP. For instance, significant correlation of DUP and certain sub-domains such as avolition and asociality had been demonstrated in this research. With the assumptions that different sub-constructs of negative symptoms might emerge differently during DUI, this study attempted to further explore the association between DUI and the five main sub-constructs of negative symptoms, including avolition, asociality, anhedonia, alogia and bunt affect. (Kirkpatrick et al., 2006, Makinen et al., 2008) 1.5 DUI, DUP and functional outcome People who suffered from psychosis might have experienced certain degree of functional deterioration in domains such as occupational performance, social functioning and ADL functioning in relation to their psychotic symptoms and brain damages. Yet, research result regarding the association of DUI / DUP with functional outcome appeared to be mixed. On one hand, there were a number of studies showing that DUP was significantly associated with functional outcomes. For instance, Bottlender et al. (2003) has concluded that people with 1-year DUP demonstrated reduced global functioning as compared that with 6-month DUP. And there were also other studies showing that shorter DUP was moderately correlated to better social and occupational functioning. (Larsen et al., 1996, Carbone et al., 1999, McGlashan, 1999, Harris M.G et al., 2005). And the longest prospective study of the cohort of first-episode psychosis has shown compatible results that longer DUP was associated with global functioning and quality of life. (M. Hill et al., 2012) Though certain level of significant results has been demonstrated among research which 4

12 attempted to explore how the duration of untreated psychosis contributed to one s functional outcome, there were still some studies which demonstrated insignificant association of DUP and functional outcome. According to Perkins D. et al. (2007), they did not find an association of DUP with social and vocational functioning after 2 year follow-up period. And other study also failed to demonstrate any relationship between DUP and 6-month social and vocational outcome. (Ho B-C. et al., 2001). With the discrepancies illustrated among studies, this might imply that functional outcome appeared to be a relatively complex outcome variable. And this might help account for the inconclusiveness regarding DUP and functional outcome. Similar to that of negative symptoms, despite scholar s suggestion on the importance of DUI to one s functional decline, there was still lack of research investigating its significance on functional outcome. It appeared that most of the research put their focus on DUP rather than DUI Therefore, this study aimed to provide further insight and yield more evidence on how DUI took a role to influence one s functional outcome among psychotic population in Hong Kong. At the same time, differences in research context and culture might also be one of the factors contributing to the inconsistency as well. With the above speculation, this increased the need to yield more preliminary evidences in Hong Kong context regarding the association of DUP and functional outcome 1.6 Hypothesis of the study Several hypothesis was about to be investigated in this study in respect to DUI and DUP. Firstly, it was hypothesized that there was difference in how DUI and DUP correlated with and predicted negative symptoms severity and its corresponding sub-domain among people with psychosis in Hong Kong population. Secondly, this study also aimed to find out the difference of DUI and DUP in correlation with and predicting functional outcome among people with psychosis in Hong Kong. 5

13 Chapter 2 Methodology and procedures 2.1 Subject characteristics and recruitment procedures Potential subjects were recruited from multiple in-patient and out-patient psychiatric service units of hospitals in Hong Kong since 2009 to Totally, there were three hundred and sixty one subjects being recruited into this study. Subjects would be eligible to join the research if they fulfilled the following inclusion criteria. The including inclusion criteria were as follows: years of age Cantonese speaking Chinese Being diagnosed as schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, psychotic disorder not otherwise specified, or manic episodes with psychotic features according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) First-episode psychosis, defined as treatment of no more than 12 months following the first episode illness Able to achieve a level of understanding and express capacity sufficient to communicate adequately with the study coordinator Absence of organic brain conditions, substance-induced psychosis, known history of intellectual disability or suicidal/violent risks Trained research assistants would conduct an in-person interview with individual subjects. During the contact time, demographic background of each subject was collected during the data collection which comprised of gender, age, age of onset, educational level, occupation, family history of mental illness and diagnosis being given. Afterwards, they would be assessed by different designated assessments including interview of DUI and DUP, SANS and SOFAS. Before 6

14 commencing the research, risk of participating the research was explained and written consent was provided for each subjects. 2.2Ethical approval The study was carried out in accordance with Good Clinical Practice and with the Declaration of Helsinki. The study was approved by the Institutional Review Boards at each site. 2.3Assessments The length of DUI and DUP In this study, the duration of untreated illness (DUI) and duration of untreated illness (DUP) were assessed by interviewing the subjects his/herself, their family members or significant others. And the period of DUI and DUP was defined with reference of empirical studies. (Peralta V. et al., 2004) Therefore, in this study, DUI was defined as the period of first appearance of changes in illness related cognitive or affective complaints as well as changes in behavioral as compared with premorbid functioning to first contact of psychiatric services. And DUP was defined as the first emergence of active psychotic symptoms to the first contact of psychiatric services The scale for the Assessment of Negative symptoms (SANS) The Scale for the Assessment of Negative Symptoms (SANS) was a common assessment tools used to measure the severity of negative symptoms of psychotic clients. (Andreasen, 1989) Its factorial structure consisted of 5 major domains which included affective blunting; alogia (impoverished thinking); avolition/apathy; anhedonia/asociality; and disturbance of attention. This assessment tool adopted a six-point Likert scale to examine the severity of various negative symptoms, which ranged from 0 (not at all) to 5 (severe). Regarding the psychometric properties, SANS had demonstrated adequate internal consistency and good-magnitude test-retest reliability according to research studies (Andreasen, N. C., 2000). At the same time, studies had analyzed the validity and factorial structure of SANS and results showed that SANS had demonstrated a good 7

15 concurrent and convergent validity as well as a relatively stable factor model. (Grube BS, et al., 1998) Social and occupational functioning assessment scale (SOFAS) To examine the general functioning of the subjects, social and occupational functioning assessment scale (SOFAS) was chosen. It was widely used as a tool which was developed from DSM-IV, Axis V to assess functioning of people with psychosis. While comparing the tools with other functional assessments, it was differed from other functioning assessment in which it exclusively focused on the social functioning and occupational functioning of one individual independent of one psychological symptom. At the same time, SOFAS had taken one s s medical conditions into consideration while evaluating social and occupational functioning. Regarding the rating method, it adopted a global criterion-based rating of current functioning ranging from 0 to 100, with lower scores representing lower functioning and higher scores representing higher functioning performance. Regarding the psychometric properties, SOFAS demonstrated reliability in an excellent range, good validily and stable factor structure (Goldman H.H, et al., 1992, Hilsenroth M. J., et al., 2000) 2.4 Statistical model SPSS version 19 was used as a statistical tool for data analysis. Socio-demographic data of our samples was extracted and examined by descriptive analyses. Mean and standard deviation were generated to examine the general characteristic of our samples. At the same time, a correlation matrix was generated to examine the correlation of DUI/DUP with various variables including gender, age, negative symptoms, sub-domains of negative symptoms and functional outcome. Yet, since the data collected for DUI and DUP appeared to be greatly skewed and not overtly normally distributed, non-parametric bivariate correlation model was utilized to analyze the association of DUI or DUP with different parameters. Last but not the least, both linear and multiple regression models were used to analyze how DUI or DUP took part on predicting the negative symptoms severity of psychosis (SANS) and the functional outcome (SOFAS). In respect 8

16 to negative symptoms severity, linear regression model was used to explore how DUI or DUP appeared to explain the variance in difference of negative symptom severity. For investigating aspect of functional outcome, since negative symptom severity might exist as a confounding variable in interacting with functional outcome, the regression model would comprise of both DUI /DUP and negative symptoms in order to obtain a more comprehensive scenario of how predicting factors accounted for individual s functional outcome. And a backward multiple regression model was chosen to analyze how DUI and DUP took a role to account for variance in functional outcome (SOFAS). 9

17 Chapter 3 Results 3.1 Clinical characteristics In total, three hundred and sixty one subjects had been recruited to the study. Of these participants, sixteen subjects were found to have missing values for certain variables, resulting in the finalized sample size to be three hundred and forty five subjects. Table 1 presented the socio-demographic characteristics of the sample recruited. Generally, the nature of the sample was relatively heterogeneous the sample (N=345) comprised of 42.6 % males and 57.4% of females. The mean age of our sample was 38.2 (SD=8.4). Among our samples, around one-third of them reported to have family history of mental illness of either psychosis or mood disorders. And the sample came from a wide range of schizophrenic-spectrum disorders. Regarding the variety of diagnosis, there was largest proportion of participants who suffered from schizophrenia (42.6 %), with the second predominant diagnosis was manic episodes with psychotic features (17.4 %). 11.9% of the samples suffered from schizophreniform disorders. Since the study recruited participants whose nature of illness was either acute or chronic, the length of DUP or DUI showed great variations and this resulted in a relatively great range for DUI and DUP. The range of both periods was apparently large which were found to be 9648 and 6756 respectively and the skewness was 3.8 and 3 for DUP and DUI. In general, the average duration of untreated psychosis (DUP) was 388 days (SD=807) while that of duration of untreated illness (DUI ) was 848 days (SD = 1451). In respect to the results negative symptoms severity and functional outcome, table 1 had illustrated the descriptive statistics for SANS, its sub-domains scoring and SOFAS of our samples. Regarding negative symptom severity, the mean of total score of SANS was 10.5 with standard deviation Negative symptoms had been further divided into five sub-domains for further investigation. 10

18 Among the five sub-domains identified, the mean score of anhedonia was ranked highest with 4.2 (SD=5.5) while the lowest ranked one was alogia with mean score of 0.8 (SD=2.5). The mean score of avolition, blunt effect and attention were 2.0 (SD=3.6), 3.1 (SD=2.3) and 0.4 (SD=1.6) respectively. Finally, in respect to functional outcome, the mean score of SOFAS was 59.5 with standard deviation of

19 Gender Male, n(%) Female, n(%) 147(42.6) 198 (57.4) Age, years, mean(sd) 38.2 (8.4) Age of onset, Years, Mean(SD) 36.7 (8.6) Educational level, years, mean, SD 10.7 (3.8) Family history, n (%) 107 (29.7) Diagnosis Schizophrenia, n(%) Schizophreniform disorder, n(%) Schizoaffective disorder, n(%) Delusional disorder, n(%) 147 (42.6) 41 (11.9) 19 (5.5) 69 (2.0) Brief psychotic disorder, n(%) 5 (1.4) Psychotic disorder not otherwise specified, n(%) 4 (1.2) manic episodes with psychotic features, n(%) 60 (17.4) Duration of untreated psychosis (DUP), days, mean, SD 388 (1159) Duration of untreated illness (DUI), days, mean, SD 848 (1451) SANS Total, Mean, SD 10.5 (14.3) Blunt affect, Mean, SD 3.1 (2.29) Alogia, Mean, SD 0.8 (2.5) Avolition, Mean, SD 2.0 (3.6) Anhedonia, Mean, SD 4.2 (5.5) Attention, Mean, SD.4 (1.6) SOFAS, mean, SD 59.5 (13.4) Table 1: Demographic and clinical characteristics of the samples 12

20 3.2 Correlation of DUI and DUP with overall negative symptoms, sub-domains of negative symptoms and functional outcome Table 2 had illustrated a correlation matrix showing the correlations of DUI and DUP with parameters including gender, negative symptoms, sub-domains of negative symptom (avolition, alogia, anhendonia, attention and blunt affect) and SOFAS. Generally, despite significance identified, the overall correlations of DUI and DUP with designated variables were relatively weak, ranging from.109 to.262. specifically, there was no significant gender difference found in the length of DUI and DUP. In regard to negative symptoms severity, only DUI showed significant positive correlation with total score of SANS which correlation coefficient was.124 (p<0.05). DUP, on the other hand, did not demonstrate significant correlation with overall negative symptom construct. Negative symptom construct had been further analyzed by correlating DUI/DUP with its sub-domains. While analyzing the correlation of negative symptoms sub-domains, only anhendonia domain demonstrated significant positive correlation with DUI and DUP. Yet, comparatively, DUI showed stronger positive correlation with anhedonia domain than that of DUP, with the correlation of DUI was.150 (p<0.01) while that of DUP was.119 (p<0.05). Other sub-domains, in contrary, did not show significant correlation with the length of DUI / DUP. Finally, functional outcome showed significant negative association with both DUI and DUP construct as well. However, similar as the results of negative symptoms, DUI appeared to demonstrate a strong negative correlation with SOFAS that that of DUP. The strength of correlation of DUI and SOFAS was (p<0.01) while that of DUP was (p<0.01) respectively, which was a relatively weak correlation strength. 13

21 Duration of untreated psychosis (DUP) Duration of untreated illness (DUI) Gender Age of onset -.164** -.109** SANS (total) * Avolition Alogia Blunt affect Anhedonia.119*.150** Attention SOFAS -.249** -.262** ** correlation is significant at 0.01 level *correltation is significan tat 0,05 level Table 2 Correlation matrix of DUP / DUI with gender, age of onset, negative symptoms and SOFAS 14

22 3.3 DUI and DUP as predictors for negative symptoms severity and functional outcome Linear regression model was used to analyze how DUI or DUP differed to act as a predictor for negative symptoms severity. Findings and results were illustrated in table 3. As shown in the table, it showed that DUI and DUP accounted for similar variance for the severity of negative symptoms of psychosis. DUI explained for 29% (F (2,341) = 10.1, P = 0.02) of variances whilst DUP explained for 30 % (F(2,341) = 10.7, p=0,01) of variances respectively for the total score of SANS. Interestingly, when we recapped the correlation matrix in table 1, only the association of DUI, but not DUP, was found to be significant with negative symptom severity. So there might be possibilities that some other confounding variables systematically changed with DUP in predicting the severity of negative symptoms. Meanwhile, multiple logistic regression analysis has been adopted to investigate how the length of DUI and DUP appeared to account for variance of and functional outcome. Table 4 showed the results of how DUI or DUP acted predictors for functional outcome. Since negative symptom was possibly interacted with DUI / DUP and played a role as a confounder of functional outcome, the construct of negative symptoms had been included as a dependent variable into the regression model. From the result shown in table 4, the construct of DUI together with negative symptoms accounted 24.2% of variance for overall social and vocational outcome (F (2, 341)=35.729, P=.00). Whilst for the result of DUP with negative symptoms as predictor parameters, they totally accounted for only 22.5 % of variance of SOFAS. (F (2, 341) = 54.62, P=.00). Since negative symptoms and DUI together accounted for greater variance than that of negative symptoms and DUP, it provide evidence that DUI showed strong strength on predicting one s social and vocational outcome (SOFAS). 15

23 R Explained variance SE of the Sig. F of R square estimate DUP DUI Predictors: DUI or DUP Dependent variables: Total score of SANS Table 3: Linear regression model of DUI / DUP as a predictor for negative symptom severity (SANS) R Explained variance SE of Sig. F R square estimate DUP DUI Predictors: (constant), DUP/DUI, total score of SANS Dependent variable: SOFAS Table 4: Multiple regression model of DUI / DUP and negative symptoms as predictors for functional outcome (SOFAS) 16

24 Chapter 4 Discussion 4.1 DUI or DUP and negative symptoms severity and functional outcome In general, this study had provided more evidences on how the length of DUI and DUP contributed differently in associating with and predicting outcome parameters associated with psychosis, particularly negative symptoms and social and occupational functioning among Hong Kong population. Concerning the association of negative symptoms severity with DUP, the results failed to generate similar results as TIPS study and empirical study by Malla et al., (2002, 2004). Rather, it replicated findings with some previous studies in that DUP failed to show significant positive correlation with negative symptoms severity. (Criag et al., 2000, Black et al., 2001, N. Schimitz et al., 2007) This implied that negative symptoms might appear to be relatively static during the stage of DUP. Some researcher had also suggested that the partial relationship with poor pre-morbid functioning might act as a confounder for both DUP and negative symptoms, which lead to the spurious relationship between DUP and negative symptoms (Larsen et al., 2000). In contrary, the results regarding DUI showed agreement with our hypothesis that it demonstrated significant positive correlation with negative symptoms severity, as echoed with previous studies and scholar speculations. (Hafner et al., 1993) This helped providing more information to this area that the prodromal period might play a more important role on predicting the development of negative symptoms. And the result can also give more confident direction towards the development of early intervention among psychotic population. This study thus provide us with another concrete evidences that prevention and early intervention might be the best way to enhance clients outcome on symptom severity. Apart from analyzing negative symptom severity as a whole, this study also attempted to yield more evidences on how DUI / DUP appeared to account for variances in sub-domains of 17

25 negative symptoms. However, among the five sub-domains, only the sub-construct of anhedonia showed significant positive association with DUI and DUP in this study. This showed discrepancy with Malla et al. (2002) that only avolition and asociality sub-domains showed correlation with DUP. Despite of inconsistency with previous research, investigating how DUP/DUI correlated with negative symptoms sub-domains might be worth to be emphasized in the future direction due to the limited body of evidences. For instance, in current clinical practice, negative symptoms in prodromal period was relatively less obvious, and it was difficult for patients themselves to aware the existence of negative symptoms as well. Thus, if we can know which negative symptoms appear to be more prominent in the stage of DUI, detections can be done more effectively and interventions can be shifted to an early phase of the illness. Yielding more information about how sub-domains associated with DUI can also provide more prediction to the prognosis of the client and more intensive interventions can be offered during early stage of psychosis. In regard to functional outcome, in accordance with some empirical studies (Larsen et al., 1996, Carbone et al., 1999, McGlashan, 1999, Harris M.G et al., 2005), both the length of DUI and DUP showed significant negative association with scoring of SOFAS. Both DUI and DUP were also found to be significant predictors for social and occupational functioning. Therefore, this piece of evidence help further confirming the hypothesis that longer DUI or DUP might lead to worsening of functional outcome. Though the correlation strength was weak, DUI had appeared to demonstrate a greater association with SOFAS than that of DUP. And as illustrated from the regression model, comparatively, the construct of DUI explained slightly greater variances for social and occupational functioning than that of DUP as well. Hence, the prodromal period might be speculated to act as a more crucial factor in indicating the development of functional outcome of individuals with psychosis. Yet, it was still inconclusive among studies regarding to what extent DUI or DUP contributed to account for level of functional deterioration since other factors might exist to vary with the duration itself such as the effectiveness of treatment provided. 4.2 Limitations 18

26 Despite significant results can be demonstrated in this study, several limitations existed in term of methodology which may affect the strength and specificity of the study. Firstly, DUP and DUI were not solely existed in associating with functional outcome and symptom severity. As a matter of fact, other potential variables might act to systematically vary with DUI / DUP and interacted with DUI/DUP under the regression analysis. These variables might include premorbid adjustment, treatment effectiveness, mode of onset, positive symptoms severity and community resources in the neighbourhood. Yet, in this study, only negative symptom severity had been considered as one of the confounding variables in the regression model. Therefore, it was worth to consider comprising more potential confounders in the study so as to help generate a more holistic picture in how different variables acted to affect the functional outcome and symptoms severity of individual with early psychosis. The second inadequacy of this study was that only cross-sectional relationship was being examined between different variables. Therefore, it was unknown on how the development of negative symptoms and functional outcome appeared to be when time varied. More specifically, there was limited information concerning how temporal factors contributed to affect the association of DUI /DUP with negative symptoms and functional outcome. According to one of the latest systematic review of DUP (N. Boonstra et al., 2012), it suggested that the temporal pattern in DUP or DUI might contribute to the inconsistency in respect to association of negative symptoms and functional outcome with DUI/DUP. For instance, this piece of review showed clear illustration that decline in social functioning would appear in a later phase of illness onset. Thus, it suggested the possibility that temporal factor may take a role in affecting functional outcome of a person with psychosis. On the other hand, there were also empirical studies suggesting how the different phase of DUP help influencing the correlation of DUP with negative symptoms. For example, Marshell et al., (2005) had concluded that association of DUP and negative symptom was found at six and twelve months of DUP while no association was demonstrated at baseline and twenty-four months. Another study also yielded some evidences of temporal elements for this area 19

27 in which strength of correlation differed at various points on timeline (Perkin et al., 2005). Thirdly, this study was only confident to draw conclusion on the association of DUI/DUP with negative symptoms and social and occupational functioning. No causal relationship had been illustrated in this study. For example, it might be possible that DUP /DUI lead to worsening of symptom severity. At the same time, the scenario might appear to be the enduring negative symptoms or other deficits hindered the motivation of help-seeking behavior of an individual at early phase of the illness. (Edwards et al., 2002) Therefore, further study might be in need to yield more evidences on how DUI / DUP interacted with different parameters in term of causality. At the same time, despite the significance resulted, the strength of correlations yielded in this study were relatively weak. This gave rise to the possibility that other confounding variables might have existed to partially correlated with DUI / DUP, functional outcome and negative symptoms, and thus affect DUI s significance on predicting negative symptoms. Although this study had provided some insight that DUP and DUI together might play a role in predicting functional outcome, they were not the sole factor being involved. Other parameters, such as premorbid adjustment, cognitive functioning, family and social context were suggested by empirical research to interact with individual s negative symptom severity. (Malla et al., 2004, Larsen et al., 2000) In the multiple regression model for functional outcome, both DUI / DUP and negative symptoms had been added as potential predictors for social and occupational functional outcome. Yet, since interaction and co-variance might occur between DUI / DUP and negative symptoms, it may be unclear to show how DUI / DUP solely contributed on predicting functional outcome. Last but not the least, there was limitation for the opted statistical model in analysis the data collected. As mentioned before, the sample pool in this study was relatively heterogeneous in nature. Yet, this feature might contradict with the basic assumptions of the regression model. No matter it was linear or multiple regression models, they assumed that population being analysed was homogenous. So, regarding to the high level of heterogeneity nature of people with psychosis and the sample itself in this study, the application of these models in analysing the cohort with 20

28 psychosis might be questionable. 4.3 Further directions There were some suggestions for further direction regarding studies for DUI or DUP by echoing the limitations identified in this study. First of all, in view of the high heterogeneity, it was suggested that the sample can be further divided into sub-groups by diagnosis, length of illness chronicity and premorbid functioning. And narrower inclusion criteria can be considered to enhance the group s homogeneity. This might help to yield more information on the characterized association pattern of DUI / DUP with various dependent variables in different combination of sub-groups features. This can also minimize the limitations associated with the assumptions of regression model as well. Secondly, further longitudinal studies can be conducted to investigate the development of negative symptoms and functional outcome under the influence of length of DUI / DUP. And temporal relationship was also an interesting factor to be incorporated into the studies as well to see how different stages of DUI / DUP showed effect on various outcomes. At the same time, to grasp a more comprehensive picture, other potential predictors should be taken into consideration as well in future study. For instance, cognition performance had been suggested as a potential predictor for severity of negative symptoms (Milev et al., 2005). And they appeared to overlap with each other on explaining variance in functional outcome as well (Bilder et al.,2000). And more potential variables can be added in regard to their association with DUI and DUP. This would probably help generating more information and future directions for planning of early intervention services in Hong Kong. 21

29 Chapter 5 Conclusion In conclusion, this study had provided a general insight on how the construct of DUI / DUP interacted with negative severity and function outcome among people with psychosis in Hong Kong. Although no significant association had been found between DUP and negative symptoms, the association of DUI and negative symptoms and functional outcome, in contrary, had reinforced the importance of untreated prodromal period towards persistent deficits suffered by the cohort with psychosis. Yet, it was worth to note that the causal relationship between these variables was remained inconclusive. And several limitations have been identified as mentioned previously. Hence, it should be admitted that further work-up on refining the information regarding association between DUI / DUP and outcome variables was crucial to provide concrete basis for the future development of psychiatric services for psychotic population in Hong Kong. 22

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