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1 Stigma and Health 2015 American Psychological Association 2016, Vol. 1, No. 1, /16/$ Dynamic Changes of Self-Stigma, Quality of Life, Somatic Complaints, and Depression Among People With Schizophrenia: A Pilot Study Applying Kernel Smoothers Chung-Ying Lin National Cheng Kung University Chih-Cheng Chang Chi Mei Medical Center, Tainan, Taiwan, and King s College London Tsung-Hsien Wu Chi Mei Medical Center, Liouying, Taiwan Jung-Der Wang National Cheng Kung University The aims of this study are to verify this sequential structure and to determine if self-stigma is associated with lower quality of life (QoL) and depression. A total of 160 patients with schizophrenia participated in this study. Each completed the Self-Stigma Scale-Short Form (SSS-S), the World Health Organization (WHO) questionnaire on the Quality of Life, Brief Form (WHOQOL-BREF), and the Depression and Somatic Symptoms Scale (DSSS) instruments. Dynamic changes of the measures of self-stigma and related QoL were analyzed using a kernel-type smoother. The effects of self-stigma on QoL and depression were assessed using multiple regression models. The dynamic changes of self-stigma scores seem to support a sequential structure. The general pattern is elevated for around 12 months, exceeds 2.5 after 54 months, and reaches a peak of about 90 months after diagnosis of schizophrenia, then declines and appears to be stabilized later on. While the DSSS scores synchronize with those of self-stigma, those of the WHOQOL-BREF seem to show an opposite trend. Self-stigma appears to be a dominator for QoL and depression for people with schizophrenia. Patients with schizophrenia may develop self-stigma around 1 year after diagnosis. Early detection and management may improve patient QoL and minimize depression. However, the results of this pilot study should be interpreted with caution because of the cross-sectional design. Keywords: depression, dynamic changes, schizophrenia, self-stigma, quality of life People with schizophrenia have both positive and negative symptoms (American Psychiatric Association, 2013), which are very likely to This article was published Online First September 28, Chung-Ying Lin, Department of Public Health, College of Medicine, National Cheng Kung University; Chih- Cheng Chang, Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan, and Health Service and Population Research Department, Institute of Psychiatry, King s College London; Tsung-Hsien Wu, Department of Psychiatry, Chi Mei Medical Center, Liouying, Taiwan; Jung-Der Wang, Department of Public Health, College of Medicine, National Cheng Kung University, and Departments of Internal Medicine and Occupational and Environmental Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University. Chung-Ying Lin is now at Department of Rehabilitation Sciences, The Hong Kong Polytechnic University. influence their health-related outcomes (Lysaker, Davis, Warman, Strasburger, & Beattie, 2007; Riggs, Grant, Perivoliotis, & Beck, 2012; Chung-Ying Lin and Chih-Cheng Chang contributed equally to this article. This research was supported by Grant CLFHR10028 from the Chi Mei Medical Center, Liouying, Taiwan. Chung-Ying Lin was financially supported by the project of Health Cloud Project, Academia Sinica, which has no conflicts of interest. We thank the staffs of the Departments of Psychiatry, Chi Mei Medical Center, Tainan and Liouying, for their support with data collection. Correspondence concerning this article should be addressed to Jung-Der Wang, Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Chen Kung University, 1 University Road, Tainan 70101, Taiwan. 29

2 30 LIN, CHANG, WU, AND WANG Ritsher & Phelan, 2004). Moreover, adequate public understanding of the course and impact of schizophrenia, especially their positive and negative symptoms, are crucial to minimize discrimination against people with schizophrenia (Link & Phelan, 2001; Omori, Mori, & White, 2014). Unfortunately, people with schizophrenia may translate discrimination into selfdevaluation and in turn feel that they do not belong to the society in which they live (Chang, Wu, Chen, Wang, & Lin, 2014; Livingston & Boyd, 2010; Ritsher, Otilingma, & Grajales, 2003). This self-devaluation is called selfstigma or internalized stigma, and has been suggested as one of the especially painful and destructive effects of stigma (Ritsher et al., 2003). Although discussion of the self-stigma has increased over the past few decades (Jacobsson, Ghanean, & Törnkvist, 2013), and many efforts toward reducing stigma are underway (Corrigan, 2000; Huang & Lin, 2015; Sibitz, Unger, Woppmann, Zidek, & Amering, 2011), there is little empirical evidence regarding the first appearance and dynamic changes of selfstigma in people with schizophrenia. Because early recognition of the problem and identification of its dynamic changes over time could give mental health professionals good insights into the care of people with schizophrenia, this study intends to examine the course of self-stigma over time. Substantial evidence has shown that self-stigma has devastating effects on the health of patients with mental illness: self-stigma decreases the self-esteem and self-efficacy of a person with severe mental illness and ultimately jeopardizes his or her quality of life (QoL; Fung, Tsang, Corrigan, Lam, & Cheung, 2007; Mak, Poon, Pun, & Cheung, 2007; Mashiach- Eizenberg, Hasson-Ohayon, Yanos, Lysaker, & Roe, 2013). Moreover, self-stigma reduces the readiness to change and the adherence to treatment in patients with schizophrenia (Fung, Tsang, & Cheung, 2011; Fung, Tsang, & Corrigan, 2008; Tsang, Fung, & Chung, 2010). Therefore, any mental health professional should understand the course of selfstigma, acknowledge its impacts, and apply appropriate management strategies to prevent and/or reduce it during the treatment of people with schizophrenia. Self-stigma, as well as public stigma, has been conceptualized to contain the three components including stereotypes, prejudice, and discrimination (Corrigan & Watson, 2002). It was later proposed that these three components correspond to cognition (as stereotypes define negative beliefs about self), affect (as prejudice defines negative emotional reaction), and behavior (as discrimination defines behavioral response to prejudice; Brohan, Slade, Clement, & Thornicroft, 2010; Mak & Cheung, 2010). The three components are suggested to be closely linked together and possibly sequential in both public stigma (Corrigan & Watson, 2002) and self-stigma (Mak & Cheung, 2010). When people with schizophrenia accept a stereotype of schizophrenia (i.e., cognition), they likely experience strong negative emotional reactions, which later lead to behavioral responses such as social withdrawal (see Figure 1). Most widely used instruments on self-stigma follow the cognition, affect, and behavior concepts (Brohan et al., 2010; Mak & Cheung, 2010), including the Self-Stigma of Mental Illness Scale (SSMIS; Corrigan et al., 2012; Corrigan, Watson, & Barr, 2006), the Internalized Stigma of Mental Illness (ISMI; Boyd, Adler, Otilingam, & Peters, 2014; Ritsher et al., 2003), and the Self-Stigma Scale-Short (SSS-S; Mak & Cheung, 2010; Wu, Chang, Chen, Wang, & Lin, 2015). Although most researchers agree that these three components are embedded in the self-stigma concept, there has been no empirical study to explore how these concepts are linked together sequentially. If the theoretical sequential model is supported, people with schizophrenia would first develop self-stigma in cognition (recognize self-stereotype), followed by the self-stigma in affect (agree with prejudice), and then in behavior (show withdrawal in response). Because of the lack of long-term follow-up on the current measurements of selfstigma for people with schizophrenia, the above hypotheses and the dynamic changes of selfstigma are difficult to observe or test. In this study, we apply a kernel smoothing method on a cross-sectional sample (Hwang, Tsauo, & Wang, 1996) to summarize the dynamic changes of self-stigma and test the above hypotheses. Because each participant of the crosssectional sample has his or her own duration of illness recorded from the date of diagnosis to the interview (or, duration-to-date), the dynamic changes can be examined somewhat us-

3 DYNAMIC CHANGES OF SELF-STIGMA IN SCHIZOPHRENIA 31 Cognition Negative belief about self; stereotypes Quality of life (Physical; Psychological; Social; Environment) Self Stigma Affect Negative emotional reaction; prejudice Behavior Behavior response to prejudice; discrimination ing the different durations if it is a random or quasi-random sample. In other words, the mean self-stigma value of different duration-to-dates can be estimated through the kernel smoother. For example, 5 patients with different durationto-dates reported their self-stigma scores as follows: Patient A scores 2 measured 10 months after diagnosis, Patient B scores 2.4 at 11 months, Patient C scores 2.3 at 12 months, Patient D scores 2.1 at 13 months, and Patient E scores 1.9 at 14 months. The kernel smoother estimates patient average self-stigma score as ( )/ at 11 months, and ( )/ at 12 months after diagnosis. In addition to the self-stigma, we are also concerned with patient-reported outcomes (PROs) in people with schizophrenia (European Medicines Agency, 2005; Food and Drug Administration, 2009; Hunter, Cameron, & Norrie, 2009; McCabe, Saidi, & Priebe, 2007). Selfstigma may result in lower QoL, somatic complaints, and depression, which have been found in both cross-sectional (Chan & Mak, 2014; Lysaker et al., 2007; Ritsher et al., 2003; Vauth, Kleim, Wirtz, & Corrigan, 2007; Yanos, Roe, Markus, & Lysaker, 2008) and longitudinal follow-up studies (Lysaker et al., 2007; Ritsher & Phelan, 2004). Therefore, self-stigma likely impacts the health-related outcomes of people Somatic complaints Depression Figure 1. A path diagram of self-stigma, quality of life, somatic complaints, and depression in people with schizophrenia. with schizophrenia, as summarized in Figure 1. Furthermore, many longitudinal studies on people with schizophrenia have demonstrated dynamic changes of QoL and depression as well as their relationships with the course of schizophrenia and the clinical outcomes. People with schizophrenia are likely to become depressed during posthospital period because of increased psychosis, decreased work functioning, and poor posthospital adjustment (Birchwood, Mason, MacMillan, & Healy, 1993; Sands & Harrow, 1999). Moreover, studies on dynamic changes of QoL indicate that an improved QoL is followed by reduced psychotic symptoms and functional disability (Björkman & Hansson, 2002; Heider et al., 2007; Huppert & Smith, 2001; Priebe, Roeder-Wanner, & Kaiser, 2000) in people with schizophrenia. Although the association between self-stigma and PROs are well-established, and the dynamic changes of the QoL and depression are well-documented, the dynamic changes related to the association between self-stigma and PROs have seldom been examined. The purposes of the study were to (a) compare the sequential model of self-stigma to dynamic changes in people with schizophrenia, (b) to investigate the dynamic changes of several different PROs in people with schizophrenia, and (c) to probe the relationship be-

4 32 LIN, CHANG, WU, AND WANG tween self-stigma and PROs in a Taiwanese sample group diagnosed with schizophrenia. Participants Methods The Research and Ethics Review Board of the Chi Mei Medical Center (IRB number: L06) approved the study, and 161 individuals were recruited from Chi Mei Medical Center s psychiatric outpatient (n 128), day care (n 30), and home care (n 2) centers and wards (n 1). All participants were diagnosed with schizophrenia based on the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM IV TR; American Psychiatric Association, 2000) and met the following inclusion criteria: (a) older than 20 years; (b) able to communicate using Mandarin Chinese or Taiwanese; (c) agreed to participate in the study after being informed of the study purpose. Each participant provided written informed consent, and completed four questionnaires: the Self-Stigma Scale-Short Form (SSS- S), the WHO questionnaire on the Quality of Life, Brief Form (WHOQOL-BREF), the Depression and Somatic Symptoms Scale (DSSS), and a background information sheet. Data Collection Procedure Two branches of the Chi Mei Medical Center (the Tainan and Liouying branches) helped recruit the participants and collect the data. Several psychiatrists examined their patients consecutively, extended an invitation to participate to those who fulfilled the recruitment criteria, and introduced the purposes of the study. Moreover, the psychiatrists interviewed the candidate patients to ensure that their psychotic symptoms were stable and that they were fully capable of signing a consent and completing the study. Afterward, the psychiatrists obtained the written informed consents from the patients who agreed to participate in the study and transferred the patients to research assistants who supervised the participants while they filled out four questionnaires and a background information sheet. Measures SSS-S form. The 9-item SSS-S contains 3 domains (viz., cognition, affect, and behavior), each having 3 items. All questions use a 4-point Likert scale (1 strongly disagree; 4 strongly agree). The first version of SSS-S was designed for minority groups including mental health consumers and immigrants (Mak & Cheung, 2010), and its psychometric properties have been supported for mental illness groups: internal consistency (.80 to 0.95), concurrent validity (r.335 to with the DSSS and to with WHOQOL-BREF), and construct validity (comparative fit index, CFI to 0.991). Moreover, the measurement invariance of the SSS-S has been supported across genders in a sample with mental illnesses (Wu et al., 2015). A higher score in the SSS-S means a higher level of self-stigma. WHOQOL-BREF. The 28-item WHOQOL- BREF Taiwan version has physical (7 items), psychological (6 items), social (4 items), and environment (9 items) domains, and 2 additional generic items that measure overall QoL and general health. All items on the WHOQOL- BREF are on a 5-point Likert scale, and each domain score can be calculated into a range from4to20(yao, Chung, Yu, & Wang, 2002). In addition to the satisfactory psychometric properties of the WHOQOL-BREF for the Taiwanese general population, the WHOQOL- BREF has been validated using a Rasch analysis for heroin users (Chang, Wang, Tang, Cheng, & Lin, 2014) and using a confirmatory factor analysis for people with schizophrenia (Su, Ng, Yang, & Lin, 2014). A higher score in each domain and item of the WHOQOL-BREF indicates a better QoL. DSSS. The 22-item DSSS measures somatic complaints (10 items) and depression (12 items) because somatic symptoms may confound depression. All items of the DSSS are on a 4-point Likert scale (0 absent, 1 mild, 2 moderate, and 3 severe) with satisfactory internal consistency ( ), test retest reliability (r ), convergent validity (r ), and known group validity (ability to distinguish chronic depression). A higher score in the DSSS means more somatic complaints and deeper depression (Hung, Weng, Su, & Liu, 2006). Statistical Analysis Dynamic changes of all PROs were analyzed using the free software, isqol (isqol soft-

5 DYNAMIC CHANGES OF SELF-STIGMA IN SCHIZOPHRENIA 33 ware, 2014), and other statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) 15.0 (SPSS Inc., Chicago, IL). The mean self-stigma, QoL, somatic complaints, and depression scores were estimated using a kernel-type smoother (Hwang et al., 1996) given by: n i 1 P i( i x) Pˆ(t k x) K i t k b n i 1 K i t k k 0,1...,I; K(w) 1if w 1, 0 otherwise, where Pˆ t k x is the estimated self-stigma, QoL, somatic complaint, or depression values at kth time; i is the ith patient s assessment time; P i ( i x) represents the PRO values of the patient at time i, and b is the bandwidth parameter, which was set at 10% in this study. Because we were concerned that a skewed distribution of duration after diagnosis may influence the results generated from the kernel smoother, we tested its normality in advance. The results of the normality testing showed that duration after diagnosis was normally distributed or nearly normally distributed based on the nonsignificant Kolmogorov Smirnov test and skewness (0.828) and kurtosis (0.856) values that were less than 1. Descriptive analyses were used for the demographic data, and the frequencies of age and gender were compared with a sample representative of the entire Taiwanese population diagnosed with schizophrenia (Chien et al., 2009). The compared sample was retrieved from a database containing 1,000,000 random subjects who participated in the Taiwan National Health Insurance (NHI) program in Pearson correlations were used to investigate the relationship between each PRO. Moreover, the effects of self-stigma on QoL, somatic complaints, and depression were examined using several regression models adjusting for age (by year), gender (reference: male), years of education, and onset duration (by month). Because we speculated that the three self-stigma domains (cognition, affect, and behavior) would be highly correlated, we used a variance inflation factor (VIF) to test for collinearity. If the VIF 4(O Brien, 2007), an overall SSS-S score was used instead b ; of the three domain scores in the regression models. Several power analyses based on correlations between self-stigma and QoL, and between selfstigma and depression were conducted to help us understand the essential sample size. The correlation between self-stigma and QoL was based on a meta-analysis (r 0.38 to 0.47), and that between self-stigma and depression on a sample with schizophrenia living in Hong Kong (r 0.26 to 0.28; Chan & Mak, 2014). Given a two-sided correlation test with power at 0.8, a Type I error of 0.05 and applying a range of correlation coefficients between 0.26 and 0.47, we would need a minimal sample size of 33 to 113. Because we also applied kernel smoothing methods to determine the dynamic changes of several PROs, we decided to enlarge the sample size to more than 150, and finally, 161 participants were recruited. Results One 34-year-old female participant receiving day care was excluded for all analyses due to a lack of onset information, which left a total of 160 participants for final analysis. About half of the participants were male (51.9%); most participants were single (69.4%), and only slightly more than one third (35.6%) were employed. Although the participants were middle age (40.5 years) during the study, their mean age of first contact with mental health service was 26.7 years. In addition, 3 participants had a diagnosed duration of schizophrenia for more than 450 months; 12 had durations of more than 310 months, and others had durations between 7 to 302 months (see Table 1). This allowed dynamic changes to be investigated up to 300 months after onset. The mean (SD) scores of SSS-S were 2.4 (0.8) for cognition, and 2.2 (0.8) for both affect and behavior; WHOQOL- BREF scores were 13.2 (2.5) for physical, 12.1 (3.3) for both psychological and social, and 12.7 (2.8) for environment. The DSSS scores were 0.5 (0.6) for somatic complaints and 0.7 (0.7) for depression, respectively. Moreover, our sample had slightly more middle-age adults versus elderly and young adults as compared with the 1,000,000 random subjects retrieved from the Taiwan NHI ( , df 5, p.004). However, the gender distribution in our sample

6 34 LIN, CHANG, WU, AND WANG Table 1 Demographic Characteristics for Participants (N 160) and People With Schizophrenia (N 4,417) From a 1,000,000 Subject Random Sample Retrieved From the 2005 Taiwan National Health Insurance (NHI) Records was similar to that of the NHI sample ( , df 1, p.51). The dynamic change of self-stigma showed that the domain score for cognition was highest after the onset of schizophrenia, followed by the scores for affect and behavior. Nonetheless, all scores showed similar trends in that they first developed around 12 months after diagnosis and climbed up to the highest point (around 2.5 to 2.8) about 54 to 86 months after the initial diagnosis. After 86 months, the average selfstigma scores dropped down to below 2.5 and seemed to stabilize. When the cognition selfstigma scores begin to decline, the nearly synchronous scores of affect and behavior selfstigma mirror the declining trend of the cognition score (Figure 2a). The WHOQOL-BREF scores also begin to drop at the 12th month after initial diagnosis of schizophrenia. Thereafter, all domain scores of WHOQOL-BREF decrease consistently to about 89 months, followed by a short period of elevation from the 89th month to the 99th This study 2005 NHI Mean or (n) SD or (%) Mean or (n) SD or (%) Gender (Female) (77) (48.1%) (2010) (45.5%) Age (year) (24) (15.0%) (811) (18.4%) (53) (33.1%) (1217) (27.6%) (62) (38.8%) (1272) (28.8%) (12) (7.5%) (693) (15.7%) (6) (3.8%) (263) (6.0%) 70 (3) (1.9%) (161) (3.7%) Marital status Single (111) (69.4%) Currently married (29) (18.1%) Others (20) (12.5%) Currently employed (Yes) (57) (35.6%) Age at first contact with MHS (years) Years of education Months after onset (23) (14.4%) (38) (23.7%) (32) (20.0%) (29) (18.1%) (22) (13.8%) 300 (16) (10.0%) Note. MHS mental health service. month for three domains (viz., psychological, social, and environment). The scores for the physical domain were usually the highest among all four domains, followed by that of the environment domain. However, all domain scores abruptly dropped at the 100th month and gradually climbed up afterward. In the case of the DSSS, the dynamic changes in the scores for somatic complaints and depression appear to be synchronized with those of self-stigma and were generally low (i.e., 1) throughout the 300 months of observation. The trends of the somatic complaints and depression scores were similar. Both progressively increased from onset to the 100th month with 2 peaks (90th and 100th month). After 100 months, both somatic complaint and depression scores slowly decreased and became stable (Figure 2c). There seems a general trend where the WHO- QOL-BREF domain scores increase after those of the SSS-S decrease, while the DSSS scores tend to synchronize with the SSS-S scores. The

7 DYNAMIC CHANGES OF SELF-STIGMA IN SCHIZOPHRENIA 35 Figure 2. Dynamic changes of self-stigma, quality of life, somatic complaints, and depression for people with schizophrenia from onset to 25 years. The vertical dashed line indicates 12 months after diagnosis, and the solid line indicates 86 months after diagnosis. SSS-S Self-Stigma Scale-Short Form; A affect; B behavior; C cognition; WHOQOL- BREF The WHO questionnaire on the Quality of Life, Brief Form; Env environment; Phy physical; Psy psychological; Soc social; DSSS Depression and Somatic Symptoms Scale. See the online article for the color version of this figure. SSS-S scores increased at the 12th month after initial diagnosis, while the WHOQOL-BREF scores began to decrease almost at the same time but dropped more at the 22th month. Conversely, the DSSS scores increased at the 22th month (see Figure 2). Pearson correlations among the PROs show that the hypothesized relationships between self-stigma and QoL, somatic complaints, and depression were supported (see Table 2). Because the domains of cognition, affect, and behavior in SSS-S were highly correlated (r.81

8 36 LIN, CHANG, WU, AND WANG Table 2 Correlation Matrix for Patient-Report Outcomes (PROs) to 0.86) and tended to show collinearity (VIF 4 to 5), the average score of the 9 SSS-S items was used. After adjusting for age, gender, years of education, and duration after schizophrenia diagnosis, the multiple linear regression model construction disclosed self-stigma dominantly explained QoL ( to 0.253; p.001), somatic complaints, and depression ( and 0.501; p.001) in people with schizophrenia (see Table 3). Moreover, all independent variables together explained 13.8% to 27.0% of QoL, 13.6% of the somatic complaints, and 17.4% of the depression SSS-S 1. Cognition Affect Behavior WHOQOL-BREF 4. Physical Psychological Social Environment DSSS 8. Somatic Depression.77 Note. SSS-S Self-Stigma Scale-Short Form; WHOQOL-BREF The WHO questionnaire on the Quality of Life, Brief Form; DSSS Depression and Somatic Symptoms Scale. All p.001. Discussion To the best of our knowledge, this is the first study to explore the dynamic changes of selfstigma, QoL, somatic complaints, and depression for a sample of individuals with schizophrenia. The results seem to support the sequential structure of the three components in self-stigma (see Figure 2). While the self-stigma scores began to elevate around 1 year after diagnosis, they synchronized with depression scores and symptoms, and the QoL scores showed the opposite trend. The multiple linear Table 3 Effects of Self-Stigma on Quality of Life, Somatic Complaint, and Depression in People With Schizophrenia Dependent variable Independent variable (SE) Age (year) Gender a (year) Education Duration (month) Self-stigma b Adjusted R 2 WHOQOL-BREF Physical.001 (.022).067 (.367).038 (.062).002 (.002).168 (.027) Psychological.027 (.027).205 (.458).055 (.077).001 (.003).253 (.034) Social.038 (.029).319 (.500).134 (.084).001 (.003).173 (.037) Environment.007 (.024).766 (.410).069 (.069).002 (.002).161 (.031) DSSS Somatic.060 (.054) (.920).054 (.155).008 (.006).306 (.069) Depression.056 (.068).307 (1.150).007 (.192).001 (.007).501 (.086) Note. WHOQOL-BREF The WHO questionnaire on the Quality of Life, Brief Form; DSSS Depression and Somatic Symptoms Scale. a Reference group: Male. b Self-stigma score is the average score of all 9 SSS-S item scores due to collinearity among cognition, affect, and behavior domains (VIF 4to5). p.051. p.001. F

9 DYNAMIC CHANGES OF SELF-STIGMA IN SCHIZOPHRENIA 37 regression models also corroborate these close relationships. We examined the evidence before making further inferences. However, because we did not use a longitudinal design but rather used a cross-sectional design with kernel smoothing methods, more evidence is warranted to corroborate our initial findings. The cognitive, affect, and behavior components embedded in self-stigma have been investigated using different psychometrical methods on several self-stigma instruments (Boyd et al., 2014; Brohan et al., 2010; Corrigan et al., 2006, 2012; Mak & Cheung, 2010). Mak and Cheung (2010) further proposed a relationship between the three components based on cognitivebehavior theory (Barlow, Allen, & Choate, 2004), suggesting that people with schizophrenia first endorse the incorrect belief that they are insane, dangerous, and so on, which is followed by negative emotions and behavioral responses. In Figure 2, we observed the first elevation of the score for cognition self-stigma around the end of the first year after diagnosis, which was closely followed by the affect and behavior self-stigma scores. When the score for cognition self-stigma begins to drop, the two other scores also simultaneously drop, thus demonstrating a clear synchronization trend. This corroborates the sequential hypothesis proposed by Mak and Cheung (2010) and Corrigan and Watson (2002). We found a negative relationship between self-stigma and QoL, and a positive relationship between self-stigma and somatic complaints/ depression. All the relationships were maintained after adjustment for age, gender, years in education, and duration-to-dates (see Table 3). These findings corroborate those found in previous studies (Chan & Mak, 2014; Lysaker et al., 2007; Ritsher et al., 2003; Vauth et al., 2007; Yanos et al., 2008). Although we used a cross-sectional study, which characteristically has weak ability to decide causal effect, the dynamic changes of self-stigma and other PROs demonstrated that self-stigma could be the cause of other PROs. The highest self-stigma was observed before the lowest QoL was concurrent with the highest somatic complaints and depression (see Figure 2). Based on the regression models and dynamic changes, we tentatively conclude that self-stigma is a determinant for QoL, somatic complaints, and depression for people with schizophrenia. Based on the dynamic changes in Figure 2, we found the self-stigma of patients begins to elevate 12 months after initial diagnosis and persists until around 86 months after. Despite the fact that all patients diagnosed with schizophrenia are likely to receive regular medication to control their symptoms (Essock, Hargreaves, Covell, & Goethe, 1996; Geddes, Freemantle, Harrison, & Bebbington, 2000; Lieberman et al., 2005; McEvoy et al., 2006), these prescriptions may not be effective for treating selfstigma. Instead, this problem seems to occur after control of the patients positive symptoms, as shown in Figure 2. Because a higher level of self-stigma is found to be correlated with better insight (Cavelti, Rüsch, & Vauth, 2014; Mak & Wu, 2006), we hypothesize that self-stigma may develop after symptom control of patients with schizophrenia and possibly after increased insight into their illness. In other words, the increased self-stigma may be attributed to their understanding (or, misunderstanding) of their illness. Afterward, the self-stigma seemed to influence their QoL, somatic complaints, and depression. There was a declining trend around 86 months after diagnosis, indicating possible development of stigma resistance (Brohan et al., 2010; Chang et al., 2014; Sibitz et al., 2011), which might be related to nonpharmacological interventions such as occupational therapy during this period. When we stratified our sample into two groups according to employment, we found that the currently employed group appears less vulnerable to the development of self-stigma (see Figure 3). Conversely, the unemployed group had a longer duration of high self-stigma (i.e., self-stigma score 2.5; Boyd et al., 2014) than the employed group. Our results may imply a possible effect from employment and/or occupational therapy. However, a comprehensive, longitudinal follow-up study is needed to corroborate these hypotheses. Another possibility that could explain the declining self-stigma may be related to the course of symptoms and process of family acceptance. Breier, Schreiber, Dyer, and Pickar (1991) proposed a model supported by Eaton and colleagues (Eaton, Bilker et al., 1992; Eaton, Mortensen et al., 1992) where they observed that chronic schizophrenia is characterized by relative stability in the middle stage ( months), which may lead to the drop in self-

10 38 LIN, CHANG, WU, AND WANG (a) Currently employed SSSA SSSB SSSC (b) Currently unemployed stigma scores. During this stable period, the patient and his or her family may shift their attitude away from denying the illness (Frese, Knight, & Saks, 2009) to accepting and living with it. This study has several limitations. First, although the kernel smoother we used shed some light on the dynamic changes of PROs using a cross-sectional sample, it is largely based on an assumption that each participant in the sample has similar personal characteristics, which may not be realistic. Although the most accurate way to probe dynamic change is through conducting a longitudinal follow-up study with the recently developed self-stigma instruments (ISMI was developed in 2003, SSMIS in 2006, and SSS-S in 2010), it is currently infeasible to explore such long-term (say, years) changes. As the problem and potential impact of self-stigma are so important in the everyday care of patients with schizophrenia, we turned to this alternative SSSA SSSB SSSC (Month) Figure 3. Dynamic changes of self-stigma for people with schizophrenia stratified by employment status from onset to 25 years. The horizontal dashed line indicates a high-level of self-stigma. SSS-S Self-Stigma Scale-Short; A affect; B behavior; C cognition. See the online article for the color version of this figure. method for investigating the dynamic changes based on a cross-sectional sample. Coupling two simultaneous measurements of depression and QoL, we hypothesized and predicted to detect the reciprocal dynamic changes with a kernel smoothing estimator, and we were able to corroborate our hypotheses. As the application of the kernel smoother was developed from a previous simulation study of a random sample with a minimum size of 50 (Hwang et al., 1996), and empirical studies were tested and corroborated on patients with cancer (Hung, Wu et al., 2014; Yang et al., 2014), hemodialysis (Hung, Sung, Chang, Hwang, & Wang, 2014), stroke (Hung, Hsieh, Hwang, Jeng, & Wang, 2013), and those using prolonged mechanical ventilation (Hung et al., 2012), we tentatively considered it acceptable for this pilot study. Nevertheless, our results derived from the kernel smoothers should be interpreted with caution, and future studies using

11 DYNAMIC CHANGES OF SELF-STIGMA IN SCHIZOPHRENIA 39 longitudinal design are needed to corroborate our statements. Second, the time of initial schizophrenia diagnosis was not able to be precisely reported in this study. The starting point of the dynamic change we showed is possibly later than the real onset of schizophrenia because the real onset of the disease is often not marked by psychotic symptoms but rather by unspecific symptoms such as irritability, restlessness, and moodiness (an der Heiden & Häfner, 2000). We adopted the age of their first contact with mental health services instead. The third limitation of this study is that we did not collect detailed treatment information. Therefore, we were unable to examine the treatment effects on dynamic changes in PROs. Future studies are warranted to simultaneously and repeatedly collect the information for different treatments (e.g., occupational therapy, psychotherapy, or family therapy) and PROs. Then, a mixed effects model may be constructed to explore their effects on PROs, including self-stigma, in people with schizophrenia. Fourth, we did not stratify the duration after diagnosis to recruit participants in this study, which may have resulted in sparse data over certain durations. For example, Table 1 shows that 90% of the durations-to-date of our participants were within 300 months after diagnosis. Therefore, we were unable to make any inference over the dynamic changes after 300 months. Future studies are encouraged to conduct sampling stratified by different durationsto-date, which would ensure sufficient sample sizes for different durations after diagnosis. Fifth, although the psychiatrists verified that psychotic symptoms (positive and negative symptoms) were stable for all participants during the recruitment, the examinations were based on interviews instead of a standard measurement. While such a potential misclassification or measurement error might bias the results, it generally leads toward the null (Marshall & Hastrup, 1996). In other words, it may reduce the overall impact of self-stigma instead of inducing a spurious effect. Finally, many potential confounders, including mental state, age of onset, employment status, social support, and so forth, were not controlled in this pilot study. We recommended that future studies adopt a stratified sampling strategy taking major potential confounders into consideration, namely, applying kernel smoothers on each homogeneous stratum. Prevention and management of self-stigma should be emphasized for mental health professionals because our results and previous findings (Björkman & Hansson, 2002; Chan & Mak, 2014; Fung et al., 2007, 2008; Heider et al., 2007) indicate that self-stigma substantially impacts outcomes and the motivation for treatment. Moreover, our results corroborate with those of the sequence hypothesis (Corrigan & Watson, 2002; Mak & Cheung, 2010), which asserts that self-stigma is generated from cognition, to which the effort could first focus on education to reduce public stigma as suggested by Corrigan and his colleague (Corrigan, 2000; Corrigan et al., 2001). In addition, two effective programs (Fung et al., 2011; Yanos, Roe, West, Smith, & Lysaker, 2012) on reducing selfstigma both use psychoeducation at the beginning of the programs. Therefore, future studies that examine the effects of education on preventing self-stigma for people with schizophrenia are warranted. Moreover, according to the timeline found in this study (see Figure 2), we recommend that such a program be implemented within the first year after diagnosis for prevention, and perhaps immediately after the acute symptoms have become under control by medication, and the patients begin to develop insights into their illness. In conclusion, people with schizophrenia reported the highest self-stigma at 54 to 86 months after their onset. This is followed by the lowest QoL and the highest somatic complaints and depression at 89 to 100 months after diagnosis. The above findings corroborate the hypothesis that self-stigma in patients with schizophrenia affects their QoL and may result in more somatic complaints and depression. However, because of the cross-sectional collection of data and no adjustment for potential confounders (e.g., psychotic symptoms, social support, etc.), this study could only be regarded as a pilot study. Future longitudinal follow-up studies should be conducted to corroborate the above hypothesis, explore the determinants, and test possible prevention and management strategies to avoid and/or reduce self-stigma as well as poor QoL in people with schizophrenia.

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