Predictors of quality of life in inpatients with schizophrenia

Predictors of quality of life in inpatients with schizophrenia

Psychiatry Research 197 (2012) 199–205 Contents lists available at SciVerse ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/loc...

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Psychiatry Research 197 (2012) 199–205

Contents lists available at SciVerse ScienceDirect

Psychiatry Research journal homepage: www.elsevier.com/locate/psychres

Predictors of quality of life in inpatients with schizophrenia Koichiro Fujimaki a,⁎, Shigeru Morinobu b, Hidehisa Yamashita b, Terumichi Takahashi c, Shigeto Yamawaki b a

Faculty of Health and Welfare, Prefectural University of Hiroshima, 1-1 Gakuen-Machi, Mihara, Japan Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan c Mihara Hospital, Mihara, Japan b

a r t i c l e

i n f o

Article history: Received 5 September 2011 Accepted 31 October 2011 Keywords: Schizophrenia Quality of life Inpatients Negative symptoms

a b s t r a c t Shortening hospital stays has become a key focus in psychiatric care in recent years. However, patients with schizophrenia account for about 60% of inpatients in psychiatry departments in Japan. This study was designed to investigate the relationship between quality of life (QOL) and key indicators for long-term hospital stays among schizophrenia inpatients. A further aim was to elucidate the clinical determinants of QOL among long-stay inpatients. The study sample consisted of 217 inpatients with schizophrenia. Age, duration of illness, duration of hospitalization, years of education, body mass index, neurocognitive function, druginduced extrapyramidal symptoms, involuntary movements, psychiatric symptoms, and dose equivalents of antipsychotics and anticholinergic agents were used as index factors. Pearson linear correlation and regression analyses were performed to examine the associations between QOL and the above-mentioned factors. Negative symptoms, psychological discomfort, and resistance as rated on the Brief Psychiatric Rating Scale (BPRS) were correlated with all subscale scores of the Japanese version of the Schizophrenia Quality of Life Scale (JSQLS). Stepwise regression showed that negative symptoms, psychological discomfort, and resistance predicted the dysfunction of psycho-social activity score and the dysfunction of motivation and energy score on the JSQLS. This study shows that active treatment for negative symptoms, psychological discomfort, and resistance should be recommended to improve QOL among inpatients with schizophrenia. © 2012 Elsevier Ireland Ltd. All rights reserved.

1. Introduction In recent years, attention has focused on quality of life (QOL) for patients with schizophrenia, as well as on shortening hospital stays. Moreover, although the number of cases for whom ambulatory treatment is possible has increased in recent years due to advancements in treatment methods, patients with schizophrenia still account for about 60% of inpatients in psychiatry departments, and the number of patients being hospitalized in each decade has increased over time (Ministry of Health, 2008a). Many long-term inpatients feel that life in the hospital is comfortable; however, long-term hospitalization makes it difficult for these patients to become independent. QOL assessments provide valuable information about outcomes in patients with chronic illnesses. These assessments can be used to measure incremental improvements rather than a complete cure, account for a wide range of factors associated with daily living, and be used across various medical disciplines (Oliver et al., 1996).

⁎ Corresponding author at: Department of Occupational Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima, 1-1 Gakuen-Machi, Mihara, Hiroshima 723-0053, Japan. Tel.: +81 848 601120; fax: +81 848 601134. E-mail address: [email protected] (K. Fujimaki). 0165-1781/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2011.10.023

Various clinical factors related to QOL have been identified. Several studies have suggested that depressed mood may be the most important determinant of QOL (Dickerson et al., 1998; Fitzgerald et al., 2001; Huppert et al., 2001; Reine et al., 2003; Tomotake et al., 2006; Aki et al., 2008). Other studies have reported that positive symptoms (Norman et al., 2000) or akathisia symptoms, as well as the total severity of psychopathology (Awad et al., 1997a), help predict subjective QOL. In some studies, the severity of negative symptoms (Fitzgerald et al., 2001; Strejilevich et al., 2005; Tomotake et al., 2006; Aki et al., 2008) or the presence of tardive dyskinesia (Browne et al., 1996) was reported to be associated with a poor objective QOL. Knowledge about the illness has not been shown to be significantly related to QOL levels (Browne et al., 1998). In addition to clinical symptoms, sociodemographic factors also influence objective QOL of patients with schizophrenia (Caron et al., 2005). In recent years, greater attention has been given to the cognitive dimension of schizophrenia. One reason for this change is that atypical antipsychotics improve cognitive function, while conventional antipsychotics produce minimal cognitive improvement (Voruganti et al., 2000; Davis et al., 2003). Poor performance on neurocognitive tasks has been observed to be associated with poor performance on measures of community functioning, psychosocial skill acquisition, and social problem solving (Green, 1996). Several studies indicate that cognitive function has a greater impact on QOL in patients with schizophrenia than

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do positive symptoms (Breier et al., 1991; Green, 1996; Ho et al., 1998). Executive functioning and verbal learning appear to be especially valid predictors of work status (Green, 1996; Meltzer et al., 1996; Velligan et al., 1997; Meltzer and McGurk, 1999). Social and occupational impairments have long been recognized as core features of schizophrenia affecting social interactions, vocational and instrumental functioning skills, self-care, and recreation (Bellack et al., 1994). Both negative and positive symptoms of schizophrenia have also been found to be associated with functional outcomes. Few studies, however, have sought to compare the magnitude of the associations of neurocognition and symptoms with functioning, and the results that have been published are somewhat conflicting (Dickerson et al., 1996; Velligan et al., 1997; Dickinson and Coursey, 2002; Kurtz et al., 2005; Wegener et al., 2005). Some cross-sectional studies of chronic schizophrenia have suggested that psychopathology might be more strongly correlated with community functioning than cognition (Heslegrave et al., 1997; Kurtz et al., 2005), whereas others have concluded that cognition is the strongest correlate with community functioning (Green, 1996). Weight gain and obesity are associated with negative health consequences and are prevalent in patients with schizophrenia (Newcomer and Haupt, 2006). High body mass index (BMI) is associated with impaired QOL in the general population (Han et al., 1998), and weight gain is related to poorer QOL for individuals with schizophrenia (Allison et al., 2003). With these concerns in mind, this study was designed to investigate the relationship between QOL and key indicators for long-term hospital stays for schizophrenia inpatients. A further aim was to elucidate clinical determinants of QOL among long-stay inpatients. QOL was assessed using the Japanese version of the Schizophrenia Quality of Life Scale (JSQLS). Schizophrenia symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS). Analysis for the present study was based on four orthogonal dimensions: positive symptoms, negative symptoms, psychological discomfort, and resistance. In this study, the relative strength of association of measures of community functioning, as assessed by the JSQLS, with measures of the amount of medication, drug-induced extrapyramidal symptoms, involuntary movements, neurocognitive function, and psychiatric symptoms, was examined. The manner in which the four orthogonal dimensions, as well as age, duration of illness, duration of hospitalization, years of education, BMI, dose of antipsychotics, dose of anticholinergic agents, neurocognitive function, drug-induced extrapyramidal symptoms, and involuntary movements, affected QOL was investigated. 2. Methods 2.1. Subjects A total of 217 patients with schizophrenia were recruited from among psychiatric inpatients in Mihara Hospital. A diagnosis of schizophrenia was confirmed with the Structured Clinical Interview for ICD-10 and a medical chart review. No patient had any other psychiatric disorder. The antipsychotic regimen had not been changed for at least 20 weeks before recruitment in any subject. Data collection took place from 2008 to 2009. The study was approved by the ethics committee of Mihara Hospital. The experiments were thoroughly explained to the subjects, and written informed consent was obtained from all participants. 2.2. Variables assessed Variables assessed included age, duration of illness, duration of hospitalization, years of education, BMI, amount of medication, neurocognitive function, drug-induced extrapyramidal symptoms, involuntary movements, psychiatric symptoms, and QOL. Data collection of these variables took place from 2008 to 2009. These variables, except for the assessment of QOL, were assessed by treating psychiatrists. A self-assessment scale was used for the assessment of QOL. These variables were all assessed on the same day. Each variable was assessed a single time. 2.2.1. Age, duration of illness, and duration of hospitalization Age, duration of illness, and duration of hospitalization were assessed based on medical charts.

2.2.2. Years of education Years of education are included in the registry for the current study years. Completed years of formal education are recorded in the registry during the study period. To clarify the meaning of years of education, a total of 12 years of education corresponds to patients having completed tertiary level studies in Japan. 2.2.3. Body mass index Body weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, using standardized equipment and procedures, and BMI was calculated (kg/m2). 2.2.4. Amount of medication All patients were taking typical antipsychotics or atypical antipsychotics. Typical antipsychotics included bromperidol (12–54 mg/day, n= 14), clocapramine (75–225 mg/day, n = 2), chlorpromazine (12.5–400 mg/day, n =25), fluphenazine (2–9 mg/day, n = 2), haloperidol (0.75–33 mg/day, n = 35), levomepromazine (5–600 mg/day, n =41), mosapramine (75–150 mg/day, n = 2), nemonapride (20–60 mg/day, n = 3), perphenazine (12–16 mg/day, n = 3), pimozide (3 mg/day, n = 1), propericiazine (15–30 mg/day, n = 4), sulpiride (100–1600 mg/day, n = 6), timiperone (12 mg/day, n =1), and zotepine (25–450 mg/day, n =37). Atypical antipsychotics included risperidone (0.5–12 mg/day, n = 73), olanzapine (2.5–20 mg/day, n= 64), aripiprazole (6–30 mg/day, n = 19), quetiapine (10–750 mg/day, n= 50), and perospirone (4–48 mg/day, n = 7). The amount of medication for antipsychotics, typical antipsychotics, atypical antipsychotics, and anticholinergic agents was calculated, and the chlorpromazine equivalent (mg) was used to assess the amount of antipsychotics, typical antipsychotics, and atypical antipsychotics (Inagaki and Inada, 2006), while the biperiden equivalent (mg) was used to assess the amount of anticholinergic agents. 2.2.5. Neurocognitive function Neurocognitive functioning was measured using nine items on the Revised Hasegawa's dementia scale (HDS-R). The total score ranges from 0 to 30, with higher scores indicating higher neurocognitive function (Hasegawa, 1990). Word fluency was also assessed as part of neurocognitive function. The Word Fluency Test (WFT) was used to examine naming of words starting with the letters “Ta”, “Te”, and “Sa”. The total scores were measured by requiring subjects to name as many words as possible beginning with “Ta”, “Te”, and “Sa” in three separate 1-minute segments. The number of valid words pronounced in 3 min was used as the total score (Sumiyoshi et al., 2005). 2.2.6. Drug-induced extrapyramidal symptoms The Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) was used to evaluate and exclude the effects of drug-induced extrapyramidal symptoms that could affect the severity of symptoms in schizophrenia patients (Inada, 1996). This scale is based on nine items rated from 0 to 4, with higher scores indicating more severe symptoms. 2.2.7. Involuntary movements The Abnormal Involuntary Movement Scale (AIMS) is a rating scale that was designed in the 1970s to measure involuntary movements known as tardive dyskinesia (Guy, 1976). Tardive dyskinesia is a disorder that sometimes develops as a side-effect of longterm treatment with neuroleptic (antipsychotic) medications. The AIMS test has a total of 12 items that rate involuntary movements of various areas of the patient's body. These items are rated on a 5-point scale of severity from 0 to 4, where 0 = none, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe. The total score of items 1 through 7 represents observed movements. Item 8 can be used in isolation as an indication of overall severity of symptoms. Items 9 and 10 provide additional information that may be useful in clinical decision making. Items 11 and 12 provide information that may be useful in determining lip, jaw, and tongue movements. The total score on AIMS items 1 to 7 ranges from 0 to 28. Scores for items 8, 9, and 10 on the AIMS range from 0 to 4. 2.2.8. Psychiatric symptoms The Brief Psychiatric Rating Scale (BPRS) was used to evaluate the severity of psychiatric symptoms (Kolakowska, 1976). Each of 18 BPRS items was scored on a 7-point scale (0 to 6), with higher scores indicating more severe symptoms. Each of 17 items, except for 1 item, was classified into four categories. The four categories were positive symptoms, negative symptoms, psychological discomfort, and resistance (Lachar et al., 2001). Positive symptoms were represented by the total score of five items. In the same way, negative symptoms, psychological discomfort, and resistance were each represented by the total score of three items, five items, and four items, respectively. The total BPRS score is the sum of scores for all items. 2.2.9. QOL The primary dependent measure of interest was assessed using the Japanese version of the Schizophrenia Quality of Life Scale (JSQLS), a rater-administered scale that assesses overall QOL and functioning on 30 items rated from 0 to 4, with higher scores reflecting worse quality of life; this scale has been shown to have good reliability and validity for measuring QOL specific to patients with schizophrenia (Wilkinson et al., 2000; Kaneda et al., 2002). This scale yields measures on three subscales that address 1) dysfunction of psycho-social activity, 2) dysfunction of motivation and energy, and 3) level of symptoms and side-effects. This scale shows high sensitivity to both changes and treatment effects and moderate-to-high correlations with other measures

K. Fujimaki et al. / Psychiatry Research 197 (2012) 199–205 of QOL, and it has been shown to have substantial sensitivity to subtle changes and treatment effects. Each subscale score is transformed to have a range from 0 (the best status as measured on JSQLS) to 100 (the worst status as measured on JSQLS), with each scale calculated as follows: the scale score (SS) equals the total of raw scores of each item in the scale (RStot), divided by the maximum possible raw score of all the items in the scale (RSmax), all multiplied by 100: SS = (RStot / RSmax) × 100 (Wilkinson et al., 2000). 2.3. Statistical analysis The Pearson linear correlations between the JSQLS score and age, duration of illness, duration of hospitalization, BMI, cognitive dysfunction (HDS-R score, WFT score), drug-induced extra-pyramidal symptoms (DIEPSS score), abnormal involuntary movements (AIMS score), psychiatric symptoms (BPRS score), and dose equivalence of antipsychotics and anti-cholinergic agents were determined. A stepwise multiple regression analysis was conducted to determine the unique contributions of clinical variables to QOL (JSQLS score). Then, using clinical variables that showed significant correlations, stepwise multiple regression analysis was done to determine which clinical variables were the best predictors of QOL (JSQLS score). Each variable was entered into the multiple regression analysis if its F value was >4. A p value b 0.05 was considered significant. Statistical analyses were performed using SPSS 15.0 software (SPSS Inc., Chicago, IL).

3. Results The subjects' characteristics are shown in Table 1. All subjects were Japanese; 129 were male, and 88 were female. Overall, 292 patients were originally invited to participate, and 52 patients refused to participate simply because they refused to cooperate in research. The request for research cooperation was withdrawn due to a decrease in comprehension ability in 23 patients. 3.1. Correlation between JSQLS and age, duration of illness, and duration of hospitalization The participants' mean age was 55.1 ± 14.5 years; thus, most longstay patients were middle-aged or older. The mean duration of illness Table 1 Subjects' baseline characteristics. Characteristics

Mean values (standard deviation)

Participants, no. Age (years) Duration of illness (months) Duration of hospitalization (months) Years of education (years) BMI (score) Amount of medication [antipsychotics] (mg/day)a Amount of medication [typical antipsychotics] (mg/day)a Amount of medication [atypical antipsychotics] (mg/day)a Amount of medication [anticholinergic agent] (mg/day)b HDS-R total (score) WFT total (score) DIEPSS total (score) AIMS [1 to 7] (score) AIMS [8] (score) AIMS [9] (score) AIMS [10] (score) BPRS total (score) BPRS [positive symptoms] (score) BPRS [negative symptoms] (score) BPRS [psychological discomfort] (score) BPRS [resistance] (score) JSQLS [dysfunction of psycho-social activity] (score) JSQLS [dysfunction of motivation and energy] (score) JSQLS [level of symptoms and side effects] (score)

217 55.1 ± 14.5 413.4 ± 174.7 124.9 ± 72.3 10.94 ± 1.95 24.34 ± 17.26 797.96 ± 388.98 352.87 ± 140.18 545.09 ± 232.38 1.67 ± 0.73 21.99 ± 8.36 12.36 ± 9.20 4.53 ± 2.95 1.27 ± 0.59 0.35 ± 0.23 0.24 ± 0.18 0.11 ± 0.08 18.03 ± 8.71 7.54 ± 4.0 5.12 ± 2.71 5.35 ± 2.78 2.82 ± 1.14 30.48 ± 13.09 38.26 ± 12.28 25.50 ± 12.79

Data are presented as mean ± S.D. unless otherwise indicated. BMI, Body mass index; HDS-R, Revised Hasegawa's dementia scale; WFT, Word fluency test; DIEPSS, The Drug-Induced Extrapyramidal Symptoms Scale; AIMS, The Abnormal Involuntary Movement Scale; BPRS, Brief Psychiatry Rating Scale; JSQLS, the Schizophrenia Quality of Life Scale, a Japanese version. a Chlorpromazine equivalent (mg/day). b Biperiden equivalent (mg/day).

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and the mean duration of hospitalization were 413.4 ± 174.7 months and 124.9 ± 72.3 months, respectively. There was no correlation between the JSQLS scores and age, duration of illness, and duration of hospitalization (Table 2). 3.2. Correlation between JSQLS and years of education The participants' mean length of education was 10.94 ± 1.95 years. There was no correlation between the JSQLS scores and years of education (Table 2). 3.3. Correlation between JSQLS and body mass index The participants' mean BMI was 24.34 ± 17.26 kg/m 2. There was no correlation between the JSQLS scores and BMI (Table 2). 3.4. Correlation between JSQLS and amount of medication Correlations between the JSQLS scores and other clinical variables are shown in Table 2. The relationships between the amount of antipsychotic medication for each patient and the subscale scores for level of symptoms and side-effects on the JSQLS were examined. Anticholinergic agents were significantly correlated with the level of symptoms and side-effects on the JSQLS. No significant correlation was observed between the amount of antipsychotics and the subscale scores on the JSQLS. The amount of typical or atypical antipsychotics was not correlated with any subscale score on the JSQLS. 3.5. Correlation between JSQLS and neurocognitive function The relationships between each subscale score on the JSQLS and the HDS-R score and WFT score were examined. The HDS-R score was significantly negatively correlated with the dysfunction of psycho-social activity subscale score and the dysfunction of motivation and energy subscale score on the JSQLS (Table 2). No significant correlation was seen between the WFT score and any subscale score on the JSQLS. 3.6. Correlation between JSQLS and extrapyramidal symptoms/involuntary movements The relationships between each subscale score on the JSQLS and the DIEPSS score and AIMS score were examined. No significant correlation was observed between the DIEPSS score and any subscale score on the JSQLS (Table 2). A correlation was found between AIMS (1 to 7) and the dysfunction of psycho-social activity subscale score on the JSQLS. AIMS (8), (9), and (10) were not correlated with any subscale score on the JSQLS. 3.7. Correlation between JSQLS and psychiatric symptoms Scores of all subscales on the JSQLS were correlated with the negative symptoms subscale score on the BPRS (p b 0.01). Furthermore, significant correlations were found between the scores of all subscales on the JSQLS and the psychological discomfort subscale score and the resistance subscale score on the BPRS (Table 2). No significant correlations were observed between the positive symptoms subscale score on the BPRS and any subscale score on the JSQLS. 3.8. Stepwise regression analysis Table 3 shows the results of the stepwise regression analysis on the JSQLS. The dysfunction of psycho-social activity score and the dysfunction of motivation and energy score on the JSQLS were significantly predicted by the negative symptoms subscale score, the resistance subscale score, and the psychological discomfort subscale

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Table 2 Correlation coefficients between domains on the JSQLS and age, duration of illness, length of education, body mass index, amount of medication, neurocognitive function, druginduced extrapyramidal symptoms, involuntary movements, and psychiatric symptoms.

Age Duration of Illness Duration of hospitalization Years of education BMI Amount of medication (antipsychotics) Amount of medication (typical. antipsychotics) Amount of medication (atypical. antipsychotics) Amount of medication (anticholinergic agent) HDS-R total WFT total DIEPSS total AIMS (1 to 7) AIMS (8) AIMS (9) AIMS (10) BPRS total BPRS (positive symptoms) BPRS (negative symptoms) BPRS (psychological discomfort) BPRS (resistance)

JSQLS (dysfunction of psycho-social activity)

JSQLS (dysfunction of motivation and energy)

JSQLS (level of symptoms and side effects)

− 0.309† − 0.157 − 0.036 − 0.025 0.155 0.119 0.055 0.099 0.121 − 0.226† 0.140 0.092 0.190† 0.180 − 0.145 0.058 0.014 − 0.022 0.825† 0.759† 0.703†

− 0.113 − 0.094 0.005 − 0.102 0.101 0.103 0.032 0.103 0.130 − 0.226† 0.103 0.109 0.138 0.151 − 0.104 0.069 − 0.017 − 0.084 0.740† 0.666† 0.634†

− 0.132 − 0.159 0.019 − 0.028 0.127 0.076 0.012 0.088 0.228† 0.092 0.046 0.041 0.090 0.097 − 0.037 0.131 0.048 0.052 0.712† 0.824† 0.562†

See Table 1 for expansion of abbreviation. † p b 0.01.

score on the BPRS. The level of the symptoms and side-effect score on the JSQLS was significantly predicted by the psychological discomfort subscale score and the negative symptoms subscale score on the BPRS. The dysfunction of psycho-social activity subscale score on the JSQLS was also predicted by age, with a negative correlation between these items. Furthermore, the dysfunction of psycho-social activity subscale score was slightly predicted by HDS-R. 4. Discussion This study examined the relationship of both schizophrenia symptoms and neurocognitive function to QOL (Spaulding et al., 1986) using the JSQLS. Except for positive symptoms alone, symptoms and cognition had significant associations with scores on the subscales of the JSQLS; some symptoms had significantly stronger associations on some measures than others. Whether symptom severity would predict QOL, independently of neurocognition, was also examined in a multiple regression analysis. The present study included only chronically ill inpatients. In addition, the present study did not primarily involve observations of

outpatients residing in community settings. In Japan, the mental health care system remains predominantly hospital-based (Oshima et al., 2005). Japan has the greatest number of psychiatric beds in the world, and the hospitalization stay is approximately five-fold longer than that of other countries. In addition, >70% of psychiatric inpatients remain in a hospital for >1 year, and their QOL is reported to be very poor (Matsushita et al., 2004) (Ministry of Health, 2008b). It is worth noting that few systematic efforts at deinstitutionalization have been made in Japan (Oshima et al., 2002). Furthermore, many patients are hospitalized for a long period because there is no support for them after hospital discharge even if their symptoms are stabilized (Okada et al., 1996). In such circumstances, chronic schizophrenia inpatients participate actively in recreation and are treated with psychiatric occupational therapy (Nogi, 2008). Taking the environment around inpatients and the number of long-stay inpatients in Japan into consideration, we think that it is meaningful to examine the factors that predict the level of subjective QOL, understanding that inpatient wards are characterized by very restrictive environments (Oshima et al., 1996; Oshima et al., 2002). In other words, patients' abilities are made use of to the maximum in hospital where

Table 3 Stepwise regression for JSQLS. Dependent variable

Independent variable

Adjusted R2

β

JSQLS (dysfunction of psycho-social activity)

BPRS (negative symptoms) BPRS (resistance) BPRS (psychological discomfort) Age HDS-R total BPRS (negative symptoms) BPRS (resistance) BPRS (psychological discomfort) BPRS (psychological discomfort) BPRS (negative symptoms)

0.793⁎⁎

0.478⁎⁎ 0.235⁎⁎ 0.245⁎⁎ − 0.114⁎ − 0.077⁎ 0.466⁎⁎ 0.268⁎⁎ 0.162⁎ 0.644⁎⁎ 0.251⁎⁎

JSQLS (dysfunction of motivation and energy)

JSQLS (level of symptoms and side effects) ⁎P b 0.05. ⁎⁎P b 0.01.

0.623⁎⁎

0.706⁎⁎

K. Fujimaki et al. / Psychiatry Research 197 (2012) 199–205

they can be protected, and measuring a subjective QOL scale including the satisfaction rating in patients' life situation has meaning (Matsushita et al., 2004). In recent years, greater attention has been given to QOL in schizophrenia, and several symptoms have been reported to be related to patient QOL. Recent studies indicate that cognitive function has a greater impact on QOL in patients with schizophrenia than do positive symptoms (Green, 1996) (Breier et al., 1991). Therefore, particular attention was paid to the scores of HDS-R and WFT to explore the relationship between neurocognitive dysfunction and patient QOL. There was a significant negative correlation between the score on the HDS-R and the dysfunction of psycho-social activity subscale score and the dysfunction of motivation and energy subscale score on the JSQLS. However, there was no significant correlation between the score on WFT and each subscale score of the JSQLS. Some researchers have reported on clinical factors related to QOL. Dickerson et al. (1998) reported that patients' subjective QOL, as measured by the Quality of Life interview, was related to the depression factor on the Positive and Negative Syndrome Scale (PANSS). Huppert et al. (2001) reported that more severe depression, as rated on the BPRS, was associated with lower subjective QOL measured by the Quality of Life interview. In the present study, negative symptoms, psychological discomfort, and resistance, as rated on the BPRS, were correlated with all subscale scores of the JSQLS, and stepwise regression showed that negative symptoms, psychological discomfort, and resistance on the BPRS predicted the dysfunction of psycho-social activity subscale score and the dysfunction of motivation and energy subscale score on the JSQLS. The present results are consistent with those reported by Tomotake et al. (2006) and Aki et al. (2008) who assessed subscale scores with the Schizophrenia Quality of Life Scale (SQLS) and the scale of symptoms for schizophrenia, respectively. Considering the results of previous studies, as well as the present study, active treatment for negative symptoms of schizophrenia is recommended to improve patient QOL. In the current study, the relationship of drug-induced extrapyramidal symptoms to subscale scores of the JSQLS was also examined, and a stepwise regression analysis was performed to determine if the DIEPSS predicted subscale scores of the JSQLS. The influence of extrapyramidal adverse effects has already been documented. Ritsner et al. (2000) used the Montgomery-Asberg Depression Rating Scale (MADRS), the Talbieh Brief Distress Inventory (TBDI), the AIMS, and the Quality of Life Enjoyment and Satisfaction Questionnaire in schizophrenia patients and reported that the depression score on the TBDI and the score on the AIMS were predictors of poor QOL. The present results suggest that the DIEPSS total is not correlated with each subscale score of the JSQLS. However, AIMS scores influenced the dysfunction of psycho-social activity subscale score on the JSQLS. DIEPSS represents a general assessment of extrapyramidal symptoms. On the other hand, AIMS assesses dyskinesia, that is, a single drug-induced extrapyramidal symptom. The present results suggest that dyskinesia affects QOL of patients more than bradykinesia, sialorrhea, rigidity, and tremor, all of which are extrapyramidal symptoms. QOL is greatly influenced by psychopathology, dyskinesia, and patients' subjective tolerance of medications. Therefore, the psychiatrist should strive to minimize the side-effects of antipsychotic drugs. Awad et al. (1997a) used the PANSS, the Hillside Akathisia scale, and the Drug Attitude Inventory to show that subjective QOL is greatly influenced by psychopathology, akathisia, and patients' subjective tolerance of medications, and they concluded that efforts should be directed toward effective control of psychiatric symptoms and minimizing the side-effects of antipsychotic drugs to improve the QOL of patients with schizophrenia. The present study suggests that patients with drug-induced extrapyramidal symptoms that primarily include involuntary movements have subjective discomfort with respect to their symptoms and side-effects. In regard to the

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influence of typical or atypical antipsychotics on extrapyramidal symptoms, Crossley et al. (2010) reported that patients on typical antipsychotics experienced more extrapyramidal side effects than patients on atypical antipsychotics. Previous studies reported that atypical antipsychotics were perceived to be more effective and have fewer adverse effects than typical antipsychotics (Voruganti et al., 2000; Davis et al., 2003). Considering the results of previous studies, the influence of typical or atypical antipsychotics on QOL was examined. In addition, the amount of antipsychotics was significantly correlated with the amount of anticholinergic agents in the present study (data not shown). Therefore, we thought that the amount of antipsychotics would affect QOL. However, in the present study, the amount of typical or atypical antipsychotics was not correlated with any subscale scores on the JSQLS and did not predict QOL. The influence of atypical antipsychotics on QOL has been documented. Taniguchi et al. used the Quality of Life Scale (QLS), SQLS, BPRS, and DIEPSS to show that replacement of previous drugs, including both typical and atypical antipsychotics, with quetiapine improved patients' subjective and objective QOL, clinical symptoms, and extrapyramidal symptoms (Taniguchi et al., 2006). On the other hand, a randomized, controlled trial provided evidence that patients treated with typical antipsychotics showed an improvement in the QLS score and PANSS total and positive, negative, and general symptoms, and concluded that there is no disadvantage over 1 year in terms of QOL and symptoms in using typical antipsychotics rather than atypical antipsychotics (Jones et al., 2006). Further well-controlled studies are needed to elucidate the influence of antipsychotics on QOL. The present study suggests that negative symptoms predict all subscale scores of the JSQLS. On the other hand, positive symptoms were not significantly related to JSQLS. The influence of negative symptoms on objective QOL has already been documented. Fitzgerald et al. (2001)used QLS, PANSS, and MADRAS to show a significant positive relationship between all four QLS subscales and PANSS negative scores, but none of the QLS subscales was significantly related to PANSS positive scores or MADRAS scores. The present results are consistent with those reported by Fitzgerald et al. (2001), as well as reports by Tomotake et al. and Aki et al., who assessed objective QOL and negative symptoms using the QLS and BPRS, respectively (Tomotake et al., 2006) (Aki et al., 2008). Considering that QLS was originally designed to assess deficit symptoms and dysfunctions related to these symptoms (Heinrichs et al., 1984), the correlation between negative symptoms and JSQLS scores seems reasonable. Many studies have reported clinical variables with a strong association to objective QOL, whereas few studies have reported clinical variables with associations with subjective QOL. In the present study, JSQLS, a subjective QOL scale, was used. One reason for using it is that there is general agreement that chronic schizophrenia patients are able to evaluate their QOL themselves (Voruganti et al., 1998). Furthermore, Awad et al. (1997b) concluded that the following factors are important in choosing or developing a QOL measure for schizophrenia: QOL is a multidimensional concept that has to be reflected in its measurement; the scale has to be appropriate for the purpose as well as the population studied; and measurement has to include patients' self-reports about their QOL. Therefore, subjective QOL was evaluated in the present study. In the present study, whether symptom severity would predict QOL was also examined in the multiple regression analysis. Negative symptoms, resistance, and psychological discomfort on the BPRS together were the main contributors to the explained variance in the dysfunction of psycho-social activity on the JSQLS, whereas neurocognition contributed slightly. Greater attention has been given to the cognitive dimension in schizophrenia in recent years. Previous studies reported that verbal associative fluency tasks are sensitive to the presence of cerebral lesions (Pendleton et al., 1982), and that neurocognitive function, which is impaired in schizophrenia, is associated with the low WFT score measured as part of neurocognitive function (Laurent et al., 2000; Stip et al., 2003; Brazo et al., 2005). Furthermore, several studies

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indicated that cognitive function has a greater impact on QOL than positive symptoms in patients with schizophrenia (Breier et al., 1991; Ho et al., 1998; Green, 2007). In the present study, HDS-R, which represents measures of cognitive function, was negatively correlated with the dysfunction of psycho-social activity subscale score on the JSQLS, but stepwise regression showed that negative symptoms, resistance, and psychological discomfort on the BPRS, but not HDS-R, significantly predicted the dysfunction of psycho-social activity subscale score and the dysfunction of motivation and energy subscale score on the JSQLS. Karow et al. (2005) performed a longitudinal study and reported that only one subscale of five in the short form of the subjective Wellbeing under Neuroleptics Scale (SWN) correlated with the PANSS cognitive factor in the acute and mid-term phases, whereas the PANSS depression factor correlated with total scores of the SWN in the acute, mid-term, and long-term phases. These reports, including our own, suggest that cognitive dysfunction has little association with subjective QOL. In regard to the limitations of the clinical assessment of cognitive function in the present study, Keefe et al. (2004) suggested that clinical assessment of cognitive deficits on the Mini Mental Status Examination (MMSE) using the same items as the HDS-R is not a viable alternative to neuropsychological testing to obtain information about cognitive functioning in schizophrenia. Their findings limit the interpretation of the present results. To elucidate the influence of cognitive dysfunction on QOL, further studies using neuropsychological tests such as the Brief Assessment of Cognition in Schizophrenia (Hofer et al., 2006) are necessary. The strengths of this study are the large number of subjects and their random selection. However, this study should be interpreted with caution due to certain methodological limitations. First, the study was confined to clinically stable schizophrenia patients from one hospital. Its results may not be applicable to other parts of Japan and to schizophrenia patients with different clinical conditions. Second, since the study was cross-sectional, causality of relationships between QOL and clinical variables could not be explored. In conclusion, the relationship between clinical factors and QOL was examined in schizophrenia inpatients in the chronic phase with schizophrenia QOL measures. Consistent with past reports, the present results indicate that negative symptoms and psychological discomfort predict QOL. The present results also showed that resistance had an apparent influence on QOL. Active treatment for negative symptoms, psychological discomfort, and resistance might lead to improvement of QOL in inpatients with schizophrenia. Acknowledgments The authors wish to thank the staff of Mihara Hospital (Mihara, Japan) for their assistance with this study. References Aki, H., Tomotake, M., Kaneda, Y., Iga, J., Kinouchi, S., Shibuya-Tayoshi, S., Tayoshi, S.Y., Motoki, I., Moriguchi, K., Sumitani, S., Yamauchi, K., Taniguchi, T., Ishimoto, Y., Ueno, S., Ohmori, T., 2008. Subjective and objective quality of life, levels of life skills, and their clinical determinants in outpatients with schizophrenia. Psychiatry Research 158, 19–25. Allison, D.B., Mackell, J.A., McDonnell, D.D., 2003. The impact of weight gain on quality of life among persons with schizophrenia. Psychiatric Services 54, 565–567. Awad, A.G., Voruganti, L.N., Heslegrave, R.J., 1997a. A conceptual model of quality of life in schizophrenia: description and preliminary clinical validation. Quality of Life Research 6, 21–26. Awad, A.G., Voruganti, L.N., Heslegrave, R.J., 1997b. Measuring quality of life in patients with schizophrenia. PharmacoEconomics 11, 32–47. Bellack, A.S., Sayers, M., Mueser, K.T., Bennett, M., 1994. Evaluation of social problem solving in schizophrenia. Journal of Abnormal Psychology 103, 371–378. Brazo, P., Delamillieure, P., Morello, R., Halbecq, I., Marie, R.M., Dollfus, S., 2005. Impairments of executive/attentional functions in schizophrenia with primary and secondary negative symptoms. Psychiatry Research 133, 45–55. Breier, A., Schreiber, J.L., Dyer, J., Pickar, D., 1991. National Institute of Mental Health longitudinal study of chronic schizophrenia. Prognosis and predictors of outcome. Archives of General Psychiatry 48, 239–246.

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