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Long-term course of cognitive function in chronically hospitalized patients with schizophrenia transitioning to community-based living
Schizophrenia Research, 1-3, 155, pages 90 - 95
Schizophrenia is associated with impairments in social interactions, and the conditions under which patients live and undergo treatment appear to have an important role in the course of the disease. However, the influences of care settings on the course of cognition remain controversial. The closure of psychiatric hospitals and the transition to community-based living is a golden opportunity to address this issue. The aims of the present study were to examine (1) the longitudinal course of cognition as well as the psychopathology and social functioning of schizophrenia patients who had been chronically hospitalized and then discharged, and (2) the key cognitive predictors of the functional outcome of such patients. Seventy-eight patients were transferred to the community after the closure of a psychiatric hospital. These patients were followed-up for 5 years and underwent annual examinations that included measures of cognition, psychiatric symptoms, and social functioning. Fifty-six patients completed all the assessments. Although consistent improvements were shown in the cognitive domains for attention and memory, the initial improvements in global cognition and processing speed ultimately began to decline. Symptoms and global functioning improved almost consistently over the course of the follow-up period. Stepwise multiple regressions revealed category fluency at baseline predicted social functioning at 5 years. However, this correlation was no longer significant when psychopathological variables were included as predictors. These results suggest that care settings affect the course of cognition, and addressing these conditions may lead to a certain degree of cognitive improvement even among schizophrenia patients who have been chronically institutionalized.
Keywords: Cognition, Community, Deinstitutionalization, Psychiatric rehabilitation, Schizophrenia, Social functioning.
Schizophrenia is associated with impairments in day-to-day social interactions, and the conditions under which patients live and undergo treatment appear to have an important role in the course of the disease. Regarding the long-term course of cognitive function in patients with schizophrenia, the influences of care settings have been examined mainly by contrasting chronic inpatients and outpatients who are inevitably elderly, although cognition in patients with schizophrenia is thought to be stable over an individual's lifespan. Many of the longitudinal studies on cognition in patients with chronic schizophrenia have been performed by two research groups: one in New York, and the other in San Diego. The New York group has mainly examined cognition in chronically hospitalized patients with schizophrenia based on limited cognitive assessments; this group has demonstrated a cognitive decline after a few years of follow-up in these subjects (Harvey et al, 1999a, Harvey et al, 1999b, and McGurk et al, 2000). In contrast, the San Diego group has studied cognition in community-dwelling elderly patients using global screening or measures and has reported stable cognitive function over a follow-up period of a few years (Heaton et al, 2001, Palmer et al, 2003, and Nayak Savla et al, 2006).
It is difficult to interpret the results of studies in which inpatients and outpatients are directly compared because patients who have a better cognitive performance are more likely to be discharged, and cognitive deficits might serve as selection factors for long-term institutionalization, rather than long-term institutionalization being a cause of cognitive deficits ( Abrahamson, 1993 ). A previous study adopted a longitudinal comparison of the courses of outpatients with schizophrenia who varied in their history of institutionalization to address the question of the influences of care settings on cognitive function ( Harvey et al., 2010 ); however, this study was limited in that the duration during which the participants dwelled within and became adjusted to the community varied. One ideal study design would be a longitudinal comparison of cognitive performance in pairs of schizophrenic patients admitted at the same time and to the same institution, matched for most clinical and cognitive variables, with the exception that one group of patients was continuously institutionalized while the other group was immediately discharged and never or only briefly readmitted ( Davidson and Haroutunian, 1995 ). However, such studies are practically impossible. The closure of psychiatric hospitals and the transition to community-based living seems to be a golden opportunity to address this issue.
A trend toward deinstitutionalization, including the closure or downsizing of large psychiatric hospitals and the establishment of alternative community services, began in the 1950s ( Avison and Speechley, 1987 ), and psychiatric care in the community is common at present and is taken completely for granted by patients with schizophrenia, with comprehensive services having been advanced. A number of reports on the transition to community-based living have been published, and good psychopathology and functional outcomes generally appear to be associated with patients who have been discharged from psychiatric hospitals into the community with the support and care provided by service centers, whereas poor outcomes are associated with a continued inpatient status ( Davidson and Haroutunian, 1995 ).
The course of cognitive impairments in schizophrenia patients during their transition from psychiatric hospitals to the community remains obscure. Trieman et al. (1996) demonstrated that geriatric schizophrenic patients who were discharged from hospital, but not those who remained institutionalized, exhibited preserved levels of cognitive and living function during a 3-year follow-up period. This result could be interpreted as evidence that care settings are causally related to cognitive impairment; however, only one cognitive measure was administered.
The Sasagawa Project, the earliest large-scale project to enable a total transition from a psychiatric hospital to a residential facility in Japan, was established in Koriyama City, Fukushima (Mizuno et al, 2005 and Ryu et al, 2006). In this project, 78 chronic patients with schizophrenia were transferred to the community after the closure of a psychiatric hospital. Many of these patients were followed for 5 years and underwent annual examinations that included measures of cognitive function, psychiatric symptoms, and social functioning.
The aims of the present study were to examine (1) the longitudinal course of cognitive function as well as the psychopathology and social functioning of schizophrenia patients who had been chronically hospitalized and then discharged in relation to a change from inpatient to outpatient psychiatric care, and (2) the key cognitive predictors of the functional outcome of such patients.
In the Sasagawa Project, 78 Japanese patients with schizophrenia (51 men, 27 women) who had been chronically admitted at the Sasagawa Hospital made preparations to be discharged in 2001 and received psychosocial training for one year based on the Optimal Treatment Project (OTP; Falloon et al., 2004 ) for their transition to the community. Two trained psychiatrists independently diagnosed the participants using the ICD-10 criteria ( World Health Organization, 1993 ). The mean age of the patients was 54.6 years (SD = 7.2 years), the mean number of years of education was 10.4 years (SD = 1.8 years), the mean age of onset was 23.1 years (SD = 5.7 years), and the mean length of hospitalization was 25.6 years (SD = 10.2 years). All the patients were taking antipsychotic medications (708.3 mg/day chlorpromazine equivalent, SD = 503.2). The subjects had previously been excluded from the study if they had a history of alcohol dependence, substance abuse, or a neurological illness.
The patients were then discharged from the hospital and were transferred to a supported residential facility called the Sasagawa Village immediately after the closure of the hospital at the end of March 2002. Since that time, the patients gradually left the residential facility and completed their move into the neighboring community by 2007, where they now mainly live in group homes and several apartment houses. They attend various programs to enrich their lives including sports, cooking, playing musical instruments, and learning computer skills at a daycare center and a community care center. They also receive regular nursing care visits. Some of them began participating in a job-training program and then earned spending money. As the entrance hall at the residential facility was utilized as a meeting place where local people could get together and many events were held for the community, the patients could naturally keep in contact with people in the neighborhood. In this manner, they were able to resume their own lives and to enjoy a free way of life.
Our institutional review board approved the protocol of the present study. After providing the subjects with a complete description of the study, written informed consent was obtained from every subject. The entire assessment procedure for the Sasagawa Project ( Mizuno et al., 2005 ) and the 2-year outcomes with regard to psychopathology and social functioning ( Ryu et al., 2006 ) have been published elsewhere.
Measures of cognition included the Letter Cancellation Test (LCT, number of correct responses; Diller et al., 1974 ) as a measure of attention, the Digit Span (DS) of the WAIS-R (scores for forward and backward; Wechsler, 1981 ) as a measure of attention/working memory, the Rey–Osterrieth Complex Figure Test (ROCFT, scores for the immediate and delayed recall trial; Lezak et al., 2004 ) as a measure of memory, the Word Fluency Test (WFT, scores for letter and category fluency;Benton, 1968 and Nemoto et al, 2005) as a measure of executive function, the Trail Making Test Part A (TMTA, required time; Reitan, 1958 ) as a measure of processing speed, and the Mini-Mental State Examination (MMSE; Folstein et al., 1975 ) as a measure of global cognition.
The Positive and Negative Syndrome Scale (PANSS; positive symptoms, negative symptoms, and general psychopathology subscales; Kay et al., 1987 ) were used to assess psychiatric symptoms, and the Social Functioning Scale (SFS, total score;Birchwood et al, 1990 and Nemoto et al, 2008) was used to assess social functioning. In addition, the Global Assessment of Functioning (GAF; American Psychiatric Association, 1994 ) was used to measure global functioning (clinical and social combined). Clinical assessments and cognitive tests were administered at baseline and annually for 5 years.
2.3. Data analyses
All the statistical analyses were performed using PASW Statistics 18. A one-way repeated-measures analysis of variance (ANOVA) was used to examine each statistical change in the cognitive, psychopathological, and functional variables, and the Tukey HSD was used on a post-hoc basis. Stepwise multiple regressions were used to examine the predictability of cognition using two functional outcome measures (SFS and GAF). The cognitive domain consisted of the 9 variables described above.
Four patients were re-hospitalized chronically (for over 1 year) because of the exacerbation of their mental illnesses, and 3 patients were hospitalized because of physical illnesses during the follow-up period. Fifty-six patients (71.8%) among the 78 patients completed all the assessments and cognitive tests. The demographic characteristics of these patients at baseline were as follows: 38 men and 18 women; mean age, 54.6 years old (SD = 7.3 years); education, 10.5 years (SD = 2.0 years); the mean duration of illness, 31.5 years (SD = 8.7 years); length of hospitalization, 25.5 years (SD = 9.9 years); medication dose, 710.4 mg/day chlorpromazine equivalent (SD = 530.8).
3.2. Course of cognitive function
A one-way repeated-measures ANOVA test revealed significant differences in some repeated cognitive variables. Significant changes over 5 years were observed for the MMSE results (F = 2.824,df = 5, 275,P = 0.032), LCT (F = 6.775,df = 5, 275,P = 0.002), ROCFT immediate recall (F = 2.530,df = 5, 275,P = 0.040), ROCFT delayed recall (F = 16.728,df = 5, 275,P < 0.001), WFT letter fluency (F = 7.138,df = 5, 275,P < 0.001), WFT category fluency (F = 2.560,df = 5, 275,P = 0.042), and TMTA (F = 3.109,df = 5, 275,P = 0.020). The results are summarized in Table 1 . Data for the measures in which significant changes were demonstrated between baseline and each follow-up point using the Tukey HSD post-hoc test are graphically presented in Fig. 1 . Although consistent improvement was shown for the LCT and the ROCFT delayed recall, the initial improvement in the MMSE and TMTA began to decline within a few years.
|Baseline||1 year||2 years||3 years||4 years||5 years||ANOVA|
|Delayed recall||9.8||6.8||13.7||7.6||14.7||8.7||15.9||9.1||15.3||9.4||16.1||9.5||16.728||< 0.001|
|Letter fluency||15.8||8.1||17.9||8.6||18.7||9.5||20.5||11.2||19.5||10.2||18.7||10.3||7.138||< 0.001|
Note: ANOVA, Analysis of Variance; MMSE, Mini-Mental State Examination; LCT, Letter Cancellation Test; DS, Digit Span; ROCFT, Rey–Osterrieth Complex Figure Test; WFT, Word Fluency Test; TMTA, Trail Making Test Part A.
3.3. Course of psychiatric symptoms and social functioning
One-way repeated-measures ANOVA tests revealed significant differences in repeated clinical variables. Significant changes over 5 years were observed for positive symptoms (F = 8.134,df = 5, 275,P = 0.001), negative symptoms (F = 34.169,df = 5, 275,P < 0.001), and the general psychopathology subscales of the PANSS (F = 38.310,df = 5, 275,P < 0.001) and the GAF (F = 17.841,df = 5, 275,P < 0.001). The results are summarized in Table 2 . Data for the measures in which significant changes were demonstrated between baseline and each follow-up point using the Tukey HSD post-hoc test are graphically presented in Fig. 2 .
|Baseline||1 year||2 years||3 years||4 years||5 years||ANOVA|
|Negative symptoms||17.7||5.8||15.4||5.5||14.7||5.5||14.4||5.5||14.3||5.4||14.1||5.3||34.169||< 0.001|
|General psychopathology||26.8||6.0||24.6||5.6||22.8||5.1||22.3||4.9||22.5||4.8||22.2||4.9||38.310||< 0.001|
Note: ANOVA, Analysis of Variance; PANSS, Positive and Negative Syndrome Scale; SFS, Social Functioning Scale; GAF, Global Assessment of Functioning.
3.4. Predictor of 5-year functional outcome
A stepwise multiple regression analysis using cognitive variables at baseline and demographic variables (age and duration of illness) as independent variables was generated for each functional outcome variable at 5 years to identify predictors that were closely associated with the future functional outcome.
The model for the SFS was significant (F = 7.099,df = 1, 54,P = 0.010; adjustedR2 = 0.100), with the category fluency score identified as a statistically significant predictor (Beta = 0.341,P = 0.010). The model for the GAF was also significant (F = 9.189,df = 1, 54,P = 0.004; adjustedR2 = 0.130) and included the category fluency score as a significant predictor (Beta = 0.381,P = 0.004). These results indicated that a higher semantic fluency ability at baseline contributed to a higher level of social functioning at 5 years. As a second step, psychopathological variables (3 subscales of the PANSS) were also used as independent variables in addition to the cognitive and demographic variables. The model for the SFS was significant (F = 34.182,df = 1, 54,P < 0.001; adjustedR2 = 0.376), with the negative symptoms of the PANSS identified as a statistically significant predictor (Beta = − 0.623,P < 0.001). The model for the GAF was also significant (F = 11.649,df = 2, 53,P < 0.001; adjustedR2 = 0.279) and included both the positive symptoms (Beta = − 0.394,P = 0.002) and the negative symptoms (Beta = − 0.293,P = 0.017) as significant predictors. When including psychopathological variables as independent variables, the category fluency score was no longer a significant predictor of functional outcomes.
4.1. Course of cognitive function
The results suggested that even patients with schizophrenia who have been chronically hospitalized could show a certain degree of improvement in some cognitive deficits after dwelling within the community following their discharge from hospital, although the changes in the variables were relatively small. Cognitive deficits in patients with schizophrenia are generally considered to be relatively stable over long periods of time ( Rund, 1998 ). Heaton et al. (2001) described the stability of cognitive function over an average follow-up period of 3 years among community-dwelling subjects, while cognition has typically been shown to decline in institutionalized patients. Trieman et al. (1996) also reported a preserved cognitive function during a 3-year follow-up period in outpatients. A review described middle-aged and elderly institutionalized patients with schizophrenia as showing a decline in gross measures of cognitive function ( Kurtz, 2005 ). To the best of our knowledge, no previous report has demonstrated a change for the better in cognitive function after a transition to the community among chronically hospitalized patients with schizophrenia. Cross-sectional reports suggest that elderly patients with schizophrenia have mostly consistent impairments in executive function and verbal fluency, although impairments have less consistently been observed for memory, attention, and working memory ( Rajji and Mulsant, 2008 ). The present results suggest that even impairments in executive function and verbal fluency may be partly improved by transitioning chronically hospitalized patients to community-based living. Furthermore, as the participants in the present study continuously received well-planned comprehensive interventions based on the OTP (Mizuno et al, 2005 and Ryu et al, 2006), it is reasonable to think that appropriate community services, in addition to living in a community, might have also contributed to the improvements in cognition seen in the subjects. Compared with their previous passive lifestyles, in which the hospital staff made decisions regarding their daily life, the transitioned patients experienced a dramatic change to an active lifestyle, in which they were expected to solve their own problems and to make decisions by themselves.
Global cognition and processing speed improved for a few years and then began to decline thereafter, although the patients' symptoms and global functioning improved consistently. This change might represent a genuine decline, and aging might have also influenced this decline, since the mean age of the subjects was almost 60 years at the end of the follow-up period. Some longitudinal studies suggest that patients with late-life schizophrenia start to decline cognitively at around the age of 65 years ( Rajji and Mulsant, 2008 ), although this decline appears to be inconsistent with either normal aging or typical degenerative diseases ( Davidson and Haroutunian, 1995 ).
4.2. Course of psychiatric symptoms and social functioning
Psychiatric symptoms and global functioning almost consistently improved over the 5-year follow-up period. A former report of our project revealed that psychiatric symptoms and social functioning improved during a 2-year follow-up period ( Ryu et al., 2006 ). These findings are consistent with a previous study ( Furlan et al., 2009 ), although the findings of published research examining the long-term course of symptoms and functioning after deinstitutionalization have varied. A review examining the long-term outcome of schizophrenia concluded that psychopathological symptoms generally remain relatively stable over the course of the illness ( Lang et al., 2013 ). A large-scale prospective study on deinstitutionalization in London, the Team for the Assessment of Psychiatric Services (TAPS), described that social functioning improved but that psychiatric symptoms did not change (Trieman et al, 1996 and Leff and Trieman, 2000). Mancevski et al. (2007) reported that the lifetime course of chronically hospitalized patients with schizophrenia is characterized by a decrease in positive symptoms and an increase in negative symptoms. Dwelling in the community while receiving adequate care may lead to an amelioration of symptoms and social functioning.
4.3. Predictor of functional outcome in 5 years
Performance on the category fluency test at baseline was extracted as a predictor of social functioning at 5 years, as measured using the SFS and the GAF among cognitive and demographic variables. However, it was no longer a significant predictor of functional outcomes when psychopathological variables were included as independent variables. The category fluency score was significantly correlated with the PANSS scores. These results suggest that cognitive function partly contributes to the longitudinal prediction of functional outcome in chronic patients with schizophrenia who are transitioning to the community. However, not all aspects of cognitive impairments appear to have an equivalent significance regarding the functional outcome. Verbal fluency has been reported to be correlated with social functioning in patients with schizophrenia (Green et al, 2000 and Bowie et al, 2004). Depending on the task, category fluency demands a semantic search based on organization and logical associations within semantic networks, whereas letter fluency demands a lexical search based on phonology; patients with schizophrenia exhibit differential impairments in category fluency, compared with letter fluency ( Bokat and Goldberg, 2003 ). Such semantic fluency might contribute to functional outcomes that rely on producing solutions in social settings and navigating the complexities of social interactions to a greater degree than phonological fluency in patients with schizophrenia. We previously demonstrated that divergent thinking ability, as measured using fluency tests, contributed to community functioning in younger schizophrenic patients ( Nemoto et al., 2007 ). Divergent thinking ability also appeared to be vital to elderly patients dwelling in the community, and cognitive remediation focusing on this ability may be useful, as it was in our previous study ( Nemoto et al., 2009 ).
There are some limitations in the present study. It might have been preferable to set a control group for considering the practice effect of cognitive measures, although this did not seem practical. Furthermore, it is difficult to clarify which conditions are essential for optimizing cognitive and functional improvements following discharge because the participants dwelled in the community and several of them benefitted from various community services over a long period of 5 years. However, making sustained efforts to characterize cognitive impairments and their course might suggest clues to ameliorating impairments and the type of support that is most needed (Brier et al, 1991 and Wykes, 1994).
Various efforts, including biological and pharmacological approaches as well as psychosocial ones, have been made towards improving cognitive function, even in chronic patients ( Ehrenreich et al., 2007 ). The results of the present study suggest that care settings affect the course of cognitive function, and addressing these conditions may lead to a certain degree of cognitive improvement, even in schizophrenia patients who have been chronically institutionalized.
Role of funding source
The authors would like to state that there was no funding for this study.
Masafumi Mizuno designed the study and wrote the protocol. Kei Sakuma was involved at the conceptualization level of the project. Yonosuke Ryu collected the data. Takahiro Nemoto and Hidehito Niimura analyzed the data. Takahiro Nemoto wrote the first draft of this manuscript. All authors contributed to and have approved the final manuscript.
Conflict of interest
The authors have declared that there are no conflicts of interest in relation to the subject of this study.
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a Department of Neuropsychiatry, Toho University School of Medicine, Tokyo, Japan
b Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan
c Asaka Hospital, Koriyama, Fukushima, Japan
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