International Journal of Psychiatry in Clinical Practice, 2010; 14: 33–40
ORIGINAL ARTICLE
Cognitive function, social functioning and quality of life in first-episode psychosis: A 1-year longitudinal study RAFFAELE POPOLO1, GIANCARLO VINCI2 & ANDREA BALBI2
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1Terzo
Centro di Psicoterapia Cognitiva, Associazione di Psicologia Cognitiva (APC), Rome, Italy, Early Intervention in Psychosis Network, Rome, Italy
2Roma/D
Abstract Objective. The majority of patients with schizophrenia have cognitive deficits early in the disease. We evaluated the relationship between cognitive function, social functioning and quality of life in patients with first-episode psychosis. Methods. This was a longitudinal study in 15 patients aged 18–30 years who had recently experienced a first psychotic episode and were treated with the atypical antipsychotic aripiprazole, cognitive-behavioural therapy, psycho-educational sessions, family supportive sessions and social interventions. Patients were evaluated at baseline and after 1 year. Cognitive assessment included attention, memory, language skills and problem solving. Social functioning, quality of life, and psychopathological evaluation were performed with validated tools. Results. At baseline, patients had a severe impairment of social functioning and a low quality of life, while a specific pattern of cognitive functions was not identified. After 1-year, we observed a significant improvement in social functioning and quality of life, without a significant decrease in cognitive function. Conclusion. Contrary to previous findings, we found that social functioning and quality of life are related, but independent of cognitive impairment. The use of antipsychotic agents that do not interefere with cognitive function plus psychological assistance is a valuable treatment approach in patients with first-episode schizophrenia. Key Words: Cognition, cognition disorders, psychotic disorders, quality of life, social behaviour
Introduction It is generally accepted that cognitive deficit is present in the majority of patients with schizophrenia [1] and represents a core aspect of the schizophrenic illness. Global intellectual impairment has been observed in patients with schizophrenia [2,3], particularly in the domains of memory, attention, executive function, processing speed and social cognition [2,4–9]. In the last decade, there has been an increasing interest in cognitive alterations during the early course of the disease [10]. Neurocognitive deficits may be important in the pathogenesis of early psychosis [11], particularly attention deficits which could predict for developing psychosis [12]. Global impairment across the majority of cognitive domains has previously been observed prior to the onset of psychotic symptoms and the first psychotic episode [13–15]. The principal impairment may still be
modest in the initial phase of schizophrenia [10,14] and can affect memory, language, attention, and psychomotor processing [16–21]. Variation of cognitive deficit over time is still poorly defined, although it is accepted that the initial cognitive deficits remain stable over the first years [22]. A specific decline in visual memory and attention set-shifting has been reported [23], but it has also been shown that deficits in all cognitive domains except for verbal memory remain stable and may even improve during the first year [24]. The consequences of neurocognitive deficits for community functioning have been reviewed previously [25]. Deficits in attention, memory and executive functions can impair present and future social functioning [25,26]; this manifests as difficulty with instrumental and problem-solving skills, and may affect the efficacy of psychosocial rehabilitation programs [27,28]. Cognitive deficit reduces the patients’
Correspondance: Dr Raffaele Popolo, Terzo Centro di Psicoterapia Cognitiva, Via Ravenna 9/c, Rome, Italy. Tel/Fax: +39 6 44 23 38 78. E-mail: popolo.r@ libero.it (Received 8 May 2009; accepted 24 August 2009) ISSN 1365-1501 print/ISSN 1471-1788 online © 2010 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) DOI: 10.3109/13651500903282881
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ability to maintain successful employment [29], thus playing a central role in functional disability [25]. However, some authors contest that, although they are related, impairment of social functioning may be independent from cognitive deficits [13]. The correlation between cognitive impairment, quality of life and community functioning in firstepisode psychosis has not been fully investigated. The aim of our longitudinal study was primarily to examine the variation of cognitive function after 1 year in a sample of first-episode schizophrenic patients. Secondly, we sought to compare cognitive function with social functioning, and quality of life. We also evaluated the global psychopathological picture of each patient and compared it to the other variables; our purpose was to obtain a complete view of the disorder course and to exclude that relationships observed here were the products of other clinical variables not measured
Methods Patients The study included patients who had recently experienced a first psychotic episode, consecutively admitted for 6 months to the Roma/D Early Intervention in Psychosis Network, a public community service for persons aged 18–30 years living in an urban area of 500,000 inhabitants [30]. This study is part of a larger longitudinal research project, involving the entire Department of Mental Hygiene, conducted with the aim of evaluating the cognitive function of psychotic patients and its variation thorough time. These patients all had been given a timely diagnosis of a schizophrenia spectrum disorder (i.e., schizophrenic disorder, schizophreniform disorder, schizoaffective disorder, brief psychotic disorder, delusional disorder) [31]. Patients with possible causes of cognitive impairment other than schizophrenia were excluded from the study, as were patients with mental retardation, known systemic or neurological illness, affective disorder, drug abuse for more than 6 months, and epilepsy. All subjects participating in the study signed a written informed consent.
anxiolytic treatment were also administered where necessary. Assessment of cognitive measures Using a comprehensive battery of cognitive tests, we assessed cognition at baseline and 1-year follow-up; all patients completed the evaluations after being stabilised on medication for at least 6 weeks. Cognitive measures were chosen because of their widespread use in clinical practice. Neuropsychological testing was performed at baseline and 1 year by a researcher trained in the use of the scales. We assessed every patient using specific tests for each ability area: memory-verbal-encoding using the Rey auditory verbal learning test [32]; cognitive flexibility and problem solving ability using the Wisconsin Card Sorting Test (WCST) [33]; attention using the Span Selective Attention (SEL/AT) [34] and Spinnler attention matrices [35]; semantic-lexical memory storage recall and improvement capability using the Verbal Fluency Task (FAS) [36]; and logical deductive capabilities measurement under visuoperceptive stimuli using the Coloured Progressive Matrices (CPM) [37]. Psychopathological evaluation, social functioning and quality of life Psychopathological variables were measured using Brief Psychiatric Rating Scale (BPRS) [38] and Clinical Global Impression (CGI) [39] performed by an experienced psychiatrist at baseline and at the end of the observation period. Using BPRS we considered the average total score in order to evaluate the psychopathological severity of the disorders and the effectiveness of the treatments. In this study the aim was not to examine the correlation between the symptom constructs and the other variables. The evaluation of social functioning was performed by experienced psychiatrists at baseline and after 1 year using Health of the Nation Outcome Scale (HoNOS) [40] and Valutazione Globale Del Funzionamento (VGF) [41] scales. Quality of life was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [42].
Treatment
Statistical analyses
Patients received biopsychosocial treatment. All patients were treated with the atypical antipsychotic aripiprazole at a dosage of 10–30 mg/day, supplemented with cognitive-behavioural therapy (a mean of 20 sessions), psycho-educational sessions (12 sessions), family supportive sessions (six sessions per year), and social interventions. Mood stabilisers and
Clinical and neuropsychological characteristics were analyzed at baseline and after 1 year. Statistical analysis was performed using Microsoft Office Excel 2003. The main statistical parameters were calculated for each dimension evaluated (cognitive function, psychopathological aspects, social functioning and quality of life). In this way it was possible to quanti-
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Cognitive function in first-episode schizophrenia
tatively evaluate these parameters and monitor the variation thorough time. Statistical significance was evaluated by t-test analysis; Pearson’s correlation was used to examine correlations. The reliability of the t-test analysis (probability of detecting significant differences between the two samples) was determined. For the psychopathological variables (BPRS, CGI, VGF) the test is 99.99% reliable however, the reliability for the subscale of HoNOS is not acceptable for financial conditions (42% for environmental opportunities and relative relationships, up to 73% for social relationships, and up to 99% reliable for the others). In the Q-LES-Q scale the t-test is not reliable for the subscales of school activities only, while for the others it is 45% reliable for domestic activities, 65% occupation and activities, 99% for those remaining. Overall there were no differences between the two samples regarding cognitive function.
the mean ( SD) duration of school attendance was 12.2 2.9 years. Patient diagnosis in accordance with DSM-IV TR [41] was schizophrenia in 12 patients, brief psychotic disorder in two patients, and delusional disorder in one patient. In addition to aripirazole, six patients received a mood stabilizer (valproic acid 500–1000 mg/day in four patients and carbamazepine 400–800 mg/day in two patients) and 12 patients received anxiolytic treatment with lorazepam 2.5–7.5 mg/day, for various perioids during the study but not for the complete observation period.
Results Demographics Twelve of the 15 patients enrolled in this study were male, the mean (SD) age was 22.9 2.9 years, and the mean disease duration was 1.6 years. Seventy-three percent of patients had attended school for 10 years;
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Cognitive functioning Patients were seen to have impairments of cognitive function at trial entry (Figure 1). At baseline, almost half of the patients had some deficit in memory, attention and logical skills, while fewer patients had impairment of verbal fluency and executive function. The percentage of patients with cognitive deficits decreased during the 1-year study period in the domains of attention (46.7 vs. 33.3%), working memory (54.0 vs. 34.0%) and executive function (20.0 vs. 14.0%) (Figure 1). The percentage of patients with deficits in verbal fluency increased over the study period (33.3 vs. 40.0%) and cognitive function concerning long-term memory and logical abilities remained stable during the study period.
Figure 1. Percentage of patients with deficits in diffe rent cognitive function domains at baseline and 1 year. CPM, coloured progressive matrices.
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However, there were no statistically significant differences in any single cognitive function between baseline and 1 year. Examination of variation of cognitive function in each patient revealed different trends. Verbal fluency was associated with the highest incidence of worsening and the lowest incidence of improvement during the study period. Long-term memory and selective attention were associated with the most evident improvement; long-term memory was improved in 10 patients, whereas selective attention improved in nine subjects and worsened only in one, although this patient did not exhibit a deficit. Working memory and logical abilities improved in about half of the patients and remained stable in the remained. Executive functions were the most stable cognitive function and only varied only in three patients, in whom there was an improvement. Psychopathological evaluation, social functioning and quality of life Significant reductions from baseline in mean (SD) global BPRS (89.40 10.73 vs. 50.60 6.45; α 0.01, P 4.67 × 10–11) and CGI (5.00 0.99 vs. 2.13 0.82; α 0.01, P 5.37 × 10–10) scores were seen at 1-year follow-up. This improvement was associated with a global increase in quality of life. The evaluation of psychosocial and working function using the VGF scale shows a significant increase from baseline in the mean score at 1 year (39.6 13.54
vs. 68.8 9.15; α 0.01, P 2.54 10–9). The mean total HoNOS score was significantly decreased from baseline at 1 year (37.6 5.77 vs. 24.93 3.95; α 0.01, P 5.10 10–7) and improved in every patient. All sub-scales significantly improved at 1 year, with the exception of financial condition, which remained stable (Table I). Quality of life improved markedly during the first year (Table I). Mean values for all Q-LES-Q subscales significantly improved from baseline at 1-year except for school activities, which improved numerically but not significantly (Table I). No significant correlation between cognitive measures and the functional impairment sub-scale of HoNOS was seen. The comparison of cognitive functions and Q-LES-Q items did not show any significant correlation, except for the correlation between selective attention and “Health” (P 0.03) and “Emotions” (P 0.036) items at baseline, and between “General Activities” and “Attention” (P 0.033) as well as between long-term memory (P 0.001) and Logical Abilities (P 0.038) after 1 year. Discussion Mounting evidence suggests that compromised neurocognitive function is a central feature of schizophrenia [43]. Cognitive decline begins before the onset of the illness [44] and is often already present in the illness prodromal phase [23]. In a young
Table I. Change from baseline in mean values in the different Health of the Nation Outcome Scale (HoNOS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) subscales. Mean (SD) Baseline
Subscale HoNOS Total Relationships Social relations Activities of daily living Occupation and activities Living conditions Family load Environmental opportunities Q-Les-Q Health active Emotions Work Domestic activities School activities Pleisure activities Social actitivies General activities 1Stastically
significant when α = 0.01.
2Non-significant.
1 year
P value
37.60 2.47 3.13 3.07 3.20 2.07 3.40 2.60
(5.77) (0.83) (0.92) (0.59) (0.68) (0.80) (0.51) (0.83)
24.93 (3.95) 1.87 (0.52) 2.20 (0.68) 1.87 (0.52) 1.93 (0.80) 2.07 (0.70) 2.53 (0.64) 2.00 (0.53)
5.10 2.50 1.51 9.02 6.54 1(2) 1.40 7.04
× 10–7 (1) × 10–3 (1) × 10–4 (1) × 10–7 (1) × 10–6 (1)
24.47 24.47 4.60 8.80 10.07 40.73 26.87 26.73
(9.89) (12.66) (10.25) (9.58) (14.28) (17.40) (12.29) (13.07)
61.47 55.53 27.27 30.40 25.73 70.07 58.47 64.27
9.32 6.51 7.10 4.96 0.13 1.90 1.01 6.42
× 10–8 (1) × 10–7 (1) × 10–3 (1) × 10–3 (1)
(15.27) (14.91) (27.85) (32.76) (34.87) (11.20) (13.64) (12.61)
× 10–5 (1) × 10–3 (1)
(2)
× 10–7 (1) × 10–7 (1) × 10–7 (1)
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Cognitive function in first-episode schizophrenia
first-episode patient, particular attention should be paid to cognitive impairment when defining the therapeutic strategy as this may interfere with therapy and rehabilitation programs based on learning capabilities. This study provides comprehensive neuropsychological characterisation of patients at the first episode of illness. Measurement of cognitive function at baseline and at 1 year allows an evaluation of their variation over time and their association with clinical indicators and social functioning. Patients in this study showed impaired cognition at the early stages of a psychotic illness. Cognitive flexibility was the most preserved function, while memory and attention were the most impaired. Executive functions, measured by WCST categories, appear to be preserved in many patients. The neuropsychological profile observed in this study differs, at least in part, from the results obtained in similar studies in firstepisode patients in which memory was highly impaired, language function was relatively spared, and executive function emerged as a relative deficit [19,21,45]. The degree of impairment of the individual cognitive functions observed in our study at an early stage of disease appears to be lower than that observed in patients with a more chronic course of illness, confirming a previous study [16]. In fact, only memory, attention and logical abilities were impaired in a high number of patients (about 50% of the sample). The percentage of patients with deficits is lower for other functions. This study highlights the fact that a proportion of patients appear to remain neuropsychologically intact, while others have a diversified cognitive impairment. This may be attributed to the heterogeneity which characterises schizophrenia. It has been suggested that several patterns of neurocognitive dysfunction could contribute to the heterogeneity of the illness and its variable functional outcome [46]. Whether these patients are a specific subgroup with different characteristics or whether cognitive deficits do not reach a clinical threshold in some cases because of a higher cognitive compensation (“brain reserve”) is still unclear [47]. Whether these deficits reflect primitive functional impairment or are the result of the deteriorating course of the disease remains unclear. The cognitive deficit of our patients appears to be stabilised, except for cognitive flexibility which worsened. We observed a tendency towards improved cognitive function, but this did not reach statistical significance. These findings suggest that cognitive deficit remains constant over the first year of the disease and confirms other literature that shows little evidence of cognitive decline over time in schizophrenics patients [13,48].
Several studies have shown that neuropsychological function does not worsen and may even improve during treatment in first-episode groups [22,49,50]. While cognitive function was relatively stable, we observed a significant clinical improvement, as seen by a decrease in BPRS and CGI scores, in all patients after 1-year of treatment. An improvement was observed in both symptoms and psychosocial functioning, indicating an increase in the perceived quality of life. We did not observe any significant correlation between cognitive impairment and psychopathological dimension, a finding consistent with other groups [46–54]. The results of our study suggest that social functioning deficits and symptoms may be independent of cognitive impairment. The lack of neuropsychological correlation with symptoms and social functioning should be interpreted with caution. This finding might suggest that the pathophysiology underlying cognitive deficits may be distinct from the one causing some of the clinical features in schizophrenia [55]. This observation does not exclude a reciprocal interaction, thus contributing to the stabilisation of symptoms and limiting the development and enhancement of cognitive functions. The rapid and early improvement in clinical aspects can be attributed to the effect to the interventions on the different mental dimensions contributing to symptoms onset. The complex treatment allowed an intensive intervention on dimensions other than patients’ mental status, by modifying them and reducing their influence on symptoms, according to the vulnerability-stress model of psychosis [56]. Above all, it appears to have modified emotional factors, such as anxiety and depression, which seem to be important in schizophrenia, since they precede or follow the psychotic crisis [57]. The improvement observed in our patients during the first year of treatment may depend upon the interventions out patients received. However, we do believe that the stabilisation of these therapeutic targets requires an intervention targeting cognitive function and administered over a longer time period. Cognitive rehabilitation allows significant improvements in attention, memory, logical deductive abilities but not cognitive flexibility. To obtain the best results we should employ cognitive training at an early phase of the illness and when the WCST value is still normal. The choice of a pharmacological treatment, which plays a central role in the therapy of psychosis, should take these considerations into account and an agent that allows cognitive improvement should be used [58]. Current evidence supports the use of new antipsychotic drugs as they have a lower tendancy to impair cognitive functioning [59]. Studies in first-episode patients suggest a positive
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effect of these drugs on cognitive performance, but these findings should be interpreted with caution because of the small sample size [60,61]. Our study has several limitations which limit the interpretation of the results. The patient number is low and heterogeneous, and the study is monocentric; moreover it is an open trial without a control group. We can not exclude that the course of the observed variables could depend on other factors or could represent a natural evolution of those variables. The clinical practice shows that, for example, many patients can provide for cognitive deficits using strategies of personal coping to the difficulties happened; this will permit an improvement in the social functioning but it will be possible only if the patient will have the ability of supervising and controling his own cognitive functions [62]. Furthermore, the statistical analysis, based on the identification of correlations, does not allow the definition of cause–effect relationships between psychological dimensions. However, despite these limitations, we believe that our work offers interesting results emerging in real isitutional practice so to complete the results found in randomized clinical trials. The next target will be to verify the observed data in a larger sample and to involve other centres devoted to the study of early psychosis. In conclusion, we have shown that in our sample social functioning and quality of life are strictly related, but independent of cognitive impairment. These findings appear to be contrary to other findings in the literature that have demonstrated that cognition is significantly associated with social functioning [13,63,64]; but are not surely suggesting a complete lack of relationship between the two dimensions because the small number of patients. In the discussion about this issue, our findings can stimulate some reflections in order to better understand cognitive abnormalities and their influence on social functioning. Further research is required in this area, particularly in two promising research fields for the comprehension of psychosis. The first is the area of social cognition. Social cognition refers to how people think about themselves and others in the social world; it refers to the mental operations underlying social interactions, which involve the perception, interpretation and processing of social information [65–69]. It may be that cognitive impairment does exert an influence on social functioning via social cognition [27]. This interaction could be better understood starting from a primary domain of inquiry of the social cognition: the metacognitive functioning that is the abilities to think about thinking. Several studies have shown that different deficits in metacognition may be linked to different neurocognitive capacities [70]; cognitive and metacognitive disfunctions seem to sustain each other in the
manner of a vicious cycle [70]. It is possible that the impact of neurocognition on social functioning is mediated by metacognition. For istance, difficulties in flexibility in abstract thought as in memory make difficult distinguishing internal states and understanding properly other people’s intentionality [70]; in this way metacognitive disfunctions could make difficult any relationship and mastering problematic events, with the conseguent worsening of the quality of life [71]. The second area of future research would investigate the association between metacognition, quality of life, neurocognitions and symptoms [71]. Key points • Patients with schizophrenia exhibit cognitive impairment at an early stage in the disease. In this study we found that cognitive flexibility was the most preserved function and memory and attention the most impaired • The degree to which cognitive function is impaired in psychotic patients varies, with some patients remaining neurologically intact while others have diverse cognitive impairment. This may be a reflection of the hetergenous nature of schizophrenia • Cognitive impairment does not appear to decline during the course of schizophrenia but remains constant or may even improve • Symptoms, psychosocial functioning and quality of life are independent of cognitive function and may improve during the course of the disease • Cognitive rehabilitation is important in the treatment of schizophrenia and the use of antipsychotic agents that allow cognitive improvement is preferred Acknowledgements Wolters Kluwer Medical Communications provided medical writing assistance on behalf of Bristol-Myers Squibb. Dr A. Borriello elaborated the neurocognitive battery. This study was made possible by cooperation from Department of Mental Health of ASL Roma /D. Statement of interest None. References [1] Kelly C, Sharkey V, Morrison G, Allardyce J, McCreadie RG, et al. Nithsdale Schizophrenia Surveys. 20. Cognitive function in a catchment-area-based population of patients with schizophrenia. Br J Psychiatry 2000;177:348–53.
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[45] Saykin AJ, Shtasel DL, Gur RE, et al. Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Arch Gen Psychiatry 1994;51(2):124–31. [46] Heinrichs RW, Awad AG. Neurocognitive subtypes of chronic schizophrenia. Schizophr Res 1993;9(1):49–58. [47] Holthausen EA, Wiersma D, Sitskoorn MM, et al. Schizophrenic patients without neuropsychological deficits: Subgroup, disease severity or cognitive compensation? Psychiatry Res 2002;112(1):1–11. [48] Rund BR. A review of longitudinal studies of cognitive functions in schizophrenia patients. Schizophr Bull 1998;24(3): 425–35. [49] Gold S, Arndt S, Nopoulos P, et al. Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia. Am J Psychiatry 1999;156(9):1342–8. [50] Hoff AL, Sakuma M, Wieneke M, et al. Longitudinal neuropsychological follow-up study of patients with first-episode schizophrenia. Am J Psychiatry 1999;156(9):1336–41. [51] Addington J, Addington D. Neurocognitive and social functioning in schizophrenia: A 2.5 year follow-up study. Schizophr Res 2000;44(1):47–56. [52] Hughes C, Kumari V, Soni W, et al. Longitudinal study of symptoms and cognitive function in chronic schizophrenia. Schizophr Res 2003;59(2–3):137–46. [53] Keefe RS, Bilder RM, Harvey PD, et al. Baseline neurocognitive deficits in the CATIE schizophrenia trial. Neuropsychopharmacology 2006;31(9):2033–46. [54] Strauss ME. Relations of symptoms to cognitive deficits in schizophrenia. Schizophr Bull 1993;19(2):215–31. [55] Goldberg TE, Greenberg RD, Griffin SJ, et al. The effect of clozapine on cognition and psychiatric symptoms in patients with schizophrenia. Br J Psychiatry 1993;162:43–8. [56] Zubin J, Spring B. Vulnerability – a new view of schizophrenia. J Abnorm Psychol 1977;86(2):103–26. [57] Stefanis NC, Hanssen M, Smirnis NK, et al. Evidence that three dimensions of psychosis have a distribution in the general population. Psychol Med 2002;32(2):347–58. [58] Buchanan RW, Davis M, Goff D, et al. A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull 2005;31(1):5–19.
[59] Keefe RS, Silva SG, Perkins DO, et al. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: A review and meta-analysis. Schizophr Bull 1999; 25(2):201–22. [60] Good KP, Kiss I, Buiteman C, et al. Improvement in cognitive functioning in patients with first-episode psychosis during treatment with quetiapine: An interim analysis. Br J Psychiatry 2002;43(Suppl):s45–9. [61] Keefe RS, Seidman LJ, Christensen BK, et al. Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: A randomized, double-blind trial of olanzapine versus low doses of haloperidol. Am J Psychiatry 2004;161(6):985–95. [62] Stratta P, Bustini M, Daneluzzo E, et al. La valutazione della capacità metacognitiva nel disturbo schizofrenico: Dalla funzione cognitiva al mondo reale. G Ital Psicopatol 2008; 14:75–79. [63] Penn DL, Corrigan PW, Bentall RP, et al. Social cognition in schizophrenia. Psychol Bull 1997;121(1):114–32. [64] Pinkham AE, Penn DL, Perkins DO, et al. Implications for the neural basis of social cognition for the study of schizophrenia. Am J Psychiatry 2003;160(5):815–24. [65] Brothers L. The neural basis of primate social communication. Motiv Emotion 1990;14:81–91. [66] Fiske ST, Taylor SE. Social cognition. 2nd ed. New York: McGraw-Hill Book Co.; 1991. [67] Kunda Z. Social cognition: Making sense of people. Cambridge, MA: MIT Press; 1999. [68] Green MF, Olivier B, Crawley JN, et al. Social cognition in schizophrenia: recommendations from the measurement and treatment research to improve cognition in schizophrenia new approaches conference. Schizophr Bull 2005;31(4):882–87. [69] Penn DL, Sanna LJ, Roberts DL. Social cognition in schizophrenia: An overview. Schizophr Bull 2008;34(3):408–11. [70] Lysaker PH, Dimaggio G, Buck KD et al. Metacognition within narratives of schizophrenia: Associations with multiple domains of neurocognition. Schizophr Res 2007;93:278–87. [71] Lysaker PH, Carcione A, Dimaggio G, et al. Metacognition amidst narratives of self and illness in schizophrenia: Associations with neurocognition, symptoms, insight and quality of life. Acta Psychiatr Scand 2005;112(1):64–71.
ORIGINAL ARTICLE
Cognitive function, social functioning and quality of life in first-episode psychosis: A 1-year longitudinal study RAFFAELE POPOLO1, GIANCARLO VINCI2 & ANDREA BALBI2
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1Terzo
Centro di Psicoterapia Cognitiva, Associazione di Psicologia Cognitiva (APC), Rome, Italy, Early Intervention in Psychosis Network, Rome, Italy
2Roma/D
Abstract Objective. The majority of patients with schizophrenia have cognitive deficits early in the disease. We evaluated the relationship between cognitive function, social functioning and quality of life in patients with first-episode psychosis. Methods. This was a longitudinal study in 15 patients aged 18–30 years who had recently experienced a first psychotic episode and were treated with the atypical antipsychotic aripiprazole, cognitive-behavioural therapy, psycho-educational sessions, family supportive sessions and social interventions. Patients were evaluated at baseline and after 1 year. Cognitive assessment included attention, memory, language skills and problem solving. Social functioning, quality of life, and psychopathological evaluation were performed with validated tools. Results. At baseline, patients had a severe impairment of social functioning and a low quality of life, while a specific pattern of cognitive functions was not identified. After 1-year, we observed a significant improvement in social functioning and quality of life, without a significant decrease in cognitive function. Conclusion. Contrary to previous findings, we found that social functioning and quality of life are related, but independent of cognitive impairment. The use of antipsychotic agents that do not interefere with cognitive function plus psychological assistance is a valuable treatment approach in patients with first-episode schizophrenia. Key Words: Cognition, cognition disorders, psychotic disorders, quality of life, social behaviour
Introduction It is generally accepted that cognitive deficit is present in the majority of patients with schizophrenia [1] and represents a core aspect of the schizophrenic illness. Global intellectual impairment has been observed in patients with schizophrenia [2,3], particularly in the domains of memory, attention, executive function, processing speed and social cognition [2,4–9]. In the last decade, there has been an increasing interest in cognitive alterations during the early course of the disease [10]. Neurocognitive deficits may be important in the pathogenesis of early psychosis [11], particularly attention deficits which could predict for developing psychosis [12]. Global impairment across the majority of cognitive domains has previously been observed prior to the onset of psychotic symptoms and the first psychotic episode [13–15]. The principal impairment may still be
modest in the initial phase of schizophrenia [10,14] and can affect memory, language, attention, and psychomotor processing [16–21]. Variation of cognitive deficit over time is still poorly defined, although it is accepted that the initial cognitive deficits remain stable over the first years [22]. A specific decline in visual memory and attention set-shifting has been reported [23], but it has also been shown that deficits in all cognitive domains except for verbal memory remain stable and may even improve during the first year [24]. The consequences of neurocognitive deficits for community functioning have been reviewed previously [25]. Deficits in attention, memory and executive functions can impair present and future social functioning [25,26]; this manifests as difficulty with instrumental and problem-solving skills, and may affect the efficacy of psychosocial rehabilitation programs [27,28]. Cognitive deficit reduces the patients’
Correspondance: Dr Raffaele Popolo, Terzo Centro di Psicoterapia Cognitiva, Via Ravenna 9/c, Rome, Italy. Tel/Fax: +39 6 44 23 38 78. E-mail: popolo.r@ libero.it (Received 8 May 2009; accepted 24 August 2009) ISSN 1365-1501 print/ISSN 1471-1788 online © 2010 Informa UK Ltd. (Informa Healthcare, Taylor & Francis AS) DOI: 10.3109/13651500903282881
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ability to maintain successful employment [29], thus playing a central role in functional disability [25]. However, some authors contest that, although they are related, impairment of social functioning may be independent from cognitive deficits [13]. The correlation between cognitive impairment, quality of life and community functioning in firstepisode psychosis has not been fully investigated. The aim of our longitudinal study was primarily to examine the variation of cognitive function after 1 year in a sample of first-episode schizophrenic patients. Secondly, we sought to compare cognitive function with social functioning, and quality of life. We also evaluated the global psychopathological picture of each patient and compared it to the other variables; our purpose was to obtain a complete view of the disorder course and to exclude that relationships observed here were the products of other clinical variables not measured
Methods Patients The study included patients who had recently experienced a first psychotic episode, consecutively admitted for 6 months to the Roma/D Early Intervention in Psychosis Network, a public community service for persons aged 18–30 years living in an urban area of 500,000 inhabitants [30]. This study is part of a larger longitudinal research project, involving the entire Department of Mental Hygiene, conducted with the aim of evaluating the cognitive function of psychotic patients and its variation thorough time. These patients all had been given a timely diagnosis of a schizophrenia spectrum disorder (i.e., schizophrenic disorder, schizophreniform disorder, schizoaffective disorder, brief psychotic disorder, delusional disorder) [31]. Patients with possible causes of cognitive impairment other than schizophrenia were excluded from the study, as were patients with mental retardation, known systemic or neurological illness, affective disorder, drug abuse for more than 6 months, and epilepsy. All subjects participating in the study signed a written informed consent.
anxiolytic treatment were also administered where necessary. Assessment of cognitive measures Using a comprehensive battery of cognitive tests, we assessed cognition at baseline and 1-year follow-up; all patients completed the evaluations after being stabilised on medication for at least 6 weeks. Cognitive measures were chosen because of their widespread use in clinical practice. Neuropsychological testing was performed at baseline and 1 year by a researcher trained in the use of the scales. We assessed every patient using specific tests for each ability area: memory-verbal-encoding using the Rey auditory verbal learning test [32]; cognitive flexibility and problem solving ability using the Wisconsin Card Sorting Test (WCST) [33]; attention using the Span Selective Attention (SEL/AT) [34] and Spinnler attention matrices [35]; semantic-lexical memory storage recall and improvement capability using the Verbal Fluency Task (FAS) [36]; and logical deductive capabilities measurement under visuoperceptive stimuli using the Coloured Progressive Matrices (CPM) [37]. Psychopathological evaluation, social functioning and quality of life Psychopathological variables were measured using Brief Psychiatric Rating Scale (BPRS) [38] and Clinical Global Impression (CGI) [39] performed by an experienced psychiatrist at baseline and at the end of the observation period. Using BPRS we considered the average total score in order to evaluate the psychopathological severity of the disorders and the effectiveness of the treatments. In this study the aim was not to examine the correlation between the symptom constructs and the other variables. The evaluation of social functioning was performed by experienced psychiatrists at baseline and after 1 year using Health of the Nation Outcome Scale (HoNOS) [40] and Valutazione Globale Del Funzionamento (VGF) [41] scales. Quality of life was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) [42].
Treatment
Statistical analyses
Patients received biopsychosocial treatment. All patients were treated with the atypical antipsychotic aripiprazole at a dosage of 10–30 mg/day, supplemented with cognitive-behavioural therapy (a mean of 20 sessions), psycho-educational sessions (12 sessions), family supportive sessions (six sessions per year), and social interventions. Mood stabilisers and
Clinical and neuropsychological characteristics were analyzed at baseline and after 1 year. Statistical analysis was performed using Microsoft Office Excel 2003. The main statistical parameters were calculated for each dimension evaluated (cognitive function, psychopathological aspects, social functioning and quality of life). In this way it was possible to quanti-
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Cognitive function in first-episode schizophrenia
tatively evaluate these parameters and monitor the variation thorough time. Statistical significance was evaluated by t-test analysis; Pearson’s correlation was used to examine correlations. The reliability of the t-test analysis (probability of detecting significant differences between the two samples) was determined. For the psychopathological variables (BPRS, CGI, VGF) the test is 99.99% reliable however, the reliability for the subscale of HoNOS is not acceptable for financial conditions (42% for environmental opportunities and relative relationships, up to 73% for social relationships, and up to 99% reliable for the others). In the Q-LES-Q scale the t-test is not reliable for the subscales of school activities only, while for the others it is 45% reliable for domestic activities, 65% occupation and activities, 99% for those remaining. Overall there were no differences between the two samples regarding cognitive function.
the mean ( SD) duration of school attendance was 12.2 2.9 years. Patient diagnosis in accordance with DSM-IV TR [41] was schizophrenia in 12 patients, brief psychotic disorder in two patients, and delusional disorder in one patient. In addition to aripirazole, six patients received a mood stabilizer (valproic acid 500–1000 mg/day in four patients and carbamazepine 400–800 mg/day in two patients) and 12 patients received anxiolytic treatment with lorazepam 2.5–7.5 mg/day, for various perioids during the study but not for the complete observation period.
Results Demographics Twelve of the 15 patients enrolled in this study were male, the mean (SD) age was 22.9 2.9 years, and the mean disease duration was 1.6 years. Seventy-three percent of patients had attended school for 10 years;
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Cognitive functioning Patients were seen to have impairments of cognitive function at trial entry (Figure 1). At baseline, almost half of the patients had some deficit in memory, attention and logical skills, while fewer patients had impairment of verbal fluency and executive function. The percentage of patients with cognitive deficits decreased during the 1-year study period in the domains of attention (46.7 vs. 33.3%), working memory (54.0 vs. 34.0%) and executive function (20.0 vs. 14.0%) (Figure 1). The percentage of patients with deficits in verbal fluency increased over the study period (33.3 vs. 40.0%) and cognitive function concerning long-term memory and logical abilities remained stable during the study period.
Figure 1. Percentage of patients with deficits in diffe rent cognitive function domains at baseline and 1 year. CPM, coloured progressive matrices.
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However, there were no statistically significant differences in any single cognitive function between baseline and 1 year. Examination of variation of cognitive function in each patient revealed different trends. Verbal fluency was associated with the highest incidence of worsening and the lowest incidence of improvement during the study period. Long-term memory and selective attention were associated with the most evident improvement; long-term memory was improved in 10 patients, whereas selective attention improved in nine subjects and worsened only in one, although this patient did not exhibit a deficit. Working memory and logical abilities improved in about half of the patients and remained stable in the remained. Executive functions were the most stable cognitive function and only varied only in three patients, in whom there was an improvement. Psychopathological evaluation, social functioning and quality of life Significant reductions from baseline in mean (SD) global BPRS (89.40 10.73 vs. 50.60 6.45; α 0.01, P 4.67 × 10–11) and CGI (5.00 0.99 vs. 2.13 0.82; α 0.01, P 5.37 × 10–10) scores were seen at 1-year follow-up. This improvement was associated with a global increase in quality of life. The evaluation of psychosocial and working function using the VGF scale shows a significant increase from baseline in the mean score at 1 year (39.6 13.54
vs. 68.8 9.15; α 0.01, P 2.54 10–9). The mean total HoNOS score was significantly decreased from baseline at 1 year (37.6 5.77 vs. 24.93 3.95; α 0.01, P 5.10 10–7) and improved in every patient. All sub-scales significantly improved at 1 year, with the exception of financial condition, which remained stable (Table I). Quality of life improved markedly during the first year (Table I). Mean values for all Q-LES-Q subscales significantly improved from baseline at 1-year except for school activities, which improved numerically but not significantly (Table I). No significant correlation between cognitive measures and the functional impairment sub-scale of HoNOS was seen. The comparison of cognitive functions and Q-LES-Q items did not show any significant correlation, except for the correlation between selective attention and “Health” (P 0.03) and “Emotions” (P 0.036) items at baseline, and between “General Activities” and “Attention” (P 0.033) as well as between long-term memory (P 0.001) and Logical Abilities (P 0.038) after 1 year. Discussion Mounting evidence suggests that compromised neurocognitive function is a central feature of schizophrenia [43]. Cognitive decline begins before the onset of the illness [44] and is often already present in the illness prodromal phase [23]. In a young
Table I. Change from baseline in mean values in the different Health of the Nation Outcome Scale (HoNOS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) subscales. Mean (SD) Baseline
Subscale HoNOS Total Relationships Social relations Activities of daily living Occupation and activities Living conditions Family load Environmental opportunities Q-Les-Q Health active Emotions Work Domestic activities School activities Pleisure activities Social actitivies General activities 1Stastically
significant when α = 0.01.
2Non-significant.
1 year
P value
37.60 2.47 3.13 3.07 3.20 2.07 3.40 2.60
(5.77) (0.83) (0.92) (0.59) (0.68) (0.80) (0.51) (0.83)
24.93 (3.95) 1.87 (0.52) 2.20 (0.68) 1.87 (0.52) 1.93 (0.80) 2.07 (0.70) 2.53 (0.64) 2.00 (0.53)
5.10 2.50 1.51 9.02 6.54 1(2) 1.40 7.04
× 10–7 (1) × 10–3 (1) × 10–4 (1) × 10–7 (1) × 10–6 (1)
24.47 24.47 4.60 8.80 10.07 40.73 26.87 26.73
(9.89) (12.66) (10.25) (9.58) (14.28) (17.40) (12.29) (13.07)
61.47 55.53 27.27 30.40 25.73 70.07 58.47 64.27
9.32 6.51 7.10 4.96 0.13 1.90 1.01 6.42
× 10–8 (1) × 10–7 (1) × 10–3 (1) × 10–3 (1)
(15.27) (14.91) (27.85) (32.76) (34.87) (11.20) (13.64) (12.61)
× 10–5 (1) × 10–3 (1)
(2)
× 10–7 (1) × 10–7 (1) × 10–7 (1)
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Cognitive function in first-episode schizophrenia
first-episode patient, particular attention should be paid to cognitive impairment when defining the therapeutic strategy as this may interfere with therapy and rehabilitation programs based on learning capabilities. This study provides comprehensive neuropsychological characterisation of patients at the first episode of illness. Measurement of cognitive function at baseline and at 1 year allows an evaluation of their variation over time and their association with clinical indicators and social functioning. Patients in this study showed impaired cognition at the early stages of a psychotic illness. Cognitive flexibility was the most preserved function, while memory and attention were the most impaired. Executive functions, measured by WCST categories, appear to be preserved in many patients. The neuropsychological profile observed in this study differs, at least in part, from the results obtained in similar studies in firstepisode patients in which memory was highly impaired, language function was relatively spared, and executive function emerged as a relative deficit [19,21,45]. The degree of impairment of the individual cognitive functions observed in our study at an early stage of disease appears to be lower than that observed in patients with a more chronic course of illness, confirming a previous study [16]. In fact, only memory, attention and logical abilities were impaired in a high number of patients (about 50% of the sample). The percentage of patients with deficits is lower for other functions. This study highlights the fact that a proportion of patients appear to remain neuropsychologically intact, while others have a diversified cognitive impairment. This may be attributed to the heterogeneity which characterises schizophrenia. It has been suggested that several patterns of neurocognitive dysfunction could contribute to the heterogeneity of the illness and its variable functional outcome [46]. Whether these patients are a specific subgroup with different characteristics or whether cognitive deficits do not reach a clinical threshold in some cases because of a higher cognitive compensation (“brain reserve”) is still unclear [47]. Whether these deficits reflect primitive functional impairment or are the result of the deteriorating course of the disease remains unclear. The cognitive deficit of our patients appears to be stabilised, except for cognitive flexibility which worsened. We observed a tendency towards improved cognitive function, but this did not reach statistical significance. These findings suggest that cognitive deficit remains constant over the first year of the disease and confirms other literature that shows little evidence of cognitive decline over time in schizophrenics patients [13,48].
Several studies have shown that neuropsychological function does not worsen and may even improve during treatment in first-episode groups [22,49,50]. While cognitive function was relatively stable, we observed a significant clinical improvement, as seen by a decrease in BPRS and CGI scores, in all patients after 1-year of treatment. An improvement was observed in both symptoms and psychosocial functioning, indicating an increase in the perceived quality of life. We did not observe any significant correlation between cognitive impairment and psychopathological dimension, a finding consistent with other groups [46–54]. The results of our study suggest that social functioning deficits and symptoms may be independent of cognitive impairment. The lack of neuropsychological correlation with symptoms and social functioning should be interpreted with caution. This finding might suggest that the pathophysiology underlying cognitive deficits may be distinct from the one causing some of the clinical features in schizophrenia [55]. This observation does not exclude a reciprocal interaction, thus contributing to the stabilisation of symptoms and limiting the development and enhancement of cognitive functions. The rapid and early improvement in clinical aspects can be attributed to the effect to the interventions on the different mental dimensions contributing to symptoms onset. The complex treatment allowed an intensive intervention on dimensions other than patients’ mental status, by modifying them and reducing their influence on symptoms, according to the vulnerability-stress model of psychosis [56]. Above all, it appears to have modified emotional factors, such as anxiety and depression, which seem to be important in schizophrenia, since they precede or follow the psychotic crisis [57]. The improvement observed in our patients during the first year of treatment may depend upon the interventions out patients received. However, we do believe that the stabilisation of these therapeutic targets requires an intervention targeting cognitive function and administered over a longer time period. Cognitive rehabilitation allows significant improvements in attention, memory, logical deductive abilities but not cognitive flexibility. To obtain the best results we should employ cognitive training at an early phase of the illness and when the WCST value is still normal. The choice of a pharmacological treatment, which plays a central role in the therapy of psychosis, should take these considerations into account and an agent that allows cognitive improvement should be used [58]. Current evidence supports the use of new antipsychotic drugs as they have a lower tendancy to impair cognitive functioning [59]. Studies in first-episode patients suggest a positive
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effect of these drugs on cognitive performance, but these findings should be interpreted with caution because of the small sample size [60,61]. Our study has several limitations which limit the interpretation of the results. The patient number is low and heterogeneous, and the study is monocentric; moreover it is an open trial without a control group. We can not exclude that the course of the observed variables could depend on other factors or could represent a natural evolution of those variables. The clinical practice shows that, for example, many patients can provide for cognitive deficits using strategies of personal coping to the difficulties happened; this will permit an improvement in the social functioning but it will be possible only if the patient will have the ability of supervising and controling his own cognitive functions [62]. Furthermore, the statistical analysis, based on the identification of correlations, does not allow the definition of cause–effect relationships between psychological dimensions. However, despite these limitations, we believe that our work offers interesting results emerging in real isitutional practice so to complete the results found in randomized clinical trials. The next target will be to verify the observed data in a larger sample and to involve other centres devoted to the study of early psychosis. In conclusion, we have shown that in our sample social functioning and quality of life are strictly related, but independent of cognitive impairment. These findings appear to be contrary to other findings in the literature that have demonstrated that cognition is significantly associated with social functioning [13,63,64]; but are not surely suggesting a complete lack of relationship between the two dimensions because the small number of patients. In the discussion about this issue, our findings can stimulate some reflections in order to better understand cognitive abnormalities and their influence on social functioning. Further research is required in this area, particularly in two promising research fields for the comprehension of psychosis. The first is the area of social cognition. Social cognition refers to how people think about themselves and others in the social world; it refers to the mental operations underlying social interactions, which involve the perception, interpretation and processing of social information [65–69]. It may be that cognitive impairment does exert an influence on social functioning via social cognition [27]. This interaction could be better understood starting from a primary domain of inquiry of the social cognition: the metacognitive functioning that is the abilities to think about thinking. Several studies have shown that different deficits in metacognition may be linked to different neurocognitive capacities [70]; cognitive and metacognitive disfunctions seem to sustain each other in the
manner of a vicious cycle [70]. It is possible that the impact of neurocognition on social functioning is mediated by metacognition. For istance, difficulties in flexibility in abstract thought as in memory make difficult distinguishing internal states and understanding properly other people’s intentionality [70]; in this way metacognitive disfunctions could make difficult any relationship and mastering problematic events, with the conseguent worsening of the quality of life [71]. The second area of future research would investigate the association between metacognition, quality of life, neurocognitions and symptoms [71]. Key points • Patients with schizophrenia exhibit cognitive impairment at an early stage in the disease. In this study we found that cognitive flexibility was the most preserved function and memory and attention the most impaired • The degree to which cognitive function is impaired in psychotic patients varies, with some patients remaining neurologically intact while others have diverse cognitive impairment. This may be a reflection of the hetergenous nature of schizophrenia • Cognitive impairment does not appear to decline during the course of schizophrenia but remains constant or may even improve • Symptoms, psychosocial functioning and quality of life are independent of cognitive function and may improve during the course of the disease • Cognitive rehabilitation is important in the treatment of schizophrenia and the use of antipsychotic agents that allow cognitive improvement is preferred Acknowledgements Wolters Kluwer Medical Communications provided medical writing assistance on behalf of Bristol-Myers Squibb. Dr A. Borriello elaborated the neurocognitive battery. This study was made possible by cooperation from Department of Mental Health of ASL Roma /D. Statement of interest None. References [1] Kelly C, Sharkey V, Morrison G, Allardyce J, McCreadie RG, et al. Nithsdale Schizophrenia Surveys. 20. Cognitive function in a catchment-area-based population of patients with schizophrenia. Br J Psychiatry 2000;177:348–53.
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Cognitive function in first-episode schizophrenia
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