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Neurocognitive functioning and facial affect recognition in treatment-resistant schizophrenia treated with clozapine
Schizophrenia Research 106 (2008) 371–372
Contents lists available at ScienceDirect
Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s
Letter to the Editors Neurocognitive functioning and facial affect recognition in treatment-resistant schizophrenia treated with clozapine
Dear Editors, Along with the negative and positive syndromes, cognitive deterioration is a core feature of schizophrenia, and some authors suggest that strategies addressing better social insertion of schizophrenic patients must consider this dimension of the disorder (McGurk, 1999). Except for a few sparse reports of cognitive improvement, five decades of neuroleptic treatment have proved virtually unable to halt or reverse the progressive cognitive impairment of the condition. An apparent change in this pattern of failure was the introduction, in 1971, of the antipsychotic clozapine. Clozapine has been reported to have beneficial effects on attention, verbal fluency, executive functions, and working memory (Grace et al., 1996; Hoff et al., 1996) and is recommended for the management of treatment-resistant schizophrenia. The most widely adopted criteria for treatment resistance have been proposed by Kane et al. (1988) and can be summarized in three points: lack of periods of good functioning for 5 years; no response to two neuroleptics of different classes; and moderate to severe symptomatology. The percent of patients that fulfill these criteria ranges between 20% and 30%, a subpopulation that comprises mainly males, characterized by
more hospitalizations, earlier onset, and greater social and cognitive impairment compared to treatment-responsive patients. In addition to cognitive deterioration, emotional recognition deficits have been shown to be strongly related to functional outcome (Fakra et al., 2008). Impaired emotion recognition is consistent in schizophrenia; however, to our knowledge, only two studies investigated this function in the treatment-resistant form of the disorder (Ibarrarán-Pernas et al., 2003; Ramos et al., 2001), none of them focused on the effects of clozapine. This study is the first to investigate neurocognitive functioning and facial emotion recognition in a sample of treatmentresistant schizophrenic patients treated with clozapine. Fifteen treatment-resistant schizophrenic patients (11 male; 29.93 ± 8.13 years) were recruited at our university hospital. Diagnosis was confirmed with the Structured Clinical Interview for DSM IV-clinical version. The average daily dose of clozapine was 470 ± 173 mg/day. Another 15 healthy volunteers were matched to the patients in the experimental group according to sex, age, and education. The local ethics committee approved the study and informed consents were provided by all participants. Experimental sessions included verbal fluency (FAS — Benton and Hamsher, 1976), working memory (N-back), and selective attention (SCWT — Stroop, 1935) tests, in addition to a facial emotion recognition task (ERT) built with stimuli from the
Fig. 1. Time and standard error means for judgments of fearful and disgusted facial expressions in treatment-resistant schizophrenic patients and healthy controls (⁎ indicates statistical significance with p ≤ 0.05). 0920-9964/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2008.09.012
372
Letter to the Editors
series Pictures of Facial Affect (Ekman and Friesen, 1976) depicting six basic emotions – happiness, sadness, fear, disgust, anger, surprise – in different intensities and neutral faces. Compared to controls, patients spent more time to complete the ERT (F = 4.52; p = 0.042), with no differences in recognition accuracy or emotional intensity required for judging. The analysis of individual emotions showed a specific time-related deficit for the recognition of fear (F = 7.48; p = 0.01) and disgust (F = 5.36; p = 0.03) in patients (Fig. 1). Concerning neurocognition, patients and controls had similar performance in the N-back and FAS, with significant differences only in time interference in the SCWT (t = 3.18; p b 0.01). Consistent with previous reports, our results show that schizophrenic patients have impaired emotion recognition abilities and selective attention deficits, expressed in terms of the time required to perform these tasks as compared with healthy controls. Patients required more time to judge fearful and disgusted faces, which is in accordance with evidence of a negative bias for facial emotions in schizophrenia. Regardless of this speed-related impairment, patients were as accurate as controls both in the ERT and the cognitive tests, with the same rates of correct answers. Given the amount of evidence regarding impaired emotion recognition and deficitary cognitive functioning in schizophrenia, we believe that the equivalence of accurate responses in both groups is enough to suggest that clozapine may be effective for treating consistently described neurocognitive and emotion recognition deficits in schizophrenia, which appear to be related to these patients' functional outcome. Future studies involving larger samples and other patient groups for comparison are strongly recommended in order to investigate the effects of atypical neuroleptics on functions that do not respond to the typical antipsychotic treatment. References Benton, A.L., Hamsher, K., Sivan, A.B., 1976. Multilingual Aphasia Examination, Iowa City, IA: AJA. Ekman, P., Friesen, W.V., 1976. Pictures of Facial Affect. Consulting Psychologist Press, Palo Alto. Fakra, E., Salgado-Pineda, P., Delaveau, P., Hariri, A.R., Blin, O., 2008. Neural bases of different cognitive strategies for facial affect processing in schizophrenia. Schizophr. Res. 100 (1–3), 191–205.
Grace, J., Bellus, S.B., Raulin, M.L., Herz, M.I., Priest, B.L., Brenner, V., Donnely, K., Smith, P., Gunn, S., 1996. Long-term impact of clozapine and psychosocial treatment on psychiatric symptoms and cognitive functioning. Psychiatr. Serv. 47 (1), 41–45. Hoff, A.L., Faustman, W.O., Wieneke, M., Espinoza, S., Costa, M., Wolkowitz, O., Csernansky, J.G., 1996. The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology 15 (4), 361–369. Ibarrarán-Pernas, G.Y., Guevara, M.A., Cerdán, L.F., Ramos-Loyo, J., 2003. Olanzapine effects on emotional recognition in treatment refractory schizophrenics. Actas. Esp. Psiquiatr. 31 (5), 256–262. Kane, J., Honigfeld, G., Singer, J., Meltzer, H., 1988. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch. Gen. Psychiatry. 45 (9), 789–796. McGurk, S.R., 1999. The effects of clozapine on cognitive functioning in schizophrenia. J. Clin. Psychiatry. 60 (Suppl 12), 24–29. Ramos, J., Cerdán, L.F., Guevara, M.A., Amezcua, C., 2001. Impairments in attention and facial emotion recognition in treatment of refractory and non refractory schizophrenics evaluated through an odd-ball paradigm. Rev. Neurol. 33 (11), 1027–1032. Stroop, J.R., 1935. Studies of interference in serial verbal reactions. J. Exp. Psychol. 18, 643–662.
João Paulo Machado de Sousa Jaime Eduardo Cecílio Hallak⁎ Department of Neurology, Psychiatry, and Medical Psychology of the Ribeirão Preto Medical School-University of São Paulo, Brazil ⁎Corresponding author. Departamento de Neurologia, Psiquiatria e Psicologia Médica, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, Av. dos Bandeirantes, 3900, 3° andar, CEP: 14025-048, Brazil. Tel./fax: 55 16 3602 2703/3602 2853. E-mail address: [email protected] (J.E.C. Hallak). 14 July 2008
Contents lists available at ScienceDirect
Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s
Letter to the Editors Neurocognitive functioning and facial affect recognition in treatment-resistant schizophrenia treated with clozapine
Dear Editors, Along with the negative and positive syndromes, cognitive deterioration is a core feature of schizophrenia, and some authors suggest that strategies addressing better social insertion of schizophrenic patients must consider this dimension of the disorder (McGurk, 1999). Except for a few sparse reports of cognitive improvement, five decades of neuroleptic treatment have proved virtually unable to halt or reverse the progressive cognitive impairment of the condition. An apparent change in this pattern of failure was the introduction, in 1971, of the antipsychotic clozapine. Clozapine has been reported to have beneficial effects on attention, verbal fluency, executive functions, and working memory (Grace et al., 1996; Hoff et al., 1996) and is recommended for the management of treatment-resistant schizophrenia. The most widely adopted criteria for treatment resistance have been proposed by Kane et al. (1988) and can be summarized in three points: lack of periods of good functioning for 5 years; no response to two neuroleptics of different classes; and moderate to severe symptomatology. The percent of patients that fulfill these criteria ranges between 20% and 30%, a subpopulation that comprises mainly males, characterized by
more hospitalizations, earlier onset, and greater social and cognitive impairment compared to treatment-responsive patients. In addition to cognitive deterioration, emotional recognition deficits have been shown to be strongly related to functional outcome (Fakra et al., 2008). Impaired emotion recognition is consistent in schizophrenia; however, to our knowledge, only two studies investigated this function in the treatment-resistant form of the disorder (Ibarrarán-Pernas et al., 2003; Ramos et al., 2001), none of them focused on the effects of clozapine. This study is the first to investigate neurocognitive functioning and facial emotion recognition in a sample of treatmentresistant schizophrenic patients treated with clozapine. Fifteen treatment-resistant schizophrenic patients (11 male; 29.93 ± 8.13 years) were recruited at our university hospital. Diagnosis was confirmed with the Structured Clinical Interview for DSM IV-clinical version. The average daily dose of clozapine was 470 ± 173 mg/day. Another 15 healthy volunteers were matched to the patients in the experimental group according to sex, age, and education. The local ethics committee approved the study and informed consents were provided by all participants. Experimental sessions included verbal fluency (FAS — Benton and Hamsher, 1976), working memory (N-back), and selective attention (SCWT — Stroop, 1935) tests, in addition to a facial emotion recognition task (ERT) built with stimuli from the
Fig. 1. Time and standard error means for judgments of fearful and disgusted facial expressions in treatment-resistant schizophrenic patients and healthy controls (⁎ indicates statistical significance with p ≤ 0.05). 0920-9964/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2008.09.012
372
Letter to the Editors
series Pictures of Facial Affect (Ekman and Friesen, 1976) depicting six basic emotions – happiness, sadness, fear, disgust, anger, surprise – in different intensities and neutral faces. Compared to controls, patients spent more time to complete the ERT (F = 4.52; p = 0.042), with no differences in recognition accuracy or emotional intensity required for judging. The analysis of individual emotions showed a specific time-related deficit for the recognition of fear (F = 7.48; p = 0.01) and disgust (F = 5.36; p = 0.03) in patients (Fig. 1). Concerning neurocognition, patients and controls had similar performance in the N-back and FAS, with significant differences only in time interference in the SCWT (t = 3.18; p b 0.01). Consistent with previous reports, our results show that schizophrenic patients have impaired emotion recognition abilities and selective attention deficits, expressed in terms of the time required to perform these tasks as compared with healthy controls. Patients required more time to judge fearful and disgusted faces, which is in accordance with evidence of a negative bias for facial emotions in schizophrenia. Regardless of this speed-related impairment, patients were as accurate as controls both in the ERT and the cognitive tests, with the same rates of correct answers. Given the amount of evidence regarding impaired emotion recognition and deficitary cognitive functioning in schizophrenia, we believe that the equivalence of accurate responses in both groups is enough to suggest that clozapine may be effective for treating consistently described neurocognitive and emotion recognition deficits in schizophrenia, which appear to be related to these patients' functional outcome. Future studies involving larger samples and other patient groups for comparison are strongly recommended in order to investigate the effects of atypical neuroleptics on functions that do not respond to the typical antipsychotic treatment. References Benton, A.L., Hamsher, K., Sivan, A.B., 1976. Multilingual Aphasia Examination, Iowa City, IA: AJA. Ekman, P., Friesen, W.V., 1976. Pictures of Facial Affect. Consulting Psychologist Press, Palo Alto. Fakra, E., Salgado-Pineda, P., Delaveau, P., Hariri, A.R., Blin, O., 2008. Neural bases of different cognitive strategies for facial affect processing in schizophrenia. Schizophr. Res. 100 (1–3), 191–205.
Grace, J., Bellus, S.B., Raulin, M.L., Herz, M.I., Priest, B.L., Brenner, V., Donnely, K., Smith, P., Gunn, S., 1996. Long-term impact of clozapine and psychosocial treatment on psychiatric symptoms and cognitive functioning. Psychiatr. Serv. 47 (1), 41–45. Hoff, A.L., Faustman, W.O., Wieneke, M., Espinoza, S., Costa, M., Wolkowitz, O., Csernansky, J.G., 1996. The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology 15 (4), 361–369. Ibarrarán-Pernas, G.Y., Guevara, M.A., Cerdán, L.F., Ramos-Loyo, J., 2003. Olanzapine effects on emotional recognition in treatment refractory schizophrenics. Actas. Esp. Psiquiatr. 31 (5), 256–262. Kane, J., Honigfeld, G., Singer, J., Meltzer, H., 1988. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch. Gen. Psychiatry. 45 (9), 789–796. McGurk, S.R., 1999. The effects of clozapine on cognitive functioning in schizophrenia. J. Clin. Psychiatry. 60 (Suppl 12), 24–29. Ramos, J., Cerdán, L.F., Guevara, M.A., Amezcua, C., 2001. Impairments in attention and facial emotion recognition in treatment of refractory and non refractory schizophrenics evaluated through an odd-ball paradigm. Rev. Neurol. 33 (11), 1027–1032. Stroop, J.R., 1935. Studies of interference in serial verbal reactions. J. Exp. Psychol. 18, 643–662.
João Paulo Machado de Sousa Jaime Eduardo Cecílio Hallak⁎ Department of Neurology, Psychiatry, and Medical Psychology of the Ribeirão Preto Medical School-University of São Paulo, Brazil ⁎Corresponding author. Departamento de Neurologia, Psiquiatria e Psicologia Médica, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP, Av. dos Bandeirantes, 3900, 3° andar, CEP: 14025-048, Brazil. Tel./fax: 55 16 3602 2703/3602 2853. E-mail address: [email protected] (J.E.C. Hallak). 14 July 2008