Article

Schizophrenic syndromes and frontal lobe performance.

Royal Postgraduate Medical School, Hammersmith Hospital, London.
The British Journal of Psychiatry (Impact Factor: 7.34). 04/1991; 158:340-5. DOI: 10.1192/bjp.158.3.340
Source: PubMed

ABSTRACT A battery of neuropsychological tests sensitive to frontal lobe impairment was administered to 43 chronic schizophrenic patients to delineate the abnormality of mental processing associated with the syndromes of psychomotor poverty and disorganisation, which had been identified in a previous study of the segregation of schizophrenic symptoms. Psychomotor poverty was found to be associated with slowness of mental activity, including slowness of generating words. The disorganisation syndrome was associated with impairment in tests in which the subject is required to inhibit an established but inappropriate response.

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    ABSTRACT: B y modulating the "glutamate-NO (nitric oxide)-cGMP" pathway," a new paradigm for the treatment of schizophrenia seems to arise. Indeed, our group has recently pub-lished a double-blind placebo (PLB) con-trolled trial showing that an infusion of sodium nitroprusside (SNP), a nitric oxide donor, improved positive, negative, anxiety, and depressive symptoms of schizophrenic patients in a matter of hours. 1 During this study, it seemed of interest to test the idea that SNP might also be effective in treating cognitive symptoms found in schizophrenia. For this purpose, it was performed, in the same subjects just mentioned, a pilot study where the patients were evaluated by a battery of cognitive tests on 2 occasions: 1 hour be-fore the start of SNP or PLB infusion and at 8 hours after the end of SNP or PLB infusion. Twenty-four patients agreed to partici-pate and were assessed for eligibility; 4 sub-jects subsequently refused to participate, and 20 individuals were randomized to receive either SNP or placebo. Two subjects from the SNP group refused to participate in the sec-ond cognitive evaluation (cognitive evaluation at 8 hours after the end of the SNP infusion). The other 18 participants who were random-ized completed all the study procedures. The SNP was administered as an endovenous infusion of 0 . 5 μg/kg per min-ute for 4 hours. The placebo was a 5% glu-cose solution that was endovenous infused over the same length of time. The following cognitive tests were con-ducted: (a) Stroop Color Word Test (SCWT) is a test to assess selective attention. Two cards instead of the 3 cards originally pro-posed by Stroop were used, following the procedure used by Liddle and Morris. 2 On the first card 100 words designating 5 colors, printed in black, were used; and on the sec-ond card, 100 words for the same colors, printed in colors incongruent with the des-ignation were used. The task was to read card 1 and designate the colors of card 2. Time spent on the task was measured in seconds and number of errors committed, according to the method proposed by Seabra (1987). (b) N-Back is a test to assess work-ing memory. It lasts about 6 minutes and consists of examining a series of numbers where it is required, at varying intervals, to report the number seen "n" positions back in the sequence. A printed version of the test on laminated cards was used in this study, with 2 distinct blocks presented in-terchangeably. The first and the third blocks contain 5 questions each about the last num-ber seen ("0-Back," task control), and the sec-ond and fourth blocks contain 5 questions each about which number was submitted before the last 2 cards ("2-Back"). The num-ber of errors made during the task was com-puted. (c) FAS (the Verbal Fluency Test) is a test widely used in the literature to measure verbal fluency, which is known to be impaired in schizophrenic patients. The task consists of a period of 3 minutes (1 minute for each letter—F, A, and S) where the volunteer must produce the largest number of words begin-ning with those letters. Brand names, proper names, or variations from the same root (eg, words like fall and fallen) are not allowed. Data were analyzed using the Statistical Package for the Social Sciences (SPSS 17·0). 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An interac-tion between time and drug was found for the number of errors on naming incongru-ent colors on card 2 (F = 5.54, df = 1–15, P = 0.03), but no effect of time (F = 0.57, df = 1–15, P = 0.46) or of drug alone (F = 0.03, df = 1–15, P = 0.85). Regarding the time for naming incongruent colors, the ANOVA for repeated measures showed no effect of time (F = 0.02, df = 1–15, P = 0.89), drug (F = 0.71, df = 1–15, P = 0.42), or in-teraction between them (F = 2.32, df = 1–15, P = 0.15). In situations where the ANOVA for repeated measures identified some in-teraction, the paired t test was performed, considering the groups independently. The paired t test for the 2 groups individually (SNP and PLB) showed that those patients who received SNP made fewer errors in the second evaluation of naming incongruent colors, but those who received PLB did not. (b) FAS—the ANOVA for repeated measures showed an effect of time (F = 9.37, df = 1–16, P = 0.01), but not of drug (F = 0.08, df = 1–16, P = 0.78) and no interaction between time and drug (F = 0.03, df = 1–16, P = 0.85). (c) N-Back—the ANOVA for repeated mea-sures identified an effect of time (F = 7.63, df = 1–14, P = 0·01), drug (F = 7.76, df = 1–14, P = 0.01), and also an interaction be-tween these 2 (F = 15.24, df = 1–14, P < 0.01). Thus, the paired t test was conducted for the SNP and PLB groups alone, which showed that those who received the SNP infusion pre-sented significant improvement in congnitive performance, whereas those who received the PLB infusion did not (Table 1). To our knowledge, this is the first time that improvements on executive functions that are frequently impaired in patients with schizophrenia were shown after SNP admin-istration. The improvement in SCWT and N-back performance that was observed in the SNP group, but not in the PLB group, suggests that treatment with SNP had an impact on patients cognitive functioning by improving selective attention 3 and work-ing memory 4 deficits. These beneficial effects could be ex-plained through SNP capacity, as a NO do-nor, to act by increasing the concentrations of the second messenger cGMP and medi-ating the neuronal communication in the CNS (central nervous system). 5,6 In this way, NO has been shown to influence learning and memory. 7 NO donors such as SNP have been found to stimulate neuronal growth in vitro 8 and have been proposed as potential new drugs to treat patients with age-related neurodegenerative disease such as Alzheimer disease. 9,10 On the other hand, too much NO could produce neurotoxicity due to accumu-lation of its toxic metabolite, peroxynitrite. 11 The small amount of patients studied is the limitation of this work. 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Unauthorized reproduction of this article is prohibited. factors from demographic and clinical vari-ables, the selection and pairing of subjects were performed carefully and showed no differences between the 2 groups in any of the parameters evaluated (these results have been discussed elsewhere). 1 Despite the cognitive deficits being considered as the strongest predictors of long-term functional recovery in patients with schizophrenia, they have been among the symptoms most refractory to the treat-ment by both second-and first-generation antipsychotics. 12,13 Perhaps, the develop-ment of drugs that enhance NO levels, such as SNP, could be a productive target to pur-sue in the development of the next genera-tion of antipsychotic drugs. However, the findings here reported are modest and need to be confirmed for future studies. ACKNOWLEDGMENTS The authors thank their respective universities for the continuous support and Dr Judy Baker for the editorial and secretarial assistance.
    Journal of clinical psychopharmacology 02/2015; 35(1):1. DOI:10.1097/JCP.0000000000000258 · 5.09 Impact Factor
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