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). For the SCWT, N-Back, and the FAS scores, separate analyses of variance (ANOVAs) for repeated measures were carried out, with treatment (SNP/PLB) and time (every point of evaluation) as factors. If the ANOVAs were significant, a paired 2-tailed t test was per-formed, considering the groups independently. The following results were found: (a) SCWT—the ANOVA for repeated mea-sures concerning card 1 reading time showed an effect of the time factor (F = 6.98, df = 1–15, P = 0.02), but not drug (F = 1.46, df = 1–15, P = 0.24) and no interaction between time and drug (F = 0.03, df = 1–15, P = 0.85). The analysis of the number of errors on card 1 showed no effect of time (F = 2.4, df = 1–15, P = 0.14), drug (F = 0.18, df = 1–15, P = 0.68), or interaction between time and drug (F = 0.03, df = 1–15, P = 0.86). 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. Future studies with a larger number of patients are needed. The usual NPS safe dose rate used to treat hypertension is 0.5 to 10 μg/kg per minute. Therefore, we decide to work with its low-est dose to minimize cardiovascular effects. Indeed, no clear effect of NPS on the vascu-lar system was observed (these results have been discussed elsewhere). 1 Further works should investigate the effects of multiple and different doses of SNP and other rele-vant issues like how frequently do we have to administer SNP to sustain its effect in long-term. To minimize possible learning effects, cognitive tests were performed only on 2 occasions. To avoid confounding LETTER TO THE EDITORS Journal of Clinical Psychopharmacology • Volume 35, Number 1, February 2015 1 Copyright © 2014 Wolters Kluwer Health, Inc. 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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    ABSTRACT: Actions are goal-directed behaviours that usually involve movem ent. There is evidence that intentional self-generated actions (willed actions) are controlled differently from routine, stereotyped actions that are externally triggered by environmental stimuli. We review evidence from investigations using positron emission tomography (PET), recordings of movement-related cortical potentials (MRCPs) or transcranial magnetic stimulation (TMS), and conclude that willed actions are controlled by a network of frontal cortical (dorsolateral prefrontal cortex, supplementary motor area, anterior cingulate) and subcortical (thalamus and basal ganglia) areas. We also consider evidence suggesting that some of the cognitive and motor deficits of patients with frontal lesions, Parkinson's disease, or schizophrenia as well as apathy and abulia and rarer phenomena such as primary obsessional slowness can be considered as reflecting im pairment of willed actions. We propose that the concept of a willed action system based on the frontostriatal circuits provides a useful framework for integrating the cognitive, motor, and motivational deficits found in these disorders. Problems remaining to be resolved include: identification of the component processes of willed actions; the specific and differential role played by each of the frontal cortical and subcortical areas in the control of willed actions; the specific mechanisms of impairm ent of willed actions in Parkinson's disease, schizophrenia, and frontal damage; and the precise role of the neurotransmitter dopamine in the willed action system .
    Cognitive Neuropsychology 09/1998; 15. DOI:10.1080/026432998381005 · 1.96 Impact Factor
  • Advances in Psychiatric Treatment 01/2000; 6(3):161-168. DOI:10.1192/apt.6.3.161


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