以阴性症状为主的精神分裂症患者认知功能与局部脑血流的 …

目的 动态观察药物对局部脑血流量（ｒＣＢＦ）的影响,探索以阴性症状为主的精神分裂症患者潜隐的局部脑功能异常。方法 对２１例符合Ａｎｄｒｅａｓｏｎ阴性精神分裂症标准的患者（以下简称患者组）于氯氮平治疗前后进行威斯康星卡片分类测验（ＷＣＳＴ）和单光子发射计算机断层扫描（ＳＰＥＣＴ）检查,以４０名正常人为对照组（其中２８名为ＷＣＳＴ对照组,１２名为ＳＰＥＣＴ对照组）。结果 患者组氯氮平治疗前后ＷＣＳＴ的     

The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.     

The relationship between regional cerebral blood flow and the Wisconsin Card Sorting Test in negative schizophrenia

The purpose of this study was to explore the relationship between regional cerebral blood flow (rCBF) and problem-solving thinking in negative schizophrenia. Twenty-one negative schizophrenic patients and 12 normal controls were studied with single photon emission computed tomography (SPECT). Measures of regional cerebral blood flow (rCBF) were taken both at rest and during a prefrontal activation task using Wisconsin Card Sorting Test (WCST). Compared with controls, poor performances on the WCST of total trials category (TT), perseverative errors (PE) and non-perseverative errors (NE) were found in negative schizophrenic (P < 0.05). During WCST activation, patients showed interhemispheric differences in the prefrontal region, but under rest conditions, no such differences manifested. The negative schizophrenia group had a significantly lower rCBF change rate in profrontal lobe during stimulant WCST than those in normal controls (P < 0.05). The negative schizophrenic patient has executive function deficits and lower rCBF perfusion in left profrontal lobes, which suggest that the negative schizophrenic patient has dysfunction of the left profrontal region.     

The effect of apomorphine on regional cerebral blood flow in schizophrenia

A double-blind, placebo-controlled crossover study of the effects of apomorphine on regional cerebral blood flow (rCBF) during a prefrontal cortex activation task was undertaken to explore the role of dopamine on cortical function. The subjects were eight drug-free, chronically psychotic patients; six patients had schizophrenia. In each, apomorphine increased the relative prefrontal flow. The results suggest that enhanced prefrontal dopamine activity may reverse deficits in prefrontal cortex metabolism in schizophrenia.     

Clinical symptoms and regional cerebral blood flow in schizophrenia

This study examined the relationship between clinical symptoms and regional cerebral blood flow (rCBF) in schizophrenic patients using single photon emission computed tomography (SPECT). The subjects were 26 medicated schizophrenic patients diagnosed according to DSM-III-R criteria. Clinical symptoms were assessed using the Scale for the Assessment of Negative Symptoms (SANS), selected items for the Positive and Negative Syndrome Scale (PANSS), and the scale for Schneider's first rank symptoms. Resting rCBF was measured using N-isopropyl-p-[I-123] iodoamphetamine (I-123 IMP) SPECT, and relative rCBF distribution was evaluated in nine regions of interest in each hemisphere. Factor analysis of symptom ratings indicated four separate syndromes: psychomotor poverty, alienation (hallucination and disturbance of the self), delusion, and disorganization. Stepwise multiple regression analysis showed the psychomotor poverty syndrome to be correlated with decreased rCBF in bilateral superior frontal areas and increased rCBF in the left thalamus and right basal ganglia. The disorganization syndrome was correlated with increases rCBF in bilateral anterior cingulates and decreased rCBF in bilateral midolle frontal areas. The alienation syndrome was shown related to increased rCBF in the right inferior frontal area and parietal area. Dysfunction in distinctive neural networks involving various prefrontal areas would thus appear to underlie these syndromes in schizophrenia.     

The Danish PET/depression project: cognitive function and regional cerebral blood flow

OBJECTIVE: To clarify the relationship between cognitive functions and regional cerebral blood flow (rCBF) in a large group of depressed patients compared with healthy controls. METHOD: A set of principal components was extracted from scores of a battery of neuropsychological tests of 40 patients suffering from major depression and 49 healthy controls. The components were correlated by multiple linear regression analyses to selected regions of interest in the brain obtained from positron emission tomography images. RESULTS: In contrast to findings in the healthy controls, cognitive functions in the depressed patients correlated significantly with rCBF in specified regions of interest in only a few instances. CONCLUSION: Our study indicates that disturbed cognitive functions in depression do not relate to specific areas of the brain in the same way as normal cognitive functioning, suggesting that the abnormalities of brain function in major depression may be qualitative, rather than quantitative, in nature.     

The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.

Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients. The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone--share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin2a relative to dopamine2 receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediated neurotransmission as the possible basis for their ability to improve cognition are discussed. It is suggested that the development of drugs for schizophrenia should focus on improving the key cognitive deficits in schizophrenia: executive function, verbal fluency, working memory, verbal and visual learning and memory, and attention.     

Comparison of the effects of risperidone and haloperidol on regional cerebral blood flow in schizophrenia.

BACKGROUND: Atypical antipsychotics, such as risperidone, have been shown to be more effective for the treatment of the symptoms of schizophrenia and have a greater beneficial effect on neurocognition compared to the conventional antipsychotics. The present study used [(15)O]H(2)O positron emission tomography imaging of regional cerebral blood flow to examine and compare the effects of haloperidol and risperidone on brain function. METHODS: Thirty-two subjects with schizophrenia participated in the study. Each subject was scanned in a medication-free state, and after being on a stable clinically assigned dose of either risperidone or haloperidol for 3 weeks. The off-medication scan was subtracted from the on-medication scan, using a within-subjects design. A randomization analysis was used to determine differences between the effects of haloperidol and risperidone on regional cerebral blood flow. RESULTS: Haloperidol was associated with a significantly greater increase in regional cerebral blood flow in the left putamen and posterior cingulate, and a significantly greater decrease in regional cerebral blood flow in frontal regions compared to risperidone. Risperidone was associated with a significantly greater decrease in regional cerebral blood flow in the cerebellum bilaterally compared to haloperidol. CONCLUSIONS: The results show that risperidone and haloperidol have significantly different effects on brain function, which may be related to their differences in efficacy and side effects. Further work is required to more precisely determine the mechanisms by which different antipsychotic medications exert their therapeutic effects on the clinical symptoms and cognition in schizophrenia. These findings emphasize the importance of controlling for both medication status and the individual antipsychotic in neuroimaging studies.     

Cocaine's time action profile on regional cerebral blood flow in the rat

Cocaine is a powerful psychostimulant the high abuse liability of which in man appears to be linked, at least in part, to its pharmacokinetic properties. For example, intravenous and inhalation routes of administration result in appreciably higher level of dependence than either the oral or intranasal route, while cocaine's behavioral and physiologic profile is both route- and time-dependent. Therefore, to determine if various aspects of the drug's profile of effects are due to alterations in regional neuronal activity, we measured the effects of cocaine on regional cerebral blood flow (rCBF) 1, 2, 5, 15 and 45 min after a single 1.0 mg/kg i.v. cocaine injection. rCBF is known to directly reflect the state of local neuronal activity and, when measured autoradiographically using the method of Sakurada et al., can be resolved with a very high temporal resolution (30 s). A heterogeneous pattern of cerebral activation was seen. Of those regions which responded to cocaine, all but three did so with a threshold to effect of less than 1 min. Several groups of structures were evident: (1) those regions where blood flow returned to baseline prior to the 5 min measurement group (including several amygdaloid nuclei and lateral septum); (2) those returning to baseline prior to the 15 min sacrifice point (including limbic cortex); (3) regions activated for at least 15 but less than 45 min (including such motor-related regions as the caudate, substantia nigra and globus pallidus); and (4) those demonstrating persistent rCBF alterations for the entire 45 min observation period (including nucleus accumbens, olfactory tubercle, hippocampus, various thalamic nuclei and medial prefrontal cortex). It thus appears that cocaine's duration of action varies heterogenously across both time and brain structure, with many limbic regions displaying either very brief or prolonged duration of action while many motor-related structures display intermediate times of action. This regionally distinct time-course may reflect the diverse behavioral profile seen after cocaine administration in the rat.     

Lateralisation of cortical function during cognitive tasks: regional cerebral blood flow studies of normal individuals and patients with schizophrenia.

To assess cognitively-related regional asymmetries of brain function, regional cerebral blood flow (rCBF) was determined by the xenon inhalation method while normal subjects performed 10 different tasks and also while they were at rest. In addition to healthy subjects, patients with schizophrenia were also studied. A total of 447 rCBF studies were carried out during the following conditions: the Wisconsin Card Sort Test, a numbers matching test, a symbols matching test, Raven''s Progressive Matrices, an auditory discrimination test, an auditory control task, two versions of a visual continuous performance task, line orientation, semantic classification, and resting. On the whole, those tasks that seem to require or allow for internal verbalisation resulted in the greatest activation of the left hemisphere compared with the right; right hemisphere activation predominated only in the two tasks primarily involving attention and vigilance. Furthermore, a consistent regional topography of normal cerebral functional laterality was seen: under most conditions left prefrontal cortical activity exceeded that of right prefrontal cortex; during all non-auditory tasks, parieto-occipital cortical activity had an opposite pattern-greater right than left. During most conditions the schizophrenic patients displayed the same pattern. While several cognitively specific between-group differences were found, no single cortical region was consistently implicated and no specific direction of abnormal asymmetry predominated. These data suggest that there is a predominant task-independent functional pattern of cortical activity emphasising relatively greater left anterior and right posterior activation. This pattern may reflect the verbal and attentional primacy of these areas, respectively.     

氯氮平和维思通对精神分裂症认知功能的影响

目的：比较氯氮平和维思通对精神分裂症对知功能的影响,以阴性症状为主。方法对５７例接受氯氮平或维思通治疗的精神分裂症病人,采用韦氏记忆量表,数字划销测验、威斯康星卡片分类测验评估其治疗前和治疗８周后记忆、注意及执行功能。结果氯氮平和维思通能显著改善记忆,注意及执行功能,氯氮平对以阳性症状为主分裂症的注意改善优于维思通,维思能对以阴性症状为主分裂症图片成绩优于氯氮平,结论两种药物均有助于改善精神分理解     

奥氮平和氯氮平对慢性精神分裂症的认知功能的影响

目的了解奥氮平和氯氮平对慢性精神分裂症患者的认知功能的影响。方法78例经典型抗精神病药物治疗疗效不显著或不能耐受不良反应的慢性精神分裂症患者随机替换为奥氮平及氯氮平治疗,分别在入组前、12周、6个月进行PANSS量表评定、认知功能测定,包括言语学习、记忆、注意、执行功能、精神运动。结果奥氮平组32例和氯氮平组34例完成了6个月的治疗,这些患者疗程结束时均显示精神症状显著改善,认知功能显著提高,表现为言语流畅性、言语学习、言语视觉记忆、执行功能方面。二者之间无显著差异。结论奥氮平和氯氮平均可改善慢性精神分裂症的认知功能,且二者的疗效相似。     

The effects of tacrine on regional cerebral blood flow in Alzheimer's disease

Regional cerebral blood flow (rCBF) was studied in nine patients with Alzheimer's disease before and after treatment with tacrine. A small but significant improvement in cognitive functioning on the drug was not accompanied by significant changes in rCBF for the group as a whole. However, when the analysis was repeated excluding the only patient who showed no clinical response to the drug a significant increase in rCBF was seen to the right posterior temporal area. This preliminary study shows that some caution is necessary when interpreting studies of rCBF as changes in cognitive functioning may not always be accompanied by parallel changes in rCBF. Separate analysis of drug responders and non-responders may be a fruitful area for further research.     

Relations between cognitive and symptom profile heterogeneity in schizophrenia.

Although numerous studies have consistently revealed cognitive heterogeneity in schizophrenia, the relationships between such heterogeneity and clinical phenomenology are not clear. Clusters derived from cognitive heterogeneity studies may or may not be associated with symptom profile or severity of illness. The purpose of this study was to examine the relationship between cognitive heterogeneity and demographic and clinical phenomenological measures. We examined cognitive heterogeneity in schizophrenia by empirically deriving clusters of patients based upon WAIS-R subtest scores and then analyzed the way in which these clusters related to demographic and symptom variables and to DSM-III-R diagnostic subtypes. Four cognitive clusters were identified that were consistent with previous research. These clusters were differentiated on the basis of educational level and occupational status but not on the basis of symptom profile, severity, or DSM-III-R subtypes. Results suggest that cognitive measures are independent of severity of the disorder and phenomenological symptom presentation in these subgroups of schizophrenic patients.     

Contingent negative variation and regional cerebral blood flow in senile dementia and cerebral aging

Relationships between contingent negative variation (CNV) amplitude, regional cerebral blood flow (CBF), mini mental status examination score (MMSE) and reaction time (RT) have been studied in young subjects, non-demented old subjects and patients with primary degenerative senile dementia. Significant correlations have been found between CNV amplitude and global CBF, MMSE score and reaction time. Factorial analysis has shown 3 factors weighted respectively by MMSE and CNV, antero-posterior ratio fort left hemispheric CBF and age, and antero-posterior ratio for right hemispheric CBF and reaction time. Discriminant analysis has shown 2 discriminant functions differentiating young from old subjects with 90% accuracy and demented from non-demented patients with 75% accuracy.     

Abnormal resting regional cerebral blood flow patterns and their correlates in schizophrenia

Regional cerebral blood flow (CBF) was measured under resting conditions in 108 right-handed schizophrenic inpatients and a matched group of normal controls with the xenon 133 inhalation technique. Forty-six patients were free of all medication for two weeks. There were no significant differences in CBF to the two hemispheres. The patients showed a comparatively reduced anteroposterior (AP) gradient for CBF. Though there were no differences in frontal flow, the patients had higher flow to several postcentral brain regions, bilaterally. Cerebral blood flow in the patients correlated inversely with age and positively with carbon dioxide level. Women had higher flow than men. Duration of the illness was the only significant predictor of the reduced AP gradient in patients. Higher left temporal and right parietal flow were found to be the best discriminators between patients and controls. Mean hemispheric flow to both hemispheres and several brain regions correlated with the total score and the item, unusual thought content, of the Brief Psychiatric Rating Scale. There were no differences in regional CBF between medicated and unmedicated patients.     

Cognitive function and regional cerebral blood flow in partial seizures

Patients with partial seizures have cognitive function impairments that have been attributed to the toxic side effects of anticonvulsants and structural cerebral damage. However, even when these factors are absent, neuropsychological (NP) deficits have been demonstrated, although of milder degree than in structurally brain-damaged patients. Assessment of cerebral metabolism using positron emission tomography and cerebral blood flow with single photon emission computed tomography (SPECT) reveals focal physiologic deficits in structurally normal areas. Using both SPECT and NP assessment with the Halstead-Reitan Battery, we evaluated 50 patients with partial seizures. Comparison of the location of visually identified regional cerebral blood flow (rCBF) deficits in these patients with the location of the NP deficits revealed a significant correlation. Additional analyses indicated that rCBF quantification in visually identified areas of hypoperfusion was significantly lower than in "normal" areas and that quantified NP variables significantly discriminated patients with and without visual rCBF deficits in temporal and frontal brain regions.     

Analysis of cognitive function and regional cerebral blood flow in Parkinson's disease by 123I-IMP SPECT]

To investigate the relationship between the alterations of regional cerebral blood flow (rCBF) and the cognitive impairment in parkinsonian patients, I studied forty-one patients affected by Parkinson's disease (19 men and 22 women) using single photon emission computed tomography (SPECT) and N-isopropyl-p-[123I] iodoamphetamine (123I-IMP) as a tracer. I evaluated the cognitive function with the Mini-Mental State examination (MMS), the Hasegawa's Dementia Scale (HDS), the Kana-pick up test (KT), and the figure drawing test (FDT). I evaluated the motor impairment with the Hoehn and Yahr stage. SPECT scanning was performed with a rotating digital gamma camera TOSHIBA 901-A. A semiquantitative method of assessing regional tracer uptake was used. Regions of interest (ROI; 3 x 3 pixels, 15.9 x 15.9 mm2) were drawn on the cerebellar hemispheres, cortical regions (frontal, temporal, parietal and occipital), and basal ganglia bilaterally. The RI count index was expressed as a ratio of activity in each ROI to mean counting rate over cerebellar regions. I considered the RI count index as the index of rCBF in each ROI. There were strong positive correlations between MMS and rCBF of frontal, parietal and occipital lobes (p less than 0.001). There were positive correlations between HDS and rCBF of frontal (p less than 0.01), parietal (p less than 0.001) and occipital lobes (p less than 0.01). There were positive correlations between KT and rCBF of frontal (p less than 0.01), occipital (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effortful cognitive resource allocation and negative symptom severity in chronic schizophrenia

BACKGROUND: The relationship between negative symptoms, early visual information-processing deficits, and effortful processing resource allocation was investigated. METHODS: Older patients with chronic schizophrenia (n = 58) and healthy controls (n = 71) participated. Pupillary responses were recorded during performance of the span of apprehension task (blocks of 3- and 10-letter arrays) as an index of resource allocation or mental effort during the task. RESULTS: Patients and controls showed larger pupillary responses in higher relative to lower processing loads both during array processing and just prior to array onset (preparation). Both groups, therefore, invested more cognitive effort preparing for and then processing larger arrays. A subgroup of patients with abnormally small pupillary responses and impaired performance showed greater negative symptom severity relative to a subgroup of patients with normal pupillary responses. Smaller pupillary responses in the patients were also significantly correlated with greater negative symptom severity, independent of positive symptom severity. Patients with reduced effortful resource allocation, therefore, exhibited greater negative symptomatology. A subgroup of patients with normal pupillary responses still showed impaired detection accuracy relative to controls, suggesting that reduced cognitive effort or resource allocation problems cannot account for impairments in early visual information processing in this subgroup. CONCLUSIONS: The study illustrates important relationships between cognitive effort and performance that can impact conclusions about the nature of cognitive impairments and associations between negative symptoms and neurocognition in schizophrenia.