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.     

Abnormal patterns of regional cerebral blood flow in schizophrenia with primary negative symptoms during an effortful auditory recognition task.

OBJECTIVE: Using functional brain imaging, the authors sought to replicate their earlier finding of low metabolism in the middle frontal and inferior parietal cortices of schizophrenic patients with primary negative symptoms. METHOD: According to the presence or absence of enduring negative symptoms, patients with schizophrenia were classified as having deficit or nondeficit schizophrenia, respectively. Twelve normal volunteers and 18 drug-free schizophrenic volunteers (deficit, N=8; nondeficit, N=10) were trained in a tone discrimination task. They were trained to perform with 70%-80% accuracy and were then scanned with positron emission tomography with [(15)O]H(2)O during three conditions: rest, sensory-motor control task, and decision task. RESULTS: Levels of performance of the auditory recognition task were similar in the three groups. An initial hypothesis-driven analysis revealed that across tasks the deficit group failed to show significant activation in the middle frontal cortex. This was in contrast to both the normal volunteers and nondeficit patients. When the patient groups were contrasted, the deficit patients showed significantly less activation in the middle frontal cortex bilaterally during the control task and in the right middle frontal cortex and inferior parietal cortex during the decision task. An exploratory analysis contrasting deficit and nondeficit patients across conditions did not reveal further differences between groups. CONCLUSIONS: This study replicated the finding of low activation in the middle frontal cortex and inferior parietal cortex in deficit schizophrenia. This deficit was observed without performance confound and may provide a marker of primary negative symptoms and a target for new therapies.     

Determinants of resting regional cerebral blood flow in normal subjects

Study of brain function via cerebral blood flow and metabolism measurements is believed to be of considerable significance in psychiatry. The present study examined the factors that determined patterns of regional cerebral blood flow (CBF) in 140 physically and mentally healthy, drug-free volunteers under resting conditions. Age, sex, and end-tidal CO2 levels were identified as the most powerful determinants of CBF, in that order. Age-related CBF reduction was found to be most marked in the frontal region. Women had higher CBF than men, and the difference was most obvious in the frontal region. The correlations between CO2 and CBF showed less striking, but significant, regional variations. Hematocrit was found to exert only minimal influence in the control of resting CBF.     

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.     

Nicotine effects on regional cerebral blood flow in awake, resting tobacco smokers

The hypothesis for this research was that regional cerebral blood flow (rCBF) would increase following nasal nicotine administration to overnight abstinent tobacco smokers in relationship to the known brain distribution of nicotinic cholinergic receptors (nAChRs). Nine male and nine female healthy adult smokers were studied. They abstained overnight from tobacco products for 10 or more hours prior to study the next morning. Nicotine nasal spray was given in doses of 1-2.5 mg total with half in each nostril while the subject was awake and resting in a supine position. Oleoresin of pepper solution in a similar volume was used as an active placebo to control for the irritating effects of nicotine. Both substances were given single blind to the subjects. Positron emission tomography (PET) with H(2)(15)O was used to measure rCBF. The data from each subject volunteer were normalized to global activity to better assess regional brain changes. Both nasal nicotine and pepper spray produced similar increases in CBF in somesthetic area II, consistent with the irritant effects of both substances. The mean rCBF effects of nasal pepper were subtracted from those of nasal nicotine to determine the actions of nicotine alone. The latter produced increases in rCBF in the thalamus, pons, Brodman area 17 of the visual cortex, and cerebellum. Some brain areas that contain a large number of nAChRs, such as the thalamus, showed an increase in CBF. Other areas that have few nAChRs, such as the cerebellum, also showed an increase in relative CBF. The hippocampal/parahippocampal areas showed greater regional decreases (left) and lesser increases (right) in CBF that correlated with the increase in plasma arterial nicotine concentrations. The results obtained indicate complex primary and secondary effects of nicotine in which only some regional brain CBF changes correlate with the known distribution of nAChR. No gender differences were noted.     

Active and remitted schizophrenia: psychopathological and regional cerebral blood flow findings

Single photon emission computed tomography with technetium-99m-d,l-hexamethylpropyleneamine oxime (^99mTc-HMPAO) was used to assess regional cerebral blood flow (rCBF) during both florid and remitted stages of schizophrenia. Forty schizophrenic patients in an active phase of illness (diagnosis by DSM-III-R) were examined in two clinical states (ill vs. improved). At study entry, 24 patients were drug-naive, five were currently drug-free, and 11 were being treated with antipsychotic medication. Twenty medical patients who suffered from non-specific headaches but were free of neurological and psychiatric symptoms served as control subjects. At initial examination during the active phase of illness, cerebral perfusion patterns in the schizophrenic patients were characterized by both hypofrontality and hypotemporality. After remission, hypofrontality was no longer apparent in two of four frontal regions, and hypotemporality disappeared completely. As assessed with the Positive and Negative Syndrome Scale (PANSS), formal thought disorders, hallucinations, and ideas of grandiosity correlated with rCBF in the active phase of illness, but not after remission. In the remitted but not in the florid state, blunted affect, difficulties in abstract thinking, lack of spontaneity, and stereotyped thoughts correlated with rCBF. Correlations of five symptoms with rCBF changed significantly from first to second examination. The present study suggests that correlations between single psychotic symptoms and rCBF differ significantly in florid vs. remitted phases of schizophrenia.     

Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms

OBJECTIVE: Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. METHOD: Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. RESULTS: SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. CONCLUSION: Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.     

Active and remitted schizophrenia: psychopathological and regional cerebral blood flow findings.

Single photon emission computed tomography with technetium-99m-d,l-hexamethylpropyleneamine oxime (99mTc-HMPAO) was used to assess regional cerebral blood flow (rCBF) during both florid and remitted stages of schizophrenia. Forty schizophrenic patients in an active phase of illness (diagnosis by DSM-III-R) were examined in two clinical states (ill vs. improved). At study entry, 24 patients were drug-naive, five were currently drug-free, and 11 were being treated with antipsychotic medication. Twenty medical patients who suffered from non-specific headaches but were free of neurological and psychiatric symptoms served as control subjects. At initial examination during the active phase of illness, cerebral perfusion patterns in the schizophrenic patients were characterized by both hypofrontality and hypotemporality. After remission, hypofrontality was no longer apparent in two of four frontal regions, and hypotemporality disappeared completely. As assessed with the Positive and Negative Syndrome Scale (PANSS), formal thought disorders, hallucinations, and ideas of grandiosity correlated with rCBF in the active phase of illness, but not after remission. In the remitted but not in the florid state, blunted affect, difficulties in abstract thinking, lack of spontaneity, and stereotyped thoughts correlated with rCBF. Correlations of five symptoms with rCBF changed significantly from first to second examination. The present study suggests that correlations between single psychotic symptoms and rCBF differ significantly in florid vs. remitted phases of schizophrenia.     

Sex differences in brain-behavior relationships between verbal episodic memory and resting regional cerebral blood flow

Women have better verbal memory, and higher rates of resting regional cerebral blood flow (rCBF). This study examined whether there are also sex differences in the relationship between verbal episodic memory and resting rCBF. Twenty eight healthy right-handed volunteers (14 male, 14 female) underwent a neuropsychological evaluation and a Positron Emission Tomography (PET) (15)O-water study. Immediate and delayed recall was measured on the logical memory subtest of the Wechsler Memory Scale - Revised (WMS-R), and on the California Verbal Learning Test (CVLT). Resting rCBF (ml/100 g/min) was calculated for four frontal, four temporal, and four limbic regions of interest (ROIs). Women had better immediate recall on both WMS-R and CVLT tasks. Sex differences in rCBF were found for temporal lobe regions. Women had greater bilateral blood flow in a mid-temporal brain region. There were also sex differences in rCBF correlations with performance. Women produced positive correlations with rCBF laterality in the temporal pole. Greater relative CBF in the left temporal pole was associated with better WMS-R immediate and delayed recall in women only. These results suggest that trait differences in temporal pole brain-behavior relationships may relate to sex differences in verbal episodic memory.     

Ventricular size and regional cerebral blood flow in schizophrenia: an attempted replication.

We attempted to replicate the finding of Berman et al. (1987) that frontal cortical blood flow correlated inversely with ventricular size in schizophrenia. Computed tomography and high-resolution 99m-Tc-HMPAO single photon emission computed tomography were performed in 25 right-handed chronic schizophrenic men engaged in a word-fluency task. Weak, nonstatistically significant inverse correlations were found between the ventricle-brain ratio (VBR) and frontal cortical blood flow. The VBR was significantly inversely correlated with the ratio of left to right medial frontal blood flow.     

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     

Cortical "stress tests" in schizophrenia: regional cerebral blood flow studies

A total of 261 regional cerebral blood flow (rCBF) studies were carried out on 34 medication-free patients with chronic schizophrenia and 50 normal subjects. rCBF, an indicator of local cortical metabolism and activity, was measured during the resting state and also during four cognitive activation tasks or "cortical stress tests." The latter included the Wisconsin Card Sort (WCS), a test of prefrontal lobe function; a simple numbers matching task, and two versions of a visual Continuous Performance Task (CPT). Multivariate comparisons of the two subject groups were performed for each of the five testing conditions, and discriminant function analyses for each condition were carried out to define mathematical models that differentiated normal subjects from medication-free patients. The best such model was determined and was then applied to another group of patients who had diagnoses other than schizophrenia or for whom the diagnosis was unclear. This group included two patients with clinical "frontal lobe syndrome" and radiological evidence of frontal lobe damage. The most robust differences between the groups were seen in frontal rCBF during the WCS. In the discriminant function analysis, rCBF during the WCS was the best discriminator between the two groups, retrospectively classifying 85% of the subjects correctly. rCBF during the resting state and one of the CPTs correctly classified subjects at a rate only marginally better than chance. When the model derived from WCS rCBF was applied to a second group of patients, the two patients with known frontal lobe disease were classified as "schizophrenic" with 100% certainty. Three other patients with psychotic illnesses were also assigned to this group with greater than 80% certainty, whereas a patient with character disorder (rule-out affective disorder) was classified as "normal" with a high level of confidence. These data suggest (1) that schizophrenia is characterized by a deficit in prefrontal function that is revealed when regionally specific demand exceeds the physiological capacity, and (2) that functional brain imaging studies, such as rCBF, can best identify brain abnormalities during "cortical stress tests."     

Cycloid psychosis: regional cerebral blood flow correlates of a psychotic episode.

Eight patients meeting Leonhard's criteria for cycloid psychosis were investigated on repeated occasions during a psychotic episode, with regional cerebral blood flow measurements and clinical ratings. The results showed that, at admission to the hospital, when the patients were clinically exacerbated, the mean hemispheric blood flow was significantly elevated compared with values from a normal control group. The hemispheric blood flow level covaried significantly with the degree of clinical symptoms, such that the more elevated the cortical blood flow was, the more behaviorally disturbed was the patient. At discharge from the hospital, the patients had no residual symptoms and the cortical blood flow was normal. These findings differ distinctly from those commonly made in other psychoses, such as schizophrenia.     

Caffeine-induced cerebral blood flow changes in schizophrenia

Summary Cerebral blood flow (CBF) measurements and mental status examinations were performed before and 30 min after oral administration of 250 mg of caffeine or a placebo given under double-blind conditions, in two groups of patients with schizophrenia. Caffeine produced significant CBF reductions but no changes in the patient's clinical condition.     

Effect of age on regional cerebral blood flow patterns in Alzheimer's disease patients

The purpose of this study was to explore the influence of age on regional cerebral blood flow (rCBF) patterns in patients with Alzheimer's disease (AD). Single photon emission computed tomography (SPECT) was performed in 79 patients with AD, including 31 younger and 48 older patients divided according to age at examination (<70 and > or = 70 years), and the SPECT data were analyzed using three-dimensional stereotactic surface projection. Although no significant differences in severity and duration of disease between the two groups were found, there were some differences in rCBF patterns. Patients with younger AD had a more severe decrease of rCBF in the parietotemporal and posterior cingulate cortex, while patients with older AD had a more severe decrease of rCBF in the medial temporal region and medial frontal lobe. This observer-independent analysis of SPECT data provides an objective assessment of cortical rCBF abnormalities in patients with AD and is useful in demonstrating the differences in rCBF patterns between younger and older patients with AD.     

盐酸丁咯地尔对不同亚型精神分裂症局部脑血流的影响

目的 探讨脑血管扩张药盐酸丁咯地尔对不同亚型精神分裂症局部脑血流的影响.方法 选择中山大学附属第三医院精神心理科自2007年2月至2009年2月收治的符合《中国精神障碍分类与诊断标准》第3版中精神分裂症诊断标准患者共286例,分型后分别在各型中按照随机数字表法分为治疗组(采用抗精神病药加盐酸丁咯地尔治疗)和安慰组(采用抗精神病药加安慰剂生理盐水),其中Ⅰ型86例(治疗组46例,安慰组40例)、Ⅱ型63例(治疗组34例,安慰组29例)、Ⅲ型137例(治疗组72例,安慰治疗组65例).在治疗第1天和治疗第4周末采用经颅多普勒(TCD)测量不同亚型中2组患者双侧大脑前动脉、大脑中动脉、大脑后动脉、椎动脉和基底动脉的血流量. 结果 (1)Ⅰ型精神分裂症:2组治疗前后及2组之间各项TCD检测结果比较差异均无统计学意义(P＞0.05).(2)Ⅱ型精神分裂症:在治疗第1天时,2组大脑各动脉血流量比较差异均无统计学意义(P＞0.05).在第4周末时,治疗组双侧大脑前动脉、大脑中动脉、大脑后动脉血流量明显高于安慰组,差异有统计学意义(P＜0.05);同时治疗组双侧大脑前动脉、大脑中动脉、大脑后动脉血流量明显高于治疗第1天时,差异有统计学意义(P＜0.05),而安慰组大脑各动脉血流量与治疗第1天比较差异均无统计学意义(P＞0.05).(3)Ⅲ型精神分裂症:在治疗第1天时,2组大脑各动脉血流量比较差异均无统计学意义(P＞0.05).在第4周末时,治疗组左侧大脑前动脉、左侧大脑中动脉和右侧大脑中动脉脑血流量明显高于安慰治疗组,差异有统计学意义(P＜0.05);同时治疗组双侧大脑前动脉、大脑中动脉血流量明显高于治疗第1天时,差异有统计学意义(P＜0.05),而安慰组大脑各动脉血流量与治疗第1天比较差异均无统计学意义(P＞0.05). 结论 (1)不同亚型精神分裂症的脑血流状况是不同的,Ⅱ型精神分裂症脑动脉血流量下降最明显,所涉及脑动脉最多,其次是Ⅲ型,而Ⅰ型则相对不明显.(2)精神分裂症脑动脉血流量的下降可能有一定的先后顺序,以左侧大脑中动脉最先开始.(3)Ⅱ型和Ⅲ型精神分裂症脑动脉血流量下降的情况是可以用药物进行干预的.     

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.     

Regional cerebral blood flow in catatonic schizophrenia

Single photon emission computed tomography (SPECT) with ¹²³I-iodoamphetamine (IMP) as tracer was used to study regional cerebral blood flow (rCBF) distribution in six patients with the catatonic subtype of schizophrenia (DSM-III-R). IMP-SPECT imaging revealed a significant reduction of rCBF in the parietal lobes of both hemispheres. Three-dimensional reconstruction of the SPECT images identified the superior region of the frontoparietal lobe as the most severely affected region. The pattern of rCBF deficits observed in catatonic schizophrenia differs markedly from that seen in 13 patients with other subtypes of schizophrenia and 7 normal control subjects. These observations indicate that parietal lobe dysfunction may be an important component in the pathology of the catatonic subtype of schizophrenia.     

Cognitive profiles and regional cerebral blood flow patterns in dementia of the Alzheimer type

Individual cognitive profiles and correlations between cognitive functions and regional cerebral blood flow (rCBF) were analyzed in 20 consecutive patients with a clinical diagnosis of probable Alzheimer's disease (AD). CBF was measured with high resolution single photon emission computed tomography (SPECT) and [^99mTc]d,l-HMPAO. The analysis of cognitive profiles was based on the composite scores for six cognitive domains, derived from a detailed neuropsychological test battery, as compared with corresponding test data obtained in a control group of 28 age-matched healthy volunteers. The cognitive profiles displayed a marked heterogeneity as concerned the general level of cognitive impairment, the number of significantly affected cognitive domains, the spectrum of affected and non-affected cognitive domains, and the severity of each cognitive dysfunction. Statistically significant correlations with rCBF were found for memory scores (right frontal and temporal cortex), abstraction scores (frontal/parietal ratio of rCBF), language scores (left frontal and temporal cortex), visual perception scores (rCBF throughout the right hemisphere), and for visuo-construction scores (side-to-side asymmetry of parietal rCBF). We conclude that the previously observed topographical heterogeneity of rCBF distribution patterns in probable AD was reflected by differences in cognitive profiles. The observed heterogeneities stress the relevance of analyzing individual cognitive and rCBF data, as a supplement to group comparisons of data, in the investigation of diseases with potential heterogeneous affections of the brain.