Cerebral Blood Flow In Schizophrenia Research Articles

Reduced cortical cerebral blood flow in antipsychotic-free first-episode psychosis and relationship to treatment response.

Altered cerebral blood flow (CBF) has been found in people at risk for psychosis, with first-episode psychosis (FEP) and with chronic schizophrenia (SCZ). Studies using arterial spin labelling (ASL) have shown reduction of cortical CBF and increased subcortical CBF in SCZ. Previous studies have investigated CBF using ASL in FEP, reporting increased CBF in striatum and reduced CBF in frontal cortex. However, as these people were taking antipsychotics, it is unclear whether these changes are related to the disorder or antipsychotic treatment and how they relate to treatment response. We examined CBF in FEP free from antipsychotic medication (N = 21), compared to healthy controls (N = 22). Both absolute and relative-to-global CBF were assessed. We also investigated the association between baseline CBF and treatment response in a partially nested follow-up study (N = 14). There was significantly lower absolute CBF in frontal cortex (Cohen's d = 0.84, p = 0.009) and no differences in striatum or hippocampus. Whole brain voxel-wise analysis revealed widespread cortical reductions in absolute CBF in large cortical clusters that encompassed occipital, parietal and frontal cortices (Threshold-Free Cluster Enhancement (TFCE)-corrected <0.05). No differences were found in relative-to-global CBF in the selected region of interests and in voxel-wise analysis. Relative-to-global frontal CBF was correlated with percentage change in total Positive and Negative Syndrome Scale after antipsychotic treatment (r = 0.67, p = 0.008). These results show lower cortical absolute perfusion in FEP prior to starting antipsychotic treatment and suggest relative-to-global frontal CBF as assessed with magnetic resonance imaging could potentially serve as a biomarker for antipsychotic response.

Cerebral Blood Flow in Schizophrenia: What About Perfusion and Clinical Symptoms?

Arterial spin-labeling (ASL) is becoming an increasingly used MRI-based technique to investigate cerebral blood flow (CBF) as a potential pathophysiological mechanism in schizophrenia spectrum and other psychotic disorders (SSD). Being non-invasive and having high-quality spatial/temporal resolution, ASL has provided new opportunities for imaging CBF, notably in the context of its link with the clinical dimensions of psychosis. There is no comprehensive summary of that literature, so we conducted a systematic review of MRI-based perfusion studies exploring CBF in individuals with SSD.

The Effects of Aging on Changes in Regional Cerebral Blood Flow in Schizophrenia

Aims: Although there have been no conclusive pathophysiological findings in support of the degeneration theory in the etiology of schizophrenia to date, results of our neuroimaging studies suggest functional changes in the brains of schizophrenics. We evaluated age-related changes of brain perfusion in medicated patients with schizophrenia. Method: In this study, we evaluated age-related changes in brain perfusion in medicated schizophrenia patients (n = 44) and control subjects (n = 37) undergoing ^99mTc-ethyl cysteinate dimer single-photon emission computed tomography. Result: Although the regional cerebral blood flow (rCBF) was found to be reduced in bilateral frontal lobes by analysis with age in the patients with schizophrenia, significant differences compared to controls in age effects on perfusion were found in the patients with schizophrenia in bilateral temporal lobes. Moreover, in multiple regression analysis including age, total time of treatment and overall neuroleptic dose, rCBF was found to be reduced in bilateral frontal and parietal lobes. As a result, cerebral perfusion in temporal lobes with schizophrenia might be related to age rather than medication. Conclusion: In this study, the patients with schizophrenia appeared to have significant bilateral temporal hypoperfusion related to age compared with controls. And bilateral temporal rCBF is decreased in patients with schizophrenia and even more in older schizophrenia patients. These changes might be consistent with degenerative changes observed in patients with schizophrenia and be a promising method for the efficient development of a treatment strategy by measuring temporal perfusion in patients with schizophrenia.

Resting quantitative cerebral blood flow in schizophrenia measured by pulsed arterial spin labeling perfusion MRI

Arterial spin labeling (ASL) perfusion MRI is a relatively novel technique that can allow for quantitative measurement of cerebral blood flow (CBF) by using magnetically labeled arterial blood water as an endogenous tracer. Available data on resting CBF in schizophrenia primarily come from invasive and expensive nuclear medicine techniques that are often limited to small samples and yield mixed results. The noninvasive nature of ASL offers promise for larger-scale studies. The utility of this approach was examined in 24 healthy controls and 30 patients with schizophrenia. Differences between groups in quantitative CBF were assessed, as were relationships between CBF and psychiatric symptoms. Group comparisons demonstrated greater CBF for controls in several regions including bilateral precuneus and middle frontal gyrus. Patients showed increased CBF in left putamen/superior corona radiata and right middle temporal gyrus. For patients, greater severity of negative symptoms was associated with reduced CBF in bilateral superior temporal gyrus, cingulate gyrus, and left middle frontal gyrus. Increased severity of positive symptoms was related to both higher CBF in cingulate gyrus and superior frontal gyrus and decreased CBF in precentral gyrus/middle frontal gyrus. These findings support the feasibility and utility of implementing ASL in schizophrenia research and expand upon previous results.

P.1.e.002 Aging effects on the changes of regional cerebral blood flow in schizophrenia

P.1.e.002 Aging effects on the changes of regional cerebral blood flow in schizophrenia

Age and Regional Cerebral Blood Flow in Schizophrenia: Age Effects in Anterior Cingulate, Frontal, and Parietal Cortex

Positron emission tomography ([15O] water PET) was used to examine the relationship between age and regional cerebral blood flow (rCBF) in schizophrenia. Forty-nine unmedicated male patients, ages 20–51, underwent imaging during an eyes-closed resting condition. Negative correlations were observed between age and rCBF in the anterior cingulate, as well as in frontal (Brodmann area 8) and parietal cortex (area 40) bilaterally. The observation of reduced rCBF in the anterior cingulate with increased age is consistent with previous findings in healthy subjects. In contrast, the reduced flow observed in the frontal and parietal regions may be unique to schizophrenia.

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

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. 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. 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. 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.

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 [ 15O]H 2O 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.

Regional Cerebral Blood Flow in Schizophrenia Using Stable Xenon-Enhanced Computed Tomography

To investigate the regional cerebral blood flow (rCBF) and the factors affecting the rCBF in schizophrenia, we measured the rCBF using stable xenon-enhanced computed tomography in 118 schizophrenic patients and 21 healthy subjects. A multiple regression analysis was applied to assess the potential affecting factors, i.e. age, gender, duration of illness, dose of antipsychotics and usage of antiparkinsonism and antianxiety drugs. The rCBF of the schizophrenic patients was significantly lower than that of the healthy subjects in all regions except for the occipital region. The rCBF was decreased with increasing age in both groups to the same extent. The dosage of antipsychotic drugs taken had a significant regression relationship with the rCBF in the bilateral thalamus.

Regional Cerebral Blood Flow in Schizophrenia and the Local Circuit Neurons Hypothesis

It has been suggested that nitric oxide, a nonconventional intra- and intercellular messenger involved in various biological and nervous system functions, may play a crucial role in a sophisticated cerebral microvascular system that regulates cerebral blood flow (CBF) under resting and activated conditions. A review of regional cerebral blood flow (rCBF) studies is schizophrenia shows that in schizophrenia patients this microvascular regulatory system may be deficient, failing to selectively raise rCBF in areas of the frontal and temporal lobes to respond to the physiological load placed on brain cells in these areas during certain neuropsychological tasks. A hypothesis about the more general role of local circuit neurons (LCNs) in the pathophysiology of schizophrenia is revised in light of recent information about both the characterization of LCN subpopulations and the interactions of multiple neuro-transmitter systems in midbrain, striatum, and cortex. This revision helps explain the subtle rCBF regulatory failure, as well as other failures in information processing, in schizophrenia patients and points to interneurons as likely sites for the action of both typical and atypical antipsychotic drugs.

Cerebral blood flow in schizophrenia: Effects of memory processing on regional activation

Regional cerebral blood flow (rCBF) was measured with the 133Xenon clearance technique and a high resolution (254 detectors) scanner during the performance of a verbal and a facial memory task in 18 patients with schizophrenia and 18 sociodemographically matched controls. Patients and controls had comparable resting rCBF, but differed in global and hemispheric rCBF changes induced by the memory tasks. Patients had less global increase, which was relatively higher in the left hemisphere, and this was more pronounced for the verbal task. Although controls showed appropriate laterality changes (L > R for verbal and R > L for facial memory) in the midtemporal region, patients failed to show such a focal pattern. They did not show appropriate laterality change in the midtemporal region, but instead showed such changes in other regions. Patients showed greatest impairment in specificity of verbal recognition performance, and this correlated with severity of hallucinations and delusions. This supports a model of left temporal lobe dysfunction in schizophrenia.

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.

Patterns of cerebral blood flow in schizophrenia.

Positron emission tomography was used to study the relationship between rCBF and symptom profiles in 30 schizophrenic patients. Factor analysis confirmed that the symptoms segregated into three syndromes--psychomotor poverty, disorganisation, and reality distortion--described previously. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in paralimbic and association cortex, and in related subcortical nuclei. The study confirmed predictions that psychomotor poverty and disorganisation are associated with altered perfusion at different loci in the pre-frontal cortex, and reality distortion with altered perfusion in the medial temporal lobe. The perfusion patterns suggest that the abnormalities of brain function underlying each of the three syndromes are not confined to single loci, but involve distributed neuronal networks.

The effect of L-DOPA on negative symptoms, cognitive performance, and regional cerebral blood flow in schizophrenia : David G. Daniel, M.D., Nancy Breslin, M.D., James Clardy, M.D., Terry Goldberg, Ph.D., James Gold, Ph.D., Joel Kleinman, M.D., Ph.D., Daniel R. Weinberger, M.D. Clinical Brain Disorders Branch, National Institute of Mental Health, Neuropsychiatric Research Hospital, Washington, D.C. 20032

The effect of L-DOPA on negative symptoms, cognitive performance, and regional cerebral blood flow in schizophrenia : David G. Daniel, M.D., Nancy Breslin, M.D., James Clardy, M.D., Terry Goldberg, Ph.D., James Gold, Ph.D., Joel Kleinman, M.D., Ph.D., Daniel R. Weinberger, M.D. Clinical Brain Disorders Branch, National Institute of Mental Health, Neuropsychiatric Research Hospital, Washington, D.C. 20032

Regional cerebral blood flow in schizophrenia: Repeated studies during a psychotic episode

Regional cerebral blood flow in schizophrenia: Repeated studies during a psychotic episode

Regional cerebral blood flow in schizophrenia: Repeated studies during a psychotic episode

Regional cerebral blood flow (rCBF) measurements and clinical ratings were performed on 17 schizophrenic patients and a subgroup of 10 medicationfree patients before and after treatment. While clinically exacerbated patients had normal blood flow, patients in remission showed a redistribution of flow with lower values in frontal areas. Anteroposterior ratios correlated with the degree of behavioral disturbances, suggesting that the level of frontal lobe activity in schizophrenia may be a function of the patient's clinical state at the time of study.

Frontality, Laterality, and Cortical-Subcortical Gradient of Cerebral Blood Flow in Schizophrenia: Relationship to Symptoms and Neuropsychological Functions

According to the three hypotheses on the regional brain dysfunction in schizophrenia that have received some support in studies of cerebral blood flow (CBF) and cerebral metabolic rate, we calculated eight CBF measurement indices in 59 schizophrenic patients; frontality, laterality, cortical to subcortical gradients and superior to inferior difference. Four factors were selected from these eight indices, treated by principal component factor analysis (factor 1: cortical to subcortical gradient; factor 2: inferior frontality; factor 3: superior frontality; factor 4: laterality). We investigated their correlations with clinical and demographic characteristics. Factor 1 correlated with duration of illness. Factor 2 related most highly to numbers of perseverative errors on the Wisconsin Card Sorting Test and moderately to anhedonia. Factor 4 related to attentional impairment score of the Scale for the Assessment of Negative Symptoms. The schizophrenia specific symptom score calculated from the Brief Psychiatric Rating Scale did not relate to any of these factors. It seemed that there were various dimensions of neural deficits in schizophrenia, corresponding to various aspects of symptomatology or neuropsychological functions.

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.

Regional cerebral blood flow in schizophrenia: a preliminary report.

Regional cerebral blood flow in schizophrenia: a preliminary report.