Regional cerebral blood flow in depression

In the review article, the results of studies on regional cerebral blood flow (rCBF) in major depression are presented. Most studies have reported global and regional deficits in cerebral blood flow in major depression as compared to healthy controls. Longitudinal studies show that after recovery from depression an increase of CBF has been observed. The influence of different biological treatment methods on rCBF is also discussed. Findings regarding lateral asymmetries of cerebral function in patients with major depression are inconclusive but the deficit of rCBF is often more pronounced in the left hemisphere. The nature of regional brain flow abnormalities in depression is unclear. Structural changes of the brain and biochemical abnormalities are under consideration.     

Regional cerebral blood flow in depression

Regional cerebral blood flow (rCBF) was measured in patients with endogenous depression by the single photon emission computed tomography (SPECT) using N-isopropyl-p-[123I]iodoamphetamine (IMP). The subjects were 32 patients with endogenous depression and 20 normal controls. These 32 patients, who were divided into 10 unmedicated group and 22 medicated group, were reexamined when the depressed patients reverted to a euthymic state (remission). The value of rCBF was assessed by the corticocerebellar ratio (CCR), which was expressed as a ratio of activity per pixel in the cerebral regions of interests (ROIs) to the activity per pixel in the cerebellum. The depressive patients showed a decrease in rCBF all over the cerebral regions and, especially, the lower rCBF in the left than in the right hemisphere. These changes turned toward normal in a remitted state following treatments, though there was no significant difference in rCBF between the medicated and unmedicated patients. There was a significantly negative correlation between the severity of depressive symptoms and the mean rCBF in a total of patients with depression. These results suggest that psychiatric symptoms in the depressive patients might be related to the left hemispheric dysfunction.     

Regional cerebral blood flow abnormalities in late-life depression:Relation to refractoriness and chronification

Abstract We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and (^99mTc-hexamethyl-propylenamine oxime (^99mTc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefrontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dysfunction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-refractory subgroup, rCBF decreased significandy in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfusion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression.     

Regional cerebral blood flow in depression and mania

Forty-three depressed inpatients, referred for electroconvulsive therapy, and 30 manic patients were examined with clinical ratings and regional cerebral blood flow (rCBF) determinations. The depressed patients were mainly medication free, while most of the manic patients were medicated. Both patient groups showed a normal cerebral blood flow level and regional distribution compared with age- and sex-matched normal controls. In the depressed group and especially in the unipolar subgroup, a significant positive relationship was found between the mean rCBF and symptoms of depression and cognitive dysfunction. Eighteen of the depressed and 18 of the manic patients were reexamined in a euthymic state following treatment and recovery. Only minor and statistically nonsignificant flow changes were found in connection with the clinical improvement. In the manic patients, a significant negative relationship was found between neuroleptic dosage and rCBF.     

Regional cerebral metabolism in early Alzheimer's disease with clinically significant apathy or depression.

BACKGROUND: Alzheimer's disease (AD) is clinically characterized by cognitive impairment and behavioral disturbances. The aim of the study was to identify regional alterations in brain function associated with neuropsychiatric symptoms in early AD. METHODS: Patients underwent measures of cerebral glucose metabolism applying positron emission tomography (PET) and (18)F-fluorodeoxyglucose. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI). Positron emission tomography images of patients suffering a neuropsychiatric symptom of clinical significance (NPI subscore for a specific item >/=4 points) were compared with the images of patients without the specific symptom under study (NPI subscore for a specific item = 0 points). RESULTS: A total of 53 patients with AD (Mini-Mental State Examination [MMSE] 22.5 +/- 2.94 points) entered the study. Of all symptoms, apathy and depression were most frequently encountered. The patient group with apathy (n = 17) revealed significant decreases in left orbitofrontal regions when compared with patients free of apathy. Depression of clinical significance (n = 10) was associated with hypometabolism in dorsolateral prefrontal regions. CONCLUSIONS: These findings support the notion that different functional circuits underlie apathy and depression in early AD.     

Regional cerebral blood flow alterations in unipolar depression

Forty-seven symptomatic inpatients and outpatients with major depression (13 nonendogenous, 23 endogenousand 11 psychotic by Research Diagnostic Criteria) were compared with 138 normal control subjects. Absolute regional cerebral blood flow (rCBF, ml/minute/100 g) was measured with ¹³³Xe single photon emission computed tomography. Flow ratios (region of interest/ global flow) and residual scores (the difference between patient flow ratios and expected normal flow ratios, as derived from the control population) were also computed. Results revealed significant age × region × depression subtype interactions for absolute, ratio, and residual flow data. Consequently, a test of group means (or analysis of covariance) could not be used to examine between-group differences. Multiple regression analyses were employed to study the effects of age on rCBF. This analysis revealed that different, though sometimes overlapping, regions exhibited different age effects on rCBF in different depressive subtypes. Thus, diagnostic-subtype-dependent age effects on rCBF precluded comparisons of mean values within or across regions for subject groups, but distinguished between symptomatic depressed patients and control subjects and among patient groups. Possible causes of such effects include variations in duration of illness or medication history or sensitization phenomena.     

Regional cerebral blood flow abnormalities in chronic solvent abusers

This study aimed to reveal regional abnormalities of cerebral blood flow (CBF) and their relation to amotivational syndrome which causes poor social prognosis in solvent abusers Sixteen chronic solvent abusers (12 males and four females) along with five normal subjects underwent single photon emission computed tomography with N-isopropyl-p[123I]iodoamphetamine. The patients received a clinical evaluation with the Scale for the Assessment of Negative Symptoms. Using a semiquantitative method (normalized by the parietal cortex count), patients showed a statistically significant decrease in regional cerebral blood flow (rCBF) in the bilateral prefrontal cortices (P<0.01). In addition, the severity of hypoperfusion in the bilateral prefrontal cortices was related to the degree of severity of the avolition-apathy scale on SANS (left; P<0.05, right; P<0.01) even after excluding the effect of antipsychotics. These results suggest that rCBF abnormalities, especially in the prefrontal cortex, develop in chronic solvent abusers, and that this frontal hypoperfusion may be a biological basis of amotivational syndrome.     

Regional cerebral blood flow changes associated with ethanol intoxication

Regional cerebral blood flow (CBF) was measured via the 133Xenon inhalation technique in 26 healthy volunteers before and 60 minutes after the oral administration of ethyl alcohol or placebo on a double-blind basis. The cerebral blood flow values, corrected for test-retest differences in carbon dioxide showed a significant bilateral increase after ethanol administration. Blood levels of ethanol, estimated with a breath analyser, did not correlate with the CBF changes.     

Regional cerebral blood flow abnormalities in depressed patients with cognitive impairment.

Depression with cognitive impairment, so called depressive pseudodementia, is commonly mistaken for a neurodegenerative dementia. Using positron emission tomography (PET) derived measures of regional cerebral blood flow (rCBF) a cohort of 33 patients with major depression was studied. Ten patients displayed significant and reversible cognitive impairment. The patterns of rCBF of these patients were compared with a cohort of equally depressed non-cognitively impaired depressed patients. In the depressed cognitively impaired patients a profile of rCBF abnormalities was identified consisting of decreases in the left anterior medial prefrontal cortex and increases in the cerebellar vermis. These changes were additional to those seen in depression alone and are distinct from those described in neurodegenerative dementia. The cognitive impairment seen in a proportion of depressed patients would seem to be associated with dysfunction of neural systems distinct from those implicated in depression alone or the neurodegenerative dementias.     

Regional cerebral blood flow changes associated with emotions in children

Combining a wireless telemetry system and a portable near-infrared instrument, we developed a movable optical spectroscopy system for monitoring cerebral hemodynamic changes. The patient carries a miniaturized near-infrared spectroscopy instrument on the back, and data are sent by a wireless telemetry system to a computer, without restricting patient movement. We used this system to detect hemodynamic changes associated with being startled, anticipation, and pleasant and unpleasant emotions in the bilateral prefrontal cortices of 16 right-handed 4- to 6-year-old preschool children while they were watching a 21-minute video clip consisting of various scenes that elicited emotional responses, interpolated with neutral scenes for comparison. The children were relaxed and cooperative when they were studied. Anticipation was associated with increases in cerebral blood flow in the left prefrontal cortex of the 6-year-old children, and unpleasant emotion was associated with decreases in cerebral blood flow bilaterally compared with neutral emotion, irrespective of age. No hemodynamic changes associated with the startle response were observed. Although this study should be considered preliminary, it is suggested that the emotional response is age-dependent and that the left prefrontal cortex participates in anticipation. Our newly developed system will open a window into brain physiology in children.     

Regional cerebral blood flow in patients with Parkinson's disease.

Regional cerebral blood flow (rCBF) was measured by the xenon 133 inhalation method in 60 patients with Parkinson's disease and compared with flow data obtained in 51 age-matched normal control subjects. Mean brain rCBF was significantly reduced in patients with parkinsonism (9.5%, P less than .001). The most marked and significant rCBF decreases were observed in the older patients (18.8%, P less than .001). There was no correlation between degree of rCBF reduction and duration of parkinsonism. Decreases in hemispheric mean rCBF values were similar in both hemispheres even in patients with unilateral signs. The present study provides additional evidence for involvement of the cerebral cortex in Parkinson's disease. The rCBF decline may be associated in part with high prevalence of mental impairment and cortical atrophy and with diminished cerebral metabolic rate due to brain dopamine deficiency in patients with parkinsonism.     

Regional cerebral blood flow changes in depression after electroconvulsive therapy

A large number of studies have documented regional cerebral blood flow (rCBF) abnormalities in depression. A smaller yet significant number of studies have examined changes in rCBF before and after treatment. The findings, however, have been variable with regard to changes before and after electroconvulsive therapy (ECT). A consecutive series of patients (n=10) with drug-resistant major depressive episode according to DSM-IV with 17-item Hamilton Rating Scale for Depression (HRSD) scores greater than or equal to 14 gave their informed consent and were studied with technetium-99m ethyl cysteinate dimer single-photon emission computed tomography (99mTc-ECD SPECT) before and after a course of ECT. The results were analyzed with statistical parametric mapping version 99. No region showed significant positive correlations between rCBF patterns of changes and HRSD changes, but three clusters emerged as showing significant negative correlations. These regions corresponded with left frontopolar gyrus, left amygdala, globus pallidus and nucleus accumbens, and left superior temporal gyrus. It was speculated that ECT affected both the prefrontal cortex, commonly assumed to be involved in depression, and the amygdala, known to play a central role in the processing of emotional stimuli, through the limbic-cortical-striatal-pallidal-thalamic circuit.     

Eye-head coordination abnormalities and regional cerebral blood flow in Alzheimer's disease

1. Three patients with Alzheimer's disease (AD) and three healthy controls (HC) were examined for eye-head coordination. Regional cerebral blood flow (rCBF) was measured in AD patients. 2. Eye-head coordination was analyzed using a Vision analyzer, and magnetic sensors. The authors measured the rCBF with 123I-IMP, and 99mTc-ECD SPECT. 3. AD reduced gaze accuracy and head movements, and prolonged the latency of saccade as compared to HC. AD patients had a tendency to focus on the target by using eye movements only. 4. AD reduced the rCBF in the inferior parietal part and the visual area, relative to the motor area. Damage of these areas may have caused the eye-head coordination disorders in the AD patients.     

Regional cerebral blood flow during spreading cortical depression in conscious rats

Spreading cortical depression (SCD) of EEG activity was induced in one cerebral hemisphere of conscious restrained rats by direct current stimulation of the lateral frontal cortex. Regional CBF was measured using [14C]iodoantipyrine and brain dissection. An early phase of increased CBF was not measured in conscious rats, but an early relative hyperperfusion was measured if the resting CBF was first reduced by treatment with pentobarbital or indomethacin. A long-lasting reduction in CBF was measured in conscious rats following the passage of SCD. This flow reduction resolved after 3 h. In conscious rats, CBF decreased in the striatum and thalamus ipsilateral to the SCD, paralleling the CBF changes occurring in the cortex. The CBF change in these deep structures was abolished by pentobarbital. An early transient increase in regional CBF was measured in the cerebral cortex contralateral to the hemisphere involved with SCD in conscious rats. This early contralateral hyperperfusion was also abolished by pentobarbital or indomethacin but not by atropine or propranolol. The vascular response to SCD in conscious rats differs from that which occurs in anesthetized rats.     

Regional cerebral blood flow and prognostic evaluation in Alzheimer's disease

The present investigation reports the application of regional cerebral blood flow (rCBF; (133)Xe method) to prognostic purposes in a consecutive series of 76 patients (mean age 68.4 +/- 8.7 years) with probable Alzheimer's disease (AD; NINCDS-ADRDA criteria). The likelihood that rCBF from a posterior temporal-inferior parietal area in each hemisphere at the first visit may predict timing of achievement of three endpoints (i.e. loss of activity of daily living, ADL, incontinence and death due to end-stage AD) was tested by the 'lifereg' procedure of the Statistical Analysis System package. With respect to baseline evaluation, 32 patients lost ADL 20.6 +/- 17.4 months later, 31 developed incontinence 27.1 +/- 19.0 months later, and 16 patients died after 40.9 +/- 23.8 months of follow-up. Baseline rCBF significantly predicted all end-points: the loss of ADL (left hemisphere: p = 0.04; right hemisphere: p = 0.02), incontinence (p = 0.02 in both hemispheres) and death (p = 0.01 in both hemispheres). Statistical significance was maintained for the loss of ADL and incontinence both in a subgroup of mildly demented patients, in whom death was not considered due to the low number of patients who died, and in a multivariate analysis including patient age, age at onset, sex, duration of illness, Mini-Mental State Examination score and presence of extrapyramidal signs and psychotic symptoms at the first visit. This study shows that rCBF measurement in a posterior temporal-inferior parietal area may give prognostic information on timing of evolution of AD, whenever performed during the course of the disease, and may be utilized both in clinical practice and for social planning.     

Regional cerebral blood flow in patients with leuko-araiosis and atherosclerotic carotid artery disease

The relation between white-matter lesions (WMLs), demonstrated with magnetic resonance imaging, and regional cerebral blood flow (CBF), measured with dynamic positron emission tomography and [18F] fluoromethane, was investigated in 20 patients with atherosclerotic disease of the internal carotid artery. There was no correlation between the extent of small patchy WMLs and hemispheric CBF, but hemispheric CBF was significantly reduced in 5 patients with multiple large or confluent lesions. Distinct focal cortical CBF reductions were observed when large WMLs (greater than 5 mm) were located directly beneath the cortex, whereas large WMLs in deeper white matter were associated with a more diffuse decrease of cortical perfusion. There was no evidence of preferential CBF reduction in vascular border zones with increasing severity of WMLs or stenosis of the internal carotid artery. The side of previous transient ischemic symptoms correlated significantly with hemispheric CBF asymmetries, but not with asymmetries of WMLs and internal carotid artery stenosis. It can be concluded from these results that the presence of small patchy WMLs shown by magnetic resonance imaging cannot be used as evidence of impaired cerebral perfusion, while large lesions indicate clinically relevant cerebrovascular disease affecting cortical blood flow.     

Volume cerebral blood flow reduction in pre-clinical stage of Alzheimer disease:

The association of decreased cerebral blood flow with the development of Alzheimer's disease (AD) has been a recent target of interest. By using neuroimaging techniques, growing attention has been devoted to the identification of preclinical AD.In this study, color duplex sonography of cervical arteries was used to measure mean cerebral blood flow (CBF) on 55 amnestic Mild Cognitive Impairment (MCI) patients. Two years after enrollment, excluding patients who progressed to dementia other than AD, two subgroups were identified, patients who developed AD (MCI converters) and patients with preserved cognitive and functional level (MCI non-converters). Examining the mean difference of CBF measured at baseline in the two subgroups obtained, a significant difference was noticed (MCI converters 539.3 +/- 114.3 vs MCI non converters 636.0 +/- 143.9, p < 0.05). MCI patients with CBF higher than median value (558 ml/min) had lower risk of developing AD (specificity 72.2%, sensitivity 68.4%) within a two year follow-up. Ultrasonography of the cervical arteries is a simple, non invasive and widespread technique useful in detecting CBF decline during the MCI stage, thus identifying patients who later will convert to AD.