Search results
Found 18093 matches for
New models for depression
Ebert D, Ebmeier KP (eds): New Models for Depression. Adv Biol Psychiatry. Basel , Karger, 1998, vol 19, pp 1–33 ............................ Cognitive ...
Effects of a single dose of the acetylcholinesterase inhibitor velnacrine on recognition memory and regional cerebral blood flow in Alzheimer's disease.
The effects of a single oral dose of the acetylcholinesterase inhibitor velnacrine maleate on word and object recognition memory and regional uptake of 99mTc-exametazime were examined in patients with Alzheimer's disease. Word recognition memory was marginally improved 2 h after 75 mg velnacrine. With the same dose of velnacrine a relative increase in superior frontal uptake of 99mTc-exametazime was shown with single photon emission computed tomography (SPECT). This suggests increased regional perfusion and metabolism as a consequence of cholinergic stimulation. The effect did not co-vary with the degree of memory improvement, but, instead, more cognitively impaired patients showed a greater increase in tracer uptake after velnacrine, suggesting cholinergic hypersensitivity in the brains of Alzheimer patients.
A comparison of Tc-99m HM-PAO and I-123 IMP cerebral SPECT images in Alzheimer's disease and multi-infarct dementia.
SPECT images of the brain can be obtained using either 123I labelled amines or 99mTc-hexamethylpropyleneamineoxime (HM-PAO). Both materials produce images which are blood flow dominated and so appear similar in normal subjects, although the respective mechanisms of uptake are not yet finally established. It seems likely, however, that the different mechanisms of uptake are responsible for recent reports of some differences seen in images obtained with the two types of agent in patients with cerebral pathology, mainly cerebrovascular disease. In this study, 12 demented patients, 6 with dementia of the Alzheimer type (DAT) and 6 with multi infarct dementia (MID), were imaged with 123I-isopropylamphetamine (IMP) and 99mTc-HM-PAO and the images compared. Significantly more lesions were seen with IMP than HM-PAO (P less than 0.02); out of a possible 120 sites, 41 lesions were seen with IMP compared to 28 with HM-PAO, 23 being seen with both agents. However, it is concluded that either agent can be used for the differential diagnosis of dementia, a task for which the new cerebral blood flow agents seem well suited.
Neuropsychological function and diurnal variation in depression.
Twenty-six patients suffering from DSM-III-R major depressive episode with diurnal variation of mood were examined at approximately 8 AM and 8 PM, using a neuropsychological test battery. We found that tests of executive function, especially the verbal fluency test, were sensitive measures of diurnal variation, but that personality measures were relatively robust in that they were not significantly affected by diurnal variations of mood. The relevance of detecting and assessing diurnal changes of mood with reliable, objective measures of performance is discussed.
Cognitive brain potentials and regional cerebral blood flow equivalents during two- and three-sound auditory "oddball tasks".
Ten healthy volunteers were examined with single photon emission tomography and 99mTc-exametazime. They were studied on 2 occasions, during a 2- and a 3-sound auditory discrimination (oddball) task. Twenty healthy volunteers were used as controls, studied once at rest. During the 2-tone task there was a bilateral posterior (occipito-) temporal and medial frontal activation, a left pericentral increase, and posterior cingulate suppression. During the 3-sound task activation was again found in posterior (occipito-) temporal, medial frontal cortex, left pericentral, with a small non-significant reduction in posterior cingulate uptake. Compared with the 2-tone task, there was a trend towards higher activity in left medial frontal, right posterior temporal and posterior cingulate cortex in the 3-sound task. P3b amplitudes were negatively correlated with posterior cingulate tracer uptake during both tasks. Positive correlations with P3b amplitudes were found in various frontal and temporal regions. These results are consistent with more invasive localisation studies of P3b. Posterior cingulate cortex appears to be inhibited during the oddball tasks, the more so, the more restricted the range of stimuli, and the greater the task-related recruitment of neurones (P3b amplitude). As expected from its more frontal distribution, P3a amplitude was positively correlated with anterior cingulate tracer uptake, and negatively correlated with temporal cortical activity.
Diurnal variation of mood and neuropsychological function in major depression with melancholia.
20 DSM-III-R melancholics with clinically evident diurnal symptoms and 20 controls were assessed with a battery of neuropsychological tests, a test of maximum voluntary hand-grip, and neuroendocrine measures of hypothalamic-pituitary-adrenal axis function morning and evening in a 24-h period, using a balanced design. The morning pattern of neuropsychological impairment in the melancholics was comprehensive, affecting attention and concentration/working memory, episodic memory, reaction time and, strikingly, the speed of simultaneous match to sample, which was performed more slowly than the version of the task delayed to 0 or 4 s. The melancholics were significantly weaker than controls, on a measure of maximal voluntary contraction. Significantly improved neuropsychological function was seen in the melancholic patients in the evening, in line with diurnal improvement in mood; there was also a large increase in strength. Slowing on the digit symbol substitution test, the simultaneous match to sample task, total errors on the match to sample and hand-grip remained impaired in the evening compared to controls; other neuropsychological measures were no longer statistically different from control values which were often worsened. Neuroendocrine measures showed significantly raised levels of cortisol and ACTH morning and evening in the melancholics. Morning cortisol in the melancholics correlated with the diurnal improvement in neuropsychological functioning. The results have implications for the timing of neuropsychological assessment in major depression. Indices of neuropsychological and motor function may be as reliable quantitative estimates of illness severity as subjective estimates of mood.
State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment.
Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.
The elevation of plasma beta-endorphin levels in major depression.
Day-time plasma beta-endorphin/beta-lipotrophic hormone (beta-ENDO/beta-LPH), ACTH and cortisol have been determined in 26 patients with major depression and 25 controls. beta-ENDO/beta-LPH and cortisol were significantly elevated in patients, while ACTH was not. Cortisol levels were significantly negatively correlated with age in controls as were beta-ENDO/beta-LPH and ACTH. In patients, by contrast, cortisol levels were positively, albeit not significantly, related to age. Peptide levels were not related to age in the patient group. Instead, beta-ENDO/beta-LPH was negatively correlated with clinical ratings of symptom severity in patients and positively associated with an acute psychosocial precipitant. The findings cast further light on beta-ENDO/beta-LPH as a measure of hypothalamic-pituitary over activity in depressive illness. A negative association with symptom severity suggests that beta-ENDO/beta-LPH responses are, like those of ACTH, down-regulated in the course of depressive illness.
Selecting controls for schizophrenia research studies: the use of the National Adult Reading Test (NART) is a measure of premorbid ability.
The National Adult Reading Test (NART) has achieved popularity as a measure of pre-morbid intellectual ability, based on the premises that pronunciation of irregular words is unaffected in many clinical disorders and that performance is highly correlated with general intellectual ability. Recently, schizophrenia research studies have begun to appear in the literature, where the NART has been used to estimate pre-morbid ability. However, this use has preceded the basic required demonstration that, in fact, NART performance is unaffected by the schizophrenic process. In the present study, NART performance was compared across three groups; 20 acutely ill unmedicated DSM-IIIR schizophrenics, 10 other unmedicated acute psychotics, and 20 control subjects. When demographic variability between the groups was controlled for, there were no group differences in terms of NART performance. NART performance was not correlated with Brief Psychiatric Rating Scale scores, and in all three groups, no significant differences emerged when demographically predicted intelligence quotients were compared with NART estimated intelligence quotients. NART performance (predicted on the basis of demographic variables) was not significantly different from observed NART performance in any of the three experimental groups. However, within the sample with schizophrenia, NART estimated pre-morbid IQ was significantly higher than currently measured intellectual abilities. These results suggest that the National Adult Reading Test provides a reasonable estimate of pre-morbid ability in acutely ill, unmedicated schizophrenic patients.
Mortality and causes of death in idiopathic Parkinson's disease: results from the Aberdeen whole population study.
Two hundred and forty-nine patients with Parkinson's disease previously examined by Mutch et al 1,2 were followed up three and a half years after the original study. Cognitive impairment, age, some postural signs and symptoms of Parkinson's disease and high scores on the Hoehn and Yahr scale predicted premature death. Patients were more likely to die from respiratory infections than controls. Respiratory diseases as cause of death recorded on the death certificate were not related to kyphosis, posture scores or Hoehn and Yahr scores before death. The hypothesis is advanced that death of respiratory causes might be associated with signs of general autonomic dysregulation.
Statistical parametric mapping of (99m)Tc-HMPAO-SPECT images for the diagnosis of Alzheimer's disease: normalizing to cerebellar tracer uptake.
BACKGROUND: For a quantitative comparison of images obtained during (99m)Tc-hexamethylpropylene amine oxime (HMPAO) single-photon emission computed tomography (SPECT), brain activity values are usually normalized to a reference region. In studies of Alzheimer-type dementia (ATD), the cerebellum is often used as a reference region, assuming that it is spared any major pathological involvement. Statistical parametric mapping (SPM) may enhance the evaluation of SPECT scans in ATD patients. However, current SPM software only allows scaling to average whole brain activity (i.e., global normalization). The aim of this study was to develop an easily applied, objective, and reproducible method for determining average cerebellar tracer uptake so that images can be scaled specifically to cerebellar activity prior to the performance of SPM analysis. We also investigated whether cerebellar normalization increases the sensitivity and specificity of SPM analysis of ATD patients compared with global normalization. METHODS: Image files were taken from a parallel study investigating the use of SPECT as a diagnostic tool for early onset of ATD. Two methods for determining cerebellar activity were developed: one manually, using templates, the other automated, using specified coordinates entered into a Matlab routine. Group comparison of ATD patients versus controls (= healthy volunteers and depressed patients) was performed on a voxel-by-voxel basis using SPM 96 on Windows 95. Receiver operator characteristics (ROC) were computed for 20 student raters examining patient and control scans with and without single-subject SPMs. RESULTS: The reduction of cerebral blood flow in the group of ATD patients appeared 1.7 times greater in spatial extent when the tracer uptake was normalized to cerebellum rather than to average whole brain activity. Computing the reverse contrast (reductions in the control group compared with ATD patients) produced clusters of significance in globally normalized images which were not manifest after normalizing to cerebellum. This is consistent with the notion that the cerebellum is spared in ATD. Analysis of the area under the ROC curve showed that cerebellar-normalized SPM produced significantly improved accuracy over perfusion scans alone. CONCLUSION: An easily applied, objective, reproducible method was developed for normalizing images to cerebellum prior to the performance of SPM analysis. Cerebellar normalization produced more extensive abnormalities in SPM analyses of ATD patients than global normalization. Furthermore, cerebellar normalization produced marginally more accurate diagnostic results in single-scan SPM analysis of ATD patients than did global normalization.
Clinical and psychometric correlates of dopamine D2 binding in depression.
BACKGROUND: Single photon emission tomography (SPET) with the dopamine D2/3 ligand 123I-IBZM gives a semi-quantitative estimate of dopamine binding. In depressed patients, we predicted evidence of reduced function, i.e. increased binding, particularly in more retarded patients. METHODS: Fifteen depressed patients with major depressive illness and 15 healthy, age- and sex- matched volunteerS were examined with a clinical and neuropsychological test battery and high resolution IBZM-SPET. Estimates for specific binding were computed by averaging striatum to whole slice or frontal uptake ratios over 8-10 scans acquired from 70 min after tracer injection. RESULTS: Using whole slice as reference, left striatal uptake ratios did not significantly differ for patients from controls. Right ratios were significantly higher in patients than controls (P = 0.03). There were significant correlations between IBZM binding in left and right striatum and measures of reaction time and verbal fluency. CONCLUSIONS: Increased IBZM binding in striatum probably reflects reduced dopamine function, whether due to reduced release of dopamine, or secondary up-regulation of receptors. The observed abnormalities may be trait or state related, an issue that needs to be addressed with longitudinal study designs. The possible role of medication as a confounding variable requires further exploration.
Temporal lobe abnormalities in dementia and depression: a study using high resolution single photon emission tomography and magnetic resonance imaging.
OBJECTIVES: Perfusion SPECT and MRI were used to test the hypothesis that late onset depression is associated with brain abnormalities. METHODS: Forty depressed patients (DSM-III-R major depressive episode, not demented at two year follow up) were recruited who were either drug free, or on a stable dose of antidepressants for at least three weeks, as well as 22 demented patients (DSM-IIIR and NINCDS/ADRDA criteria for probable Alzheimer's disease). Patients were imaged at rest with a high resolution single slice 12 detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-exametazime (HM-PAO). Temporal lobe templates were fitted with brains pitched by 20 degrees-30 degrees. A subgroup of 41 patients (22 depressed) were also scanned using a Siemens Magnetron 1.0 Tesla magnetic resonance imager, using a FLAIR imaging sequence for the assessment of white matter hyperintensities, and a Turbo FLASH sequence for the measurement of medial temporal lobe width. RESULTS: Demented patients showed reduced perfusion, particularly in the left temporoparietal cortex. In these regions of interest, patients with late onset depression tended to have perfusion values intermediate between patients with early onset depression and demented patients. Differences in changes in white matter between demented and early and late onset depressive patients did not reach conventional levels of significance. Temporal lobe width differed between demented and depressed patients, but not between early and late onset depressed patients. Perfusion and temporal lobe width were not associated, but reductions of perfusion were associated with periventricular white matter changes. Mini mental state examination scores were associated with temporal perfusion in demented patients and with changes in deep white matter in depressed patients. Finally, severity of depressive symptoms was associated with decreased perfusion in frontotemporal and basal ganglia regions of interest. CONCLUSION: A cumulative effect of duration of illness on regional cerebral perfusion could not be confirmed. Late onset depression may show more abnormalities of deep white matter and of left temporoparietal perfusion than early onset depression, but the underlying pathology remains to be established.
Alzheimer's disease in adults with Down's syndrome: the relationship between regional cerebral blood flow equivalents and dementia.
Twenty adult patients suffering from Down's syndrome (DS) were recruited from hospitals and the community, together with 14 age- and sex-matched controls of normal intelligence. Dementia was diagnosed in patients using a structured psychiatric and physical examination as well as a carer interview and case notes. All patients and controls were imaged using single photon emission computerized tomography with 99mTc-exametazime. Four patients were clinically demented and all of them showed regional cerebral blood flow (rCBF) changes commonly found in patients with Alzheimer's disease, namely bilateral temporo-parietal deficits. These changes were also observed in about half of the patients without clinical evidence of dementia, but in none of the healthy controls. Across the group of patients, temporo-parietal rCBF deficits were associated with evidence of deterioration, but not with advancing age.
Estimating pre-morbid intellectual ability in the Alcoholic Korsakoff syndrome.
The National Adult Reading Test (NART) is widely used in clinical and research settings to estimate pre-morbid intellectual levels. The validity of the NART in estimating premorbid ability in Alcoholic Korsakoff Syndrome (AKS) is examined in the present study. Twenty AKS subjects were compared with 40 healthy controls. The validity of the NART as a pre-morbid measure in AKS was examined using four methods. AKS subjects made more NART errors than controls, had lower NART predicted IQ than demographically predicted IQ, made more NART errors than predicted by demographic variables and demonstrated NART performance which correlated with degree of memory impairment. It is concluded that NART performance is detrimentally affected by the AKS and that estimating pre-morbid intellectual level in Korsakoff's psychosis using the NART may be invalid. Furthermore, it is postulated that the impaired ability to pronounce correctly irregular words in AKS may reflect a failure in cognitive 'error checking' which may represent a consequence of frontal lobe dysfunction.
Altered cerebral perfusion measured by SPECT in relatives of patients with schizophrenia. Correlations with memory and P300.
BACKGROUND: Genetic studies in schizophrenia are hampered by the complex heterogeneous clinical phenotype. Biological variables identified as trait markers of risk could clarify the mode of inheritance, define clinical subgroups and provide clues about aetiology. AIMS: To use single photon emission computed tomography (SPECT) to compare brain perfusion maps in patients with schizophrenia (n = 19), their asymptomatic 'high-risk' relatives (n = 36) and control subjects (n = 34) and to examine the relationships between imaging, memory and P300 event-related potential. METHOD: SPECT, memory tests and P300 recording were carried out. RESULTS: In the patients with schizophrenia and their relatives, perfusion was reduced in left inferior prefrontal and anterior cingulate cortex and increased bilaterally in a subcortical region. Perfusion significantly correlated with verbal memory and P300 amplitude in left inferior prefrontal cortex and with P300 latency in anterior cingulate cortex. CONCLUSIONS: Medication- and symptom-free relatives had altered regional perfusion intermediate between subjects with schizophrenia and controls. Impaired perfusion, verbal memory and P300 appear to be related traits associated with an increased risk of illness.
Limbic dysfunction in schizophrenia and mania. A study using 18F-labelled fluorodeoxyglucose and positron emission tomography.
BACKGROUND: Diagnostic classes (derived from CATEGO) can be correlated with regional brain metabolism in patients with major psychiatric disorders. METHOD: Seventeen patients with schizophrenia, 15 with mania, 10 with depression and 10 healthy Volunteers were examined with positron emission tomography (PET) and 18F-labelled fluorodeoxyglucose, as a marker for glucose metabolism. The number of possible comparisons of regions of interest was reduced by principal-components analysis, and differences in factor scores were determined between diagnostic groups. RESULTS: Four independent factors, representing distributed brain systems, emerged: an anterior-posterior (1), a left-right temporal (2), a temporofrontal (3), and a mediofrontal (4) system, of which (1), (2) and (3) were abnormal in schizophrenia, (1) and (2) in mania, and (1) in depression. CONCLUSIONS: Abnormal patterns of metabolism could be detected, in decreasing order, in schizophrenia, mania and depression. Some of these abnormalities are likely to be due to medication, but others will be associated with structural or functional abnormalities of the frontolimbic system in the diagnostic groups.