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Researchers from the NIHR Oxford Health Biomedical Research Centre (a partnership between the University of Oxford and the Oxford Health NHS Foundation Trust), like many others across the country, are responding to the call to support frontline NHS services and meet the challenge of COVID-19.
Explaining and understanding in psychopathology.
Psychoanalytical methodology has been described as causal explanation or hermeneutic understanding. This methodological dichotomy has been introduced into psychopathology by Karl Jaspers. Contemporary authors' contributions in the area are discussed. Although these authors accept a role for both methods, they agree with Jaspers that psychoanalysis should be subjected to the logical limitations of hermeneutic analysis. A logical framework for the interaction of explaining with understanding is presented and discussed in relation to psychiatric research.
Further evidence that reading ability is not preserved in Alzheimer's disease.
BACKGROUND: Pre-morbid intelligence level is routinely assessed in Alzheimer's disease using the National Adult Reading Test (NART). This practice is based on the assumption that pronunciation of irregular words remains unaffected by the disease process. Recent reports have suggested that reading ability may become compromised in moderately demented subjects. METHOD: Sixty-eight probably Alzheimer patients were classified into stages of severity (minimal, mild and moderate) using the Mini-Mental State Examination (MMSE). NART and demographic equations were used to estimate pre-morbid ability. RESULTS: A significant correlation emerged between dementia severity and reading ability, NART v. MMSE scores, r = 0.46, P < 0.01. When the total sample was subdivided into moderate, mild and minimal subgroups, significant between-group differences emerged, despite the groups being well matched for age, sex, and years of full-time education. Pre-morbid IQ, as estimated by demographic regression equations, did not correlate with dementia severity. CONCLUSION: NART performance is compromised in moderate Alzheimer disease, and the measure provides a serious underestimate of pre-morbid IQ in patients with an MMSE of 13 or less.
Follow-up study of depression in the elderly. Clinical and SPECT data.
BACKGROUND: Imaging studies in depression of the elderly are often small and highly selective. AIMS: To investigate a large group of elderly depressed patients in order to assess changes in clinical, imaging and neuropsychological variables at follow-up. METHOD: Patients (n = 175, age range 65-91 years) with clinical depression were identified from consecutive local referrals. Clinical interviews, neuropsychological tests and SPECT scans were carried out at referral and at two-year follow-up. RESULTS: Of 84 re-examined patients, 46.5% were well, 9.5% were ill, 33% partially recovered and 11% had developed dementia. Duration of illness before index assessment was the only factor to predict outcome. Thirty-nine patients could be scanned and followed up. There were no differences between patients with good or poor depressive outcome on SPECT. Ten clinically improved patients could be re-examined with SPECT. There were relative increases in right cingulate gyrus and right cerebellum at follow-up. CONCLUSIONS: The patients group was comparable with other studies showing high levels of residual depressive symptoms. Activity changes in limbic cortex are implicated in depression of old age.
Brain imaging and treatment response in spasmodic torticollis.
A patient with spasms of the neck, occurring when he turned his head to the left, responded to treatment with benzhexol. Cerebral blood flow imaging demonstrated reduced uptake in the right corpus striatum compared with the left. The study demonstrates the presence of an abnormality in the basal ganglia; it also illustrates response to drug treatment. Cerebral blood flow imaging may be useful in the detection of basal ganglia abnormalities in spasmodic torticollis and assist in the selection of cases which should be targeted for treatment with drugs.
Magnetic resonance imaging and single photon emission tomography in treatment-responsive and treatment-resistant schizophrenia.
BACKGROUND: Patients with schizophrenia differ from controls in several measures of brain structure and function, but it is uncertain how these relate to clinical features of the illness. We dichotomised patient groups by treatment response to test the hypothesis that treatment-resistant patients exhibit more marked biological abnormalities than treatment-responsive patients. METHOD: Twenty treatment-responsive and 20 treatment-resistant patients with schizophrenia, matched for sex, age, and illness duration, were compared by magnetic resonance imaging, single photon emission tomography, and detailed neuropsychological assessment. RESULTS: Brain-imaging variables were not statistically related to treatment response, although poorly responsive patients had lower volumes of most brain structures. Several highly significant differences emerged between patient groups on neuropsychological testing. Episodic memory functioning distinguished patient groups even after we controlled for global cognitive impairment. CONCLUSIONS: Cerebral structure and blood flow have a limited effect on treatment response in schizophrenia, but long-term episodic memory impairment is associated with, and may predict, poor prognosis.
A single photon emission computerised tomography study of regional brain function underlying verbal memory in patients with Alzheimer-type dementia.
Ten patients with Alzheimer-type dementia and nine age-matched normal controls were examined with SPECT, using split-dose 99mTc-labelled exametazime. The baseline condition involved repetition of the word 'yes' or 'no'. The activation condition involved recognition (indicated by a 'yes' or 'no') of words from a previously learned list presented along with distractor words. Patients who performed this task successfully were selected, and efforts were made to match the patients with controls according to their performance on the task, although this was not fully achieved. Uptake of 99mTc-exametazime was estimated at baseline and during the word-recognition task for predetermined regions of interest drawn from a standard neuroanatomical atlas. The baseline task appeared to normalise tracer uptake for frontal, temporal and parietal cortex in the patient group. However, during the recognition task, controls but not patients showed activation effects. These were most prominent in dorsolateral frontal cortex and adjacent anterior cingulate cortex. Among patients, successful performance was correlated with activation of dorsolateral frontal and parietal cortex on the left side. The results confirm the central role of frontal mechanisms in a recognition memory task. The study highlights some of the difficulties of using cognitive challenge tests in clinical groups.
A single photon emission computerised tomography study of regional brain function in elderly patients with major depression and with Alzheimer-type dementia.
The uptake, at rest, of 99mTc-exametazime into different brain regions was compared using SPECT for 20 elderly subjects with major depressive disorder, 20 with Alzheimer-type dementia, and 30 age-matched normal volunteers. Uptake was referred to calcarine-occipital cortex as a reference sensory area. Cross-sectional differences between the three groups were highly statistically significant, but reflected primarily the reductions in cortical uptake in the Alzheimer group. A detailed comparison of depressed patients and controls identified decrements in anterior cingulate, temporal and frontal cortex and in caudate and thalamus in men only. These decrements were correlated with impairment of performance on a trail-making task, but were also associated with continuing treatment with antidepressants or benzodiazepines. However, most depressed patients had quantitatively normal scans for posterior parietal association cortex, and this suggests that SPECT may find a limited role in the differential diagnosis of depression and dementia. The reduced brain function in some depressed patients may parallel the findings from studies of brain structure in elderly depressives; there was between good outcome at 6-18 months and increased tracer uptake in subcortical areas.
Multimodal imaging in Alzheimer's disease. The relationship between MRI, SPECT, cognitive and pathological changes.
Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.
The neuropsychiatric sequelae of mercury poisoning. The Mad Hatter's disease revisited.
BACKGROUND: The detailed effects of mercury poisoning on cognitive function, brain anatomy and regional brain function are largely unknown. We report the case of a 38-year-old man who was exposed to toxic levels of inorganic mercury. METHOD: Four years after exposure, the patient was assessed using magnetic resonance imaging (MRI), single-photon emission computerised tomography (SPECT) and detailed neuropsychological evaluation. RESULTS: The patient developed a myriad of physical and psychiatric complaints, including stomatitis, muscle spasm, tremor, skin rash and the psychiatric syndrome known as 'erythism' (Mad Hatter's disease). Neuropsychological evaluation revealed marked and significant deficits of attention concentration, particularly when under time pressure. The MRI scan was unremarkable; however, SPECT revealed hypermetabolism of the posterior cingulate CONCLUSIONS: Mercury poisoning appeared to result in a dysregulation of posterior cingulate cortex, which was associated with attention/concentration deficits and marked anxiety/agitation.
Estimation of premorbid intelligence in schizophrenia.
To determine whether the National Adult Reading Test (NART) would provide a valid estimate of premorbid intelligence in schizophrenia, two schizophrenic samples were recruited, one consisting of 35 patients resident in long-stay wards, the other of 29 patients normally resident in the community. Schizophrenic patients were individually matched for age, sex, and education with a healthy, normal subject. Both schizophrenic samples scored significantly lower on the Wechsler Adult Intelligence Scale (WAIS) than their respective control groups. NART-estimated IQ did not differ significantly between the community-resident schizophrenics and their controls, suggesting that the NART provides a valid means of estimating premorbid intelligence in such a population. NART-estimated IQ was significantly lower in the long-stay sample than in their controls. Although low NART scores in this latter sample could be a valid reflection of low premorbid IQ, the alternative explanation that NART performance was impaired by onset of the disease cannot be ruled out.
Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression. Controlled magnetic resonance imaging study.
BACKGROUND: The aetiology of treatment-resistant major depression is little understood; its apparent intractability may reflect brain abnormality. METHOD: Magnetic resonance images of the brains of 20 subjects with major depression lasting for two years or more were compared with 20 healthy control subjects and 20 other subjects who had completely recovered from depression. Subjects were individually matched for age, gender, years of education and premorbid IQ. Grey matter was segmented from the images, and compared between groups on a voxel-by-voxel basis. RESULTS: Subjects with chronic depression showed reduced grey matter density in the left temporal cortex including the hippocampus. There was also a trend for reduction in the right hippocampus. Left hippocampal grey matter density was correlated with measures of verbal memory, supporting the functional significance of the observed magnetic resonance imaging changes. CONCLUSIONS: Our results potentially challenge the accepted view of depression as a functional and fully reversible illness, implying instead that more permanent brain changes may be associated with chronicity. Confirmatory longitudinal and prospective studies are required to determine whether these differences pre-date the onset of depression or are the result of the chronic illness process or its treatment.
Reduced cortical excitability in depression. Impaired post-exercise motor facilitation with transcranial magnetic stimulation.
BACKGROUND: In healthy controls, preactivation of muscles by exercise results in enhanced motor-evoked potential (MEP) responses to transcranial magnetic stimulation (TMS). AIMS: We tested the hypothesis that medicated, depressed patients would show reduced post-exercise MEP facilitation compared with controls. METHOD: Ten patients with DSM-IV depression (two male, eight female) and ten controls (three male, seven female) participated. MEPs were elicited at rest, then after exercising the contralateral abductor pollicis brevis muscle, using TMS of the primary motor cortex. RESULTS: The mean MEP amplitude recorded after exercise (expressed as a percentage of baseline) was 210% in controls and 130% in patients. There was a significant difference in post-exercise MEP between patients and controls (P = 0.03). CONCLUSIONS: Post-exercise MEP facilitation was demonstrated in controls but not in patients. This supports the hypothesis that the modulation of cortical excitability may be impaired in depression.
Uptake of 99mTc-exametazime shown by single photon emission computed tomography before and after lithium withdrawal in bipolar patients: associations with mania.
BACKGROUND: Early manic relapse following lithium discontinuation offers an important opportunity to investigate the relationship between symptoms, effects of treatment and regional brain activation in bipolar affective disorder. METHOD: Fourteen stable bipolar patients on lithium were examined with neuropsychological measures, clinical ratings and single photon emission computed tomography (SPECT) before and after acute double-blind withdrawal of lithium. Brain perfusion maps were spatially transformed into standard stereotactic space and compared pixel-by-pixel. A parametric analysis was used to examine the change in brain perfusion on lithium withdrawal, and the relationship between symptom severity and brain perfusion separately both between and within subjects. RESULTS: Lithium withdrawal was associated with an important redistribution of brain perfusion, with increases in inferior posterior regions and decreases in limbic areas, particularly anterior cingulate cortex. Seven of the 14 patients developed manic symptoms during the placebo phase, correlating with relative increases in perfusion of superior anterior cingulate and possibly left orbito-frontal cortex. CONCLUSIONS: The important effect of lithium withdrawal on brain perfusion implies that after withdrawal of lithium, the brain develops an abnormal state of activity in limbic cortex. The structures involved did not co-localise with those apparently modulated by manic symptoms.
Cerebral perfusion correlates of depressed mood.
BACKGROUND: The spontaneous diurnal variation of mood and other symptoms provides a substrate for the examination of the relationship between symptoms and regional brain activation in depression. METHOD: Twenty unipolar depressed patients with diurnal variation of mood were examined at 8 a.m. and 8 p.m. with neuropsychological measures, clinical ratings and single photon emission tomography (SPET). Brain perfusion maps were spatially transformed into standard stereotactic space and compared pixel-by-pixel. A parametric (correlational) analysis was used to examine the relationship between symptom severity and brain perfusion, both between and within subjects. RESULTS: Global depression severity and an independent 'vital' depression factor were associated in subjects with increased perfusion in cingulate and other paralimbic areas. In addition there was a probable association between an increase in an anxious-depression factor and reduced frontal neocortical perfusion. CONCLUSIONS: Depressive symptom changes are associated with metabolic changes in the cingulate gyrus and associated paralimbic structures.
An MRI, SPECT and neuropsychological study of a patient presenting with Capgras syndrome.
A 25 year old male patient presented with the "delusion of doubles" (Capgras syndrome). The patient underwent detailed neuropsychological, single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) investigations. The neuropsychological results indicated that he was of average premorbid intelligence, which was consistent with current estimates, and had a degree of everyday memory dysfunction which was below norms derived from healthy controls, but was average relative to schizophrenic norms. He demonstrated average or above average recognition memory for patterns, spaces or words, but exhibited a marked and disproportionate impairment in face recognition, performing at the 5th percentile. In addition he demonstrated markedly impaired performance on various tests of executive function. MRI scanning revealed no focal abnormality; slight ventricular dilatation was noted. SPECT scanning, however, revealed marked right/left asymmetries of tracer uptake, restricted to occipital and calcarine cortices. These asymmetries were well outside those derived from a cohort of healthy controls. These results are discussed in relation to current neuropsychological models of Capgras syndrome.