RESUMEN
BACKGROUND: Recent studies have suggested that subjects with depression suffer a diagnosis-specific motivational deficit, characterized by an abnormal response to negative feedback that endures beyond clinical recovery. Furthermore, it has been suggested that negative feedback may motivate non-depressed controls, but not depressed patients, to improve their performance in neuropsychological tests. METHODS: We describe two studies. The first compared performance on the simultaneous and delayed match to sample (SDMS) task from the CANTAB neuropsychological test battery, in 20 patients with severe depression with 20 with acute schizophrenia, 40 with chronic schizophrenia and 40 healthy controls. The second examined the performance of depressed patients with diurnal variation in symptoms and cognitive function. RESULTS: All patients groups showed impairments on the simultaneous and delayed match to sample task compared to controls. Depressed patients did not show an abnormal response to negative feedback. Controls did not show a motivational effect of negative feedback. Depressed patients with diurnal variation showed no variation in their response to perceived failure. There was no evidence of abnormal response to negative feedback in any patient group using the 'runs test' or of a motivational effect in controls. Conditional probability analysis was not independent of the total number of errors made in the SDMS task. CONCLUSIONS: Further studies are suggested to examine whether an abnormal response to negative feedback characterizes particular subgroups of patients suffering from depression.
Asunto(s)
Biorretroalimentación Psicológica , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/psicología , Enfermedad Aguda , Adulto , Enfermedad Crónica , Trastorno Depresivo/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Esquizofrenia/complicaciones , Esquizofrenia/diagnóstico , Índice de Severidad de la EnfermedadRESUMEN
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.
Asunto(s)
Circulación Cerebrovascular/fisiología , Trastorno Depresivo/fisiopatología , Adulto , Ansiedad/fisiopatología , Ritmo Circadiano , Trastorno Depresivo/diagnóstico por imagen , Femenino , Lóbulo Frontal/diagnóstico por imagen , Humanos , Masculino , Compuestos de Organotecnecio , Oximas , Exametazima de Tecnecio Tc 99m , Tomografía Computarizada de EmisiónRESUMEN
BACKGROUND: the effect of single-dose and long-term cholinergic enhancement with tacrine on regional cerebral perfusion was examined in patients with Alzheimer's disease using single-photon emission tomography (SPET). METHOD: 23 patients with probable Alzheimer's disease (DSM-III-R and NINCDS-ADRDA criteria) were scanned before and after a single oral dose of tacrine at the start of the study and again after 12 weeks of randomized, double-blind treatment with tacrine or placebo, using high resolution (99m)Tc-Exametazime SPET. Patients also underwent neuropsychological testing with the CAMCOG, the Mini-Mental State Examination and the Rivermead Behavioural Memory Test before and after 12 weeks of treatment. RESULTS: occipital count ratios in all regions of interest declined by 3% over 12 weeks, indicating a progression of the disease. Acute tacrine challenge resulted in a 16% increase in the superior frontal and a 11% decrease in the anterior temporal cortex. The acute effects of tacrine were modified by 12 weeks of treatment, particularly in the medial frontal (cingulate) cortex where active treatment was associated with a reduced acute tacrine response. There were no changes in cognitive function associated with active treatment. CONCLUSION: the study demonstrates the sensitivity of cerebral perfusion measures to changes during acute and medium-term tacrine treatment.
RESUMEN
15 patients suffering from DSM-III-R major depression were compared with 15 age-, sex- and intelligence-matched controls on a battery of memory tests, aimed at fractionating memory dysfunction in depression. Patients were unimpaired relative to controls on measures of short-term memory, recognition, semantic memory and implicit memory. There was no evidence of a hedonic bias in recall of positive vs. negatively valenced stimuli, nor was there any correlation between depression severity and level of memory impairment. Psychotic patients did not demonstrate greater memory impairment relative to nonpsychotic depressed patients. As a group, however, depressed patients demonstrated deficits in psychomotor speed and in free recall of material (both immediate and delayed). The selective recall deficit suggests that material has been encoded but that patients are particularly impaired with regard to search and retrieval processes.
Asunto(s)
Trastorno Depresivo/diagnóstico , Trastornos de la Memoria/diagnóstico , Recuerdo Mental , Pruebas Neuropsicológicas , Adulto , Anciano , Atención , Trastorno Depresivo/psicología , Femenino , Humanos , Masculino , Trastornos de la Memoria/psicología , Memoria a Corto Plazo , Escala del Estado Mental , Persona de Mediana Edad , Inventario de Personalidad , Desempeño Psicomotor , Tiempo de Reacción , Retención en Psicología , Aprendizaje VerbalRESUMEN
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.
Asunto(s)
Afecto , Trastorno Bipolar/diagnóstico , Ritmo Circadiano , Trastorno Depresivo/diagnóstico , Pruebas Neuropsicológicas , Hormona Adrenocorticotrópica/sangre , Adulto , Afecto/fisiología , Anciano , Atención/fisiología , Trastorno Bipolar/fisiopatología , Trastorno Bipolar/psicología , Ritmo Circadiano/fisiología , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología , Femenino , Fuerza de la Mano/fisiología , Humanos , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Recuerdo Mental/fisiología , Persona de Mediana Edad , Inventario de Personalidad , Sistema Hipófiso-Suprarrenal/fisiopatología , Escalas de Valoración Psiquiátrica , Desempeño Psicomotor/fisiología , Tiempo de Reacción/fisiología , Retención en Psicología/fisiologíaRESUMEN
Eight patients suffering from the alcoholic Korsakoff syndrome (AKS) were entered in a double-blind cross-over trial of fluvoxamine 200 mg per day for 4 weeks versus matched placebo for 4 weeks. At the end of each phase, patients were assessed using a detailed neuropsychological test battery. Verbal fluency performance was significantly impaired following fluvoxamine treatment. No significant differences emerged on any of the other cognitive test measures when fluvoxamine was compared with placebo. However, two of the patients developed a major depressive episode while receiving fluvoxamine.
Asunto(s)
Trastorno Amnésico Alcohólico/tratamiento farmacológico , Cognición/efectos de los fármacos , Fluvoxamina/uso terapéutico , Afecto/efectos de los fármacos , Anciano , Trastorno Amnésico Alcohólico/psicología , Estudios Cruzados , Método Doble Ciego , Fluvoxamina/efectos adversos , Humanos , Memoria/efectos de los fármacos , Conducta Verbal/efectos de los fármacos , Escalas de WechslerRESUMEN
The effects upon regional brain function of infusing either saline or clonidine (1.5 microgram/kg) has been examined in 18 patients with alcoholic Korsakoff's psychosis using 99mTc-hexamethylpropyleneamineoxime (99mTc-HMPAO or 99mTc-Exametazime) and Single Photon Emission Tomography (SPET or SPECT). The hypothesis tested was that frontal lobe function would be increased by adrenoceptor stimulation. This was confirmed by an increase in the uptake of 99mTc-Exametazime into anterior cingulate regions of the frontal lobes. Patients were scanned before and after saline or clonidine infusion during performance of a verbal fluency task. There was a significantly increased performance of verbal fluency in patients given clonidine. This effect was variable and could not be unequivocably distinguished from increases in performance in the saline treated group. Nevertheless, the increase in neuropsychological performance was also correlated with increased function in left dorsolateral frontal cortex within the clonidine treated group. An exploratory examination of other brain areas suggested that relative increases in posterior cingulate cortex and changes in the symmetry of function within the thalamus may also be produced by acute infusion of clonidine in Korsakoff patients. The findings support the idea that adrenergic mechanisms may modulate cognitive performance by actions on attentional systems within the brain. These appear to be located primarily within limbic cortex. It is, of course, notable that this can occur in patients with profound and disabling amnesia.
Asunto(s)
Trastorno Amnésico Alcohólico/diagnóstico , Clonidina/farmacología , Giro del Cíngulo/metabolismo , Cloruro de Sodio/farmacología , Compuestos de Tecnecio , Adulto , Anciano , Trastorno Amnésico Alcohólico/complicaciones , Trastorno Amnésico Alcohólico/metabolismo , Circulación Cerebrovascular , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Giro del Cíngulo/diagnóstico por imagen , Giro del Cíngulo/efectos de los fármacos , Humanos , Persona de Mediana Edad , Escalas de Valoración Psiquiátrica , Receptores Adrenérgicos/efectos de los fármacos , Método Simple Ciego , Compuestos de Tecnecio/farmacocinética , Tomografía Computarizada de Emisión de Fotón Único , Conducta Verbal/efectos de los fármacosRESUMEN
The method of comparing premorbid versus current intellectual ability has become established clinical practice in the differential diagnosis of dementia versus depression. Recently, Schlosser & Ivison (1989) suggested that the comparison of premorbid ability versus current memory function may offer a more sensitive method of assessing early dementia. In the present study, a variety of within-subject discrepancy analyses comparing premorbid estimates with current measures of memory and intellectual functioning were compared across three groups: patients with dementia of the Alzheimer type, patients with major depression and healthy controls. The results revealed that, while mean group differences were easily demonstrated, the overlap between Alzheimer and depressed patients was large. It is concluded that none of the simple neuropsychological discrepancy analyses examined in the present study can be recommended for use in clinical practice for the differential diagnosis of dementia from major depression.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Trastorno Depresivo/diagnóstico , Pruebas Neuropsicológicas/estadística & datos numéricos , Anciano , Enfermedad de Alzheimer/clasificación , Enfermedad de Alzheimer/psicología , Sesgo , Trastorno Depresivo/clasificación , Trastorno Depresivo/psicología , Diagnóstico Diferencial , Femenino , Humanos , Inteligencia , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Escalas de Wechsler/estadística & datos numéricosRESUMEN
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.
Asunto(s)
Antidepresivos/uso terapéutico , Encéfalo/irrigación sanguínea , Trastorno Depresivo/tratamiento farmacológico , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Mapeo Encefálico , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/efectos de los fármacos , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/psicología , Dopamina/fisiología , Metabolismo Energético/efectos de los fármacos , Metabolismo Energético/fisiología , Femenino , Estudios de Seguimiento , Humanos , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Compuestos de Organotecnecio , Oximas , Inventario de Personalidad , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , Exametazima de Tecnecio Tc 99mRESUMEN
Ten patients suffering from DSM-III-R simple phobia were studied under two conditions: (a) while listening to a 4 min relaxation tape, and (b) while listening to a 4 min audio tape describing exposure to the phobic stimulus. During each condition, subjects were injected with 99mTc-Exametazime, a marker of regional cerebral blood flow. Subjective and psychophysiological measures indicated a marked effect of the anxiety induction procedure. Ratio analysis of the SPET data revealed reductions in tracer uptake largely confined to posterior cerebral regions bilaterally. Analysis of brain regions of interest normalised to the whole brain slice showed reductions confined to right temporal/occipital regions. In general there was no clear association between subjective and physiological variables and changes in regional uptake of tracer as a consequence of the anxiety induction procedure. The changes in tracer uptake were dissimilar to those previously reported for other cognitive activation paradigms, providing some reassurance that those functional brain changes were not artefacts of non-specific changes in state anxiety. These posterior brain changes may reflect alterations in activation of the GABA/benzodiazepine complex.
Asunto(s)
Ansiedad/fisiopatología , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular , Compuestos de Organotecnecio , Oximas , Trastornos Fóbicos/fisiopatología , Tomografía Computarizada de Emisión de Fotón Único , Estimulación Acústica , Ansiedad/diagnóstico por imagen , Ansiedad/etiología , Encéfalo/fisiopatología , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Occipital/irrigación sanguínea , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/fisiopatología , Inventario de Personalidad , Trastornos Fóbicos/diagnóstico , Trastornos Fóbicos/diagnóstico por imagen , Escalas de Valoración Psiquiátrica , Exametazima de Tecnecio Tc 99m , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiopatologíaRESUMEN
Eighteen patients suffering from Alcoholic Korsakoff's Syndrome participated in a placebo-controlled double-blind cross-over trial of clonidine 0.3 mg b.d. for two weeks versus matched placebo for two weeks. A detailed neuropsychological assessment was carried out at the end of each treatment phase and staff ratings of behaviour were also obtained. Clonidine treatment resulted in no significant improvement over placebo on any of the cognitive measures employed. The results contradict previous smaller studies which had suggested that chronic treatment with clonidine had a memory-enhancing effect in Korsakoff's syndrome.
Asunto(s)
Trastorno Amnésico Alcohólico/tratamiento farmacológico , Clonidina/uso terapéutico , Pruebas Neuropsicológicas , Anciano , Trastorno Amnésico Alcohólico/psicología , Atención/efectos de los fármacos , Clonidina/efectos adversos , Método Doble Ciego , Femenino , Lóbulo Frontal/efectos de los fármacos , Humanos , Masculino , Recuerdo Mental/efectos de los fármacos , Persona de Mediana Edad , Solución de Problemas/efectos de los fármacosRESUMEN
We examined 20 actively psychotic unmedicated schizophrenic patients and 20 matched control subjects by using single-photon emission, computed tomography (SPECT) with 99mtechnetium-exametazime. Patients showed a hyperfrontal pattern of tracer uptake with significant relative increases in superior prefrontal cortex. This abnormality was less pronounced in patients with higher symptom scores for psychomotor poverty. In addition, patients showed associations between certain schizophrenic syndrome scores, such as psychomotor poverty, disorganization, and reality distortion, and tracer uptake to a number of cortical and subcortical brain regions. This syndrome-related pattern of tracer uptake was, at least in part, consistent with similar associations previously reported in chronically medicated schizophrenic patients. SPECT therefore provides a readily available method to examine the relationship between symptom pattern and regional brain metabolism in psychotic patients. Any observed patterns of association will depend on the current mental and medication status of the patients examined.
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Corteza Cerebral/irrigación sanguínea , Esquizofrenia/diagnóstico por imagen , Psicología del Esquizofrénico , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Nivel de Alerta/fisiología , Dominancia Cerebral/fisiología , Femenino , Lóbulo Frontal/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Organotecnecio , Oximas , Escalas de Valoración Psiquiátrica , Flujo Sanguíneo Regional/fisiología , Esquizofrenia/clasificación , Exametazima de Tecnecio Tc 99mRESUMEN
Over the past two years a series of different mutations has been discovered in the amyloid precursor protein (APP) gene in patients with Alzheimer's disease. All have been clustered in exons 16 and 17, a region encoding the beta A4 peptide found in the amyloid deposits of neuritic plaques and cerebral blood vessels. We have used the powerful technique of denaturing gradient gel electrophoresis to screen for mutations in exons 7, 16 and 17 of the APP gene in a cohort of 105 patients with presenile dementia of the Alzheimer type and 71 patients with autopsy-confirmed senile Alzheimer's disease. No new mutations were found, confirming earlier suggestions that APP mutations account for only a small proportion of cases of familial and sporadic Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/genética , Análisis Mutacional de ADN , Pruebas Genéticas , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Secuencia de Bases , Estudios de Cohortes , Demencia/genética , Exones , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , MutaciónRESUMEN
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.
Asunto(s)
Trastorno Amnésico Alcohólico/diagnóstico , Alcoholismo/complicaciones , Anciano , Trastorno Amnésico Alcohólico/etiología , Escolaridad , Femenino , Humanos , Inteligencia , Masculino , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Agudeza Visual , Escalas de WechslerRESUMEN
Forty patients with a major depressive episode were investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, an intravenous ligand taken into brain in proportion to regional cerebral blood flow, thereby providing an estimate of regional metabolism. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. They also completed a range of neuropsychological tests. They were compared with 20 control subjects matched for age, gender, premorbid intelligence and education. The uptake of 99mTc-exametazime was expressed for a range of anatomically defined regions of interest relative to calcarine/occipital cortex. The depressed group showed reduced uptake in the majority of cortical and sub-cortical regions examined, most significantly in temporal, inferior frontal and parietal areas. Unexpectedly, there was a strong positive association between uptake and scores on the Newcastle scale, especially in cingulate areas and frontal cortex. After removing the variance attributable to the Newcastle ratings, however, there emerged the expected negative association between Hamilton scores and anterior tracer uptake. The associations between neuropsychological impairment and regional brain uptake of tracer in part reflected the pattern seen with the Newcastle scale: for example, impairment of memory function correlated with higher uptake into posterior cingulate areas. We propose that depressive illness may be characterised by two processes. One leads to an overall reduction in anterior neocortical function, perhaps related to symptom severity. The other mechanism is manifest as relatively increased function, most notably within cingulate and frontal areas of the cerebral cortex in association with psychotic symptoms. The findings offer new understanding of the brain states underlying depressive illness and a potential focus to subsequent neuropharmacological analysis.
Asunto(s)
Trastornos Psicóticos Afectivos/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Trastorno Depresivo/diagnóstico por imagen , Metabolismo Energético/fisiología , Trastornos Neuróticos/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Trastornos Psicóticos Afectivos/fisiopatología , Trastornos Psicóticos Afectivos/psicología , Mapeo Encefálico , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología , Femenino , Lóbulo Frontal/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Trastornos Neuróticos/fisiopatología , Trastornos Neuróticos/psicología , Compuestos de Organotecnecio , Oximas , Inventario de Personalidad , Flujo Sanguíneo Regional/fisiología , Tecnecio , Exametazima de Tecnecio Tc 99mRESUMEN
Following reports of mutations of codon 717 in exon 17 of the amyloid precursor protein (APP) gene in early-onset familial Alzheimer's disease, we screened exon 17 for new mutations in presenile dementia. The majority of the 105 patients screened had definite or probable Alzheimer's disease, but we also included atypical cases and some chronic schizophrenics. We identified a single abnormal case--a chronic schizophrenic with cognitive defects. Sequencing revealed a C to T nucleotide substitution which produces an alanine to valine change at codon 713. We were unable to detect the mutation in the remaining members of the original cohort nor in a further 100 chronic schizophrenics and 100 non-demented controls. Nonetheless, the position of the mutation in a critical portion of the APP gene suggests that it may well prove to be pathogenic.