RESUMEN
The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin.
Asunto(s)
Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Ganglios Basales/anomalías , Ganglios Basales/efectos de los fármacos , Antagonistas Colinérgicos/farmacología , Antagonistas Colinérgicos/uso terapéutico , Clopentixol/farmacología , Clopentixol/uso terapéutico , Risperidona/farmacología , Risperidona/uso terapéutico , Esquizofrenia/diagnóstico , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/administración & dosificación , Ganglios Basales/fisiopatología , Núcleo Caudado/anomalías , Núcleo Caudado/efectos de los fármacos , Núcleo Caudado/fisiopatología , Clopentixol/administración & dosificación , Esquema de Medicación , Femenino , Lateralidad Funcional/fisiología , Globo Pálido/anomalías , Globo Pálido/efectos de los fármacos , Globo Pálido/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Núcleo Accumbens/anomalías , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/patología , Núcleo Accumbens/fisiopatología , Putamen/efectos de los fármacos , Putamen/patología , Putamen/fisiopatología , Risperidona/administración & dosificación , Esquizofrenia/fisiopatología , Factores de TiempoRESUMEN
The low density of cerebellar dopamine D(2)/D(3) receptors provides the basis for using the cerebellum as a representation of free- and non-specifically bound radioligand in positron emission tomography (PET) and single photon emission computed tomography (SPECT) studies. With the development of ultra high-affinity dopamine D(2)/D(3) ligands like [(123)I]epidepride, [(18)F]fallypride, and [(11)C]FLB-457, quantification of extrastriatal low density receptor populations including the cerebellum is possible with important implications for calculation of binding parameters. [(123)I]epidepride-SPECT was performed in 23 patients with schizophrenia before and after 3 months of antipsychotic treatment with either risperidone (n=14) or zuclopenthixol (n=9). In the unblocked situation and partially blocked situation, the average distribution volumes were 5.2+/-1.3 mL/mL and 4.0+/-0.8 mL/mL, respectively. The paired distribution volumes were reduced by 22+/-15% (mean+/-SD) after antipsychotic treatment (p<0.0001, paired Student's t-test). From the paired distribution volumes in cerebellum and extrastriatal regions, the average distribution volume representing free and non-specifically bound [(123)I]epidepride was calculated to be 3.3+/-0.8 mL/mL. Both the % [(123)I]epidepride fraction of plasma radioactivity (p>0.76) and the plasma [(123)I]epidepride concentration (p>0.45) were unchanged after antipsychotic treatment (paired Student's t-test). These results strongly suggest the presence of "non-negligible" specific [(123)I]epidepride binding to dopamine D(2)/D(3) receptors in the cerebellum. Using the cerebellum as a representation of free and non-specifically bound radioligand and neglecting the specifically bound component may lead to results that erroneously imply that antipsychotic drugs bind to extrastriatal dopamine D(2)/D(3) receptors with a higher affinity than to striatal dopamine D(2)/D(3) receptors.
Asunto(s)
Benzamidas/farmacocinética , Cerebelo/metabolismo , Radioisótopos de Yodo , Pirrolidinas/farmacocinética , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Adulto , Unión Competitiva , Cerebelo/diagnóstico por imagen , Humanos , Cinética , Radiografía , Ensayo de Unión Radioligante/métodos , Valores de Referencia , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
BACKGROUND: The aim of the study was to examine extrastriatal dopamine D(2/3) receptor binding and psychopathology in schizophrenic patients, and to relate binding potential (BP) values to psychopathology. METHODS: Twenty-five drug-naive schizophrenic patients and 20 healthy controls were examined with single-photon emission computerized tomography (SPECT) using the D(2/3)-receptor ligand [123I]epidepride. RESULTS: In the hitherto largest study on extrastriatal D(2/3) receptors we detected a significant correlation between frontal D(2/3) BP values and positive schizophrenic symptoms in the larger group of male schizophrenic patients, higher frontal BP values in male (n = 17) compared to female (n = 8) patients, and - in accordance with this - significantly fewer positive schizophrenic symptoms in the female patients. No significant differences in BP values were observed between patients and controls; the patients, however, had significantly higher BP in the right compared to the left thalamus, whereas no significant hemispheric imbalances were observed in the healthy subjects. CONCLUSIONS: The present data are the first to confirm a significant correlation between frontal D(2/3) receptor BP values and positive symptoms in male schizophrenic patients. They are in agreement with the hypothesis that frontal D(2/3) receptor activity is significant for positive psychotic symptoms. Additionally, the data support a thalamic hemispheric imbalance in schizophrenia.
Asunto(s)
Lóbulo Frontal/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D3/metabolismo , Esquizofrenia/metabolismo , Psicología del Esquizofrénico , Caracteres Sexuales , Adulto , Benzamidas/farmacocinética , Mapeo Encefálico , Escalas de Valoración Psiquiátrica Breve/estadística & datos numéricos , Estudios de Casos y Controles , Medios de Contraste/farmacocinética , Femenino , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/efectos de los fármacos , Humanos , Isótopos de Yodo/farmacocinética , Masculino , Pirrolidinas/farmacocinética , Esquizofrenia/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único/métodosRESUMEN
Prepulse inhibition (PPI) is used as a measure for sensorimotor gating. Studies in animals have indicated that hippocampus and entorhinal cortex, structures which are affected in mild Alzheimer's disease (AD), are involved in the regulation of PPI. The objectives of this study were to determine if patients with very mild AD had altered PPI, and to study possible correlations between PPI and cognitive performance or neuropsychiatric symptoms. A passive acoustic PPI paradigm was applied in 48 patients with either mild AD or Mild Cognitive Impairment (MCI) and in 49 healthy controls. No differences were found between patients and healthy controls regarding PPI. Further, PPI was not found to correlate with cognitive performance or neuropsychiatric symptoms. PPI is significantly altered in patients with neuropsychiatric disorders associated with dopaminergic, glutamatergic and/or serotonergic dysfunctions, such as schizophrenia. Since mild AD is primarily associated with loss of cholinergic markers in the limbic regions this study suggests that acetylcholine only plays a minor role in the regulation of PPI.
Asunto(s)
Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Trastornos del Conocimiento/fisiopatología , Inhibición Neural/fisiología , Reflejo de Sobresalto/fisiología , Acetilcolina/metabolismo , Estimulación Acústica , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/psicología , Encéfalo/metabolismo , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Corteza Entorrinal/metabolismo , Corteza Entorrinal/fisiopatología , Femenino , Habituación Psicofisiológica/fisiología , Hipocampo/metabolismo , Hipocampo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Tiempo de Reacción/fisiologíaRESUMEN
BACKGROUND: Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogeneous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal. OBJECTIVE: The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogeneous group of drug-naive first-episode schizophrenic patients in a longitudinal setting. METHODS: First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N=25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naive, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time. RESULTS: The patients showed considerable cognitive deficits when drug-naive. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls. CONCLUSION: The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naive schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.
Asunto(s)
Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Clopentixol/farmacología , Clopentixol/uso terapéutico , Cognición/efectos de los fármacos , Risperidona/farmacología , Risperidona/uso terapéutico , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/administración & dosificación , Clopentixol/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Risperidona/administración & dosificaciónRESUMEN
The relationship between needs for care and support and subjective quality of life was investigated in a cross-sectional multi-center study including 418 individuals with schizophrenia from 10 centers in Nordic countries. Needs in 22 domains were investigated by interviews with key workers and their patients using the Camberwell Assessment of Need scale, and quality of life by the Lancashire Quality of Life Profile. The results showed that key workers rated slightly more needs than patients. To have more unmet needs, as rated by both key workers and patients, were correlated to a worse overall subjective quality of life, while met needs showed no such association. A regression analysis, controlling for clinical and social characteristics of the patients, showed more unmet needs to be associated with a worse quality of life, accounting for 6% out of a total of 41% explained variance in subjective quality of life. Regression analyses of the relationship of unmet needs in specific life domains and overall quality of life showed that unmet needs in five domains as perceived by patients accounted for 17% of the explained variance in overall quality of life. More than half of this variance was related to an unmet need in the domain of social relationships. It is concluded that unmet needs are of specific importance in needs assessment and that attention must be paid to separate met needs for care and services from unmet needs, since the latter seem more important to consider in order to improve outcome of interventions with regard to quality of life. Specific attention should in this context also be paid to unmet needs concerning social relationships and problems with accommodation.
Asunto(s)
Servicios Comunitarios de Salud Mental , Evaluación de Necesidades , Calidad de Vida , Esquizofrenia/terapia , Adulto , Atención Ambulatoria , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Escandinavos y NórdicosRESUMEN
BACKGROUND: Disturbances in sensorimotor gating measured by prepulse inhibition of the startle response (PPI) have frequently been reported in medicated and unmedicated schizophrenia spectrum patients and in their relatives, suggesting that the deficit represents a stable vulnerability marker for schizophrenia. Clinical data on the effects of antipsychotics on PPI disturbances are scarce, but from preclinical studies, antipsychotics have been shown to influence PPI. To differentiate pathogenetic mechanisms from drug related effects, longitudinal clinical studies on the effect of antipsychotic treatment on PPI in drug-naive first-episode schizophrenic patients are needed. METHODS: First-episode schizophrenic patients never previously medicated with antipsychotics were examined at inclusion and after 3 months of treatment with the atypical antipsychotic compound, risperidone, or the typical drug, zuclopenthixol. Healthy controls were used as a comparison group. RESULTS: The results confirm deficits in PPI in drug-naive first-episode patients. No effect of antipsychotic treatment on PPI dysfunction was observed in any of the treatment groups. CONCLUSIONS: The data are the first to show the possible effect of treatment with antipsychotic drugs on PPI disturbances in a longitudinal study of drug-naive schizophrenic patients. The data do not support any influence of treatment with antipsychotic drugs on sensorimotor gating deficits. Instead, the results point to the impairment in PPI as a stable vulnerability indicator.