RESUMEN
In our previous studies, we identified that exploratory eye movement (EEM) dysfunction appears to be specific to schizophrenia. The availability of a biological marker specific to schizophrenia would be useful for clinical diagnosis of schizophrenia. Consequently, we performed the discriminant analysis between schizophrenics and non-schizophrenics on a large sample using the EEM test data and examined an application of the EEM for clinical diagnosis of schizophrenia. EEM performances were recorded in 251 schizophrenics and 389 non-schizophrenics (111 patients with mood disorders, 28 patients with neurotic disorders and 250 normal controls). The patients were recruited from eight university hospitals and three affiliated hospitals. For this study with a large sample, we developed a new digital computerized version of the EEM test, which automatically handled large amounts of data. We measured four parameters: number of eye fixations (NEF), total eye scanning length (TESL), mean eye scanning length (MESL) and responsive search score (RSS). These parameters of schizophrenics differed significantly from those of the other three groups. The stepwise regression analysis selected the TESL and the RSS as the valid parameters for discriminating between schizophrenics and non-schizophrenics. In the discriminant analysis using the RSS and TESL as prediction parameters, 184 of the 251 clinically diagnosed schizophrenics were discriminated as having schizophrenia (sensitivity 73.3%); and 308 of the 389 clinically diagnosed non-schizophrenic subjects were discriminated as non-schizophrenics (specificity 79.2%). Based on our findings we believe that the EEM measures may be useful for the clinical diagnosis of schizophrenia.
Asunto(s)
Conducta Exploratoria , Movimientos Oculares , Fijación Ocular , Desempeño Psicomotor , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Adulto , Diagnóstico Diferencial , Medidas del Movimiento Ocular/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Humor/diagnóstico , Trastornos del Humor/fisiopatología , Trastornos del Humor/psicología , Pruebas Neuropsicológicas/estadística & datos numéricos , Trastornos Neuróticos/diagnóstico , Trastornos Neuróticos/fisiopatología , Trastornos Neuróticos/psicología , Escalas de Valoración Psiquiátrica , Análisis de Regresión , Adulto JovenRESUMEN
This study examined the effects of subsequent, subchronic, treatment with choline uptake enhancer MKC-231 on the behavioral and cellular deficits induced by repeated PCP exposure in rats. Prior subchronic PCP exposure resulted in increased locomotion following an acute PCP or cocaine challenge, but resulted in decreased locomotor activity in response to a carbachol-challenge. MKC-231 significantly antagonized the alterations in the locomotor responses to cocaine and carbachol, but not to PCP. In the novel object recognition test, repeated PCP exposure caused cognitive deficits in rats, and the PCP-induced cognitive deficits were antagonized by MKC-231. In contrast, no effects of PCP exposure were shown in the repeated passive avoidance test. Furthermore, repeated PCP exposure decreased a number of choline acetyltransferase (ChAT)-positive cells in the medial septum and increased dynorphin A expression in the ventral striatum. Moreover, MKC-231 significantly antagonized the changes in septal ChAT-positive cells, but not the changes in ventrostriatal dynorphin A expression. These results suggest that MKC-231 could be a therapeutic drug for the treatment of schizophrenia.
Asunto(s)
Acetilcolina/metabolismo , Trastornos Mentales/tratamiento farmacológico , Neuronas/efectos de los fármacos , Fenciclidina , Quinolinas/administración & dosificación , Tabique del Cerebro/patología , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Colina O-Acetiltransferasa/metabolismo , Esquema de Medicación , Interacciones Farmacológicas , Conducta Exploratoria/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Trastornos Mentales/inducido químicamente , Trastornos Mentales/patología , Actividad Motora/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
A couple of papers indicate that patients with depression show a decrease in serum neuropeptide Y (NPY). To study the role of NPY in depression, we examined the effects of infusion of NPY into the hippocampus of learned helplessness (LH) rats (an animal model of depression). Infusion of NPY into the cerebral ventricle of LH rats showed antidepressant-like effects. Infusion of NPY into the CA3 region, but not the dentate gyrus (DG), produced antidepressant-like effects in the LH paradigm. Infusion of NPY did not affect locomotor activity or aversive learning ability. Coadministration of BIBO3304 (a Y1 receptor antagonist) with NPY to the CA3 region blocked the antidepressant-like effects of NPY, whereas coadministration of NPY with BIIE0246 (a Y2 receptor antagonist) to the CA3 region failed to block antidepressant-like effects. Furthermore, infusions of [Leu(31) Pro(34)]PYY (a Y1 and Y5 receptor agonist) alone and BIIE0246 alone into the CA3 region produced the antidepressant-like effects in LH rats. These results suggest that infusion of NPY into the CA3 region of hippocampus of LH rats produces antidepressant-like activity through Y1 receptors and attenuating effects through Y2 receptors.
Asunto(s)
Antidepresivos/farmacología , Hipocampo/efectos de los fármacos , Neuropéptido Y/farmacología , Receptores Acoplados a Proteínas G/fisiología , Receptores de Neuropéptido/fisiología , Animales , Antidepresivos/uso terapéutico , Arginina/análogos & derivados , Arginina/farmacología , Reacción de Prevención/efectos de los fármacos , Conducta Animal , Benzazepinas/farmacología , Depresión/tratamiento farmacológico , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Conducta Exploratoria/efectos de los fármacos , Desamparo Adquirido , Hipocampo/fisiología , Inyecciones Intraventriculares/métodos , Masculino , Neuropéptido Y/uso terapéutico , Péptido YY/farmacología , Ratas , Ratas Sprague-Dawley , Tiempo de Reacción/efectos de los fármacos , Receptores Acoplados a Proteínas G/agonistas , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores de Neuropéptido/agonistas , Receptores de Neuropéptido/antagonistas & inhibidoresRESUMEN
The goal of this study was to evaluate the utility of using plasma levels of amino acids as an indicator of the severity of depression. The samples were collected from 23 depressed patients receiving antidepressant medication, and were compared to 31 healthy subjects. The plasma levels of amino acids were determined using HPLC with fluorometric detection. The severity of depression was evaluated using the Hamilton Depression Rating Scale (HAM-D) scores. Plasma levels of glutamate, glutamine, glycine and taurine were significantly increased in the depressed patients compared to the controls. Statistical analysis indicated a positive correlation between glutamate and alanine levels and HAM-D scores and a negative correlation of L-serine with HAM-D scores. The results indicate that plasma level of glutamate, alanine and L-serine could reflect the severity of depression rather than glutamine, glycine and taurine.
Asunto(s)
Alanina/sangre , Trastorno Depresivo/sangre , Trastorno Depresivo/psicología , Ácido Glutámico/sangre , Serina/sangre , Adulto , Aminoácidos/sangre , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Escalas de Valoración Psiquiátrica , Espectrometría de FluorescenciaRESUMEN
Plasma levels of ACTH, cortisol and monoamines were examined in 23 depressed patients and 31 healthy subjects. Patients showed increased plasma cortisol levels, but not plasma adrenocorticotropic hormone (ACTH) levels. The plasma levels of a dopamine metabolite, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), were significantly decreased in the patients. In contrast, the plasma levels of a serotonin (5-HT) metabolite, hydroxyindoleacetic acid (5-HIAA), and 5-HT turnover (5-HIAA/5-HT) were increased in the depressed patients. Therefore, plasma levels of HVA and 5-HIAA are proven to be dissociable. Furthermore, plasma levels of 5-HIAA and L-DOPA have positive relationships with severity of depression. On the basis of this and the previous studies, we speculate that an increase in the plasma 5-HIAA levels might be a compensatory mechanism for stress, whereas 5-HT turnover might reflect depressive state. Taken together, plasma levels of HVA and 5-HIAA, and 5-HT turnover (5-HIAA/5-HT) could be good markers for evaluating depression.
Asunto(s)
Depresión/sangre , Ácido Homovanílico/sangre , Hidrocortisona/sangre , Ácido Hidroxiindolacético/sangre , Serotonina/sangre , Adulto , Estudios de Casos y Controles , Electroquímica/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Radioinmunoensayo/métodosRESUMEN
Narp (neuronal activity-regulated pentraxin) is a secreted immediate early gene product functioning as a cluster factor for the AMPA receptor subtype of glutamate receptors. This study was designed to examine the effects of acute administration of methamphetamine (MAP) on the Narp gene in rat brain using reverse transcription - polymerase chain reaction (RT-PCR). Acute administration of MAP [4.6 mg/kg, intraperitoneally (i.p.)] increased Narp mRNA in the prefrontal cortex, whereas the same treatment with MAP decreased Narp mRNA in the hippocampus. Therefore, Narp gene could be involved in the MAP-induced effects.
Asunto(s)
Proteína C-Reactiva , Estimulantes del Sistema Nervioso Central/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Metanfetamina/farmacología , Proteínas del Tejido Nervioso , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , ARN Mensajero , Animales , Proteína C-Reactiva/efectos de los fármacos , Proteína C-Reactiva/genética , Proteína C-Reactiva/metabolismo , Estimulantes del Sistema Nervioso Central/administración & dosificación , Esquema de Medicación , Masculino , Metanfetamina/administración & dosificación , Proteínas del Tejido Nervioso/efectos de los fármacos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Neurosteroids administered during the neonatal period affect the development of several brain systems. We examined the effects of neonatal treatment with pregnenolone and dehydroepiandrosterone (DHEA) on a marker of neuronal dendrites, microtubule-associated protein 2 (MAP-2), in rat brain. Neonatal treatment with pregnenolone and DHEA increased the expression of MAP-2 in the hippocampus and nucleus accumbens but not in the prefrontal cortex, striatum or amygdala in adulthood.
Asunto(s)
Encéfalo/crecimiento & desarrollo , Deshidroepiandrosterona/farmacología , Dendritas/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Vías Nerviosas/crecimiento & desarrollo , Pregnenolona/farmacología , Animales , Animales Recién Nacidos , Biomarcadores/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Dendritas/efectos de los fármacos , Dendritas/ultraestructura , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/crecimiento & desarrollo , Hipocampo/metabolismo , Masculino , Proteínas Asociadas a Microtúbulos/efectos de los fármacos , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/metabolismo , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/crecimiento & desarrollo , Núcleo Accumbens/metabolismo , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
Learned helplessness, but not immobilization stress, decreased the numbers of neuropeptide Y (NPY)-positive cells (interneuron), but not calcitonin gene-related peptide (CGRP)-positive cells (mossy cell), in the hilus of the hippocampus. Subchronic treatment of learned helplessness rats, but not naive rats, with imipramine ameliorated the decrease in the number of NPY-positive cells. Therefore, NPY-positive cells in the hippocampus may contribute to depression.
Asunto(s)
Antidepresivos Tricíclicos/administración & dosificación , Desamparo Adquirido , Hipocampo/metabolismo , Imipramina/administración & dosificación , Interneuronas/metabolismo , Neuropéptido Y/metabolismo , Animales , Péptido Relacionado con Gen de Calcitonina/metabolismo , Recuento de Células , Esquema de Medicación , Hipocampo/citología , Hipocampo/efectos de los fármacos , Interneuronas/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Restricción Física/fisiologíaRESUMEN
Schizophrenia is associated with deficits in information processing. Several studies have shown impairments in attentional functions of visual perception in schizophrenic patients. Attentional function is thought to consist of two stages; preattentive processing and attentive processing. Preattentive processing enables an individual to detect a target without scanning stimuli one by one. The search time is almost constant as distoractors increase. On the other hand, attentive processing needs sequential scanning of stimuli to detect a target. Here, the search time increases as distractors increase. In this paper, preattentive information processing was investigated in 30 schizophrenic patients and 30 control subjects using visual search tasks. Subjects were instructed to find a target and press a button in two kinds of visual search tasks. The figures of tasks were constructed with one 'L' and 5, 17, 35 'X's in the high-pop-out task, and one 'L' and 5, 17, 35 'T's in the low-pop-out task. The performance of the high-pop-out task requires preattentive processing. The time to push the button, the time for the viewpoint to reach the target and the direction of the first saccade were recorded using the eye-mark recorder. The reaction time to push the button in schizophrenics was generally longer than that in controls, irrespective of the levels of pop-out. In addition, the time for the viewpoint to reach the target was also greater in schizophrenics. Also, in the direction of the first saccade, schizophrenics showed a lower rate of making the first saccade toward the target than controls in the high-pop-out task. In conclusion, the present results suggests that there is some kind of deficit in preattentive processing of visual information in schizophrenic patients.
Asunto(s)
Procesos Mentales/fisiología , Psicología del Esquizofrénico , Percepción Visual , Atención , Humanos , Tiempo de ReacciónRESUMEN
Rats exposed to learned helplessness (LH), an animal model of depression, showed a recovery following an intracerebroventricular injection of nor-binaltorphimine dihydrochloride (norBNI; a kappa-opioid antagonist). To investigate the potential role of dynorphin A and dynorphin B, we examined the effects of different stress/depression models on dynorphin A and dynorphin B immunoreactivity in hippocampus and nucleus accumbens (NAc). Immobilization stress (3 h) caused an increase in levels of dynorphin A and dynorphin B immunoreactivity in the hippocampus and the NAc. Forced swim stress also temporally increased dynorphin A levels in the hippocampus. Furthermore, exposure to LH produced a similar increase in dynorphin A and dynorphin B in the hippocampus and NAc. Infusions of norBNI into the dentate gyrus or CA3 regions of hippocampus and into the shell or core regions of NAc produced antidepressant-like effects in the LH paradigm. The degrees of norBNI's effects were stronger in the CA3 region and NAc shell and less effective in the dentate gyrus of hippocampus and NAc core. These results indicate that both dynorphin A and dynorphin B contribute to the effects of stress, and suggest that blockade of kappa-opioid receptors may have therapeutic potential for the treatment of depression.