No abstract

No abstract

No abstract

No abstract

No abstract

Rodents treated with N-methyl-D-aspartate (NMDA) antagonists have been thought to be an animal model of schizophrenia. In this study, we examined gene expression in the amygdala of rats chronically treated with MK-801, as well as behavioral changes, such as social behavior, in these animals. The social interaction test, a measure of social behavior, and locomotor activity was performed in male Wistar rats injected with MK-801 (0.13 mg/kg i.p.) or saline for 14 days. Changes in mRNA levels were analyzed using a GeneChip microarray system. Real-time quantitative PCR (RT-qPCR) assay was subsequently conducted to confirm the results of the microarray analysis. MK-801 decreased social interaction and increased locomotor activity in rats, consistent with previous reports. We found 23 downregulated genes and 16 upregulated genes, with the gene encoding arginine-vasopressin (AVP) being most downregulated, and that for transthyretin (Ttr) most upregulated. mRNA levels, quantified by RT-qPCR assay, were altered for genes related to neuropeptides (AVP, Sstr2), the arachidonic cascade (Ptgds), myelination (Mobp, Enpp2), neurotrophic factors (Igfbp2), and hormonal milieu (Ttr). Downregulation of the AVP gene in the amygdala of MK-801-treated rats may provide a basis for the ability of AVP-analogues to ameliorate the behavioral disturbances caused by blockade of the NMDA receptor. The results of this study provide an insight into the neural substrates responsible for the generation of psychotic symptoms.

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.

No abstract