Influence of instruction on the Japanese Verbal Learning Test in patients with schizophrenia.
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Attention↗
Biomedical subjects
Masayoshi Kurachi
Publications and source records attributed to Masayoshi Kurachi.
Dopamine D1 and D2 receptors regulate extracellular lactate and glucose concentrations in the nucleus accumbens.
Glucose and lactate have been shown to play a significant role in energy metabolism in the brain. In the present study, the relationship between extracellular glucose and lactate concentrations in the nucleus accumbens (NAC) was determined with in vivo microdialysis technique. We further evaluated the effect of dopamine (DA) receptor agonists on energy metabolism. Extracellular glucose levels were increased following inactivation of neurons by tetrodotoxin (TTX) perfusion, whereas neural activation by veratridine or K(+) perfusion decreased extracellular glucose concentrations. By contrast, lactate levels were increased by veratridine or K(+) perfusion, but were unaltered by TTX. Apomorphine (0.05 mg/kg), a mixed D1/D2 receptor agonist, did not alter the extracellular glucose and lactate concentrations, while a higher dose (0.5 mg/kg) increased them. Bromocriptine, a selective D2 receptor agonist, increased extracellular glucose, but not lactate concentrations. These results indicate that extracellular lactate levels may be a more suitable indicator of acute neural activation than glucose levels, and that simultaneous stimulation of D1 and D2 receptors enhances energy demands of DA neurons in the NAC.
Animals↗
Novel G423S mutation of human alpha7 nicotinic receptor promotes agonist-induced desensitization by a protein kinase C-dependent mechanism.
The alpha7 nicotinic acetylcholine receptor subunit (CHRNA7) gene harbors a high degree of polymorphism. In this study, we found a novel variant (1267 G to A) in exon 10 of the CHRNA7 gene in a Japanese population. This variant results in glycine-to-serine substitution at position 423 (G423S) located in the large cytoplasmic loop of the protein. To clarify the possibility that the G423S mutation alters the pharmacological properties of alpha7 receptors, acetylcholine (ACh)-elicited current through alpha7-G423S mutant receptors expressed in Xenopus laevis oocytes was measured using the two-electrode voltage-clamp technique. We found that the current elicited by ACh (1 mM, 5 s) through alpha7-G423S receptors, but not through alpha7 receptors, was significantly decreased by treatment with a protein kinase C activator, phorbol-12-myristate-13-acetate (PMA, 10-30 nM). In addition, PMA (10 nM) selectively promoted a progressive decrease in alpha7-G423S current induced by repetitive application of ACh pulses (1 mM, 0.1 s, 0.17-0.33 Hz) compared with alpha7 current. PMA also enhanced the inactivation of alpha7-G423S mutant receptors induced by a prolonged application of choline (30 microM) without affecting alpha7 receptor responses. Western blot analysis showed that the treatment with PMA (30 nM) increased the serine phosphorylation level of the alpha7-G423S mutant receptors but not that of the wild-type receptors. These findings demonstrate that the G423S mutation promotes receptor desensitization by a protein kinase C-dependent mechanism. Thus, we provide the first evidence that a variant in the human CHRNA7 gene alters the function of alpha7 nicotinic receptors.
Adult↗
Parietal lobe volume deficits in schizophrenia spectrum disorders.
There has been little attention given to whether parietal lobe structural deficits are present in patients with schizophrenia and related personality disorders. The current study was designed to examine parietal volume alterations between schizophrenia and schizotypal personality disorder. Twenty-five patients with schizotypal disorder, 53 patients with schizophrenia, and 59 healthy volunteers were scanned using high-resolution magnetic resonance imaging (MRI). Volume measurements of the postcentral gyrus (PoCG), precuneus, superior parietal gyrus (SuPG), supramarginal gyrus (SMG), and angular gyrus (AGG) were performed on consecutive 1-mm coronal slices. Gray matter volumes were reduced in all parietal subregions in patients with schizophrenia compared with healthy controls. White matter volumes were also reduced in the SuPG and PoCG. In contrast, the schizotypal subjects had gray matter reductions only in the PoCG, while other regions were not affected. In addition, there was a lack of normal significant-leftward asymmetry in the SMG in schizophrenia. These findings demonstrate that volume reductions in the somatosensory cortices are common morphological characteristics in schizophrenia spectrum disorders. The additional volume alterations in schizophrenia may support the notion that a deficit in the posterior parietal region is critical for the manifestation of overt psychotic symptoms.
Adult↗
Multivariate voxel-based morphometry successfully differentiates schizophrenia patients from healthy controls.
Currently available laboratory procedures might provide additional information to psychiatric diagnostic systems for more valid classifications of mental disorders. To identify the correlative pattern of gray matter distribution that best discriminates schizophrenia patients from healthy subjects, we applied discriminant function analysis techniques using the multivariate linear model and the voxel-based morphometry. The first analysis was conducted to obtain a statistical model that classified 30 male healthy subjects and 30 male schizophrenia patients diagnosed according to current operational criteria. The second analysis was performed to prospectively validate the statistical model by successfully classifying a new cohort that consisted of 16 male healthy subjects and 16 male schizophrenia patients. Inferences about the structural relevance of the gray matter distribution could be made if the individual profile of pattern expression could be linked to the specific diagnosis of each subject. The result was that 90% of the subjects were correctly classified by the eigenimage, and the Jackknife approach revealed well above chance accuracy. The pattern of the eigenimage was characterized by positive loadings indicating gray matter decline in the patients in the lateral and medial prefrontal regions, insula, lateral temporal regions, medial temporal structures, and thalamus as well as the negative loadings reflecting gray matter increase in the patients in the putamen and cerebellum. When the eigenimage derived from the original cohort was applied to classify data from the second cohort, it correctly assigned more than 80% of the healthy subjects and schizophrenia patients. These findings suggest that the characteristic distribution of gray matter changes may be of diagnostic value for schizophrenia.
Adult↗
Electrical brain activity and response to olanzapine in schizophrenia: a study with LORETA images of P300.
The aim of this study was to evaluate the change in the distribution for the P300 generator, as demonstrated by Low Resolution Electromagnetic Tomography (LORETA) images, in patients with schizophrenia during treatment with olanzapine. Data were obtained from five right-handed patients treated with olanzapine for 6 months. Five right-handed normal volunteers also participated in the study. LORETA images of P300 in response to the odd-ball auditory discrimination task revealed a left dominant lateralized high current source density in the temporal lobes in all control subjects. Although this pattern of brain activation was not evident in patients at baseline, 6-month treatment with olanzapine recovered the left dominant pattern of the electrical density in the temporal regions, such as the Heschl gyrus, and improved performance on a test of verbal learning and memory. Scores of the Brief Psychiatric Rating Scale and the Global Assessment of Functioning Scale also improved during treatment. These results provide the first suggestion that enhancement of verbal memory and the functional status by treatment with some antipsychotic drugs may be associated with modulations of the anatomical configuration of electrical brain activity in patients with schizophrenia.
Adult↗
Impairment of event schema in patients with schizophrenia: examination of script for shopping at supermarket.
The purpose of this study was to examine event schema, the conceptualization of past experience based on script theory, in Japanese patients with schizophrenia. Subjects comprised 25 patients meeting DSM-IV criteria for schizophrenia and 31 normal individuals who gave informed consent. This experiment used three script tasks measuring free recall, frequency judgment, and sequencing of events encountered when shopping at a supermarket. Patients with schizophrenia performed significantly worse than did control subjects on all tasks. In particular, patients committed more errors when judging the events that "occasionally happen" in the frequency judgment task. On the other hand, these patients judged "seldom occurring events" relatively well. Patients with schizophrenia made more errors than normal people in the free recall task. Specifically, patients made more intrusion errors and failed to close scripts. There was a negative correlation between scores the Scale for the Assessment of Positive Symptoms and performance on the free recall task. The results of the present study suggest that event schemas (semantic structure) in patients with schizophrenia are impaired which may be associated with positive symptoms and frontal lobe dysfunction.
Activities of Daily Living↗
Temporal lobe gray matter in schizophrenia spectrum: a volumetric MRI study of the fusiform gyrus, parahippocampal gyrus, and middle and inferior temporal gyri.
Although several brain morphologic studies have suggested abnormalities in the temporal regions to be a common indicator of vulnerability for the schizophrenia spectrum, less attention has been paid to temporal lobe structures other than the superior temporal gyrus or the medial temporal region. In this study, we investigated the volume of gray matter in the fusiform gyrus, the parahippocampal gyrus, the middle temporal gyrus, and the inferior temporal gyrus using magnetic resonance imaging in 39 schizotypal disorder patients, 65 schizophrenia patients, and 72 age and gender matched healthy control subjects. The anterior fusiform gyrus was significantly smaller in the schizophrenia patients than the control subjects but not in the schizotypal disorder patients, while the volume reduction of the posterior fusiform gyrus was common to both disorders. Volumes for the middle and inferior temporal gyri or the parahippocampal gyrus did not differ between groups. These findings suggest that abnormalities in the posterior region of the fusiform gyrus are, as have been suggested for the superior temporal gyrus or the amygdala/hippocampus, prominent among the temporal lobe structures as a common morphologic substrate for the schizophrenia spectrum, whereas more widespread alterations involving the anterior region might be associated with the development of full-blown schizophrenia.
Adult↗
Role of 5-HT(1A) receptors in the modulation of stress-induced lactate metabolism in the medial prefrontal cortex and basolateral amygdala.
RATIONALE: Lactate has been shown to play a significant role in energy metabolism and reflect neural activity in the brain. OBJECTIVES: Using in vivo microdialysis technique, we measured extracellular lactate concentrations in the medial prefrontal cortex (mPFC) and the basolateral amygdaloid (BLA) nucleus of rats under electric foot shock stress. Moreover, to examine the role of serotonin (5-HT)(1A) receptors in brain energy metabolism in response to stressors, we attempted to determine whether the stress-induced changes of extracellular lactate levels in the mPFC and BLA are attenuated by tandospirone, a partial agonist at 5-HT(1A) receptors, or perospirone, a novel atypical antipsychotic with a 5-HT(1A) receptor partial agonist and 5-HT(2A)/dopamine-D(2) antagonist property. RESULTS: Foot shock stress led to an increase in extracellular lactate concentrations both in the mPFC and BLA. Tandospirone (2 mg/kg) attenuated the foot shock stress-induced increase of extracellular lactate concentrations in both of the brain regions, which was blocked by pretreatment with WAY-100635, a selective 5-HT(1A) antagonist. On the other hand, perospirone (0.3 mg/kg) attenuated the increment of extracellular lactate concentrations in the mPFC and BLA, which was unaltered by pretreatment with WAY-100635. CONCLUSIONS: These results indicate that the foot shock stress-induced increase in lactate metabolism is partly regulated by 5-HT(1A) receptors both in cortical and limbic regions.
Amygdala↗
Morphologic alterations of the parcellated superior temporal gyrus in schizophrenia spectrum.
Morphologic abnormalities of the superior temporal gyrus (STG) as well as its sub-regions such as Heschl's gyrus (HG) or planum temporale (PT) have been reported in schizophrenia patients, but have not been extensively studied in schizotypal subjects. In the present study, magnetic resonance images were acquired from 65 schizophrenia patients, 39 schizotypal disorder patients, and 72 healthy controls. Volumetric analyses were performed using consecutive 1-mm coronal slices on the temporal pole (TP) and superior temporal sub-regions [planum polare (PP), HG, PT, rostral STG, and caudal STG]. The HG was significantly smaller in schizophrenia patients compared with controls but not in schizotypal patients, while volume reductions of the left PT and bilateral caudal STG were common to both disorders. The TP gray matter was larger in female schizotypal patients compared with female schizophrenia patients. There were no significant group differences in the PP and rostral STG volume. In the subgroup of early phase schizophrenia patients (illness duration <1.0 year), smaller volumes for the left PP and rostral STG were correlated with hallucinations and delusions. Our findings suggest that morphologic changes in the posterior regions of the STG are common to the schizophrenia spectrum, whereas less involvement of the HG, and possibly the PP and rostral STG might be related to the sparing of schizotypal patients from developing overt psychosis.
Adolescent↗
Verbal memory deficits in a preadolescent case of lesions of the left parahippocampal gyrus associated with a benign tumor.
The authors report cognitive functions of a 13-year-old boy with a cavernous angioma occupying the posterior left parahippocampal gyrus (PHG) and part of the left fusiform gyrus but not hippocampus. Neuropsychological examinations soon after the removal of the tumor showed selective deficits in semantic memory function, as evaluated by the Category Fluency Task and the Wechsler Memory Scale-Revised, while visual memory, attention, and IQ were not affected. These observations suggest the involvement of the PHG in the processing of semantic memory and provide an insight into the neural substrates underlying the distinct cognitive deficits in some of the psychiatric diseases such as schizophrenia.
Adolescent↗
Impairment of memory organization in patients with schizophrenia or schizotypal disorder.
Verbal learning and the organization of memory in patients with schizophrenia or schizotypal disorder were compared with normal subjects. Three indices of memory organization (semantic clustering, serial clustering, and subjective clustering) were calculated from participants' responses on the Japanese Verbal Learning Test. Schizophrenic and schizotypal patients showed similar decrements in semantic organization compared with normal subjects. Neither patient group showed any effect of learning on their use of semantic organization, although both groups recalled more items as the number of trials increased. These results suggest that impairment of memory organization is a common characteristic of schizophrenia spectrum disorders.
Adolescent↗
[For the preparation for psychiatric specialist training programs: from a viewpoint of university hospitals].
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Education, Medical, Graduate↗
Enhancement of lactate metabolism in the basolateral amygdala by physical and psychological stress: role of benzodiazepine receptors.
Lactate is considered to play a significant role in energy metabolism and reflect neural activity in the brain. Using in vivo microdialysis technique, we measured extracellular lactate concentrations in the basolateral amygdaloid nucleus (BLA) of rats under electric footshock or psychological stress. We also attempted to determine whether the stress-induced changes of extracellular lactate concentrations in the BLA are attenuated by diazepam, an agonist at benzodiazepine receptors, and whether FG7142, an inverse agonist at benzodiazepine receptors, have a facilitative effect on energy metabolism in the BLA. Both footshock and psychological stress led to an increase in extracellular lactate concentrations in the BLA. Similar increment of extracellular lactate levels was observed by administration of FG7142. Pretreatment with diazepam attenuated the ability of FG7142, as well as physical or psychological burden, to increase lactate levels in the BLA. These results indicate that a variety of stressors enhances energy metabolism in the BLA, and suggest that some stress-induced changes in energy metabolism are regulated by benzodiazepine receptors.
Amygdala↗
Prefrontal abnormalities in patients with simple schizophrenia: structural and functional brain-imaging studies in five cases.
Simple schizophrenia is an uncommon disorder with unknown pathophysiology, and its position in the current diagnostic system is ambiguous. Brain-imaging studies may help to elucidate its pathophysiology. Five patients fulfilling both ICD-10 criteria for simple schizophrenia and DSM-IV criteria for simple deteriorative disorder underwent computed tomography, magnetic resonance imaging, and single photon emission computed tomography. These scans were assessed individually by visual inspection as well as automatically by comparison with scans in normal controls or other schizophrenia subtype patients using voxel-based image analyses. Three of the five simple schizophrenia patients had findings of atrophy and reduced cerebral perfusion in the frontal areas. Voxel-based analyses also showed prefrontal grey matter deficits and hypoperfusion in simple schizophrenia patients compared with the controls. Although this study is limited by the small number of patients with simple schizophrenia, the results suggest that simple schizophrenia, or at least this subpopulation, may have rather homogeneous morphological and functional deficits in the prefrontal cortex. It is also suggested that simple schizophrenia may occupy an extreme position of the schizophrenic continuum where the prefrontal deficits and negative symptoms are most purely manifested.
Adult↗
NC-1900, an arginine-vasopressin analogue, ameliorates social behavior deficits and hyperlocomotion in MK-801-treated rats: therapeutic implications for schizophrenia.
We previously reported that chronic administration of N-methyl-D-aspartate (NMDA) antagonists reduced the density of vasopressin V1a receptors in several brain regions in rats that demonstrated social interaction deficits and increased locomotor activity. These observations indicate the ability of arginine-vasopressin (AVP), or its analogues, to modulate behavioral abnormalities associated with blockade of NMDA receptors. The present study was performed to investigate the effect of NC-1900, an AVP analogue, on social behavior and locomotor activity in rats treated with MK-801, a non-competitive NMDA receptor antagonist. Male Wistar rats were administered MK-801 (0.13 mg/kg/day ip) or saline for 14 days. Social behavior and locomotor activity were measured 45 min after the injection of NC-1900 (10 ng/kg sc) or saline together with the last MK-801 or vehicle administration. Social interaction was quantified by an automated video-tracking system, and stereotyped behavior and ataxia were manually measured. Acute administration of NC-1900 partially reversed MK-801-induced hyperlocomotion and deficits in social interaction, while NC-1900 itself did not affect these behavioral measures in animals chronically treated with vehicle saline. These results suggest that the central AVP system may interact with glutamatergic and dopaminergic transmissions, and indicate potential therapeutic effects of AVP analogues on positive and negative symptoms of schizophrenia.
Analysis of Variance↗
Improvement of occipital alpha activity by repetitive hyperbaric oxygen therapy in patients with carbon monoxide poisoning: a possible indicator for treatment efficacy.
OBJECTIVES: The main aim of this study was to evaluate the efficacy of repetitive hyperbaric oxygen (HBO) treatments with monitoring of quantitative electroencephalography (qEEG) for symptoms of acute carbon monoxide (CO) poisoning and prevention of delayed neuropsychiatric sequelae. METHODS: Eight patients with acute CO poisoning received repetitive HBO treatments five times a week and qEEG was recorded once a week. Peak alpha frequency, peak alpha power, and absolute and relative alpha power in the occipital region were evaluated. The repetitive HBO treatments were discontinued when the peak alpha frequency increased to and maintained a maximum in each patient. RESULTS: The mean number of HBO treatments was 20.3. The peak alpha frequency and the relative alpha power significantly increased after repetitive HBO treatments. The absolute alpha power and the peak alpha power insignificantly improved. Total numbers of HBO treatments were not correlated with age, duration of CO exposure, initial level of COHb, or interval to the first HBO treatment. After the completion of repetitive HBO treatments, no patient developed delayed neuropsychiatric sequelae. CONCLUSIONS: These results suggest that repetitive HBO treatments may prevent the delayed neuropsychiatric sequelae of CO poisoning when applied individually with monitoring of the peak alpha frequency as an indicator of efficacy.
Adult↗
Volumetric analysis of sulci/gyri-defined in vivo frontal lobe regions in schizophrenia: Precentral gyrus, cingulate gyrus, and prefrontal region.
Methodological limitations in most previous magnetic resonance imaging (MRI)-based volumetric studies might have contributed to the inconsistent results regarding the frontal lobe regions of schizophrenia. Thus, applying the largest sample to date among those that have fully taken account of the intrinsic anatomical landmarks, this study aimed at clarifying the volumetric alterations of the frontal lobe and its subregions in schizophrenia. Participants comprised 59 patients with schizophrenia and 58 healthy controls. Measurements were performed on consecutive 1-mm-thick coronal slices reformatted from three-dimensional 1.5-T MR images. The whole frontal lobe was demarcated and then subdivided into the precentral gyrus (PCG), anterior cingulate, and posterior cingulate, and the remainder temporarily as the prefrontal region. Patients with schizophrenia had significant cortical volume reductions in the bilateral whole frontal lobe, prefrontal region, PCG, posterior cingulate, and right anterior cingulate. This study has confirmed that patients with schizophrenia do have cortical volume reductions in the whole frontal lobe and its subregions. Volume reduction in the PCG suggests that the primary motor cortex might contribute to the mechanisms of schizophrenia, considering its important role in the processing of multiple motor-related cognitive functioning suggested by the recent literature.
Adult↗