Biomedical subjects

Tomiki Sumiyoshi

Publications and source records attributed to Tomiki Sumiyoshi.

At least 19 recordsLinked to original sources

PubMed2026

Autistic-like traits and longitudinal changes in health-related quality of life among individuals with bipolar disorder: A 12-month study.

OBJECTIVE: Autistic-like traits are common in bipolar disorder (BD) and have been linked to poor functional outcomes, yet their longitudinal impact on quality of life (QOL) remains unclear. This study examined whether autistic-like traits are associated with 12-month changes in health-related QOL in BD. METHODS: Seventy-eight outpatients with BD who completed 12-month follow-up assessments were included (mean age = 34.9 years). Autistic-like traits were assessed using the Social Responsiveness Scale for Adults (SRS-A), with participants classified into elevated- and non-elevated-traits groups. Depressive and manic symptoms were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17) and the Young Mania Rating Scale (YMRS). QOL was measured using the 36-Item Short-Form Health Survey (SF-36). Linear mixed models were used to examine longitudinal changes. RESULTS: HAMD-17 scores demonstrated significant main effects of time and group, reflecting overall improvement but persistently higher depressive symptoms in the elevated-traits group. YMRS scores indicated a significant group effect only. Physical QOL remained stable, while mental QOL improved over time without group differences. Role/social QOL showed significant main effects of time and group, with consistently lower scores in the elevated-traits group. No group × time interactions emerged, suggesting similar rates of change between groups. CONCLUSIONS: This prospective study suggests that autistic-like traits in BD are associated with persistently poorer role/social functioning over time rather than differences in recovery trajectories. Assessing autistic-like traits may help identify patients at risk of poorer functioning and guide tailored psychosocial interventions.

Autistic-like traits↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

Psychosis pathways converge via D2high dopamine receptors.

The objective of this review is to identify a target or biomarker of altered neurochemical sensitivity that is common to the many animal models of human psychoses associated with street drugs, brain injury, steroid use, birth injury, and gene alterations. Psychosis in humans can be caused by amphetamine, phencyclidine, steroids, ethanol, and brain lesions such as hippocampal, cortical, and entorhinal lesions. Strikingly, all of these drugs and lesions in rats lead to dopamine supersensitivity and increase the high-affinity states of dopamine D2 receptors, or D2High, by 200-400% in striata. Similar supersensitivity and D2High elevations occur in rats born by Caesarian section and in rats treated with corticosterone or antipsychotics such as reserpine, risperidone, haloperidol, olanzapine, quetiapine, and clozapine, with the latter two inducing elevated D2High states less than that caused by haloperidol or olanzapine. Mice born with gene knockouts of some possible schizophrenia susceptibility genes are dopamine supersensitive, and their striata reveal markedly elevated D2High states; suchgenes include dopamine-beta-hydroxylase, dopamine D4 receptors, G protein receptor kinase 6, tyrosine hydroxylase, catechol-O-methyltransferase, the trace amine-1 receptor, regulator of G protein signaling RGS9, and the RIIbeta form of cAMP-dependent protein kinase (PKA). Striata from mice that are not dopamine supersensitive did not reveal elevated D2High states; these include mice with knockouts of adenosine A2A receptors, glycogen synthase kinase GSK3beta, metabotropic glutamate receptor 5, dopamine D1 or D3 receptors, histamine H1, H2, or H3 receptors, and rats treated with ketanserin or aD1 antagonist. The evidence suggests that there are multiple pathways that convergetoelevate the D2High state in brain regions and that this elevation may elicit psychosis. This proposition is supported by the dopamine supersensitivity that is a common feature of schizophrenia and that also occurs in many types of genetically altered, drug-altered, and lesion-altered animals. Dopamine supersensitivity, in turn, correlates with D2High states. The finding that all antipsychotics, traditional and recent ones, act on D2High dopamine receptors further supports the proposition.

Animals↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2005

Atypical antipsychotic drugs and organization of long-term semantic memory: multidimensional scaling and cluster analyses of category fluency performance in schizophrenia.

Organization of semantic memory, one of the domains of cognitive function, is impaired in patients with schizophrenia, and is predictive of functional outcomes. The Category Fluency Task (CFT) has been used to evaluate organization of long-term semantic memory by means of visualizing semantic associations in the form of 'cognitive map' and cluster structures. While atypical antipsychotic drugs (AAPDs) have been shown to ameliorate overall cognitive deficits, little is known about the efficacy of AAPDs for improving higher cognitive functions, such as semantic memory organization. The purpose of the present study was to determine if treatment with olanzapine or ziprasidone has beneficial influence on organization of semantic memory, as revealed by analysis of data from the CFT, in patients with schizophrenia. A retrospective analysis of an open-label trial was conducted for 33 patients with schizophrenia who were treated with either olanzapine or ziprasidone. Nineteen subjects were unmedicated at baseline. The CFT and Letter Fluency Task, as well as the Brief Psychiatric Rating Scale (BPRS) and Quality of Life Scale (QLS), were administered at baseline and 6 wk of the treatment. Semantic structures were obtained by multidimensional scaling analysis and hierarchical cluster analysis of verbal outputs from the CFT. At baseline, no meaningful dimension or cluster was observed in the semantic structure; however, knowledge-based dimensions (wild vs. domestic) appeared after treatment with olanzapine or ziprasidone. Cluster structures also became organized, especially after treatment with olanzapine. Scores of QLS, but not those of BPRS, improved during treatment with the AAPDs. These results suggest a facilitative influence of AAPDs on higher cognitive functions, such as organization of semantic memory, in patients with schizophrenia.

Adult↗

PubMed2005

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↗

PubMed2005

Perospirone in the treatment of schizophrenia: effect on verbal memory organization.

The present study was performed to determine if perospirone, a novel antipsychotic drug with D2/5-HT2A antagonist and partial 5-HT1A agonist properties, would improve memory organization in twelve patients with chronic schizophrenia. Switching to equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in indices of verbal memory organization of the Auditory Verbal Learning Test. Negative symptoms and extrapyramidal side effects were also ameliorated after switching to perospirone. The distinct cognitive enhancement profile of perospirone may be attributable to its partial 5-HT1A agonist action.

Adult↗

PubMed2005

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↗

PubMed2005

Increased proportion of high-affinity dopamine D2 receptors in rats with excitotoxic damage of the entorhinal cortex, an animal model of schizophrenia.

Excitotoxic lesions of the left entorhinal cortex (EC) cause dopamine supersensitivity. In order to determine if these lesions selectively alter the high-affinity state of dopamine D2 receptors (D2(High)), these high-affinity states were measured by competition between dopamine and [3H]domperidone in striata from lesioned rats and sham-operated animals. The proportion of D2(High) sites was significantly elevated by 200% in the EC-lesioned rats while that of the D1(High) sites, measured by dopamine/[3H]SCH23390 competition, was unaltered. These results provide a biochemical basis for behavioral supersensitivity in rats with EC lesions.

Animals↗

PubMed2005

Prediction of the ability of clozapine to treat negative symptoms from plasma glycine and serine levels in schizophrenia.

We previously reported that plasma levels of glycine, a co-agonist at N-methyl-D-asparate (NMDA)-type glutamate receptors, are decreased in patients with schizophrenia, and that glycine levels are negatively correlated with negative symptoms. The aim of the present study was to determine if glycine, or its ratio to serine, a precursor of glycine, predicts change in negative symptoms in subjects with schizophrenia during treatment with clozapine, an atypical antipsychotic drug with multiple effects on glutamatergic activity. Plasma levels of glycine, serine, and their ratio, were measured in 44 patients with schizophrenia who were subsequently treated with clozapine. Baseline glycine levels or glycine/serine ratios predicted the Scale for the Assessment of Negative Symptoms - Sum of the Global Scales and Avolition-Apathy after 6 wk of clozapine treatment. These results indicate the association of these amino acid measures with response to clozapine in terms of negative symptoms in patients with schizophrenia.

Adult↗

PubMed2005

Disorganization of semantic memory underlies alogia in schizophrenia: an analysis of verbal fluency performance in Japanese subjects.

Patients with schizophrenia exhibit impaired semantic memory as well as deficits in a wide range of language-related functions, such as verbal fluency, comprehension and production of complex sentences. Since language and memory disturbances may underlie some of the psychotic symptoms of schizophrenia, the present study investigated the specific association between alogia (i.e. poverty of speech, poverty of content of speech, blocking, and increased latency of response) and semantic memory organization using the category fluency task (CFT) as a measure of verbal fluency. Thirty-eight patients with schizophrenia and an equal number of normal controls entered the study. Semantic structure was derived from multidimensional scaling analysis using sequential word outputs from the CFT. Patients with schizophrenia revealed disorganized semantic structure (e.g. irregular association of category members) compared with controls, consistent with previous reports. The patients were then divided into two groups, i.e. alogia- and non-alogia subjects, based on the Alogia scores from the Scale for the Assessment of Negative Symptoms (SANS). The symptom-based analysis showed that the semantic structure for the alogia group (Alogia score < or =2) was more disorganized than that for the non-alogia group (Alogia score <1) although the number of words produced did not differ between the two groups. The results of cluster analysis revealed the presence of bizarre coherence specifically in the alogia group. These results indicate that semantic memory disorganization may contribute to the symptom of alogia in schizophrenia. In addition, this is one of the few studies that examined verbal fluency in Japanese patients with schizophrenia and suggest that the language abnormalities in schizophrenia are universal.

Adult↗

PubMed2004

Enhanced locomotor activity in rats with excitotoxic lesions of the entorhinal cortex, a neurodevelopmental animal model of schizophrenia: behavioral and in vivo microdialysis studies.

In order to examine the construct validity of rats with excitotoxic damage of the left entorhinal cortex (EC) as an animal model of schizophrenia, we measured dopamine (DA)-related behaviors and methamphetamine (MAP)-induced DA release in the accumbens nucleus (NAC) in these animals. Quinolinic acid (lesion group) or phosphate buffer (sham group) was infused into the left EC of adolescent (postnatal 7 weeks) male Wistar rats. On the 14th and 28th postoperative day, spontaneous and MAP (1 mg/kg, i.p.)-induced locomotor activities, as well as MAP-induced stereotypy, were measured. The lesioned rats exhibited significantly greater spontaneous or MAP-induced locomotor activity on both of the postoperative days than did sham-operated animals, while EC lesions did not affect MAP-induced stereotypy on either occasion. MAP (1 mg/kg, i.p.)-induced DA release in NAC was measured by in vivo microdialysis on the 28th postoperative day. Lesioned rats did not show a significant change in MAP (1 mg/kg, i.p.)-induced DA release in NAC compared to sham-operated animals. These results suggest that excitotoxic damage of the left EC produces behavioral changes consistent with altered mesolimbic dopaminergic transmissions, possibly mediated by postsynaptic supersensitivity.

Animals↗

PubMed2004

Effect of orthography on the verbal fluency performance in schizophrenia: examination using Japanese patients.

Letter fluency performance is less impaired than the category fluency performance in alphabetical-language speakers with schizophrenia. The purpose of this study was to determine whether the same pattern in the performance on the two verbal fluency tasks exists in subjects using a non-alphabetical language. In the Japanese orthography, there is one-to-one correspondence between sound (syllable) and graphemes ("kana" script), in contrast to one-to-many associations in alphabetical languages (e.g. English, French). The category fluency task (ANIMAL, FRUIT) and the letter fluency task ("KA", "TA" in "kana" script) were administered on 38 patients with schizophrenia and the equal number of normal controls. In order to examine the influence of psychotic symptoms on the verbal fluency performance, the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were administered. The patients performed significantly worse both in the letter- and category fluency tasks compared with control subjects. However, performance on the letter fluency task and category fluency task was similarly impaired in Japanese patients with schizophrenia, unlike the results in previous studies with alphabetical-language speakers. On the other hand, Alogia symptoms, as assessed by SANS, was a significant predictive variable in the regression model for the category fluency task score (ANIMAL), whereas the factor of the other domains of negative symptoms as a whole was a significant predictive variable in the model for the letter fluency task score (TA), which confirmed the findings in previous studies with alphabetical-language subjects. These results suggest that the pattern of impairment in the verbal fluency performance in schizophrenia is dependent on the specific language systems used by the patients although the degradation of the verbal fluency performance is influenced by some types of negative symptoms irrespective of the language system.

Adult↗

PubMed2004

Prediction of changes in memory performance by plasma homovanillic acid levels in clozapine-treated patients with schizophrenia.

RATIONALE: Cognitive dysfunction in schizophrenia has been demonstrated to be dependent, in part, on dopaminergic activity. Clozapine has been found to improve some domains of cognition, including verbal memory, in patients with schizophrenia. OBJECTIVES: This study tested the hypothesis that plasma homovanillic acid (pHVA) levels, a peripheral measure of central dopaminergic activity, would predict the change in memory performance in patients with schizophrenia treated with clozapine. METHODS: Twenty-seven male patients with schizophrenia received clozapine treatment for 6 weeks. Verbal list learning (VLL)-Delayed Recall (VLL-DR), a test of secondary verbal memory, was administered before and after clozapine treatment. Blood samples to measure pHVA levels were collected at baseline. RESULTS: Baseline pHVA levels were negatively correlated with change in performance on VLL-DR; the lower baseline pHVA level was associated with greater improvement in performance on VLL-DR during treatment with clozapine. Baseline pHVA levels in subjects who showed improvement in verbal memory during clozapine treatment ( n=13) were significantly lower than those in subjects whose memory performance did not improve ( n=14). CONCLUSIONS: The results of this study indicate that baseline pHVA levels predict the ability of clozapine to improve memory performance in patients with schizophrenia.

Adult↗