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Biomedical subjects

Kiyoto Kasai

Publications and source records attributed to Kiyoto Kasai.

At least 19 recordsLinked to original sources

Human brain structural change related to acute single exposure to sarin.

OBJECTIVE: This study aimed to identify persistent morphological changes subsequent to an acute single-time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long-lasting somatic and cognitive symptoms in victims exposed to sarin. METHODS: Thirty-eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1-weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated. RESULTS: The voxel-based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel-based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05). INTERPRETATION: Sarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals.

Adult↗

Aging in the CNS: comparison of gray/white matter volume and diffusion tensor data.

This study investigated the global and regional effects of aging on brain volume, mean diffusivity (MD), and fractional anisotropy (FA) in 73 normal female subjects using voxel-based analysis. On a global scale, gray matter volume and FA were negatively correlated, whereas MD was positively correlated with age. Voxel-wise analyses showed brain volume and FA were negatively correlated predominantly in anterior structures, whereas MD was positively correlated in the cortical gray matter and periventricular white matter. Volume preservation was observed in the cingulate gyrus and subjacent white matter. FA increase was observed in the putamen. Voxel-based direct comparisons of volume and diffusion properties showed FA was more strongly negatively correlated in the fronto-temporal white matter, compared with volume and MD. Stronger positive correlation of MD was observed in the thalamus, caudate nucleus, and midbrain and stronger negative correlation of brain volume was observed in the frontal lobe and basal ganglia, compared with the other. These results indicate that diffusion properties and brain volume are complementary markers to the effects of aging.

Adult↗

Auditory P300 latency prolongation with age in schizophrenia: gender and subcomponent effects.

Previous studies showing prolongation of auditory P300b latency with increasing age provided support for post-onset progressive change in schizophrenia. We sought to extend the findings by evaluating the effects of gender and the subcomponents (P3b versus P3a) in schizophrenia (N=108) and controls (N=70). P3b latency significantly correlated with age in schizophrenia (Spearman's rho=0.214, P=0.026) and in male patients with schizophrenia (rho=0.260, P=0.049) whereas, it did not reach significance in female patients with schizophrenia (rho=0.174, P=0.23). P3a latency showed no correlation. Our findings may provide evidence for progressive change in the brain function in schizophrenia, and this change may be slower in female than male patients. P3b may serve as a more sensitive index for cognitive decline than P3a.

Adult↗

No association between the metabotropic glutamate receptor type 3 gene (GRM3) and schizophrenia in a Japanese population.

Several lines of evidence have suggested that the metabotropic glutamate receptor 3 (GRM3) gene is a candidate susceptibility gene for schizophrenia. To our knowledge, six studies have investigated the genetic association between GRM3 and schizophrenia, although the results have been quite controversial. In the present study, we investigated the association between the GRM3 gene and schizophrenia in 402 Japanese people by analyzing 10 single nucleotide polymorphisms (SNPs), including all SNPs that showed significant results in previous studies. We observed no significant difference in allelic frequencies or genotypic distributions of the 10 SNPs between the controls and patients. A permutation test showed no significant global differences in estimated haplotype frequencies between the controls and patients. Thus, the present study provides no positive evidence of an association between the GRM3 gene and schizophrenia in the Japanese population.

Adult↗

No evidence for an association between the BDNF Val66Met polymorphism and schizophrenia or personality traits.

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family, which plays a critical role in neurodevelopment. Based on the neurodevelopmental hypothesis, the BDNF gene has been a candidate locus for schizophrenia. In Caucasians, recent studies identified an association with the Val66Met polymorphism, which has been suggested to affect episodic memory and hippocampal function in humans. However, in other populations, the association has not been replicated. In the present study, we investigated the association between the Val66Met polymorphism of the gene and schizophrenia in 401 Japanese patients with schizophrenia and 569 controls. As a result, we did not observe a significant difference in genotypic distribution or allele frequencies between the patients and controls (chi2=0.56, df=2, p=0.76 and chi2=0.39, df=1, p=0.53, respectively). We also investigated the association between the polymorphism and personality traits in the controls; however, no significant association was observed. Thus, the present study did not provide evidence for an association between the BDNF gene and schizophrenia or personality traits in the Japanese population.

Asian People↗

Phonetic mismatch negativity predicts verbal memory deficits in schizophrenia.

Deficits in auditory sensory memory at the electrophysiological level as indexed by mismatch negativity and those in auditory verbal memory at the neuropsychological level have been independently demonstrated in previous studies of schizophrenia. We predicted a specific association between these indices in schizophrenia. Mismatch negativities elicited by change in tone duration and phoneme duration were recorded in 23 schizophrenia patients, who were also evaluated for auditory verbal memory and executive function. Lower amplitude of mismatch negativity under the phoneme-duration condition was significantly associated with worse verbal memory. Phoneme-duration mismatch negativity was not correlated with executive function, nor was tone-duration mismatch negativity correlated with verbal memory. These results suggest that electrophysiological auditory sensory memory dysfunction underlies the basis for neuropsychological auditory verbal memory deficits in schizophrenia.

Adult↗

Decreased prefrontal activation during letter fluency task in adults with pervasive developmental disorders: a near-infrared spectroscopy study.

Functional neuroimaging studies have suggested that dysfunction of prefrontal cortex (PFC) is present in persons with pervasive developmental disorders (PDD). Recently, the development of near-infrared spectroscopy (NIRS) has enabled noninvasive bedside measurement of regional cerebral blood volume. Although NIRS enables the noninvasive clarification of brain functions in many psychiatric disorders, it has not yet been used to examine subjects with PDD. The aim of our study was to conduct an NIRS cognitive activation study to verify PFC dysfunction in PDD. The subjects were 10 adults with PDD and 10 age- and gender-matched healthy subjects. Hemoglobin concentration changes were measured with a 24-channel NIRS machine during the letter fluency task. While the number of words generated during the letter fluency task did not differ significantly between groups, the analysis of covariance including IQ as a confounding covariate showed that the PDD group was associated with bilateral reduction in oxy-hemoglobin concentration change as compared with the control group. The statistical results did not change when only IQ-matched high-functioning subjects (N=7) were included. Moreover, reduced oxy-hemoglobin concentration change for the right PFC was significantly correlated with verbal communication deficits within the PDD group. The present findings are consistent with proposed prefrontal dysfunction in PDD subjects identified by other neuroimaging modalities. The present results may be also potentially useful for applying NIRS to clinical settings of child psychiatry.

Adolescent↗

The effect of perospirone on auditory P300 in schizophrenia: a preliminary study.

The present study was performed to determine the effect of perospirone, a novel antipsychotic drug with D(2)/5-HT(2A) antagonist and partial 5-HT(1A) agonist properties, on auditory P300 in eight patients with chronic schizophrenia. Switching to an equivalent dose of perospirone from prior antipsychotic medication was associated with a significant improvement in the negative symptoms of the positive and negative syndrome scale (PANSS). The change in P300 amplitude following a switch to perospirone correlated significantly with the improvement of general psychopathology symptoms, as well as with the change in scores on items of delusions, hallucinatory behavior, emotional withdrawal, depression, poor attention, and disturbance of volition. These results suggest that clinical improvement in response to perospirone in some patients may, at least in part, be mediated through cognitive change indexed by P300 in chronic schizophrenia.

Adult↗

Voxel-based diffusion tensor analysis reveals aberrant anterior cingulum integrity in posttraumatic stress disorder due to terrorism.

Recent functional neuroimaging work has suggested that interregional functional connectivity between the anterior cingulate cortex (ACC), other limbic, and prefrontal regions may be involved in the pathophysiology of posttraumatic stress disorder (PTSD). However, less attention has been paid to the white matter network. Voxel-based analysis enables an exploration of morphological or functional changes throughout the entire brain. Here we undertook the first application of this technology to diffusion tensor data in patients with PTSD. Participants were 9 victims of the Tokyo subway sarin attack with PTSD and 16 matched victims of the same traumatic event without PTSD. The voxel-based analysis showed a significant fractional anisotropy increase in the left anterior cingulum, subjacent to the left ACC gray matter where we previously found a volume decrement, in PTSD subjects. Moreover, the severity was positively, but not significantly associated with the fractional anisotropy of the left anterior cingulum in the victims with PTSD, using the region of interest defined in the native space with the inverse normalization technique. The present study demonstrated further evidence of abnormalities of both the ACC, a structure that is pivotally involved in attention, emotional regulation, and fear conditioning, and of subjacent white matter in the pathology of PTSD.

Adult↗

Comparison between mismatch negativity amplitude and magnetic mismatch field strength in normal adults.

The auditory mismatch negativity (MMN) or its magnetic counterpart (magnetic mismatch field, MMF) has been widely used to assess the ability of stimulus-driven change detection process in humans. The authors evaluated the similarity of inter-individual variation of the response strength between MMN and MMF recordings. Three types of MMN or MMF were recorded in ten healthy subjects: change in duration of pure-tone stimuli, change in duration of the Japanese vowel /a/, and difference between the Japanese vowels /a/ and /o/. There was no significant correlation between MMN amplitude and MMF strength under any condition and in either hemisphere. These results suggest that widely used indices of MMN in the two technologies, i.e., EEG-amplitude and MEG-ECD may not be proportional in an individual. To further clarify the differential significance of recording MMN/MMF may be important to establish MMN/MMF as clinical indices of individual ability of preattentive stage of auditory processing.

Adult↗

Procedural memory predicts social skills in persons with schizophrenia.

Despite a growing number of studies that have investigated the relationship between neurocognition and psychosocial outcome in schizophrenia, no studies have looked at the relationship between procedural memory and social skills measures in schizophrenia. The goal of this study was to investigate whether procedural memory, often preserved in schizophrenia, could predict nonverbal social skills in chronic patients with schizophrenia. Fourteen outpatients with schizophrenia participated in our study. Procedural memory was evaluated using the Mirror Reading Test, and nonverbal and verbal social skills were evaluated using a structured role play test. As predicted, there was a significant positive correlation between the learning index of the Mirror Reading Test and nonverbal skills (Spearman rho=0.559, p = 0.038), but not for verbal communication skills or processing skills. Although preliminary, these results provide the first evidence of an association between procedural memory and nonverbal social skills in patients with schizophrenia.

Adult↗

Estimation of premorbid IQ in individuals with Alzheimer's disease using Japanese ideographic script (Kanji) compound words: Japanese version of National Adult Reading Test.

The National Adult Reading Test (NART) is widely used as a measure of premorbid IQ of the English-speaking patients with dementia. The purpose of the present study was to develop a Japanese version of the NART (JART), using 50 Japanese irregular words, all of which are Kanji (ideographic script) compound words. Reading performance based on JART and IQ as measured by the Wechsler Adult Intelligence Scale-Revised (WAIS-R) was examined in a sample of 100 normal elderly (NE) persons and in 70 age-, sex-, and education-matched patients with Alzheimer's disease (AD). The NE group was randomly divided into the NE calculation group (n=50) and the NE validation group (n=50). Using the NE calculation group, a linear regression equation was obtained in which the observed full-scale IQ (FSIQ) was regressed on the reading errors of the JART. When the regressed equation computed from the NE calculation group was applied to the NE validation group, the predicted FSIQ adequately fit the observed FSIQ (R2=0.78). Further, independent t-tests showed that the JART-predicted IQs were not significantly different between the NE and AD groups, whereas the AD group performed worse in the observed IQs. The reading ability of Kanji compound words is well-preserved in Japanese patients with AD. The JART is a valid scale for evaluating premorbid IQ in patients with AD.

Aged↗

Effect of subjective reasoning and neurocognition on medication adherence for persons with schizophrenia.

OBJECTIVE: This study investigated the relationship between patients' reasoning about medication adherence and neurocognitive and clinical indices for a treatment-compliant sample of Japanese patients with schizophrenia. METHODS: Subjective reasoning about medication adherence was assessed by the Rating of Medication Influences (ROMI) scale. General intelligence, executive function, and verbal memory were assessed by the Wechsler Adult Intelligence Scale-Revised, Wisconsin Card Sorting Test, and Rey Auditory Verbal Learning Test, respectively. RESULTS: Higher prevention scores were associated with lower executive functioning and older age. Influence of others was associated with years of education, medication dosage, and IQ, and medication affinity was associated with education. CONCLUSIONS: These results suggest that executive functioning, education, and general IQ may all be important factors in individual motivation for medication adherence.

Adult↗

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↗

Prefrontal cortex and amygdala volume in first minor or major depressive episode after cancer diagnosis.

BACKGROUND: Major and minor depressive episodes in cancer patients are frequent and are frequently seen as the first depressive episode in a patient's life. However, the neurological basis of these depressive episodes remains largely unknown. METHODS: Subjects were 51 breast cancer survivors (BCS) who had no history of any depressive episode before the cancer diagnosis (11 BCS with a history of a first minor depressive episode after cancer diagnosis, 11 BCS with a history of a first major depressive episode after cancer diagnosis, and 29 BCS with no history of any depressive episode after cancer diagnosis). We analyzed the prefrontal cortex (PFC) and amygdala volumes in a 1.5-Tesla Magnetic Resonance Imaging scanner. We characterized the structural correlates of depression using two complementary approaches. The first was voxel-based morphometry (VBM) that allowed us to scan the entire brain for reactive gray matter deficit. The second was classical volumetry focusing on the amygdala. RESULTS: Voxel-based morphometry revealed no brain region, including PFC, for which volume was significantly different among the three groups. There were trend-level differences in the left amygdala volume in the manual tracing method among the three groups. The left amygdala volumes in the subjects with a first minor and/or major depressive episode were significantly smaller than in those with no history of any depressive episode. CONCLUSIONS: It might be suggested that amygdala volume was associated with a first minor and/or major depressive episode after cancer diagnosis.

Adult↗

Confirmation of a relationship between reduced auditory P300 amplitude and thought disorder in schizophrenia.

We have previously reported an association between reduced amplitude of auditory P300 event-related potential and severity of positive thought disorder as assessed by the Comprehensive Index of Positive Thought Disorder in a sample of patients with chronic schizophrenia. Here we replicate those findings using a different measure, Thought Disorder Index (TDI), in a new larger sample of 55 patients. The auditory P300 amplitude showed a significant negative correlation with scores on TDI. This correlation was relatively more pronounced in the left temporal region than in the right temporal region. These results further suggest that electrophysiological abnormalities of information processing may underlie positive thought disorder in schizophrenia.

Adult↗

Parahippocampal activation evoked by masked traumatic images in posttraumatic stress disorder: a functional MRI study.

Posttraumatic stress disorder (PTSD) has been widely studied, but its neural mechanism is still unclear. The purpose of this study is to identify dysfunctional areas in PTSD throughout the whole brain to help to elucidate the neural mechanisms of PTSD. Sixteen patients with PTSD and sixteen healthy controls participated in this study. Traumatic images under perceptual threshold including scenes of earthquakes, traffic accidents, ambulances, emergency rooms, and crimes were presented to the participants, and brain activation was measured using functional MRI. Functional brain images of both groups were evaluated with random effect analysis for the whole brain. In the control group, activation in the ventral frontoparietal areas correlated significantly with presentation of the masked traumatic stimuli. In the PTSD group, activation was not observed in these areas, but significant activation correlated with the masked traumatic stimuli in the parahippocampal region including the left parahippocampal gyrus and tail of the left hippocampus. These results suggest that in PTSD patients activation in the ventral frontoparietal network associated with visual attention processing is attenuated, while the left hippocampal area associated with episodic and autobiographical memory is abnormally easily activated. This pattern of activation corresponds well to the clinical characteristics of PTSD, in which even slight traumatic stimuli tend to induce intrusive recollection or flashbacks, despite a general decrease in attention and ability to concentrate.

Adult↗