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Biomedical subjects

Tetsuro Ohmori

Publications and source records attributed to Tetsuro Ohmori.

At least 19 recordsLinked to original sources

Gene expression and association analysis of LIM (PDLIM5) in major depression.

LIM (PDLIM5) is a small protein that interacts with protein kinase C-epsilon and the N-type calcium channel alpha-1B subunit and modulates neuronal calcium signaling. Recently, the LIM mRNA expression in postmortem brains and immortalized lymphoblastoid cells from mood disorder patients was reported to be changed and seems to be involved in its pathophysiology. We hypothesized that the expression of the LIM mRNA in the native peripheral leukocytes may be a good candidate for the biological marker for mood disorders. Twenty patients with major depression and age- and sex-matched control subjects were included in this expression study. The LIM mRNA levels in the peripheral leukocytes from drug-naive depressive patients were significantly lower than those from control subjects and increased significantly after 4-week paroxetine treatments, to almost the same level as controls'. Hamilton depressive scores (HAM-D) were improved about 50% after 4-week treatment but neither paroxetine concentrations nor the changes of HAM-D scores showed significant correlation with the change of the mRNA levels. Then, we genotyped three single nucleotide polymorphic markers of LIM gene, which were reported to be associated with bipolar disorder in patients with major depression and control subjects (n=130, each), but there were no associations between these SNPs and major depression. Our investigation indicates that the lower expression levels of LIM mRNA in the peripheral leukocytes are associated with the depressive state and that its recovery after treatment may be an adaptive change induced by the antidepressant.

Adaptor Proteins, Signal Transducing↗

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in schizophrenia is associated with age at onset and symptoms.

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that promotes several functions of neurons and modulates neurotransmissions. It has been reported that there are alterations of BDNF levels in schizophrenic brains and that BDNF gene expressional changes would be responsible for the etiology of schizophrenia. Recent studies have shown that a variation of BDNF gene (Val66Met polymorphism) affects the function of neurons, and is associated with several neurological and psychiatrical disorders. We investigated the relationship between BDNF Val66Met polymorphism and the onset age as well as levels of clinical symptoms in 159 of chronic schizophrenia in-patients diagnosed by DSM-IV. The mean onset ages were 27.5+/-9.5 for BDNF Val/Val, 25.5+/-7.4 for BDNF Val/Met and 22.9+/-6.0 for BDNF Met/Met and this polymorphism was significantly associated with age at onset (P=0.023). The mean Brief Psychiatric Rating Scale scores (BPRS) were significantly different among those three groups (P=0.003). No significant differences were demonstrated comparing the BDNF genotype distributions of positive and negative family history (P=0.21). Our investigation indicates that the BDNF gene Val66Met polymorphism is related to the onset age of schizophrenia and the levels of clinical symptoms that remain after long-term antipsychotic treatment.

Adult↗

Proton magnetic resonance spectroscopy reveals an abnormality in the anterior cingulate of a subgroup of obsessive-compulsive disorder patients.

Numerous neuroimaging studies have suggested that obsessive-compulsive disorder (OCD) patients had a neurobiological abnormality in the frontal-subcortical circuits. On the other hand, there are distinct differences in the responses to pharmacological treatment among OCD patients. In the present study, we measured the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with different pharmacological responses. Participants comprised 20 patients and 26 healthy control subjects. OCD patients were divided into three groups according to the pharmacological response; responders to a selective serotonin reuptake inhibitor (SSRI) (group A: n=7), responders to SSRI with an atypical antipsychotic (group B: n=8) and non-responders to either SSRI or SSRI with an atypical antipsychotic (group C: n=5). Short echo proton MRS was used to measure NAA concentrations in the anterior cingulate, the left basal ganglia and the left prefrontal lobe of subjects. A significantly lower NAA concentration was observed only in group B compared with control subjects in the anterior cingulate. Our results suggest that a subgroup of OCD patients who respond to an SSRI with an atypical antipsychotic have distinct biological abnormalities in the anterior cingulate.

Adult↗

Activation of the prefrontal cortex during the Wisconsin Card Sorting Test as measured by multichannel near-infrared spectroscopy.

BACKGROUND: The Wisconsin Card Sorting Test (WCST) is a neuropsychological test to evaluate the function of the prefrontal cortex (PFC). However, inconsistent results have been reported concerning whether this task activates the PFC symmetrically or asymmetrically. OBJECTIVES: To investigate the brain activation in the PFC during the WCST, we examined blood oxygenation changes of healthy subjects by using multichannel near-infrared spectroscopy (NIRS). METHODS: Subjects were 32 healthy volunteers, 18 males and 14 females. The WCST was administered using a computerized version, and the hemodynamic changes of the PFC during the WCST were measured by a 24-channel NIRS system. RESULTS: A bilateral increase in oxygenated hemoglobin (oxyHb) was observed in the PFC in 20 subjects during the WCST. However, 5 subjects showed predominant activation on the left side and 3 subjects one on the right side. No oxyHb change was observed in 4 subjects, although they had good performances in the WCST. CONCLUSIONS: These results directly confirmed that the PFC was activated during the WCST in vivo by using the optical technique and suggested that the distribution of the activation in the PFC is different among healthy individuals.

Adult↗

Effect of antipsychotic replacement with quetiapine on the symptoms and quality of life of schizophrenic patients with extrapyramidal symptoms.

Replacement of antipsychotic drugs with quetiapine (QTP) was tried in a naturalistic setting in chronic schizophrenic patients who still showed moderate psychiatric symptoms and either showed extrapyramidal symptoms (EPS) or took anti-parkinson drugs for the EPS. QTP was added on and gradually increased while the previous drugs were tapered and discontinued whenever possible. Clinical symptoms, objective and subjective QOL, and EPS were measured before and 6 months after QTP addition, using Brief Psychiatric Rating Scale (BPRS), Quality of Life Scale (QLS), Schizophrenia Quality of Life Scale (SQLS) and Drug-Induced Extrapyramidal Symptom Scale (DIEPSS), respectively. Twenty-one patients completed the trial and received the assessment. It was found that replacement with QTP-improved clinical symptoms, objective and subjective QOL and EPS. This improvement was equally observed in not only patients who switched to QTP monotherapy (n = 11) but also patients who took QTP together with reduced small doses (4.4 +/- 4.3 mg/day) of previous drugs (n = 11). The results suggest that replacement with QTP improves symptoms as well as objective and subjective QOL in a subgroup of schizophrenia.

Adolescent↗

Clock mutant mice with Jcl/ICR background shows an impaired learning ability in water maze, but not in passive avoidance, at the beginning of dark phase.

We observed the learning ability in Clock mutant mice with Jcl/ICR background (Clockj), a mice model of evening-type individuals, in the early part of dark phase. In order to estimate the learning ability, Morris water maze (WM) and passive avoidance (PA) test were performed. Release of acetylcholine, 5 hydroxytryptophan (5-HT) and dopamine (DA) in hippocampus was measured by in vivo microdialysis method. Clockj showed the impaired learning ability in the WM, but not in PA test. Hippocampal acetylcholine release was significantly attenuated in the Clockj in comparison to the wild-type mice. Neither 5-HT nor DA in the hippocampus was affected by the Clock mutation. Clock, an essential gene controlling circadian rhythm, may have an important role on the spatial learning and hippocampal cholinergic function, at least, at the beginning of the dark phase.

5-Hydroxytryptophan↗

Subjective and objective measures of quality of life have different predictors for people with schizophrenia.

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p <.001), and with the scores on Interpersonal Relations subscale -.42 (p <.001), Instrumental Role subscale -.28 (p = .005), Intrapsychic Foundations subscale -.39 (p<.001), and Common Objects and Activities subscale -.25 (p =.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p =.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.

Adult↗

[Two cases of tardive Tourette syndrome].

Tardive Tourette syndrome is an extrapyramidal symptom which appears after long-term neuroleptic use. We report two cases of this syndrome and review case reports to introduce this extrapyramidal symptom. The first case is a 40-year-old male with schizophrenia. After 6 years of neuroleptic therapy, he began to have barking and grunting vocalizations and show neck and shoulderjerking. The second case is a 53-year-old male with alcoholism. Sulpride was prescribed for three years to treat mood symptoms. Oral dyskinesia appeared after sulpride was stopped. About five weeks after amantadine and trihexyphenidyl hydrochloride was started, he began to have grunting vocalizations and show neck jerking. The involuntary movement disappeared quickly after intraveneous administration of haloperidol. Including our two cases, there are 17 case reports of tardive Tourette syndrome. Twelve cases were schizophrenic patients. In addition to typical movements, patients had coplolalia in 6 cases, and oral dyskinesia in 9 cases. In 8 cases, tardive Tourette syndrome appeared during neuroleptic treatment, and in 9 cases the syndrome appeared after neuroleptics were stopped. Our two cases and previous case reports showed that tardive Tourette syndrome appeared after long-term neuroleptic therapy, it was improved transiently by an increase of neuroleptics and exacerbated by their decrease, it was exacerbated by dopaminergic and anticholinergic drugs, and tardive dyskinesia was often seen concomitantly, indicating that tardive Tourette syndrome has a similar pathophysiology to tardive dyskinesia. Tardive Tourette syndrome should not be misdiagnosed as an exacerbation of schizophrenic symptoms responsive to an increase of neuroleptics. This side effect should be recognized widely and treated properly.

Adult↗

Serotonin transporter mRNA expression in peripheral leukocytes of patients with major depression before and after treatment with paroxetine.

Serotonin transporter (5HTT) is thought to be involved in the pathophysiology of major depression and the target of antidepressants. We hypothesized that 5HTT mRNA levels in peripheral leukocytes may be associated with depressive states and the therapeutic response to antidepressant treatments. Fifteen patients with major depression and age-, sex-matched control subjects were studied. 5HTT mRNA levels were determined with quantitative real-time PCR method. 5HTT mRNA levels in leukocytes were significantly higher in depressive patients at baseline (before medication) than in control subjects. 5HTT mRNA levels were decreased significantly after 8 weeks of paroxetine medication compared with those at baseline. Our investigation suggested that the increased expression of 5HTT mRNA in peripheral leukocytes may be related with the pathophysiology of depression and its reduction after treatment may reflect the adaptive change induced by the antidepressant.

Adult↗

Expression analysis of psychological stress-associated genes in peripheral blood leukocytes.

In this study, we have developed a microarray including 1467 cDNAs that were selected to specifically measure stress response in peripheral blood leukocytes. Venous blood was collected from 10 graduate students 2 h before and 2 or 24 h after an open presentation for their Ph.D. The mRNA levels in leukocytes were compared with those prepared 4 weeks before the presentation. Hierarchical cluster showed that distinct groups of genes uniformly changed their expression values in response to the stress. Bayesian t test identified significantly up-regulated 49 genes and down-regulated 21 genes. Most of them are categorized into cytokines, cytokine receptors, growth- or apoptosis-related molecules, and heat shock proteins, suggesting that stressful life events trigger acute responses in leukocytes. Our results suggest that gene expression profile in peripheral blood leukocytes may be a potentially useful method for the assessment of complex stress responses.

Adult↗

Left atrial thrombosis associated with antipsychotic drugs.

The authors report a case of a 36-year-old shizophrenic patient with left atrial thrombosis. There have been small number of case reports of antipsychotic drugs-associated thromboembolic events. All of them are venous ones. This paper describes the first case of atrial thrombosis associated with antipsychotic drugs.

Adult↗

Assessment of human stress and depression by DNA microarray analysis.

Precise assessment of stress is an imminent issue to deal with stress-related social, medical and psychological problems. Psychological stress is known to stimulate the neuroendocrine, sympathetic nervous, and immune systems. By analyzing mRNA expression levels in leukocytes, which express receptors for hormones, neurotransmitters, growth factors, cytokines, and other stress related signals, levels of stress may be adequately measured. In a series of studies, our group has developed a cDNA microarray specifically designed to measure the mRNA levels of stress-related genes in peripheral blood leukocytes. This microarray enabled us to sensitively detect the response to psychological stress. In addition, our preliminary study suggests that the array could differentiate patients with depression from sex- and age-matched control subjects.

Biomarkers↗

Hemodynamic changes in the prefrontal cortex during mental works as measured by multi channel near-infrared spectroscopy (NIRS).

To investigate the brain activation in the prefrontal cortex (PFC) during mental works, we examined blood oxygenation changes of healthy subjects by using multi channel near infrared spectropcopy (NIRS). It was directly confirmed that the PFC was activated during mental tasks in vivo and it was suggested that distribution of the activation in the PFC is different among healthy individuals.

Functional Laterality↗

Stress control and human nutrition.

Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation.

Antioxidants↗

Effects of quetiapine on gonadal axis hormones in male patients with schizophrenia: a preliminary, open study.

PURPOSE: The authors investigated the effects of a novel antipsychotic agent, quetiapine administration on hypothalamo-pituitary-gonadal (HPG) axis hormones in patients with chronic schizophrenia. METHODS: In this prospective, open-label study, the subjects were nine male inpatients. We tried to switch the patients from typical antipsychotics to quetiapine. The patients took a mean dose of 636.1 mg quetiapine daily for a mean period of 104.7 days. RESULTS: (i) Although the total Brief Psychiatric Rating Scale score did not show significant changes, no patients needed anticholinergic medications after the switch. (ii) Before the switch, only the prolactin concentration showed a significant difference between the patients and normal subjects. After the switch, neither prolactin nor HPG axis hormone concentrations showed significant differences between the groups. CONCLUSIONS: Our preliminary results indicated that quetiapine might not affect prolactin and HPG axis hormones at least in chronic schizophrenia patients with normal levels of HPG axis hormones.

Adult↗

Impact of risperidone medication on quality of life and gonadal axis hormones in schizophrenia male patients with acute exacerbation.

We investigated the effects of risperidone on quality of life (QoL) and hypothalamo-pituitary-gonadal (HPG) axis hormones. In this prospective, open-label study, the subjects were 10 male schizophrenia patients with acute exacerbation. After a mean period of 44.6 d treatment, patients were taking a mean dose of 7.0 mg risperidone daily. After treatment, we found that (i) the total BPRS score decreased, (ii) the scores on psychosocial and motivation/energy subscales in the Japanese version of the Schizophrenia Quality of Life Scale decreased, but the scores on symptoms/side-effects subscale did not, (iii) prolactin increased, but the HPG axis hormones did not change, and (iv) the mean plasma homovanillic acid concentration decreased. Eight patients needed anticholinergic medications, one patient reported impotence, and one patient reported ejaculatory dysfunction during treatment. Our findings suggested that risperidone might improve psychosocial and motivation/energy QoL subscales, and increase prolactin without affecting the HPG axis hormones.

Adult↗

Repetitive behaviors in chronic schizophrenia: using the Japanese version of the Elgin Behavior Rating Scale (JEBRS).

The main aim of this study was to test the reliability and value of the Japanese Elgin Behavior Rating Scale (JEBRS) with 92 schizophrenia patients. Cronbach's alpha for the JEBRS was 0.61. All inter-rater reliability coefficients were in the satisfactory range. The JEBRS had a high stability over time. Almost all of the correlations among the nine item scores and total score in the JEBRS were significant. The total score for nine repetitive behaviors in the JEBRS was positively correlated with positive and negative symptoms. This study showed that the JEBRS is a useful and reliable scale.

Adult↗