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Objective: The present study aimed to investigate the relationship between serum oxytocin (OT) and logical memory among older people in rural Japan. Methods: This was a cross-sectional study using a survey conducted from October 2009 through March 2011. Most of the study was conducted as part of a national prevalence survey of dementia in Japan. The final sample comprised 385 community-dwelling people aged 65 years or older living in rural Japan. The mean age and standard deviation were 75.7 ± 6.76 years (144 men, mean age 75.0 ± 6.48 years; 241 women, mean age 76.2 ± 6.91 years). The participants underwent screening examinations for a prevalence survey of dementia. The screening examinations were the Mini-Mental State Examination, Clinical Dementia Rating, and “logical memory A” from the Wechsler Memory Scale–Revised (WMSR). We used the WMSR Logical Memory II delayed recall score (LM II-DR) to assess logical memory. Levels of serum OT were obtained using the enzyme immunoassay method. Results: Serum OT levels were significantly higher among women than men. The present study revealed that serum OT levels were positively associated with LM II-DR in older women living in rural Japan in multiple linear regression analyses. Conclusions: The present results suggested a positive correlation between OT and logical memory in older women living in rural Japan.

BackgroundThis study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in older adults.MethodsThe survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and clinical dementia rating (CDR) were performed at Time 1 (2009–2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016–2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1–Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping.ResultsParticipants in this study had lower MMSE and higher CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal.ConclusionSerum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in older adults aged 65 years and above.

BackgroundThis study aimed to investigate the association between serum levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2), a soluble form of an innate immune receptor expressed on the microglia, and brain volume in elderly people.MethodsThe survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum sTREM2 level measurements, brain MRI, Mini-Mental State Examination (MMSE), and Clinical Dementia Rating (CDR) were performed at Time 1 (2009–2011). Follow-up brain MRI, MMSE, and CDR were performed at Time 2 (2016–2017). The interval between Time 1 and Time 2 was approximately 7 years. Sixty-nine participants (16 men, mean age 72.69 ± 3.18 years; 53 women, mean age 72.68 ± 4.64 years) completed this study. We analyzed the correlation between serum sTREM2 levels (Time 1) and brain volume (Time 1, Time 2, and Time 1–Time 2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping.ResultsParticipants in this study had lower MMSE and CDR scores 7 years after the baseline evaluation. However, analyses at the cluster level by applying multiple comparison corrections (family wise error; P < 0.05) showed no correlation between serum sTREM2 levels and volume of different brain regions, either cross-sectional or longitudinal. ConclusionsSerum sTREM2 level could not serve as an immune biomarker of aging-related volume changes in brain regions closely related to cognitive function in elderly people aged 65 years and above.

Oxytocin is deeply involved in human relations. In recent years, it is becoming clear that oxytocin is also involved in social cognition and social behaviour. Oxytocin receptors are also thought to be present in the hippocampus and amygdala, and the relationship between oxytocin and the structure and function of the hippocampus and amygdala has been reported. However, a few studies have investigated oxytocin and its relationship to hippocampus and amygdala volume in elderly people. The aim of this study is to investigate the association between serum oxytocin levels and hippocampus and amygdala volume in elderly people. The survey was conducted twice in Kurokawa-cho, Imari, Saga Prefecture, Japan, among people aged 65 years and older. We collected data from 596 residents. Serum oxytocin level measurements, brain MRI, Mini–Mental State Examination and Clinical Dementia Rating were performed in Time 1 (2009–11). Follow-up brain MRI, Mini–Mental State Examination and Clinical Dementia Rating were performed in Time 2 (2016–17). The interval between Time 1 and Time 2 was about 7 years. Fifty-eight participants (14 men, mean age 72.36 ± 3.41 years, oxytocin 0.042 ± 0.052 ng/ml; 44 women, mean age 73.07 ± 4.38 years, oxytocin 0.123 ± 0.130 ng/ml) completed this study. We analysed the correlation between serum oxytocin levels (Time 1) and brain volume (Time 1, Time 2 and Times 1–2 difference) using voxel-based morphometry implemented with Statistical Parametric Mapping. Analysis at the cluster level (family-wise error; P, The aim of this study is to investigate the association between serum oxytocin levels and hippocampus and amygdala volume in elderly people. Oxytocin levels in people aged 65 years and older may be associated with aging-related changes in hippocampus and amygdala volume., Graphical Abstract Graphical Abstract

Objective Previous research suggests that spirituality/religiosity has benefits for both mental and physical health, measured using biological indices such as cortisol and IL-6. However, there have been few studies concerning the association of religious beliefs with oxytocin, a neuropeptide hormone secreted by the pituitary. Levels of peripheral oxytocin are thought to reflect the strength of bonding and stress regulation in social relationships. As such, the oxytocin system may underpin the biological mechanisms by which belief in life after death is associated with good mental and physical health. Here, we examine associations between oxytocin and belief in life after death. Methods We recruited 317 community-dwelling people, aged 65 or older, without cognitive or mental deficits, and living in rural Japan. We recorded demographics, belief in life after death, and logical memory using the Wechsler Memory Scale. Levels of serum oxytocin were obtained using an enzyme immunoassay method. Results Serum oxytocin levels were higher among women than men and were negatively associated with strength of belief in life after death. Conclusions Our findings could be interpreted differently depending on whether the anxiogenic or anxiolytic function of the oxytocin system is considered. Greater endorsement of afterlife beliefs may reduce secure attachment. Alternatively, based on the literature suggesting that basal levels of oxytocin are lower in those with reduced relational distress or anxiety, afterlife beliefs may play a role in these reductions. Copyright © 2016 John Wiley & Sons, Ltd.

Objectives Research has found that spirituality/religiosity has a salutary association with mental/physical health. However, the association of belief in life after death with well-being has rarely been studied, and the same is true of its association with biological indices, such as monoamine transmitters. Therefore, we examined the associations between well-being and religiosity, salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), and demographic characteristics. Methods The participants were 346 community-dwelling people, aged 65 years or older, without cognitive or mental deficits, in rural Japan. Measures of religiosity consisted of belief in life after death, attachment to life, and experiences related to death and religion. The measures were assessed by scales specifically suited for Japanese religious orientations. Participants' well-being was assessed by a life satisfaction scale containing two subscales. We also measured sMHPG, a major metabolite of noradrenaline that is thought to reflect certain psychological states, such as psychomotor retardation and effortful attention. Results One subscale of life satisfaction was positively associated with belief in life after death and sMHPG, and the other life satisfaction subscale was positively associated with education and death/religion-related experiences (e.g., visiting family graves or loss of a friend). Gender differences were found in afterlife beliefs and each life satisfaction subscale. Conclusions These results suggest that religiosity, including belief in life after death and death/religion-related experiences, is salubriously associated with mental health among older people, especially women, living in rural Japan. The basal level of sMHPG was positively associated with life satisfaction, but not with belief in life after death. Copyright © 2014 John Wiley & Sons, Ltd.

Background Late-life depressive disorder is becoming an important issue in health economics in the world, as it has been reported to be one of major risk factors for incidence of dementia. Identification of predictive markers associated with depression in later life is therefore of high priority in public health. The aim of the study was to examine the association of salivary cortisol levels with a later depressive state in elderly healthy people living in a rural Japan community. Methods Salivary cortisol levels were measured in 68 elderly healthy people (24 men; 44 women) followed by completion of the BDI, MMSE, and FAB from 2004 to 2006. The same cohort underwent BDI again from 2007 to 2009. Results In healthy elderly women subject, a significant positive correlation was found between salivary cortisol levels at baseline and BDI scores at follow-up, but not at baseline. Salivary cortisol levels at baseline were not correlated with the score of either MMSE or FAB. When the cut-off point of BDI scores were set at 20/21, logistic regression analyses revealed that salivary cortisol levels at baseline had a significant positive relationship with a later depressive state. Age and gender were also significantly related with a later depressive state. Limitations The present study involves small number of participants. Conclusions Higher salivary cortisol levels were associated with a later depressive state in elderly healthy women living in rural community. Salivary cortisol might be a predictive marker for a later depressive state in elderly women.

An accumulating body of evidence point to the significance of neuroinflammation and immunogenetics also in schizophrenia. Recent genome-wide studies in schizophrenia suggest immune involvement in schizophrenia. Microglia are the resident macrophage of the brain and major players in innate immunity in the CNS. They respond rapidly to even minor pathological changes in the brain and may contribute directly to the neuronal degeneration by producing various pro-inflammatory cytokines and free radicals. In many aspects, the neuropathology of schizophrenia is closely associated with microglial activation. We and other researchers have shown the inhibitory effects of some typical or atypical antipsychotics on the release of inflammatory cytokines and free radicals from activated microglia, both of which are not only directly toxic to neurons but also cause a decrease in neurogenesis as well as white matter abnormalities in the brains of the patients with schizophrenia. The treatment through the inhibition of microglial activation may shed new light on the therapeutic strategy of schizophrenia.

Objective This study compared saliva levels of 3-methoxy-4-hydroxyphenylglycol (sMHPG) in patients with major depressive disorder (MDD) to levels in healthy controls and explored whether sMHPG levels in patients with MDD were a predictive marker for antidepressant efficacy. Methods sMHPG levels were compared in 53 patients with MDD and 275 age-matched healthy controls. Patients' depressive symptoms were assessed by the 17-item Hamilton Rating Scale for Depression at baseline and 4 weeks after treatment with selective serotonin reuptake inhibitors (SSRIs, n = 23) or mirtazapine (n = 30), followed by saliva sampling. The mirtazapine group included nine patients who had been treated with an SSRI for more than 4 weeks without any improvement. sMHPG levels were measured by gas chromatography–mass spectrometry. Results sMHPG levels in MDD patients were significantly higher than in controls. The responder rate to drug treatment at 4 weeks was 62% for mirtazapine (13/21), 57% for SSRIs (13/23), and 89% (8/9) for SSRI plus mirtazapine. sMHPG at baseline in 13 responders treated with SSRIs, but not mirtazapine, was significantly higher than that in non-responder group and showed consequent reduction 4 weeks after treatment. The area under the receiver operating characteristic (ROC) curves of sMHPG for discrimination of SSRI responders and non-responders was 0.86 ± 0.10 (95% confidence interval: 0.64–1.0, p = 0.005). In contrast, the ROC curve of sMHPG levels for discrimination of mirtazapine responders and non-responders was not significant. Adjunctive treatment with mirtazapine to SSRI non-responders was effective, regardless of baseline sMHPG levels. Conclusion sMHPG in patients with MDD was higher than in healthy controls. High baseline sMHPG levels in patients with MDD maybe a predictive marker for SSRI response. Copyright © 2012 John Wiley & Sons, Ltd.

Community-based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimer's disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5-year age strata between 65 and 99 years was 5.8-77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011-2012.

The aim of the study was to explore the relation between saliva level of 3-methoxy-4-hydroxy-phenylglycol (MHPG) and a later cognitive decline in non-demented elderly subjects. We have reported that sMHPG in 214 elderly subjects living in the community (age 74.5 ± 5.9 years) was associated with scores on the Mini-Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB) in 2004 to 2006 (Time A). The same cohort underwent these cognitive tests again from 2007 to 2009 (Time B). The cognitive function of the 147 of 214 subjects could be reassessed by the same cognitive tests. The score on the FAB, but not the MMSE, was significantly reduced at Time B (14.6 ± 2.6) compared with that of Time A (15.2 ± 1.9). There was a significant negative correlation between the baseline sMHPG and the changes in the FAB score subtracted from Time B to Time A or the scores on the FAB at Time B in men, but not at Time A. These correlations were not found in women. These data indicate that high sMHPG might be associated with subsequent cognitive decline assessed by the FAB in non-demented elderly men living in the community.

Microglia are intrinsic immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO) and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca 2+ concentration ([Ca 2+ ]i) is important for microglial functions, such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. We have recently reported that BDNF induces a sustained increase in [Ca 2+ ]i through binding with the truncated TrkB receptor, resulting in activation of the PLC pathway and store-operated calcium entry (SOCE) in rodent microglial cells. Sustained activation of SOCE, possibly mediated by TRP channels, occurred after brief BDNF application and contributed to the maintenance of sustained [Ca 2+ ]i elevation. Pretreatment with BDNF significantly suppressed the release of NO from activated microglia. Additionally, selective serotonin reuptake inhibitors (SSRIs), including paroxetine or sertraline, potentiated the BDNFinduced increase in [Ca 2+ ]i in rodent microglial cells This article provides a review of recent findings on the role of BDNF in the pathophysiology of neuropsychiatric disorders, especially by focusing on its effect on intracellular Ca 2+ signaling in microglial cells.

Objective The aim of the study was to examine the association of saliva levels of 3-methoxy-4-hydroxyphenylglycol (sMHPG) with a later depressive state in older people living in a rural community. Methods Baseline sMHPG levels were measured in 214 older subjects followed by completion of the Beck Depression Inventory (BDI) from 2004 to 2006 (time A). The same cohort underwent BDI again from 2007 to 2009 (time B). Results One hundred forty-four subjects (44 men, 100 women) were reassessed by the BDI. Baseline sMHPG levels in men with a BDI score of ≤9 at time A and a BDI score of ≥10 at time B were significantly higher than those in men with a BDI score of ≤9 at times A and B. In men, there was a significant correlation between baseline sMHPG levels and BDI score at time B (r = 0.40, p = 0.007) but not at time A (r = 0.29, p = 0.06). This association was not significant in women. Conclusion These data indicate that high sMHPG levels at time A could be associated with a later depressive state in older men living in a community. Copyright © 2011 John Wiley & Sons, Ltd.

Aims: A large number of studies on the monoamine systems in Alzheimer's disease (AD) have found abnormalities of the noradrenergic system in the brain, but there has been no report concerning the relationship between noradrenergic activity and cognitive function in elderly living in a community. The aim of the present study was to explore the relationship between saliva level of 3-methoxy-4-hydroxyphenylglycol (sMHPG) and mental health in this population. Methods: The study was to examine the relationship between sMHPG and performance on the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Beck Depression Inventory (BDI) in 213 elderly people living in the local community. Results: sMHPG in female subjects was positively correlated with age (r = 0.24, P = 0.003) and negatively correlated with scores on the MMSE (r = −0.26, P = 0.0016) and FAB (r = −0.19, P = 0.024), even after controlling for the effect of age (MMSE r = −0.20, P = 0.013). Notably, sMHPG was correlated with the pentagon drawing score (P = 0.0008) of MMSE. sMHPG was significantly correlated with BDI score in male subjects, but negatively correlated in female subjects. A gender difference was found in the relationship between the sMHPG and BDI score. Conclusion: The measurement of sMHPG may be a useful marker of mental health in elderly community-dwelling subjects.

Following a symptom-free interval of 2 weeks after acute carbon monoxide poisoning a 38-year-old previously healthy man gradually developed impairment of drive and movement, disturbed memory, disorientation, mutism and abnormal gait. Finally, an apallic syndrome developed. After a total of 40 periods of hyperbaric oxygen administration the patient recovered completely and resumed his work. The EEG improved during the treatment more rapidly than the clinical picture. The electropolysomnograph changed in parallel to the clinical picture. Computed tomography on admission to hospital demonstrated a zone of lower density in the region of the right globus pallidus. This finding was no longer demonstrable after the patient had fully recovered. Language: de

We identified an age effect on biopterin and biogenic amine metabolites in the cerebrospinal fluid from 56 neurologically normal patients, aged 1 mo to 80 y. The levels of total and reduced forms of biopterin, homovanillic acid, and 5-hydroxyindoleacetic acid were found to peak during the first year of life. The levels of these metabolites then gradually decreased, plateauing at the age of 20 y. We found significant correlations between biopterin, homovanillic acid, and 5-hydroxy-indoleacetic acid.

Using 4 and 8-channel super-parallel magnetic resonance (MR) microscopes with a horizontal bore 2.34T superconducting magnet developed for 3-dimensional MR microscopy of the large Kyoto Collection of Human Embryos, we acquired T(1)-weighted 3D images of 1204 embryos at a spatial resolution of (40 microm)(3) to (150 microm)(3) in about 2 years. Similarity of image contrast between the T(1)-weighted images and stained anatomical sections indicated that T(1)-weighted 3D images could be used for an anatomical 3D image database for human embryology.

Previous research suggests that spirituality/religiosity has benefits for both mental and physical health, measured using biological indices such as cortisol and IL-6. However, there have been few studies concerning the association of religious beliefs with oxytocin, a neuropeptide hormone secreted by the pituitary. Levels of peripheral oxytocin are thought to reflect the strength of bonding and stress regulation in social relationships. As such, the oxytocin system may underpin the biological mechanisms by which belief in life after death is associated with good mental and physical health. Here, we examine associations between oxytocin and belief in life after death.We recruited 317 community-dwelling people, aged 65 or older, without cognitive or mental deficits, and living in rural Japan. We recorded demographics, belief in life after death, and logical memory using the Wechsler Memory Scale. Levels of serum oxytocin were obtained using an enzyme immunoassay method.Serum oxytocin levels were higher among women than men and were negatively associated with strength of belief in life after death.Our findings could be interpreted differently depending on whether the anxiogenic or anxiolytic function of the oxytocin system is considered. Greater endorsement of afterlife beliefs may reduce secure attachment. Alternatively, based on the literature suggesting that basal levels of oxytocin are lower in those with reduced relational distress or anxiety, afterlife beliefs may play a role in these reductions. Copyright © 2016 John WileySons, Ltd.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Objective In our study, we explored the associations among anxiety, the dimensions of Cloninger's theoretically based and empirically validated psychobiological model of personality (Temperament and Character Inventory, TCI) and fatigue in order to clarify the personality risk factors for fatigue. Methods Fifth-year students (n=89) and freshmen (n=162) at Saga Medical School and psychiatric outpatients of Saga Medical School Hospital (n=101) were investigated with the State–Trait Anxiety Inventory (STAI, Japanese version), the TCI (Japanese version), the General Health Questionnaire (GHQ-30) and the self-rating Fatigue Symptom Checklist (FSC), which describe fatigue along three subscales (general, physical and psychological fatigue). Correlation and ANOVA analyses were performed in this study. Results The analysis identified a significant relation (P Conclusion There is an inherent relationship among trait anxiety, the temperament dimension of harm avoidance, character dimension of self-directedness and fatigue. The TCI dimensions, harm avoidance and self-directedness, might be considered as predictors for fatigue-related disorders.

Background The relationship between the pathophysiology of dementia and neuroinflammation is well-known. The number of reports stating that depression is a risk factor for dementia has recently been increasing. These epidemiological findings suggest the possibility that both depression and dementia have common pathophysiological backgrounds of neuroinflammation. Methods The sample consists of 64 non-demented community-dwelling older participants aged 65 years or over. Participants were assessed at baseline (2004–2006) and 3 years later (2007–2009). Plasma concentration of markers of inflammation (interleukins (IL)-1β, IL-2, IL-6, soluble interleukin-2 receptor (sIL-2R), soluble interleukin-6 receptor (sIL-6R), high sensitivity C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α) were measured at baseline. Depression symptoms were assessed with the Beck Depression Inventory (BDI) and cognitive decline was assessed with the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Clock Drawing Test (CDT) at baseline and follow-up. All analyses were adjusted for age, gender and years of education. Results In the cross-sectional analysis, the present study found soluble IL-2 receptor (sIL-2R) to be associated only with the MMSE score at baseline in men. In the longitudinal analysis, none of our inflammatory biomarkers were associated with either depressive symptoms or cognitive decline. Limitations The present study consists of small number of participants and body mass index (BMI) scores were not obtained. Conclusions Our findings suggest that sIL-2R is associated with current cognitive function in men. None of our inflammatory markers predicted future depressive state or cognitive decline in our community-dwelling healthy older sample.

Research has found that spirituality/religiosity has a salutary association with mental/physical health. However, the association of belief in life after death with well-being has rarely been studied, and the same is true of its association with biological indices, such as monoamine transmitters. Therefore, we examined the associations between well-being and religiosity, salivary 3-methoxy-4-hydroxyphenylglycol (sMHPG), and demographic characteristics.The participants were 346 community-dwelling people, aged 65 years or older, without cognitive or mental deficits, in rural Japan. Measures of religiosity consisted of belief in life after death, attachment to life, and experiences related to death and religion. The measures were assessed by scales specifically suited for Japanese religious orientations. Participants' well-being was assessed by a life satisfaction scale containing two subscales. We also measured sMHPG, a major metabolite of noradrenaline that is thought to reflect certain psychological states, such as psychomotor retardation and effortful attention.One subscale of life satisfaction was positively associated with belief in life after death and sMHPG, and the other life satisfaction subscale was positively associated with education and death/religion-related experiences (e.g., visiting family graves or loss of a friend). Gender differences were found in afterlife beliefs and each life satisfaction subscale.These results suggest that religiosity, including belief in life after death and death/religion-related experiences, is salubriously associated with mental health among older people, especially women, living in rural Japan. The basal level of sMHPG was positively associated with life satisfaction, but not with belief in life after death.

Anxiolytic potency of 1 week of treatment with alprazolam or tandospirone in psychiatric outpatients with anxiety disorders was evaluated by changes in the scores on the Hamilton Anxiety Scale and the State and Trait Anxiety Inventory and in the saliva level of free-3-methoxy-4-hydroxyphenylglycol (free-MHPG). Saliva level of free-MHPG was significantly reduced by 1 week of treatment with alprazolam but not with tandospirone. Reductions in the HAS score after 1 week of drug treatment were greater in patients treated with alprazolam than in those treated with tandospirone. These results indicate that the short-term anxiolytic potency of alprazolam is greater than that of tandospirone and that the saliva level of MHPG would be a useful marker for the evaluation of the therapeutic potency of anxiolytic agents. Copyright 2001 John Wiley & Sons, Ltd.

Background: The disruption of prepulse inhibition of acoustic startle (PPI) is an animal model for some aspects of schizophrenia. Phencyclidine causes psychotomimetic symptoms in human and disrupts PPI in animals, however, the mechanism underlying this disruption remains unclear. The present experiment tested the hypothesis that serotonin 2A receptor blocking property of drugs reverses the phencyclidine-induced PPI disruption. Methods: The ED50 value of spiperone, haloperidol, chlorpromazine, clozapine, risperidone, olanzapine, seroquel, pipamperone, mianserin, or desipramine to reverse the phencyclidine- or apomorphine-induced PPI disruption in rats was determined. Then the correlation between the ED50 value and the affinity for the serotonin 2A, 2C, dopamine D2, or α-1 receptor of each drug was examined. Results: The ED50 value of the drugs to reverse the phencyclidine-induced PPI disruption was significantly correlated with the affinity for the serotonin 2A receptor, but not for the dopamine D2, serotonin 2C, or α-1 receptor of each drug. In contrast, the ED50 value of the drugs to reverse the apomorphine-induced PPI disruption was significantly correlated with the affinity for the dopamine D2 receptor, but not for the serotonin 2A receptor. Conclusions: An activation of serotonin 2A receptors would mediate the phencyclidine-induced PPI disruption.

As a measurement of the level of anxiety in psychiatric outpatients with anxiety, we determined the saliva level of free 3-methoxy-4-hydroxyphenyleglycol (MHPG) using gas chromatography- mass spectrometry and scored the levels of anxiety with the Hamilton Anxiety Scale (HAS) in patients, before and after drug treatment with alprazolam for 1 week. The saliva level of free-MHPG at first visit to hospital was significantly higher than that of control individuals and disease control individuals and was reduced by alprazolam treatment for 1 week. There was no correlation between MHPG level and the HAS score at the first hospital visit. The MHPG levels after treatment correlated with the HAS scores. The reduction of the anxiety level as scored by the HAS correlated with the reduction of MHPG level. These results indicate that the free saliva MHPG level may be a useful indicator for assessing not only the level of anxiety, but also the response to drug treatment for anxiety in these patients.

To assess the role of beta-phenylethylamine in aspects of dopamine release, we measured the level of beta-phenylethylamine in the rat striatum after killing the rats by microwave irradiation. We then investigated the effect of beta-phenylethylamine on electrically evoked dopamine release from rat striatal slices in vitro. The striatal beta-phenylethylamine level was 46.5 +/- 3.5 ng/g wet tissue, equivalent to 0.3 micromol/l. Superfusion with low concentrations of beta-phenylethylamine up to 1 micromol/l had no effect on spontaneous or electrically evoked dopamine release from striatal slices. Quinpirole reduced the evoked dopamine release from slices in a concentration-dependent manner. The quinpirole-induced reduction of evoked dopamine release was attenuated 30% by superfusion with 0.3 micromol/l beta-phenylethylamine. Moreover, the (-)-sulpiride (0.1 micromol/l)-induced increase in evoked dopamine release was also attenuated by superfusion with 0.3 micromol/l beta-phenylethylamine. These data indicate that submicromolar levels of beta-phenylethylamine could modify the dopamine autoreceptor mediated changes in evoked dopamine release from rat striatal slices.

OBJECTIVE—To determine the concentrations of β-phenylethylamine (PEA) in CSF in patients with Parkinson's disease, and to evaluate the relation between concentration of PEA in CSF and severity of Parkinson's disease. METHODS—Using gas chromatography-chemical ionisation mass spectrometry, CSF concentrations of PEA were measured in 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2) years), of whom three were at Hoehn and Yahr stage II, 11 were at stage III, and nine were at stage IV. Comparison was made with eight patients with neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controls without neurological disease (mean age, 57.6 (SD 4.8) years). RESULTS—Concentrations of PEA in CSF in Parkinson's disease were significantly lower (mean 205 (SD 131) pg/ml) than in patients with peripheral neuropathy (433 (SD 254) pg/ml) and controls (387 (SD 194) pg/ml). The concentrations of PEA in CSF correlated negatively with Hoehn and Yahr stage (P

Mianserin suppositories (10–90 mg) were administered at bedtime to 16 patients with post-operative delirium (mean age 69·5 years). By the Delirium Rating Scale (DRS: Trzepacz et al., 1988), the average score decreased from 21·2 prior to administration to 14·5 on the first day of treatment and to 7·1 on the seventh day. Improvement was observed in all cases (marked in 85 per cent and slight in 15 per cent). The plasma concentration of mianserin was 65 ng/ml on day 1, 93 ng/ml on day 3 and 65 ng/ml on day 5, having reached therapeutic levels within 24 h of beginning treatment. Decreases in the free-3-methoxy-4-hydroxyphenyl(ethylene)glycol (MHPG) concentrations in plasma were observed after drug administration, but free-homovanillic acid (HVA) concentrations in plasma showed no significant change with the drug treatment. We consider mianserin suppositories to be an effective treatment for post-operative delirium. © 1997 John Wiley & Sons, Ltd.

Sixty-six patients (47 men, 19 women, mean age 65 years) with delirium were treated with mianserin (10-60 mg/day) or haloperidol (2-6 mg/day) at Kurume University Hospital. The clinical effects of these drugs were compared before and after treatment using the Delirium Rating Scale. At the same time, blood was sampled to analyse plasma mianserin, free-3-methoxy-4-hydroxyphenyl(ethylene)glycol (MHPG) and homovanillic acid concentrations. Marked improvement after 1 week was observed in 69.4% of patients undergoing mianserin treatment, and in 70.6% of those receiving haloperidol. A statistically significant difference in the clinical effects of these drugs was not observed. Although improvement in the delirious state and a decrease in the plasma free-MHPG concentration were observed after drug administration, the plasma free-homovanillic acid concentration showed no significant change. The higher plasma free-MHPG concentration in the delirious state suggests the existence of a preparatory state whereby noradrenaline metabolism is involved in the appearance of the abnormal behaviour associated with delirium. These data suggest that free-MHPG concentrations could potentially be used as a predictor of delirium.

Mianserin HCl (10–60 mg/day) was administered orally before bedtime to 46 patients (mean age: 63 years) with delirium at Kurume University Hospital. The therapeutic effects of mianserin were assessed pre- and post-treatment using the Delirium Rating Scale (DRS: Trzepacz et al., 1988). The mean pre-treatment DRS score was 21. This score decreased significantly (p

Treatment with 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) has been suggested to improve autistic behavior. Cerebrospinal fluid (CSF) levels of total biopterin, oxidized and reduced forms of biopterin, homovanillic acid, and 5-hydroxyindoleacetic acid were measured in 14 autistic children and 18 controls to clarify the mechanism of action of R-THBP. The 14 autistic children received R- THBP orally at 1 mg/kg per day; 7 children showed clinical improvement (responders) and the other 7 patients did not (nonresponders). There were no significant differences between responders, nonresponders, and controls in the CSF levels of the metabolites before R- THBP administration. When lumbar puncture was repeated in 6 autistic children in the 24th week of R-THBP therapy, there was no significant change in the CSF levels of any metabolites.

The effects of dopamine-receptor antagonists on electrically-evoked dopamine release were compared in the nucleus accumbens and striatal slices of rats. (-)-Sulpiride induced a concentration-dependent increase in the evoked dopamine release from both regions, the increase in the nucleus accumbens being significantly greater than that in the striatum. Clozapine also increased evoked dopamine release from the nucleus accumbens, but not from the striatum. The haloperidol-induced increase in evoked dopamine release from the nucleus accumbens was less than that from the striatum. These findings indicate that, in terms of dopamine transmission, (-)-sulpiride and clozapine, but not haloperidol, predominantly affect the nucleus accumbens rather than the striatum. We have previously reported that the contribution of D3 receptors to the regulation of dopamine release from dopamine nerve terminals is much greater in the nucleus accumbens than that in the striatum. (-)-Sulpiride and clozapine have relatively higher affinity for D3 receptors than does haloperidol. The regional differences in responsiveness of dopamine release to dopamine antagonists could be due to the different affinities to D2 or D3 receptors of the dopamine antagonists.

Community-based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimer's disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5-year age strata between 65 and 99 years was 5.8-77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011-2012.

This study compared saliva levels of 3-methoxy-4-hydroxyphenylglycol (sMHPG) in patients with major depressive disorder (MDD) to levels in healthy controls and explored whether sMHPG levels in patients with MDD were a predictive marker for antidepressant efficacy.sMHPG levels were compared in 53 patients with MDD and 275 age-matched healthy controls. Patients' depressive symptoms were assessed by the 17-item Hamilton Rating Scale for Depression at baseline and 4 weeks after treatment with selective serotonin reuptake inhibitors (SSRIs, n = 23) or mirtazapine (n = 30), followed by saliva sampling. The mirtazapine group included nine patients who had been treated with an SSRI for more than 4 weeks without any improvement. sMHPG levels were measured by gas chromatography-mass spectrometry.sMHPG levels in MDD patients were significantly higher than in controls. The responder rate to drug treatment at 4 weeks was 62% for mirtazapine (13/21), 57% for SSRIs (13/23), and 89% (8/9) for SSRI plus mirtazapine. sMHPG at baseline in 13 responders treated with SSRIs, but not mirtazapine, was significantly higher than that in non-responder group and showed consequent reduction 4 weeks after treatment. The area under the receiver operating characteristic (ROC) curves of sMHPG for discrimination of SSRI responders and non-responders was 0.86 ± 0.10 (95% confidence interval: 0.64-1.0, p = 0.005). In contrast, the ROC curve of sMHPG levels for discrimination of mirtazapine responders and non-responders was not significant. Adjunctive treatment with mirtazapine to SSRI non-responders was effective, regardless of baseline sMHPG levels.sMHPG in patients with MDD was higher than in healthy controls. High baseline sMHPG levels in patients with MDD maybe a predictive marker for SSRI response.

Exposure to a stress task activates the sympathetic nervous system. Salivary 3-methoxy-4-hydroxy-phenylglycol (MHPG; the major metabolite of norepinephrine) concentrations closely reflect the plasma MHPG levels and are used as indices of noradrenergic activity. On the contrary, exposure to a stress task also activates the hypothalamic– pituitary–adrenal (HPA) axis resulting in the secretion of cortisol from the adrenal cortex. The level of salivary cortisol elevates in response to a stress task including oral presentations. We examined concentrations of salivary MHPG (sMHPG) and cortisol levels in a sample of doctors in training (6 males: mean age = 29.6 ± 3.0 years; 6 females: 26.8 ± 0.2 years) exposed to oral presentations. All the participants gave written informed consent, and this study was approved by the ethic committee of the Faculty of Medicine, Saga University. Each subject gave an oral presentation in a training course. In brief, each participant gave an oral presentation about the same theme: ‘‘How to treat patients who suffered from diabetes mellitus’’ to the audience who were invited. All the presentations were started in the afternoon at 2 p.m. and lasted for 1 h. After the presentation, the performance of each trainee was evaluated by the audience. Salivary sample was collected three times (just before the beginning of the presentation, immediately, and at 10 min after the presentation) for each participant. The concentration of sMHPG was measured by the gas chromatography-mass spectrometry. Salivary cortisol was measured using a commercially available enzyme immunoassay kit [1, 2]. The mean concentration of sMHPG did not change in both male (pre, 11.7 ± 2.1; post, 12.2 ± 1.3; 10 min, 11.7 ± 2.0 in ng/mL) and female (pre, 10.8 ± 1.7; post, 10.7 ± 2.1; 10 min, 10.5 ± 2.0) participants after the oral presentation. In contrast, the mean concentration of salivary cortisol was significantly increased in males (pre, 0.16 ± 0.03; post, 0.43 ± 0.09; 10 min, 0.31 ± 0.06 in lg/dL) but not in females (pre, 0.21 ± 0.05; post, 0.29 ± 0.07; 10 min, 0.24 ± 0.07) immediately and at 10 min after the oral presentation. Two-way analysis of variance with repeated measures revealed that the cortisol 9 sex interaction was significant (F = 5.64, P = 0.039). Male subjects are reported to show greater cortisol responses compared with females in response to public speaking. In contrast, female subjects show greater increase in cortisol levels in response to social rejection challenges [3]. Situations involving interpersonal concerns are perceived as more stressful for females, while the intellectual inferiority or failures of performance are perceived as more stressful for males. Our study supports recent findings suggesting that oral presentations might be more stressful for males. There are few reports on how stress tasks affect sMHPG and cortisol concentrations in a same population. Challenging behavioral tasks including simulated public speaking elevate sMHPG but not cortisol concentrations in volunteers who were injected with typhoid vaccine [4]. This suggests that a psychological stress could affect sMHPG but not cortisol concentrations. Our preliminary report suggests that a psychological stress could affect salivary cortisol but not MHPG concentrations. Y. Mizoguchi (&) A. Sakami Y. Imamura T. Tsuruta M. Egami S. Yamada Department of Neuropsychiatry, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan e-mail: ymizo@pk2.so-net.ne.jp

To examine biopterin fractions and biogenic amine metabolites in cerebrospinal fluid in aseptic meningitis, the concentrations of homovanillic acid, 5-hydroxyindoleacetic acid, and the total, the oxidized form, and the reduced form of biopterin were determined in cerebrospinal fluid specimens from 15 children with aseptic meningitis in the acute phase, 15 children with aseptic meningitis in the recovery phase, and six other children as controls. The concentration of each substance was significantly higher in the acute phase than in the recovery phase. Homovanillic acid in the acute phase was significantly increased compared to that in the control group. The concentrations of the total, the oxidized form, and the reduced form of biopterin, and 5-hydroxyindoleacetic acid were higher in the acute phase than those in the controls; however, the differences were not significant. The concentration of each substance in the recovery phase was not significantly different from that in the controls. There was no difference in the 5-hydroxyindoleacetic acid/homovanillic acid ratio or in the reduced form/total biopterin ratio among the patients in acute and recovery phases and the controls. These results suggested that levels of biopterin and biogenic amine metabolites in cerebrospinal fluid are increased in the acute phase of aseptic meningitis and return to normal during the recovery phase. This is the first report of increased concentrations of biopterin fractions and biogenic amine metabolites in aseptic meningitis. (J Child Neurol 1994;9:22-25).

The aim of the study was to examine the association of saliva levels of 3-methoxy-4-hydroxyphenylglycol (sMHPG) with a later depressive state in older people living in a rural community.Baseline sMHPG levels were measured in 214 older subjects followed by completion of the Beck Depression Inventory (BDI) from 2004 to 2006 (time A). The same cohort underwent BDI again from 2007 to 2009 (time B).One hundred forty-four subjects (44 men, 100 women) were reassessed by the BDI. Baseline sMHPG levels in men with a BDI score of ≤9 at time A and a BDI score of ≥10 at time B were significantly higher than those in men with a BDI score of ≤9 at times A and B. In men, there was a significant correlation between baseline sMHPG levels and BDI score at time B (r = 0.40, p = 0.007) but not at time A (r = 0.29, p = 0.06). This association was not significant in women.These data indicate that high sMHPG levels at time A could be associated with a later depressive state in older men living in a community.

The effects of the benzamide derivatives, (-)-sulpiride, sultopride and nemonapride, on spontaneous and electrically evoked dopamine (DA) release from striatal slices of rats were investigated. Nemonapride at concentrations of 100 nM or higher caused a dose-dependent increase in spontaneous DA release from the slices. (-)-Sulpiride and sultopride had little effect on spontaneous DA release. The electrically evoked DA release was enhanced by (-)-sulpiride at concentrations of 100 nM or higher in the superfusate and reduced by nemonapride at 100 nM or higher. Sultopride caused a small increase in the evoked release of DA. The different activities of these drugs on DA release may account for the different clinical results they produce.

OBJECTIVE—To evaluate the correlation between changes in platelet monoamine oxidase type B (MAO-B) activity and plasma β-phenylethylamine (PEA) concentrations in patients with Parkinson's disease and controls. METHODS—Platelet MAO-B activity and plasma PEA were measured with gas chromatography-mass spectrometry (GC-MS) in patients with Parkinson's disease treated with levodopa (12 men and 12 women) or selegiline (three men and three women), and physically healthy subjects as a control group (10 men and 10women). RESULTS—Platelet MAO-B activity was significantly higher in the Parkinson's disease group (mean 542 (SD 318) pmol/107 platelets/30 min) than in the control group (mean 349 (SD 307) pmol/107 platelets/30 min) (p

The aim of the study was to explore the relation between saliva level of 3-methoxy-4-hydroxy-phenylglycol (MHPG) and a later cognitive decline in non-demented elderly subjects. We have reported that sMHPG in 214 elderly subjects living in the community (age 74.5±5.9years) was associated with scores on the Mini-Mental State Examination (MMSE) and the Frontal Assessment Battery (FAB) in 2004 to 2006 (Time A). The same cohort underwent these cognitive tests again from 2007 to 2009 (Time B). The cognitive function of the 147 of 214 subjects could be reassessed by the same cognitive tests. The score on the FAB, but not the MMSE, was significantly reduced at Time B (14.6±2.6) compared with that of Time A (15.2±1.9). There was a significant negative correlation between the baseline sMHPG and the changes in the FAB score subtracted from Time B to Time A or the scores on the FAB at Time B in men, but not at Time A. These correlations were not found in women. These data indicate that high sMHPG might be associated with subsequent cognitive decline assessed by the FAB in non-demented elderly men living in the community.

We report the case of a 19-year-old woman who had developed obsessive-compulsive disorder after a hemorrhagic infarct in the left caudate nucleus after neurosurgery. Four years after the operation, her obsessive-compulsive disorder symptoms showed a remarkable reduction within a week of starting low-dose fluvoxamine, without any behavioral or psychological treatment.

We report the clinical, laboratory, and magnetic resonance imaging results of 4 adult patients (ages 25, 26, 29, and 35 years) with stage IV Rett syndrome. The patients were diagnosed at an institution for the handicapped. Two of them had been previously diagnosed as having cerebral palsy. All were microcephalic and had seizures, although the frequency of seizures decreased with advancing age. Three patients had scoliosis. Magnetic resonance imaging demonstrated marked craniofacial disproportion in 2 patients, bilateral atrophy of the frontotemporal lobes in 3, and cerebellar atrophy in 1. The cerebrospinal fluid concentrations of biopterin and homovanillic acid did not differ significantly in these Rett syndrome patients from age-matched controls.