Developmental dysregulation of excitatory-to-inhibitory GABA-polarity switch may underlie schizophrenia pathology: A monozygotic-twin discordant case analysis in human iPS cell-derived neurons.

Schizophrenia is a major psychiatric disorder, but the molecular mechanisms leading to its initiation or progression remain unclear. To elucidate the pathophysiology of schizophrenia, we used an in vitro neuronal cell culture model involving human induced pluripotent stem cells (hiPSCs) derived from a monozygotic-twin discordant schizophrenia pair. The cultured neurons differentiated from hiPSCs were composed of a mixture of glutamatergic excitatory neurons and gamma aminobutyric acid (GABA)ergic inhibitory neurons. In the electrophysiological analysis, a different pattern of spontaneous neuronal activity was observed under the condition without any stimulants. The frequency of spontaneous excitatory post-synaptic currents (sEPSCs) was significantly higher in the hiPSC-derived neurons of the patient with schizophrenia than in the control sibling at day-in-vitro 30. However, the synaptic formation was not different between the patient with schizophrenia and the control sibling during the same culture period. To explain underlying mechanisms of higher excitability of presynaptic cells, we focused on the potassium-chloride co-transporter KCC2, which contributes to excitatory-to-inhibitory GABA polarity switch in developing neurons. We also revealed the altered expression pattern of KCC2 in hiPSC-derived neurons from the patient with schizophrenia, which could contribute to understanding the pathology of schizophrenia in the developing nervous system.

Smoking bans in mental health hospitals in Japan: barriers to implementation.

BACKGROUND: A number of studies have reported that smoking rates are higher and smoking cessation rates are lower in patients with mental disorders than in the general population. Despite the harmful effects of smoking, implementing total smoking bans in mental health hospitals is difficult. We investigate the status of smoking bans and the barriers to the implementation of total smoking bans in Japanese mental health hospitals. METHODS: A questionnaire survey was administered to the directors of 1242 Japanese mental health hospitals in March 2013. RESULTS: Forty-nine percent (n = 612) of the hospital directors responded. Of these, 24 % implemented total smoking bans and 14 % limited the bans to hospital buildings. In 66 and 68 % of the remaining hospitals, smoking rooms were located in open and closed wards, respectively, and completely separate from nonsmoking areas. Hospitals that had not implemented total smoking bans were concerned that introducing a total ban would exacerbate patients' psychiatric symptoms (46 %) or increase the incidence of surreptitious smoking (65 %). However, of the hospitals that had implemented total smoking bans, only 2 and 30 % identified "aggravation of psychiatric symptoms" and "increased surreptitious smoking" as disadvantages, respectively. The other concerns regarding the implementation of total smoking bans were staff opposition (21 %) and incidence of smoking around hospital grounds (46 %). These concerns were overcome by educating staff about smoking and cleaning the area around the hospital. CONCLUSIONS: There are some barriers to implementing total smoking bans in Japanese mental health hospitals. However, our study indicates that implementation of total smoking bans in mental health hospitals was minimally problematic and that barriers to the implementation of smoking bans could be overcome. As the current number of hospitals that have implemented total smoking bans is low in Japan, more hospitals should introduce total smoking bans.

Gray and white matter changes in subjective cognitive impairment, amnestic mild cognitive impairment and Alzheimer's disease: a voxel-based analysis study.

Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimer's disease. The subjects in this study were 39 Alzheimer's disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimer's disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimer's disease.

Longitudinal white matter changes in Alzheimer's disease: a tractography-based analysis study.

Alzheimer's disease (AD) classically presents with gray matter atrophy, as well as feature significant white matter abnormalities. Previous evidence indicates the overall burden of these pathological changes continues to advance as the disease progresses. The aim of this study was to investigate whether pathological alterations of white matter tracts correlate with the course of AD disease progression. 35 AD patients and 29 normal controls were recruited to the study and administered baseline magnetic resonance diffusion tensor imaging (DTI) acquisition and a cognitive function assessment at the time of initial evaluation. Subjects were re-evaluated with secondary DTI scan and cognitive function assessment at intervals of about 1.5 years on average. For the DTI acquired scans, we calculated diffusion tensor parameters, fractional anisotropy (FA), apparent diffusion coefficient (ADC), radial diffusivity (DR), and axial diffusivity (DA) along with the uncinate fasciculus (UNC), the inferior longitudinal fasciculus (ILF), and the inferior occipitofrontal fasciculus (IOFF). Compared to baseline, a significant mean FA reduction of the bilateral UNC, as well as a significant mean DR increase of the left UNC, was evident in AD patients at follow-up. Compared with normal controls, AD patients exhibited significant diffusion parameter abnormalities in their UNC, ILF, and IOFF. Taken together, these results indicate that progressive pathological white matter alterations can be quantified using the DTI parameters utilized here and may prove to be a useful biological marker for monitoring the pathophysiological course of AD.

Association between depressive symptoms and metabolic syndrome in Japanese community-dwelling older people: a cross-sectional analysis from the baseline results of the Fujiwara-kyo prospective cohort study.

OBJECTIVE: Metabolic syndrome contains many risks for medical diseases such as cardiovascular disease and diabetes, which might precipitate depressive symptoms in the older people. However, the association between depressive symptoms and metabolic syndrome in Japanese community-dwelling older people is unclear. This study was performed to answer this important question. METHODS: Cross-sectional analyses were performed on 3796 community-dwelling independent older people (≥ 65 years, 1911 men and 1885 women) from the 2007-2008 baseline examination of the Fujiwara-kyo study, a prospective cohort study on successful aging. Depressive symptoms were assessed using the 15-item short form of the Geriatric Depression Scale and metabolic syndrome was defined according to the 2005 International Diabetes Federation. Covariates were social supports, negative life events, health behavior, education, cognitive function, anthropometric status, and others. Multiple logistic regression analyses were performed to determine the relationships between depressive symptoms and these variables. RESULTS: The prevalence of depressive symptoms (Geriatric Depression Scale-15 ≥ 6) and metabolic syndrome were 14.8% and 16.6%, respectively. Significant protective factors against depressive symptoms were higher education, more opportunity for drinking of alcohol, better social supports, and more walking daily. Metabolic syndrome was statistically associated with depressive symptoms (adjusted odds ratio = \ 1.32, 95% confidence interval = 1.03-1.68). Other risk factors significantly associated with depressive symptoms were sleep disturbance, visual or hearing impairment, and negative life events. CONCLUSIONS: The present study showed an association between metabolic syndrome and depressive symptoms in ambulatory Japanese older people, as in western countries.

Abnormalities of the uncinate fasciculus and posterior cingulate fasciculus in mild cognitive impairment and early Alzheimer's disease: a diffusion tensor tractography study.

Mild cognitive impairment (MCI) is considered the transitional stage between normal cognition and dementia. The aim of this study was to use tractography based analysis to elucidate alterations in subjects with MCI compared with subjects with early Alzheimer's disease (AD) and controls. Seventeen subjects with early AD, 16 with MCI and 16 controls underwent magnetic resonance diffusion tensor imaging (DTI) and neuropsychological assessment. Diffusion tensor tractographies were computed and fiber-tract maps were generated using "dTV II" DTI software. We measured mean fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the uncinate fasciculus (UNC), posterior cingulate fasciculus (PCF) and corticospinal tract (CST). There were statistically significant differences in the FA and ADC values of the UNC and PCF between subjects with early AD and controls. Subjects with MCI exhibited significantly lower FA values on both sides of the PCF relative to controls. However, there were no significant differences between subjects with early AD and MCI for any measurement. Our results suggest that alterations in the PCF precede the onset of dementia.