Haloperidol treatment induces tissue- and sex-specific changes in DNA methylation: a control study using rats

BACKGROUND: We previously found that there is a subtle difference in the global methylation state of blood leukocyte DNA between male subjects with and without schizophrenia. The aim of the current study was to determine whether this difference was a primary effect of the disease state, or a secondary effect of antipsychotics administered to these patients. METHODS: We examined the methyl cytosine (mC) content of DNA from the leukocytes, brain, and liver of rats using high performance liquid chromatography. A total of 40 male and female rats received for 21 days daily injection of haloperidol or vehicle solution alone. RESULTS: In control rats injected with buffer only, there was a sex-dependent difference in mC content in leukocyte DNA (male > female; P = 0.028, n = 10), similar to our previous observations in human peripheral leukocytes. No difference in mC content between the sexes was observed in the brain or liver in buffer-treated animals. Haloperidol treatment slightly decreased the mC content of leukocytes in male rats, but unexpectedly, increased the mC content of leukocytes in females. We observed a trend toward a higher level of mC in the liver in both sexes following haloperidol treatment, compared to buffer-treated animals. In contrast, haloperidol treatment resulted in a decrease in mC content in the brain in females, and this difference was statistically significant (P = 0.026). CONCLUSION: These results indicate that haloperidol can affect DNA methylation states in the brain, as well as in certain other tissues, and raise the possibility that antipsychotic drugs play a role in the observed disparity in mC content in male subjects with and without schizophrenia

Responsivity of Negative Symptoms to Typical Neuroleptic Drugsin Schizophrenia

The psychopharmacological management of schizophrenia consists primarily of neuroleptics. These drugs have successfully changed the scenario of psychiatry since the 1950s. They have mainly been used for controlling positive symptoms in schizophrenia, but on closer look it is evident that positive and negative symptoms both respond to neuroleptics in the acute and chronic stages of schizophrenia separate reports are cited for acute and chronic stages with an aim to quantitate the response. The early as well as recent studies support these obervations with few exceptions. However, greater responsivity has been observed in the acute stages of schizophrenia

Goblet Cell Hyperplasia and Muscular Layer Thickening in the Small Intestine of a Cynomolgus Monkey

We report here the interesting case of a 5-year-old male cynomolgus monkey with goblet cell hyperplasia and thickening of the muscular layer throughout the small intestine without exhibiting any clinical symptoms. Necropsy examination showed diffuse thickening of the intestinal wall from the jejunum to the ileum, with an appearance likened to a rubber tube. Histopathologically, marked thickening was observed in both the mucosal and muscular layers in the jejunum and ileum, and slight thickening was observed in the duodenum. Goblet cell hyperplasia with extension of the circular folds and villi was prominently observed. The mucosal surface was covered with a thick mucus layer containing desquamated mucosal epithelial cells, and both the inner and outer muscular layers were markedly thickened due to smooth muscle hypertrophy. Neither macroscopic nor histopathological examination identified any causative factors, such as infection, enteritis and intestinal stenosis, or obstruction that may have caused development of this lesion. Given these observations, this case may simply be considered of spontaneous goblet cell hyperplasia and muscular layer thickening in the small intestine of a cynomolgus monkey

Remaining structures at the N- and C-terminal regions of alpha-synuclein accurately elucidated by amide-proton exchange NMR with fitting

AbstractAlpha-synuclein is analyzed in physiological conditions by CLEANEX-PM methodology, in which the amide-proton exchange can be monitored at millisecond scale. The relationship between kex and [OH]− is confirmed as a linear correlation with slope 1, indicating EX2 regime. There are significant residual structures at the N- and C-terminal regions. The structure at the C-terminal region is more stable than that of the N-terminal region. The middle part including NAC region is not completely protected. The data acquired at various pH and mixing time conditions followed by linear fitting give accurate information about residual structures

Change in the electronic structure of the bismuth chalcogenide superconductor CsBi4-xPbxTe6 by dissociation of the bismuth dimers

CsBi4−x Pb x Te6 is synthesized and the superconductivity associated with the structural transition from Pb substitution is studied. Photoemission spectroscopy measurements are performed in order to elucidate the relationship between the electronic structure and the occurrence of the superconductivity. When Bi is substituted with Pb, an electron doping-like change in the electronic structure is directly observed which is contrary to the naive expectation of hole doping. This observation is consistent with band structure calculations and appears to be a unique characteristic of CsBi4−x Pb x Te6 because of the dissociation of Bi dimers upon Pb substitution. These results indicate that it may be possible to control the electron and hole doping via manipulating the Bi dimers through Pb substitution

The development of agoraphobia is associated with the symptoms and location of a patient's first panic attack

<p>Abstract</p> <p>Background</p> <p>The place where a patient experiences his/her first panic attack (FPA) may be related to their agoraphobia later in life. However, no investigations have been done into the clinical features according to the place where the FPA was experienced. In particular, there is an absence of detailed research examining patients who experienced their FPA at home. In this study, patients were classified by the location of their FPA and the differences in their clinical features were explored (e.g., symptoms of FPA, frequency of agoraphobia, and severity of FPA).</p> <p>Methods</p> <p>The subjects comprised 830 panic disorder patients who were classified into 5 groups based on the place of their FPA (home, school/office, driving a car, in a public transportation vehicle, outside of home), The clinical features of these patients were investigated. Additionally, for panic disorder patients with agoraphobia at their initial clinic visit, the clinical features of patients who experienced their FPA at home were compared to those who experienced their attack elsewhere.</p> <p>Results</p> <p>In comparison of the FPAs of the 5 groups, significant differences were seen among the 7 descriptors (sex ratio, drinking status, smoking status, severity of the panic attack, depression score, ratio of agoraphobia, and degree of avoidance behavior) and 4 symptoms (sweating, chest pain, feeling dizzy, and fear of dying). The driving and public transportation group patients showed a higher incidence of co-morbid agoraphobia than did the other groups. Additionally, for panic disorder patients with co-morbid agoraphobia, the at-home group had a higher frequency of fear of dying compared to the patients in the outside-of-home group and felt more severe distress elicited by their FPA.</p> <p>Conclusion</p> <p>The results of this study suggest that the clinical features of panic disorder patients vary according to the place of their FPA. The at-home group patients experienced "fear of dying" more frequently and felt more distress during their FPA than did the subjects in the other groups. These results indicate that patients experiencing their FPA at home should be treated with a focus on the fear and distress elicited by the attack.</p

自閉症スペクトラム児の不安に対する指導支援 : 鉄道路線図による不安の可視化

自閉症スペクトラム障害 (ASD) 児は不安やストレスへの対処能力の低さ (White et al. 2009)が指摘されている。本研究では不安の強い ASD 児に対して,対象児の興味関心のある鉄道路線図を不安の程度の尺度として用い,不安,緊張場面の想起,不安,緊張の数値化,対処法ついて指導者とやり取りを行った。指導前後の不安,緊張の高い場面だけではなく,期待に関する場面の想起があり,鉄道路線図が不安以外の感情のスケールとしても用いることができると考えられた。対象児の中には不安,緊張の高い場面であっても,事前に知らされている場合や有効な対処法を利用させることで,不安が軽減する場合もあった。不安を可視化することにより,自己の不安状態や対処法を客観視することにつながり,ASD 児自身が不安な出来事に対する事前の構えを持つこと,さらに,周囲の大人が ASD 児と共通のスケールを持つことによって,ASD 児の不安状態を把握することが可能である。Children with autism spectrum disorder (ASD) are indicated to be weak against stress and anxiety (White et al., 2009) .In this study, four children with ASD participated. We adapted the intervention for children with ASD. The railway map was used as a measure of anxiety levels, because of subjects were interested in it. The purpose of this study is to investigate effectiveness of intervention that visualized about the degree of anxiety using the railroad map in children with ASD. The subjects proposed recent stressed events and fun events. To visualize the degree of anxiety and strategies solving anxiety events, they could evaluate them and communicate about their anxiety by the railroad map. We suggested that some of thechildren with ASD could reduce in anxiety by envisaging stressed events and their schedule. Children with ASD varied anxiety level and their anxiety expression. That showed children with ASD would express their degree of anxiety and other affects using the railroad map