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1.
BMC Res Notes ; 12(1): 613, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547866

RESUMO

OBJECTIVE: Although studies have shown inconsistent results in terms of prevalence of eating disorders, the Eating Attitudes Test (EAT-26) was used to screen students for abnormal eating behaviors. The results of the self-reported EAT-26 and body frame, as well as the efficacy of using self-administered questionnaires (SAQs) were examined to detect eating disorders in new college students. RESULTS: An anonymous questionnaire (EAT-26) was provided to 7738 new students; 4552 (58.8%) responders were included in the final analysis. Semi-structured interviews were conducted for 131 (1.7%) students. Among them, 6 students showed a high EAT-26 score, but were not diagnosed with an eating disorder based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). Three students were diagnosed with an eating disorder using SCID-I, but their EAT-26 scores were below the threshold. From these results, in a non-clinical population, findings on EAT-26 do not agree with those on SCID-I in terms of the diagnosis of eating disorders, and this battery is not appropriate for detecting eating disorders.

2.
eNeuro ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31540999

RESUMO

Bipolar disorder (BP) and schizophrenia (SCZ) are major psychiatric disorders, but the molecular mechanisms underlying the complicated pathologies of these disorders remain unclear. It is difficult to establish adequate in vitro models for pathological analysis because of the heterogeneity of these disorders. In the present study, to recapitulate the pathologies of these disorders in vitro, we established in vitro models by differentiating mature neurons from human induced pluripotent stem cells (hiPSCs) derived from BP and SCZ patients with contributive copy number variations (CNVs): two BP patients with PCDH15 deletion and one SCZ patient with RELN deletion. Glutamatergic neurons and GABAergic neurons were induced from hiPSCs under optimized conditions. Both types of induced neurons from both hiPSCs exhibited similar phenotypes of MAP2-positive dendrite shortening and decreasing synapse numbers. Additionally, we analyzed isogenic PCDH15- or RELN-deleted cells. The dendrite and synapse phenotypes of isogenic neurons were partially similar to those of patient-derived neurons. These results suggest that the observed phenotypes are general phenotypes of psychiatric disorders, and our in vitro models using hiPSC-based technology may be suitable for analysis of the pathologies of psychiatric disorders.Significance Statement Useful in vitro models of psychiatric disorders such as schizophrenia and bipolar disorder are urgently required for pathological analysis and drug discovery. In this study, mature excitatory and inhibitory neurons were induced from patient-derived induced pluripotent stem cells. The patients-derived induced neurons exhibited abnormalities in dendrite and synapse formation in vitro, which are similar to the previously reported findings observed in the postmortem brains. Our in vitro model may reflect general phenotypes of psychiatric disorders and can be used to further examine therapeutic targets.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31461559

RESUMO

AIMS: Recent studies have revealed that the interplay between polygenic risk scores (PRS) and large copy number variants (CNV; >500kb) is essential for the etiology of schizophrenia (SCZ). To replicate previous findings, including those for smaller CNV (>10kb), the PRS between SCZ patients with and without CNV were compared. METHODS: The PRS were calculated for 724 patients with SCZ and 1178 healthy controls (HC), genotyped using array-based comparative genomic hybridization and single nucleotide polymorphisms chips, and comparisons were made between cases and HC, or between subjects with and without 'clinically significant' CNV. RESULTS: First, we replicated the higher PRS in patients with SCZ compared to that in HC (without taking into account the CNV). For clinically significant CNV, as defined by the American College of Medical Genetics ('pathogenic' and 'uncertain clinical significance, likely pathogenic' CNV), 66 patients with SCZ carried clinically significant CNV, whereas 658 SCZ patients had no such CNV. In the comparison of PRS between cases with/without the CNV, despite no significant difference in PRS, significant enrichment of the well-established risk CNV (22q11.2 deletion and 47,XXY/47,XXX) was observed in the lowest decile of PRS in SCZ patients with the CNV. CONCLUSION: Although the present study failed to replicate the significant difference in PRS between SCZ patients with and without clinically significant CNV, SCZ patients with well-established risk CNV tended to have a lower PRS. Therefore, we speculate that the CNV in SCZ patients with lower PRS may contain 'genuine' risk; PRS is a possible tool for prioritizing clinically significant CNV because the power of the CNV association analysis is limited due to their rarity.

5.
Sci Rep ; 9(1): 11352, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31388057

RESUMO

Healthy aging is associated with structural and functional changes in the brain even in individuals who are free of neurodegenerative diseases. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of participants, we examined cross sectional changes in the functional organization of several large-scale brain networks over the adult lifespan and its potential association with general cognitive performance. Converging results from multiple analyses at the voxel, node, and network levels showed widespread reorganization of functional brain networks with increasing age. Specifically, the primary processing (visual and sensorimotor) and visuospatial (dorsal attention) networks showed diminished network integrity, while the so-called core neurocognitive (executive control, salience, and default mode) and basal ganglia networks exhibited relatively preserved between-network connections. The visuospatial and precuneus networks also showed significantly more widespread increased connectivity with other networks. Graph analysis suggested that this reorganization progressed towards a more integrated network topology. General cognitive performance, assessed by Addenbrooke's Cognitive Examination-Revised total score, was positively correlated with between-network connectivity among the core neurocognitive and basal ganglia networks and the integrity of the primary processing and visuospatial networks. Mediation analyses further indicated that the observed association between aging and relative decline in cognitive performance could be mediated by changes in relevant functional connectivity measures. Overall, these findings provided further evidence supporting widespread age-related brain network reorganization and its potential association with general cognitive performance during healthy aging.

6.
Clin Exp Hypertens ; : 1-7, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266382

RESUMO

Purpose: The prevalence of sleep-disordered breathing (SDB) increases with aging. SDB is a risk of hypertension, and both might lead to cognitive decline. However, the role of SDB and hypertension on the pathogenesis of age-related cognitive decline remains unclear. We examined the effects of these two diseases on cognitive function in elderly adults. Methods: Fifty-two elderly individuals (mean age, 69.6 ± 4.0 years) free from impairment in daily living activities participated in this study. Apnea/hypopnea index (AHI) and minimum oxygen saturation (SpO2) were assessed using a portable home monitoring device. We evaluated excessive daytime sleepiness with the Epworth sleepiness scale (ESS). Cognitive performance was assessed using the Wisconsin card sorting test (WCST), continuous performance test-Identical pairs (CPT-IP), and N-back task. Hypertension and diabetes mellitus were evaluated via questionnaire and blood pressure value. Results: The WCST category achievement was significantly lower in participants with minimum SpO2 <90% than those with minimum SpO2 ≥90%. The percentage of correct answer on the 0- and 1-back tasks was significantly lower in the hypertensives than normotensives. Minimum SpO2 was correlated with category achievement on the WCST. Multiple regression analysis including age, sex, body mass index, AHI, minimum SpO2, ESS, hypertension, and diabetes mellitus revealed that hypertension was the most significant factor for percentage correct answers on the 0- and 1-back tasks. There were no significant correlations between body mass index, ESS or diabetes mellitus and the parameters of WCST, CPT-IP, or N-back tasks. Conclusion: In elderly adults, nocturnal hypoxia and hypertension had a negative effect on cognitive function.

7.
Eur Neuropsychopharmacol ; 29(8): 914-924, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31303267

RESUMO

Alterations of the glutamatergic system components, including N-methyl-d-aspartate (NMDA) receptors are relevant to the pathophysiology of schizophrenia. Repeated phencyclidine (PCP) administration induces several schizophrenia-like psychobehavioral abnormalities and decreases extracellular glutamate levels, which are associated with increased levels of glial glutamate and aspartate transporter (GLAST) in the prefrontal cortex (PFC) of mice. In the present study, we investigated the functional roles of GLAST in the emotional and cognitive abnormalities in mice following repeated PCP administration by using GLAST heterozygous (+/-) mice, since GLAST mutant mice are a useful tool for elucidating the contribution of glutamate dysfunction to the pathophysiology of schizophrenia. PCP-administered GLAST wild-type (+/+) mice showed enhancement of immobility in a forced swimming test, impairments of visual recognition memory in a novel object recognition test, decrease in high potassium (K+)-induced extracellular glutamate release, and overexpression of GLAST and S100 proteins in the PFC, compared to saline-administered GLAST+/+ mice. Such behavioral and neurochemical abnormalities were not observed in PCP-administered GLAST+/- mice. In conclusion, these results clearly suggest that genetic GLAST dysfunction and glial activation play important roles in the development of emotional and cognitive abnormalities in PCP-administered GLAST+/+ mice.

8.
Neuropathology ; 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264738

RESUMO

Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder characterized by the presence of chorea, psychiatric symptoms, and dementia. Although motor symptoms are thought to be correlated with the degeneration of the striatum, there is little information regarding the neuropathological basis of psychiatric symptoms. The ventral part of the striatum is known as the nucleus accumbens (Acb) and is a region of interest as a responsible focus of psychiatric symptoms. The purpose of this study was to investigate the neuronal changes in the Acb and its relevance to psychiatric symptoms in HD. We investigated the brains of 16 HD patients (three patients presented psychiatric symptoms as the onset phenotype (HD-P), 13 patients presented motor symptoms as the onset phenotype (HD-M)) and four control subjects. The numerical cell densities for each of the large and small striatal neurons in the Acb, caudate nucleus and putamen were measured at three levels from the caudal to rostral region. As the result, the median small neuronal densities in all striatal regions in the HD brains were significantly lower than controls. Regarding the median small neuronal density in the caudate nucleus and putamen among the three levels, there were significant differences in the HD brains, but not in controls. The median large neuronal density in the Acb was significantly higher in the HD-P than in the HD-M, but there was no difference in the median small neuronal density between them. In the present study, we revealed that the Acb as well as the caudate nucleus were affected in HD brains. In terms of neuronal size and caudal to rostral levels, non-uniform neurodegeneration was observed in the striatum of the HD brains. The pathological difference in the Acb between HD-P and HD-M may be one of the factors involved in the development of psychiatric symptoms.

9.
J Neural Transm (Vienna) ; 126(8): 1095-1104, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230267

RESUMO

Rapid eye movement (REM) sleep without atonia (RWA), which is a hallmark of REM sleep behavior disorder (RBD) on polysomnography (PSG), may represent specific characteristics of prodromal Parkinson's disease (PD)/dementia with Lewy bodies (DLB), even when dream-enactment behavior is absent. We investigated the clinical profiles associated with PD/DLB in late-onset psychiatric patients exhibiting incidental RWA. Among patients who underwent PSG in our psychiatric ward, eight with incidental RWA, nine with idiopathic RBD, and seven with PD or DLB who had preceding RBD were included. Clinical variables, including the percentage of RWA in the total REM sleep (%RWA), were compared among the three groups. The frequency of depressive disorders as a primary psychiatric diagnosis and antidepressant usage were significantly higher in the incidental RWA group than in the other groups. There were no differences in the prevalence of supportive features of DLB among the three groups. The median %RWA was significantly lower in the incidental RWA group than in the other groups. Although the cardiac 123I-metaiodobenzylguanidine uptake was significantly higher in the incidental RWA group compared with the other groups, the groups showed overlap in the specific binding ratios on dopamine transporter imaging. All patients in the three groups exhibited cingulate island sign ratios on brain perfusion single-photon emission computed tomography within a threshold of 0.281, which is the optimal cut-off value for a diagnosis of DLB. In this series, late-onset psychiatric patients with incidental RWA partially shared common clinical profiles with idiopathic RBD and PD/DLB.

10.
BMC Psychiatry ; 19(1): 190, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221108

RESUMO

BACKGROUND: Postpartum depression (PPD) is a major depressive disorder that occurs after childbirth. Objective diagnostic and predictive methods for PPD are important for early detection and appropriate intervention. DNA methylation has been recognized as a potential biomarker for major depressive disorder. In this study, we used methylation analysis and peripheral blood to search for biomarkers that could to lead to the development a predictive method for PPD. METHODS: Study participants included 36 pregnant women (18 cases and 18 controls determined after childbirth). Genome-wide DNA methylation profiles were obtained by analysis with an Infinium Human Methylation 450BeadChip. The association of DNA methylation status at each DNA methylation site with PPD was assessed using linear regression analysis. We also conducted functional enrichment analysis of PPD using The Database for Annotation, Visualization and Integrated Discovery 6.8 to explore enriched functional-related gene groups for PPD. RESULTS: In the analysis with postpartum depressed state as an independent variable, the difference in methylation frequency between the postpartum non-depressed group and the postpartum depressed group was small, and sites with genome-wide significant differences were not confirmed. After analysis by The Database for Annotation, Visualization and Integrated Discovery 6.8, we revealed four gene ontology terms, including axon guidance, related to postpartum depression. CONCLUSIONS: These findings may help with the development of an objective predictive method for PPD.

11.
Nagoya J Med Sci ; 81(2): 249-258, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31239594

RESUMO

Majority of head and neck cancer (HNC) patients are male, and more than 85% of patients with HNC have the habit of smoking and drinking. Due to the specific demographic characteristics, HNC patients are anticipated to have specific coping styles, affecting psychological distress, survival, and quality of life. We explored the subscales of the Mental Adjustment to Cancer (MAC) Scale in male patients with HNC, and then examined the correlation between revised subscales of the MAC scale and anxiety/depression. Participants were 150 male inpatients with HNC, and their demographic and medical data were obtained. Coping style was assessed by MAC scale. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Out of 40 items in the original MAC scale, 19 items were excluded by factor analysis, and the remaining 21 items were divided into three factors: Negative Adjustment, Positive Adjustment, and Abandonment. Negative and Positive Adjustments were similar to the copings of mixed gender patients with heterogeneous cancers, and Abandonment was a new subscale specific to male patients with HNC. This subscale had a weak positive correlation with anxiety and depression. Male HNC patients revealed a specific coping style of Abandonment, related with psychological distress. We believe that an understanding of the Abandonment coping style revealed in our study will improve the psychological support offered to male patients with HNC.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31216562

RESUMO

3q29 microdeletion, a rare recurrent copy number variant (CNV), greatly confers an increased risk of psychiatric disorders, such as schizophrenia and autism spectrum disorder (ASD), as well as intellectual disability. However, disease-relevant cellular phenotypes of 3q29 deletion syndrome remain to be identified. To reveal the molecular and cellular etiology of 3q29 deletion syndrome, we generated a mouse model of human 3q29 deletion syndrome by chromosome engineering, which achieved construct validity. 3q29 deletion (Df/+) mice showed reduced body weight and brain volume and, more importantly, impaired social interaction and prepulse inhibition. Importantly, the schizophrenia-related impaired prepulse inhibition was reversed by administration of antipsychotics. These findings are reminiscent of the growth defects and neuropsychiatric behavioral phenotypes in patients with 3q29 deletion syndrome and exemplify that the mouse model achieves some part of face validity and predictive validity. Unbiased whole-brain imaging revealed that neuronal hyperactivation after a behavioral task was strikingly exaggerated in a restricted region of the cortex of Df/+ mice. We further elucidated the cellular phenotypes of neuronal hyperactivation and the reduction of parvalbumin expression in the cortex of Df/+ mice. Thus, the 3q29 mouse model provides invaluable insight into the disease-causative molecular and cellular pathology of psychiatric disorders.

13.
J Affect Disord ; 255: 168-176, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158779

RESUMO

BACKGROUND: Many women experience depressive symptoms during pregnancy and postpartum periods. These depressive symptoms are often accompanied by other inflammatory morbidities present during pregnancy. Tryptophan (TRP) metabolism has attracted considerable attention due to its influence on the onset of depression via induction of inflammation. We examined the changes in plasma levels of TRP metabolites in pregnant women with depressive symptoms during pregnancy and/or the postpartum period. METHODS: In line with a previous analysis using the Edinburgh Postnatal Depression Scale (EPDS), participants were divided into a non-depressive (ND) group, a postpartum depressive (PD) group, a temporary gestational depressive (TG) group, and a continuous depressive (CD) group. Blood samples were collected before and 1 month after delivery. The concentrations of plasma TRP metabolites were measured using high-performance liquid chromatography (HPLC). RESULTS: There are differences in plasma levels of TRP metabolites during pregnancy and postpartum periods between the ND group and the PD group, but not the TG or CD group. In the PD group, plasma levels of kynurenine (KYN) and kynurenic acid (KA), and KYN/TRP and KA/KYN ratio during the pregnancy period were higher and 3-hydroxyanthranilic acid (3HAA) during the postpartum period was lower than those in the ND group. LIMITATIONS: Histories regarding mood disorders before pregnancy were not assessed. CONCLUSIONS: The higher plasma levels of KYN and KA, and KYN/TRP and KA/KYN ratio during pregnancy period and lower plasma level of 3HAA during the postpartum period could be useful predictive and diagnostic markers of postpartum depressive symptoms.

14.
Hum Psychopharmacol ; 34(4): e2698, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31125145

RESUMO

OBJECTIVE: Burning mouth syndrome (BMS) and atypical odontalgia (AO) are examples of somatic symptom disorders with predominant pain around the orofacial region. Neuroinflammation is thought to play a role in the mechanisms, but few studies have been conducted. We aimed to better understand the role of neuroinflammation in the pathophysiology and treatment of BMS/AO. METHODS: Plasma levels of 28 neuroinflammation-related molecules were determined in 44 controls and 48 BMS/AO patients both pretreatment and 12-week post-treatment with duloxetine. RESULTS: Baseline plasma levels of interleukin (IL)-1ß (p < .0001), IL-1 receptor antagonist (p < .001), IL-6 (p < .0001), macrophage inflammatory protein-1ß (p < .0001), and platelet-derived growth factor-bb (.04) were significantly higher in patients than in controls. Plasma levels of granulocyte macrophage colony stimulating factor were significantly higher in patients than in controls (p < .001) and decreased with treatment (.009). Plasma levels of eotaxin, monocyte chemoattractant protein-1, and vascular endothelial growth factor decreased significantly with treatment (p < .001, .022, and .029, respectively). CONCLUSIONS: Inflammatory mechanisms may be involved in the pathophysiology and/or treatment response of somatic symptom disorders with predominant pain around the orofacial region.

15.
Brain ; 142(7): 2127-2136, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31096266

RESUMO

Discrepancies in efficacy between single-dose and repeated administration of oxytocin for autism spectrum disorder have led researchers to hypothesize that time-course changes in efficacy are induced by repeated administrations of the peptide hormone. However, repeatable, objective, and quantitative measurement of autism spectrum disorder's core symptoms are lacking, making it difficult to examine potential time-course changes in efficacy. We tested this hypothesis using repeatable, objective, and quantitative measurement of the core symptoms of autism spectrum disorder. We examined videos recorded during semi-structured social interaction administered as the primary outcome in single-site exploratory (n = 18, crossover within-subjects design) and multisite confirmatory (n = 106, parallel-group design), double-blind, placebo-controlled 6-week trials of repeated intranasal administrations of oxytocin (48 IU/day) in adult males with autism spectrum disorder. The main outcomes were statistical representative values of objectively quantified facial expression intensity in a repeatable part of the Autism Diagnostic Observation Schedule: the maximum probability (i.e. mode) and the natural logarithm of mode on the probability density function of neutral facial expression and the natural logarithm of mode on the probability density function of happy expression. Our recent study revealed that increases in these indices characterize autistic facial expression, compared with neurotypical individuals. The current results revealed that oxytocin consistently and significantly decreased the increased natural logarithm of mode on the probability density function of neutral facial expression compared with placebo in exploratory (effect-size, -0.57; 95% CI, -1.27 to 0.13; P = 0.023) and confirmatory trials (-0.41; -0.62 to -0.20; P < 0.001). A significant interaction between time-course (at baseline, 2, 4, 6, and 8 weeks) and the efficacy of oxytocin on the natural logarithm of mode on the probability density function of neutral facial expression was found in confirmatory trial (P < 0.001). Post hoc analyses revealed maximum efficacy at 2 weeks (P < 0.001, Cohen's d = -0.78; 95% CI, -1.21 to -0.35) and deterioration of efficacy at 4 weeks (P = 0.042, Cohen's d = -0.46; 95% CI, -0.90 to -0.01) and 6 weeks (P = 0.10, Cohen's d = -0.35; 95% CI, -0.77 to 0.08), while efficacy was preserved at 2 weeks post-treatment (i.e. 8 weeks) (P < 0.001, Cohen's d = -1.24; 95% CI, -1.71 to -0.78). Quantitative facial expression analyses successfully verified the positive effects of repeated oxytocin on autistic individuals' facial expressions and demonstrated a time-course change in efficacy. The current findings support further development of an optimized regimen of oxytocin treatment.

16.
Transl Psychiatry ; 9(1): 146, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053702

RESUMO

The original Article required a few updates; one co-author name, which was given as Hiroki Kiumura, has been updated to Hiroki Kimura. Furthermore, supplementary information has been updated, and grant numbers have been added. These updates have been made to both the PDF and HTML versions of this Article.

17.
Transl Psychiatry ; 9(1): 126, 2019 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-31011151

RESUMO

Although a number of studies have identified several convincing candidate genes or molecules, the pathophysiology of schizophrenia (SCZ) has not been completely elucidated. Therapeutic optimization based on pathophysiology should be performed as early as possible to improve functional outcomes and prognosis; to detect useful biomarkers for SCZ, which reflect pathophysiology and can be utilized for timely diagnosis and effective therapy. To explore biomarkers for SCZ, we employed fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) of lymphoblastoid cell lines (LCLs) (1st sample set: 30 SCZ and 30 CON). Differentially expressed proteins were sequenced by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and identified proteins were confirmed by western blotting (WB) (1st and 2nd sample set: 60 SCZ and 60 CON). Multivariate logistic regression analysis was performed to identify an optimal combination of biomarkers to create a prediction model for SCZ. Twenty protein spots were differentially expressed between SCZ and CON in 2D-DIGE analysis and 22 unique proteins were identified by LC-MS/MS. Differential expression of eight of 22 proteins was confirmed by WB. Among the eight candidate proteins (HSPA4L, MX1, GLRX3, UROD, MAPRE1, TBCB, IGHM, and GART), we successfully constructed logistic regression models comprised of 4- and 6-markers with good discriminative ability between SCZ and CON. In both WB and gene expression analysis of LCL, MX1 showed reproducibly significant associations. Moreover, Mx1 and its related proinflamatory genes (Mx2, Il1b, and Tnf) were also up-regulated in poly I:C-treated mice. Differentially expressed proteins might be associated with molecular pathophysiology of SCZ, including dysregulation of immunological reactions and potentially provide diagnostic and prognostic biomarkers.

18.
Neurochem Int ; 128: 127-134, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30998952

RESUMO

Blonanserin differs from other antipsychotic drugs, such as risperidone and olanzapine, and exhibits a higher affinity for dopamine-D2/3 receptors than for serotonin 5-HT2A receptors. We investigated the involvement of dopamine-D3 receptors in the effect of blonanserin on the social deficit observed in an animal model of schizophrenia and sought to elucidate the molecular mechanism underlying its action. Mice received phencyclidine (PCP: 10 mg/kg/day, s.c.), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, once a day for 14 consecutive days. We then evaluated the sociability, using a social interaction test, and the expression of GluN1 subunit, an essential subunit of the NMDA receptors, in these mice. Blonanserin significantly ameliorated the PCP-induced social deficit, whereas olanzapine and haloperidol did not. This effect of blonanserin was antagonized by 7-OH-DPAT, a dopamine-D3 receptor agonist, and SCH23390, a dopamine-D1 receptor antagonist. However, the ameliorating effect of blonanserin was not inhibited by DOI, a serotonin 5-HT2A receptor agonist. The PCP-induced social deficit was also ameliorated by U99194, a dopamine-D3 receptor antagonist and SKF38393, a dopamine-D1 receptor agonist, being effects antagonized by 7-OH-DPAT or SCH23390. Blonanserin significantly inhibited the decrease in the phosphorylation levels of GluN1 at Ser897 by protein kinase A (PKA) in the prefrontal cortex (PFC) in PCPadministered mice. These results suggest that activation of NMDA receptors due to Ser897-phosphorylation of GluN1 subunit, which is a step linked to dopamine-D1 receptor-PKA signaling through dopamine-D3 receptor antagonism in the PFC, is required for the ameliorating effect of blonanserin on the PCP-induced social deficit. These findings also provide in vivo evidence that blonanserin antagonism of the dopamine-D3 receptors may be useful as a novel treatment strategy and that the dopamine-D3 receptors can be a novel therapeutic target molecule for the social deficit observed in schizophrenia.

19.
Nutrients ; 11(3)2019 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-30832404

RESUMO

Multiple studies on the dynamics of inflammatory cytokines in patients with anorexia nervosa (AN) have been published, although results are not consistent among reports. Thus the pathophysiologic roles of these cytokines are not clear. We performed an exploratory analysis that included (1) comparisons of plasma interleukin-18 (IL-18) concentrations between patients with AN (n = 21) and healthy controls (n = 39), and (2) correlations between body mass index (BMI) and IL-18 concentrations in both groups, exploring the relationship between malnourishment and IL-18. Plasma IL-18 levels were significantly decreased in patients with AN compared with controls. Plasma IL-18 levels correlated to BMI in controls, but not in patients with AN. These results suggest that a decline in plasma IL-18 levels in patients with AN is not only due to malnourishment, but other pathophysiologic changes as well. IL-18 has a role in the brain's reaction to sadness and chronic stress. Therefore, decreased levels of IL-18 may commonly occur in patients with chronic AN.


Assuntos
Anorexia Nervosa/sangue , Interleucina-18/sangue , Desnutrição/sangue , Adulto , Anorexia Nervosa/complicações , Anorexia Nervosa/fisiopatologia , Índice de Massa Corporal , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Japão , Desnutrição/psicologia , Adulto Jovem
20.
Medicine (Baltimore) ; 98(8): e14613, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813188

RESUMO

INTRODUCTION: Although automobile driving is often necessary in daily life, most package inserts for psychotropic drugs in Japan prohibit patients from driving under the influence of medication. This may be partially because no system to evaluate the influence of drugs on driving performance has been established. Standardized evaluation methods have been established in the Netherlands and the United States, but these cannot be implemented in Japan because of differences in road situations, traffic laws, and ethnicities. Therefore, to establish a method to evaluate the influence of drugs on driving performance in Japan, we planned a validation study using alcohol and a driving simulator (DS) and set a clinically meaningful threshold involving the standard deviation of lateral position (SDLP), which is a criterion standard evaluation item. METHODS: This study was designed as a double-blind, placebo-controlled, randomized, 4-way, fourth-order crossover trial (Williams design). Twenty-four healthy Japanese men aged 21 to 64 years will be recruited through advertisements. The participants will be required to drive daily for over 3 years and to carry the active-type aldehyde dehydrogenase (ALDH) gene polymorphism (ALDH 2*1/*1). Participants will be randomly assigned to 4 groups based on blood alcohol concentration (BAC): 0% (placebo), 0.025%, 0.05%, and 0.09%. The amount of alcohol intake will be calculated based on Widmark formula using a beverage that is a mixture of 40% vodka and orange juice. After a practice period, each examination period will be set with 6-day intervals. The primary outcome is SDLP in a 60-minute road-tracking test using the DS. The secondary outcomes are other evaluation items in the DS tasks and DS sickness and sleepiness according to questionnaire responses. The estimated difference in SDLP between BAC levels of 0.05% and 0% will be calculated using a linear model. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee at Hakata Clinic and the Nagoya University Medical School Hospital Bioethics Review Committee. The trial results will be disseminated through peer-reviewed publications and international conferences. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov NCT 03572985 on June 28, 2018.


Assuntos
Consumo de Bebidas Alcoólicas/sangue , Aldeído Liases/genética , Condução de Veículo/estatística & dados numéricos , Simulação por Computador/estatística & dados numéricos , Desempenho Psicomotor/efeitos dos fármacos , Adulto , Concentração Alcoólica no Sangue , Estudos Cross-Over , Método Duplo-Cego , Genótipo , Humanos , Japão , Masculino , Polimorfismo Genético , Projetos de Pesquisa , Adulto Jovem
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