Publications by authors named "Toru Nishikawa"

143 Publications

Transcriptome analysis of human neural cells derived from isogenic embryonic stem cells with 16p11.2 deletion.

Neurosci Res 2021 Mar 27. Epub 2021 Mar 27.

RIKEN Brain Science Institute, Wako, Saitama, 351-0198, Japan; Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences (Medicine), Tokyo Medical and Dental University, Bunkyo, Tokyo, 113-8519, Japan; Department of Physiology and Cell Biology, Kobe University School of Medicine, Chuo, Kobe, 650-0017, Japan. Electronic address:

16p11.2 deletion is one of the most influential copy number variations (CNVs) associated with autism spectrum disorder (ASD). Previous studies have investigated the pathophysiology of 16p11.2 deletion both in vitro and in vivo, and have identified features such as NMDAR dysfunction, excitation-inhibition imbalance, transcriptional dysregulation, and impaired cortical development. However, little is known about the transcriptional profiles of human neural cells. Here, we constructed an isogenic human embryonic stem (hES) cell model with 16p11.2 deletion using a CRISPR/Cas9 system and performed transcriptome analyses of hES-derived 2-dimensional neural cells. We identified several characteristics which may correlate with the neuropathology of 16p11.2 deletion: predisposition to differentiate into neural lineages, enhanced neurogenesis, and dysregulation of G protein-coupled receptor signaling and RAF/MAPK pathway. We also found upregulation of fragile X mental retardation protein (FMRP) target genes including GRM5, which is implicated as a common trait between 16p11.2 deletion and fragile X syndrome. Extending our knowledge into other ASD models would help us to understand the molecular pathology of this disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neures.2021.03.005DOI Listing
March 2021

Therapeutic potential for insulin on type 1 diabetes-associated periodontitis: Analysis of experimental periodontitis in streptozotocin-induced diabetic rats.

J Diabetes Investig 2020 Nov 28;11(6):1482-1489. Epub 2020 May 28.

Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.

Aims/introduction: The association between diabetes and periodontal disease is considered to be bidirectional. However, there is still controversy surrounding the relationship between periodontal disease and type 1 diabetes. We investigated whether insulin improves periodontitis without any local treatments for periodontitis under type 1 diabetes conditions using the ligature-induced experimental periodontitis model.

Materials And Methods: Type 1 diabetic rats were induced by streptozotocin injection. Experimental periodontitis was induced by ligature in normal and diabetic rats. Half of the diabetic rats were treated with insulin. Two weeks after the ligature, periodontitis was evaluated.

Results: Insulin treatment significantly improved inflammatory cell infiltration and inflammatory cytokine gene expression, leading to suppression of alveolar bone loss, in the periodontitis of diabetic rats. Insulin also suppressed the periodontitis-increased nitric oxide synthase-positive cells in periodontal tissue of the diabetic rats. Even without induction of periodontitis, diabetic rats showed decreased gingival blood flow and an increased number of nitric oxide synthase-positive cells in the gingiva and alveolar bone loss compared with normal rats, all of which were ameliorated by insulin treatment. We further confirmed that insulin directly suppressed lipopolysaccharide-induced inflammatory cytokine expressions in THP-1 cells.

Conclusions: There were abnormalities of periodontal tissue even without the induction of periodontitis in streptozotocin-induced diabetic rats. Insulin treatment significantly ameliorated periodontitis without local periodontitis treatment in diabetic rats. These data suggest the therapeutic impacts of insulin on periodontitis in type 1 diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.13276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610127PMC
November 2020

[A Case of Ureteroarterial Fistula Successfully Treated with Endovascular Stent Graft].

Hinyokika Kiyo 2019 Jul;65(7):299-303

The Department of Radiology, Kishiwada City Hospital.

We report a case of right uretero-external iliac artery fistula. A 46-year-old woman diagnosed with left ovarian cancer with peritoneal dissemination underwent simple hysterectomy, bilateral adnexal removal, partial omentectomy and appendectomy. Sixteen months after the operation, a computed tomography scan showed right hydronephrosis due to the development of tumor within the pelvis. A ureteral stent was placed into the right ureter in order to preserve renal function. The ureteral stent was replaced at regular intervals. Five months after the ureteral stent placement, the patient was hospitalized urgently with gross hematuria. She was diagnosed with right uretero-external iliac artery fistula based on the angiographic examination that was conducted to detect the source of hemorrhage. She was treated successfully with endovascular stent grafting in the right external iliac artery. She has since shown no episode of hematuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14989/ActaUrolJap_65_7_299DOI Listing
July 2019

A follow-up study of the effect of training using the Hybrid Assistive Limb on Gait ability in chronic stroke patients.

Top Stroke Rehabil 2019 10 18;26(7):491-496. Epub 2019 Jul 18.

Rehabilitation Unit, Kyoto University Hospital , Kyoto , Japan.

: Recently, use of the Hybrid Assistive Limb (HAL) that is effective for improvement of gait ability in chronic stroke patients has been reported. However, how long the effects are maintained remains unknown. The purpose of the present study was to investigate whether the effect of gait training using the HAL on gait ability was maintained for 3 months after the intervention. : A longitudinal, observational study with an intervention for a single group that adhered to the STROBE guidelines was performed. Nine chronic stroke patients were enrolled in this study. The patients performed gait training sessions using the HAL, 2-5 sessions/week for 3 weeks. Gait speed, stride length, cadence, and 2-minute walk distance (2MWD) were measured before and after intervention and at 3-month follow-up. The clinical trial registration number of this study is UMIN000012764 R000014756. : Compared to the initial status, gait speed ( = .02), stride length ( = .03), cadence ( = .01), and 2MWD ( < .05) were significantly increased immediately after the intervention. Moreover, gait speed ( < .01), cadence ( = .03), and 2MWD ( = .02) remained significantly higher 3 months after the intervention. There were no significant changes in all outcome measures between after intervention and at 3-month follow-up. : This study showed that gait training using the HAL resulted in significant improvement of gait ability after the intervention and the effect was maintained for 3 months after the training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10749357.2019.1640001DOI Listing
October 2019

Spatiotemporal gait characteristic changes with gait training using the hybrid assistive limb for chronic stroke patients.

Gait Posture 2019 06 3;71:205-210. Epub 2019 May 3.

Rehabilitation Unit, Kyoto University Hospital, Japan; Department of Orthopaedic Surgery, Kyoto University Graduate School of Medicine, Japan.

Background: Robotic rehabilitation has been attracting attention as a means to carry out "intensive", "repetitive", "task-specific", gait training. The newly developed robotic device, the Hybrid Assistive Limb (HAL), is thought to have the possibility of having an excellent effect on gait speed improvement over the conventional automatic programed assist robot. The purpose of this study was to investigate the spatiotemporal characteristics related to gait speed improvement using the HAL in chronic stroke patients.

Research Question: To investigate the effects of robotic gait training on gait speed and gait parameters.

Methods: An observational study with an intervention for single group was used. Intervention was conducted in University Hospital. Eleven chronic stroke patients were enrolled in this study. The patients performed 8 gait training sessions using the HAL, 2-5 sessions/week for 3 weeks. Gait speed, stride length, cadence, time of gait cycle (double-limb stance phases and single-limb stance phases) and time asymmetry index were measured before and after intervention.

Results: After intervention, gait speed, stride length, and cadence were significantly improved (Effect size = 0.39, 0.29, and 0.29), the affected initial double-limb stance phase was significantly shortened (from 15.8 ± 3.46%-13.3 ± 4.20%, p =  .01), and the affected single-limb stance phase was significantly lengthened (from 21.8±7.02%-24.5±7.95%, p <  .01). The time asymmetry index showed a tendency to improve after intervention (from 22.9±11.8-17.6±9.62, p =  .06). There was a significant correlation between gait speed and the stride length increase rate (r = .72, p =  .01).

Significance: This study showed that increasing stride length with lengthening of the affected single-stance phase by gait training using the HAL improved gait speed in chronic stroke patients. However, the actual contributions on HAL cannot be separated from gait training because this study is an observational research without a control group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gaitpost.2019.05.003DOI Listing
June 2019

Oral dysesthesia associated with autistic traits: a retrospective chart review.

Eur J Oral Sci 2019 08 9;127(4):347-350. Epub 2019 May 9.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Oral dysesthesia denotes a condition characterized by abnormal sensations in oral regions without a somatic basis, and is often seen in people with autistic traits, including those with autism spectrum disorder. This study aimed to examine the association between the symptoms of oral dysesthesia and the degree of autistic traits. A retrospective chart review was performed on 44 patients with oral dysesthesia, and associations among the subscales of the Oral Dysesthesia Rating Scale (Oral DRS), Autism Spectrum Quotient (AQ), and Glasgow Sensory Questionnaire (GSQ) were investigated. A Pearson correlation analysis revealed a significant, positive correlation between AQ scores and the A3 (squeezing or pulling) subscale of the Oral DRS (r = 0.37), but there were no significant correlations between the AQ and other subscale scores. There was a significant correlation between the AQ and GSQ score, but no correlation was detected between the GSQ and A3 scores or any other Oral DRS subscale scores. In conclusion, an abnormal squeezing or pulling sensation in oral regions without a somatic basis was associated with autistic traits and could be highlighted as a specific abnormality in sensory processing in autism spectrum disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eos.12620DOI Listing
August 2019

Stability and low induction propensity of cefiderocol against chromosomal AmpC β-lactamases of Pseudomonas aeruginosa and Enterobacter cloacae.

J Antimicrob Chemother 2018 11;73(11):3049-3052

Shionogi & Co., Ltd, Toyonaka, Osaka, Japan.

Objectives: The siderophore cephalosporin cefiderocol possesses in vitro activity against MDR Gram-negative bacteria. The stability of cefiderocol against serine- and metallo-type carbapenemases has been reported previously, but little is known about how cefiderocol interacts with chromosomal AmpC β-lactamases. We investigated a number of features of cefiderocol, namely antibacterial activity against AmpC overproducers, stability against AmpC β-lactamases and propensity for AmpC induction using Pseudomonas aeruginosa and Enterobacter cloacae.

Methods: MICs were determined by broth microdilution according to CLSI guidelines. The MIC of cefiderocol was determined in iron-depleted CAMHB. Hydrolysis of the antibiotics was determined by monitoring the changes in the absorbance in the presence of AmpC β-lactamase, and AmpC induction was evaluated by double disc diffusion and nitrocefin degradation assays.

Results: The MICs of ceftazidime and cefepime for PAO1 increased 4- to 16-fold with inactivation of either ampD or dacB, whereas cefiderocol MICs were little affected by these inactivations (<2-fold increase). Cefiderocol has 17- and 740-fold lower affinity (higher Ki) to AmpCs of P. aeruginosa SR24-12 and E. cloacae P99, respectively, compared with ceftazidime. Both disc diffusion and nitrocefin degradation assays indicated that cefiderocol did not induce AmpC β-lactamases of P. aeruginosa PAO1 and ATCC 27853 and E. cloacae ATCC 13047, whereas imipenem did.

Conclusions: Cefiderocol showed in vitro activity against the AmpC-overproducing strains, low affinity for chromosomal AmpC β-lactamases, and a low propensity of temporal induction of AmpC β-lactamases of P. aeruginosa and E. cloacae. These features relating to chromosomal AmpC could explain the potent antibacterial activity of cefiderocol against drug-resistant strains producing AmpC β-lactamases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jac/dky317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198743PMC
November 2018

Clinical characteristics and course of oral somatic delusions: a retrospective chart review of 606 cases in 5 years.

Neuropsychiatr Dis Treat 2018 13;14:2057-2065. Epub 2018 Aug 13.

Department of Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Objective: Oral cenesthopathy is characterized by foreign body sensations without medical and dental evidence for them. It is thought to be a rare disease in psychiatry, but many patients are visiting dental clinics seeking treatment to remove a foreign body. Even though the features of oral cenesthopathy might be different between a psychiatric clinic and a dental clinic, there has been no clinic-statistical study from dentists. In this study, we report a clinico-statistical study of patients with oral cenesthopathy in dentistry.

Methods: This is a retrospective chart review of 606 outpatients with oral cenesthopathy in Tokyo Medical and Dental University from April 2010 through to March 2015.

Results: A total of 159 male and 447 female patients were included in this study. The mean age was 62.08 years, and female patients were older than male patients. The trigger of the dental treatment and the acute phase of depression at the onset were significantly related (=0.037). Only 128 patients (36%) had clinically significant improvement after 6 months of pharmacotherapy. No history of psychiatric disorders (odds ratio [OR] 0.479 [95% confidence interval {CI}: 0.262-0.875], =0.017) and longer duration of illness (>18 months) (OR 2.626 [95% CI: 1.437-4.799], =0.002) were significant factors for clinical outcomes.

Conclusion: Patients with oral cenesthopathy in our clinic were predominantly elderly female patients. Dental treatment in the acute phase of depression might be a risk factor for oral cenesthopathy. Therefore, comprehending the situation of psychiatric disorder and obtaining adequate informed consent might be required to prevent the trouble concerning oral cenesthopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/NDT.S167527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6095116PMC
August 2018

[A Case Report of Granulomatous Renal Masses Following Intravesical Instillation of Bacillus Calmette-Guérin Therapy].

Hinyokika Kiyo 2018 May;64(5):225-230

The Department of Urology, Kishiwada Tokushukai Hospital.

Transurethral resection of bladder tumor (TURBT) was performed on the bladder tumor of a 68-yearold male patient. Bacillus Calmette-Guérin (BCG) intravesical therapy was performed to prevent recurrence (Immunobladder : ○R 80 mg once/week×6 times). A 40 mm tumor was noted in the left kidney by renal ultrasound performed two months after the completion of BCGintravesical therapy. Computed tomography (CT) showed non-enhanced multiple mass lesions in the left kidney. Renal tuberculous granuloma, hypovascular renal cell carcinoma or malignant lymphoma was suspected and CT-guided needle biopsy was performed. The patient was diagnosed with renal tuberculous granuloma that developed after BCGintravesical therapy as epithelioid cell granulomas were noted in the biopsy results. Treatment with anti-tuberculosis drugs was started and the tumor showed signs of shrinkage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14989/ActaUrolJap_64_5_225DOI Listing
May 2018

Cefiderocol (S-649266), A new siderophore cephalosporin exhibiting potent activities against Pseudomonas aeruginosa and other gram-negative pathogens including multi-drug resistant bacteria: Structure activity relationship.

Eur J Med Chem 2018 Jul 8;155:847-868. Epub 2018 Jun 8.

Pharmaceutical Research Division, Shionogi & Co., Ltd., 1-1, Futabacho, 3-chome, Toyonaka, 561-0825, Osaka, Japan.

The structure-activity relationship (SAR) for a novel series of catechol conjugated siderophore cephalosporins is described with their in vitro activities against multi-drug resistant Gram-negative pathogens including Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Enterobacteriaceae. Cefiderocol (3) was one of the best molecules which displayed well-balanced and potent activities against multi-drug resistant Gram-negative pathogens including carbapenem resistant bacteria among the prepared compounds with the modified C-7 side chain and the modified C-3 side chain. Cefiderocol (3) is a highly promising parenteral cephalosporin for the treatment of multi-drug resistant Gram-negative infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2018.06.014DOI Listing
July 2018

Prediction of Insulin Secretion Ability With Microcirculation Evaluated by Contrast-enhanced Ultrasonography in Pancreas Transplantation.

Pancreas 2018 May/Jun;47(5):617-624

Objectives: Contrast-enhanced ultrasonography can evaluate microcirculation. Thus, we used contrast-enhanced ultrasonography in evaluating pancreas graft perfusion and examined the relationship between graft circulation and function.

Methods: Contrast-enhanced ultrasonography was performed in 17 cases within 24 hours and at 1, 3, 5, 7, 14, 21, and 28 days after transplantation (Tx). The time between the time to peak intensity in the parenchyma and that in the vein was defined as delta-Tp(P-V). Graft function was evaluated with oral glucose tolerance test (OGTT) at 1 and 3 months after Tx, and glucagon stimulation test at 1 month after Tx.

Results: Differences in delta-Tp(P-V) between individual cases were more significant early after Tx, and delta-Tp(P-V) within 24 hours (delta-Tp[P-V]24h) was used in the subsequent analysis. Delta-Tp(P-V)24 hours showed a negative correlation with C-peptide increment in the glucagon stimulation test and the area under the curve of insulin level in oral glucose tolerance test. The cases were divided into the following 2 groups: the standard group (delta-Tp[P-V]24h ≤6.10 seconds) and the delayed group (>6.10 seconds). The area under the curve of insulin level increased significantly from 1 to 3 months after Tx in the standard group only.

Conclusions: These results suggest that delta-Tp(P-V)24 hours affects insulin secretion after Tx. Contrast-enhanced ultrasonography is useful in predicting endocrine function of the graft.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPA.0000000000001051DOI Listing
October 2018

Paroxetine ameliorates whole-body allodynia.

Eur J Clin Pharmacol 2018 Jul 11;74(7):979-980. Epub 2018 Apr 11.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, 113-8519, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00228-018-2438-0DOI Listing
July 2018

Feasibility Study of Weekly Nanoparticle Albumin-Bound Paclitaxel (150 mg/m) Followed by Fluorouracil, Epirubicin, and Cyclophosphamide Therapy as Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer.

Clin Breast Cancer 2018 10 11;18(5):374-379. Epub 2018 Jan 11.

Division of Breast and Endocrine Surgery, Department of Surgery, St Marianna University School of Medicine, Miyamae, Japan.

Background: Although several studies have shown efficacy of nanoparticle albumin-bound (nab) paclitaxel use as a neoadjuvant treatment in breast cancer, dosage and schedules were varied or used in combination and the data are still limited for weekly regimens. We evaluated the feasibility of weekly nab-paclitaxel followed by FEC (5-FU [fluorouracil], epirubicin, and cyclophosphamide) treatment feasibility as neoadjuvant chemotherapy for breast cancer.

Patients And Methods: Thirty-three patients with no previous chemotherapy were enrolled to receive nab-paclitaxel 150 mg/m the first 3 of 4 weeks (3q4w) followed by FEC as neoadjuvant treatment. The trial was powered for analyses of feasibility.

Results: Twenty-five patients completed the treatment as per protocol, and the completion rate was 75.8% (95% confidence interval, 59.0-87.2; P = .44). The regimen completion group was younger than those with regimen incompletion (average 45.1 vs. 56.6 years). The pathological complete response (ypT0-is/N0) rate was 30.3% in 33 patients, which was higher in triple-negative patients (58.3%). Grade 3/4 neutropenia was seen in 48.5%, although there was no febrile neutropenia. Grade 3 peripheral neuropathy was seen in 33.3%.

Conclusion: Our study showed that weekly nab-paclitaxel 150 mg/m 3q4w followed by FEC as neoadjuvant regimen might be sufficient in efficacy, although with a relatively high severe adverse event occurrence rate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clbc.2018.01.002DOI Listing
October 2018

Association studies of WD repeat domain 3 and chitobiosyldiphosphodolichol beta-mannosyltransferase genes with schizophrenia in a Japanese population.

PLoS One 2018 8;13(1):e0190991. Epub 2018 Jan 8.

Department of Psychiatry and Behavioral Sciences, Graduate School of Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

Schizophrenia and schizophrenia-like symptoms induced by the dopamine agonists and N-methyl-D aspartate type glutamate receptor antagonists occur only after the adolescent period. Similarly, animal models of schizophrenia by these drugs are also induced after the critical period around postnatal week three. Based upon the development-dependent onsets of these psychotomimetic effects, by using a DNA microarray technique, we identified the WD repeat domain 3 (WDR3) and chitobiosyldiphosphodolichol beta-mannosyltransferase (ALG1) genes as novel candidates for schizophrenia-related molecules, whose mRNAs were up-regulated in the adult (postnatal week seven), but not in the infant (postnatal week one) rats by an indirect dopamine agonist, and phencyclidine, an antagonist of the NMDA receptor. WDR3 and other related proteins are the nuclear proteins presumably involved in various cellular activities, such as cell cycle progression, signal transduction, apoptosis, and gene regulation. ALG1 is presumed to be involved in the regulation of the protein N-glycosylation. To further elucidate the molecular pathophysiology of schizophrenia, we have evaluated the genetic association of WDR3 and ALG1 in schizophrenia. We examined 21 single nucleotide polymorphisms [SNPs; W1 (rs1812607)-W16 (rs6656360), A1 (rs8053916)-A10 (rs9673733)] from these genes using the Japanese case-control sample (1,808 schizophrenics and 2,170 matched controls). No significant genetic associations of these SNPs were identified. However, we detected a significant association of W4 (rs319471) in the female schizophrenics (allelic P = 0.003, genotypic P = 0.008). Based on a haplotype analysis, the observed haplotypes consisting of W4 (rs319471)-W5 (rs379058) also displayed a significant association in the female schizophrenics (P = 0.016). Even after correction for multiple testing, these associations remained significant. Our findings suggest that the WDR3 gene may likely be a sensitive factor in female patients with schizophrenia, and that modification of the WDR3 signaling pathway warrants further investigation as to the pathophysiology of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190991PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5757935PMC
February 2018

Effects of selective calcium-permeable AMPA receptor blockade by IEM 1460 on psychotomimetic-induced hyperactivity in the mouse.

J Neural Transm (Vienna) 2018 04 21;125(4):705-711. Epub 2017 Dec 21.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Diminished glutamate neurotransmission via the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been considered to be involved in the pathophysiology of schizophrenia based upon the observation that the antagonists and autoantibodies of NMDAR cause positive, negative and cognitive symptomatologies similar to those of schizophrenia. The possible reduced extracellular levels of D-serine by overstimulation of the calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamate receptor (CP-AMPAR) following the NMDAR hypofunction-induced compensatory increase in the glutamate release could aggravate the NMDAR hypofunction in the brain of the drug- or antibody-associated psychoses and schizophrenia, because D-serine is an intrinsic coagonist for the NMDAR. To obtain an insight into the therapeutic approach to such a glutamate-linked psychotic state, we have studied the effects of the systemic administration of the CP-AMPAR-selective antagonist, IEM 1460 (N,N,N-trimethyl-5- [(tricyclo[3.3.1.1]dec-1-ylmethyl)amino]-1-pentanaminium bromide hydrobromide), on the hyperactivity following an injection of a schizophrenomimetic NMDAR antagonist, phencyclidine, in the mouse. The subcutaneous IEM 1460 application produced a dose-dependent inhibition of the increased movement counts after the subcutaneous injection of phencyclidine. This inhibiting influence was also seen on the hyperactivity elicited by another NMDAR antagonist, dizocilpine. Moreover, the IEM 1460 administration attenuated the ability of a schizophrenomimetic dopamine agonist, methamphetamine, to increase spontaneous movements. These findings indicate that dysregulation of the CP-AMPAR could, at least in part, be implicated in the glutamate pathology of schizophrenia and/or related psychotic symptoms and be a potential target for the development of their novel treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00702-017-1827-3DOI Listing
April 2018

Effects of selective calcium-permeable AMPA receptor blockade by IEM 1460 on psychotomimetic-induced hyperactivity in the mouse.

J Neural Transm (Vienna) 2018 04 21;125(4):705-711. Epub 2017 Dec 21.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Diminished glutamate neurotransmission via the N-methyl-D-aspartate type glutamate receptor (NMDAR) has been considered to be involved in the pathophysiology of schizophrenia based upon the observation that the antagonists and autoantibodies of NMDAR cause positive, negative and cognitive symptomatologies similar to those of schizophrenia. The possible reduced extracellular levels of D-serine by overstimulation of the calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate glutamate receptor (CP-AMPAR) following the NMDAR hypofunction-induced compensatory increase in the glutamate release could aggravate the NMDAR hypofunction in the brain of the drug- or antibody-associated psychoses and schizophrenia, because D-serine is an intrinsic coagonist for the NMDAR. To obtain an insight into the therapeutic approach to such a glutamate-linked psychotic state, we have studied the effects of the systemic administration of the CP-AMPAR-selective antagonist, IEM 1460 (N,N,N-trimethyl-5- [(tricyclo[3.3.1.1]dec-1-ylmethyl)amino]-1-pentanaminium bromide hydrobromide), on the hyperactivity following an injection of a schizophrenomimetic NMDAR antagonist, phencyclidine, in the mouse. The subcutaneous IEM 1460 application produced a dose-dependent inhibition of the increased movement counts after the subcutaneous injection of phencyclidine. This inhibiting influence was also seen on the hyperactivity elicited by another NMDAR antagonist, dizocilpine. Moreover, the IEM 1460 administration attenuated the ability of a schizophrenomimetic dopamine agonist, methamphetamine, to increase spontaneous movements. These findings indicate that dysregulation of the CP-AMPAR could, at least in part, be implicated in the glutamate pathology of schizophrenia and/or related psychotic symptoms and be a potential target for the development of their novel treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00702-017-1827-3DOI Listing
April 2018

Short- and long-term evaluation of cognitive functions after electroconvulsive therapy in a Japanese population.

Psychiatry Clin Neurosci 2018 Feb 29;72(2):95-102. Epub 2017 Nov 29.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Aim: While electroconvulsive therapy (ECT) is a well-established, safe, and effective treatment for mental illnesses, the potential for adverse effects on cognitive functions remains controversial. We aimed to evaluate multiple cognitive functions in different time periods before and after ECT in a Japanese population.

Methods: A battery of five neurocognitive tests was administered to patients who underwent a course of ECT treatment at three time points: before, immediately after, and 4 weeks after ECT.

Results: A transient but significant decline in letter fluency function was observed immediately after ECT, but had recovered well by 4 weeks. We also observed a significant improvement in the trail-making task at 4 weeks after ECT.

Conclusion: In a Japanese population, adverse effects of ECT on verbal fluency function-related and other cognitive impairments were transient. Over the longer term, we detected significant improvements in the performance of tasks that presumably reflected information processing speed and executive functions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pcn.12614DOI Listing
February 2018

Antibacterial Properties of Cefiderocol, a Novel Siderophore Cephalosporin, against Gram-Negative Bacteria.

Antimicrob Agents Chemother 2018 01 21;62(1). Epub 2017 Dec 21.

Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.

Cefiderocol (CFDC; S-649266), a novel parenteral siderophore cephalosporin conjugated with a catechol moiety, has a characteristic antibacterial spectrum with a potent activity against a broad range of aerobic Gram-negative bacterial species, including carbapenem-resistant strains of and nonfermenting bacteria such as and Cefiderocol has affinity mainly for penicillin-binding protein 3 (PBP3) of and nonfermenting bacteria similar to that of ceftazidime. A deficiency of the iron transporter PiuA in or both CirA and Fiu in caused 16-fold increases in cefiderocol MICs, suggesting that these iron transporters contribute to the permeation of cefiderocol across the outer membrane. The deficiency of OmpK35/36 in and the overproduction of efflux pump MexA-MexB-OprM in showed no significant impact on the activity of cefiderocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/AAC.01454-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5740388PMC
January 2018

Genetic and molecular risk factors within the newly identified primate-specific exon of the SAP97/DLG1 gene in the 3q29 schizophrenia-associated locus.

Am J Med Genet B Neuropsychiatr Genet 2017 Dec 9;174(8):798-807. Epub 2017 Oct 9.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

The synapse-associated protein 97/discs, large homolog 1 of Drosophila (DLG1) gene encodes synaptic scaffold PDZ proteins interacting with ionotropic glutamate receptors including the N-methyl-D-aspartate type glutamate receptor (NMDAR) that is presumed to be hypoactive in brains of patients with schizophrenia. The DLG1 gene resides in the chromosomal position 3q29, the microdeletion of which confers a 40-fold increase in the risk for schizophrenia. In the present study, we performed genetic association analyses for DLG1 gene using a Japanese cohort with 1808 schizophrenia patients and 2170 controls. We detected an association which remained significant after multiple comparison testing between schizophrenia and the single nucleotide polymorphism (SNP) rs3915512 that is located within the newly identified primate-specific exon (exon 3b) of the DLG1 gene and constitutes the exonic splicing enhancer sequence. When stratified by onset age, although it did not survive multiple comparisons, the association was observed in non-early onset schizophrenia, whose onset-age selectivity is consistent with our recent postmortem study demonstrating a decrease in the expression of the DLG1 variant in early-onset schizophrenia. Although the present study did not demonstrate the previously reported association of the SNP rs9843659 by itself, a meta-analysis revealed a significant association between DLG1 gene and schizophrenia. These findings provide a valuable clue for molecular mechanisms on how genetic variations in the primate-specific exon of the gene in the schizophrenia-associated 3q29 locus affect its regulation in the glutamate system and lead to the disease onset around a specific stage of brain development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajmg.b.32595DOI Listing
December 2017

Cerebrospinal fluid D-serine concentrations in major depressive disorder negatively correlate with depression severity.

J Affect Disord 2018 01 27;226:155-162. Epub 2017 Sep 27.

Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan. Electronic address:

Background: D-serine is an endogenous co-agonist of N-methyl-D-aspartate receptor (NMDAR) and plays an important role in glutamate neurotransmission. Several studies suggested the possible involvement of D-serine related in the pathophysiology of psychiatric disorders including major depression disorders (MDD). We tried to examine whether cerebrospinal fluid (CSF) or plasma D-serine concentrations are altered in MDD and whether D-serine concentrations correlated with disease severity.

Methods: 26 MDD patients and 27 healthy controls matched for age, sex and ethnicity were enrolled. We measured amino acids in these samples using by high-performance liquid chromatography with fluorometric detection.

Results: D-serine and L-serine, precursor of D-serine, levels in CSF or plasma were not significantly different in patients of MDD compared to controls. Furthermore, a significant correlation between D-serine levels in CSF and Hamilton Depression Rating Scale (HAMD)-17 score was observed (r = -0.65, p = 0.006). Furthermore, we found a positive correlation between CSF D-serine and HVA concentrations in MDD patients (r = 0.54, p = 0.007). CSF D-serine concentrations were correlated with those of plasma in MDD (r = 0.61, p = 0.01) but not in controls. In CSF, we also confirmed a significant correlation between D-serine and L-serine levels in MDD (r = 0.72, p < 0.0001) and controls (r = 0.70, p < 0.0001).

Conclusions: The study has some limitations; sample size was relatively small and most patients were medicated. We revealed that CSF D-serine concentrations were correlated with depression severity and HVA concentrations and further investigation were required to reveal the effect of medication and disease heterogeneity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2017.09.035DOI Listing
January 2018

Involvement of neuronal and glial activities in control of the extracellular d-serine concentrations by the AMPA glutamate receptor in the mouse medial prefrontal cortex.

Neurochem Int 2018 10 28;119:120-125. Epub 2017 Sep 28.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Center for Brain Integration Research, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address:

It has been well accepted that d-serine may be an exclusive endogenous coagonist for the N-methyl-d-aspartate (NMDA)-type glutamate receptor in mammalian forebrain regions. We have recently found by using an in vivo dialysis method that an intra-medial prefrontal cortex infusion of S-α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (S-AMPA), a selective AMPA-type glutamate receptor agonist, causes a reduction in the extracellular levels of d-serine in a calcium-permeable AMPA receptor antagonist-sensitive manner. The inhibitory influence by the AMPA receptor on the extracellular d-serine, however, contradicts the data obtained from in vitro experiments that the AMPA receptor stimulation leads to facilitation of the d-serine liberation. This discrepancy appears to be due to the different cell setups between the in vivo and in vitro preparations. From the viewpoints of the previous reports indicating (1) the neuronal presence of d-serine synthesizing enzyme, serine racemase, and d-serine-like immunoreactivity and (2) the same high tissue concentrations of d-serine in the glia-enriched white matter and in the neuron-enriched gray matter of the mammalian neocortex, we have now investigated in the mouse medial prefrontal cortex, the effects of attenuation of neuronal and glial activities, by tetrodotoxin or fluorocitrate, respectively, on the S-AMPA-induced downregulation of the extracellular d-serine contents. In vivo dialysis studies revealed that a local infusion of tetrodotoxin or fluorocitrate eliminated the ability of S-AMPA given intra-cortically to cause a significant decrease in the dialysate concentrations of d-serine without affecting the elevating effects of S-AMPA on those of glycine, another intrinsic coagonist for the NMDA receptor. These findings suggest that the control by the AMPA receptor of the extracellular d-serine levels could be modulated by the neuronal and glial activities in the prefrontal cortex. It cannot be excluded that fluorocitrate would indirectly alter the modulation by changing synaptic neurotransmission via glial activity attenuation as previously reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuint.2017.09.009DOI Listing
October 2018

Phencyclidine-induced dysregulation of primary cilia in the rodent brain.

Brain Res 2017 Nov 23;1674:62-69. Epub 2017 Aug 23.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Center for Brain Integration Research (CBIR), Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address:

Significant roles of the primary cilia in the central nervous system have been reported in neural generation and cognitive functions. However, little is known about the possible pathological changes in brain primary cilia in neuropsychiatric disorders. To obtain an insight into the relationship between cilial dysregulation and schizophrenia, we presently investigated the effects of psychotomimetics, phencyclidine, MK-801 (dizocilpine), and methamphetamine, on morphological and molecular indices in the rodent brain. Using an immunohistochemical technique, we found that a subcutaneous injection of phencyclidine, an NMDA type glutamate receptor (NMDAR) antagonist, caused a reduction in the long axis length of a primary cilium in the CA1 region of the hippocampus without affecting that in the dentate gyrus and medial prefrontal cortex of rats and mice. The region-selective modulation of primary cilia was mimicked by another NMDAR antagonist, MK-801, but not by the indirect dopamine agonist methamphetamine. Furthermore, systemic administration of phencyclidine, but not methamphetamine, down-regulated mRNA expression of primary cilium morphology-related genes, including kif3a, 5-HTR6, RPGRIP1L, and TMEM67, and of genes composing the cilial Wnt/β-catenin signaling pathway, β-catenin, syn2 and Bcl-2, in the hippocampus, but not in the cerebral cortex of rats. These findings suggest that NMDAR hypofunction-induced dysregulation of CA1 primary cilia could be involved in the pathophysiology of dopamine transmission-independent symptoms of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2017.08.022DOI Listing
November 2017

Evidence for Tonic Control by the GABA Receptor of Extracellular D-Serine Concentrations in the Medial Prefrontal Cortex of Rodents.

Front Mol Neurosci 2017 2;10:240. Epub 2017 Aug 2.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental UniversityTokyo, Japan.

Endogenous D-serine is a putative dominant co-agonist for the N-methyl-D-aspartate glutamate receptor (NMDAR) in the mammalian forebrain. Although the NMDAR regulates the higher order brain functions by interacting with various neurotransmitter systems, the possible interactions between D-serine and an extra-glutamatergic system largely remain elusive. For the first time, we show in the rat and mouse using an microdialysis technique that the extracellular D-serine concentrations are under tonic increasing control by a major inhibitory transmitter, GABA, via the GABA (GABAR) in the medial prefrontal cortex (mPFC). Thus, an intra-mPFC infusion of a selective GABAR antagonist, bicuculline (BIC), caused a concentration-dependent and reversible decrease in the extracellular levels of D-serine in the rat mPFC without affecting those of another intrinsic NMDAR coagonist, glycine and an NMDAR agonist, L-glutamate. The decreasing effects of BIC were eliminated by co-infusion of a selective GABA agonist, muscimol (MUS) and were mimicked by a GABA antagonist, gabazine (GBZ). In contrast, selective blockade of the GABA or homomeric ρGABA (formerly GABA) receptor by saclofen or (1,2,5,6-tetrahydropyridin-4-yl)-methylphosphinic acid (TPMPA), respectively, failed to downregulate the prefrontal extracellular D-serine levels. Moreover, the local BIC application attenuated the ability of NMDA given to the mPFC to increase the cortical extracellular concentrations of taurine, indicating the hypofunction of the NMDAR. Finally, in the mouse mPFC, the reduction of the extracellular D-serine levels by a local injection of BIC into the prefrontal portion was replicated, and was precluded by inhibition of the neuronal or glial activity by co-local injection with tetrodotoxin (TTX) or fluorocitrate (Fluo), respectively. These findings suggest that the GABAR-mediated regulation of the D-serine signaling may exert fine-tuning of the NMDAR function and require both neuronal and glial activities in the mammalian mPFC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnmol.2017.00240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5539225PMC
August 2017

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

BMC Psychiatry 2017 07 12;17(1):249. Epub 2017 Jul 12.

Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan.

Background: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs.

Methods: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales.

Results: D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower.

Conclusion: It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity.

Trial Registration: UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12888-017-1410-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5508614PMC
July 2017

A distinctive abnormality of diffusion tensor imaging parameters in the fornix of patients with bipolar II disorder.

Psychiatry Res Neuroimaging 2017 Aug 8;266:66-72. Epub 2017 Jun 8.

Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.

Diffusion tensor imaging (DTI) studies have revealed a changed integrity in the white matter of bipolar disorder. However, only a few investigations have examined bipolar II disorder (BP-II). A cross-sectional study was conducted to compare thirty-eight patients with BP-II (mean age = 38.26 years, F/M = 19/19) with thirty-eight age- and gender-matched healthy controls (mean age = 34.45 years, F/M = 18/20). Tract Based Spatial Statistics (TBSS) analysis of the fractional anisotropy (FA) was done with age, gender and education years as covariates, then a complementary atlas-based region-of-interest (ROI) analysis including the axial diffusivity (AD) and radial diffusivity (RD) was conducted to obtain further information. The patients with BP-II showed a significant decrease in FA in the corpus callosum (commissure fibers), fornix (association fibers) and right anterior corona radiata (projection fibers) compared to the controls. Moreover, a significant increase in the RD was observed in all of the fibers of the BP-II patients, while the AD significantly increased only in the fornix of the patients. Thus, in addition to the abnormal integrity of the commissure and projection fibers, the present study suggested an involvement of the limbic association fibers in the pathophysiology of BP-II induced by a distinctive neuropathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pscychresns.2017.06.005DOI Listing
August 2017

Role of poly(ADP-ribose) polymerase activation in the pathogenesis of periodontitis in diabetes.

J Clin Periodontol 2017 Oct 30;44(10):971-980. Epub 2017 Aug 30.

Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.

Aim: The aetiology of progressive periodontitis in diabetes has not yet been elucidated. We previously demonstrated that nitrosative stress is increased in diabetic rats with periodontitis. Nitrosative stress induces poly(ADP-ribose) polymerase (PARP) activation. Here, we demonstrated the involvement of PARP activation in diabetic periodontitis and detailed the therapeutic effects of PARP inhibitor.

Materials And Methods: Experimental periodontitis was induced by placing a nylon thread ligature. Half of the normal and diabetic rats received the PARP inhibitor, 1,5-isoquinolinediol, for 2 weeks. Gingival PARP activation was detected by immunostaining for poly(ADP-ribose). Periodontitis was evaluated by gingival inflammatory cell infiltration, inflammatory gene expressions and micro-CT analyses.

Results: Although both periodontitis and the presence of diabetes increased PARP activation in the gingiva, diabetic rats with periodontitis had the highest activation of PARP. Diabetic rats with periodontitis also showed significant increases in monocyte/macrophage invasion into the gingiva, inflammatory gene expressions, nitrotyrosine-positive cells in the gingiva and alveolar bone loss, all of which were suppressed by treatment with the PARP inhibitor.

Conclusions: These results indicate the involvement of PARP activation in the pathogenesis and aggravation of periodontal disease in diabetes and suggest the therapeutic potential of PARP inhibition for treating periodontal disease, especially in patients with diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpe.12758DOI Listing
October 2017

Unilateral Atonia and Asymmetric Cholinergic Dysfunction in Ross Syndrome.

Biol Psychiatry 2018 01 3;83(2):e31-e32. Epub 2017 May 3.

Department of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopsych.2017.04.010DOI Listing
January 2018

Plasma and cerebrospinal fluid G72 protein levels in schizophrenia and major depressive disorder.

Psychiatry Res 2017 08 27;254:244-250. Epub 2017 Apr 27.

Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan. Electronic address:

G72 is a modulator of D-amino acid oxidase, the enzyme that degrades D-serine, an amino acid that plays a critical role in glutamate neurotransmission, and has been implicated in psychiatric disorders. The aim of this study was to examine whether plasma or cerebrospinal fluid (CSF) G72 protein levels were altered in either schizophrenia or major depressive disorder (MDD) and whether any correlation between G72 levels and disease severity existed. Initially, 27 schizophrenic patients, 26 MDD patients, and 27 healthy controls matched for age, sex, and ethnicity were enrolled. Compared to those of controls, plasma or CSF G72 levels were not significantly different in patients with schizophrenia or MDD. Although we found a significant positive correlation between plasma G72 levels and a positive symptoms score on the positive and negative syndrome scale (PANSS), this was not replicated in the second study (40 schizophrenic patients). CSF G72 levels showed no significant correlation with PANSS scores. In MDD, neither plasma nor CSF G72 levels correlated significantly with depression severity. Since severity of our patients were relatively mild, further investigations in a large number of subjects including drug-free patients, younger patients, and more severely affected patients are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2017.04.060DOI Listing
August 2017

Two Cases of Oral Somatic Delusions Ameliorated With Brain Perfusion Asymmetry: A Case Report.

Clin Neuropharmacol 2017 Mar/Apr;40(2):97-99

*Psychosomatic Dentistry Clinic, Dental Hospital and Departments of †Psychiatry and Behavioral Sciences, ‡Diagnostic Radiology and Nuclear Medicine, and §Psychosomatic Dentistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

Background: Oral cenesthopathy is the complaint of abnormal oral sensation where no underlying organic cause can be identified. It is also called oral dysesthesia or oral somatic delusion and classified as delusional disorder, somatic type. The patients with oral cenesthopathy show right > left asymmetric regional cerebral blood flow (rCBF) in the broad brain region. However, the studies scrutinizing the rCBF change before and after the successful treatment are still a few so far.

Case: We present 2 cases of oral cenesthopathy, who responded well to aripiprazole. The asymmetric rCBF patterns were attenuated after successful treatment in both cases.

Conclusions: We found a marked improvement of oral cenesthopathy with aripiprazole. It is suggested that right > left rCBF asymmetry in the frontal and temporal lobes and thalamus, and the dopaminergic and serotonergic dysfunctions are involved in the pathology of oral cenesthopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNF.0000000000000207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349303PMC
May 2017