Special Lecture(SL) |
P1-4 A meta-analysis of the effects of multi-session transcranial direct current stimulation on cognition in dementia and mild cognitive impairment TAKUMA INAGAWA 1, Zui Narita 1, Norio Sugawara 1, Kazushi Maruo 2, Sticley Andrew 1, Yuma Yokoi 1, Tomiki Sumiyoshi 1
There have been growing efforts to investigate the effects of neuromodulation techniques, such as transcranial direct current stimulation (tDCS), on cognitive impairment in dementia and related conditions. In this systematic review and meta-analysis, we assessed the efficacy of multisession anodal tDCS compared to sham-stimulation for improving global cognition and specific cognitive domains in both Alzheimer's disease and mild cognitive impairment (MCI). Eight articles meeting the criteria for inclusion in the meta-analysis were selected. Five studies used the Mini- Mental State Examination (MMSE) to examine MCI and dementia. In a fixed effect model, there was a mean difference in the change score of -0.13 points. Three trials for dementia using the Alzheimer's Disease Assessment Scale- Cognition (ADAS-Cog) showerd a mean difference of -0.53 points. At present, there is a lack of clear evidenceconcerning the efficacy of multi-session anodal tDCS due to the small number of studies and different measures used. This underscores the need for further investigations using larger samples and common outcome measures.
|
P3-2 The large scale disturbed white matter fibre in schizophrenia revealed by local connectometry TAKASHI OHNISHI 1, Kiyotaka Nemoto 5, Fumio Nemoto 6, Hidenaga Yamamori 3, Yuka Yasuda 3,Michiko Fujimoto 3, Noriko Kudo 3, Hirotsugu Azechi 3, Yoshiyuki Watanabe 4, Ryota Hashimoto 2,3
Background & Purpose: Using DTI data, we applied new analytical technique called 'local connectometry' to investigate differences of the degree of connectivity between adjacent voxels within a white matter fascicle defined by the density of the diffusing spins between healthy controls (HCs) and patients with chronic schizophrenia. Furthermore, to investigate how oligodendroglial and myelin (OM) related gene affect connectomes, we examine genotype effects of polymorphisms of ANK3 and ERBB4 genes on local connectome. Methods; 77 patients with schizophrenia and 231 HCs participated in the present study. Written informed consent was obtained before participation. The current study was approved by the Research Ethical Committee of Osaka University and the Ethical Committee of the Faculty of Medicine. Local connectometry was analysed by using DSI studio. Results: Compared with HCs, connectometry analysis identified significantly decreased connectivity in the corpus callosum, cortico thalamic, and inferior fronto occipital fasciculus. Furthermore, the connectometry analysis identified significantly decreased connectivity in corpus callosum, bilateral cortico thalamic, and bilateral external capsule associated with cognitive dysfunction in schizophrenia. A significantly decreased connectivity in minor allele carriers of the ANK3 gene in the corpus callosum, bilateral cortico thalamic, external capsule, and left frontal aslant tract was noted. Conclusion: Our results suggest that schizophrenia be a disorder of global brain structural connectivity. Genetic factors might contribute to such a fibre disintegrity.
|
P4-4 Difference in executive function among with patients with schizophrenia, their first degree relatives and healthy subjects YUZURU KATAOKA 1, Kazutaka Ohi 1,2, Takamitsu Shimada 1, Aki Kuwata 1, Hiroaki Okubo 1, Kohei Kimura 1, Toshiki Yasuyama 1, Takashi Uehara 1, Yasuhiro Kawasaki 1
Background: Patients with schizophrenia (SCZ) exhibit severe impairments in executive function compared with healthy controls (HC). The Wisconsin Card Sorting Test (WCST) is a set-switching task used extensively to study impaired executive function in SCZ. Previous studies investigated whether unaffected their first-degree relatives (FR) show worse executive function, mainly perseveration, compared with HC. In this study, we investigated difference in executive function using the WCST among SCZ (n=40), unaffected FR (n=40) and HC (n=40). Methods: To evaluate perseveration of executive function, we used total errors (TE), perseverative errors of Nelson (PEN), and percentage of PEN (%PEN) in the WCST. The difference among SCZ, FR and HC was analyzed using analysis of covariance (ANCOVA), with TE, PEN, and %PEN. Written informed consent was obtained from all subjects after the procedures were fully explained. This study was performed according to the World Medical Association's Declaration of Helsinki and was approved by the Research Ethical Committee of Kanazawa Medical University. Results: There was significant difference in perseverative performance in executive function among three diagnostic groups. SCZ had worse perseverative performance than HC and FR. There was no significant difference in the performance between HC and FR. Conclusion: Perseverative performance scores could be the state marker of SCZ. And there may be some significant differences by increasing the numbers of the sample.
|
P6-1 Glutamatergic Neurometabolite Levels in Patients with Ultra Treatment-Resistant Schizophrenia: a Cross-sectional 3T Proton MRS study YUSUKE IWATA 1, Shinichiro Nakajima 1,2, Eric Plitman 3, Fernando Caravaggio 3, Julia Kim 3, Parita Shah 3, Sofia Chavez 3, Vincenzo De Luca 1, Masaru Mimura 2, Gary Remington 1, Philip Gerretsen 1,3, Ariel Graff-Guerrero 1,3
Background: In terms of antipsychotic treatment response, patients with schizophrenia can be classified into three groups: (1) treatment-resistant to both non-clozapine (CLZ) antipsychotics and CLZ (ultra treatment-resistant schizophrenia [URS]), (2) treatment-resistant to non-CLZ antipsychotics but CLZ-responsive schizophrenia [non-URS]), and (3) responsive to firstline antipsychotics (treatment non-resistant schizophrenia [TnRS]). This study aimed to compare glutamatergic neurometabolite levels among these three patient groups and healthy controls (HCs), using proton magnetic resonance spectroscopy (1H-MRS).Methods: Glutamate (Glu) and glutamate+glutamine (Glx) levels were assessed in the caudate, the anterior cingulate cortex (ACC), and the dorsolateral prefrontal cortex (DLPFC) using 3T 1H-MRS (PRESS, TE=35ms). Glutamatergic neurometabolite levels were compared between the groups using analyses of variance. Results: A total of 100 participants were included, which consisted of 26 patients with URS, 27 patients with non-URS, 21 patients with TnRS, and 26 HCs. Group differences were detected in ACC Glx levels (F[3,96]=2.93, p=0.038); patients with URS showed higher ACC Glx levels than HCs (p=0.038). There were no group differences in the caudate or DLPFC. Conclusions: Higher levels of glutamatergic neurometabolites in the ACC may be a trait marker of treatment-resistant schizophrenia, which may become prominent after initial antipsychotic treatment failure and persist even after CLZ administration.
|
P6-5 Analysis of clozapine use and safety using comprehensive national data from the Japanese Clozapine Patient Monitoring Service KEN INADA 1, Hidehiro Oshibuchi 1, Masahiko Kawano 1,2, Jun Ishigooka 3, Katsuji Nishimura 1
Objective: The aim of this study was to investigate clozapine use and its associated adverse effects in patients in Japan. Methods: We analyzed data recorded from July 2009 to January 2016 (n = 3780 patients) in the Clozaril Patient Monitoring Service, which was established in Japan in 2009 and includes all Japanese patients who have been prescribed clozapine. Results: The treatment discontinuation rate was 23.9% (869/3780 cases). The average treatment duration was 234.9±306.9 (median, 115) days and the average dosage was 186.41 ± 151.6 mg/day. The estimated treatment continuation rates resulting from all-cause discontinuation were 78.2 and 72.9% after treatment for 1 and 2 years, respectively. The incidence of neutropenia/leucopenia was 5.4% (206/3780 cases). The average dose prior to discontinuation was 233.36±168.15 mg (median, 200 mg; range, 4-600 mg). The incidence of glucose intolerance was 15.4% (583/3780 cases). Of the 3780 patients, 98 and 485 (2.67 and 12.8%) developed glucose intolerance before and after clozapine administration, respectively. The average time from treatment initiation to new onset of glucose intolerance was 382.2±420.2 days (median, 216 days; range, 4-2053 days). Conclusion: The data obtained in this study, particularly on the incidence of clozapine-induced adverse events, will enable the optimal and safe use of clozapine in Japanese patients with treatment-resistant schizophrenia.
|
P7-1 Time Courses of Central Dopamine D2 Receptor Occupancy andPeripheral Blood Concentrations of Antipsychotics: A Systematic Review SHIN KUROSE 1, Hiroyuki Uchida 1, Keisuke Takahata 2, Takefumi Suzuki 3, Masaru Mimura 1, Hiroyoshi Takeuchi 1
Objective: To elucidate whether dopamine D2 receptor occupancy with an antipsychotic in the brain changes with time in parallel to its blood concentration, we conducted a systematic review of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies. Methods: We systematically searched MEDLINE and Embase, and included studies that met the following criteria: (1) including patients with schizophrenia spectrum disorders and/or healthy subjects; (2) using PET or SPECT; and (3) examining the time courses of D2 occupancy and blood concentrations of antipsychotics. We calculated the ratio of % D2 occupancy reduction rate from peak to % blood concentration reduction rate from peak. Results: 18 studies were identified (3, 2, 4, 2, 1, 1, 1, 2, 2, 1, 1, 1, 3, and 1 studies for risperidone, olanzapine, quetiapine immediate release (IR), quetiapine extended release (XR), aripiprazole, ziprasidone, perospirone, haloperidol, sulpiride, clozapine, long-acting injectable risperidone, long-acting injectable haloperidol, and intramuscular injection of zuclopenthixol, respectively). The ratios were less than 1 except those for quetiapine IR 300/450 mg/day, and quetiapine XR 300 mg/day whose peak D2 occupancy levels were below 40%. Conclusion: The findings indicate that the reduction rate of D2 occupancy is lower than that of blood concentrations when peak D2 occupancy levels are not low.
|
P9-5 Associations of ABCB1 gene polymorphisms with aripiprazole-induced autonomic nervous system dysfunction in schizophrenia SAKI HATTORI 1, Akira Suda 1, Ikuko Kishida 1,2, Masatoshi Miyauchi 1, Yohko Shiraishi 1, Mami Fujibayashi 3, Natsuki Tsujita 4, Chie Ishii 2, Norio Ishii 2, Toshio Moritani 5, Yoshio Hirayasu 1,6
There are interindividual differences in the adverse effects of atypical antipsychotic aripiprazole, which includes autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of aripiprazole in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in 48 patients with schizophrenia. All the patients were treated with aripiprazole monotherapy. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier-rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier-rs2235048 non-C allele carrier group. In addition, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642-rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582). We suggest that ABCB1 gene polymorphisms are associated with the adverse effects of aripiprazole and that they could be used as a biomarker to predict the aripiprazole response. (The institutional ethics committee approved the study protocol, and all participants signed written informed consent statements after being provided with a full explanation of the study protocol.)
|
P14-1 Impact of subjective vs. objective remission status on subjective cognitive impairments in depression KYOSUKE SAWADA 1, Kazunari Yoshida 1,2, Chisa Ozawa 1, Yuya Mizuno 1,3, Takefumi Suzuki 1,4, Masaru Mimura 1, Hiroyuki Uchida 1,5
Objective: The impact of subjective versus objective illness severity on subjective cognitive impairment in depression has not been addressed. Methods: This study is a post-hoc analysis of our cross-sectional study in Japanese outpatients with depression. The participants received assessments with the Japanese version of the Perceived Deficits Questionnaire (J-PDQ), Quick Inventory of Depressive Symptomatology (QIDS), and Montgomery- Asberg Depression Rating Scale (MADRS). First, multiple regression analysis was conducted to examine effects of demographic and clinical characteristics including illness severity and medications on the PDQ total score. Next, we categorized the participants into 4 groups based on the presence/absence of subjective and objective symptom remission (i.e. QIDS total score of ?5 and MADRS total score of ?9, respectively), and compared the differences in PDQ total scores between the QIDS- and MADRS-remitted group and the QIDS-non-remitted but MADRS-remitted group. Results: 102 participants (mean age: 50.5 years) were included. Higher QIDS and MADRS total scores were significantly associated with a greater PDQ total score (both p's<0.001) while other factors did not exhibit any associations. The QIDS-non-remitted but MADRS-remitted group showed a significantly higher PDQ total score than that of the QIDS- and MADRSremitted group (p<0.001). Conclusions: These findings suggest that objective remission in the absence of subjective remission may not be adequate in terms of subjective cognitive function.
|
P19-1 NETWORK MODEL OF DEPRESSIVE AND MANIC SYMPTOMS IN THE STEP-BD STUDY Cynthia Siu、Carla Brambilla
Bipolar disorders are characterized by mood swings involving manic and depressive episodes and changes in sleep, energy, thinking and behavior. This study applies network analysis approach to examine the interactive effects of depressive and manic features on a symptom basis, using data from the National Institute of Mental Health's Systematic Treatment Enhancement Program for Bipolar Disorder (STEP?BD) study (N=3730). We tested the hypotheses that "sleep disturbance", an overlapping symptom (bridge symptom) in depression and mania, partly explained the complex presentations of manic?depressive illness. We applied the partial correlation network model with graphical LASSO to analyze the relationships between Montgomery?Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) items. The overall network shows clustering patterns of depressive and manic symptoms (nodes) within the disorder, and significant direct connections between depression and mania through the bridge "sleep" symptoms. Correlation between YMRS Sleep item 4 and MADRS Sleep item 4 was 0.74 (Spearman rank correlation, P<0.001). Absence of the bridge symptom (MADRS Sleep item =0; YMRS Sleep item =0) was associated with significantly less manic and/or depressive symptoms, and predicted greater improvement of MADRS score at month 6. Our findings suggest that "sleep" symptoms, which occur in both mania and depression, can play a critical role in effective treatment of mixed depressive and manic symptoms in bipolar disorders.
|
P27-6 Relationship of high neuroticism with increased methylation of the BDNF gene in healthy subjects TOSHINORI SHIRATA 1, AKIHITO SUZUKI 1, YOSHIHIKO MATSUMOTO 1, NANA TAKAHASHI 1, KEISUKE NOTO 1, KAORU GOTO 2, KOICHI OTANI 1
Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has an important function in neuroplasticity and neuronal development. Recent study suggested that increased methylation of the BDNF gene resulting in decreased BDNF activity is associated with depression. Meanwhile, neuroticism is a well-known risk factor for developing depression. The present study examined the relationship between methylation of the BDNF gene and personality traits including neuroticism. Methods: The subjects were 98 healthy Japanese volunteers. Methylation levels of the BDNF gene were determined by the bisulfite-pyrosequencing method. Personality traits including neuroticism were assessed by the NEO Personality Inventory-Revised. The protocol of this study was approved by the Ethics Committee of Yamagata University School of Medicine. After complete explanation of the study, written informed consent was obtained from all subjects. Results: There was a positive correlation between neuroticism scores and methylation levels of the BDNF gene (p=0.023). In the two-way analysis of covariance, the subjects with higher neuroticism scores had higher (p=0.005) levels of BDNF gene methylation compared with those with lower neuroticism scores. Meanwhile, other personality traits were not associated with BDNF gene methylation. Conclusions:The present study suggests that high neuroticism is related to increased methylation of the BDNF gene.
|
|