記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The number of suicides in Japan decreased during the period from 2012 through 2019. Because data on factors associated with this decline are limited, we conducted a retrospective longitudinal study of psychiatric diagnoses of serious suicide attempters before 2012 and after 2019. METHODS: Serious suicide attempters admitted to the critical care medicine (CCM) department of Nippon Medical School Hospital between 2006 and 2017 were included and classified as those before and after the suicide decline in 2012. Chi-square test and residual analysis were used to analyze changes in the proportion of suicide attempters among all patients admitted to CCM and to examine differences in the proportion of psychiatric diagnoses. RESULTS: The proportion of suicide attempters among CCM hospitalized patients decreased overall (χ2 (1) =18.29, p<.01). The proportion of psychiatric diagnoses changed significantly (χ2 (8) =62.21, p<0.001); specifically, it decreased for schizophrenia (residual: -2.28), depressive disorders (residual: -5.39), persistent mood disorders (residual: -3.58), and reaction to stress disorders (residual: -2.73). Depressive disorders decreased and had a large contribution ratio in both sexes. CONCLUSIONS: The decrease in the proportion of attempted suicides among patients admitted to CCM was consistent with the decline in suicides in Japan. Analysis by psychiatric diagnosis confirmed a significant decrease in the proportion of suicide attempts associated with depressive disorders, schizophrenia, and reaction to stress disorders, which were the most common disorders associated with attempted suicide. Depressive disorders made the greatest contribution to the reduction in suicide attempts.

DOI： 10.1272/jnms.JNMS.2022_89-405

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for depressive disorders, although its molecular mechanism of action is unknown. The serotonin 1B (5-HT1B) receptor is a potential target for treatment of depression and low 5-HT1B receptor binding in limbic regions has been reported in previous positron emission tomography (PET) studies of depression. METHODS: The objective of this longitudinal PET study was to examine the effect of ECT for depression on 5-HT1B receptor binding. Fifteen hospitalized patients with major depressive episodes were examined with PET and the 5-HT1B receptor selective radioligand [11C]AZ10419369, before and after ECT. Fifteen controls matched for age and sex were examined. Limbic regions with previously reported low 5-HT1B receptor binding in depression and a dorsal brain stem region were selected. RESULTS: Thirteen patients completed the study according to protocol. Eleven out of thirteen patients responded to ECT. 5-HT1B receptor binding in hippocampus increased with 30 % after ECT (p=0.021). Using linear mixed effects modelling, we observed increases in 5-HT1B receptor binding following ECT with a moderate to large effect size, which did not differ significantly between regions. In an exploratory analysis, strong correlations between changes in 5-HT1B receptor binding and agitation scores on the Hamilton Depression Rating Scale after ECT were observed. LIMITATIONS: Albeit representative of a PET study, the sample size is still small and there are potential confounding effects of medication. CONCLUSIONS: Increased 5-HT1B receptor binding was observed following ECT for depression, corresponding to previous findings of increased 5-HT1B receptor binding in hippocampus after rapid acting ketamine for treatment resistant depression.

DOI： 10.1016/j.jad.2021.07.060

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.jnms.2021_88-607

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：日本語   出版者・発行元：日本うつ病学会・日本認知療法・認知行動療法学会  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/pcn.13208

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/pcn.13208

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Rationale

Unlike other antipsychotics, our previous positron emission tomography (PET) study demonstrated that a single dose of blonanserin occupied dopamine D₃ as well as dopamine D₂ receptors in healthy subjects. However, there has been no study concerning the continued use of blonanserin.

Objectives

We examined D₂ and D₃ receptor occupancies in patients with schizophrenia who had been treated with blonanserin.

Methods

Thirteen patients with schizophrenia participated. PET examinations were performed on patients treated with clinical dosage of blonanserin or olanzapine alone. A crossover design was used in which seven patients switched drugs after the first scan, and PET examinations were conducted again. D₂ and D₃ receptor occupancies were evaluated by [¹¹C]-(+)-PHNO. We used nondisplaceable binding potential (BP_ND) of 6 healthy subjects which we previously reported as baseline. To consider the effect of upregulation of D₃ receptor by continued use of antipsychotics, D₃ receptor occupancy by blonanserin in seven subjects who completed 2 PET scans were re-analyzed by using BP_ND of olanzapine condition as baseline.

Results

Average occupancy by olanzapine (10.8 ± 6.0 mg/day) was as follows: caudate 32.8 ± 18.3%, putamen 26.3 ± 18.2%, globus pallidus − 33.7 ± 34.9%, substantia nigra − 112.8 ± 90.7%. Average occupancy by blonanserin (12.8 ± 5.6 mg/day) was as follows: caudate 61.0 ± 8.3%, putamen 55.5 ± 9.5%, globus pallidus 48.9 ± 12.4%, substantia nigra 34.0 ± 20.6%. EC₅₀ was 0.30 ng/mL for D₂ receptor for caudate and putamen (df = 19, p &lt; 0.0001) and 0.70 ng/mL for D₃ receptor for globus pallidus and substantia nigra (df = 19, p &lt; 0.0001). EC₅₀ for D₃ receptor of blonanserin changed to 0.22 ng/mL (df = 13, p = 0.0041) when we used BP_ND of olanzapine condition as baseline.

Conclusions

Our study confirmed that blonanserin occupied both D₂ and D₃ receptors in patients with schizophrenia.

DOI： 10.1007/s00213-020-05698-3

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その他リンク： https://link.springer.com/article/10.1007/s00213-020-05698-3/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.neulet.2021.135716

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/psyg.12683

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/psyg.12683

掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

Background

Transdermal antipsychotic patch formulations offer potential benefits, including improved adherence. This study investigated the striatal dopamine D2 receptor occupancy with daily blonanserin transdermal patch application.

Methods

This open-label, phase II study enrolled 18 Japanese outpatients (20 to &amp;lt;65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale score &amp;lt;120 at screening) treated with blonanserin 8-mg or 16-mg tablets. Patients continued tablets for 2–4 weeks at their current dose and were then assigned to once-daily blonanserin patches (10/20/40/60/80 mg daily) for 2–4 weeks based on the oral dose. [11C]raclopride positron emission tomography scanning determined blonanserin striatal dopamine D2 receptor occupancy (primary endpoint). Secondary endpoints included assessment of receptor occupancy by dose, changes in Positive and Negative Syndrome Scale and Clinical Global Impressions-Severity of Illness-Severity scores, patient attitudes towards adherence, and patch adhesiveness.

Results

Of 18 patients who started the blonanserin tablet treatment period, 14 patients completed treatment. Mean D2 receptor occupancy for blonanserin tablets 8 mg/d (59.2%, n = 5) and 16 mg/d (66.3%, n = 9) was within the values for blonanserin patches: 10 mg/d (33.3%, n = 3), 20 mg/d (29.9%, n = 2), 40 mg/d (61.2%, n = 3), 60 mg/d (59.0%, n = 3), and 80 mg/d (69.9%, n = 3). Occupancy generally increased with increasing blonanserin dose for both formulations with the half maximal receptor occupancy for tablets and patches associated with doses of 6.9 mg/d and 31.9 mg/d, respectively. Diurnal variability in occupancy was lower during transdermal patch treatment than during tablet treatment. Blonanserin transdermal patches were well tolerated with no major safety concerns.

Conclusions

Blonanserin patches (40/80 mg/d) have lower diurnal variability in occupancy than blonanserin tablets (8/16 mg/d), and patches at doses of 40 mg/d and 80 mg/d appear to be a suitable alternative for blonanserin tablets at doses of 8 mg/d and 16 mg/d, respectively. Blonanserin patches represent a potential new treatment option for patients with schizophrenia.

Trial registry

JAPIC Clinical Trials Information registry (www.clinicaltrials.jp; JapicCTI-No: JapicCTI-121914).

DOI： 10.1093/ijnp/pyaa071

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その他リンク： http://academic.oup.com/ijnp/article-pdf/24/2/108/36267824/pyaa071.pdf

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aims: This study aimed to analyze the performance of multi-atlas MRI-based parcellation for 123I-FP-CIT SPECT (DAT-SPECT) in healthy volunteers. The proposed method was compared with the SPECT-atlas-based and Bolt methods. 18F-FE-PE2I-PET (DAT-PET) was used as a reference. Methods: Thirty healthy subjects underwent DAT-SPECT, DAT-PET, and 3D-T1WI-MRI. We calculated the striatum uptake ratio (SUR/SBR), caudate uptake ratio (CUR), and putamen uptake ratio (PUR) for DAT-SPECT using the multi-atlas MRI-based method, SPECT-atlas-based method, and Bolt method. In the multi-atlas MRI-based method, the cerebellum, occipital cortex, and whole-brain were used as reference regions. The correlation of age with DAT-SPECT activity and the correlations of SUR/SBR, CUR, and PUR between DAT-SPECT and DAT-PET were calculated by each of the three methods. Results: The correlation between age and SUR/SBR for DAT-SPECT based on the multi-atlas MRI-based method was comparable to that based on the SPECT-atlas-based method (r = -0.441 to -0.496 vs. -0.488). The highest correlation between DAT-SPECT and DAT-PET was observed using the multi-atlas MRI-based method with the occipital lobe defined as the reference region compared with the SPECT-atlas-based and Bolt methods (SUR, CUR, and PUR: 0.687, 0.723, and 0.676 vs. 0.698, 0.660, and 0.616 vs. 0.655). Conclusion: Multi-atlas MRI-based parcellation with the occipital lobe defined as the reference region was at least comparable to the clinical methods.

DOI： 10.3389/fmed.2021.662233

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Dysfunction of dopaminergic neurons in the central nervous system is considered to be related to major depressive disorder (MDD). Especially, MDD in geriatric patients is characterized by anhedonia, which is assumed to be associated with reduced dopamine neurotransmission in the reward system. Dopamine transporter (DAT) is considered to reflect the function of the dopamine nerve system. However, previous DAT imaging studies using single photon emission computed tomography or positron emission tomography (PET) have shown inconsistent results. The radioligand [18 F]FE-PE2I for PET enables more precise evaluation of DAT availability. Hence, we aimed to evaluate the DAT availability in geriatric patients with MDD using [18 F]FE-PE2I. METHODS: Eleven geriatric patients with severe MDD and 27 healthy controls underwent PET with [18 F]FE-PE2I, which has high affinity and selectivity for DAT. Binding potentials (BPND ) in the striatum (caudate and putamen), nucleus accumbens (NAc), and substantia nigra were calculated. BPND values were compared between MDD patients and healthy controls. RESULTS: MDD patients showed significantly lower DAT BPND in the NAc (P = 0.009), and there was a trend of lower BPND in the putamen (P = 0.032) compared to controls. CONCLUSION: We found low DAT in the NAc and putamen in geriatric patients with severe MDD, which could be related to dysregulation of the reward system.

DOI： 10.1111/pcn.13020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Electroconvulsive therapy (ECT) is an effective treatment for major depression. Previous studies suggested that dopaminergic neurotransmission plays a crucial role in the mechanism of the action of ECT. Since dopamine transporters (DAT) regulate extracellular dopamine concentration, DAT represents an interesting target for the study of the mechanism of action of ECT. Eight inpatients (7 patients with major depressive disorder and 1 patient with bipolar disorder with a DSM-IV diagnosis) received a series of 7-15(11.3±5.2) bilateral ECT sessions.The severity of symptoms was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and Clinical Global Impression-Severity (CGI-S). All patients were examined with [18F]FE-PE2I positron emission tomography (PET) at pre-ECT, after the 10th ECT, and at post-ECT. Striatal DAT-binding potential (BPND) of all patients was reduced, with an average change ratio of DAT-BPND of -13.1±5.6%. In the 2 cases with 15 ECT sessions, the ratio change of DAT-BPND after the 15th ECT was larger than that after the 10th ECT. Also, HDRS and CGI-S were reduced. These results indicate that the dopamine nervous system is part of themechanism of action of ECT.

DOI： 10.1016/j.pscychresns.2020.111086

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The rising older population in Japan is associated with a rise in cases of dementia. Support for the increased number of family caregivers of people living with dementia is crucial, as caring may negatively affect a family caregiver's health. This study seeks to evaluate the feasibility and applicability of a recently developed Japanese version of START (STrAtegies for RelaTives). START is a psychosocial coping intervention program developed in the United Kingdom that has been shown to improve caregivers' mood and quality of life in a randomized controlled trial. We made changes to START (e.g., idioms, linguistic nuance, and providing care insurance information suited for Japan) to make it culturally appropriate. Fourteen Japanese female family caregivers of relatives with mild dementia (n = 10) or mild cognitive impairment (n = 4) were referred to the study, but six were excluded owing to illness and busyness. This single-arm study had a before-after trial evaluating psychological outcomes including depression, anxiety, quality of life, and subjective care burden. The acceptance retention and satisfaction rate suggest the feasibility and acceptability of the START program; 8/14 (>55%) eligible, prospective participants consented and were included in this study, all (8/8) of whom completed all START sessions. The mean program satisfaction score was 30.25 (standard deviation = 2.25) out of a potential 32. The results suggest that it is feasible and acceptable to deliver START in Japanese and based on the results of analysis using a linear mixed model, there is initial indication that the intervention improved family caregivers' quality of life, depressive symptoms, and care burden.

DOI： 10.1177/1471301220919938

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study investigated the feasibility of a cognitive behavioral therapy (CBT) program for improving mood and quality of life in an older woman with mild cognitive impairment (MCI), depression, and anxiety. The program comprised eight 30-minute weekly sessions; interventions included behavioral activation, relaxation, and cognitive reconstruction, in which the patient's caregiver also participated. The patient's condition was assessed before and immediately after the intervention. After 3 and 12 months, the caregiver reported the patient's behavioral and psychological symptoms by using self-reported psychological scales for depression, anxiety, and quality of life. Although CBT helped to improve mood and quality of life in the short term (3 months), the results were not sustained over the long term (12 months). Even though improvement in psychological symptoms did not persist and only one patient with MCI was evaluated, these results suggest that CBT is a feasible nonpharmacological treatment option and provide preliminary support for wider use of CBT in Japan. CBT programs should be tailored to the needs of patients with MCI and dementia, and regular follow-up sessions should be used to evaluate program feasibility and improvement in patient mental health.

DOI： 10.1272/jnms.JNMS.2019_86-603

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記述言語：日本語   出版者・発行元：(一社)日本総合病院精神医学会  

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記述言語：英語   出版者・発行元：(一社)日本核医学会  

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DOI： 10.1007/s00213-019-05337-6

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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DOI： 10.2147/PPA.S204465

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DOI： 10.1272/jnms.JNMS.2019_86-205

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記述言語：日本語   出版者・発行元：日本医科大学  

CiNii Books

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The aim of this multicenter trial was to generate a [123I]FP-CIT SPECT database of healthy controls from the common SPECT systems available in Japan. METHODS: This study included 510 sets of SPECT data from 256 healthy controls (116 men and 140 women; age range, 30-83 years) acquired from eight different centers. Images were reconstructed without attenuation or scatter correction (NOACNOSC), with only attenuation correction using the Chang method (ChangACNOSC) or X-ray CT (CTACNOSC), and with both scatter and attenuation correction using the Chang method (ChangACSC) or X-ray CT (CTACSC). These SPECT images were analyzed using the Southampton method. The outcome measure was the specific binding ratio (SBR) in the striatum. These striatal SBRs were calibrated from prior experiments using a striatal phantom. RESULTS: The original SBRs gradually decreased in the order of ChangACSC, CTACSC, ChangACNOSC, CTACNOSC, and NOACNOSC. The SBRs for NOACNOSC were 46% lower than those for ChangACSC. In contrast, the calibrated SBRs were almost equal under no scatter correction (NOSC) conditions. A significant effect of age was found, with an SBR decline rate of 6.3% per decade. In the 30-39 age group, SBRs were 12.2% higher in women than in men, but this increase declined with age and was absent in the 70-79 age group. CONCLUSIONS: This study provided a large-scale quantitative database of [123I]FP-CIT SPECT scans from different scanners in healthy controls across a wide age range and with balanced sex representation. The phantom calibration effectively harmonizes SPECT data from different SPECT systems under NOSC conditions. The data collected in this study may serve as a reference database.

DOI： 10.1007/s00259-018-3976-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Verlag  

Background: Tramadol is an analgesic with monoamine reuptake inhibition and μ-opioid receptor activation. Although tramadol has been widely used for treatment of various pain conditions, there is controversy over the risk of abuse potential. We examined the effects of tramadol on the reward system in humans using functional magnetic resonance imaging (fMRI) to assess the potential of tramadol for drug abuse or dependence. Methods: A randomized, double-blind, placebo-controlled, crossover study was conducted for 19 healthy adults under tramadol or placebo. In association with subjective mood questionnaires, monetary incentive delay (MID) task was performed to assess the neural response to reward anticipation during fMRI. Subjective mood measures and blood oxygenation level-dependent (BOLD) signal during gain and loss anticipation were compared between tramadol and placebo. Results: Tramadol significantly reduced anxiety (Z = − 2.513, p = 0.012) and enhanced vigor (Z = − 2.725, p = 0.006) compared with placebo. By Mood Rating Scale, tramadol provoked contented (Z = − 2.316, p = 0.021), relaxed (Z = − 2.236, p = 0.025), and amicable feelings (Z = − 2.015, p = 0.044) as well as increased alertness (Z = − 1.972, p = 0.049) and contentedness domains (Z = − 2.174, p = 0.030) compared with placebo. Several brain regions including nucleus accumbens (NAc) were activated during gain anticipation in the MID task under both tramadol and placebo. Tramadol increased the %BOLD signal change in NAc at +\500 cue significantly more than the placebo (Z = − 2.295, p = 0.022). Conclusion: Tramadol enhances the reward system and thereby may have abuse potential or precipitate drug abuse in human.

DOI： 10.1007/s00213-018-4955-z

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/ijnp/pyy004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3233/JAD-170956

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Modafinil is a wake-promoting agent and has been reported to be effective in improving attention in patients with attentional disturbance. However, neural substrates underlying the modafinil effects on attention are not fully understood.
We employed a functional magnetic resonance imaging (fMRI) study with the attention network test (ANT) task in healthy adults and examined which networks of attention are mainly affected by modafinil and which neural substrates are responsible for the drug effects.
We used a randomized placebo-controlled within-subjects cross-over design. Twenty-three healthy adults participated in two series of an fMRI study, taking either a placebo or modafinil. The participants performed the ANT task, which is designed to measure three distinct attentional networks, alerting, orienting, and executive control, during the fMRI scanning. The effects of modafinil on behavioral performance and regional brain activity were analyzed.
We found that modafinil enhanced alerting performance and showed greater alerting network activity in the left middle and inferior occipital gyri as compared with the placebo. The brain activations in the occipital regions were positively correlated with alerting performance.
Modafinil enhanced alerting performance and increased activation in the occipital lobe in the alerting network possibly relevant to noradrenergic activity during the ANT task. The present study may provide a rationale for the treatment of patients with distinct symptoms of impaired attention.

DOI： 10.1007/s00213-017-4614-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.dadm.2017.08.002

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Sixteen healthy volunteers were enrolled and divided into four groups according to the single administration of 10 mg or 20 mg escitalopram, 50 mg sertraline, or 20 mg paroxetine. Four positron emission tomography scans with [C-11]DASB were performed on each subject, the first prior to taking the drug, followed by the others at 4, 24, and 48 h after. Serotonin transporter occupancies of the drugs at each time point were calculated. All drugs showed maximum occupancy at 4 h after dosing and then decreasing occupancies with time. Escitalopram and sertraline showed high occupancies of 69.1-77.9% at 4 h, remaining at 52.8-57.8% after 48 h. On the other hand, paroxetine showed relatively low occupancy of 44.6%, then decreasing to 10.3% at 48 h. Escitalopram (both 10 mg and 20 mg) and sertraline (50 mg) showed high and sustained occupancy. Paroxetine (20 mg) showed relatively low and rapidly decreasing occupancy, possibly due to the low plasma concentration by single dosing schedule. Applying the reported concentration of multiple dosing, 20 mg paroxetine will induce over 80% occupancy. The present study suggested that these drugs and doses would be sufficient for the treatment of depression. (C) 2016 Published by Elsevier Ireland Ltd.

DOI： 10.1016/j.pscychresns.2016.03.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

BackgroundWe examined patients with mild cognitive impairment (MCI) with a history of geriatric depression (GD) and healthy controls (HC) to evaluate the effect of beta-amyloid (A) pathology on the pathology of GD by using [F-18]florbetapir PET.
MethodsThirty-three elderly patients (76.74.2years) and 22 healthy controls (HC; 72.04.5years, average +/- SD) were examined by [F-18]florbetapir positron emission tomography (PET) to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI to determine the degree of atrophy, by Mini-Mental State Examination for cognitive functions, and by Geriatric Depression Scale for the severity of depression, and by Clinical Dementia Rating for activity of daily living (ADL). The cut-off value of 1.08 for SUVR was defined as A-positive.
ResultsOf the patients and HC, 39.4% and 27.3%, respectively, were beta-amyloid-positive. The onset age of GD was significantly correlated with SUVR (r=0.44, p&lt;0.01). Compared to patients without A (GD-A), patients with A (GD+A) did not differ in terms of age, cognitive function, severity of depression and ADL, and brain atrophy. GD+A had significantly older average +/- SD age at onset of GD (73.6 +/- 7.1 versus 58.7 +/- 17.8, p&lt;0.01) and significantly shorter average +/- SD time between onset of GD and PET scan day (3.1 +/- 5.2years versus 18.1 +/- 18.6years, p&lt;0.001) than GD-A.
ConclusionsOur results showed that the rate of A positivity was higher in late-onset GD and that onset-age was associated with SUVR, suggesting that the later the onset of GD, the more A pathology affected its onset. Copyright (c) 2014 John Wiley & Sons, Ltd.

DOI： 10.1002/gps.4215

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

ObjectiveWe compared amyloid positron emission tomography (PET) and magnetic resonance imaging (MRI) in subjects clinically diagnosed with Alzheimer's disease (AD), mild cognitive impairment (MCI), and older healthy controls (OHC) in order to test how these imaging biomarkers represent cognitive decline in AD.
MethodsFifteen OHC, 19 patients with MCI, and 19 patients with AD were examined by [F-18]florbetapir PET to quantify the standard uptake value ratio (SUVR) as the degree of amyloid accumulation, by MRI and the voxel-based specific regional analysis system for AD to calculate z-score as the degree of entorhinal cortex atrophy, and by mini-mental state examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive componentJapanese version (ADAS-Jcog) for cognitive functions.
ResultsBoth cutoff values for measuring AD-like levels of amyloid (1.099 for SUVR) and entorhinal cortex atrophy (1.60 for z-score) were well differentially diagnosed and clinically defined AD from OHC (84.2% for SUVR and 86.7% for z-score). Subgroup analysis based on beta-amyloid positivity revealed that z-score significantly correlated with MMSE (r=-0.626, p&lt;0.01) and ADAS-Jcog (r=0.691, p&lt;0.01) only among subjects with beta-amyloid.
ConclusionsThis is the first study to compare [F-18]florbetapir PET and MRI voxel-based analysis of entorhinal cortex atrophy for AD. Both [F-18]florbetapir PET and MRI detected changes in AD compared with OHC. Considering that entorhinal cortex atrophy correlated well with cognitive decline only among subjects with beta-amyloid, [F-18]florbetapir PET makes it possible to detect AD pathology in the early stage, whereas MRI morphometry for subjects with beta-amyloid provides a good biomarker to assess the severity of AD in the later stage. Copyright (c) 2014 John Wiley & Sons, Ltd.

DOI： 10.1002/gps.4173

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FRONTIERS RESEARCH FOUNDATION  

Recent neuroimaging studies have demonstrated that Contactin-associated protein-like2 (CNTNAP2) polymorphisms affect left-hemispheric function of language processing in healthy individuals, but no study has investigated the influence of these polymorphisms on right-hemispheric function involved in human voice perception. Further, although recent reports suggest that determination of handedness is influenced by genetic effect, the interaction effect between handedness and CNTNAP2 polymorphisms for brain activity in human voice perception and language processing has not been revealed. We aimed to investigate the interaction effect of handedness and CNTNAP2 polymorphisms in respect to brain function for human voice perception and language processing in healthy individuals. Brain function of 108 healthy volunteers (74 right-handed and 34 non-right-handed) was examined while they were passively listening to reverse sentences (rSEN), identifiable non-vocal sounds (SND), and sentences (SEN). Full factorial design analysis was calculated by using three factors: (1) rs7794745 (A/A or A/T), (2) rs2710102 [G/G or A carrier (A/G and A/A)], and (3) voice-specific response (rSEN or SND). The main effect of rs7794745 (A/A or A/T) was significantly revealed at the right middle frontal gyrus (MFG) and bilateral superior temporal gyrus (STG). This result suggests that rs7794745 genotype affects voice-specific brain function. Furthermore, interaction effect was significantly observed among MFG-STG activations by human voice perception, rs7794745 (A/A or A/T), and handedness. These results suggest that CNTNAP2 polymorphisms could be one of the important factors in the neural development related to vocal communication and language processing in both right-handed and non-right-handed healthy individuals.

DOI： 10.3389/fnbeh.2015.00087

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

Objective: To report a case of Alzheimer's disease (AD) following mild traumatic brain injury (TBI).
Method: Case report.
Results: We report the time course of AD following mild TBI with evidence of AD pathology. A patient complained of minor memory disturbance 6 months after TBI and was diagnosed with mild cognitive impairment 1.5 years after TBI, and she was finally diagnosed as probable AD 4 years after TBI. Amyloid PET revealed brain accumulation of beta-amyloid at a pathological AD level.
Conclusion: Our case well illustrated how TBI can accelerate the AD process. Clinicians should carefully follow up patients with persistent cognitive impairment after TBI. (C) 2015 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.genhosppsych.2014.09.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

The nucleus accumbens (NAc) works as a key brain structure of the reward system, in which reward-related neural activity is well correlated with dopamine release from mesolimbic dopaminergic neurons.
Since modafinil can modulate dopaminergic transmission through re-uptake inhibition of dopamine, we investigated whether modafinil affects the reward-related brain activity in the NAc in healthy subjects.
Twenty healthy participants underwent two series of functional magnetic resonance imaging while performing monetary incentive delay task in which they were cued to anticipate and respond to a rapidly presented target to gain or avoid losing varying amounts of money, under modafinil or placebo condition. Blood oxygenation-level dependent (BOLD) activation signals during gain and loss anticipations were analyzed in the NAc as an a priori region of interest as well as the whole brain.
Modafinil significantly changed subjective feelings toward positive ones. The activation of BOLD signals was observed during gain anticipation under the placebo and modafinil conditions in the left and bilateral NAc, respectively. The modafinil condition showed significantly higher BOLD signal change at the highest gain (+Ayen500) cue compared to the placebo condition.
The present study showed that modafinil affects reward processing in the NAc in healthy subjects through enhancing more positive anticipation, and it may provide a basis for the use of this drug for treating anhedonia observed in psychiatric disorders.

DOI： 10.1007/s00213-014-3499-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Tramadol is used for the treatment of pain, and it is generally believed to activate the -opioid receptor and inhibit serotonin (5-HT) and norepinephrine (NE) transporters. Recent findings from animal experiments suggest that 5-HT reuptake inhibition in brain is related to pain reduction. However, there has been no report of 5-HT transporter (5-HTT) occupancy by tramadol at clinical doses in humans. In the present study, we investigated 5-HTT occupancy by tramadol in five subjects receiving various doses of tramadol by using positron emission tomography (PET) scanning with the radioligand [C-11]DASB. Our data showed that mean 5-HTT occupancies in the thalamus by single doses of tramadol were 34.7% at 50mg and 50.2% at 100mg. The estimated median effective dose (ED50) of tramadol was 98.1mg, and the plasma concentration was 0.33g/ml 2h after its administration; 5-HTT occupancy by tramadol was dose-dependent. We estimated 5-HTT occupancy at 78.7% upon taking an upper limit dose (400mg) of tramadol. The results of the present study support the finding that 5-HTT inhibition is involved in the mechanism underlying the analgesic effect of tramadol in humans, and a clinical dose of tramadol sufficiently inhibits 5-HTT reuptake; this inhibition is similar to that shown by selective serotonin reuptake inhibitors (SSRIs).

DOI： 10.1017/S1461145713001764

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Mazindol, an appetite suppressant, inhibits the reuptake of dopamine in the synaptic cleft. It has been considered that mazindol might enhance dopamine transmission in the human brain. However, there has been no study that investigated the extracellular dopamine concentration in vivo.
Using positron emission tomography (PET), we aimed to measure the effect of mazindol on the extracellular dopamine concentration and to evaluate how mazindol affects the dopamine system in the healthy human brain.
Eleven healthy individuals (six males, five females, age 30.9 +/- 4.9 years) were enrolled in this study. Each participant was scanned with [C-11]raclopride on 1 day without any medicine as baseline condition, and on another day with mazindol as drug condition. In the drug condition, participants took mazindol 0.5 mg (N = 5) or 1.5 mg (N = 6) 2 h before the PET scan. Plasma concentrations of mazindol were measured before the injection of [C-11]raclopride, and urine concentrations of mazindol were measured after the scan.
After taking mazindol, the calculated decrease in binding potential (Delta BP) in the striatum was 1.74 % for 0.5 mg and 8.14 for 1.5 mg, and the correlation with the blood concentration of mazindol was significant (P = 0.0016, R (2) = 0.69). Delta BP was not significantly correlated with the urine concentration of mazindol (P = 0.84, R (2) = 0.005).
Mazindol increased the extracellular concentration of dopamine in the human brain, and its effect was dose dependent. A single administration of mazindol, even at usual dosage, elevated dopamine concentration similarly to other addictive drugs, suggesting that the risk of dependence may increase with the mazindol dose.

DOI： 10.1007/s00213-013-3392-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1017/S1461145713001612

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：INFORMA HEALTHCARE  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12149-013-0798-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Norepinephrine transporter (NET) plays important roles in the treatment of various neuropsychiatric disorders, such as depression and attention deficit hyperactivity disorder (ADHD). Nortriptyline is a NET-selective tricyclic antidepressant (TCAs) that has been widely used for the treatment of depression. Previous positron emission tomography (PET) studies have reported over 80% serotonin transporter occupancy with clinical doses of selective serotonin reuptake inhibitors (SSRIs), but there has been no report of NET occupancy in patients treated with relatively NET-selective antidepressants. In the present study, we used PET and (S,S)-[18¹⁸F]FMeNER-D₂ to investigate NET occupancies in the thalamus in 10 patients with major depressive disorder taking various doses of nortriptyline, who were considered to be responders to the treatment. Reference data for the calculation of occupancy were derived from age-matched healthy controls. The result showed approximately 50-70% NET occupancies in the brain as a result of the administration of 75-200 mg/d of nortriptyline. The estimated effective dose (ED₅₀) and concentration (EC₅₀) required to induce 50% occupancy was 65.9 mg/d a

DOI： 10.1017/S1461145713001521

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1017/S1461145713001521

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記述言語：英語   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

DOI： 10.1272/jnms.81.2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

The descriptive term behavioral and psychological symptoms of dementia (BPSD) is used to cover a range of noncognitive disturbances including anxiety, depression, irritability, aggression, agitation, eating disorders, and inappropriate social or sexual behaviors. Behavioral and psychological symptoms of dementia are seen in about 90% of patients with dementia. We aimed to compare the efficacy and tolerability of risperidone, yokukansan, and fluvoxamine used for BPSD in elderly patients with dementia. Ninety inpatients with dementia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria were investigated in Sato Hospital, Koutokukai. We conducted an 8-week, rater-blinded, randomized trial, administering flexibly dosed risperidone, yokukansan, or fluvoxamine. Primary outcome measures were Neuropsychiatric Inventory in Nursing Home Version total score and its items. Secondary outcome measures were cognitive function measured by Mini-Mental State Examination and daily life function measured by Functional Independence Measure (FIM). Neurological adverse effects were measured by the Drug-Induced Extra-Pyramidal Symptoms Scale. At the end of the study, we analyzed 76 patients (92.7%). Mean Neuropsychiatric Inventory in Nursing Home Version total score decreased in all 3 drug groups, with no significant between-group differences. Mini-Mental State Examination and Functional Independence Measure scores did not change significantly. Drug-Induced Extra-Pyramidal Symptoms Scale scores did not change in the yokukansan and fluvoxamine groups, but increased significantly in the risperidone group. Risperidone, yokukansan, and fluvoxamine were equally effective in the treatment of BPSD in elderly patients. However, yokukansan or fluvoxamine for BPSD showed a more favorable profile in tolerability compared with risperidone. This trial is registered at UMIN Clinical Trials Registry (identifier: UMIN000006146).

DOI： 10.1097/JCP.0b013e31829798d5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1017/S1461145712001678

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Antidepressants used for treatment of depression exert their efficacy by blocking reuptake at serotonin transporters (5-HTT) and/or norepinephrine transporters (NET). Recent studies suggest that serotonin and norepinephrine reuptake inhibitors that block both 5-HTT and NET have better tolerability than tricyclic antidepressants and may have higher efficacy compared to selective serotonin reuptake inhibitors. Previous positron emission tomography (PET) studies have reported &gt;80% 5-HTT occupancy with clinical doses of antidepressants, but there has been no report of NET occupancy in patients treated with antidepressants. In the present study, we investigated both 5-HTT and NET occupancies by PET using radioligands [C-11]DASB and (S,S)-[F-18]FMeNER-D-2, in six patients, each with major depressive disorder (MDD), using various doses of milnacipran. Our data show that mean 5-HTT occupancy in the thalamus was 33.0% at 50 mg, 38.6% at 100 mg, 60.0% at 150 mg and 61.5% at 200 mg. Mean NET occupancy in the thalamus was 25.3% at 25 mg, 40.0% at 100 mg, 47.3% at 125 mg and 49.9% at 200 mg. Estimated ED50 was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupancies were observed in a dose-dependent manner. Both 5-HTT and NET occupancies were about 40% by milnacipran at 100 mg, the dose most commonly administered to MDD patients.

DOI： 10.1017/S1461145712001009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Antidepressants used for treatment of depression exert their efficacy by blocking reuptake at serotonin transporters (5-HTT) and/or norepinephrine transporters (NET). Recent studies suggest that serotonin and norepinephrine reuptake inhibitors that block both 5-HTT and NET have better tolerability than tricyclic antidepressants and may have higher efficacy compared to selective serotonin reuptake inhibitors. Previous positron emission tomography (PET) studies have reported >80% 5-HTT occupancy with clinical doses of antidepressants, but there has been no report of NET occupancy in patients treated with antidepressants. In the present study, we investigated both 5-HTT and NET occupancies by PET using radioligands [(11)C]DASB and (S,S)-[(18)F]FMeNER-D(2), in six patients, each with major depressive disorder (MDD), using various doses of milnacipran. Our data show that mean 5-HTT occupancy in the thalamus was 33.0% at 50 mg, 38.6% at 100 mg, 60.0% at 150 mg and 61.5% at 200 mg. Mean NET occupancy in the thalamus was 25.3% at 25 mg, 40.0% at 100 mg, 47.3% at 125 mg and 49.9% at 200 mg. Estimated ED(50) was 122.5 mg with the dose for 5-HTT and 149.9 mg for NET. Both 5-HTT and NET occupancies were observed in a dose-dependent manner. Both 5-HTT and NET occupancies were about 40% by milnacipran at 100 mg, the dose most commonly administered to MDD patients.

DOI： 10.1017/S1461145712001009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Blonanserin is a novel antipsychotic with high affinities for dopamine D-2 and 5-HT2A receptors, and it was recently approved for the treatment of schizophrenia in Japan and Korea. Although double-blind clinical trials have demonstrated that blonanserin has equal efficacy to risperidone, and with a better profile especially with respect to prolactin elevation, its profile of in vivo receptor binding has not been investigated in patients with schizophrenia. Using positron emission tomography (PET), we measured striatal and extrastriatal dopamine D-2 receptor occupancy by blonanserin in 15 patients with schizophrenia treated with fixed doses of blonanserin (ie, 8, 16, and 24 mg/d) for at least 4 weeks before PET scans, and in 15 healthy volunteers. Two PET scans, 1 with [C-11]raclopride for the striatum and 1 with [C-11]FLB 457 for the temporal cortex and pituitary, were performed on the same day. Striatal dopamine D2 receptor occupancy by blonanserin was 60.8% (3.0%) [mean (SD)] at 8 mg, 73.4% (4.9%) at 16 mg, and 79.7% (2.3%) at 24 mg. The brain/plasma concentration ratio calculated from D-2 receptor occupancy in the temporal cortex and pituitary was 3.38, indicating good blood-brain barrier permeability. This was the first study to show clinical daily dose amounts of blonanserin occupying dopamine D-2 receptors in patients with schizophrenia. The clinical implications obtained in this study were the optimal therapeutic dose range of 12.9 to 22.1 mg/d of blonanserin required for 70% to 80% dopamine D-2 receptor occupancy in the striatum, and the good blood-brain barrier permeability that suggested a relatively lower risk of hyperprolactinemia.

DOI： 10.1097/JCP.0b013e3182825bce

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim The aim of this study was to investigate the influences of menopause on brain morphological changes in schizophrenia using magnetic resonance imaging (MRI). Methods Forty female schizophrenia patients, 20 premenopausal and 20 postmenopausal, and 50 female controls underwent cerebral MRI. Optimized voxel-based morphometry was performed with Statistical Parametric Mapping version 5. Results Compared with controls, regional gray matter reductions in schizophrenia patients were observed in the insula, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, and thalamus. Direct comparison between the patient groups showed that the gray matter of postmenopausal patients was significantly smaller when compared with premenopausal patients in the left middle frontal gyrus, and no region had significantly lower gray matter volume in premenopausal patients relative to postmenopausal patients. Significant negative correlation between gray matter volume and the interval after menopause was found in the right superior frontal gyrus in the postmenopause patient group. Conclusion Differential morphological alterations between postmenopausal and premenopausal schizophrenia patients were observed, suggesting that the female hormone plays a protective role against schizophrenia. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

DOI： 10.1111/pcn.12003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Patients with schizophrenia and their families have suffered greatly from stigmatizing effects. Although many efforts have been made to eradicate both prejudice and stigma, they still prevail even among medical professionals, and little is known about how contact with schizophrenia patients affects their attitudes towards schizophrenia.
Methods: We assessed the impact of the renaming of the Japanese term for schizophrenia on clinical residents and also evaluated the influence of contact with schizophrenia patients on attitudes toward schizophrenia by comparing the attitudes toward schizophrenia before and after a one-month clinical training period in psychiatry. Fifty-one clinical residents participated. Their attitudes toward schizophrenia were assessed twice, before and one month after clinical training in psychiatry using the Implicit Association Test (IAT) as well as Link's devaluation-discrimination scale.
Results: The old term for schizophrenia, "Seishin-Bunretsu-Byo", was more congruent with criminal than the new term for schizophrenia, "Togo-Shitcho-Sho", before clinical training. However, quite opposite to our expectation, after clinical training the new term had become even more congruent with criminal than the old term. There was no significant correlation between Link's scale and IAT effect.
Conclusions: Renaming the Japanese term for schizophrenia still reduced the negative images of schizophrenia among clinical residents. However, contact with schizophrenia patients unexpectedly changed clinical residents' attitudes towards schizophrenia negatively. Our results might contribute to an understanding of the formation of negative attitudes about schizophrenia and assist in developing appropriate clinical training in psychiatry that could reduce prejudice and stigma concerning schizophrenia.

DOI： 10.1186/1471-244X-12-205

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記述言語：英語   出版者・発行元：MEDICAL ASSOC NIPPON MEDICAL SCH  

DOI： 10.1272/jnms.79.318

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記述言語：英語   出版者・発行元：SPRINGER TOKYO  

DOI： 10.1007/s10384-011-0058-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Inflammatory/immunological process and glial contribution are suggested in the pathophysiology of schizophrenia. We investigated peripheral benzodiazepine receptors in brains of patients with chronic schizophrenia, which were reported to be located on mitochondria of glial cells, using [C-11]DAA1106 with positron emission tomography. Fourteen patients and 14 age- and sex-matched normal controls participated in this study. PET data were analysed by two-tissue compartment model with metabolite-corrected plasma input. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale. There was no significant difference between [C-11]DAA1106 binding of the cortical regions of normal controls and patients with schizophrenia, whereas the patients showed a positive correlation between cortical [C-11]DAA1106 binding and positive symptom scores. There was also a positive correlation between [C-11]DAA1106 binding and duration of illness. Although the correlations need to be interpreted very cautiously, involvement of glial reaction process in the pathophysiology of positive symptoms or progressive change of schizophrenia might be suggested.

DOI： 10.1017/S1461145710000313

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1272/jnms.77.188

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aim:
Somatoform pain disorder is characterized by persistent and chronic pain at one or more sites without an associated general medical condition and in which psychological factors are thought to play a role. This study aimed to investigate the pathological features of somatoform pain disorder localized to the oral region by single photon emission computed tomography (SPECT).
Methods:
Ten patients (nine females and one male; average age 55.0 +/- 14.4 years) having somatoform pain disorder with oral symptoms participated. SPECT was performed using N-isopropyl-4-[123I] iodoamphetamine intravenous injections, and regional cerebral blood flow (rCBF) was assessed by three-dimensional stereotactic surface projections. We also selected 12 healthy individuals (seven females and five males; average age 61.8 +/- 13.2 years) to act as controls.
Results:
Both the patient and control groups showed no atrophy or infarction on CT or magnetic resonance imaging. The patient group showed higher rCBF in the subcortical area, especially in the thalamus and cingulate gyri, than the control group. In contrast, the patient group showed lower rCBF in the bilateral frontal and occipital lobes as well as in the left temporal lobe.
Conclusions:
These results suggest that the biological process involved in somatoform pain disorder of the oral region is characterized by changes in limbic and cortical functions. The finding that somatoform pain disorder with oral symptoms is associated with brain functional changes will help to develop treatment regimes for this disorder and clarify the underlying pathology.

DOI： 10.1111/j.1440-1819.2010.02119.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Background and aim In Alzheimer's disease (AD), regional cerebral blood flow (rCBF) in the posterior cingulate gyrus and precuneus has been reported to decrease even at a very early stage. We performed a multicentre SPECT study to evaluate the discrimination ability of an easy Z-score imaging system (eZIS) by detecting an rCBF decrease in this area with a common normal database between very early AD patients at the stage of mild cognitive impairment and age-matched healthy volunteers.
Methods Brain perfusion SPECT images of 40 Alzheimer's disease patients and 40 healthy volunteers were acquired from four gamma camera systems in different institutions. Systematic differences of SPECT images between different gamma cameras were corrected using conversion maps calculated from the SPECT images of the same brain phantom. Ten observers with various degrees of expertise graded eZIS results for receiver operating characteristic (ROC) curves. ROC curves for a positive Z-score in the volume of interest (VOI) of the posterior cingulate gyrus and precuneus were also analysed.
Results An area under the ROC curve value (A(Z)) for ten observers showed the highest value of 0.866 on average with the smallest standard deviation of 0.027 in the condition of the lower threshold of a Z-score map of 2 without superimposition of VOI. Automated analysis of a Z-score in the VOI showed an A(Z) value of 0.895.
Conclusion Since the degree of expertise of the observers with respect to reading eZIS did not influence the performance and an eZIS can use a common normal database by converting site-specific SPECT data to the core data, the eZIS was considered to be very useful for diagnosing early AD in routine studies in many institutions.

DOI： 10.1097/MNM.0b013e328013eb8b

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

従来からアルツハイマー病(AD)には臨床症候的、生化学的、病理学的、遺伝学的多様性が存在すると報告されている。今回、筆者らはADの多様性を解明する端緒として発症年齢に着目し、早発性アルツハイマー病(early onset Alzheimer's disease;EOAD)と晩発性アルツハイマー病(late onset Alzheimer's disease;LOAD)の局所脳血流の低下パターンの差異について検討した。NINCDS-ADRDAの診断基準を満たすprobable AD 114例をEOAD27例とLOAD87例の2群に分け、[99m Tc]ECD-SPECTを撮像し、解剖学的標準化と平滑化を加えたうえ、SPM for Windowsを用いてunpaired t-testを行った。その結果、EOADはLOADに対して側頭頭頂連合野において血流低下が高度であったのに対し、LOADではEOADに対して前部帯状回や後頭連合野において有意な脳血流低下が認められた。これらは臨床症候的・病理学的変性の分布・程度などADの多様性を反映した結果と考えられた。(著者抄録)

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2007&ichushi_jid=J02464&link_issn=&doc_id=20070202230010&doc_link_id=%2Faj2rsizd%2F2007%2F001801%2F011%2F0061-0067%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faj2rsizd%2F2007%2F001801%2F011%2F0061-0067%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background: Depression has a significant impact on poststroke recovery and mortality. There are a proportion of Patients with poststroke depression (PSD) who do not respond to antidepressants. Repetitive Transcranial Magnetic Stimulation (rTMS) might be a safe and effective alternative in these refractory cases.
Methods: We conducted a randomized, parallel, double-blind study of active versus sham left prefrontal rTMS in patients with refractory PSD. After discontinuing antidepressants, patients were randomly assigned to receive 10 sessions of active (10 Hz, 110% of the motor threshold, 20 trains of 5 seconds duration) or sham left prefrontal rTMS. Efficacy measures included HAM-D scores, response and remission rates. Patients completed a neuropsychological battery at baseline and after completing the protocol.
Results: When compared with sham stimulation, 10 sessions of active rTMS of the left dorsolateral prefrontal cortex were associated with a significant reduction of depressive symptoms. This reduction was not influenced by patient's age, type or location of stroke, volume of left frontal leukoaraiosis or by the distance of the stimulating coil to the prefrontal cortex. However, there was a significant positive correlation between the percentage of reduction of Ham-D scores and frontal gray and white matter volumes. There were no significant changes in cognitive functioning between the active and the sham stimulation groups. In addition, there were few and mild adverse effects that were equally distributed among groups.
Conclusions: Taken together, these preliminary,findings suggest that rTMS may be an effective and safe treatment alternative for patients with refractory depression and stroke.

DOI： 10.1016/j.biopsych.2003.08.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER MEDICAL ASSOC  

Backgroud: Major depression is a frequent psychiatric complication among patients with traumatic brain injury (TBI). To our knowledge, however, the clinical correlates of major depression have not been extensively studied.
Objective: To determine the clinical, neuropsychological, and structural neuroimaging correlates of major depression occurring after TBI.
Design: Prospective, case-controlled, surveillance study conducted during the first year after the traumatic episode occurred.
Settings: University hospital level I trauma center and a specialized rehabilitation unit.
Methods: The study group consisted of 91 patients with TBI. In addition, 27 patients with multiple traumas but without evidence of central nervous system injury constituted the control group. The patients' conditions were evaluated at baseline and at 3, 6, and 12 months after the traumatic episode. Psychiatric diagnosis was made using a structured clinical interview and DSM-IV criteria. Neuropsychological testing and quantitative magnetic resonance imaging were performed at the 3-month follow-up visit.
Results: Major depressive disorder was observed in 30 (33%) of 91 patients during the first year after sustaining a TBI. Major depressive disorder was significantly more frequent among patients with TBI than among the controls. Patients with TBI who had major depression were more likely to have a personal history of mood and anxiety disorders than patients who did not have major depression. Patients with major depression exhibited comorbid anxiety (76.7%) and aggressive behavior (56.7%). Patients with major depression had significantly greater impairment in executive functions than their nondepressed counterparts. Major depression was also associated with poorer social functioning at the 6-and 12-month follow-up, as well as significantly reduced left prefrontal gray matter volumes, particularly in the ventrolateral and dorsolateral regions.
Conclusions: Major depression is a frequent complication of TBI that hinders a patient's recovery. It is associated with executive dysfunction, negative affect, and prominent anxiety symptoms. The neuropathological changes produced by TBI may lead to deactivation of lateral and dorsal prefrontal cortices and increased activation of ventral limbic and paralimbic structures including the amygdala.

DOI： 10.1001/archpsyc.61.1.42

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DOI： 10.1176/jnp.16.4.426

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: As the prevalence of white matter hyperintensities detected on T 2 weighted MRI scans in patients with late-onset depression is higher than that in nondepressed patients, the concept of "vascular depression" (VDep) was introduced in 1997. However, the pathology of vascular depression has not been clarified. This study examined the differences in functional imaging between vascular and non-vascular depression (non-VDep). Methods: We utilized 123I-IMP single photon emission computed tomography (SPECT) to compare regional cerebral blood flows (rCBF) between 9 patients with VDep (Krishnan criteria) and 11 age- and sex-matched patients with non-VDep in both depressed and remitted states. Results: In both VDep and non-VDep patients, mean rCBF increased significantly as depression improved, partially aided by changes in left anterior temporal blood flow. In addition, compared to non-VDep patients, the left anterior frontal rCBF for VDep patients was significantly lower in both depressed and remitted states. Conclusions: Left anterior temporal rCBF therefore appears to represent a state marker that increases as symptoms associated with late-onset depression improve. regardless of vascular changes. Furthermore, in VDep patients, left anterior frontal rCBF was low in both states compared to non-VDep patients, and might not only represent a trait marker, but also correlated with the duration of disease and likelihood of recurrence and relapse.

DOI： 10.1272/jnms.70.321

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PSYCHIATRIC PRESS, INC  

The existence of anxiety disorders plays an important role in the prognosis and associated impairment among patients with poststroke depression. The authors examined the efficacy of nortriptyline treatment for patients with comorbid generalized anxiety disorder (GAD) and depression after stroke. Methods: Data from three studies were merged to provide 27 patients with comorbid GAD and depression, who participated in double-blind treatment studies comparing nortriptyline (N=13) and placebo (N=14). Severity of anxiety was measured with the Hamilton Rating Scale for Anxiety (Ham A), and severity of depression was measured with the Hamilton Rating Scale for Depression (Ham-D). Activities of daily living were assessed by use of the Johns Hopkins Functioning Inventory (JHFI). Results: There were no significant differences between the nortriptyline and placebo groups in demographic characteristics, stroke type, and neurological findings. Patients receiving nortriptyline treatment showed significantly greater improvement on the Ham A, Ham-D, and JHFI than patients receiving placebo. The anxiety symptoms showed earlier improvement than depressive symptoms inpatients treated with nortriptyline. Conclusions: These findings suggest that poststroke GAD comorbid with poststroke depression may be effectively treated with nortriptyline, and data indicate the need for a trial specifically designed to examine treatment of anxiety disorder.

DOI： 10.1097/00019442-200305000-00009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：American Psychiatric Publishing Inc.  

The authors assessed aggressive behavior in 89 patients with traumatic brain injury (TBI) and 26 patients with multiple trauma but without TBI using a quantitative scale (the Overt Aggression Scale) and examined its clinical correlates. Aggressive behavior was found in 33.7% of TBI patients and 11.5% of patients without TBI during the first 6 months after injury. Aggressive behavior was significantly associated with the presence of major depression, frontal lobe lesions, poor premorbid social functioning, and a history of alcohol and substance abuse. Interventions aimed at treatment of depression and substance abuse and enhancing social support may help reduce the severity of this disruptive behavior.

DOI： 10.1176/jnp.15.2.155

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PSYCHIATRIC PRESS, INC  

Objective: Authors compared poststroke major (n = 17) or minor (n = 28) depression diagnosed 3 to 6 months poststroke with major (n = 16) or minor (n = 22) depression diagnosed at 12 to 24 months to identify changes in the phenomenological characteristics of poststroke depression over time. Methods: Depressive symptoms were divided into vegetative, psychological symptoms, and melancholic features elicited by the Present State Exam (PSE). Patients were also examined for severity of depression, social impairment, and neurological findings. Results: Early-onset poststroke major depression was associated with a higher frequency of vegetative symptoms and larger lesion volume than late-onset major depression. Similarly, early-onset minor depression was associated with poorer social functioning and a higher frequency of melancholic, vegetative, and psychological symptoms than late-onset minor depression. Conclusion: These findings suggest that the phenomenological characteristics of both major and minor poststroke depression change over time and that both early-onset major and minor poststroke depression may result from similar etiological mechanisms provoked by brain injury.

DOI： 10.1097/00019442-200209000-00011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER PSYCHIATRIC PRESS, INC  

Several studies have reported an association between cognitive impairment and major depression following stroke but failed to find a similar association among patients with traumatic brain injury (TBI). This study examined the hypothesis that age differences between stroke and TBI patients would account for the differences in the effect of major depression on cognitive function. We examined subjects' cognitive function using the Mini-Mental State Examination and compared findings among patients with stroke or TBI. Results indicated that stroke patients with major depression (N = 73) were significantly older and more cognitively impaired than similar TBI patients (N = 35), even after matching patients for lesion volume and years of education. After matching for age, however, there was no association of major depression with cognitive impairment in this relatively young stroke population. These findings support the hypothesis that age, presumably related to physiological response to brain injury accounts for differences in the effect of major depression on cognitive function between stroke and TBI patients.

DOI： 10.1176/appi.psy.43.4.295

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担当区分：筆頭著者   記述言語：英語  

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：ELSEVIER SCIENCE BV  

Background. Depressive episodes are likely to be associated with reversible brain states. These can be examined with a variety of methods, such as ERP, SPECT or PET. Previous studies have reported that P300 amplitudes reduced in the depressed phase and recovered in the remitted phase. There have been some reports that anterior cingulate blood flow reduced in the depressed phase and recovered in the remitted phase.
Method. Five right-handed depressed patients were studied in both the depressed and remitted phases by using I-123-IMP SPECT and ERP.
Results. There were no significant differences in regional cerebral blood flows (rCBFs) between the depressed and remitted phases. Four of the five subjects showed parallel changes of rCBF in the anterior cingulate, frontal cortex and basal ganglia between the depressed and remitted phases. The changes of P300 amplitude at P4 between the depressed and remitted phases had positive correlation with those of rCBFs in the bilateral thalamus and right cingulate. The changes of P300 amplitude at Pt had negative correlation with those of rCBFs in the right frontal and left basal ganglia, In the anxious type, P300 amplitudes at Pt decreased and rCBFs in the frontal cortex and anterior cingulate increased. Conversely, in the retarded type, P300 amplitudes at Pt increased and rCBFs in the frontal cortex and anterior cingulate decreased.
Conclusion. Our findings of the parallel changes of rCBF in the anterior cingulate, frontal cortex and basal ganglia between the depressed and remitted phases indicates that these neuroanatomical circuits may be involved in depression. The anxious type may be different from the retarded type in the changes of rCBF between the depressed and remitted phases in the frontal cortex and anterior cingulate, and in the changes of P300 amplitudes.

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記述言語：日本語   出版者・発行元：アークメディア  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：BMJ PUBLISHING GROUP  

DOI： 10.1136/jnnp-2017-BNPA.80

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：BMJ PUBLISHING GROUP  

DOI： 10.1136/jnnp-2017-BNPA.55

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2016211678

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記述言語：日本語   出版者・発行元：科学評論社  

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その他リンク： http://search.jamas.or.jp/link/ui/2016057125

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記述言語：日本語   出版者・発行元：科学評論社  

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DOI： 10.1136/jnnp-2015-311750.64

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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統合失調症の脳形態変化における閉経の影響について、患者群を閉経患者と非閉経患者の2群に分けMRIを用いて調査した。最終月経からMRI撮像までの期間が12ヵ月以上である統合失調症女性患者20名と同時期が12ヵ月未満であり閉経患者群と年齢を一致させた統合失調症女性患者20名(平均41.8±9.0歳)を対象とした。分析の結果、非閉経患者群と比較し、閉経患者群において左中前頭回の灰白質に有意な体積減少を認めた。一方、非閉経患者群が閉経患者群と比較して有意に体積減少している部位は認められなかった。閉経患者20名において、閉経後経過年数と脳体積の相関を調べた結果、右上前頭回の灰白質体積と閉経後経過年数に負の相関が認められた。健常者が閉経する平均年齢は50から52歳の間であるとされるが、今回の閉経患者群においては、若年期に最終月経がきており、原因の一つに抗精神薬の副作用であることが考えられた。

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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記述言語：日本語   出版者・発行元：(公社)日本精神神経学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：JAPANESE PHARMACOLOGICAL SOC  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：SPRINGER  

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DOI： 10.1272/manms.7.224

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記述言語：日本語   出版者・発行元：日本臨床社  

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その他リンク： http://search.jamas.or.jp/link/ui/2012026226

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記述言語：日本語   出版者・発行元：(株)ワールドプランニング  

認知症患者の中核症状、周辺症状および日常生活動作能力の関係を明らかにするために、当院入院中の認知症患者58人を対象に向精神薬を使用せずに7日以上経過してから中核症状をMini-Mental State Examination(MMSE)で、周辺症状をNeuropsychiatric Inventory in Nursing Home Version(NPI-NH)で、日常生活動作能力をFunctional Independence Measure(FIM)でそれぞれ評価した。その結果、MMSEとNPI-NHで有意な負の相関(ρ=-0.508:p=0.000)、MMSEとFIMで有意な正の相関(ρ=0.550:p=0.000)、NPI-NHとFIMで有意な負の相関(ρ=-0.353:p=0.007)が得られた。中核症状が軽度な患者は周辺症状も軽度であり、さらに日常生活動作の水準が高いことが示された。(著者抄録)

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外傷後、健忘が遷延した48歳女性症例について検討した。注意や意識は保たれているが、短期記憶障害が顕著であった。CT・MRIに異常所見はみられなかった。作動性記憶課題の機能的磁気共鳴画像法(fMRI)を施行したところ、左下前頭回、両側海馬、左前頭葉極において、健常群よりも有意な賦活低下を認めた。COGNISTAT認知機能検査において、記銘力障害が確認された。器質性健忘症候群と考えられた。心理学的認知機能評価に加え、fMRI施行時の脳機能の変化を検証することが器質性精神疾患の補助診断に有用であることが示唆された。

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2011.07.754

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Positron Emission Tomography(PET)は標識化合物の種類により受容体、トランスポーター、合成能等のモノアミン神経系機能評価やアミロイド、P糖タンパクなどを計測できる。特異結合部位での受容体密度を反映するとされる結合能(BP)を指標にして「受容体占有率(%)=(服薬前BP-服薬後BP)/(服薬前BP)×100」を求めることで、抗精神病薬や抗うつ薬の薬効、至適用量、薬理学的特性、脳内動態の経時的変化、脳内移行性などの評価が行われている。これらの知見、特に受容体占有率に基づく至適用量設定は、我が国でも薬剤開発のPhase IやPhase II試験に利用されるようになっている。今後はマイクロドーズ臨床試験などへの利用も期待されている。本稿では、PETの臨床開発への利用と今後の可能性についてこれまでの知見を踏まえて述べたい。(著者抄録)

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：CAMBRIDGE UNIV PRESS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2009.09.1286

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記述言語：日本語   出版者・発行元：科学評論社  

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双極性障害では,モノアミン,前頭-線条-視床経路,細胞内情報伝達系の異常が推測され,これまでの画像研究結果もこれを支持しているが,個々の結果は一致しないことも多い.近年の画像診断技術の進歩が,脳内の変化のより詳細なin vivoでの評価を可能とした.陽電子放出断層撮影(PET)研究では,病相や治療の代謝への影響や,セロトニン受容体・ドーパミン受容体・トランスポーターのトレーサー開発により神経伝達系の研究が行われている.磁気共鳴イメージング(MRI)研究では,形態変化・神経化学物質の解析による細胞内情報伝達系やlithiumの神経保護作用・神経線維についての研究が行われている.近赤外線スペクトロスコピー(NIRS)研究では,まだ報告が少なくこれからの成果が期待される.脳画像研究を中心として臨床症状,薬理学研究,分子遺伝学研究などが結びつくことで,双極性障害の病態解明,鑑別診断,治療効果予測,新規治療法の開発などが今後期待される(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語  

[11C]FLB457を用いたPET検査により,抗精神病薬維持療法時の側頭皮質ドーパミンD2受容体占有率を明らかにした.抗精神病薬単剤で治療を受けている統合失調症患者10例を対象とした.側頭皮質におけるドーパミンD2受容体占有率は最小0%,最大84.3%で,平均59.1%であった.維持療法中の7例は,D2受容体占有率は最小30.8%,最大84.3%で,平均61.9%であった.維持療法中の7例中5例が70%以下の占有率であった.sulpirideについて,70〜80%をD2至適占有率として至適用量を推定すると,およそ400〜700mg/日となった.維持療法時では急性期と同様の高い占有率を必要としない可能性があり,さらなる検討が必要であることが示唆された

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記述言語：日本語  

Psychiatric disorders following traumatic brain injury (TBI) have negative influence on the recovery from TBI (e.g., they worsen the effect of rehabilitation, psychosocial function, activity of daily living, quality of life, relations with family members, etc.). Although psychiatric disorders are frequent complications of TBI (e.g., mood disorder 6&amp;sim;77%, anxiety disorder 11&amp;sim;70%, psychotic disorder 2&amp;sim;20%, and problematic behavior 11&amp;sim;90%), most of them are misdiagnosed and not treated adequately. Treatment of psychiatric disorder following TBI is not different from treatment of primary psychiatric disorder. TBI patients, however, are more sensitive to the side effects of medications, and therefore we should treat them by (1) starting low and going slow, (2) setting an adequate therapeutic trail with regard to dosage and duration of treatment, (3) frequent assessment during the treatment period, and (4) paying attention to adverse effects and drug interactions. Since psychiatric disorders may worsen the recovery process from TBI, successful treatment is especially important for TBI patients. It is essential for clinicians to be aware of any psychiatric disorders following TBI and to treat them properly.

DOI： 10.1272/manms.1.17

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

DOI： 10.1272/manms.1.17

CiNii Books

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記述言語：日本語   出版者・発行元：科学評論社  

CiNii Books

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記述言語：日本語   出版者・発行元：科学評論社  

辺縁系脳炎(LE)によりひき起こされた器質性精神障害に無痙攣性通電療法(m-ECT)が著効した症例(14歳女性)を報告した.患者は統合失調症を疑われた後にLEと診断され,脳炎治療後も続く緊張病様症状に対してm-ECTが効果的であった.精神疾患と判断することで重篤な身体症状,またはその徴候が見逃されることもあり,患者の生命予後を重視する際には除外されない身体疾患を積極的に疑い,診断を進めることが適切と考える.本症例のような経過・検査所見を示す症例に対しては,稀ではあるがARLE-MR(N)を含めLEの可能性を検討することは意義がある.また,脳炎罹患後に意識障害や身体症状が改善されて精神症状が残存する症例や,器質性精神障害としての緊張病様症状を呈する症例において,m-ECTは有効な治療法の一つと考えられた

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2005165922

記述言語：日本語  

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記述言語：日本語   出版者・発行元：アークメディア  

CiNii Books

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その他リンク： http://search.jamas.or.jp/link/ui/2005070226

記述言語：日本語   出版者・発行元：医学書院  

統合失調症急性期治療において非定型抗精神病薬であるリスペリドンに加え,クロナゼパムを使用し,症状軽快後にクロナゼパムを減量したところ,パーキンソン症候群を呈した症例(26歳女性)を報告した.クロナゼパムは統合失調症急性期治療において興奮,焦燥に対して有効な薬剤であり,抗精神病薬による錐体外路症状が比較的出現しやすい統合失調症初回エピソードにおいては錐体外路症状の予防という点でも有効である可能性がある.その一方で急性期治療の後クロナゼパムの減量を考える際には,減量によりパーキンソン症候群が発現する危険性を考慮する必用があると思われた

DOI： 10.11477/mf.1405100571

CiNii Books

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記述言語：日本語  

CiNii Books

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記述言語：日本語  

2003年1月〜10月に大学病院高度救命救急センターに自殺企図で搬送され未遂に終わった患者のうち,精神科医が関与した111例を対象に実態を調査し,特に対人関係の問題を自殺企図の動機とした未遂症例(38.4%)について検討した.その結果,IDC-10でF4カテゴリーに分類される症例が最も多かった.企図手段では,薬物・毒物によるものが最も多く,自殺企図の動機では,家族や恋人とのトラブルなどによる対人関係の問題を動機とするものが最も多かった.対人関係の問題を動機とする症例に着目すると,F4カテゴリーに分類されるものが57.1%を占め,そのほとんどがF43.2:適応障害と診断された.対人関係の問題などの些細な心因を動機とする衝動的な自殺企図の背景には,性格的な偏り,人格障害を伴っている可能性があったが,救命救急センターの短期間の入院経過では十分な情報が得られず,適応障害のみと診断された症例が多く含まれていた可能性がある

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記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：日本語   出版者・発行元：(一社)日本核医学会  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

口腔内異常感覚を訴える狭義のセネストパチー(CP)8例(A群)と,大鬱病を伴なう広義のCP5例(B群),大鬱病9例(C群)を対象に検討した.C群と比べA群では左右視床と右前部帯状回で有意に高い局所脳血流量(rCBF)を示し,B群では左視床で高いrCBFを示した.A,B群間にはrCBFの有意差を認める部位はなく,左右視床と右前部帯状回の機能変化がCP症状の出現に関与している可能性が示唆された.狭義及び広義のCPに認められた視床領域,特に左視床の所見はCP症状と密接に関連していると考えられたが,今後,正常対照群との検討が必要である

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

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記述言語：日本語  

高齢者虐待4例を報告した.被害者はADLは自立していたが家族に依存せざるを得ない生活状況にあった.虐待加害者の言動と態度により緊張感,恐怖感,うつ症状,身体症状の悪化を認めたが理解者の死去や不在のため相談できず,また,責任感の強い性格傾向と抑圧された感情から虐待を報告できなかった.加害者は同居の主介護者で身体的虐待2例の加害者は精神的脆弱性を有していた.弱者・依存者となった高齢者に対し,過去から蓄積された緊密関係,老親子間の未解決の葛藤と歪んだ相関関係から,蔑視意識,嫌悪感,差別意識が強まり,家族内において高齢者の存在は空虚化・希薄化した.このため加害者の虐待認識の欠如と家族成員の虐待に対する問題意識の欠如から,家庭内に加害者は拡大していき,結果として虐待の発見が困難になったと考えられた.以上より,虐待の原因として介護ストレス以外の要因が考えられた

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記述言語：日本語  

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