Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Language：English   Publishing type：Research paper (scientific journal)  

Neurodegenerative diseases can manifest as psychiatric symptoms in the prodromal phase, before the onset of core symptoms such as neurological, motor, and cognitive symptoms. Positron emission tomography (PET) has made it possible to detect the pathology of some neurodegenerative diseases in vivo. Many studies have indicated that depression is a preclinical symptom of neurodegenerative diseases. Approximately 10% of non-demented participants with depression developed Alzheimer's disease (AD) during the follow-up period. The prevalence of depression/dysphoria was 42.9% in the preclinical stage of dementia with Lewy bodies. Depression was present in 33.3% of patients with preclinical behavioral-variant frontotemporal lobar degeneration. Approximately 10% of patients had a history of depression at the time of diagnosis with Parkinson's disease. PET studies have revealed the pathology of neurodegenerative diseases in some cases of geriatric depression. Increased brain amyloid-beta deposition in late-onset depression is a possible reflection of prodromal AD. The severity of depression was significantly associated with greater inferior temporal tau and marginally associated with greater entorhinal cortex tau, and depression was associated with significantly greater mean cortical tau deposition. Thus, the presence of depression as a preclinical/prodromal symptom of neurodegenerative diseases has been demonstrated by epidemiological, pathological, and biomarker studies. A growing body of evidence from PET studies indicates that some cases of geriatric depression have pathologies of degenerative neurological disease. In the future, it is expected that PET will be utilized as an imaging biomarker for diagnosis of psychiatric disorders and development of new therapeutic agents.

DOI： 10.1272/jnms.JNMS.2023_90-216

PubMed

researchmap

Language：Japanese   Publisher：日本医科大学医学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Rationale

Since ephedrine has a dopamine transporter (DAT) inhibitory effect similar to amphetamine, dl-methylephedrine, a derivative of ephedrine, is considered to have the characteristics of a central nervous system stimulant due to the DAT inhibitory effect. For example, the World Anti-Doping Agency categorizes dl-methylephedrine as a stimulant in the prohibited list for competitions. Assuming to have the same effect as ephedrine, the urinary concentration of dl-methylephedrine is regulated below 10 μg/mL, as is ephedrine. However, the extent to which dl-methylephedrine affects brain function is not yet fully understood.

Objectives

The purpose of this study was to evaluate DAT occupancy by a single oral administration of a daily dose of dl-methylephedrine using positron emission tomography (PET) with [¹⁸F]FE-PE2I to characterize its stimulatory effect on the central nervous system.

Methods

Nine healthy male volunteers were enrolled in the study. The experiments were designed as a placebo-controlled randomized double-blind crossover comparative study. After the first PET scan in a drug-free state, the second and third PET scans were performed with randomized dosing at 60 mg of dl-methylephedrine or placebo. The plasma and urine concentrations of dl-methylephedrine were measured just before and after the PET scans, respectively.

Results

Mean urine and plasma concentrations of dl-methylephedrine were 13.9 μg/mL and 215.2 ng/mL, respectively. Mean DAT occupancy in the caudate was 4.4% for dl-methylephedrine and 1.2% for placebo. Mean DAT occupancy in the putamen was 3.6% for dl-methylephedrine and 0.5% for placebo. There was no significant difference of DAT occupancies between the groups.

Conclusion

In this study, the urinary concentration of dl-methylephedrine (13.9 μg/mL) was higher than the prohibited reference value (10.0 μg/mL), and there was no significant difference in DAT occupancy between dl-methylephedrine and placebo. These findings suggest that a clinical daily dose of dl-methylephedrine may exceed the doping regulation value according to urine concentration; however, it was considered that at least the central excitatory effect mediated by DAT inhibition was not observed at the daily dose of dl-methylephedrine.

DOI： 10.3389/fpsyt.2022.799319

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

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

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

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

PubMed

researchmap

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：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 < 0.0001) and 0.70 ng/mL for D₃ receptor for globus pallidus and substantia nigra (df = 19, p < 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

researchmap

Other Link： https://link.springer.com/article/10.1007/s00213-020-05698-3/fulltext.html

Publishing type：Research paper (scientific journal)   Publisher：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 <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale score <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

researchmap

Other Link： http://academic.oup.com/ijnp/article-pdf/24/2/108/36267824/pyaa071.pdf

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/pcn.13020

researchmap

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/pcn.13020

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

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

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1093/ijnp/pyy004

researchmap

Language：Japanese   Publisher：(一社)日本総合病院精神医学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1016/j.dadm.2017.08.002

researchmap

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1016/j.dadm.2017.08.002

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.pscychresns.2016.03.006

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Informa UK Limited  

DOI： 10.2147/ndt.s99577

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/gps.4215

researchmap

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/gps.4173

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.genhosppsych.2014.09.016

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1017/s1461145713001764

researchmap

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s00213-013-3392-2

researchmap

Other Link： http://link.springer.com/article/10.1007/s00213-013-3392-2/fulltext.html

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：INFORMA HEALTHCARE  

Web of Science

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

DOI： 10.1017/s1461145713001612

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s12149-013-0798-1

researchmap

Other Link： http://link.springer.com/article/10.1007/s12149-013-0798-1/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Medical Association of Nippon Medical School  

DOI： 10.1272/jnms.81.2

researchmap

Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1111/j.1440-1819.2011.02250.x

researchmap

Language：Japanese   Publisher：(公財)先進医薬研究振興財団  

researchmap

Authorship：Lead author   Language：Japanese   Publisher：(公社)日本精神神経学会  

器質性精神障害から統合失調症,気分障害までさまざまな病態でみられるカタトニア(緊張病)は,共通してベンゾジアゼピン系薬剤の効果があるとされている.しかし,今日においてカタトニアは均一な病態であると言い切ることはできず,ベンゾジアゼピン系薬剤と電気けいれん療法(ECT)によって劇的な改善を認める症例の印象に引きずられ,安易に画一的な診断・評価・治療に陥りがちになっている傾向があるように思う.いかなる症候を伴う状態像を真にカタトニアと呼称すべきかの議論も尽きないが,カタトニアは顕著な精神運動障害と意志発動の障害が特徴であり,経過や主訴を患者本人から事前に確認することは困難である.その症状のなかには昏迷のように,個別にはカタトニアの症状とは限らないものも含まれる.そのため,診断にあたっては患者が示す全体像がカタトニアによるものであるか評価することが重要である.今回,カタトニアに対する診断・評価と治療法について自験例を提示し考察した.ベンゾジアゼピン系薬剤を使用するにあたっては,「カタトニアという症候」に対しての改善効果の評価と併せて,「カタトニアを生じさせている基礎疾患」に対しても治療効果をもたらしているか留意する必要がある.カタトニアを生じさせている基礎疾患への治療アプローチなくして良好な転帰は得られない.さらに,カタトニア症状の発現から早期の治療介入がなされることが転帰に影響をもたらすと指摘されており,必要以上にベンゾジアゼピン系薬剤の投与を躊躇することはないが,投与開始にあたっては,カタトニアの症候の吟味を十分に行い,ベンゾジアゼピン系薬剤の投与によって生じるかもしれない有害事象の可能性を検討し,基礎疾患の鑑別・診断を速やかに行う必要がある.そのなかで循環器系への影響も十分検討され,かつ,基礎疾患への治療を目的として,あるいは致死的な転帰を回避する目的としてECTは選択されるべきであると考える.(著者抄録)

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00755&link_issn=&doc_id=20180302080003&doc_link_id=vol%3D120%26year%3D2018%26mag%3D0%26number%3D2%26start%3D99&url=https%3A%2F%2Fjournal.jspn.or.jp%2FDisp%3Fstyle%3Dabst%26vol%3D120%26year%3D2018%26mag%3D0%26number%3D2%26start%3D99&type=%90%B8%90_%90_%8Co%8Aw%8EG%8E%8F&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00022_2.gif

Language：Japanese   Publisher：日本生物学的精神医学会・日本神経精神薬理学会  

researchmap

Language：Japanese   Publisher：日本臨床精神神経薬理学会・日本神経精神薬理学会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：日本臨床精神神経薬理学会・日本神経精神薬理学会  

researchmap

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Language：Japanese   Publisher：(公社)日本精神神経学会  

researchmap

Presentation type：Symposium, workshop panel (nominated)  

researchmap