{"title":"Tetrabenazine-induced acute dystonic reaction during the treatment of comorbid tics in a young woman with autism spectrum disorder.","authors":"Marcelo D Mendonça, J Bernardo Barahona-Corrêa","doi":"10.1111/pcn.13705","DOIUrl":"10.1111/pcn.13705","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minji Bang, Kisung Park, Seoung-Ho Choi, Sung Soo Ahn, Jinna Kim, Seung-Koo Lee, Yae Won Park, Sang-Hyuk Lee
{"title":"Identification of schizophrenia by applying interpretable radiomics modeling with structural magnetic resonance imaging of the cerebellum.","authors":"Minji Bang, Kisung Park, Seoung-Ho Choi, Sung Soo Ahn, Jinna Kim, Seung-Koo Lee, Yae Won Park, Sang-Hyuk Lee","doi":"10.1111/pcn.13707","DOIUrl":"10.1111/pcn.13707","url":null,"abstract":"<p><strong>Aims: </strong>The cerebellum is involved in higher-order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1-weighted magnetic resonance imaging (T1-MRI) of the cerebellum.</p><p><strong>Methods: </strong>A total of 336 participants (174 schizophrenia; 162 healthy controls [HCs]) were allocated to training (122 schizophrenia; 115 HCs) and test (52 schizophrenia; 47 HCs) cohorts. We obtained 2568 radiomic features from T1-MRI of the cerebellar subregions. After feature selection, a light gradient boosting machine classifier was trained. The discrimination and calibration of the model were evaluated. SHapley Additive exPlanations (SHAP) was applied to determine model interpretability.</p><p><strong>Results: </strong>We identified 17 radiomic features to differentiate participants with schizophrenia from HCs. In the test cohort, the radiomics model had an area under the curve, accuracy, sensitivity, and specificity of 0.89 (95% confidence interval: 0.82-0.95), 78.8%, 88.5%, and 75.4%, respectively. The model explanation by SHAP suggested that the second-order size zone non-uniformity feature from the right lobule IX and first-order energy feature from the right lobules V and VI were highly associated with the risk of schizophrenia.</p><p><strong>Conclusion: </strong>The radiomics model focused on the cerebellum demonstrates robustness in diagnosing schizophrenia. Our results suggest that microcircuit disruption in the posterior cerebellum is a disease-defining feature of schizophrenia, and radiomics modeling has potential for supporting biomarker-based decision-making in clinical practice.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multivariate sharp-wave ripples in schizophrenia during awake state.","authors":"Takefumi Ohki, Zenas C Chao, Yuichi Takei, Yutaka Kato, Masakazu Sunaga, Tomohiro Suto, Minami Tagawa, Masato Fukuda","doi":"10.1111/pcn.13702","DOIUrl":"10.1111/pcn.13702","url":null,"abstract":"<p><strong>Aims: </strong>Schizophrenia (SZ) is a brain disorder characterized by psychotic symptoms and cognitive dysfunction. Recently, irregularities in sharp-wave ripples (SPW-Rs) have been reported in SZ. As SPW-Rs play a critical role in memory, their irregularities can cause psychotic symptoms and cognitive dysfunction in patients with SZ. In this study, we investigated the SPW-Rs in human SZ.</p><p><strong>Methods: </strong>We measured whole-brain activity using magnetoencephalography (MEG) in patients with SZ (n = 20) and sex- and age-matched healthy participants (n = 20) during open-eye rest. We identified SPW-Rs and analyzed their occurrence and time-frequency traits. Furthermore, we developed a novel multivariate analysis method, termed \"ripple-gedMEG\" to extract the global features of SPW-Rs. We also examined the association between SPW-Rs and brain state transitions. The outcomes of these analyses were modeled to predict the positive and negative syndrome scale (PANSS) scores of SZ.</p><p><strong>Results: </strong>We found that SPW-Rs in the SZ (1) occurred more frequently, (2) the delay of the coupling phase (3) appeared in different brain areas, (4) consisted of a less organized spatiotemporal pattern, and (5) were less involved in brain state transitions. Finally, some of the neural features associated with the SPW-Rs were found to be PANSS-positive, a pathological indicator of SZ. These results suggest that widespread but disorganized SPW-Rs underlies the symptoms of SZ.</p><p><strong>Conclusion: </strong>We identified irregularities in SPW-Rs in SZ and confirmed that their alternations were strongly associated with SZ neuropathology. These results suggest a new direction for human SZ research.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vortioxetine for depression in adults: A systematic review and dose-response meta-analysis of randomized controlled trials.","authors":"Xin Yang, Shuping Fang, Wenqi Lyu, Yongbo Hu, Huifang Xu, Xiao Jiang, Yurou Zhao, Yuwei Zhang, Jin Li, Weihong Kuang","doi":"10.1111/pcn.13709","DOIUrl":"10.1111/pcn.13709","url":null,"abstract":"<p><strong>Aim: </strong>Major depressive disorder (MDD) is a prevalent psychiatric condition and vortioxetine offers promising antidepressant effects due to its unique pharmacological profile. However, the dose-response relationships of vortioxetine for MDD is not well established. We aimed to conduct dose-response meta-analyses to fill this gap.</p><p><strong>Methods: </strong>We systematically searched multiple electronic databases for randomized controlled trials of vortioxetine for MDD, with the last search conducted on 08 February, 2024. The dose-response relationship was evaluated using a one-stage random-effects dose-response meta-analysis with restricted cubic spline model. The primary outcome was efficacy (mean change in depression scale score), with secondary outcomes including response, dropout for any reasons (acceptability), dropout for adverse events (tolerability), and any adverse events (safety).</p><p><strong>Results: </strong>The dose-response meta-analysis comprised 16 studies, with 4,294 participants allocated to the vortioxetine group and 2,299 participants allocated to the placebo group. The estimated 50% effective dose was 4.37 mg/day, and the near-maximal effective dose (95% effective dose) was 17.93 mg/day. Visual inspection of the dose-efficacy curve suggests that a plateau possibly had not been reached yet at 20 mg/day. Acceptability, tolerability and safety decreased as the dose increased. Subgroup analysis indicated that no significant differences were observed in acceptability, tolerability and safety among the dosage groups.</p><p><strong>Conclusions: </strong>Vortioxetine may potentially provide additional therapeutic benefits when exceeding the current licensed dosage without significantly impacting safety. Conducting clinical trials exceeding the current approved dosage appears necessary to fully comprehend its efficacy and risk.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141493231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Arginine vasopressin in mood disorders: A potential biomarker of disease pathology and a target for pharmacologic intervention.","authors":"Hiroe Hu, Carlos A Zarate, Joseph Verbalis","doi":"10.1111/pcn.13703","DOIUrl":"10.1111/pcn.13703","url":null,"abstract":"<p><p>Vasopressin or arginine-vasopressin (AVP) is a neuropeptide molecule known for its antidiuretic effects and serves to regulate plasma osmolality and blood pressure. The existing literature suggests that AVP plays a multifaceted-though less well-known-role in the central nervous system (CNS), particularly in relation to the pathophysiology and treatment of mood disorders. Animal models have demonstrated that AVP is implicated in regulating social cognition, affiliative and prosocial behaviors, and aggression, often in conjunction with oxytocin. In humans, AVP is implicated in mood disorders through its effects on the hypothalamic-pituitary-adrenal (HPA) axis as well as on the serotoninergic and glutamatergic systems. Measuring plasma AVP has yielded interesting but mixed results in mood and stress-related disorders. Recent advances have led to the development of copeptin as a stable and reliable surrogate biomarker for AVP. Another interesting but relatively unexplored issue is the interaction between the osmoregulatory system and mood disorder pathophysiology, given that psychotropic medications often cause dysregulation of AVP receptor expression or signaling that can subsequently lead to clinical syndromes like syndrome of inappropriate diuresis and diabetes insipidus. Finally, pharmaceutical trials of agents that act on V1a and V1b receptor antagonists are still underway. This narrative review summarizes: (1) the neurobiology of the vasopressinergic system in the CNS; (2) the interaction between AVP and the monoaminergic and glutamatergic pathways in the pathophysiology and treatment of mood disorders; (3) the iatrogenic AVP dysregulation caused by psychotropic medications; and (4) the pharmaceutical development of AVP receptor antagonists for the treatment of mood disorders.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of disease-modifying therapies against Alzheimer's disease.","authors":"Takeshi Iwatsubo","doi":"10.1111/pcn.13681","DOIUrl":"10.1111/pcn.13681","url":null,"abstract":"<p><p>To successfully develop disease-modifying therapies (DMT) against Alzheimer's disease (AD), it is important to target the mild stage of the disease, before the pathological changes progress and dementia symptoms are fully manifested. To this end, the AD Neuroimaging Initiative (ADNI), a large-scale observational study, was initiated in the U.S. with the goal of development of DMT that are effective in the early stages of mild cognitive impairment (MCI) by utilizing imaging and biomarkers. In Japan, J-ADNI enrolled and followed up 537 patients, mainly with MCI, and established a platform for evaluation including amyloid PET, and demonstrated a high similarity in the clinical course of amyloid-positive MCI (prodromal AD) in Japan and the U.S. In 2023, the anti-Aβ antibody lecanemab successfully completed a Phase III clinical trial for early AD (prodromal AD + mild AD dementia) and was granted regulatory approval and made available both in the US and Japan. Also, phase III trial of donanemab was completed successful. The J-TRC study was initiated in Japan as a \"trial ready cohort (TRC)\" consisting of participants who met the eligibility criteria for participation in preclinical and prodromal AD trials. Based on such a platform, the development of DMT for AD will progress more rapidly in the future.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xue-Ting Liu, Xiu Chen, Na Zhao, Fan Geng, Meng-Meng Zhu, Qing-Guo Ren
{"title":"Synergism of ApoE4 and systemic infectious burden is mediated by the APOE-NLRP3 axis in Alzheimer's disease.","authors":"Xue-Ting Liu, Xiu Chen, Na Zhao, Fan Geng, Meng-Meng Zhu, Qing-Guo Ren","doi":"10.1111/pcn.13704","DOIUrl":"10.1111/pcn.13704","url":null,"abstract":"<p><strong>Background: </strong>Systemic infections are associated with the development of AD, especially in individuals carrying the APOE4 genotype. However, the detailed mechanism through which APOE4 affects microglia inflammatory response remains unclear.</p><p><strong>Methods: </strong>We obtained human snRNA-seq data from the Synapse AD Knowledge Portal and assessed the DEGs between APOE3 and APOE4 isoforms in microglia. To verify the interaction between ApoE and infectious products, we used ApoE to stimulate in vitro and in vivo models in the presence or absence of LPS (or ATP). The NLRP3 gene knockout experiment was performed to demonstrate whether the APOE-NLRP3 axis was indispensable for microglia to regulate inflammation and mitochondrial autophagy. Results were evaluated by biochemical analyses and fluorescence imaging.</p><p><strong>Results: </strong>Compared with APOE3, up-regulated genes in APOE4 gene carriers were involved in pro-inflammatory responses. ApoE4-stimulation significantly increased the levels of NLRP3 inflammasomes and ROS in microglia. Moreover, compared with ApoE4 alone, the co-incubation of ApoE4 with LPS (or ATP) markedly promoted pyroptosis. Both NF-κB activation and mitochondrial autophagy dysfunction were contributed by the increased level of NLRP3 inflammasomes induced by ApoE4. Furthermore, the pathological impairment induced by ApoE4 could be reversed by NLRP3 KO.</p><p><strong>Conclusions: </strong>Our study highlights the importance of NLRP3 inflammasomes in linking ApoE4 with microglia innate immune function. These findings not only provide a molecular basis for APOE4-mediated neuroinflammatory but also reveal the potential reason for the increased risk of AD in APOE4 gene carriers after contracting infectious diseases.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial.","authors":"Yohei Ohtani, Hideaki Tani, Kie Nomoto-Takahashi, Taisuke Yatomi, Kengo Yonezawa, Sota Tomiyama, Nobuhiro Nagai, Keisuke Kusudo, Shiori Honda, Sotaro Moriyama, Shinichiro Nakajima, Takashige Yamada, Hiroshi Morisaki, Yu Iwabuchi, Masahiro Jinzaki, Kimio Yoshimura, Tsuyoshi Eiro, Sakiko Tsugawa, Sadamitsu Ichijo, Yu Fujimoto, Tomoyuki Miyazaki, Takuya Takahashi, Hiroyuki Uchida","doi":"10.1111/pcn.13734","DOIUrl":"https://doi.org/10.1111/pcn.13734","url":null,"abstract":"<p><strong>Aim: </strong>Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD.</p><p><strong>Methods: </strong>In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score.</p><p><strong>Results: </strong>Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score.</p><p><strong>Conclusion: </strong>Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142111421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cardiovascular disease, and major depression: Study on both diseases and serum brain-derived neurotrophic factor (BDNF).","authors":"Reiji Yoshimura","doi":"10.1111/pcn.13678","DOIUrl":"10.1111/pcn.13678","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}