{"title":"New finding of brain molecular mechanisms of obsessive-compulsive disorder may uncover those of treatment-resistant cases.","authors":"Hidenori Yamasue","doi":"10.1111/pcn.13765","DOIUrl":"https://doi.org/10.1111/pcn.13765","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":"79 2","pages":"47"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080740","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}
Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim, Hyunseok Jang, Jung-Chul Kim, Byung Jo Chun, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin
{"title":"Response to [It is still an open question if cortisol levels, neuroticism and traumatic events are associated with PTSD].","authors":"Jae-Min Kim, Hee-Ju Kang, Ju-Wan Kim, Hyunseok Jang, Jung-Chul Kim, Byung Jo Chun, Ju-Yeon Lee, Sung-Wan Kim, Il-Seon Shin","doi":"10.1111/pcn.13776","DOIUrl":"10.1111/pcn.13776","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"79-80"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142839122","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}
Beatrice Bravi, Marco Paolini, Melania Maccario, Chiara Milano, Laura Raffaelli, Elisa Maria Teresa Melloni, Raffaella Zanardi, Cristina Colombo, Francesco Benedetti
{"title":"Abnormal choroid plexus, hippocampus, and lateral ventricles volumes as markers of treatment-resistant major depressive disorder.","authors":"Beatrice Bravi, Marco Paolini, Melania Maccario, Chiara Milano, Laura Raffaelli, Elisa Maria Teresa Melloni, Raffaella Zanardi, Cristina Colombo, Francesco Benedetti","doi":"10.1111/pcn.13764","DOIUrl":"10.1111/pcn.13764","url":null,"abstract":"<p><strong>Aim: </strong>One-third of patients with major depressive disorder (MDD) do not achieve full remission and have high relapse rates even after treatment, leading to increased medical costs and reduced quality of life and health status. The possible specificity of treatment-resistant depression (TRD) neurobiology is still under investigation, with risk factors such as higher inflammatory markers being identified. Given recent findings on the role of choroid plexus (ChP) in neuroinflammation and hippocampus in treatment response, the aim of the present study was to evaluate inflammatory- and trophic-related differences in these regions along with ventricular volumes among patients with treatment-sensitive depression (TSD), TRD, and healthy controls (HCs).</p><p><strong>Methods: </strong>ChP, hippocampal, and ventricular volumes were assessed in 197 patients with MDD and 58 age- and sex-matched HCs. Volumes were estimated using FreeSurfer 7.2. Treatment resistance status was defined as failure to respond to at least two separate antidepressant treatments. Region of interest volumes were then compared among groups.</p><p><strong>Results: </strong>We found higher ChP volumes in patients with TRD compared with patients with TSD and HCs. Our results also showed lower hippocampal volumes and higher lateral ventricular volumes in TRD compared with both patients without TRD and HCs.</p><p><strong>Conclusions: </strong>These findings corroborate the link between TRD and neuroinflammation, as ChP volume could be considered a putative marker of central immune activity. The lack of significant differences in all of the region of interest volumes between patients with TSD and HCs may highlight the specificity of these features to TRD, possibly providing new insights into the specific neurobiological underpinnings of this condition.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"69-77"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676588","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}
Martin Pastre, Bob-Valéry Occéan, Vincent Boudousq, Ismael Conejero, Pascale Fabbro-Peray, Laurent Collombier, Luc Mallet, Jorge Lopez-Castroman
{"title":"Serotonergic underpinnings of obsessive-compulsive disorder: A systematic review and meta-analysis of neuroimaging findings.","authors":"Martin Pastre, Bob-Valéry Occéan, Vincent Boudousq, Ismael Conejero, Pascale Fabbro-Peray, Laurent Collombier, Luc Mallet, Jorge Lopez-Castroman","doi":"10.1111/pcn.13760","DOIUrl":"10.1111/pcn.13760","url":null,"abstract":"<p><p>Obsessive-compulsive disorder (OCD) is a frequent and disabling condition, with many patients being treatment-resistant. Improved understanding of its neurobiology is vital for better therapies. Evidence is still conflicting regarding specific serotonergic-related dysfunctions in OCD. We systematically reviewed the literature to provide a quantitative assessment of the role of serotonin (5-HT) in patients with untreated OCD through imaging. We searched for neuroimaging studies investigating central 5-HT tonus in unmedicated patients with OCD, excluding studies comprising treated patients to prevent bias from antidepressant-induced changes in serotonergic tonus. We also conducted a meta-analysis using a homogeneous group of positron emission tomography and single photon emission computed tomography articles that compared 5-HT transporter (SERT) and 5-HT2A receptor (HT2AR) binding potential in different brain regions of patients with untreated OCD and healthy controls. The systematic review encompassed 18 articles, with 13 included in the subsequent meta-analysis. Risk of bias was assessed by a revised form of the Newcastle-Ottawa Scale. We provided standardized mean difference (SMD) values for SERT and 5-HT2AR binding potential measures across 15 different brain regions. Patients with OCD showed lower SERT binding potential in the brainstem (SMD = -1.13, 95% CI [-1.81 to -0.46]), midbrain (SMD = -0.54, 95% CI [-0.92 to -0.16]), and thalamus/hypothalamus regions (SMD = -0.58, 95% CI [-0.99 to -0.18]) with neglectable to moderate heterogeneity. By combining results from 2 decades of molecular imaging studies, we show that individuals with OCD exhibit lower SERT binding potential in specific brain regions, providing compelling evidence of a 5-HT system dysfunction. However, the exact mechanisms underlying this phenotype remain elusive. The limitations include heterogeneity across studies in populations, imaging techniques, and radiotracer usage.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"48-59"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11789457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606149","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":"PCN Art Brut Series No. 43, Artwork Description.","authors":"Kenjiro Hosaka","doi":"10.1111/pcn.13795","DOIUrl":"https://doi.org/10.1111/pcn.13795","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":"79 2","pages":"81"},"PeriodicalIF":5.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080871","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":"Effects of online high-definition transcranial direct current stimulation over left dorsolateral prefrontal cortex on predominant negative symptoms and EEG functional connectivity in patients with schizophrenia: a randomized, double-blind, controlled trial.","authors":"Ta-Chuan Yeh, Yen-Yue Lin, Nian-Sheng Tzeng, Yu-Chen Kao, Yong-An Chung, Chuan-Chia Chang, Hsu-Wei Fang, Hsin-An Chang","doi":"10.1111/pcn.13745","DOIUrl":"10.1111/pcn.13745","url":null,"abstract":"<p><strong>Aims: </strong>Schizophrenia, a debilitating mental disorder, is characterized by persistent negative symptoms such as avolition and anhedonia. Currently, there are no effective treatments available for these symptoms. Thus, our study aims to assess the efficacy of online high-definition transcranial direct current stimulation (online HD-tDCS) in addressing the negative symptoms of schizophrenia, utilizing a double-blind, randomized, sham-controlled trial design.</p><p><strong>Methods: </strong>Fifty-nine patients with schizophrenia were randomized to receive either active HD-tDCS or sham stimulation, targeting the left dorsolateral prefrontal cortex. Outcomes were measured by changes in the Positive and Negative Syndrome Scale Factor Score for Negative Symptom (PANSS-FSNS). Exact low-resolution electromagnetic tomography was used to assess the functional connectivity.</p><p><strong>Results: </strong>All 59 participants, including 50.84% females with an average age of 43.36 years, completed the trial. In the intention-to-treat analysis, patients receiving active HD-tDCS showed greater improvement in PANSS-FSNS scores compared to those receiving the sham procedure. The differences were 2.34 (95% confidence interval [CI], 1.28-3.40), 4.28 (95% CI, 2.93-5.62), and 4.91 (95% CI, 3.29-6.52) after the intervention, as well as at 1-week and 1-month follow-ups, respectively. A tingling sensation on the scalp was more common in the active group (63.3%) compared to the sham group (10.3%). Additionally, HD-tDCS was associated with a decrease in delta-band connectivity within the default mode network.</p><p><strong>Conclusions: </strong>High-definition transcranial direct current stimulation was effective and safe in ameliorating negative symptoms in patients with schizophrenia when combined with online functional targeting.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"2-11"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352793","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":"New treatment options for negative symptoms in schizophrenia.","authors":"Toshiaki Onitsuka","doi":"10.1111/pcn.13763","DOIUrl":"https://doi.org/10.1111/pcn.13763","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":"79 1","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915494","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":"Rare nonsynonymous germline and mosaic de novo variants in Japanese patients with schizophrenia.","authors":"Yuichiro Watanabe, Masaki Nishioka, Ryo Morikawa, Satoko Takano-Isozaki, Hirofumi Igeta, Kanako Mori, Tadafumi Kato, Toshiyuki Someya","doi":"10.1111/pcn.13758","DOIUrl":"10.1111/pcn.13758","url":null,"abstract":"<p><strong>Aim: </strong>Whole-exome sequencing (WES) studies have revealed that germline de novo variants (gDNVs) contribute to the genetic etiology of schizophrenia. However, the contribution of mosaic DNVs (mDNVs) to the risk of schizophrenia remains to be elucidated. In the present study, we systematically investigated the gDNVs and mDMVs that contribute to the genetic etiology of schizophrenia in a Japanese population.</p><p><strong>Methods: </strong>We performed deep WES (depth: 460×) of 73 affected offspring and WES (depth: 116×) of 134 parents from 67 families with schizophrenia. Prioritized rare nonsynonymous gDNV and mDNV candidates were validated using Sanger sequencing and ultra-deep targeted amplicon sequencing (depth: 71,375×), respectively. Subsequently, we performed a Gene Ontology analysis of the gDNVs and mDNVs to obtain biological insights. Lastly, we selected DNVs in known risk genes for psychiatric and neurodevelopmental disorders.</p><p><strong>Results: </strong>We identified 62 gDNVs and 98 mDNVs. The Gene Ontology analysis of mDNVs implicated actin filament and actin cytoskeleton as candidate biological pathways. There were eight DNVs in known risk genes: splice region gDNVs in AKAP11 and CUL1; a frameshift gDNV in SHANK1; a missense gDNV in SRCAP; missense mDNVs in CTNNB1, GRIN2A, and TSC2; and a nonsense mDNV in ZFHX4.</p><p><strong>Conclusion: </strong>Our results suggest the potential contributions of rare nonsynonymous gDNVs and mDNVs to the genetic etiology of schizophrenia. This is the first report of the mDNVs in schizophrenia trios, demonstrating their potential relevance to schizophrenia pathology.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"37-44"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506838","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":"Copy number variations in RNF216 and postsynaptic membrane-associated genes are associated with bipolar disorder: a case-control study in the Japanese population.","authors":"Masahiro Nakatochi, Itaru Kushima, Branko Aleksic, Hiroki Kimura, Hidekazu Kato, Toshiya Inada, Youta Torii, Nagahide Takahashi, Maeri Yamamoto, Kunihiro Iwamoto, Yoshihiro Nawa, Shuji Iritani, Nakao Iwata, Takeo Saito, Kohei Ninomiya, Tomo Okochi, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Kenichiro Miura, Kazutaka Ohi, Toshiki Shioiri, Kiyoyuki Kitaichi, Masanari Itokawa, Makoto Arai, Mitsuhiro Miyashita, Kazuya Toriumi, Tsutomu Takahashi, Michio Suzuki, Takahiro A Kato, Shigenobu Kanba, Hideki Horikawa, Kiyoto Kasai, Tempei Ikegame, Seiichiro Jinde, Tadafumi Kato, Chihiro Kakiuchi, Bun Yamagata, Shintaro Nio, Yasuto Kunii, Hirooki Yabe, Yasunobu Okamura, Shu Tadaka, Ueno Fumihiko, Taku Obara, Yasuyuki Yamamoto, Yuko Arioka, Daisuke Mori, Masashi Ikeda, Norio Ozaki","doi":"10.1111/pcn.13752","DOIUrl":"10.1111/pcn.13752","url":null,"abstract":"<p><strong>Aim: </strong>Bipolar disorder (BD) is a common psychiatric disorder characterized by alterations between manic/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population.</p><p><strong>Methods: </strong>Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene-based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%.</p><p><strong>Results: </strong>The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66-14.89], false discovery rate < 10%). The BD-associated CNV that corresponded with RNF216 also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05).</p><p><strong>Conclusion: </strong>We provide evidence that CNVs in RNF216 and postsynaptic membrane-related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"12-20"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473362","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}
Hyo-Won Kim, Ji-Hoon Kim, Un Sun Chung, Johanna Inhyang Kim, Se-Hoon Shim, Tae Won Park, Moon-Soo Lee, Jun-Won Hwang, Eun-Jin Park, Su-Kyeong Hwang, Yoo-Sook Joung
{"title":"AST-001 versus placebo for social communication in children with autism spectrum disorder: A randomized clinical trial.","authors":"Hyo-Won Kim, Ji-Hoon Kim, Un Sun Chung, Johanna Inhyang Kim, Se-Hoon Shim, Tae Won Park, Moon-Soo Lee, Jun-Won Hwang, Eun-Jin Park, Su-Kyeong Hwang, Yoo-Sook Joung","doi":"10.1111/pcn.13757","DOIUrl":"10.1111/pcn.13757","url":null,"abstract":"<p><strong>Aim: </strong>This study examined the efficacy of AST-001 for the core symptoms of autism spectrum disorder (ASD) in children.</p><p><strong>Methods: </strong>This phase 2 clinical trial consisted of a 12-week placebo-controlled main study, a 12-week extension, and a 12-week follow-up in children aged 2 to 11 years with ASD. The participants were randomized in a 1:1:1 ratio to a high-dose, low-dose, or placebo-to-high-dose control group during the main study. The placebo-to-high-dose control group received placebo during the main study and high-dose AST-001 during the extension. The a priori primary outcome was the mean change in the Adaptive Behavior Composite (ABC) score of the Korean Vineland Adaptive Behavior Scales II (K-VABS-II) from baseline to week 12.</p><p><strong>Results: </strong>Among 151 enrolled participants, 144 completed the main study, 140 completed the extension, and 135 completed the follow-up. The mean K-VABS-II ABC score at the 12th week compared with baseline was significantly increased in the high-dose group (P = 0.042) compared with the placebo-to-high-dose control group. The mean CGI-S scores were significantly decreased at the 12th week in the high-dose (P = 0.046) and low-dose (P = 0.017) groups compared with the placebo-to-high-dose control group. During the extension, the K-VABS-II ABC and CGI-S scores of the placebo-to-high-dose control group changed rapidly after administration of high-dose AST-001 and caught up with those of the high-dose group at the 24th week. AST-001 was well tolerated with no safety concern. The most common adverse drug reaction was diarrhea.</p><p><strong>Conclusions: </strong>Our results provide preliminary evidence for the efficacy of AST-001 for the core symptoms of ASD.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"21-28"},"PeriodicalIF":5.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473346","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}