{"title":"Genome-wide DNA methylation profiles in the raphe nuclei of patients with autism spectrum disorder.","authors":"Keiko Iwata, Kazuhiko Nakabayashi, Keisuke Ishiwata, Kazuhiko Nakamura, Yosuke Kameno, Kenichiro Hata, Hideo Matsuzaki","doi":"10.1111/pcn.13830","DOIUrl":"10.1111/pcn.13830","url":null,"abstract":"<p><strong>Aim: </strong>Autism spectrum disorder (ASD) has a strong genetic basis, yet its genetic complexities remain elusive. Current research highlights environmental factors and epigenetic processes, such as DNA methylation, as crucial in ASD development. This exploratory study addresses a gap in understanding epigenetic regulation in the dorsal raphe (DR)-a region regulating multiple neurotransmitters and implicated in ASD-by examining DNA methylation profiles in postmortem ASD and control brains.</p><p><strong>Methods: </strong>We comprehensively analyzed genome-wide DNA methylation profiles in the DR brain region (seven controls and five ASD) using the Infinium HumanMethylation450 BeadChip (Illumina). Additionally, quantitative polymerase chain reaction was used to measure messenger RNA levels of differentially methylated genes in ASD (11 controls and six ASD).</p><p><strong>Results: </strong>We identified differentially methylated regions (DMRs) between ASD and controls. These DMRs were located among various genomic regions, including promoters, gene bodies, and intergenic regions. Notably, we found hypermethylation in genes related to olfaction (e.g. OR2C3), which is regulated by serotonin. Additionally, we observed that the hypomethylation of promoter-associated CpG islands in RABGGTB, a gene related to autophagy and synaptic function, corresponded with its increased expression.</p><p><strong>Conclusions: </strong>Our findings reveal extensive DNA methylation changes in critical genomic regions, shedding light on potential mechanisms underlying ASD. The identification of RABGGTB as a novel candidate gene, not listed in the SFARI database, underscores its significance and warrants further research to explore its role in ASD diagnosis. This study enhances our understanding of the epigenetic landscape in ASD, emphasizing the interplay between genetic and environmental factors in its pathophysiology.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"415-424"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12232043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064448","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}
Hamit Hakan Alp, Faruk Kurhan, Halil İbrahim Akbay
{"title":"Predictive value of kynurenine pathway metabolites in the severity of patients with obsessive-compulsive disorder.","authors":"Hamit Hakan Alp, Faruk Kurhan, Halil İbrahim Akbay","doi":"10.1111/pcn.13819","DOIUrl":"10.1111/pcn.13819","url":null,"abstract":"<p><strong>Background: </strong>Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by repetitive thoughts and behaviors. The kynurenine pathway has been increasingly implicated in psychiatric disorders. This study aimed to investigate the predictive value of kynurenine pathway metabolites, including serotonin and tryptophan, in patients with varying degrees of OCD.</p><p><strong>Methods: </strong>One hundred fifty OCD patients and 30 healthy controls were included in this study. Patients were divided into mild-moderate, severe, and extremely severe OCD groups based on their Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. Serum levels of serotonin, tryptophan, kynurenine, kynurenic acid, indolamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase (TDO), 3-hydroxykynurenine, quinolinic acid and picolinic acid were measured using enzyme-linked immunosorbent assay. Logistic regression and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive value of these analytes for OCD severity.</p><p><strong>Results: </strong>Serotonin and tryptophan levels were significantly decreased in OCD patients compared to healthy controls, while kynurenine pathway metabolites were significantly increased in patients with OCD. Serum levels of kynurenine pathway metabolites increased with severity in OCD patients. As a result of ROC analysis, serotonin, tryptophan and kynurenine pathway metabolites had higher AUC values in distinguishing OCD patients from healthy volunteers, while kynurenine and tryptophan had higher AUC values in distinguishing disease severity.</p><p><strong>Conclusion: </strong>This study clarifies the role of the kynurenine pathway in the pathophysiology of OCD and suggests that kynurenine pathway metabolites, especially kynurenine, may serve as useful biomarkers to diagnose and differentiate OCD severity. Further research is needed to confirm these findings and explore therapeutic implications.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"378-388"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753821","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}
Ryo Asada, Hiroko Sugawara, Shun Inoue, Hikaru Hori
{"title":"Serotonin syndrome induced through a combination of oxycodone and amitriptyline: A case report.","authors":"Ryo Asada, Hiroko Sugawara, Shun Inoue, Hikaru Hori","doi":"10.1111/pcn.13828","DOIUrl":"10.1111/pcn.13828","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"427-428"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009423","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":"The sense of smell is a possible screening tool for identification of cognitive decline.","authors":"Shinsuke Koike","doi":"10.1111/pcn.13838","DOIUrl":"10.1111/pcn.13838","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"369"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102249","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":"Atypical tactile preferences in autism spectrum disorder: Reduced pleasantness responses to soft objects resembling human body parts.","authors":"Kai Makita, Ryo Kitada, Takuya Makino, Nodoka Sakakihara, Ayaka Fukuoka, Hirotaka Kosaka","doi":"10.1111/pcn.13808","DOIUrl":"10.1111/pcn.13808","url":null,"abstract":"<p><strong>Aim: </strong>Previous studies have reported atypical sensory responses in individuals with autism spectrum disorder (ASD) and their implications for social touch. Although adults with ASD often report discomfort with being touched by others, their preferences for the physical properties of objects are less well understood. In a prior study, we observed that, in typically developed (TD) adults, compliance (a physical correlate of softness) increased tactile pleasantness for deformable surfaces up to levels comparable to those of human body parts. In the present study, we conducted psychophysical experiments to test whether individuals with ASD show atypical affective responses to soft objects resembling human body parts.</p><p><strong>Methods: </strong>Thirty-six adults with ASD and 36 TD adults numerically estimated the perceived pleasantness or softness while lightly pressing urethane rubbers with their right index fingers.</p><p><strong>Results: </strong>The results revealed that pleasantness increased as a function of compliance, but this increase was significantly smaller for patients with ASD than TD adults, particularly at compliance levels including human body parts. However, the perceived softness increased as a function of compliance highly similarly between the ASD and TD groups.</p><p><strong>Conclusions: </strong>These findings demonstrate an atypical preference of individuals with ASD for soft objects such as human body parts, which may help explain their tendency to avoid social touch.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"319-326"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606201","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":"Efficacy and safety of each class of sleep medication for major depressive disorder with insomnia symptoms: A systematic review and meta-analysis of double-blind randomized controlled trials.","authors":"Taku Maruki, Masahiro Takeshima, Kazuhisa Yoshizawa, Yuna Maeda, Naoaki Otsuka, Yumi Aoki, Tomohiro Utsumi, Kentaro Matsui, Aran Tajika, Yoshikazu Takaesu","doi":"10.1111/pcn.13811","DOIUrl":"10.1111/pcn.13811","url":null,"abstract":"<p><p>Combination therapy with antidepressants and sleep medications is a promising candidate treatment for major depressive disorder (MDD) with insomnia. This systematic review and meta-analysis examined the efficacy and safety of combination therapy with antidepressants and sleep medication for treating MDD with insomnia compared to antidepressant monotherapy by sleep medication class (benzodiazepine, Z-drug, melatonin receptor agonist, and orexin receptor antagonist). This study was preregistered with PROSPERO (CRD42025636571). PubMed, CENTRAL, and Embase were searched for double-blind randomized controlled trials published until June 2024, resulting in eight eligible studies (1945 participants; eszopiclone = 4, zolpidem = 2, triazolam = 1, ramelteon = 1). Meta-analyses were performed based on six trials of Z-drugs. Compared with antidepressant monotherapy, combination therapy with antidepressants and Z-drugs resulted in higher remission rates from depressive symptoms (risk ratio: 1.25, 95% confidence interval [CI]: 1.08-1.45, P = 0.003), greater improvement in depressive symptoms (standardized mean difference [SMD]: 0.17, 95% CI: 0.01-0.33, P = 0.04) and insomnia symptoms (SMD: 0.43, 95% CI: 0.28-0.59, P < 0.001) in the short-term (within 12 weeks), with no difference in safety outcomes except for dizziness. Combination therapy with antidepressants and Z-drugs may be more useful for MDD with insomnia symptoms than antidepressant monotherapy in the short term. However, this study did not evaluate the benefits and harms of long-term adjunctive Z-drug therapy. Further long-term studies are needed to draw definitive conclusions regarding the efficacy and safety of combination therapy with antidepressants and Z-drugs. Moreover, further research is warranted to assess whether the findings of this study are applicable to other sleep medication classes.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"306-318"},"PeriodicalIF":6.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664477","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}
Cody A Cushing, Hakwan Lau, Mitsuo Kawato, Michelle G Craske, Vincent Taschereau-Dumouchel
{"title":"Response to: Examining the therapeutic potential and risks of multivoxel neuroreinforcement for specific phobias.","authors":"Cody A Cushing, Hakwan Lau, Mitsuo Kawato, Michelle G Craske, Vincent Taschereau-Dumouchel","doi":"10.1111/pcn.13815","DOIUrl":"10.1111/pcn.13815","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"361-362"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053960","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":"The CORE Solution: Protecting Youth Mental Health from the Digital Pandemic.","authors":"Kuan-Pin Su","doi":"10.1111/pcn.13816","DOIUrl":"10.1111/pcn.13816","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"297-298"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102060","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}
Christopher B Morrow, Vidyulata Kamath, Bradford C Dickerson, Mark Eldaief, Neguine Rezaii, Bonnie Wong, Scott McGinnis, Ryan Darby, Adam M Staffaroni, Maria I Lapid, Belen Pascual, Julio C Rojas, Joseph C Masdeu, Kyrana Tsapkini, Edward D Huey, Daniel W Fisher, Alexander Pantelyat, Akshata Balaji, Eric Sah, Irene Litvan, Katya Rascovsky, Nupur Ghoshal, Kimiko Domoto-Reilly, John Kornak, Chiadi U Onyike
{"title":"Neuropsychiatric symptoms cluster and fluctuate over time in behavioral variant frontotemporal dementia.","authors":"Christopher B Morrow, Vidyulata Kamath, Bradford C Dickerson, Mark Eldaief, Neguine Rezaii, Bonnie Wong, Scott McGinnis, Ryan Darby, Adam M Staffaroni, Maria I Lapid, Belen Pascual, Julio C Rojas, Joseph C Masdeu, Kyrana Tsapkini, Edward D Huey, Daniel W Fisher, Alexander Pantelyat, Akshata Balaji, Eric Sah, Irene Litvan, Katya Rascovsky, Nupur Ghoshal, Kimiko Domoto-Reilly, John Kornak, Chiadi U Onyike","doi":"10.1111/pcn.13810","DOIUrl":"10.1111/pcn.13810","url":null,"abstract":"<p><strong>Aim: </strong>Cognitive and behavioral phenomena define behavioral variant frontotemporal dementia (bvFTD), but neuropsychiatric symptoms (NPS) outside the core criteria are common throughout the illness. Identifying how NPS cluster in bvFTD may guide development of future therapies.</p><p><strong>Methods: </strong>Participants (n = 354) with sporadic and genetic bvFTD were enrolled in the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration Consortium. Dementia stage was defined as early (CDR® plus NACC FTLD ≤1) or advanced (CDR® plus NACC FTLD ≥1). Baseline and annual follow-up visit data were analyzed to compare NPS across stages of bvFTD. Psychiatric states were captured using the Neuropsychiatric Inventory-Questionnaire and Clinician Judgment of Symptoms. Polychoric cluster analysis was used to describe NPS clusters.</p><p><strong>Results: </strong>NPS were highly prevalent (≥90%) in early and late bvFTD. Four NPS clusters were identified based on magnitude of factor loadings: affective, disinhibited, compulsive, and psychosis. Neuropsychiatric symptoms fluctuated across visits. In the affective cluster, depression showed the least visit-to-visit stability. In the disinhibited cluster, elation showed the least stability. Symptoms in the psychosis and compulsive clusters (hallucinations, delusions, obsessions/compulsions, and hyperorality) were largely stable, persisting from visit-to-visit in more than 50% of cases. Symptoms in the affective and disinhibited cluster were associated with the highest caregiver burden, while symptoms in the obsessive cluster were associated with the most functional impairment.</p><p><strong>Conclusion: </strong>NPS in bvFTD are frequent and cluster into four discrete groups. The fluctuating nature of some NPS in bvFTD suggests that they may not be reliable markers of disease progression or stage.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"327-335"},"PeriodicalIF":6.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625823","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":"Reevaluating the safety of subcutaneous and intramuscular adrenaline injection in hemodynamically stable patients receiving therapeutic doses of antipsychotic drugs.","authors":"Shotaro Fujiwara, Takuto Ishida, Masafumi Mizuno","doi":"10.1111/pcn.13818","DOIUrl":"10.1111/pcn.13818","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"357-358"},"PeriodicalIF":5.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753908","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}