International Journal of Neuropsychopharmacology最新文献

{"title":"Sedative and hypnotic effects of nuciferine: enhancing rodent sleep via serotonergic system modulation.","authors":"Luo-Xuan Wang, Yu-Meng Liu, Yong-Fang Gu, Lu Li, Ren-Hong Qiu, Yan-Kai Wang, Jin Yang, Ji Wang, Yang Zhang, Shuo Li, Qiong-Yin Fan, Rui Xue, Jing-Cao Li, You-Zhi Zhang","doi":"10.1093/ijnp/pyaf019","DOIUrl":"10.1093/ijnp/pyaf019","url":null,"abstract":"<p><strong>Background: </strong>Insomnia is the most prevalent sleep disorder globally. Nuciferine (NF), a bioactive constituent extracted from Nelumbo nucifera leaves, is recognized for its diverse pharmacological activities. However, its sleep-regulating effects have not been investigated. This study aimed to delineate the therapeutic effects and underlying mechanisms of NF in mitigating insomnia.</p><p><strong>Methods: </strong>The sedative-hypnotic effects of NF were assessed employing locomotor activity test, pentobarbital-induced sleep test, and electroencephalography-based sleep profiling. Insomnia symptoms in rodents were induced by serotonin (5-HT) depletion and environmental stress. The potential mechanisms of NF's action through the regulation of central serotonin system were also explored.</p><p><strong>Results: </strong>Nuciferine attenuated locomotor activity and extended pentobarbital-induced sleep duration in a dose-dependent manner. It also significantly augmented total and non-rapid eye movement (NREM) sleep time and enhanced delta power at frequencies of 0.5 and 1 Hz in normal rats. Sleep analysis revealed that NF effectively reversed the reduction in total and NREM sleep time caused by environmental stress from cage changing. NF treatment also proved effective against insomnia induced by 5-HT depletion, as evidenced by increased sleep duration and reduced sleep latency. Further investigation revealed a synergetic effect of NF and 5-hydroxytryptophan, alone with increased 5-HT and 5-HT1A receptor levels in the hypothalamus of insomniac mice following NF administration.</p><p><strong>Conclusions: </strong>The results demonstrate NF's hypnotic effects and its ability to alleviate insomnia, providing preclinical evidence for its potential as a naturally derived treatment for insomnia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoking is associated with levels of the serotonin transporter in the brain: a [11C]DASB PET Study.","authors":"Paul Faulkner, Gitte M Knudsen, Vibe G Frokjaer, David Erritzoe","doi":"10.1093/ijnp/pyaf026","DOIUrl":"10.1093/ijnp/pyaf026","url":null,"abstract":"<p><strong>Background: </strong>Preclinical work suggests that chronic nicotine/tobacco use is associated with reductions in serotonin within the hippocampus, yet no research has yet shown an association of smoking behaviors and alterations in brain serotonin in humans in vivo.</p><p><strong>Methods: </strong>We therefore analyzed existing [11C]DASB PET data from the Cimbi Database to compare the availability of the serotonin transporter (SERT) in the hippocampus, midbrain (including the raphe), and neocortex of 60 healthy non-smokers, 15 ex-smokers, and 11 current smokers who also provided blood samples for determination of plasma tryptophan load. Because SERT availability is considered to be negatively associated with extracellular serotonin levels, we hypothesized that current smokers would exhibit greater SERT availability than ex-smokers and non-smokers.</p><p><strong>Results: </strong>There was a significant main effect of group on SERT binding (DASB BPND) values in the bilateral and left hippocampus, and a trend toward such in the right hippocampus. Post hoc ANOVAs revealed that current smokers exhibited greater hippocampal DASB BPND than both non-smokers and ex-smokers, while the latter 2 groups did not differ. There were no group effects on DASB BPND within the midbrain or global neocortex. Finally, there was no significant group effect on plasma tryptophan load.</p><p><strong>Conclusions: </strong>This study provides the first in vivo evidence that current smoking may be associated with elevated hippocampal SERT binding-possibly reflecting lower synaptic serotonin concentrations, and that this change may normalize following smoking cessation.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct effects of psychiatric disorder diagnoses and severe emotional dysregulation on matrix metalloproteinase-9, proinflammatory cytokines, and inhibitory control function in adolescents with attention-deficit hyperactivity disorder or first-episode major affective disorders.","authors":"Ju-Wei Hsu, Li-Chi Chen, Ya-Mei Bai, Shih-Jen Tsai, Mu-Hong Chen","doi":"10.1093/ijnp/pyaf024","DOIUrl":"10.1093/ijnp/pyaf024","url":null,"abstract":"<p><strong>Background: </strong>Severe emotional dysregulation (SED) may represent an endophenotype of attention-deficit hyperactivity disorder (ADHD) and major affective disorders. However, the specific effects of SED and related psychiatric disorders, including ADHD, bipolar disorder (BD), and major depressive disorder (MDD), on matrix metalloproteinase-9 (MMP-9), proinflammatory cytokine levels, and inhibitory control function remain unclear.</p><p><strong>Methods: </strong>This study included 48 adolescents with ADHD, 39 with first-episode BD, 53 with first-episode MDD, and 46 healthy adolescents. SED was defined according to total T scores ≥210 on the Child Behavior Checklist Dysregulation Profile. Levels of MMP-9, interleukin (IL)-6, and C-reactive protein (CRP) were measured. Inhibitory control was assessed using the go/no-go task.</p><p><strong>Results: </strong>Generalized linear models adjusted for demographic and clinical data revealed significant main effects of diagnoses on MMP-9 (P = .009), CRP (P < .001), and IL-6 (P = .029) levels and on the standard deviation of mean response time on the go/no-go task (P = .004). A significant main effect of SED on MMP-9 levels (P = .048) was also observed. Adolescents with BD exhibited the highest MMP-9 and CRP levels and the poorest performance on the go/no-go task compared with the other groups. Adolescents with SED had significantly elevated MMP-9 levels than did those without SED.</p><p><strong>Discussion: </strong>Diagnoses of adolescent psychiatric disorder were associated with increased MMP-9, IL-6, and CRP levels and with inhibitory control dysfunction. In particular, SED was associated with elevated MMP-9 levels.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"28 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathic pain impairs sleep architecture, non-rapid eye movement sleep, and reticular thalamic neuronal activity.","authors":"Martha López-Canul, Anahita Oveisi, Qianzi He, Maria Luisa Vigano, Antonio Farina, Stefano Comai, Gabriella Gobbi","doi":"10.1093/ijnp/pyaf017","DOIUrl":"10.1093/ijnp/pyaf017","url":null,"abstract":"<p><strong>Background: </strong>Neuropathic pain (NP) is a chronic and debilitating condition frequently comorbid with insomnia. However, the alterations in sleep architecture under NP conditions and the mechanisms underlying both pain and sleep disturbances remain poorly understood. The reticular thalamic nucleus (RTN) plays a crucial role in non-rapid eye movement sleep (NREMS) and pain processing, but its involvement in NP-related sleep disruptions has not been fully elucidated.</p><p><strong>Methods: </strong>To investigate sleep-related electrophysiological changes in NP, we performed continuous 24-hour electroencephalogram/electromyogram (EEG/EMG) recordings in rats exhibiting allodynia following L5-L6 spinal nerve lesions. Additionally, we assessed the in vivo neuronal activity of the RTN in both NP and sham-operated control rats. Spectral analyses were conducted to examine alterations in sleep oscillatory dynamics. Reticular thalamic nucleus neuronal responses to nociceptive pinch stimuli were classified as increased, decreased, or unresponsive.</p><p><strong>Results: </strong>Neuropathic pain rats exhibited a significant reduction in NREMS (-20%, P < .001) and an increase in wakefulness (+ 19.13%, P < .05) compared to controls, whereas rapid eye movement sleep (REMS) remained unchanged. Sleep fragmentation was pronounced in NP animals (P < .0001), with frequent brief awakenings, particularly during the inactive/light phase. Spectral analysis revealed increased delta and theta power during both NREMS and REMS. Reticular thalamic nucleus neurons in NP rats displayed a higher basal tonic firing rate, along with increased phasic activity (number of bursts), although the percentage of spikes in bursts remained unchanged.</p><p><strong>Conclusions: </strong>Neuropathic pain is characterized by disrupted sleep architecture, reduced NREMS, and heightened RTN neuronal firing activity with partial compensation of burst activity. Given that RTN burst activity is essential for optimal NREMS, its disruption may contribute to NP-induced sleep impairments. These findings suggest that altered EEG/EMG signals, alongside dysregulated RTN neuronal activity, may serve as potential brain markers for NP-related insomnia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moving toward precision and personalized treatment strategies in psychiatry.","authors":"Stefano Comai, Mirko Manchia, Marta Bosia, Alessandro Miola, Sara Poletti, Francesco Benedetti, Sofia Nasini, Raffaele Ferri, Dan Rujescu, Marion Leboyer, Julio Licinio, Bernhard T Baune, Alessandro Serretti","doi":"10.1093/ijnp/pyaf025","DOIUrl":"10.1093/ijnp/pyaf025","url":null,"abstract":"<p><p>Precision psychiatry aims to improve routine clinical practice by integrating biological, clinical, and environmental data. Many studies have been performed in different areas of research on major depressive disorder, bipolar disorder, and schizophrenia. Neuroimaging and electroencephalography findings have identified potential circuit-level abnormalities predictive of treatment response. Protein biomarkers, including IL-2, S100B, and NfL, and the kynurenine pathway illustrate the role of immune and metabolic dysregulation. Circadian rhythm disturbances and the gut microbiome have also emerged as critical transdiagnostic contributors to psychiatric symptomatology and outcomes. Moreover, advances in genomic research and polygenic scores support the perspective of personalized risk stratification and medication selection. While challenges remain, such as data replication issues, prediction model accuracy, and scalability, the progress so far achieved underscores the potential of precision psychiatry in improving diagnostic accuracy and treatment effectiveness.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and Efficacy with Esketamine in Treatment-Resistant Depression: Long-Term Extension Study.","authors":"Naim Zaki, Li Nancy Chen, Rosanne Lane, Teodora Doherty, Wayne C Drevets, Randall L Morrison, Gerard Sanacora, Samuel T Wilkinson, Allan H Young, Acioly L T Lacerda, Jong-Woo Paik, Vanina Popova, Dong-Jing Fu","doi":"10.1093/ijnp/pyaf027","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf027","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;The rates of relapse and suicide risk are higher in treatment-resistant depression (TRD) versus non-treatment-resistant major depressive disorder. Even among patients with TRD who initially respond, the majority (70%) relapse within 6 months.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To evaluate the long-term safety and efficacy of esketamine nasal spray, combined with an oral antidepressant, in patients with TRD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Phase 3, open-label, single-arm long-term extension study (SUSTAIN-3) conducted from June 2016 to December 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Outpatient.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Adults with TRD who participated in ≥1 of 6 phase 3 \"parent\" studies continued esketamine by either entering a 4-week induction phase followed by an optimization/maintenance phase of variable duration (n=458), or directly entering the optimization/maintenance phase of SUSTAIN-3 (n=690), based on their individual response to study drug at the endpoint of the parent study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;Intranasal esketamine dosing was flexible, twice-weekly during induction and individualized to depression severity during optimization/maintenance (weekly, every-other-week, or every-4-weeks), under direct supervision by site staff.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;To assess long-term safety of esketamine. Efficacy endpoint included change in depressive symptoms, assessed by Montgomery-Åsberg Depression Rating Scale (MADRS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;1,148 patients were enrolled. Total exposure to esketamine was 3,777 cumulative patient-years. Mean (median, range) exposure to esketamine in SUSTAIN-3 was 42.9 (45.8, range 0-79) months. The most common adverse events were headache (36.9%), dizziness (33.9%), nausea (33.6%), dissociation (25.5%), nasopharyngitis (23.8%), somnolence (23.1%), dysgeusia (20.2%), and back pain (20.0%). During the study, 5.3% and 6.4% of participants discontinued due to lack of efficacy or adverse event, respectively. Nine participants died: COVID-19 related (n=3), pneumonia (n=2), and completed suicide, myocardial infarction, multiple injuries, unknown cause (n=1 each). Mean MADRS total score decreased during induction, and this reduction persisted during optimization/maintenance (mean [SD] change from baseline-to-phase endpoint of each phase: induction: -12.8 [9.73]; optimization/maintenance: +0.2 [9.93]). 35.6% of participants were in remission at the induction endpoint, and 48.5% and 49.6% at week 112 and optimization/maintenance endpoint, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;In the SUSTAIN-3 final dataset, no new safety signals were identified during long-term treatment with intermittently-dosed esketamine, combined with oral antidepressant, and improvement in depression generally persisted among participants who remained on maintenance treatment. These results add to the accumulated evidence on TRD treatmen","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive improvement effects of PF-04957325, a phosphodiesterase-8 inhibitor, in mouse models of Alzheimer's disease via modulating neuroinflammation.","authors":"Tian-Yang Guo, Meng Zhang, Yu-Li Lv, Nian-Zhuang Qiu, Rui-Min Chen, Fang-Fang Zhang, Wei Chen, Feng Zhang, Yong-Feng Gao, Xiao-Dan Wang, Xue-Hui Zhang, Mei-Hua Chen, Han-Ting Zhang, Hao Wang","doi":"10.1093/ijnp/pyaf028","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf028","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory deficit and has emerged as a growing global health concern. Phosphodiesterase-8 (PDE8) is a cAMP-specific hydrolase and its correlation with AD pathogenesis remains underexplored. Here, the effects and mechanisms of PF-04957325 (denoted as PF), a PDE8 inhibitor, were investigated in reversing AD both in vitro and in vivo.</p><p><strong>Methods: </strong>Briefly, BV2 cells were incubated with amyloid-β oligomers (AβO) to construct an AD cell model. Then, 2-month-old male C57BL/6J mice injected with AβO into the hippocampus and 10-month-old-male APP/PS1 mice were used to construct AD animal models. Cells and mice were treated with PF to observe the effects of PDE8 on behavior and pathology related to AD. The Y maze, NOR, and MWM were performed to investigate cognitive function in mice. Western blot and immunofluorescence staining were used to identify microglial activation state. Lastly, Western blot and ELISA were conducted to determine the levels of inflammatory factors and the proteins of PDE8/cAMP/CREB signaling.</p><p><strong>Results: </strong>PF pretreatment reversed the conversation of pro-inflammatory microglia in BV2 cells induced by AβO, while also suppressing the levels of inflammatory factors, including IL-1β, IL-6, TNF-α, iNOS, and COX-2. In addition, AβO incubation upregulated the expression of PDE8 and concurrently down-regulated that of BDNF, cAMP, p-PKA /PKA, and p-CREB /CREB in BV2 cells, all of which were reversed by PF. In vivo experiments, as evidenced by impaired performance in the Y maze, NOR, and MWM; these effects were reversed by PF. Similarly, PF treatment significantly attenuated microglia activation and the release of the inflammatory factors, and reversed the changes in the expression of BDNF and PDE8/cAMP/CREB signaling in AD mice. Finally, PF reduced the generation of Aβ1-42 by suppressing the expression of APP and PS1 in APP/PS1 mice.</p><p><strong>Conclusion: </strong>PF alleviated AD-like changes in behavior and pathology through various mechanisms, including attenuating microglia-mediated neuroinflammation, upregulating the expression of BDNF, restoring synaptic dysfunction and inhibiting Aβ generation, which appear to be involved by PDE8/cAMP/CREB signaling. These results highlight the therapeutic potential of targeting PDE8 inhibition for AD treatment.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular targets of vortioxetine mediating glioblastoma suppression revealed by gene and protein network analyses and molecular docking simulations.","authors":"Chuanjun Zhuo, Chao Li, Qiuyu Zhang, Lei Yang, Ying Zhang, Ximing Chen, Xiaoyan Ma, Ranli Li, Lina Wang, Hongjun Tian","doi":"10.1093/ijnp/pyaf029","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf029","url":null,"abstract":"<p><strong>Background: </strong>Vortioxetine is a serotonin reuptake inhibitor and serotonin receptor modulator used for the treatment of major depressive disorder, but recent studies have also reported anticancer effects in models of glioblastoma. Given the well-established benefits of drug repositioning, we examined the pharmacological mechanism for these anticancer actions using bioinformatics and molecular docking.</p><p><strong>Methods: </strong>Putative molecular targets for vortioxetine were identified by searching DrugBank, GeneCards, SwissTargetPrediction, CTD, and SuperPred databases, while glioblastoma-related proteins were identified using GeneCards, OMIM, and TTD. A protein-protein interaction (PPI) network was constructed from vortioxetine targets also involved in glioblastoma to identify core (hub) targets, which were then characterized by GO and KEGG pathway enrichment analyses using DAVID. Cytoscape was utilized to generate a drug-pathway-target-disease network, and molecular docking simulations were performed to evaluate direct interactions between vortioxetine and core target proteins.</p><p><strong>Results: </strong>A total of 234 unique vortioxetine protein targets were identified. Among 234 vortioxetine targets identified, 48 were also related to glioblastoma. Topological analysis of the PPI network revealed five core targets: the serine/threonine kinase AKT1, transcription factor hypoxia-inducible factor (HIF)-1, cell adhesion molecule cadherin-E, NF-κB subunit p105, and prostaglandin-endoperoxide synthase 2. According to GO and KEGG pathway analyses, the anticancer efficacy of vortioxetine may be mediated by effects on glucose metabolism, cell migration, phosphorylation, inflammatory responses, apoptosis, and signaling via Rap1, chemical carcinogenesis-reactive oxygen species, and HIF-1. Molecular docking revealed moderately strong affinities between vortioxetine and four core targets.</p><p><strong>Conclusions: </strong>This study suggests that vortioxetine may inhibit glioblastoma development through direct effects on multiple targets, and further emphasizes the value of bioinformatics analyses for drug repositioning.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing blinding in classic psychedelic studies with innovative active placebos.","authors":"Jacob S Aday, Otto Simonsson, Emmanuelle A D Schindler, Deepak Cyril D'Souza","doi":"10.1093/ijnp/pyaf023","DOIUrl":"10.1093/ijnp/pyaf023","url":null,"abstract":"<p><p>Classic psychedelics have shown promise in the treatment of various neuropsychiatric disorders. However, weak blinding integrity has been argued to limit the interpretability of therapeutic effects observed in psychedelic clinical trials, highlighting the need to explore alternative active placebos. Here, we aimed to describe the drawbacks of current placebo conditions used in classic psychedelic studies, propose criteria for suitable active placebos, and review interventions that may putatively fit these criteria. Considerations for the characteristics of ideal active placebos in classic psychedelic studies include (1) acute psychoactive effects, (2) acute physiological effects, (3) onset and duration of acute effects, (4) safety, and (5) lack of therapeutic effects in the target disease. We identified several pharmacological agents that may have potential as active placebos in trials involving moderate-to-high doses of certain short-acting and long-acting classic psychedelics, as well as low-dose administration and microdosing regimes. To accurately assess the safety and efficacy of classic psychedelics as therapeutics, future research should apply a thoughtful process for selecting active placebos and consider ancillary strategies to improve blinding in trials involving these substances.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of the relationship between D-amino acid profiles and cognitive function in individuals with mild cognitive impairment: a machine learning approach.","authors":"Sou Sugiki, Shigeki Tsuchiya, Ren Kimura, Shun Katada, Koichi Misawa, Hisashi Tsujimura, Masanobu Hibi","doi":"10.1093/ijnp/pyaf016","DOIUrl":"10.1093/ijnp/pyaf016","url":null,"abstract":"<p><strong>Background: </strong>The global prevalence of dementia is significantly increasing. Early detection and prevention strategies, particularly for mild cognitive impairment (MCI), are crucial but currently hindered by the lack of established biomarkers. Here, we aimed to develop a high-precision screening method for MCI by combining D-amino acid profiles from peripheral blood samples with noninvasive subject information using nonlinear machine learning (ML) algorithms.</p><p><strong>Methods: </strong>A cross-sectional study was conducted with 200 participants aged 50-89 years, classified into cognitively normal and MCI-suspected groups based on Mini-Mental State Examination scores. High-throughput techniques were used to analyze the D-amino acid profiles, specifically D-alanine (%) and D-proline (%), in peripheral blood. Correlation analysis was performed between D-amino acid levels in venous and fingertip blood. The predictive performance of various ML models, including Logistic Regression, Random Forest, kernel Support Vector Machine (SVM), and Artificial Neural Network (ANN), was compared.</p><p><strong>Results: </strong>Nonlinear models (kernel SVM and ANN) that combined D-amino acid profiles with subject information achieved the highest area under the curve values of 0.78 and 0.79, respectively, demonstrating that the combination of D-amino acid profiles and noninvasive subject information is effective in detecting MCI.</p><p><strong>Conclusions: </strong>Combining D-amino acid profiles with noninvasive subject information using nonlinear ML models, particularly kernel SVM and ANN, shows promise as a high-precision screening tool for MCI. This approach could serve as a cost-effective preliminary screening method before more invasive and expensive diagnostic tests and significantly contribute to the early detection and development of intervention strategies for dementia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}