International Journal of Neuropsychopharmacology最新文献

{"title":"Neurobiological influences on event perception: the role of catecholamines.","authors":"Foroogh Ghorbani, Xianzhen Zhou, Veit Roessner, Bernhard Hommel, Astrid Prochnow, Christian Beste","doi":"10.1093/ijnp/pyaf008","DOIUrl":"10.1093/ijnp/pyaf008","url":null,"abstract":"<p><strong>Background: </strong>Event segmentation, the cognitive process of parsing continuous experiences into discrete events, plays a fundamental role in how humans perceive and interact with their environment. Guided by Event Segmentation Theory, this study investigates the modulation of event segmentation by the catecholaminergic system by methylphenidate (MPH).</p><p><strong>Methods: </strong>Healthy adult participants (N = 52) engaged in a double-blind, counter-balanced, placebo-controlled experiment in which they watched a movie and identified event boundaries under placebo and MPH conditions.</p><p><strong>Results: </strong>With the same information given, MPH increased the likelihood that the information was considered meaningful. Crucially, the number of situational changes and participant's prior experience had an interactive effect on the probability of event segmentation. There was a stronger relationship between environmental information and segmentation probability when catecholaminergic levels were elevated by MPH in addition to previous experience.</p><p><strong>Conclusions: </strong>The catecholaminergic system modulates how incoming information is segmented to build meaningful episodes. Prior experience supports the effects of MPH to unfold. These findings underscore the complex interplay between neurochemical modulation and cognitive processes involved in event perception.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467918","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":"Investigation of the mesencephalic astrocyte-derived neurotrophic factor-endoplasmic reticulum stress pathway in mood disorders.","authors":"Mohammad Ali, Bianca Wollenhaupt-Aguiar, Yifan Wang, Fahed Abu-Hijleh, Nicolette Rigg, Taiane de Azevedo Cardoso, Imran Ahmed, Ridhi Gopalakrishnan, Karen Jansen, Luciano Dias de Mattos Souza, Ricardo Azevedo da Silva, Thaise Campos Mondin, Flavio Kapczinski, Fernanda Pedrotti Moreira, Andrew Lofts, William D Gwynne, Todd Hoare, Ram Mishra, Benicio N Frey","doi":"10.1093/ijnp/pyaf004","DOIUrl":"10.1093/ijnp/pyaf004","url":null,"abstract":"<p><strong>Background: </strong>Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress. Mesencephalic astrocyte-derived neurotrophic factor (MANF), a trophic factor, decreases ER stress by modulating the UPR. The objective of this study is to investigate the MANF-ER stress pathway in BD and major depressive disorder (MDD) compared to healthy controls (HC).</p><p><strong>Methods: </strong>MANF protein concentration and MANF and GRP78 gene expression were assessed in peripheral blood from individuals with BD, MDD, and HC (protein: 40 BD, 55 MDD, 55 HC; gene expression: 52 BD, 61 MDD, 69 HC). MANF protein and gene expression along with GRP78 gene expression were also analyzed in postmortem brain tissue (20 BD, 20 MDD, 19 HC). MANF protein was quantified using an ELISA assay while quantitative polymerase chain reaction was used for MANF and GRP78 gene expression.</p><p><strong>Results: </strong>Peripheral MANF protein levels were reduced in individuals with BD in a depressive state compared to controls (P = .031) and euthymic BD participants (P = .013). No significant differences in MANF or GRP78 gene expression were observed in BD irrespective of mood state, or MDD compared to HC (all P > .05). No differences were observed regarding MANF/GRP78 protein or gene expression levels in postmortem tissue (P > .05).</p><p><strong>Conclusions: </strong>Individuals with BD who were in an acute depressive phase were found to have reduced peripheral MANF levels potentially signifying abnormal UPR and supporting the notion that BD is associated with increased ER stress.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970704","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":"Retraction of: Mesenchymal Stem Cell-Derived Extracellular Vesicles Alleviate M1 Microglial Activation in Brain Injury of Mice With Subarachnoid Hemorrhage via microRNA-140-5p Delivery.","authors":"","doi":"10.1093/ijnp/pyaf006","DOIUrl":"10.1093/ijnp/pyaf006","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":"28 2","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414093","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":"The development of opioid vaccines as a novel strategy for the treatment of opioid use disorder and overdose prevention.","authors":"Mustafa Tuncturk, Shikha Kushwaha, Robin M Heider, Tyler Oesterle, Richard Weinshilboum, Ming-Fen Ho","doi":"10.1093/ijnp/pyaf005","DOIUrl":"10.1093/ijnp/pyaf005","url":null,"abstract":"<p><p>Opioid use disorder (OUD) affects over 40 million people worldwide, creating significant social and economic burdens. Medication for opioid use disorder (MOUD) is often considered the primary treatment approach for OUD. MOUD, including methadone, buprenorphine, and naltrexone, is effective for some, but its benefits may be limited by poor adherence to treatment recommendations. Immunopharmacotherapy offers an innovative approach by using vaccines to generate antibodies that neutralize opioids, blocking them from crossing the blood-brain barrier and reducing their psychoactive effects. To date, only 3 clinical trials for opioid vaccines have been published. While these studies demonstrated the potential of opioid vaccines for relapse prevention, there is currently no standardized protocol for evaluating their effectiveness. We have reviewed recent preclinical studies that demonstrated the efficacy of vaccines targeting opioids, including heroin, morphine, oxycodone, hydrocodone, and fentanyl. These studies showed that vaccines against opioids reduced drug reinforcement, decreased opioid-induced antinociception, and increased survival rates against lethal opioid doses. These studies also demonstrated the importance of vaccine formulation and the use of adjuvants in enhancing antibody production and specificity. Finally, we highlighted the strengths and concerns associated with the opioid vaccine treatment, including ethical considerations.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005126","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":"Quantitative evaluation of multiple treatment regimens for treatment-resistant depression.","authors":"Yulin Feng, Yinghua Lv, Juan Yang, Ling Xu, Junchao Chen, Jihan Huang, Jiyuan Ren, Qingshan Zheng, Lujin Li","doi":"10.1093/ijnp/pyaf007","DOIUrl":"10.1093/ijnp/pyaf007","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to quantitatively evaluate the efficacy and safety of various treatment regimens for treatment-resistant depression (TRD) across oral, intravenous, and intranasal routes to inform clinical guidelines.</p><p><strong>Methods: </strong>A systematic review identified randomized controlled trials on TRD, with efficacy measured by changes in the Montgomery-Åsberg Depression Rating Scale (MADRS). We developed pharmacodynamic and covariate models for different administration routes, using Monte Carlo simulations to estimate efficacy distribution. Dropout and adverse event-related dropout rates were analyzed via single-arm meta-analysis.</p><p><strong>Results: </strong>Involving 22 studies with 56 treatment arms and 3059 patients, our findings suggest combination therapies outperform monotherapy, achieving an additional 6.5% reduction in MADRS scores over 12 weeks. The most effective combinations were olanzapine with fluoxetine and quetiapine with selective serotonin reuptake inhibitors/ selective serotonin and norepinephrine reuptake inhibitors. Injectable treatments, particularly ayahuasca, produced rapid effects, with a 77% reduction in MADRS scores at 15 days. Intranasal treatments reached efficacy sooner than oral ones, with 28-day efficacy similar to the 12-week efficacy of the olanzapine-fluoxetine combination. Dropout rates due to adverse events were similar across methods (4.5%-5.2%), but total dropouts were highest for oral (17.9%) and lowest for intranasal routes (10.6%). Additionally, there was considerable variation in the incidence of headache, dizziness, and nausea across different administration routes.</p><p><strong>Conclusions: </strong>The quantitative evaluation of 22 TRD treatments illuminates key pharmacodynamic parameters, bolstering the development of clinical guidelines and aiding the design of clinical trials and medical decision-making.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143038444","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":"A novel insight into the antidepressant effect of cannabidiol: possible involvement of the 5-HT1A, CB1, GPR55, and PPARγ receptors.","authors":"Yang Miao, Fei Zhao, Wei Guan","doi":"10.1093/ijnp/pyae064","DOIUrl":"10.1093/ijnp/pyae064","url":null,"abstract":"<p><strong>Background: </strong>Depression is a prevalent and disabling disorder that poses serious problems in mental health care, and rapid antidepressants are novel treatments for this disorder. Cannabidiol (CBD), a nonintoxicating phytocannabinoid, is thought to have therapeutic potential due to its important neurological and anti-inflammatory properties. Despite major advances in pharmacotherapy in experimental animals, the exact mechanism of antidepressant-like effects remains to be elucidated.</p><p><strong>Methods: </strong>In this paper, we review the current state of knowledge on the antidepressant properties of CBD in numerous experimental and clinical studies.</p><p><strong>Results: </strong>Accumulating evidence suggests that CBD has antidepressant properties in humans and animals with few side effects, suggesting that CBD may be a potential antidepressant. Furthermore, we discuss that CBD may therefore provide a potential treatment to exert antidepressant-like effects through various molecular targets, reducing inflammation, and enhancing neurogenesis.</p><p><strong>Conclusions: </strong>Taken together with the growing popularity of CBD as a medicine, these findings extend the limited knowledge on the antidepressant effects of CBD. This potentially opens up new therapeutic means for the patients with depression.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828260","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":"Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects.","authors":"Yingliang Dai, Ben J Harrison, Christopher G Davey, Trevor Steward","doi":"10.1093/ijnp/pyaf010","DOIUrl":"10.1093/ijnp/pyaf010","url":null,"abstract":"<p><p>Ketamine is an N-methyl-D-aspartate receptor antagonist that has shown effectiveness as a rapidly acting treatment for depression. Although advances have been made in understanding ketamine's antidepressant pharmacological and molecular mechanisms of action, the large-scale neurocognitive mechanisms driving its therapeutic effects are less clearly understood. To help provide such a framework, we provide a synthesis of current evidence linking ketamine treatment to the modulation of brain systems supporting reward processing, interoception, and self-related cognition. We suggest that ketamine's antidepressant effects are, at least in part, driven by dynamic multi-level influences across these key functional domains.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374107","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":"Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer Disease.","authors":"Dongdong Jin, Min Zhang, Lei Shi, Hengfang Liu","doi":"10.1093/ijnp/pyae038","DOIUrl":"10.1093/ijnp/pyae038","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly, characterized by severe cognitive impairment and memory loss. Emerging evidence suggests that neuroinflammation plays a significant role in AD pathogenesis, with cytokines like interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) contributing to the disease progression.</p><p><strong>Methods: </strong>We utilized Gene Expression Omnibus datasets to identify IL-6 and CXCL8 as pivotal inflammatory markers in AD. In vitro experiments were conducted using SK-N-BE(2)-M17 and THP-1 cell lines treated with IL-6 and CXCL8 to model AD. Additionally, in vivo tests on Amyloid Precursor Protein/Presenilin 1 (APP/PS1) AD mouse models were performed to assess the impact of these cytokines on cognitive functions and brain pathology.</p><p><strong>Results: </strong>The results indicated a significant decrease in cell viability, increased apoptosis, and elevated inflammatory factor secretion following IL-6 and CXCL8 treatment in vitro. In vivo, AD mouse models treated with these cytokines exhibited exacerbated emotional distress, decreased social interaction, impaired cognitive functions, and increased amyloid protein deposition in neural tissues.</p><p><strong>Conclusions: </strong>The study highlights the detrimental effects of IL-6 and CXCL8 on neuronal health and cognitive functions in AD. These findings suggest that targeting these cytokines could offer potential therapeutic interventions for improving patient outcomes in Alzheimer disease.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119775","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":"Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in Patients With Treatment-Resistant Schizophrenia (TRS): Final, 1-Year Results From a Phase 2, Open-Label, Rater-Blinded, Randomized, International Clinical Trial.","authors":"Ravi Anand, Alessio Turolla, Giovanni Chinellato, Arjun Roy, Richard D Hartman","doi":"10.1093/ijnp/pyae061","DOIUrl":"10.1093/ijnp/pyae061","url":null,"abstract":"<p><p>The results from a pilot, 1-year, randomized, open-label, add-on treatment study in treatment-resistant schizophrenia (TRS) with evenamide, a glutamate modulator, were not associated with any safety abnormalities at all doses (7.5-30 mg bid), with a high retention rate even at 6-month (~85%), and 1-year (~75%), and the absence of psychotic relapses during the 1-year treatment period. Overall, treatment with evenamide showed a gradual, sustained, and clinically important improvement up to 1 year in all efficacy measures (eg, PANSS mean change ~ -20%; CGI-S mean change ~ -1.0). In addition, compared to the results at Week 6, the responder rates generally more than doubled at 1-year (PANSS \"≥20% improvement from baseline\" = ~45%; CGI-S \"2-category of improvement\" = ~25%; CGI-C \"much improved\" = ~40%). These results, rarely replicated in other trials in TRS, support the use of evenamide as an add-on treatment in patients who are not benefiting from their current first- or second-generation antipsychotic medication.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806416","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":"Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial.","authors":"Michael J Mueller, Helena D Aicher, Dario A Dornbierer, Laurenz Marten, Dila Suay, Daniel Meling, Claudius Elsner, Ilhui A Wicki, Jovin Müller, Sandra N Poetzsch, Luzia Caflisch, Alexandra Hempe, Camilla P Steinhart, Maxim Puchkov, Jonas Kost, Hans-Peter Landolt, Erich Seifritz, Boris B Quednow, Milan Scheidegger","doi":"10.1093/ijnp/pyaf001","DOIUrl":"10.1093/ijnp/pyaf001","url":null,"abstract":"<p><strong>Background: </strong>Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.</p><p><strong>Methods: </strong>This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.</p><p><strong>Results: </strong>N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2-3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation's suitability for clinical applications.</p><p><strong>Conclusions: </strong>This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders.</p><p><strong>Clinical trial registration number: </strong>Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948349","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}