International Journal of Neuropsychopharmacology最新文献

{"title":"Understanding the therapeutic action of antipsychotics: from molecular to cellular targets with focus on the islands of Calleja","authors":"Merve Direktor, Peter Gass, Dragos Inta","doi":"10.1093/ijnp/pyae018","DOIUrl":"https://doi.org/10.1093/ijnp/pyae018","url":null,"abstract":"The understanding of the pathophysiology of schizophrenia as well as the mechanisms of action of antipsychotic drugs remains a challenge for psychiatry. The demonstration of the therapeutic efficacy of several new atypical drugs targeting multiple different receptors apart from the classical dopamine D2 receptor as initially postulated unique antipsychotic target, complicated even more conceptualization efforts. Here we discuss results suggesting a main role of the islands of Calleja, still poorly studied GABAergic granule cell clusters in the ventral striatum, as cellular targets of several innovative atypical antipsychotics (clozapine, cariprazine and xanomeline/emraclidine) effective in treating also negative symptoms of schizophrenia. We will emphasize the potential role of dopamine D3 and M4 muscarinic acetylcholine receptor expressed at highest level by the islands of Calleja, as well as their involvement in schizophrenia-associated neurocircuitries. Finally, we will discuss the implications of new data showing ongoing adult neurogenesis of the islands of Calleja, as a very promising antipsychotic target linking long-life neurodevelopment and dopaminergic dysfunction in the striatum.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140609015","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":"Outpatient antipsychotic use and severe COVID-19: avoiding the impact of age in a real-world data study","authors":"Samuel Pintos-Rodríguez, Irene Visos-Varela, Almudena Rodríguez Fernández, Maruxa Zapata-Cachafeiro, María Piñeiro-Lamas, María Teresa Herdeiro, Rosa María García Álvarez, Adolfo Figueiras, Ángel Salgado-Barreira","doi":"10.1093/ijnp/pyae020","DOIUrl":"https://doi.org/10.1093/ijnp/pyae020","url":null,"abstract":"Background The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence as regards their effect in the non-geriatric population . We aim to assess the association between antipsychotic use and risk of disease progression and hospitalisation due to COVID-19 among the general population, stratifying by age. Methods We conducted a population-based, multiple case-control study to assess: (1) risk of hospitalisation, with cases being patients with a PCR(+)test who required hospitalisation and controls being subjects without a PCR(+) test; and (2) risk of progression to hospitalisation, with cases being the same as those used in the hospitalisation substudy and controls being non-hospitalised PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. Results Antipsychotic treatment in patients <65 years was not associated with a higher risk of hospitalisation due to COVID-19 (aOR 0.94 [95%CI 0.69–1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI 0.70–1.33]). For patients aged ≥65 years, however, there was a significant, increased risk of hospitalisation (aOR 1.58 [95%CI 1.38–1.80]) and disease progression (aOR 1.31 [95%CI 1.12–1.55]). Conclusions The results of our large-scale real world data study suggest that antipsychotic use is not associated with a greater risk of hospitalisation due to COVID-19 and progression to hospitalisation among patients younger than 65 years. The effect found in the over-65-year age group might be associated with off-label use of antipsychotics.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140597127","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":"Placebo Effects Are Small on Average in the 7.5% CO2 Inhalational Model of Generalised Anxiety","authors":"Nathan T M Huneke, Cosmina Cross, Harry A Fagan, Laura Molteni, Naomi Phillips, Matthew Garner, David S Baldwin","doi":"10.1093/ijnp/pyae019","DOIUrl":"https://doi.org/10.1093/ijnp/pyae019","url":null,"abstract":"Background Anxiety disorders are highly prevalent and socio-economically costly. Novel pharmacological treatments for these disorders are needed as many patients do not respond to current agents or experience unwanted side-effects. However, a barrier to treatment development is the variable and large placebo response rate seen in trials of novel anxiolytics. Despite this, the mechanisms that drive placebo responses in anxiety disorders have been little investigated, possibly due to low availability of convenient experimental paradigms. We aimed to develop and test a novel protocol for inducing placebo anxiolysis in the 7.5% CO2 inhalational model of generalised anxiety in healthy volunteers. Methods Following a baseline 20-minute CO2 challenge, 32 healthy volunteers were administered a placebo intranasal spray labelled as either the anxiolytic ‘lorazepam’ or ‘saline’. Following this, participants surreptitiously underwent a 20-minute inhalation of normal air. Post-conditioning, a second dose of the placebo was administered, after which participants completed another CO2 challenge. Results Participants administered sham ‘lorazepam’ reported significant positive expectations of reduced anxiety (p = 0.001) but there was no group-level placebo effect on anxiety following CO2 challenge post-conditioning (p’s > 0.350). Surprisingly, we found many participants exhibited unexpected worsening of anxiety, despite positive expectations. Conclusions Contrary to our hypothesis, our novel paradigm did not induce a placebo response, on average. It is possible that effects of 7.5% CO2 inhalation on prefrontal cortex function, or behaviour in line with a Bayesian predictive coding framework, attenuated the effect of expectations on subsequent placebo response. Future studies are needed to explore these possibilities.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603402","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":"Acute Dissociation and Ketamine’s Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-controlled Trial","authors":"Sumra Sajid, Hanga C Galfalvy, John G Keilp, Ainsley K Burke, J John Mann, Michael F Grunebaum","doi":"10.1093/ijnp/pyae017","DOIUrl":"https://doi.org/10.1093/ijnp/pyae017","url":null,"abstract":"Objective Explore relationships of acute dissociative effects of intravenous ketamine with change in depression and suicidal ideation and with plasma metabolite levels in a randomized, midazolam-controlled trial. Method Data from a completed trial in suicidal, depressed participants (N=40) randomized to ketamine was used to examine relationships between ketamine treatment-emergent dissociative and psychotomimetic symptoms with pre/post-infusion changes in suicidal ideation and depression severity. Non-parametric correlational statistics were used. These methods were also used to explore associations between dissociative or psychotomimetic symptoms and blood levels of ketamine and metabolites in a subset (N=28) who provided blood samples immediately post-infusion. Results Neither acute dissociative nor psychotomimetic effects of ketamine were associated with changes in suicidal ideation or depressive symptoms from pre- to post-infusion. Norketamine had a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection (p = .064; p = .013 removing one outlier). Dehydronorketamine correlated with CADSS scores at 40 minutes (p = .034), 230 minutes (p = .014), and Day 1 (p=.012). Conclusion We did not find evidence that ketamine’s acute, transient dissociative or psychotomimetic effects are associated with its antidepressant or anti-suicidal ideation actions. The correlation of higher plasma norketamine with lower dissociative symptoms on Day 1 post-treatment suggests dissociation may be more an effect of the parent drug.","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140596951","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":"Corrigendum to: Anhedonia, Apathy, Pleasure, and Effort-Based Decision-Making in Adult and Adolescent Cannabis Users and Controls.","authors":"","doi":"10.1093/ijnp/pyae004","DOIUrl":"10.1093/ijnp/pyae004","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10965023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293419","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":"Histamine-3 Receptor Availability and Glutamate Levels in the Brain: A PET-1H-MRS Study of Patients With Schizophrenia and Healthy Controls.","authors":"Atheeshaan Arumuham, Matthew M Nour, Mattia Veronese, Katherine Beck, Ellis Chika Onwordi, David J Lythgoe, Sameer Jauhar, Eugenii A Rabiner, Oliver D Howes","doi":"10.1093/ijnp/pyae011","DOIUrl":"10.1093/ijnp/pyae011","url":null,"abstract":"<p><strong>Background: </strong>The histamine-3 receptor (H3R) may have a role in cognitive processes through its action as a presynaptic heteroreceptor inhibiting the release of glutamate in the brain. To explore this, we examined anterior cingulate cortex (ACC) and striatum H3R availability in patients with schizophrenia and characterized their relationships with glutamate levels in corresponding brain regions.</p><p><strong>Methods: </strong>We employed a cross-sectional study, recruiting 12 patients with schizophrenia and 12 healthy volunteers. Participants underwent positron emission tomography using the H3R-specific radio ligand [11C]MK-8278, followed by proton magnetic resonance spectroscopy to measure glutamate levels, recorded as Glu and Glx. Based on existing literature, the ACC and striatum were selected as regions of interest.</p><p><strong>Results: </strong>We found significant inverse relationships between tracer uptake and Glu (r = -0.66, P = .02) and Glx (r = -0.62, P = .04) levels in the ACC of patients, which were absent in healthy volunteers (Glu: r = -0.19, P = .56, Glx: r = 0.10, P = .75). We also found a significant difference in striatal (F1,20 = 6.00, P = .02) and ACC (F1,19 = 4.75, P = .04) Glx levels between groups.</p><p><strong>Conclusions: </strong>These results provide evidence of a regionally specific relationship between H3Rs and glutamate levels, which builds on existing preclinical literature. Our findings add to a growing literature indicating H3Rs may be a promising treatment target in schizophrenia, particularly for cognitive impairment, which has been associated with altered glutamate signaling.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905621","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":"Obituary - Prof Brian E. Leonard (1936-2023).","authors":"Timothy G Dinan, John F Cryan","doi":"10.1093/ijnp/pyae012","DOIUrl":"10.1093/ijnp/pyae012","url":null,"abstract":"","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905622","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":"Neural, Anti-Inflammatory, and Clinical Effects of Transauricular Vagus Nerve Stimulation in Major Depressive Disorder: A Systematic Review.","authors":"Joao Parente, Anna Carolyna Gianlorenco, Ingrid Rebello-Sanchez, Minkyung Kim, Jose Mario Prati, Chi Kyung Kim, Hyuk Choi, Jae-Jun Song, Felipe Fregni","doi":"10.1093/ijnp/pyad058","DOIUrl":"10.1093/ijnp/pyad058","url":null,"abstract":"<p><strong>Background: </strong>The discovery of effective treatments for major depressive disorder (MDD) may help target different brain pathways. Invasive vagus nerve stimulation (VNS) is an effective neuromodulation technique for the treatment of MDD; however, the effectiveness of the noninvasive technique, transauricular VNS (taVNS), remains unknown. Moreover, a mechanistic understanding of the neural effects behind its biological and therapeutic effects is lacking. This review aimed to evaluate the clinical evidence and the neural and anti-inflammatory effects of taVNS in MDD.</p><p><strong>Methods: </strong>Two searches were conducted using a systematic search strategy reviewed the clinical efficacy and neural connectivity of taVNS in MDD in humans and evaluated the changes in inflammatory markers after taVNS in humans or animal models of depression. A risk of bias assessment was performed in all human studies.</p><p><strong>Results: </strong>Only 5 studies evaluated the effects of taVNS in patients with depression. Although the studies demonstrated the efficacy of taVNS in treating depression, they used heterogeneous methodologies and limited data, thus preventing the conduct of pooled quantitative analyses. Pooled analysis could not be performed for studies that investigated the modulation of connectivity between brain areas; of the 6 publications, 5 were based on the same experiment. The animal studies that analyzed the presence of inflammatory markers showed a reduction in the level of pro-inflammatory cytokines or receptor expression.</p><p><strong>Conclusions: </strong>Data on the clinical efficacy of taVNS in the treatment of MDD are limited. Although these studies showed positive results, no conclusions can be drawn regarding this topic considering the heterogeneity of these studies, as in the case of functional connectivity studies. Based on animal studies, the application of taVNS causes a decrease in the level of inflammatory factors in different parts of the brain, which also regulate the immune system. Therefore, further studies are needed to understand the effects of taVNS in patients with MDD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10972554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49690436","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":"Network Meta-Analysis Indicates Superior Effects of Omega-3 Polyunsaturated Fatty Acids in Preventing the Transition to Psychosis in Individuals at Clinical High-Risk.","authors":"Chengfeng Chen, Yongyan Deng, Yuling Li, Meiting Zhang, Tong Yu, Kun Xie, Wuyou Bao, Peiying Li, Ling Sun, Tianhong Zhang, Yikang Zhu, Bin Zhang","doi":"10.1093/ijnp/pyae014","DOIUrl":"10.1093/ijnp/pyae014","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of pharmacological and nutritional interventions in individuals at clinical high risk for psychosis (CHR-P) remains elusive. This study aims to investigate the efficacy of pharmacological and nutritional interventions in CHR-P and whether these interventions can enhance the efficacy of psychological treatments.</p><p><strong>Methods: </strong>We systematically reviewed data from 5 databases until July 24, 2021: PubMed, Web of Science, EMBASE, China National Knowledge Infrastructure, and WanFang Data. The primary outcome was the transition to psychosis. Network meta-analyses were conducted at 3 time points (6, 12, and ≥24 months) considering both pharmacological/nutritional interventions alone and its combination with psychotherapy.</p><p><strong>Results: </strong>Out of 11 417 identified references, 21 studies were included, comprising 1983 participants. CHR-P participants receiving omega-3 polyunsaturated fatty acids treatment were associated with a lower probability of transition compared with placebo/control at 6 months (odds ratio [OR] = 0.07, 95% confidence interval [CI] = .01 to .054), 12 months (OR = 0.14, 95% CI = .03 to .66), and ≥24 months (OR = 0.16, 95% CI = .05 to .54). Moreover, risperidone plus psychotherapy was associated with a lower likelihood of transition at 6 months compared with placebo/control plus psychotherapy, but this result was not sustained over longer durations.</p><p><strong>Conclusion: </strong>Omega-3 polyunsaturated fatty acids helped in preventing transitions to psychosis compared with controls.</p><p><strong>Prospero registration number: </strong>CRD42021256209.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10949445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971800","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":"Profiling Small RNA From Brain Extracellular Vesicles in Individuals With Depression.","authors":"Pascal Ibrahim, Ryan Denniston, Haruka Mitsuhashi, Jennie Yang, Laura M Fiori, Dariusz Żurawek, Naguib Mechawar, Corina Nagy, Gustavo Turecki","doi":"10.1093/ijnp/pyae013","DOIUrl":"10.1093/ijnp/pyae013","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is a leading cause of disability with significant mortality risk. Despite progress in our understanding of the etiology of MDD, the underlying molecular changes in the brain remain poorly understood. Extracellular vesicles (EVs) are lipid-bound particles that can reflect the molecular signatures of the tissue of origin. We aimed to optimize a streamlined EV isolation protocol from postmortem brain tissue and determine whether EV RNA cargo, particularly microRNAs (miRNAs), have an MDD-specific profile.</p><p><strong>Methods: </strong>EVs were isolated from postmortem human brain tissue. Quality was assessed using western blots, transmission electron microscopy, and microfluidic resistive pulse sensing. EV RNA was extracted and sequenced on Illumina platforms. Functional follow-up was performed in silico.</p><p><strong>Results: </strong>Quality assessment showed an enrichment of EV markers, as well as a size distribution of 30 to 200 nm in diameter, and no contamination with cellular debris. Small RNA profiling indicated the presence of several RNA biotypes, with miRNAs and transfer RNAs being the most prominent. Exploring miRNA levels between groups revealed decreased expression of miR-92a-3p and miR-129-5p, which was validated by qPCR and was specific to EVs and not seen in bulk tissue. Finally, in silico functional analyses indicate potential roles for these 2 miRNAs in neurotransmission and synaptic plasticity.</p><p><strong>Conclusion: </strong>We provide a streamlined isolation protocol that yields EVs of high quality that are suitable for molecular follow-up. Our findings warrant future investigations into brain EV miRNA dysregulation in MDD.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065190","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}