International Journal of Neuropsychopharmacology最新文献

{"title":"Lurasidone response in bipolar type I depression with childhood trauma exposure.","authors":"Hernan F Guillen-Burgos, Juan F Galvez-Florez, Sergio Moreno-López, Roger S McIntyre","doi":"10.1093/ijnp/pyaf020","DOIUrl":"10.1093/ijnp/pyaf020","url":null,"abstract":"<p><strong>Importance: </strong>Childhood trauma (CT) worse the course of bipolar disorder (BD) and negatively impacts treatment outcomes. Despite the recognized influence of CT on clinical trajectories, limited evidence exists on how it affects specific pharmacological responses in BD.</p><p><strong>Objective: </strong>This study aimed to investigate the effectiveness of lurasidone in BD type I depression, with a focus on how CT exposure impacts treatment response and remission.</p><p><strong>Design: </strong>A multisite, observational, prospective, comparative effectiveness study over an 8-week period was conducted.</p><p><strong>Setting: </strong>A multisite in 4 clinical research sites in Colombia.</p><p><strong>Participants: </strong>A total of 84 adults with BD type I depression were enrolled (lurasidone = 41, lurasidone with lithium = 43).</p><p><strong>Intervention: </strong>Over an 8-week period, 41 participants were assigned to the lurasidone arm and 43 to the lurasidone plus lithium arm.</p><p><strong>Exposure: </strong>Childhood trauma exposure was measured with the Childhood Trauma Questionnaire-Short Form. BD with CT (n = 40) and BD without CT (n = 44) were included.</p><p><strong>Main outcome and measures: </strong>The primary outcome was changes in Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Secondary outcomes included changes in Clinical Global Impression-Bipolar depression severity scores and responder rates.</p><p><strong>Results: </strong>Bipolar disorder with CT exposure demonstrated a smaller mean reduction in MADRS scores compared to those without CT exposure for both treatments (monotherapy: Least Square (LS) -3.4, 95% CI, -6.03 to -0.76, P = .013; combination therapy: LS -3.1, 95% CI, -5.36 to -0.63, P = .014). The presence of CT exposure, particularly physical abuse (PA), was associated with poorer response rates. Notably, lurasidone in combination with lithium showed superior outcomes compared to monotherapy, although effectiveness was attenuated in participants with documented CT exposure.</p><p><strong>Conclusions: </strong>This study provides real-world evidence suggesting that CT exposure may modify treatment response in BD type I depression. Our findings underscore the importance of CT screening to guide personalized treatment strategies.</p><p><strong>Relevance: </strong>This study provides evidence that CT, particularly PA, attenuates the antidepressant effects of lurasidone in BD type I depression, leading to lower response and remission rates in both monotherapy and combination therapy with lithium. These findings underscore the clinical importance of screening for CT in BD to guide personalized treatment strategies. Identifying trauma history may help clinicians optimize treatment selection, considering the potential need for combination pharmacotherapy and adjunctive trauma-focused psychotherapeutic interventions to improve outcomes in this vulnerable population.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742811","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":3.7,"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":"Altered proteomics in brain extracellular vesicles from depressed individuals who died by suicide implicates synaptic processes.","authors":"Pascal Ibrahim, Haruka Mitsuhashi, Lorne Taylor, Jenna Cleyle, Naguib Mechawar, Corina Nagy, Gustavo Turecki","doi":"10.1093/ijnp/pyaf012","DOIUrl":"10.1093/ijnp/pyaf012","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is a common and debilitating disorder whose molecular neurobiology remains unclear. Extracellular vesicles (EVs) are small vesicles that are released by cells and are involved in intercellular communication. They carry bioactive molecules, such as proteins, that reflect the state of their cell of origin. In this study, we sought to investigate the proteomic cargo of brain EVs from depressed individuals as compared to EVs from matched neurotypical individuals. In addition, we investigated how the EV proteomic cargo compares to the proteomic profile of bulk tissue.</p><p><strong>Methods: </strong>Using mass spectrometry and label-free quantification, we investigated the EV and bulk tissue protein profile from anterior cingulate cortex samples from 86 individuals. We performed differential expression analysis to compare cases and controls, followed by in silico analysis to determine potential implicated functions of dysregulated proteins.</p><p><strong>Results: </strong>Extracellular vesicles display distinct proteomic profiles compared to bulk tissue. Differential expression analysis showed that 70 proteins were differentially packaged in EVs in MDD, while there was no significant difference in protein levels between groups in bulk tissue. In silico analysis points to a strong role of these differential EV proteins in synaptic functions.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first study to profile EV proteins in depression, providing novel information to better understand the pathophysiology of MDD. This work paves the way for discovering new therapeutic targets for MDD and prompts more investigations into EVs in MDD and other psychiatric disorders.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12122421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483075","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":3.7,"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":3.7,"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":"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":"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 cyclic adenosine monophosphate (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 amyloid precursor protein/presenilin-1 (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, novel object recognition (NOR), and Morris water maze (MWM) were performed to investigate cognitive function in mice. Western blot and immunofluorescence staining were used to identify the 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-04957325 pretreatment reversed the conversation of proinflammatory microglia in BV2 cells induced by AβO, while also suppressing the levels of inflammatory factors, including interleukin-1β, interleukin-6, tumor necrosis factor-α, inducible nitric oxide synthase , and cyclooxygenase-2. In addition, AβO incubation upregulated the expression of PDE8 and concurrently downregulated that of brain-derived neurotrophic factor (BDNF), cAMP, p-PKA/PKA, and p-CREB/CREB in BV2 cells, all of which were reversed by PF. In vivo experiments evidenced 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>Conclusions: </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":3.7,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116884/pdf/","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":"OA","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":3.7,"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":3.7,"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}

{"title":"Associations between clozapine availability, the diagnosis of treatment-resistant schizophrenia subgroups, antipsychotic monotherapy, and concomitant psychotropics among patients with schizophrenia: a real-world nationwide study.","authors":"Shinichiro Ochi, Fumitoshi Kodaka, Naomi Hasegawa, Takashi Tsuboi, Kazutaka Ohi, Shun Igarashi, Kentaro Fukumoto, Jun-Ichi Iga, Hiroyuki Muraoka, Hitoshi Iida, Hiromi Tagata, Hiroko Kashiwagi, Shusuke Numata, Hirotaka Yamagata, Masahiro Takeshima, Kayo Ichihashi, Naoki Hashimoto, Tatsuya Nagasawa, Toshinori Nakamura, Junya Matsumoto, Hisashi Yamada, Hikaru Hori, Shu-Ichi Ueno, Ken Inada, Ryota Hashimoto, Norio Yasui-Furukori","doi":"10.1093/ijnp/pyaf011","DOIUrl":"10.1093/ijnp/pyaf011","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>The rate of antipsychotic polypharmacy is high. One risk factor for antipsychotic polypharmacy may be the severity of schizophrenia, including treatment-resistant schizophrenia (TRS). We hypothesized that the institutions that are able to prescribe clozapine present differences in pharmacological treatment even before TRS is diagnosed.</p><p><strong>Study design: </strong>A total of 8155 patients with schizophrenia were divided into the clozapine-available institution (CAI) group and the clozapine-unavailable institution (CUI) group. The psychotropic prescription rates at discharge were compared between the two groups. Furthermore, to investigate whether the diagnosis of TRS subgroups influenced treatment efficacy, we compared CAIs and CUIs with descriptions of subgroups with TRS (DSTRS) and those without descriptions of subgroups with TRS (NDSTRS).</p><p><strong>Results: </strong>Compared to the CUI group, the rates of both antipsychotic monotherapy (58.3% vs. 50.7%; P = 2.4 × 10-7) and antipsychotic monotherapy without the concomitant use of other psychotropics (20.4% vs. 15.6%; P = 3.8 × 10-5) were significantly higher in the CAI group. The rate of antipsychotic monotherapy in the CAI with DSTRS group (63.3%) was significantly higher than that in the CAI with NDSTRS group (54.5%; P = 1.4 × 10-12), the CUI with DSTRS group (49.6%; P = 4.9 × 10-9), and the CUI with NDSTRS group (50.9%; P = 2.0 × 10-8). The rate of antipsychotic monotherapy without the concomitant use of other psychotropics in the CAI with DSTRS group (22.6%) was also significantly higher than that in the CAI with NDSTRS group (18.7%; P = 4.7 × 10-4), the CUI with DSTRS group (15.9%; P = 5.5 × 10-4), and the CUI with NDSTRS group (15.2%; P = 8.0 × 10-5). There was no significant difference in these rates between the other groups.</p><p><strong>Conclusions: </strong>Both the availability of clozapine prescriptions and the precise diagnosis of TRS subgroups at discharge can promote the development of an organizational culture that facilitates the treatment of patients with schizophrenia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11986582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735825","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":"Association of driving with blood delta-9-tetrahydrocannabinol: a systematic review.","authors":"Danial Behzad, Sampson Zhao, Reena Besa, Bruna Brands, Christine M Wickens, Marilyn A Huestis, Bernard Le Foll, Patricia Di Ciano","doi":"10.1093/ijnp/pyaf021","DOIUrl":"10.1093/ijnp/pyaf021","url":null,"abstract":"<p><strong>Importance: </strong>Driving under the influence of cannabis increases the risk of motor vehicle collisions. In some jurisdictions, deterrence rests on the ability to detect delta-9-tetrahydrocannabinol (THC) in blood. Recent evidence suggests that there may be a nuanced relationship of blood THC to driving.</p><p><strong>Objective: </strong>The purpose of this systematic review was to summarize all published papers investigating the presence of a linear relationship between blood THC and driving, primarily measured by simulated driving in the lab.</p><p><strong>Outcomes: </strong>The main outcomes assessed included \"weaving\"/lateral control (eg, standard deviation of lateral position), speed, car following (following distance; coherence), reaction time, and overall driving performance.</p><p><strong>Results: </strong>Of the 4845 records from the literature search, only 12 met the inclusion criteria. Ten of these reported no significant linear correlations between blood THC and measures of driving (8 out of 9 for \"weaving\"/lateral control, 4 out of 5 for speed, 2 of 3 for car following tasks (coherence/headway maintenance task), 1/1 for reaction time, 3/3 for overall driving performance). The studies that did find an association between driving and blood THC employed complex driving situations.</p><p><strong>Conclusions: </strong>This synthesis has important implications for road safety given driving situations can be complex due to challenging road situations and increases in potency of cannabis over the past years. Current methods of detection of impairment may be suited to some types of situations but more large-scale studies on the relationship of blood THC and driving are needed that systematically vary driving complexity and cannabis potency.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763696","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}