International Journal of Neuropsychopharmacology最新文献

{"title":"NMDA Receptor Involvement in Dopaminergic Modulation of Neuroplasticity Induced by Paired Associative Stimulation.","authors":"Marie C Beaupain, Elham Ghanavati, Amba M Frese, Lorena Melo, Min-Fang Kuo, Michael A Nitsche","doi":"10.1093/ijnp/pyaf038","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf038","url":null,"abstract":"<p><strong>Background: </strong>Dopamine (DA) modulates long-term potentiation (LTP)-like neuroplasticity. While particularly D1 and D2 receptors are thought to influence neuroplasticity through glutamatergic NMDA receptor and GABA modulation, the exact mechanisms are not completely clarified.</p><p><strong>Objective: </strong>We aimed to explore the relevance of NMDA receptor activity for DAergic modulation of focal LTP-like plasticity induced by excitatory paired associative stimulation (ePAS).</p><p><strong>Methods: </strong>In a double-blinded, randomized, and placebo-controlled design, 17 healthy participants received DAergic agents (100 mg L-Dopa for general DAergic enhancement, 10 mg bromocriptine for selective D2 receptor activation, or placebo) with different doses of the partial NMDA receptor agonist D-cycloserine (CYC; 50, 100, 200 mg or placebo) and underwent ePAS. Cortical excitability was monitored via motor-evoked potentials induced by TMS over the left motor cortex for up to two hours post-stimulation.</p><p><strong>Results: </strong>We did not find significant interactions between DAergic agents, CYC and time across the entire sample, but significant group differences depending on sensitivity to ePAS. In high-sensitivity, but not low-sensitivity participants, ePAS induced LTP-like effects. CYC produced non-linear, dose-dependent effects on plasticity in both groups. In the high-sensitivity group, LTP-like effects persisted under both DAergic agents, but were significantly reduced under bromocriptine. CYC had a non-linear effect when combined with bromocriptine. In the low-sensitivity group, ePAS under DAergic agents did not induce LTP-like effects, and only additional intervention with medium-dose CYC restored facilitatory effects under L-Dopa.</p><p><strong>Conclusion: </strong>These findings suggest that optimal NMDA receptor activation is necessary for ePAS-induced neuroplasticity and that D2 receptor activity may reduce LTP-like effects by downregulating NMDA receptor function.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181809","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 inflammation induced by the Escherichia coli lipopolysaccharide considerably increases the systemic and brain exposure of olanzapine after oral administration in mice.","authors":"Jan Hubeňák, Martin Mžik, Hana Laštůvková, David Bayer, Lenka Jandová, Jolana Schreiberová, Ctirad Andrýs, Stanislav Mičuda, Jiří Masopust, Jaroslav Chládek","doi":"10.1093/ijnp/pyaf036","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf036","url":null,"abstract":"<p><strong>Background: </strong>A detailed understanding of alterations in olanzapine pharmacokinetics during acute inflammatory states, associated with infections, remains lacking. This study aimed to investigate the impact of endotoxemia on the pharmacokinetics of olanzapine and desmethylolanzapine (DMO) in mice.</p><p><strong>Methods: </strong>C57BL/6N mice received an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) or saline (controls), followed 24 hours later by single oral or intravenous doses of olanzapine or intravenous DMO. Concentrations and unbound fractions of olanzapine and DMO were measured in the plasma and brain homogenates.</p><p><strong>Results: </strong>In LPS-injected mice, the area under the concentration-time curve (AUCs) for olanzapine increased 3.8-fold in the plasma and 5.2-fold in brain homogenates, in consequence of a higher absolute bioavailability of olanzapine (+200 %), a lower plasma clearance (-34 %), and a higher brain penetration ratio for the unbound drug relative to controls (Kp,uu,brain 6.2 vs. 4.1). LPS attenuated the hepatic mRNA expression of cytochrome P450 1A2 and the metabolism of olanzapine to DMO. However, the AUC of plasma DMO increased by 140 % due to a 4.8-fold decrease in the plasma clearance of DMO. The brain penetration of DMO was minimal (Kp,uu,brain ≤ 0.051). The LPS-injected mice exhibited a downregulation of the hepatic and ileal mRNA expression of P-glycoprotein (Abcb1a), whereas the expression of Abcb1a and Abcb1b in the brain were upregulated.</p><p><strong>Conclusion: </strong>Endotoxemia notably increases olanzapine concentrations in the plasma and brain following oral administration in mice. Further studies should clarify whether altered pharmacokinetics results in adverse effects in acutely infected patients taking oral olanzapine.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136162","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":"Exploring the Risk of Adverse Drug Events in Combination with antiparkinsonics and antipsychotics - a two-decade real-world pharmacovigilance analysis based on the FAERS database.","authors":"Junyi Wang, Sen Lin, Chen Bai, Huimin Zhang, Haoqi Liu, Min Wang, Rongjuan Guo","doi":"10.1093/ijnp/pyaf033","DOIUrl":"https://doi.org/10.1093/ijnp/pyaf033","url":null,"abstract":"<p><strong>Background: </strong>The combination of antiparkinsonics and antipsychotic drugs (AP) can improve the motor and mental symptoms of Parkinson's disease (PD) and reduce the actual burden of chronic disease care. To explore the adverse drug events (ADEs) worthy of attention in this treatment management process, we conducted a real-world pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database.</p><p><strong>Method: </strong>The Standard pharmacotherapy for PD include Levodopa/Carbidopa, Entacapone, Rasagiline, Pramipexole, Ropinirole, Rotigotine, Apomorphine and Amantadine, etc. AP includes Quetiapine, Clozapine and Pimavanserin. We collected the ADEs reports of FAERS that conformed to the combination regimens of anti-Parkinson's drugs and AP during the 20-year period from the third quarter of 2004 to the second quarter of 2024. Disproportionate analysis and subgroup analysis were conducted through five algorithms, namely Ω shrinkage measure, additive model, multiplicative model, Combination risk ratio, and Chi-square. The Time to onset (TTO) analysis was used to predict the variation of the risk size of ADEs occurrence over time. Finally, we explored the correlation between population characteristics and the occurrence of ADEs through Logistic regression.</p><p><strong>Result: </strong>We collected a total of 6,297 cases, including 38,316 ADEs records. The results of the disproportionate analysis show that The ADEs with the highest occurrence frequency include hallucination, general physical health deterioration, somnolence, stoma site discharge, urinary tract infection and memory impairment, etc. The TTO analysis results showed that the median TTO for all ADEs was 657.50 days, the median TTO for infection and inflammation was 716.00 days, and the median TTO for psychiatric symptoms was 823.00 days. All median TTOs conform to the early failure curve. The results of Logistic regression showed that gender was correlated with the occurrence of infection and inflammation, and the female population was more inclined to have IME related to infection and inflammation.</p><p><strong>Conclusion: </strong>During the combined application of antiparkinsonics and AP, in addition to ADEs such as movement disorders and emerging mental symptoms, the risks of infection and inflammation should also be given key attention. Long-term follow-up should run through the entire process of disease diagnosis and treatment, and attention should be paid to the influence of drug dosage forms and dosages. The medication plan should be adjusted in a timely manner when ADEs occur.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110712","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":"Premorbid characteristics of the SAPAP3 mouse model of obsessive-compulsive disorder: behavior, neuroplasticity, and psilocybin treatment.","authors":"Michal Lazar, Michal Brownstien, Alexander Botvinnik, Chloe Shevakh, Orr Shahar, Tzuri Lifschytz, Bernard Lerer","doi":"10.1093/ijnp/pyaf022","DOIUrl":"10.1093/ijnp/pyaf022","url":null,"abstract":"<p><strong>Background: </strong>SAPAP3-knockout (SAPAP3-KO) mice develop excessive self-grooming behavior at 4-6 months of age, serving as a model for obsessive-compulsive disorder (OCD). Given that anxiety often precedes OCD diagnosis in humans, this study investigated whether juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the self-grooming phenotype, and whether such behaviors respond to psilocybin (PSIL) treatment. The study also examined 4 key neuroplasticity-related synaptic proteins-GAP43, PSD95, synaptophysin, and SV2A-as SAPAP3 is a postsynaptic scaffold protein that interacts with PSD95 and may affect synaptic function.</p><p><strong>Methods: </strong>Two studies were conducted using male and female juvenile (10-13 weeks) SAPAP3-KO mice. Study 1 compared behavioral phenotypes between homozygous (HOM), heterozygous, and wild-type (WT) mice. Study 2 evaluated a different sample of HOM and WT mice and assessed the effect of PSIL (4.4 mg/kg) on identified behavioral differences. Both studies included comprehensive behavioral testing focused on anxiety-like behavior, social interaction, and cognitive function. Additionally, levels of 4 synaptic proteins were measured by western blots in the frontal cortex, hippocampus, amygdala, and striatum of juvenile and adult SAPAP3-KO mice.</p><p><strong>Results: </strong>In both studies, juvenile HOM SAPAP3-KO mice showed significant anxiety-like behaviors compared to WT mice, spending less time in open field center, and elevated plus maze open arms. They also buried fewer marbles and found fewer buried Oreos than WT mice. Psilocybin treatment did not improve these behavioral manifestations. Analysis of synaptic proteins revealed significant increases in GAP43, synaptophysin, and SV2A across multiple brain regions in adult male HOM mice and of SV2A in the frontal cortex of HOM females compared to WT, but not in juvenile mice of either sex.</p><p><strong>Conclusions: </strong>Juvenile SAPAP3-KO mice exhibit anxiety-like behaviors before developing the characteristic excessive self-grooming phenotype, paralleling the prodromal anxiety often seen in human OCD. Unlike in adult SAPAP3-KO mice, these manifestations were not responsive to PSIL treatment. The age-dependent increases in synaptic proteins observed in adult (but not juvenile) male SAPAP3-KO mice HOM for the deletion and to a lesser extent in female homozygotes, may represent compensatory plasticity changes in response to the phenotype. These results provide insights into the developmental trajectory of OCD-like behaviors and associated neuroplastic adaptations.</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/PMC12062877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742814","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 relapse with all-cause mortality in adult patients with stable schizophrenia.","authors":"Christoph U Correll, Brahim K Bookhart, Carmela Benson, Zhiwen Liu, Zhongyun Zhao, Wenze Tang","doi":"10.1093/ijnp/pyaf018","DOIUrl":"10.1093/ijnp/pyaf018","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia shortens the average lifespan by an estimated 15 years. This retrospective study evaluated whether relapse independently increases all-cause mortality risk in patients with stable schizophrenia.</p><p><strong>Methods: </strong>Eligible adults had ≥2 outpatient claims on separate dates or ≥1 inpatient claim with a schizophrenia diagnosis code, had ≥12 months of continuous pre-index enrollment without a relapse, and received ≥1 antipsychotic medication during the baseline period. Occurrence and number of inpatient and non-inpatient relapses and all-cause mortality were evaluated during follow-up. A marginal structural model adjusting for both baseline and time-varying confounding was used to estimate hazard ratios (HRs) and 95% CIs.</p><p><strong>Results: </strong>Mean age at index of the 32 071 patients included in the analysis was 57.6 (SD, 15.3) years; 51.0% of patients were male and 55.4% were White. During a mean follow-up of 40 (range, 1-127) months, 3974 (12.4%) patients died. Of the 9170 (28.6%) patients with relapse(s) during follow-up, most experienced 1 (53.4%) or 2 (20.0%) relapses. After adjustment for covariates, the HR for all-cause mortality was significantly higher for patients with 1 relapse vs no relapses (1.20 [95% CI, 1.14-1.26]). For the first 5 relapses, each subsequent relapse increased all-cause mortality hazard by approximately 20%. Estimated 5-year survival was 78% in patients with 1 relapse and 58% in patients with 10 relapses.</p><p><strong>Conclusions: </strong>The observed increase in all-cause mortality associated with schizophrenia relapse underscores the need for heightened attention to relapse prevention, including greater utilization of effective treatment strategies early in the course of disease.</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/PMC12076073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763724","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":"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":"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":4.5,"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":"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":4.5,"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}