Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Impact of antipsychotics on prolactin levels in youth with psychiatric disorders: A cross-sectional study.","authors":"Shuhei Wada, Kunihiro Iwamoto, Akira Yoshimi, Hirotake Hida, Shogo Hotta, Yukihiro Noda, Masashi Ikeda","doi":"10.1016/j.pnpbp.2025.111349","DOIUrl":"https://doi.org/10.1016/j.pnpbp.2025.111349","url":null,"abstract":"<p><strong>Objective: </strong>The increasing prescription of antipsychotics for children and adolescents raises concerns regarding abnormal prolactin levels. However, prolactin monitoring is rarely conducted (0.1-10 %), and the prevalence and characteristics of abnormal prolactin levels remain unclear. This study aimed to investigate the prevalence of abnormal prolactin levels and identify the factors influencing serum prolactin levels in pediatric and adolescent patients treated with antipsychotics in a real-world clinical setting.</p><p><strong>Method: </strong>This retrospective cross-sectional study was conducted at Nagoya University Hospital and included consecutive 489 patients with psychiatric disorders aged <18 years who underwent serum prolactin monitoring. Because all hospitalized patients were included, sampling bias was minimized. Data on patient demographics, psychiatric diagnoses, medications, and prolactin levels were extracted and analyzed. Multiple regression analysis was performed to identify the factors influencing serum prolactin levels. Analysis of covariance was used to assess the effects of different antipsychotics on prolactin levels.</p><p><strong>Results: </strong>Hyperprolactinemia was observed in 23.0 % of patients treated with antipsychotics, whereas hypoprolactinemia was observed in 13.7 % of patients. Domperidone, sulpiride, and antipsychotics significantly increased prolactin levels. Risperidone, olanzapine, and blonanserin were associated with significantly increased serum prolactin levels, whereas aripiprazole was associated with hypoprolactinemia.</p><p><strong>Conclusion: </strong>Approximately 40 % of pediatric patients treated with antipsychotics exhibited abnormal prolactin levels. Clinicians should routinely monitor prolactin levels and consider prolactin-related side effects when prescribing antipsychotics to children and adolescents. These findings emphasize the importance of tailored antipsychotic therapy to minimize the adverse effects in this vulnerable population.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111349"},"PeriodicalIF":5.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796936","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":"Altered neurovascular coupling in depression with childhood maltreatment","authors":"Sangni Liu ,&nbsp;Dandan Fan ,&nbsp;Cancan He ,&nbsp;Xinyi Liu ,&nbsp;Haisan Zhang ,&nbsp;Hongxing Zhang ,&nbsp;Zhijun Zhang ,&nbsp;Minggang Yang ,&nbsp;Chunming Xie","doi":"10.1016/j.pnpbp.2025.111348","DOIUrl":"10.1016/j.pnpbp.2025.111348","url":null,"abstract":"<div><h3>Background</h3><div>Childhood maltreatment (CM) is a well-established risk to major depressive disorder (MDD) worldwide. However, most previous research has predominantly examined single imaging modalities, ignoring the potential impact of aberrant couplings between cerebral perfusion and neuronal activity in MDD psychopathology. This study aims to investigate alterations of neurovascular coupling (NVC) in CM-related MDD.</div></div><div><h3>Methods</h3><div>A cross-sectional study recruited 59 MDD with CM, 36 MDD without CM, 23 healthy controls with CM, and 45 healthy controls without CM. For each participant, NVC was calculated using cerebral blood flow and regional homogeneity. Main and interactive effects were determined using two-way ANCOVA, and correlations between aberrant NVC and clinical measurements were explored via post-hoc partial correlation analyses. Furthermore, support vector machine was applied to assess the diagnostic value of NVC abnormalities in pairwise classifications.</div></div><div><h3>Results</h3><div>NVC analyses identified significant main effects of MDD in the visual, temporal, sensorimotor, and reward-related areas, alongside notable main effects of CM in sensorimotor areas. In the sensory-motor circuit, including the fusiform area, lateral prefrontal cortex, precentral gyrus, postcentral gyrus, and supramarginal gyrus/angular gyrus, MDD × CM interactive effects were observed. These aberrant NVCs correlated with the severity of CM or depression, particularly with physical neglect and cognitive disorder. Importantly, these aberrant NVCs facilitated effective pairwise classifications of CM-related MDD.</div></div><div><h3>Conclusions</h3><div>These results underscored the vulnerability of sensory-motor circuit NVC to CM in MDD patients, shedding insights into the psychopathology of MDD and its potential classification implications.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111348"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769144","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":"Integrating the COM-B model into behavioral neuroscience: A framework for understanding animal behavior","authors":"Arpád Dobolyi","doi":"10.1016/j.pnpbp.2025.111346","DOIUrl":"10.1016/j.pnpbp.2025.111346","url":null,"abstract":"<div><div>In light of the intricate nature of animal behavior regulation, a theoretical model is proposed, grounded in the COM-B (Capability, Opportunity, Motivation – Behavior) framework, which has gained considerable traction in the domain of human behavioral intervention. When extending the COM-B model to behavioral neuroscience, we first discuss the utility of the model in animal research, particularly its capacity to integrate environmental and social factors, and enhance cross-species comparisons, including animal-to-human translations and evolutionary considerations. The subsequent discussion then summarizes the advantages of utilizing the COM-B model in neuroscience are summarized, including the facilitation of a systems-level understanding of behavior and the establishment of a link between neural mechanisms and specific behavioral components. The experimental design for the application of the COM-B model in neuroscience is proposed to elucidate the brain regulatory processes that govern behavior. Finally, three specific examples are provided to illustrate the theoretical considerations, namely feeding and social behavior, and the role of neuromodulators in the control of behavior.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111346"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744563","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":"Multigene overlap analysis of bipolar disorder subtypes and educational attainment","authors":"Jianfei Zhang ,&nbsp;Wanqi Wang ,&nbsp;Yanmin Peng","doi":"10.1016/j.pnpbp.2025.111358","DOIUrl":"10.1016/j.pnpbp.2025.111358","url":null,"abstract":"<div><h3>Objective</h3><div>Bipolar disorder subtypes (BIP-I and BIP-II) differ in clinical presentation and genetic basis, yet their patterns of genetic association with educational attainment (EA) remain poorly understood. This study investigated the genetic overlap between BIP subtypes and EA, along with their underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>Using genome-wide association study (GWAS) data for BIP-I (<em>n</em> = 25,060), BIP-II (<em>n</em> = 6781), and EA (<em>n</em> = 765,283), we estimated genetic overlap using bivariate causal mixed models (MiXeR) and identified shared gene loci through the joint false discovery rate (conjFDR) method.</div></div><div><h3>Results</h3><div>MiXeR analysis revealed approximately 7.4 K single nucleotide polymorphisms (SNPs) shared between BIP-I and EA, accounting for 97.4 % of SNPs influencing BIP-I and 56.5 % of those affecting EA. ConjFDR identified 264 loci commonly associated with BIP-I and EA, including 168 novel loci for both traits. Among the 312 lead SNPs at these loci, 219 exhibited consistent effects, while 93 demonstrated opposing effects. In contrast, only two loci were co-associated between BIP-II and EA. Functional annotation and enrichment analyses showed that most loci shared by BIP-I and EA were located in intronic and intergenic regions, with associated genes enriched in processes such as protein binding and nervous system development.</div></div><div><h3>Conclusions</h3><div>This study highlights the distinct degrees and patterns of genetic association between BIP subtypes and EA, offering insights into the heterogeneity of BIP and a potential genetic basis for clinical subtyping and personalized treatment strategies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111358"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825528","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":"Investigating the disconnection between cytokine and symptom clusters in clinical high risk populations: Towards a comprehensive cross-dimensional analysis","authors":"TianHong Zhang ,&nbsp;LiHua Xu ,&nbsp;YanYan Wei ,&nbsp;XiaoChen Tang ,&nbsp;MingLiang Ju ,&nbsp;XiaoHua Liu ,&nbsp;Dan Zhang ,&nbsp;HaiChun Liu ,&nbsp;ZiXuan Wang ,&nbsp;Tao Chen ,&nbsp;Jin Gao ,&nbsp;Qiang Hu ,&nbsp;LingYun Zeng ,&nbsp;ZhengHui Yi ,&nbsp;ChunBo Li ,&nbsp;JiJun Wang","doi":"10.1016/j.pnpbp.2025.111356","DOIUrl":"10.1016/j.pnpbp.2025.111356","url":null,"abstract":"<div><h3>Objective</h3><div>Clustering individuals at the Clinical High-Risk(CHR) stage of psychosis often relies on single dimensions, and the independence or overlap of clustering results across different dimensions lacks sufficient evidence. Additionally, it remains unclear whether combining different dimensions—such as biological markers(e.g., cytokines) and symptomatic dimensions—can enhance predictive efficacy.</div></div><div><h3>Methods</h3><div>This study included 370 individuals with CHR and conducted a three-year follow-up, 50 CHR individuals transitioned to psychosis. The participants underwent thorough symptom assessments, encompassing both clinical symptoms and cognitive impairments. Baseline measurements of eight cytokines were obtained. Latent Class Analysis(LCA) was employed to construct clusters based on both symptom profiles and cytokine levels separately. Survival analysis was utilized to explore differences in conversion rates among different clusters.</div></div><div><h3>Results</h3><div>The LCA determined the selection of the four-cluster solution for symptoms, cytokines, and the integrated clusters. Symptom-Cluster-2 exhibited the most severe clinical symptoms and cognitive impairments, while Symptom-Cluster-4 displayed the mildest clinical symptoms and cognitive impairments. Cytokine-Cluster-1 was characterized by the highest levels of inflammatory cytokines, excluding vascular endothelial growth factor, whereas Symptom-Cluster-4 exhibited the lowest levels of cytokines. The clusters identified based on symptoms and cytokines showed substantial inconsistency. Survival analysis comparing conversion rates across four clusters revealed no significant difference in symptom(<em>χ</em>^<em>2</em> = 6.731, <em>p</em> = 0.081) and cytokine(<em>χ</em>^<em>2</em> = 7.139, <em>p</em> = 0.068) clusters but was significant in integrated clusters(<em>χ</em>^<em>2</em> = 9.234, <em>p</em> = 0.026).</div></div><div><h3>Conclusion</h3><div>The study emphasizes the distinct perspectives on psychosis risk offered by symptom and cytokine dimensions, advocating for the integration of these dimensions in a cross-modal approach to enhance predictive accuracy.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111356"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747327","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":"Sporadic use of classic psychedelics and neuropsychological performance: A cross-sectional analysis","authors":"Simon Reiche ,&nbsp;Tim Hirschfeld ,&nbsp;Anna Lena Gröticke ,&nbsp;Marie Traub ,&nbsp;Nicklas Jakob Hafiz ,&nbsp;Rico Haas ,&nbsp;Lara Sedlaczek ,&nbsp;Linda Ortlieb ,&nbsp;Georg Leistenschneider ,&nbsp;Lukas A. Basedow ,&nbsp;Andrea Lohse ,&nbsp;Felix Bermpohl ,&nbsp;Thomas Günther Riemer ,&nbsp;Tomislav Majić","doi":"10.1016/j.pnpbp.2025.111353","DOIUrl":"10.1016/j.pnpbp.2025.111353","url":null,"abstract":"<div><h3>Background</h3><div>Evidence on the neuropsychological consequences of classic psychedelics like psilocybin, LSD, and ayahuasca is conflicting, and little is known about how sporadic use of psychedelics under naturalistic conditions may affect cognitive functioning. Given the growing interest in the therapeutic potential of psychedelics and the rise in non-medical use, further exploration into their neuropsychological effects is needed.</div></div><div><h3>Methods</h3><div>This cross-sectional, exploratory study employed a comprehensive neuropsychological test battery to assess cognitive domains such as executive function, memory, attention, and visuospatial abilities among individuals with mild to moderate lifetime use of psychedelics. Analyses compared all users to non-users, moderate users to matched controls, and adjusted dose-response analyses were conducted within the users group.</div></div><div><h3>Results</h3><div>From 2611 screened individuals, <em>N</em> = 136 participants (84 psychedelic users and 52 controls) were included. Participants were aged 18–50 years. Neuropsychological performance was broadly equivalent between users and controls. However, matched-pair analyses showed that psychedelic users had a modest advantage in executive functions, especially superior performance on the Wisconsin Card Sorting Test (WCST) (<em>p</em> &lt; .05). Dose-response analyses further corroborated these findings, indicating a positive association between lifetime psychedelic use and performance on the WCST, specifically total errors (<em>p</em> &lt; .001), perseverative responses (<em>p</em> &lt; .001), perseverative errors (<em>p</em> &lt; .001), non-perseverative errors (<em>p</em> = .008), and conceptual level responses (<em>p</em> = .004).</div></div><div><h3>Conclusions</h3><div>The study did not detect any negative associations between sporadic lifetime psychedelic use and cognition. Instead, a moderate association with executive functioning was found, indicating increased cognitive flexibility in users. Dose-response analyses further supported this relationship.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111353"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143774788","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":"Abnormal intrinsic functional network connectivity in adolescent major depressive disorder related to severity of insomnia","authors":"Weijie Bao ,&nbsp;Yingxue Gao ,&nbsp;Ruohan Feng ,&nbsp;Xue Li ,&nbsp;Hailong Li ,&nbsp;Lingxiao Cao ,&nbsp;Zilin Zhou ,&nbsp;Mengyue Tang ,&nbsp;Yingying Wang ,&nbsp;Lihua Zhuo ,&nbsp;Hongwei Li ,&nbsp;Xinqin Ouyang ,&nbsp;Xinyue Hu ,&nbsp;Guoping Huang ,&nbsp;Xiaoqi Huang","doi":"10.1016/j.pnpbp.2025.111357","DOIUrl":"10.1016/j.pnpbp.2025.111357","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Insomnia is closely associated with depression and plays a critical role in its development. Investigating insomnia-related neuroimaging changes in depression could enhance understanding of the neural mechanisms underlying depression insomnia. However, the brain network mechanism underlying the bidirectional relationship between depression and insomnia in adolescents remains unknown.</div></div><div><h3>Methods</h3><div>We recruited 83 drug-naïve adolescents with MDD and classified them into high- (HI-aMDD) and low-insomnia (LI-aMDD) groups based on the Hamilton Depression Rating Scale sleep subscale. Static and dynamic functional network connectivity (FNC) were analyzed in 34 HI-aMDD, 49 LI-aMDD patients, and 59 gender-matched healthy controls (HCs) using independent component analysis. Partial correlation analysis examined the links between FNC differences and clinical variables.</div></div><div><h3>Results</h3><div>The HI-aMDD patients showed decreased static FNC between the cerebellum network (CeN) and both the dorsal attention (DAN) and frontoparietal networks (FPN) and decreased dynamic CeN-DAN/limbic FNC, compared to both HCs and LI-aMDD. The LI-aMDD patients exhibited decreased static CeN-DAN/FPN connectivity and decreased dynamic CeN-DAN connectivity compared to HCs. These network connectivity alterations were negatively related to insomnia symptoms in the aMDD group.</div></div><div><h3>Conclusion</h3><div>Our study revealed graded static and dynamic CeN-DAN functional connectivity associated with insomnia severity in aMDD patients. High-insomnia aMDD patients showed unique dynamic interactions between CeN and limbic network, highlighting critical neural pathways involved in depression-related insomnia. These findings suggest that cerebellum, dorsal attention and limbic networks may be specifically involved in the pathophysiology of insomnia in adolescent depression and provide new potential treatment targets.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111357"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796933","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":"Evidence for independent actions of the CRF and ghrelin systems in binge-like alcohol drinking in mice","authors":"Rani S. Richardson ,&nbsp;Lindsay A. Kryszak ,&nbsp;Janaina C.M. Vendruscolo ,&nbsp;George F. Koob ,&nbsp;Lorenzo Leggio ,&nbsp;Leandro F. Vendruscolo","doi":"10.1016/j.pnpbp.2025.111341","DOIUrl":"10.1016/j.pnpbp.2025.111341","url":null,"abstract":"<div><div>Alcohol use disorder (AUD) and binge drinking are highly prevalent public health issues. Both ghrelin and corticotrophin-releasing factor (CRF) drive stress responses and alcohol drinking. Despite evidence of a relationship between the ghrelin and CRF systems, their potential interaction in modulating alcohol drinking is unclear. We tested the effect of a brain-penetrant CRF₁ receptor antagonist (R121919) and a peripherally restricted nonselective CRF receptor antagonist (astressin) on plasma ghrelin levels. We also tested effects of R121919 and astressin alone and combined with the growth hormone secretagogue receptor (GHSR; the ghrelin receptor) antagonist JMV2959 and GHSR antagonist/inverse agonist PF-5190457 in a model of binge-like alcohol drinking in male and female C57BL/6 J mice. The intraperitoneal administration of R121919 but not astressin increased plasma ghrelin levels. R121919 but not astressin reduced binge-like alcohol drinking. CRF receptor antagonism had no effect on the ability of GHSR blockers to reduce alcohol drinking. No sex × drug treatment interactions were observed. These findings suggest that while both CRF receptor antagonism and GHSR antagonism reduce alcohol drinking, these two pharmacological approaches may not interact to mediate binge-like alcohol drinking in mice. Additionally, these results provide evidence that GHSR but not peripheral endogenous ghrelin may be key in driving binge-like alcohol drinking.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111341"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732878","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":"Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis","authors":"María Flores-López ,&nbsp;Jesús Herrera-Imbroda ,&nbsp;Nerea Requena-Ocaña ,&nbsp;Nuria García-Marchena ,&nbsp;Pedro Araos ,&nbsp;Julia Verheul-Campos ,&nbsp;Juan Jesús Ruiz ,&nbsp;Antoni Pastor ,&nbsp;Rafael de la Torre ,&nbsp;Antonio Bordallo ,&nbsp;Francisco Javier Pavón-Morón ,&nbsp;Fernando Rodríguez de Fonseca ,&nbsp;Antonia Serrano","doi":"10.1016/j.pnpbp.2025.111350","DOIUrl":"10.1016/j.pnpbp.2025.111350","url":null,"abstract":"<div><div>Substance use disorder (SUD) is a major global public health challenge, frequently co-occurring with psychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD). Endocannabinoid system (ECS) dysregulation has been implicated in both SUD and ADHD, but the interplay between these conditions remains poorly understood. This study investigates plasma concentrations of endocannabinoid-congeners in individuals with SUD, with and without comorbid ADHD, to identify potential biomarkers.</div><div>This exploratory study included 469 participants divided into three groups: (1) healthy controls (<em>n</em> = 136), (2) patients with SUD without ADHD (<em>n</em> = 267), and (3) patients with SUD and comorbid ADHD (<em>n</em> = 66). Plasma concentrations of 12 endocannabinoid-related molecules, including acylglycerols (2-AG, 2-LG, 2-OG) and acylethanolamides (AEA, DEA, DHEA, DGLEA, LEA, OEA, PEA, POEA, and SEA), were quantified using high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). A multinomial Elastic Net regression model was applied to assess their biomarker potential.</div><div>Patients with SUD exhibited significantly lower plasma concentrations of 2-AG and 2-LG compared to controls, while most acylethanolamides were elevated, except for POEA and SEA. ADHD comorbidity was associated with lower concentrations of 2-AG, 2-LG, AEA, DGLEA, DHEA, and SEA, while PEA was elevated. Machine learning analysis identified AEA, OEA, PEA, and SEA as key biomarkers, achieving an accuracy of 72.1 % and an ROC-AUC of 0.77.</div><div>This study suggests distinct ECS alterations in SUD and comorbid ADHD, highlighting endocannabinoid-congeners as potential biomarkers. Future research should validate these findings in larger cohorts and explore ECS-targeted therapeutic interventions for dual-diagnosis populations.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111350"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796934","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":"Sex and age effects on prevalence of CYP2C19 and CYP2D6 Phenoconversion risk over time in patients with psychosis","authors":"Emma Y. De Brabander ,&nbsp;Nicole K. Leibold ,&nbsp;Thérèse van Amelsvoort ,&nbsp;Roos van Westrhenen","doi":"10.1016/j.pnpbp.2025.111363","DOIUrl":"10.1016/j.pnpbp.2025.111363","url":null,"abstract":"<div><div>Pharmacogenetics in psychiatry may have benefits for medication treatment success. However, medication regimes leading to drug-drug interactions and potential phenoconversion of actionable pharmacogenetic phenotypes challenge the application of pharmacogenetics. Although polypharmacy is common, its impact in patients with psychosis is understudied, even though these patients might benefit from pharmacogenetics-guided medication adjustment. Here, we investigated the impact of two pharmacogenes relevant in psychiatric practice, CYP2C19 and CYP2D6, and the effect of sex and age. Medication use and predicted occurrence of phenoconversion was examined in a sample of patients with psychosis over a period of approximately six years. Bayesian statistics were applied to examine longitudinal effects. Our results show that women used more medications, including CYP2C19 and CYP2D6 inhibitors and (actionable) substrates. No significant sex or age differences were found for phenoconversion of either enzyme. A sex-effect on CYP2C19 inhibitor use was found but appeared to be driven by weakly inhibiting oral contraceptives, which were reported only in women. The phenoconversion rate for both enzymes appeared to change over time, suggesting that phenoconversion is a dynamic state that may affect patients differently over their lifetime. To further improve treatment in this patient population, long-term and regular updated medication monitoring in (pharmacogenetic) research as well as application in practice are recommended.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111363"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829241","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}