Translational Psychiatry最新文献

{"title":"Virtual stressors with real impact: what virtual reality-based biobehavioral research can teach us about typical and atypical stress responsivity.","authors":"Elizabeth A Shirtcliff, Tor T Finseth, Eliot H Winer, David C Glahn, Roselynn A Conrady, Stacy S Drury","doi":"10.1038/s41398-024-03129-x","DOIUrl":"https://doi.org/10.1038/s41398-024-03129-x","url":null,"abstract":"<p><p>Stress contributes to transdiagnostic morbidity and mortality across a wide range of physical and mental health problems. VR tasks have been validated as stressors with robust effect sizes for VR-based stressors to evoke stress across the most common autonomic and adrenocortical stress biomarkers. However, meta-analytic validation of VR stressors have resulted in inconsistent logic: why should something that isn't real evoke a very real suite of stress responses? This review posits that conceptually addressing this question requires differentiating a cause, \"stressor\", from effects, \"stress\". Stress comprises a series of well-delineated perturbations in biological systems, such as autonomic and adrenocortical biomarkers in response to stressors. Despite their ubiquity, decades of literature have back-calculated stressor intensity based on the magnitude of a stress response. This causal directionality is not logical, yet remains pervasive because seemingly objective stress indices have generated a wealth of findings showing how stress gets under the skin and skull. This has created challenges for providing clear guidance and strategies to measure acute stressor intensity. Binary thinking about whether something is (not) real has stifled advances in understanding how to measure the dosage of a stressful environment. As a function of being programmed, individualizable, and titrated, virtual reality (VR) based stressors offer the field a platform for quantifying the dose of a stressor and generating reliable dose-response curves. This also raises the possibility to safely and ethically integrate psychosocial stressor administration into clinical and therapeutic settings. For example, Social Evaluative Threat experiments effectively trigger a stress response both in a laboratory setting and in built environments, while also upholding hard-fought trust and rapport with care providers. By focusing attention on the measurement of the stressor, VR paradigms can advance tangible understanding of stressors themselves and the pathways to the stress response.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11487258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of nitric oxide-associated arginine metabolites in schizophrenia.","authors":"Angelo Zinellu, Sara Tommasi, Ciriaco Carru, Salvatore Sotgia, Arduino A Mangoni","doi":"10.1038/s41398-024-03157-7","DOIUrl":"10.1038/s41398-024-03157-7","url":null,"abstract":"<p><p>There is increasing interest in the pathophysiological role of arginine metabolism in schizophrenia, particularly in relation to the modulation of the endogenous messenger nitric oxide (NO). The assessment of specific arginine metabolites that, unlike NO, are stable can provide useful insights into NO regulatory enzymes such as isoform 1 of dimethylarginine dimethylaminohydrolase (DDAH1) and arginase. We investigated the role of arginine metabolomics in schizophrenia by conducting a systematic review and meta-analysis of the circulating concentrations of arginine metabolites associated with DDAH1, arginase, and NO synthesis [arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine, and ornithine] in this patient group. We searched PubMed, Scopus, and Web of Science from inception to the 31^st of May 2023 for studies investigating arginine metabolites in patients with schizophrenia and healthy controls. The JBI Critical Appraisal Checklist for analytical studies and GRADE were used to assess the risk of bias and the certainty of evidence, respectively (PROSPERO registration number: CRD42023433000). Twenty-one studies were identified for analysis. There were no significant between-group differences in arginine, citrulline, and SDMA. By contrast, patients with schizophrenia had significantly higher ADMA (DDAH1 substrate, standard mean difference, SMD = 1.23, 95% CI 0.86-1.61, p < 0.001; moderate certainty of evidence), dimethylamine (DDAH1 product, SMD = 0.47, 95% CI 0.24-0.70, p < 0.001; very low certainty of evidence), and ornithine concentrations (arginase product, SMD = 0.32, 95% CI 0.16-0.49, p < 0.001; low certainty of evidence). In subgroup analysis, the pooled SMD for ornithine was significantly different in studies of untreated, but not treated, patients. Our study suggests that DDAH1 and arginase are dysregulated in schizophrenia. Further studies are warranted to investigate the expression/activity of these enzymes in the brain of patients with schizophrenia and the effects of targeted treatments.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychological interventions for suicidal behavior in adolescents: a comprehensive systematic review.","authors":"Ainoa García-Fernández, Teresa Bobes-Bascarán, Clara Martínez-Cao, Leticia González-Blanco, Jennifer Fernández-Fernández, Paula Zurrón-Madera, Elisa Seijo Zazo, Luis Jiménez-Treviño, María Paz García-Portilla, Julio Bobes, Pilar A Sáiz","doi":"10.1038/s41398-024-03132-2","DOIUrl":"https://doi.org/10.1038/s41398-024-03132-2","url":null,"abstract":"<p><strong>Background: </strong>Recent evidence indicates that the risk of death by suicide in teenagers has increased significantly worldwide. Consequently, different therapeutic interventions have been proposed for suicidal behavior in this particular population. Therefore, the main objective of this study is to provide an updated review of the existing psychological interventions for the treatment of suicide attempts (SA) in adolescents and to analyze the efficacy of such interventions.</p><p><strong>Methods: </strong>A systematic review was conducted following PRISMA guidelines. The studies were identified by searching PubMed, PsychINFO, Web of Science, and Scopus databases from 2016 to 2022. According to the inclusion criteria, a total of 40 studies that tested the efficacy of different psychological interventions were selected.</p><p><strong>Results: </strong>Various psychological interventions for adolescents with suicidal behaviors were identified. Most of those present promising results. However, to summarize results from recent years, dialectical behavior therapy (DBT) was the most common and the only treatment shown to be effective for adolescents at high risk of suicide and SA. In contrast, empirical evidence for other psychological interventions focusing on deliberate self-harm (SH) is inconclusive.</p><p><strong>Conclusions: </strong>Interventions specifically designed to reduce suicidal risk in adolescents have multiplied significantly in recent years. There are a few promising interventions for reducing suicidal behaviors in adolescents evaluated by independent research groups. However, replication and dismantling studies are needed to identify the effects of these interventions and their specific components. An important future challenge is to develop brief and effective interventions to reduce the risk of death by suicide among the adolescent population.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional activity and connectivity signatures of ketamine and lamotrigine during negative emotional processing: a double-blind randomized controlled fMRI study.","authors":"Marvin S Meiering, David Weigner, Matti Gärtner, Luisa Carstens, Christian Keicher, Rita Hertrampf, Christian F Beckmann, Maarten Mennes, Andreas Wunder, Anne Weigand, Simone Grimm","doi":"10.1038/s41398-024-03120-6","DOIUrl":"https://doi.org/10.1038/s41398-024-03120-6","url":null,"abstract":"<p><p>Ketamine is a highly effective antidepressant (AD) that targets the glutamatergic system and exerts profound effects on brain circuits during negative emotional processing. Interestingly, the effects of ketamine on brain measures are sensitive to modulation by pretreatment with lamotrigine, which inhibits glutamate release. Examining the antagonistic effects of ketamine and lamotrigine on glutamate transmission holds promise to identify effects of ketamine that are mediated through changes in the glutamatergic system. Investigating this modulation in relation to both the acute and sustained effects of ketamine on functional activity and connectivity during negative emotional processing should therefore provide novel insights. 75 healthy subjects were investigated in a double-blind, single-dose, randomized, placebo-controlled, parallel-group study with three treatment conditions (ketamine, lamotrigine pre-treatment, placebo). Participants completed an emotional face viewing task during ketamine infusion and 24 h later. Acute ketamine administration decreased hippocampal and Default Mode Network (DMN) activity and increased fronto-limbic coupling during negative emotional processing. Furthermore, while lamotrigine abolished the ketamine-induced increase in functional connectivity, it had no acute effect on activity. Sustained (24 h later) effects of ketamine were only found for functional activity, with a significant reduction in the posterior DMN. This effect was blocked by pretreatment with lamotrigine. Our results suggest that both the acute increases in fronto-limbic coupling and the delayed decrease in posterior DMN activity, but not the attenuated limbic and DMN recruitment after ketamine, are mediated by altered glutamatergic transmission.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11479267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 plasma arachidonic acid levels with a bipolar disorder and the effects of a FADS gene variant.","authors":"Takuma Ashizawa, Takeo Saito, Tomo Okochi, Kohei Ninomiya, Kenta Ito, Rei Aoki, Masashi Ikeda, Nakao Iwata","doi":"10.1038/s41398-024-03141-1","DOIUrl":"https://doi.org/10.1038/s41398-024-03141-1","url":null,"abstract":"<p><p>Recent genome-wide association studies (GWASs) have identified fatty acid desaturase (FADS) genes, which code key enzymes involved in polyunsaturated fatty acid (PUFA) desaturation as susceptibility genes for bipolar disorder (BD). Several quantitative changes in PUFAs suggest their involvement in BD pathogenesis. Therefore, this study aimed to clarify the relationship between BD and PUFAs by conducting lipidomics covariating with the FADS gene variant (rs174550), which is associated with PUFA levels and BD susceptibility. The concentrations of 23 fatty acids were measured using plasma samples from the BD group (n = 535) and the control group (n = 107). Differences in each PUFA concentration ratio were compared between the two groups. Also, differences in each PUFA concentration ratio were compared for each genotype in rs174550. Our results showed that the BD group had significantly lower concentrations of linoleic acid (LA) (β = -0.36, p = 0.023) and arachidonic acid (AA) (β = -0.18, p = 0.013) than the control group. Concerning the effect of FADS on the PUFA concentration ratio, carriers of C-allele at rs174550 had significantly decreased γ-linolenic acid and AA concentration ratios. A previous GWAS reported that the presence of a C-allele at rs174550 increased the BD risk. This direction is consistent with the lipidomic results of the present study. In conclusion, both the FADS and BD were considered to regulate the AA concentration. Thus, as the FADS gene variant is crucial for conducting lipidomics of BD we believe that the allele frequency of FADS must be analyzed.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent gene expression patterns in alcohol and opioid use disorders lead to consistent alterations in functional networks within the dorsolateral prefrontal cortex.","authors":"Martha MacDonald, Pablo A S Fonseca, Kory R Johnson, Erin M Murray, Rachel L Kember, Henry R Kranzler, R Dayne Mayfield, Daniel da Silva","doi":"10.1038/s41398-024-03143-z","DOIUrl":"https://doi.org/10.1038/s41398-024-03143-z","url":null,"abstract":"<p><p>Substance Use Disorders (SUDs) manifest as persistent drug-seeking behavior despite adverse consequences, with Alcohol Use Disorder (AUD) and Opioid Use Disorder (OUD) representing prevalent forms associated with significant mortality rates and economic burdens. The co-occurrence of AUD and OUD is common, necessitating a deeper comprehension of their intricate interactions. While the causal link between these disorders remains elusive, shared genetic factors are hypothesized. Leveraging public datasets, we employed genomic and transcriptomic analyses to explore conserved and distinct molecular pathways within the dorsolateral prefrontal cortex associated with AUD and OUD. Our findings unveil modest transcriptomic overlap at the gene level between the two disorders but substantial convergence on shared biological pathways. Notably, these pathways predominantly involve inflammatory processes, synaptic plasticity, and key intracellular signaling regulators. Integration of transcriptomic data with the latest genome-wide association studies (GWAS) for problematic alcohol use (PAU) and OUD not only corroborated our transcriptomic findings but also confirmed the limited shared heritability between the disorders. Overall, our study indicates that while alcohol and opioids induce diverse transcriptional alterations at the gene level, they converge on select biological pathways, offering promising avenues for novel therapeutic targets aimed at addressing both disorders simultaneously.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11473550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal dynamics of negative emotional memory reprocessing during sleep.","authors":"Serik Tabarak, Ximei Zhu, Peng Li, Frederik D Weber, Le Shi, Yimiao Gong, Kai Yuan, Yanping Bao, Tengteng Fan, Suxia Li, Jie Shi, Lin Lu, Jiahui Deng","doi":"10.1038/s41398-024-03146-w","DOIUrl":"https://doi.org/10.1038/s41398-024-03146-w","url":null,"abstract":"<p><p>Memory reprocessing during sleep is a well-established phenomenon in numerous studies. However, it is unclear whether the intensity of memory reprocessing is consistently maintained throughout the night or exhibits dynamic changes. This study investigates the temporal dynamics of negative emotional memory reprocessing during sleep, with a specific focus on slow oscillation (SO)-spindle coupling and its role in memory reprocessing. In the first experiment (N = 40, mean age = 22.5 years), we detected the negative emotional memory reprocessing strength in each sleep cycle, we found that the 2nd sleep cycle after negative emotional memory learning constitute the most sensitive window for memory reprocessing, furthermore, SO-spindle coupling signals in this window plays a role in stabilizing negative emotional memory. To verify the role of SO-spindle coupling in negative emotional memory reprocessing, we utilized transcranial alternating current stimulation (tACS) to disrupt SO-spindle coupling during the 2^nd sleep cycle (N = 21, mean age = 19.3 years). Notably, the outcomes of the tACS intervention demonstrated a significant reduction in the recognition of negative emotional memories. These findings offer new insights into the mechanisms that regulate emotional memory consolidation during sleep and may have implications for addressing psychiatric disorders associated with pathological emotional memory.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11471876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of neural oscillations in escitalopram treatment: a Canadian biomarker integration network in depression study.","authors":"Benjamin Schwartzmann, Raaj Chatterjee, Yasaman Vaghei, Lena C Quilty, Timothy A Allen, Stephen R Arnott, Sravya Atluri, Pierre Blier, Prabhjot Dhami, Jane A Foster, Benicio N Frey, Stefan Kloiber, Raymond W Lam, Roumen Milev, Daniel J Müller, Claudio N Soares, Chloe Stengel, Sagar V Parikh, Gustavo Turecki, Rudolf Uher, Susan Rotzinger, Sidney H Kennedy, Faranak Farzan","doi":"10.1038/s41398-024-03110-8","DOIUrl":"https://doi.org/10.1038/s41398-024-03110-8","url":null,"abstract":"<p><p>Current pharmacological agents for depression have limited efficacy in achieving remission. Developing and validating new medications is challenging due to limited biological targets. This study aimed to link electrophysiological data and symptom improvement to better understand mechanisms underlying treatment response. Longitudinal changes in neural oscillations were assessed using resting-state electroencephalography (EEG) data from two Canadian Biomarker Integration Network in Depression studies, involving pharmacological and cognitive behavioral therapy (CBT) trials. Patients in the pharmacological trial received eight weeks of escitalopram, with treatment response defined as ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS). Early (baseline to week 2) and late (baseline to week 8) changes in neural oscillation were investigated using relative power spectral measures. An association was found between an initial increase in theta and symptom improvement after 2 weeks. Additionally, late increases in delta and theta, along with a decrease in alpha, were linked to a reduction in MADRS after 8 weeks. These late changes were specifically observed in responders. To assess specificity, we extended our analysis to the independent CBT cohort. Responders exhibited an increase in delta and a decrease in alpha after 2 weeks. Furthermore, a late (baseline to week 16) decrease in alpha was associated with symptom improvement following CBT. Results suggest a common late decrease in alpha across both treatments, while modulatory effects in theta may be specific to escitalopram treatment. This study offers insights into electrophysiological markers indicating a favorable response to antidepressants, enhancing our comprehension of treatment response mechanisms in depression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocannabinoid concentrations in major depression: effects of childhood maltreatment and relation to hippocampal volume.","authors":"Raegan Mazurka, Kate L Harkness, Stefanie Hassel, Niclas Stensson, Nikita Nogovitsyn, Jordan Poppenk, Jane A Foster, Scott D Squires, Jessie Rowe, Roumen V Milev, Katherine E Wynne-Edwards, Gustavo Turecki, Stephen C Strother, Stephen R Arnott, Raymond W Lam, Susan Rotzinger, Sidney H Kennedy, Benicio N Frey, Leah M Mayo","doi":"10.1038/s41398-024-03151-z","DOIUrl":"10.1038/s41398-024-03151-z","url":null,"abstract":"<p><p>Evidence from preclinical animal models suggests that the stress-buffering function of the endocannabinoid (eCB) system may help protect against stress-related reductions in hippocampal volume, as is documented in major depressive disorder (MDD). However, stress exposure may also lead to dysregulation of this system. Thus, pathways from marked stress histories, such as childhood maltreatment (CM), to smaller hippocampal volumes and MDD in humans may depend on dysregulated versus intact eCB functioning. We examined whether the relation between MDD and peripheral eCB concentrations would vary as a function of CM history. Further, we examined whether eCBs moderate the relation of CM/MDD and hippocampal volume. Ninety-one adults with MDD and 62 healthy comparison participants (HCs) were recruited for a study from the Canadian Biomarker Integration Network in Depression program (CAN-BIND-04). The eCBs, anandamide (AEA) and 2-arachidonylglycerol (2-AG), were assessed from blood plasma. Severe CM history was assessed retrospectively via contextual interview. MDD was associated with eCBs, though not all associations were moderated by CM or in the direction expected. Specifically, MDD was associated with higher AEA compared to HCs regardless of CM history, a difference that could be attributed to psychotropic medications. MDD was also associated with higher 2-AG, but only for participants with CM. Consistent with hypotheses, we found lower left hippocampal volume in participants with versus without CM, but only for those with lower AEA, and not moderate or high AEA. Our study presents the first evidence in humans implicating eCBs in stress-related mechanisms involving reduced hippocampal volume in MDD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutamate concentration of medial prefrontal cortex is inversely associated with addictive behaviors: a translational study.","authors":"Hui Zhou, Tiantian Hong, Xi Chen, Conghui Su, Binyu Teng, Wan Xi, Jean Lud Cadet, Yihong Yang, Fengji Geng, Yuzheng Hu","doi":"10.1038/s41398-024-03145-x","DOIUrl":"https://doi.org/10.1038/s41398-024-03145-x","url":null,"abstract":"<p><p>In both preclinical and clinical settings, dysregulated frontostriatal circuits have been identified as the underlying neural substrates of compulsive seeking/taking behaviors manifested in substance use disorders and behavioral addictions including internet gaming disorder (IGD). However, the neurochemical substrates for these disorders remain elusive. The lack of comprehensive cognitive assessments in animal models has hampered our understanding of neural plasticity in addiction from these models. In this study, combining data from a rat model of compulsive taking/seeking and human participants with various levels of IGD severity, we investigated the relationship between regional glutamate (Glu) concentration and addictive behaviors. We found that Glu levels were significantly lower in the prelimbic cortex (PrL) of rats after 20-days of methamphetamine self-administration (SA), compared to controls. Glu concentration after a punishment phase negatively correlated with acute drug-seeking behavior. In addition, changes in Glu levels from a drug naïve state to compulsive drug taking patterns negatively correlated with drug-seeking during both acute and prolonged abstinence. The human data revealed a significant negative correlation between Glu concentration in the dorsal anterior cingulate cortex (dACC), the human PrL counterpart, and symptoms of IGD. Interestingly, there was a positive correlation between Glu levels in the dACC and self-control, as well as mindful awareness. Further analysis revealed that the dACC Glu concentration mediated the relationship between self-control/mindful awareness and IGD symptoms. These results provide convergent evidence for a protective role of dACC/PrL in addiction, suggesting interventions to enhance dACC glutamatergic functions as a potential strategy for addiction prevention and treatment.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.8,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}