Translational Psychiatry最新文献

{"title":"Genetic, psychological, and environmental factors are uniquely associated with onset of alcohol use in the adolescent brain cognitive development (ABCD) study.","authors":"Maia Choi, Fazil Aliev, Peter B Barr, Megan E Cooke, Sally I Kuo, Jessica E Salvatore, Danielle M Dick, Sarah J Brislin","doi":"10.1038/s41398-025-03454-9","DOIUrl":"10.1038/s41398-025-03454-9","url":null,"abstract":"<p><p>Alcohol use during adolescence poses a significant public health problem due to its potential long-term consequences on both physical and mental health and increased risk for developing substance use disorders later in life. Both individual (e.g., genetic liability, neural functioning, personality features) and environmental (e.g., parenting, school environment) features play an important role in accelerating or buffering the progression of early alcohol consumption. This study used data from the Adolescent Brain Cognitive Development (ABCD) study (Release 5.1; N = 11,868) to provide a comprehensive examination of how genetic, neural, trait, and environmental factors are associated with risk for first sip of alcohol, first full drink, and the progression from first sip to full drink, both independently and uniquely. Cox proportional hazard models were used to examine the univariable associations between theoretically relevant genetic, neural, trait, and environmental variables and early alcohol use. Then, stepwise model-fitting was used to determine which indicators were uniquely associated with alcohol outcomes. Risk for early alcohol use was distributed across multiple domains highlighting the unique information provided by genetic, trait, and environmental variables. Results also indicated the importance of both environmental and genetic factors on time to first sip of alcohol, but that time to first full drink and the progression from sip to drink was most associated with genetic and trait factors rather than broad environmental influences. These findings highlight both potential etiological pathways driving early alcohol use as well as phenotypic and environmental process that can be targeted for early intervention efforts.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"229"},"PeriodicalIF":5.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567922","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":"Prediction of generalized anxiety disorder treatment outcomes with neurobehavioral responses to approach-avoidance conflict: a randomized clinical trial.","authors":"Hannah Berg, Timothy J McDermott, Rayus Kuplicki, Hung-Wen Yeh, Wesley K Thompson, Ryan Smith, Elisabeth Akeman, Namik Kirlic, Ashley Clausen, Mallory Cannon, Evan White, Christopher R Martell, Kate B Wolitzky-Taylor, Michelle G Craske, James L Abelson, Martin P Paulus, Robin L Aupperle","doi":"10.1038/s41398-025-03460-x","DOIUrl":"10.1038/s41398-025-03460-x","url":null,"abstract":"<p><p>Treatments for generalized anxiety disorder (GAD) often aim to address maladaptive approach-avoidance behavior patterns. Approach-avoidance conflict (AAC) offers a potential framework for identifying treatment outcome predictors and informing optimization of GAD treatment. The current study examined whether pre-treatment neurobehavioral AAC indices predict symptom improvement in behavioral activation (BA) and exposure therapy (EXP) for GAD. Treatment-seeking adults meeting criteria for GAD completed a randomized clinical trial with pre-treatment blinding, conducted from 2016-2021. Participants were randomized to complete 10 manualized sessions of BA or EXP. Participants completed an AAC task during functional magnetic resonance imaging pre-treatment. Computational parameters of task behavior were derived, and neural activity was assessed during decision-making and positive and negative outcomes of decisions. Outcome measures were GAD symptoms and depressive symptoms. Of 121 participants recruited, 56 (29 BA, 27 EXP; mean age 33.0 years; 12.5% male) treatment completers were included in analyses. Greater AAC task avoidance (d = -0.28) and greater left dorsolateral prefrontal cortex activation during negative outcomes (d = -0.32), predicted greater symptom reduction across treatments. Blunted left amygdala activation to positive outcomes was associated at a trend level with favorable symptom reduction for BA but not EXP (d = -0.20). The dorsolateral prefrontal cortex may be a target for enhancing behavior therapy outcomes generally, while left amygdala activation to positive affect may be a target for enhancing outcomes for BA. These findings may inform the optimization of behavioral therapies for GAD and hold potential for transdiagnostic applications, warranting larger, longitudinal studies in clinical settings. Clinical Trials Registration: ClinicalTrials.gov NCT02807480.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"231"},"PeriodicalIF":5.8,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12228681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567925","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":"Individual stress reactivity predicts alcohol craving and alcohol consumption in alcohol use disorder in experimental and real-life settings.","authors":"Judith Zaiser, Sabine Hoffmann, Sina Zimmermann, Tatjana Gessner, Milena Deck, Nina Kim Bekier, Martin Abel, Philipp Radler, Jens Langejürgen, Bernd Lenz, Sabine Vollstädt-Klein, Jan Stallkamp, Clemens Kirschbaum, Falk Kiefer, Patrick Bach","doi":"10.1038/s41398-025-03447-8","DOIUrl":"10.1038/s41398-025-03447-8","url":null,"abstract":"<p><p>Stress- and alcohol cues trigger alcohol craving and alcohol consumption in alcohol use disorder (AUD). However, their interactions on a physiological and psychological level and their effects on daily alcohol craving and alcohol use in real-life situations are not understood yet. We conducted a randomized-controlled experimental study to compare the effects of psychosocial stress against physical stress and a control intervention, each followed by an alcohol cue-exposure, on alcohol craving, subjective stress and saliva cortisol levels (main outcomes) in N = 121 individuals with AUD and collected data on daily alcohol use and craving during a 1-year ambulatory assessment phase. We applied linear mixed models to compare the effects of experimental interventions on the main outcomes and the relative contributions of the observed changes on the main outcomes to predicting stress and alcohol craving during the experiment and alcohol use and craving during the ambulatory assessment phase. Sequential exposure to psychosocial stress and alcohol cues induced higher cortisol levels (F_(10,580) = 10.819, p < 0.001), subjective stress (F_(2,117) = 10.520, p < 0.001) and alcohol craving (F_(6,348) = 4.313, p < 0.001) compared to the exposure to physical stress and the control condition. Subjective stress reactivity was the most influential predictor of craving during the experiment (F_(1,92) = 9.43, p = 0.003) and during the ambulatory phase (β = 0.16, p = 0.039) while cortisol levels predicted alcohol consumption in real-life settings (β = 9.76, p = 0.043). Our results highlight the impact of psychosocial stress on cue-induced craving and subjective and neuroendocrine stress responses and demonstrate links between subjective and neuroendocrine stress-reactivity and alcohol craving and alcohol use in real-life settings.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"226"},"PeriodicalIF":5.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561269","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":"Beyond homogeneity: charting the landscape of heterogeneity in neurodevelopmental and psychiatric electroencephalography.","authors":"Aida Ebadi, Sahar Allouch, Ahmad Mheich, Judie Tabbal, Aya Kabbara, Gabriel Robert, Aline Lefebvre, Anton Iftimovici, Borja Rodríguez-Herreros, Nadia Chabane, Mahmoud Hassan","doi":"10.1038/s41398-025-03441-0","DOIUrl":"10.1038/s41398-025-03441-0","url":null,"abstract":"<p><p>Electroencephalography (EEG) has been thoroughly studied for decades in neurodevelopmental and psychiatric research. Yet its integration into clinical practice as a diagnostic/prognostic tool remains unachieved. We hypothesize that a key reason is the underlying patient's heterogeneity, overlooked in EEG research relying on a case-control approach. We combine high-density EEG with normative modeling to quantify this heterogeneity using two well-established and extensively investigated EEG characteristics -spectral power and functional connectivity- across a cohort of 1674 patients with attention-deficit/hyperactivity disorder, autism spectrum disorder, learning disorder, or anxiety, and 560 matched controls. Normative models showed that deviations from population norms among patients were highly heterogeneous and frequency-dependent. Deviation spatial overlap across patients did not exceed 40% and 24% for spectral and connectivity, respectively. Considering individual deviations in patients has significantly enhanced comparative analysis, and the identification of patient-specific markers has demonstrated a correlation with clinical assessments, representing a crucial step towards attaining precision psychiatry through EEG.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"223"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12222823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555056","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":"Characterization of Neurensin-2 knockout mice: insights into stress-resilience mechanisms.","authors":"Hadas Catane Hovav, Ofer Yitzhak Kashi, Yumna Abu Ghanem, Naomi Stochinsky, Laila Agbariya, Hila Yehuda, Moriya Weitz-Aviv, Saja Baraghithy, Joseph Tam, Rami Yaka, Gali Umschweif","doi":"10.1038/s41398-025-03448-7","DOIUrl":"10.1038/s41398-025-03448-7","url":null,"abstract":"<p><p>Major depressive disorder (MDD) affects millions worldwide, yet its pathophysiology remains poorly understood. While some individuals are susceptible to developing depression, others show resilience that protects them from developing MDD. Understanding the resilience-associated mechanisms will likely result in novel therapies for MDD. We have recently reported that the vesicular protein Neurensin-2 mediates depression and that its deletion confers profound resilience to chronic stress. Nonetheless, the behavioral and molecular adaptations that underlie the stress resilience in Neurensin-2 knockout mice are still unknown. In this study, we aimed to comprehensively characterize the basal behavioral effects of Neurensin-2 deletion in mice. We used Neurensin-2 knockout male and female mice to examine how Neurensin-2 deletion affects cognitive, emotional, and motor performance in mice. In addition, we examined the impact of Neurensin-2 deletion on body weight, analyzed the stress-induced molecular changes, and tested how these changes affect the excitatory/inhibitory balance. We found that while Neurensin-2 deletion confers basal anxiolysis and weight reduction, no discernible cognitive, social, or motor impairments were detected. Furthermore, we found that Neurensin-2 knockout mice have impaired hippocampal inhibitory transmission, which is resilient to the stress-evoked excitatory/inhibitory imbalance seen in wild-type mice. Our findings suggest that Neurensin-2 deletion confers basal anxiolysis, and shifts the hippocampal excitatory/inhibitory balance. These effects are not accompanied by impaired cognitive function or weight gain. Thus, we suggest Neurensin-2 inhibition as an exciting potential strategy for developing treatments for depression and anxiety disorders as well as for promoting stress resilience.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"225"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555057","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":"Neural fingerprints of data driven cognitive subtypes across the psychosis spectrum: a B-SNIP study.","authors":"Shashwath A Meda, Madison M Dykins, Scot K Hill, Brett A Clementz, Sarah K Keedy, Jennifer E McDowell, Elena I Ivleva, Elliot S Gershon, Matcheri S Keshavan, Carol Tamminga, Godfrey D Pearlson","doi":"10.1038/s41398-025-03422-3","DOIUrl":"10.1038/s41398-025-03422-3","url":null,"abstract":"<p><p>Cognitive dysfunction is a prominent feature of psychotic spectrum disorders. Identifying neurocognitive subgroups and their neural underpinnings may help elucidate distinct pathophysiological mechanisms and inform targeted interventions. This study aimed to derive cognitive subtypes using latent profile analysis (LPA) of the Brief Assessment of Cognition in Schizophrenia (BACS) and investigate associated variations in resting-state functional connectivity among these cognitive profiles and biologically derived Biotypes. The BACS was administered to 1807 psychosis patients from the B-SNIP1 and 2 cohorts to perform LPA and identify cognitive subgroups. Regional homogeneity (ReHo), a measure of local functional connectivity, was computed from resting-state fMRI data in a subset (717 patients, 427 controls). Multivariate regression models examined associations between ReHo and cognitive LPA, Biotypes, and DSM diagnostic categories. LPA identified four cognitive profiles: cognitively comparable to controls (CCC), intermediate-1, intermediate-2, and severely impaired. These profiles showed unique dysconnectivity patterns, particularly within the striatal, default mode, salience, and executive control networks. The severely impaired group exhibited hyperconnectivity in basal ganglia and executive control networks. The intermediate groups showed default mode and salience network connectivity disruptions. The CCC group was the least impaired, with hyperconnectivity in sensory and auditory networks. Compared to Biotypes, LPA subgroups presented more domain-specific connectivity fingerprints. Psychosis patients exhibit heterogeneous cognitive profiles with divergent intrinsic functional dysconnectivity patterns. Cognitive LPA subgroups demonstrated more domain-localized neural signatures than DSM subtypes, potentially allowing for more targeted interventions. This approach highlights the utility of cognitive subtyping using standardized cognitive assessments in elucidating pathophysiological mechanisms in psychosis.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"224"},"PeriodicalIF":5.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12223097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555058","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":"Reduced neural suppression at occipital cortex in subthreshold depression.","authors":"Jinhui Li, Yuheng Tan, Zixin Zheng, Chunliang Feng, Wenjie Fang, Xiaodan Huang, Song Lin, Kwok-Fai So, Lu Huang, Chaoran Ren, Qian Tao","doi":"10.1038/s41398-025-03446-9","DOIUrl":"10.1038/s41398-025-03446-9","url":null,"abstract":"<p><p>Impaired visual perception and biochemical changes in the occipital cortex have been observed in major depression. However, the neural basis underlying these abnormalities remains yet elusive. Importantly, it remains unknown whether these abnormalities are present in the early stage of depression, known as subthreshold depression (SD). Recognized as a precursor of major depression, SD has gained a growing attention in both research and clinical fields. The current study recruit young adults with SD and demographically matched healthy controls (HC). Experiment 1 utilized a series of psychophysical tasks in a large sample (n = 95), and Experiment 2 used a functional magnetic resonance imaging (fMRI) approach in a medium sample (n = 63). Our results show that the impaired spatial suppression at the behavioural level is accompanied by a significant reduction in neural suppression in the human middle temporal complex (hMT+) and early visual cortex (EVC) within the SD group. Additionally, we found enhanced functional connectivity between hMT+ and the medial prefrontal cortex, anterior cingulate cortex, insula, and postcentral gyrus in the SD group. These findings provide new insights into the psychopathological mechanisms underlying depressive symptoms and highlight the significance of the occipital cortex in the early identification and prevention of depression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"220"},"PeriodicalIF":5.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544990","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":"Serum multi-trace elements and post-stroke cognitive impairment: a prospective observational cohort study.","authors":"Ruolin Zhou, Weijie Zhai, Lingjie Meng, Chunxiao Wei, Li Sun","doi":"10.1038/s41398-025-03420-5","DOIUrl":"10.1038/s41398-025-03420-5","url":null,"abstract":"<p><p>Post-stroke cognitive impairment (PSCI) significantly affects stroke survivors. Identifying modifiable risk factors for PSCI is essential. Serum multi-trace elements are crucial for neurological function but vary in concentration among older adults. It remains unclear whether increasing multi-trace elements can reduce the incidence of PSCI. We investigated the associations between baseline serum multi-trace elements and PSCI. The Montreal Cognitive Assessment defined PSCI. We used logistic regression analyses to evaluate the association between serum multi-trace elements and PSCI. Subsequently, we assessed the associations between serum multi-trace elements and three different cognitive domains using the Kruskal-Wallis test. We further evaluated improvements in the predictive ability of serum multi-trace elements. Finally, 626 patients (mean age: 62.85 ± 7.54 years) were followed up for a median of 1.2 years. Lower concentrations of serum iron (odds ratio [OR] = 2.498, 95% confidence interval [CI]: 1.505-4.145) and zinc (OR = 2.015, 95% CI: 1.233-3.293) were associated with a higher PSCI risk. Higher concentrations of serum iron (OR = 0.368, 95% CI: 0.227-0.595) and magnesium (OR = 0.273, 95% CI: 0.164-0.454), along with lower concentrations of serum copper (OR = 0.544, 95% CI: 0.34-0.872), were significantly correlated with a lower PSCI risk. Cognitive impairments varied across multi-trace elements. Serum iron affected wider cognition, while magnesium and copper levels were strongly associated with language and executive function. Adding serum multi-trace elements to the conventional model improved PSCI risk reclassification (area under curve: 0.676-0.718). Multi-trace elements may influence PSCI progression. This study was registered with the Chinese Clinical Trial Registry (URL: https://www.chictr.org.cn/ ; unique identifier: ChiCTR1900022675).</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"222"},"PeriodicalIF":5.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544991","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":"Nucleus accumbens dynamics in food reward seeking and regulation by sleep.","authors":"Ana L Almeida Rojo, Li Cai, Tyler R Barnhardt, Yanhua H Huang","doi":"10.1038/s41398-025-03442-z","DOIUrl":"10.1038/s41398-025-03442-z","url":null,"abstract":"<p><p>Reward-seeking behavior is essential for survival and is greatly influenced by experience, internal states, and physiological factors such as sleep. The nucleus accumbens (NAc) is reward processing hub that integrates external and internal signals to regulate reward-seeking behaviors. However, it is not well understood how NAc activities during reward seeking may be shaped by learning experience, and to what extent that it may be subject to physiological regulations such as sleep. Here, we used in vivo fiber photometry to monitor calcium (Ca²⁺) activities in the NAc of male and female mice undergoing sucrose self-administration (SA) training. We found that the NAc Ca²⁺ dynamics during sucrose SA were related to the behavioral outcome and evolved over different training stages. Moreover, acute sleep deprivation increased sucrose SA while reduced NAc Ca²⁺ responses and dampened its sensitivity to reward update. Thus, our findings suggest that the NAc response during natural reward seeking is dynamic, adaptive to learning experience, and can be blunted by acute sleep deprivation.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"219"},"PeriodicalIF":5.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544989","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":"The murine ATP-binding cassette transporter C5 (Abcc5/MRP5/cMOAT) plays a role in memory consolidation, circadian rhythm regulation and glutamatergic signalling.","authors":"Gareth Banks, Malgorzata Cyranka, Natascia Vedovato, Charlotte Meller, Alex Rawnsley, Edward O Mann, Michelle Stewart, Heidi de Wet","doi":"10.1038/s41398-025-03438-9","DOIUrl":"10.1038/s41398-025-03438-9","url":null,"abstract":"<p><p>ATP-Binding cassette (ABC) transporters are a family of integral membrane ATPases that transport a large number of structurally unrelated compounds. The physiological role of the orphan transporter Abcc5 remains poorly understood. As previous work demonstrated that the loss of Abcc5 activity leads to elevated levels of NAAG in the brain, the impact of Abcc5 ablation was ascertained using behavioural phenotyping, circadian rhythm analysis and electrophysiological recordings of brain slices from Abcc5^-/- mice and compared to wild-type littermates. Behavioural phenotyping of Abcc5^-/- mice shows that the loss of murine Abcc5 activity results in profound changes in pre-pulse inhibition (PPI) as well as altered memory consolidation. Circadian measures of activity showed a delay in the timing of Abcc5^-/- mice activity rhythm peak. Additionally, activity defined sleep analysis highlighted differences in sleep patterns in Abcc5^-/- mice compared to wild-type controls. Patch clamp recording from pyramidal cells in the 2/3 layer of the frontal cortex showed altered synaptic AMPA/NMDA receptor current ratios and increased frequency of spontaneous excitatory postsynaptic currents (sEPSC). This study demonstrates that the loss of functional Abcc5 transporters does have behavioural consequences in mammals and alters NMDA receptor activity. These results highlight a previously unknown role of Abcc5 in the brain.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"218"},"PeriodicalIF":5.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544992","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}