Progress in Neuro-Psychopharmacology & Biological Psychiatry最新文献

{"title":"Chemogenetic attenuation of PFC pyramidal neurons restores recognition memory deficits following adolescent NMDA receptor blockade","authors":"Hagar Bauminger ,&nbsp;Sailendrakumar Kolatt Chandran ,&nbsp;Hiba Zaidan ,&nbsp;Irit Akirav ,&nbsp;Inna Gaisler-Salomon","doi":"10.1016/j.pnpbp.2025.111359","DOIUrl":"10.1016/j.pnpbp.2025.111359","url":null,"abstract":"<div><div>During adolescence, the prefrontal cortex (PFC) undergoes significant developmental changes, affecting the balance between excitatory glutamate and inhibitory GABA transmission (i.e., the E/I balance). This process is critical for intact cognitive function and social behavior in adulthood and is disrupted in schizophrenia (SZ). While acute NMDA receptor (NMDAr) blockade leads to excess glutamate transmission in the PFC, less is known about the long-term impacts of NMDAr blockade in adolescence on the E/I balance and adult cognitive function and social behavior. Here we show that early-adolescence chronic MK-801 administration leads to deficits in recognition memory and social function as well as increased E/I balance in the medial prefrontal cortex (mPFC) of adult male rats, stemming from reduced inhibitory synaptic transmission rather than changes in excitatory transmission or intrinsic excitability. Interestingly, chemogenetic attenuation of prelimbic mPFC pyramidal neurons reverses adolescent MK-801-induced deficits in recognition memory, but not social behavior. These findings emphasize the critical role of intact NMDAr function during adolescence on behavior in adulthood and on the E/I balance, and imply that reduced mPFC pyramidal neuron activity may hold therapeutic potential in treating recognition memory deficits in SZ.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111359"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803950","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":"Serum multi-biomarkers for predicting relapse in patients with depressive disorders under psychopharmacotherapy","authors":"Jae-Min Kim ,&nbsp;Hee-Ju Kang ,&nbsp;Ju-Wan Kim ,&nbsp;Min Jhon ,&nbsp;Ju-Yeon Lee ,&nbsp;Sung-Wan Kim ,&nbsp;Min-Gon Kim ,&nbsp;Il-Seon Shin","doi":"10.1016/j.pnpbp.2025.111360","DOIUrl":"10.1016/j.pnpbp.2025.111360","url":null,"abstract":"<div><h3>Background</h3><div>Effective predictive biomarkers for depression relapse remain elusive. This study examined the association of a multi-modal serum biomarker panel with relapse among outpatients with depressive disorders under psychopharmacotherapy, utilizing a naturalistic 24-month prospective design.</div></div><div><h3>Methods</h3><div>atients were recruited from a University hospital in South Korea between March 2012 and April 2017. At baseline, 14 serum biomarkers along with socio-demographic and clinical characteristics were assessed in 1094 patients. Following initial antidepressant monotherapy, patients who responded (Hamilton Depression Rating Scale [HAMD] ≤ 14) at the 12-week mark (<em>N</em> = 823) were monitored for relapse (HAMD &gt;14) every three months up to 24 months (<em>N</em> = 710). Logistic regression models, adjusted for relevant covariates, were used to evaluate predictive biomarkers of relapse.</div></div><div><h3>Results</h3><div>The combined scores of four serum biomarkers (cortisol, high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and brain-derived neurotrophic factor) showed a significant and graded association with depression relapse (<em>P</em>-value &lt;0.001), even after adjustments.</div></div><div><h3>Conclusions</h3><div>The application of a combined multi-serum biomarker panel could significantly enhance the predictability of depression relapse. Further validation of these biomarkers in diverse populations and settings is warranted to confirm their utility in clinical practice.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111360"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812880","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":"Do AMPA/kainate antagonists possess potential in the treatment of addiction? Evidence from animal behavioural studies","authors":"Maria Hrickova,&nbsp;Jana Ruda-Kucerova","doi":"10.1016/j.pnpbp.2025.111355","DOIUrl":"10.1016/j.pnpbp.2025.111355","url":null,"abstract":"<div><div>Substance addiction is a complex mental disorder with significant unmet treatment needs, especially in terms of effective medications. Craving in addiction is closely linked to the interaction between dopamine and glutamate in the brain's reward pathway. Therefore, drugs targeting glutamatergic signaling may have potential for treatment. This review examines the potential of AMPA/kainate glutamatergic receptor antagonists in reducing addictive-like behaviours in experimental rodents. To this end, the text summarizes the behavioural results of preclinical studies on stimulant substances (cocaine, amphetamine, methamphetamine, MDMA), nicotine, opioids (morphine and heroin), and alcohol. These experiments employ various protocols and routes of administration, using different strains of mice and rats. The main behavioural methods used in the research include behavioural sensitization protocols, drug-induced locomotor activity assessments, conditioned behaviours, and operant self-administration models. The reviewed literature demonstrates the benefit of AMPA/kainate antagonists, mainly in the most studied cocaine dependence, and particularly in attenuating cocaine-seeking behaviour via microinjection into the nucleus accumbens core. Regarding other addictive substances, despite some conflicting results, there is a substantial body of literature showing promising outcomes following systemic or intracerebral administration of AMPA/kainate antagonists. The main issue is the variability of the research protocols used across laboratories, including differences in animal species, strains, sex and environmental conditions. Moreover, each addictive substance exhibits distinct mechanisms of action and addiction development, rendering the pursuit of a universal drug for addiction treatment unrealistic. Nevertheless, AMPA/kainate antagonists seem to have potential as a supportive treatment in addiction to cocaine as well as other substances.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111355"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789318","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":"Therapeutic potential of faecal microbiota transplantation for alcohol use disorder, a narrative synthesis","authors":"Jennifer Docherty","doi":"10.1016/j.pnpbp.2025.111354","DOIUrl":"10.1016/j.pnpbp.2025.111354","url":null,"abstract":"<div><h3>Background</h3><div>Faecal microbiota transplantation is proposed as an alternative therapy to treat alcohol use disorder and has completed a Phase 1 clinical trial, with a Phase 2 clinical trial underway. Alcohol, a modifiable risk factor for noncommunicable diseases, resulted in approximately 3 million global deaths (5 %) in 2016 according to the World Health Organization.</div></div><div><h3>Aims</h3><div>A narrative synthesis examines the effects of alcohol and faecal microbiota transplantation on gut microbiota and how gut microbiota impacts the gut-brain axis, leading to certain behavioural symptoms of alcohol use disorder. These behavioural symptoms are alcohol craving and relapse in humans; and preference for alcohol, anxiety and depression in rodents.</div></div><div><h3>Search methods and results</h3><div>Electronic databases PubMed, Embase, and Scopus were searched in January 2024 using the terms: faecal microbiota trans* AND alcohol AND microbio*. Ten studies out of 964 met the inclusion criteria of published primary studies with faecal microbiota transplantation as an intervention to study the gut-brain axis in alcohol use disorder.</div></div><div><h3>Results</h3><div>The gut microbiota is altered in alcohol use disorder, which can be modified with faecal microbiota transplantation. Behavioural symptoms such as alcohol craving and relapse are associated with inflammation due to a loss of intestinal barrier function. Beneficial microbiota produce short-chain fatty acids that maintain intestinal barrier function and reduce inflammation. Studies also reported anxiety and depression-like behaviours, in addition to a preference for alcohol in alcohol-naïve rodents after faecal microbiota transplantation from patients with alcohol use disorder.</div></div><div><h3>Conclusions</h3><div>Faecal microbiota transplantation may moderate the behavioural symptoms of alcohol use disorder by altering gut microbiota, affecting intestinal permeability and inflammation, however, specific gut microbiota composition and long-term treatment outcomes require further clinical studies.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111354"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789323","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":"Functional connectivity between subgenual anterior cingulate cortex and dorsomedial prefrontal cortex predicts clinical symptom improvement following total sleep deprivation in treatment resistant depression","authors":"Zhiliang Long ,&nbsp;Jiao Li ,&nbsp;Marco Marino","doi":"10.1016/j.pnpbp.2025.111351","DOIUrl":"10.1016/j.pnpbp.2025.111351","url":null,"abstract":"<div><div>Patients with treatment-resistant depression (TRD) can experience transient improvement in depressive symptoms after total sleep deprivation (TSD). TRD patients commonly present structural and functional alterations of subgenual anterior cingulate cortex (sgACC) and dorsomedial prefrontal cortex (dmPFC). However, at the functional level, the neuronal mechanisms underlying the depressive symptom improvement following TSD in TRD patients remains unclear. The current study included thirty-eight TRD patients and thirty-four healthy controls. We aimed to investigate whether resting-state functional connectivity (FC) between sgACC and dmPFC showed differences associated with the treatment effect following one night of TSD in TRD patients. Concerning the clinical improvement, in line with previous literature, we found that the TSD treatment reduced the Hamilton Depression Rating Scale (HDRS) score, the Stress score, the Behavioral Inhibition System score, and the Behavioral Activation System-Reward score. At the FC level, we reported that, in TRD patients, the sgACC-dmPFC FC at baseline was lower compared to the one of healthy controls, and that it significantly increased following one night of TSD. Furthermore, the sgACC-dmPFC FC at baseline in TRD patients was positively correlated with changes of HDRS score. These results suggests that the depressive symptom improvement following TSD in TRD patients might be involved in the resting-state sgACC-dmPFC FC.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111351"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769232","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":"Relationships and representations of brain structures, connectivity, dynamics and functions","authors":"Oliver Schmitt","doi":"10.1016/j.pnpbp.2025.111332","DOIUrl":"10.1016/j.pnpbp.2025.111332","url":null,"abstract":"<div><div>The review explores the complex interplay between brain structures and their associated functions, presenting a diversity of hierarchical models that enhances our understanding of these relationships. Central to this approach are structure-function flow diagrams, which offer a visual representation of how specific neuroanatomical structures are linked to their functional roles. These diagrams are instrumental in mapping the intricate connections between different brain regions, providing a clearer understanding of how functions emerge from the underlying neural architecture.</div><div>The study details innovative attempts to develop new functional hierarchies that integrate structural and functional data. These efforts leverage recent advancements in neuroimaging techniques such as fMRI, EEG, MEG, and PET, as well as computational models that simulate neural dynamics. By combining these approaches, the study seeks to create a more refined and dynamic hierarchy that can accommodate the brain’s complexity, including its capacity for plasticity and adaptation.</div><div>A significant focus is placed on the overlap of structures and functions within the brain. The manuscript acknowledges that many brain regions are multifunctional, contributing to different cognitive and behavioral processes depending on the context. This overlap highlights the need for a flexible, non-linear hierarchy that can capture the brain’s intricate functional landscape. Moreover, the study examines the interdependence of these functions, emphasizing how the loss or impairment of one function can impact others.</div><div>Another crucial aspect discussed is the brain’s ability to compensate for functional deficits following neurological diseases or injuries. The investigation explores how the brain reorganizes itself, often through the recruitment of alternative neural pathways or the enhancement of existing ones, to maintain functionality despite structural damage. This compensatory mechanism underscores the brain’s remarkable plasticity, demonstrating its ability to adapt and reconfigure itself in response to injury, thereby ensuring the continuation of essential functions.</div><div>In conclusion, the study presents a system of brain functions that integrates structural, functional, and dynamic perspectives. It offers a robust framework for understanding how the brain’s complex network of structures supports a wide range of cognitive and behavioral functions, with significant implications for both basic neuroscience and clinical applications.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111332"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733053","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":"Chronic stress enhances neuropathic pain through activation of the anterior cingulate cortex-spinal dorsal horn pathway in rats","authors":"Xin Yang ,&nbsp;Wei Xu ,&nbsp;Xinran Hou ,&nbsp;Zhuofeng Ding ,&nbsp;Chengliang Zhang ,&nbsp;Qulian Guo ,&nbsp;Wangyuan Zou ,&nbsp;Jian Wang","doi":"10.1016/j.pnpbp.2025.111352","DOIUrl":"10.1016/j.pnpbp.2025.111352","url":null,"abstract":"<div><div>Chronic stress is known to exacerbate neuropathic pain, yet the underlying mechanisms remain poorly understood. This study investigates the role of the anterior cingulate cortex (ACC) and its descending projections to the spinal dorsal horn (SDH) in mediating stress-induced pain facilitation. Using a chronic unpredictable mild stress (CUMS) model combined with a chronic constriction injury (CCI) model in male Sprague-Dawley rats, we assessed behavioral changes, neuronal activity, and molecular alterations. Our results demonstrate that CUMS significantly exacerbates mechanical allodynia in CCI rats, correlating with increased c-Fos expression in both the ACC and spinal cord, indicative of heightened neuronal activity. Chemogenetic inhibition of ACC-SDH projection neurons alleviated mechanical allodynia without affecting depressive-like behaviors, suggesting a specific role for this pathway in pain modulation. Furthermore, we identified that brain-derived neurotrophic factor (BDNF) signaling in the ACC-SDH pathway is crucial for the facilitation of neuropathic pain under chronic stress conditions. BDNF levels were elevated in the ACC of CUMS+CCI rats, and knockdown of BDNF in ACC-SDH projecting neurons attenuated stress-induced pain sensitivity. Our findings elucidate the functional capabilities of the ACC-SDH pathway in the context of chronic stress and neuropathic pain, highlighting BDNF as a potential therapeutic target for managing pain associated with affective disorders.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111352"},"PeriodicalIF":5.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759087","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":"The effect of low-dose psilocybin on brain neurotransmission and rat behavior.","authors":"Agnieszka Bysiek, Adam Wojtas, Izabela Szpręgiel, Agnieszka Wawrzczak-Bargieła, Marzena Maćkowiak, Krystyna Gołembiowska","doi":"10.1016/j.pnpbp.2025.111347","DOIUrl":"10.1016/j.pnpbp.2025.111347","url":null,"abstract":"<p><p>Psilocybin has various therapeutic effects in mental and psychological disorders, including depression and mood disorders, obsessive-compulsive disorders, substance addiction and anxiety. Pharmacodynamic properties of psilocybin depend on doses used and time after administration. The psilocybin dose range varies depending on whether it is used therapeutically or for recreational purposes in humans, but most animal studies require larger doses to induce an effect on brain neurotransmission and animal behavior. The aim of this study was to investigate the effect of psilocybin on the release of cortical neurotransmitters and rat behavior when it was administered subcutaneously at doses of 0.1, 0.3 and 0.6 mg/kg. Psilocybin affected the release of dopamine, noradrenaline, serotonin and acetylcholine in the frontal cortex as measured by microdialysis in freely moving rats. Psilocybin increased the release of aminergic transmitters in a non-linear manner with the dose of 0.3 mg/kg being the weakest. Psilocybin also increased the release of γ-aminobutyric acid, but glutamate release was enhanced only for the first 2 h after drug injection and was followed by a decrease for the rest of the experimental period. In contrast to 25I-NBOMe, an agonist of 5-HT2A receptors, psilocybin did not produce hallucinogenic activity expressed as wet dog shakes and did not disrupt sensorimotor gating in the acoustic startle response test. Furthermore, psilocybin showed anxiolytic effect in the light dark box test 1 h after administration. It also modulated the hypothalamic-pituitary-adrenal axis activity as it transiently increased serum corticosterone level, decreased serotonin, but increased dopamine turnover rates in the hypothalamus and inhibited the content of noradrenaline and adrenaline in the adrenal glands. The changes in the neurotransmitter release seem to play a role in psilocybin behavioral effects. The lack of hallucinogenic activity and disruptive effect on sensorimotor gating by psilocybin lower doses indicates that psychotomimetic effects did not occur. Psilocybin in contrast to 25I-NBOMe, ketamine and MDMA did not produce oxidative damage of DNA in the frontal cortex and hippocampus. Thus, the single low doses of psilocybin may have some beneficial properties and fewer harmful effects.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111347"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143744565","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":"Comparative analysis of gut microbiome-derived short-chain fatty acids in patients with severe mental disorder: Insights from schizophrenia and bipolar disorder","authors":"Gonzalo Paniagua ,&nbsp;Manuel Couce-Sánchez ,&nbsp;Leticia González-Blanco ,&nbsp;Carlos Sabater ,&nbsp;Ainoa García-Fernández ,&nbsp;Julia Rodríguez-Revuelta ,&nbsp;Pilar A. Sáiz ,&nbsp;Julio Bobes ,&nbsp;Abelardo Margolles ,&nbsp;M. Paz García-Portilla","doi":"10.1016/j.pnpbp.2025.111345","DOIUrl":"10.1016/j.pnpbp.2025.111345","url":null,"abstract":"<div><div>Both schizophrenia (SZ) and bipolar disorder (BD) are associated with disruptions in the gut microbiome. Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are key metabolites produced by gut bacteria that influence brain function, immune responses and behaviour. We conducted a cross-sectional observational study with 123 patients (86 with SZ and 37 with BD). We analysed faecal samples for SCFA and examined associations with clinical (psychopathology and cognition), metabolic and lifestyle factors. We performed analysis of covariance to find differences in SCFA levels between diagnostic groups, adjusting for covariates. Faecal SCFA levels were numerically higher in the SZ group than in the BD group. However, after adjusting for covariates, a significant sex-by-diagnosis interaction was observed only for acetate levels. Body mass index emerged as a key predictor of SCFA levels but we observed no significant associations with other metabolic or lifestyle variables, including diet, physical activity and blood inflammatory biomarkers. Additionally, SCFA levels showed no correlation with symptom severity or cognitive performance in either group. This study is the first to compare SCFA profiles between SZ and BD, highlighting potential differences in gut microbiota-derived metabolites between these disorders. These findings suggest greater disruption of the gut-brain axis in SZ, potentially reflecting distinct pathophysiological mechanisms involving metabolic and sex-related factors. Further research, including blood SCFA measurements, could better explain the role of SCFAs and explore microbiota-targeted therapeutic strategies for SZ and BD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111345"},"PeriodicalIF":5.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732948","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":"Development and validation of global tau severity score in Alzheimer's disease using Florzolotau (18F) PET","authors":"Mu-N Liu ,&nbsp;Hsin-I Chang ,&nbsp;Shu-Hua Huang ,&nbsp;Chi-Wei Huang ,&nbsp;Shih-Wei Hsu ,&nbsp;Kun-Ju Lin ,&nbsp;Tsung-Ying Ho ,&nbsp;Kuo-Lun Huang ,&nbsp;Chih-Ming Cheng ,&nbsp;Chiung-Chih Chang","doi":"10.1016/j.pnpbp.2025.111343","DOIUrl":"10.1016/j.pnpbp.2025.111343","url":null,"abstract":"<div><h3>Background</h3><div>Tau-specific positron emission tomography (tau-PET) is valuable for assessing Alzheimer's disease (AD) severity, with phenotypic differences between young-onset AD (YOAD) and late-onset AD (LOAD) likely driven by distinct relationships between tau pathology and cognition.</div></div><div><h3>Objective</h3><div>This study developed a global tau severity (gTS) scale using Florzolotau (18F) PET and compared it with the CenTauR score for standardizing tau burden quantification.</div></div><div><h3>Methods</h3><div>A total of 186 participants were enrolled, including a pilot group (15 cognitive unimpaired controls [CTL], 15 AD patients) and a validation group (27 CTL, 67 YOAD, and 62 LOAD patients). In the validation group, cutoffs for diagnosing YOAD and LOAD using the gTS or CenTauR score were calculated.</div></div><div><h3>Results</h3><div>The white matter region was identified as the most suitable reference for Florzolotau (18F). The gTS cutoff values of 24.1 for both AD and YOAD and 34.1 for LOAD demonstrated the highest diagnostic accuracy, as indicated by the area under the curve (AUC). The gTS score showed a higher AUC compared to CenTauR in YOAD versus CTL or LOAD versus CTL. The gTS scores significantly predicted total scores and subdomains on cognitive ability screening instruments. Cognitive-gTS curve features were found to have quadratic and linear relationships with YOAD and LOAD, respectively, illustrating different relationships between gTS scores and cognition.</div></div><div><h3>Conclusion</h3><div>The gTS score, derived from Florzolotau (18F) PET scans, provides significant predictions regarding tau burden and cognitive measurements. The higher AUC of gTS compared to the CenTauR universal scores indicates that gTS scores offer a robust method for differentiating AD from CTL.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"138 ","pages":"Article 111343"},"PeriodicalIF":5.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705614","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}