CNS Spectrums最新文献

{"title":"Longitudinal coupling between depressive symptoms and divided attention during transcranial magnetic stimulation in treatment-resistant depression.","authors":"Mao-Hsuan Huang, Yee-Lam E Chan, Jun-Ding Zhu, Wei-Chung Mao, Wei Yuan, Yia-Ping Liu, Li-Chi Chen, Feng-Chang Yen, Wei-Shen Huang, Tung-Ping Su","doi":"10.1017/S1092852926100935","DOIUrl":"10.1017/S1092852926100935","url":null,"abstract":"<p><strong>Background: </strong>Cognitive dysfunction is a core feature of major depressive disorder. During transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD), the temporal relationship between symptom changes and cognitive performance remains unclear. We examined depressive symptoms and cognitive trajectories during TMS and tested whether time-varying cognitive change was associated with symptom trajectories.</p><p><strong>Methods: </strong>This retrospective naturalistic study included 89 patients with TRD who completed 20 sessions of left dorsolateral prefrontal cortex TMS (high-frequency repetitive TMS or intermittent theta-burst stimulation). Depression severity (Hamilton Depression Rating Scale [HAMD-17]) and computerized attentional control measures from the Test of Attentional Performance were assessed at baseline, day 10, and day 20. Generalized estimating equations examined time effects and time-adjusted symptom-cognition associations. Exploratory analyses evaluated whether early cognitive change was associated with subsequent symptom improvement. Multiple comparisons were controlled.</p><p><strong>Results: </strong>Depressive symptoms decreased significantly (p < 0.001), with response and remission rates of 65.2% and 51.7%. Several attentional indices showed significant time effects; however, after false discovery rate correction, only visual divided-attention commission errors were independently associated with depressive severity beyond time effects. Person-mean centering indicated that this association was driven by within-person change (B = 0.209, p < 0.001), not between-person differences. Greater early reduction in visual divided-attention commission errors was associated with larger overall symptom improvement (B = 0.172, p = 0.016).</p><p><strong>Conclusion: </strong>Within-person changes in divided attention tracked depressive symptom trajectories during TMS. Attentional control measures may therefore help track symptom-cognition dynamics during TMS in real-world clinical settings.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e34"},"PeriodicalIF":4.6,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based differentiation of major depressive disorder and bipolar disorder using entropy-derived EEG biomarkers in drug-naïve patients.","authors":"Hyeon-Ho Hwang, Kang-Min Choi, Hyeon-Ah Lee, Sungkean Kim, Ji Sun Kim","doi":"10.1017/S1092852926100923","DOIUrl":"10.1017/S1092852926100923","url":null,"abstract":"<p><strong>Objective: </strong>Major depressive disorder (MDD) and bipolar disorder (BD) exhibit overlapping depressive presentations, making early differentiation difficult and misdiagnosis clinically consequential. Entropy-based resting-state electroencephalography (EEG) markers were evaluated for differentiating drug-naïve patients with stable MDD, converted BD, and diagnosed BD.</p><p><strong>Methods: </strong>Resting-state EEG was acquired from 92 drug-naïve patients: 50 with stable MDD, 16 who converted to bipolar II disorder over 3 years, and 26 with diagnosed BD. Band-scale entropy and cross-sample entropy (CSE) were analyzed. Group differences were tested by analysis of covariance adjusted for depressive severity; classification was evaluated by nested cross-validation with permutation testing.</p><p><strong>Results: </strong>Relative to stable MDD, diagnosed BD showed higher theta- and alpha-band entropy in frontal and central regions and lower values for selected intra- and inter-regional CSE measures. Two CSE measures correlated positively with non-planning impulsiveness in diagnosed BD. Converted BD showed intermediate values without significant pairwise differences. Prospective discrimination of stable MDD versus converted BD was modest (balanced accuracy, 65.4%; area under the receiver operating characteristic curve [ROC-AUC], 0.661). Classification was strongest for stable MDD versus diagnosed BD, yielding 78.9% pooled accuracy, 76.6% balanced accuracy, and an ROC-AUC of 0.832 when entropy features were combined with depressive severity; combined entropy outperformed either single-family configuration.</p><p><strong>Conclusions: </strong>Entropy-derived EEG measures differentiated stable MDD from diagnosed BD and suggested a weaker, intermediate profile in converted BD. They may serve as candidate adjunctive biomarkers for mood disorder differentiation, although larger prospective cohorts are required to clarify their value in predicting conversion to bipolar II disorder.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e40"},"PeriodicalIF":4.6,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147867238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical and psychiatric comorbidities and their influence on all-cause and suicide mortality: a longitudinal study of 109, 900 young patients with schizophrenia.","authors":"Shun-Chieh Yu, Shih-Jen Tsai, Tzeng-Ji Chen, Mu-Hong Chen","doi":"10.1017/S1092852926100911","DOIUrl":"10.1017/S1092852926100911","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia frequently coexists with various physical and psychiatric comorbidities, but the influence of these comorbidities on mortality outcomes, particularly suicide mortality, among young patients with schizophrenia remains inadequately understood.</p><p><strong>Methods: </strong>We followed 109 900 young patients with schizophrenia aged 10-44 years for up to 10 years. We assessed 12 physical diseases, including diabetes, myocardial infarction, chronic liver disease, and malignancies, and two psychiatric disorders, namely alcohol use disorder and substance use disorder (SUD). Time-dependent Cox regression models were used to analyze the associations of these comorbidities with all-cause and suicide mortality.</p><p><strong>Results: </strong>SUD was strongly associated with increased all-cause mortality (hazard ratio [HR]: 1.80) and suicide mortality (HR: 3.76). Malignancies (HR: 14.39) and chronic kidney disease (HR: 6.46) were also strongly linked to all-cause mortality. The risk of all-cause mortality increased with the number of comorbidities (HR: ≥2: 2.02 versus 1: 1.45). No significant association was found between physical comorbidities and suicide risk.</p><p><strong>Conclusions: </strong>SUD is a significant risk factor for suicide mortality among young patients with schizophrenia. Physical comorbidities such as malignancies and chronic kidney disease are primarily associated with increased all-cause mortality in this population.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e24"},"PeriodicalIF":4.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hospital-based management of predominant negative symptoms in schizophrenia: an observational study.","authors":"Jozef Dragašek, Zsofia Borbala Dombi, Péter László Herman, Viktor Dzurilla, Agota Barabassy","doi":"10.1017/S109285292610090X","DOIUrl":"10.1017/S109285292610090X","url":null,"abstract":"<p><strong>Objective: </strong>The present study investigated the management of predominant negative symptoms in hospitalized patients and assess the impact of targeted pharmacological and psychological interventions.</p><p><strong>Methods: </strong>This longitudinal, prospective, multicenter cohort study was conducted across multiple hospitals in Slovakia, focusing on inpatients, with assessments at admission and discharge. Eligible participants were hospitalized adults (18-65) diagnosed with schizophrenia and predominant negative symptoms. Treatment effectiveness was measured using the modified Short Assessment of Negative Domain, Self-evaluation of Negative Symptoms, Personal and Social Performance, and Clinical Global Impression scales. Means changes and effect sizes were calculated from baseline to final assessment. Differences in the perception of negative symptoms between patients and doctors were examined.</p><p><strong>Results: </strong>At discharge, patients showed significant improvements in symptom severity and functioning on all scales. Primary and secondary negative symptoms significantly decreased, especially those linked to positive and affective symptoms. Functioning improved, with fewer severe impairments in daily life. Most patients were on antipsychotic polytherapy throughout hospitalization, with around 85% receiving multiple antipsychotics at admission and at discharge. Non-pharmacological interventions were also widely used, with nearly nine out of ten patients receiving at least one such therapy during hospitalization.</p><p><strong>Conclusions: </strong>Negative symptoms in schizophrenia pose a major treatment challenge, leading to functional impairment and poor quality of life. While positive symptoms often trigger hospitalizations, negative symptoms have a lasting impact on prognosis. Results suggest both D3-receptor-targeted pharmacotherapy, particularly cariprazine, and integrated non-pharmacological interventions may contribute to meaningful improvements in negative symptoms during hospital care.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e10"},"PeriodicalIF":4.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic markers in bipolar disorder with childhood trauma exposure: a systematic review.","authors":"Hernan F Guillen-Burgos, Nicolas Montero, Isabela Orozco, Gabriela Gamba, Valentina Vanegas, Adelaida Uribe, Andrea Morelli, Sergio M Moreno-Lopez, Juan F Galvez-Florez, Roger S McIntyre","doi":"10.1017/S1092852926100881","DOIUrl":"10.1017/S1092852926100881","url":null,"abstract":"<p><p>Bipolar disorder (BD) is associated with increased cardiometabolic risk, contributing to elevated morbidity and premature mortality. Childhood trauma (CT) is a common environmental risk factor in BD and may exacerbate metabolic dysfunction, but no prior systematic synthesis has focused on their intersection. The objective of this review was to systematically review and synthesize evidence on the association between childhood trauma exposure and metabolic biomarkers in adults with bipolar disorder. This review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (ID CRD420251045565). A comprehensive search of PubMed/MEDLINE, Web of Science, Scopus, and Embase (from inception to September 2025) was conducted. Eligible studies were peer-reviewed observational studies assessing associations between CT and metabolic markers (eg, BMI, lipids, HbA1c, hs-CRP) in adult BD populations. Data extraction and NIH quality assessments were performed independently by multiple reviewers. Sixteen studies were included (total <i>n</i> ≈ 6,200 across study samples). CT was significantly associated with higher body mass index and elevated hs-CRP. Two third of studies reported adverse associations with lipid profiles, and one study showed increased HbA1c among CT-exposed BD patients. Most findings emerged from cross-sectional designs, though one longitudinal study revealed large effect sizes across multiple metabolic markers. CT is consistently associated with adverse metabolic outcomes in individuals with BD, particularly elevated BMI, inflammation, and dyslipidemia. These findings support the need for trauma-informed metabolic screening and personalized interventions in this subgroup BD population. Further prospective studies are warranted to elucidate causal pathways and inform personalized care.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e8"},"PeriodicalIF":4.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychiatric comorbidity patterns across disability-based fibromyalgia phenotypes.","authors":"Kevin V Hackshaw, Michelle M Osuna-Diaz, Katherine R Sebastian, Shreya Madhav Nuguri, Silvia deLamo Castellvi, Lianbo Yu, M Monica Giusti, Zhanna Mikulik, Luis Rodriguez-Saona","doi":"10.1017/S1092852926100893","DOIUrl":"10.1017/S1092852926100893","url":null,"abstract":"<p><strong>Objective: </strong>Fibromyalgia (FM) is a heterogeneous chronic pain condition frequently accompanied by psychiatric symptoms. Although affective symptoms are highly prevalent, they are often treated as secondary correlates of pain or disability. This study examined whether psychiatric symptom profiles parallel disability severity or represent partially independent dimensions across disability-based FM phenotypes.</p><p><strong>Methods: </strong>We analyzed a harmonized multisite cohort of adults with FM recruited from two academic medical centers. Disability-based phenotypes were defined using a validated percentile-based classification dichotomizing participants into low-impact and high-impact FM. Psychiatric domains were derived from standardized measures of depressive and anxiety-related symptoms. Multivariate clustering was used to identify affective profiles, and their distribution across disability phenotypes was examined. Dimensional analyses assessed the relationship between affective burden and functional impairment.</p><p><strong>Results: </strong>Among participants with complete psychiatric data (<i>n</i> = 613), four reproducible affective profiles were identified: minimal affective symptoms, mild affective symptoms, moderate mixed affective symptoms, and severe mixed affective symptoms. Although profiles characterized by greater affective burden were enriched among individuals with high-impact FM, all affective profiles were represented across both disability groups. Notably, a substantial proportion of individuals with high-impact FM exhibited minimal or mild affective symptoms. Dimensional analyses supported partial orthogonality between affective burden and disability severity.</p><p><strong>Conclusions: </strong>Psychiatric comorbidity in FM does not simply reflect pain severity or functional impairment. Instead, affective symptoms form partially independent dimensions that cut across disability-based phenotypes. These findings support a multidimensional neuropsychiatric framework for FM with implications for stratified assessment and personalized intervention.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e7"},"PeriodicalIF":4.6,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147503270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of ketamine on reward processing in depressive disorders: a systematic review of neuroimaging studies.","authors":"Halima Faisal, Gia Han Le, Angela T H Kwan, Sabrina Wong, Will Cheung, Christine E Dri, Bing Cao, Taeho Greg Rhee, Stavroula Bargiota, Heidi K Y Lo, Bianca Shen, Hernan F Guillen-Burgos, Roger S McIntyre","doi":"10.1017/S109285292610087X","DOIUrl":"10.1017/S109285292610087X","url":null,"abstract":"<p><strong>Background: </strong>Anhedonia and reward-processing deficits are core features of major depressive disorder (MDD) that respond poorly to traditional antidepressants. Ketamine has rapid antidepressant effects, yet its neurofunctional actions within reward circuits remain unclear. We synthesized human neuroimaging evidence on ketamine-related modulation of reward circuitry and implications for anhedonia.</p><p><strong>Methods: </strong>Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we searched Ovid Embase/MEDLINE/PsycINFO, Cochrane Library, Scopus, Web of Science, and Google Scholar. Eligible studies included adults with MDD receiving ketamine or esketamine and undergoing fMRI, PET, or related imaging during rest or reward/emotion tasks. Thirteen studies met inclusion criteria (N = 623; 482 MDD/TRD, 141 controls), mostly randomized, double-blind, and placebo-controlled; no eligible esketamine neuroimaging studies were identified.</p><p><strong>Results: </strong>Intravenous ketamine (typically 0.5 mg/kg over 40 min) was associated with short-term modulation of fronto-striatal and limbic networks. Resting-state fMRI commonly showed altered ventral striatal-prefrontal/ACC connectivity and broader DMN/salience/executive network reorganization across acute-to-subacute windows (≈2-48 h), with some effects changing at later follow-up (≈10 days). Task-based fMRI showed altered ventral striatal/putaminal responses during reward anticipation/feedback and modulation of medial prefrontal/cingulate activity during emotion processing. PET findings suggested increased prefrontal-cingulate metabolism and region-specific 5-HT₁B binding/availability changes, with baseline ventral striatal 5-HT₁B measures associated with symptom profiles and symptom change.</p><p><strong>Conclusions: </strong>Ketamine is associated with rapid reconfiguration of reward-related circuitry, but few studies directly measured anhedonia; findings likely reflect broader reward-processing and antidepressant-associated mechanisms. Larger longitudinal multimodal studies are needed to validate biomarkers and durability.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e9"},"PeriodicalIF":4.6,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147389661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and influencing factors of acupuncture in major depressive disorder: a systematic review and exploratory network meta-analysis.","authors":"Hui Zhao, Yuchen Zhang, Huan Cui, Lingxiang Tang, Yuan Gao, Cheng Tang, Weidong Shen","doi":"10.1017/S1092852926100868","DOIUrl":"10.1017/S1092852926100868","url":null,"abstract":"<p><strong>Background: </strong>Acupuncture is a clinically recognized treatment for major depressive disorder (MDD), but the associations of efficacy with dosage, treatment course, frequency, acupuncture modality, needle retention time, and manipulation remain unclear. This study evaluated the efficacy and safety of acupuncture for MDD and explored potential moderating factors.</p><p><strong>Methods: </strong>Randomized controlled trials of acupuncture for MDD were searched in CNKI, VIP Database, Wanfang Data, SinoMed, PubMed, Embase, Web of Science, and the Cochrane Library from inception to May 2025. Risk of bias was assessed using RoB 2, and certainty of evidence using GRADE. Data were analyzed in Stata 18.0.</p><p><strong>Results: </strong>36 trials involving 3843 participants were included. Compared with sham/placebo acupuncture, acupuncture showed greater antidepressant effects (SMD -1.12, 95% CI -1.57 to -0.67, P < 0.01). Very low-quality evidence suggested similar efficacy between acupuncture and antidepressants. Electroacupuncture was superior to manual acupuncture (SMD -0.24, 95% CI -0.42 to -0.07, P < 0.01). High- and moderate-dose acupuncture were more effective than low-dose regimens, and meta-regression suggested a linear dose-response relationship, with 30 sessions as the optimal dosage. Better outcomes were associated with treatment course >6 wk, 3 times weekly, needle retention time of 20-30 minutes, and electroacupuncture. No significant difference was found between needle manipulation and non-manipulation.</p><p><strong>Conclusions: </strong>Acupuncture significantly alleviates depressive symptoms in MDD. Efficacy appears to be influenced by dosage, acupuncture modality, treatment course, frequency, and needle retention time, with 30 sessions, treatment course > 6 wk, 3 sessions weekly, 20-30 minutes retention, and electroacupuncture showing the most favorable outcomes.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e6"},"PeriodicalIF":4.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Living with tardive dyskinesia: understanding the patient experience.","authors":"Leslie Citrome","doi":"10.1017/S1092852926100856","DOIUrl":"10.1017/S1092852926100856","url":null,"abstract":"<p><p>After a brief overview of tardive dyskinesia, this targeted narrative review will examine the psychosocial consequences of tardive dyskinesia on patients' daily lives, including stigma, social withdrawal, and quality of life, as well as impact on physical functioning. The extant literature on the impact of tardive dyskinesia on patients and their caregivers is described and summarized, including how patients with tardive dyskinesia perceive the severity and impact of their motor symptoms and whether this aligns with clinical observations by their treaters.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e11"},"PeriodicalIF":4.6,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13287816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the functional connectivity between central glucagon-like peptide-1 (GLP-1) and glutamatergic signaling: a systematic review.","authors":"Sabrina Wong, Gia Han Le, Kayla Teopiz, Roger S McIntyre","doi":"10.1017/S1092852926100844","DOIUrl":"10.1017/S1092852926100844","url":null,"abstract":"<p><p>Glutamatergic neurons represent 40% of neurons in the human central nervous system. Glutamate accounts for approximately 90% of all excitatory neurotransmitters. Previous research reports the presence of glucagon-like peptide-1 (GLP-1) receptors on neurons that produce glutamate. Herein, we aim to evaluate whether GLP-1 receptor agonists' (GLP-1 RAs) modulate glutamatergic signaling and whether GLP-1 RAs' anti-obesity effects are mediated through the glutamatergic system. We conducted a systematic review of extant literature published on PubMed, Ovid and Scopus databases from inception to March, 2025. Identified studies were screened independently by two reviewers (S.W. and G.H.L.) using the Covidence platform. We sought to include in vitro, in vivo, and human clinical studies. A total of 31 studies were identified as meeting eligibility for an inclusion in this review. No human studies were identified. Across the included preclinical and pharmacologic studies, GLP-1 RAs were associated with increased glutamate release, NMDA/AMPA receptor activation and increased release of neurotrophic factors associated with neurogenesis, neurodifferentiation, and synaptic plasticity. In addition, GLP-1 RA-induced suppression of food intake was reported to be dependent on AMPA, but not NMDA, receptor signaling. The effect of GLP-1 RAs on feeding behavior is mediated via central glutamatergic signaling. A comprehensive mechanistic framework mediating GLP-1 RA activity implicates crosstalk between GLP-1 and ionotropic glutamate receptors. The aforementioned trends instantiate a need to evaluate the therapeutic efficacy of GLP-1 RAs for disparate neuropsychiatric disorders. Conducting target engagement studies of GLP-1 RAs with the glutamatergic system in humans is a future research vista.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":"31 1","pages":"e4"},"PeriodicalIF":4.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}