Journal of affective disorders最新文献

{"title":"The effect of digital health intervention on perinatal negative emotions: A meta-analysis.","authors":"Yu Wang, Shuang Hu, Danni Song, Congshan Pu, Jin He, Yiyun Yang, Yajie Ding, Chunjian Shan","doi":"10.1016/j.jad.2025.120003","DOIUrl":"10.1016/j.jad.2025.120003","url":null,"abstract":"<p><strong>Background: </strong>Women are prone to negative emotions, including fear symptoms, anxiety symptoms and depressive symptoms. Digital health intervention (DHI) has the potential to alleviate these symptoms.</p><p><strong>Objective: </strong>The purpose of this study was to evaluate the efficacy of DHI on perinatal negative emotions including fear symptoms, anxiety symptoms and depressive symptoms.</p><p><strong>Methods: </strong>This was a meta-analysis of randomized controlled trials. PubMed, Embase, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature databases were searched. The risk of bias for each study was assessed using the Cochrane risk of bias tool for randomized trials (RoB 2.0) and the meta-analysis was performed using R-4.4.3 software.</p><p><strong>Results: </strong>A total of 63 randomized controlled trials were included. The results revealed that the utilization of DHI had the potential to alleviate perinatal fear (SMD = -1.90, 95 %CI [-3.49, -0.32], P < 0.05), anxiety (SMD = -0.84, 95 %CI [-1.36, -0.32], P < 0.01) and depressive symptoms (SMD = -0.54, 95 %CI [-0.77, -0.30], P < 0.05). Subgroup analysis suggested that interventions based on APP, Internet and VR significantly alleviated perinatal anxiety symptoms. Interventions based on APP and Internet significantly alleviated depressive symptoms. Both prenatal and postnatal DHI were effective in alleviating anxiety and depressive symptoms. DHI effectively alleviated perinatal depressive symptoms in women without diagnosed mental disorder, but demonstrated no statistically significant effect in patients with diagnosed mental disorder.</p><p><strong>Conclusions: </strong>This meta-analysis of randomized trials suggests that DHI could reduce perinatal fear symptoms, anxiety symptoms and depressive symptoms. We look forward to more relevant studies to strengthen the evidence base for clinical intervention of DHI.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120003"},"PeriodicalIF":4.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859231","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 structural-functional connectivity coupling in the right caudal hippocampus mediates the effects of body mass index on cognitive function.","authors":"Wenjie Xia, Shanling Ji, Defu Zhang, Yue Wang, Yuxin Du, Ranran Xue, Lifeng Wang, Xiao Zhang, Hao Yu","doi":"10.1016/j.jad.2025.120063","DOIUrl":"10.1016/j.jad.2025.120063","url":null,"abstract":"<p><strong>Background: </strong>Studies have demonstrated an association between cognitive decline and body mass index (BMI). However, the neural mechanisms that underlie this association remain unclear. This study aimed to investigate the relationship between BMI, cognitive function, and brain structural-functional connectivity (SC-FC) coupling.</p><p><strong>Methods: </strong>This study included 490 healthy subjects undergoing resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) scans and cognitive function tests. Structural connectivity (SC) was constructed using DTI, and functional connectivity (FC) was constructed using rs-fMRI. The SC-FC coupling was constructed using Spearman's correlation between the SC and FC. Linear regression analyses were conducted to investigate the associations of BMI and SC-FC with cognitive function. Finally, mediation analysis was performed to test whether SC-FC coupling mediated the relationship between BMI and cognitive function.</p><p><strong>Results: </strong>BMI was positively correlated with Fluency, TMT-A, and WMS-III-SS, while showing negative associations with BACS-SC, BVMT-R, and NAB-Mazes (all p < 0.05). Higher BMI was linked to increased SC-FC in the right caudal hippocampus (cHipp; β = 0.19) and middle temporal gyrus (MTG; β = 0.19). Mediation analyses showed that the positive effect of BMI on the right cHipp SC-FC mediated its negative impact on Fluency (45.43 % mediated); the influence of BMI on right cHipp SC-FC mediated poorer performance on NAB-Mazes (85.25 % mediated); and the positive effect of BMI on right MTG SC-FC enhanced NAB-Mazes performance (69.12 % mediated).</p><p><strong>Conclusions: </strong>BMI influences cognitive function through its effects on brain SC-FC coupling, with distinct regional SC-FC patterns mediating both detrimental and beneficial cognitive outcomes.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120063"},"PeriodicalIF":4.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859232","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":"Cortical structural signatures for early identification of bipolar disorder from depressive episode.","authors":"Hao Sun, Na Shen, Zhilu Chen, Junling Sheng, Rui Yan, Haowen Zou, Shui Tian, Lingling Hua, Yiwen Wang, Xiaoqin Wang, Qing Lu, Zhijian Yao","doi":"10.1016/j.jad.2025.120077","DOIUrl":"10.1016/j.jad.2025.120077","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore specific biomarkers for the early identification of bipolar disorder (BD) by assessing cortical morphological features.</p><p><strong>Methods: </strong>This study comprised 185 BD patients, 203 unipolar depression (UD) patients, and 257 healthy controls (HC). In addition, through follow-up, a cohort of 86 patients initially diagnosed with major depressive disorder (MDD) who later transitioned to BD were identified as having initial depressive episode BD (IDE-BD). The cortical structural indices were measured for all participants. General linear models were used to assess the deviations in cortical characteristics between each depressive episode group and HC. Cosine similarity was employed to analyze the similarity of cortical thickness deviations across the depressive episode groups. Additionally, differences in cortical thickness between the BD/IDE-BD and UD groups were analyzed, and the association with clinical characteristics was explored.</p><p><strong>Results: </strong>The BD, IDE-BD, and UD groups share similar cortical thickness deviation patterns. Compared to HC, significant alterations in bilateral entorhinal cortex (EC) thickness were observed specifically in the BD and IDE-BD groups, while no such changes were observed in the UD group. Compared to UD, BD showed significant cortical thinning in the bilateral EC. In contrast, IDE-BD exhibited significant thickening in the bilateral EC compared to UD.</p><p><strong>Conclusions: </strong>In this transdiagnostic study, we revealed shared and disease-specific cortical thickness deviation patterns between BD and UD. Additionally, we highlight bilateral EC thickening as a predictor for the early identification of BD from depressive episodes. Our findings contribute to the early identification of BD from depressive episodes.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":"391 ","pages":"120077"},"PeriodicalIF":4.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955152","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":"Demographic and clinical characteristics of patients with borderline personality disorder: Real-world insights from a retrospective observational study.","authors":"Carissa White, Suzanne St Rose, Jennifer B Dwyer, Emily O C Palmer, Joannas Yeow, Kira Griffiths, Benjamin Chee, Mayowa Oyesanya, Rashmi Patel","doi":"10.1016/j.jad.2025.120008","DOIUrl":"10.1016/j.jad.2025.120008","url":null,"abstract":"<p><strong>Background: </strong>Current treatment modalities demonstrate variable effectiveness across patients with borderline personality disorder (BPD). Here, we describe the presenting clinical characteristics of patients with BPD based on approximately 20 years of real-world data.</p><p><strong>Methods: </strong>This retrospective, observational study was based on de-identified MindLinc electronic health records of individuals (aged ≥12 years with ≥1 diagnosis of BPD) receiving mental healthcare between 1999 and 2020 across 15 US states using the NeuroBlu database (vRel21R2). Demographic and clinical characteristics at first recorded BPD diagnosis (index date), baseline (index date ±14 days), and in the 12 months prior to diagnosis were described. BPD symptoms were derived by natural language processing (NLP) of unstructured clinician-documented mental state examination (MSE) data.</p><p><strong>Results: </strong>Across the 13,444 patients analysed at baseline (mean [SD] age 33 [12.8] years; 83.6 % female; 97.5 % with psychiatric comorbidities), the most frequent comorbid psychiatric conditions were major depressive disorder (45.7 %), substance use disorder (34.6 %) and post-traumatic stress disorder (29.2 %). Emotional dysregulation (35.8 %) and suicidal intent/ideation (31.3 %) were the most frequent NLP-derived BPD symptoms. Emotional dysregulation was more common in older patients, whereas suicidal intent/ideation/attempt/self-injury were more prevalent in younger patients. Mean (SD) length of hospitalisation was 2.9 (4.2) days, with 46.5 % of patients requiring ≥1 psychiatric hospitalisation. At diagnosis, 67.7 % of patients were prescribed pharmacological treatment, including antidepressants (51.1 %), second-generation antipsychotics (34.0 %) and anticonvulsants (33.7 %).</p><p><strong>Conclusion: </strong>BPD symptoms varied according to patient characteristics, including age and gender. These insights may enable patient-specific treatment planning in the future and improve therapeutic outcomes.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120008"},"PeriodicalIF":4.9,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804170","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":"Emotion-related alcohol use motives are associated with greater parasympathetic nervous system responses to acute challenge.","authors":"Danny Rahal, Violet F Kwan, Kristin J Perry","doi":"10.1016/j.jad.2025.119846","DOIUrl":"10.1016/j.jad.2025.119846","url":null,"abstract":"<p><p>Individuals' psychophysiological responses to stress are related to alcohol use initiation and frequency, but it remains unclear whether these responses are related to drinking motives among alcohol users. College students (N = 88; M_age = 20.26, SD = 1.18; 72.7 % female; 34.1 % white, 31.8 % Asian American, 12.5 % Latine, 14.8 % biracial, 6.8 % different racial and ethnic backgrounds) who self-reported past month alcohol use completed an acute challenge task (i.e., the mirror tracing task). They reported emotion before and after the task, and electrocardiogram data were continuously collected as a means of measuring parasympathetic nervous system activity at the heart. Multilevel models revealed that individuals who endorsed greater coping motives for alcohol use tended to show greater parasympathetic nervous system withdrawal to the acute challenge task, as well as a larger decrease in negative affect from pre- to post-task. Greater enhancement motives were also related to greater parasympathetic nervous system withdrawal, whereas social motives were related to larger decreases in negative affect from pre- to post-task. These findings suggest that individuals' motives, particularly endorsement for using alcohol to regulate emotion, is related to how they physiologically respond to acute challenges. Increased physiological responses to everyday challenges may motivate individuals to use alcohol as a means of regulating their responses. Results suggest that increasing emotion regulation skills or promoting psychoeducation regarding stress and interoception may be a prevention target for individuals who use alcohol to cope.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"119846"},"PeriodicalIF":4.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600552","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":"Interaction between DRD4 and MAOA genetic polymorphisms on static and dynamic regional coherence in the prefrontal cortex of drug-naive children with ADHD.","authors":"Shuangli Chen, Beihui Xue, Ronghui Zhou, Xueqin Bai, Shiwei Zhang, Yitong Cheng, Qiuyue Li, Andan Qian, Chuang Yang, Xiaoqi Huang, Meihao Wang","doi":"10.1016/j.jad.2025.120014","DOIUrl":"10.1016/j.jad.2025.120014","url":null,"abstract":"<p><strong>Objectives: </strong>The aim of this study was to explore the genetic association between DRD4 and MAOA genotypes and local functional connectivity in drug-naive children with ADHD.</p><p><strong>Methods: </strong>We investigated the effects of individual genotypes and gene × gene interactions between DRD4 and MAOA variants on local functional connectivity in 94 children with ADHD, using both the mean static regional homogeneity (sReHo) and the coefficient of variation (CV) of dynamic ReHo (dReHo). Additionally, correlation and mediation analyses were conducted to explore the relationships between dopamine-related genes, regional brain function, and neurocognitive alterations.</p><p><strong>Results: </strong>There was a significant genetic epistasis between DRD4 and MAOA variants affecting both sReHo and dReHo in the right orbital part of the middle frontal gyrus (MFG.R), belonging to prefrontal cortex (PFC). Post-hoc pairwise analysis revealed the altered intrinsic brain connectivity related to DRD4 varied according to MAOA genotype. Furthermore, the sReHo value in MFG.R was negatively correlated with the Hyperactivity index of the Conners scale in ADHD group. Mediation analysis suggested that the relationship between the DRD4 × MAOA gene interaction and the Hyperactivity index was mediated by the regional coherence of MFG.R in the PFC.</p><p><strong>Conclusion: </strong>These results suggest that alterations in the dopamine system in ADHD may contribute to abnormalities in both static and dynamic local functional connectivity. Disruptions in DA homeostasis within the synaptic cleft of the prefrontal cortex could lead to changes in intrinsic regional neural coherence. Our findings may help clarify the genetic basis of dopaminergic mechanisms underlying prefrontal dysfunction in ADHD.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120014"},"PeriodicalIF":4.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799093","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":"Moderating and mediating effects of dysmenorrhea pain severity in the relationship between body mass index and body appreciation among adult women with primary dysmenorrhea.","authors":"Guilherme Tavares de Arruda, Maria Eduarda Chinotti Batista da Silva, Pâmela Calixto de Moraes, Patricia Driusso, Mariana Arias Avila","doi":"10.1016/j.jad.2025.119888","DOIUrl":"10.1016/j.jad.2025.119888","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether dysmenorrhea severity moderates and/or mediates the association between body mass index (BMI) and body appreciation among women with primary dysmenorrhea (PD).</p><p><strong>Methods: </strong>Cross-sectional online study with 2026 women with PD. Participants were allocated into two groups according to their menstrual status: those who were menstruated and had current menstrual pain (CMP) and those who reported pain from their last menstrual period (LMP). We assessed bivariate relationships among BMI (Kg/cm²), pain severity (Numerical Rating Scale), and body appreciation (10-item Body Appreciation Scale), along with moderation and mediation for the same variables.</p><p><strong>Results: </strong>In the LMP group, BMI was significantly and negatively correlated with body appreciation (r = -0.249, p < 0.001). Moderation analysis indicated that the negative association between BMI and body appreciation was stronger at lower pain severity (β = -0.045, p < 0.001), whereas higher pain severity attenuated this effect. Furthermore, mediation analysis revealed that dysmenorrhea severity partially mediated the relationship between BMI and body appreciation (indirect effect β = -0.001, 95 % CI [-0.002, -0.001]), accounting for approximately 3 % of the total effect. No significant moderation or mediation effects were observed in the CMP group.</p><p><strong>Conclusions: </strong>Dysmenorrhea severity plays a dual role - acting as both moderator and mediator - in linking higher BMI to lower body appreciation. These findings underscore the importance of integrating pain management with interventions designed to improve body appreciation in women with PD. Future longitudinal studies should further clarify these relationships and underlying mechanisms.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"119888"},"PeriodicalIF":4.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637004","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":"Exploring the individual contributions of the 8 adverse childhood experiences (ACEs) domains to substance use.","authors":"Fares Qeadan, Jacob France, William A Barbeau","doi":"10.1016/j.jad.2025.119923","DOIUrl":"10.1016/j.jad.2025.119923","url":null,"abstract":"<p><strong>Background: </strong>Traditionally, adverse childhood experiences (ACEs) are grouped together into a cumulative score to predict substance use.</p><p><strong>Objective: </strong>To determine the effect of individual ACE domains (physical, emotional, sexual abuse, exposure to domestic violence, parental separation, household incarceration, household substance use and household mental illness) on later life substance use.</p><p><strong>Participants and setting: </strong>BRFSS data from 2019 to 2022 were used to construct 3 cohorts analyzing 5 different substance use outcomes.</p><p><strong>Methods: </strong>Logistic regression models were constructed to determine adjusted odd ratios (aORs) of substance used for each ACE domain. Random forest models served for sensitivity analyses.</p><p><strong>Results: </strong>Effect sizes varied across ACE domains and substances. Household substance use was the strongest predictor, with the highest aORs for smoking (aOR = 1.336, 95 % CI [1.266-1.410]), e-cigarette use (aOR = 1.451, 95 % CI [1.317-1.597]), and binge drinking (aOR = 1.256, 95 % CI [1.181-1.335]). Emotional abuse was the second most influential domain, particularly associated with marijuana use (aOR = 1.475, 95 % CI [1.349-1.613]). In contrast, exposure to domestic violence showed no significant associations with any substance use outcome. Sensitivity analyses using random forest models validated these findings, emphasizing the differential contributions of individual ACE domains to substance use behaviors.</p><p><strong>Conclusions: </strong>These findings emphasize that ACEs are not all entirely equal, and a cumulative score does not represent the individual effect each ACE has on substance use outcomes. Tailoring interventions and policies toward addressing specific ACE domains could significantly reduce substance use rates in later life.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"119923"},"PeriodicalIF":4.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649532","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":"Evaluating the extent to which targets are achieved in national suicide prevention strategies.","authors":"Manuel Canal-Rivero, Jane Pirkis, Matthew J Spittal, Angela Nicholas, Miguel Ruiz-Veguilla, Benedicto Crespo-Facorro, Angela Clapperton","doi":"10.1016/j.jad.2025.120021","DOIUrl":"10.1016/j.jad.2025.120021","url":null,"abstract":"<p><strong>Background: </strong>Several countries have implemented National Suicide Prevention Strategies (NSPSs), some of which include specific targets relating to reductions in suicide and/or suicidal behaviour. This study aimed to: (1) identify the proportion of NSPSs that include targets; and (2) assess whether these targets were achieved.</p><p><strong>Methods: </strong>A comprehensive review of NSPSs was conducted using relevant databases to identify those with defined targets. Official agencies were consulted to verify target achievement and to gather data on suicidal behaviour.</p><p><strong>Results: </strong>We identified 54 national strategies for analysis, of which 27 (50 %) included specific, quantitative targets. Eleven of these strategies had passed their target date and had available data for assessment. Of these eleven, only two countries, Chile and Israel, achieved their targets. For the remaining nine, outcomes varied: non-statistically significant reductions were observed in Bulgaria and Panama. Ireland also saw a reduction that, while numerically surpassing its target, was not statistically significant. Rates remained stable in England, and increased in Northern Ireland, the United States, Scotland, and Uruguay.</p><p><strong>Limitations: </strong>Although the data were sourced from official records, potential biases may have affected the quality and accuracy of the analysis.</p><p><strong>Conclusions: </strong>A significant proportion of NSPSs lack specific targets and even among those that have specific targets, achieving these remains a challenge for many. However, the presence of specific targets could at least facilitate the identification of barriers hindering the attainment of these targets.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120021"},"PeriodicalIF":4.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799170","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":"Blood-based biomarkers in ketamine treatment: A blueprint for translational drug development in mood disorders.","authors":"Alan C Courtes, Gregory H Jones, Ioline D Henter, Lokesh Shahani, Gabriel R Fries, Mario F Juruena, Jair C Soares, Carlos A Zarate, Rodrigo Machado-Vieira","doi":"10.1016/j.jad.2025.120016","DOIUrl":"10.1016/j.jad.2025.120016","url":null,"abstract":"<p><p>Over the past two decades, the N-methyl-d-aspartate receptor antagonist ketamine has emerged as a transformational, rapid-acting therapy for both unipolar and bipolar depression-particularly in treatment refractory cases. However, its specific mechanism of action remains unclear. Furthermore, although repeatable neuroimaging-based and electrophysiological biomarkers of treatment response to ketamine have been identified, they cannot provide specific molecular targets with which to advance precision psychiatry with rapid-acting antidepressants. This review explores blood-based biomarkers of ketamine response with an eye towards elucidating ketamine's intricate and varied antidepressant effects. Key findings indicate that ketamine modulates inflammatory, neurotrophic, and metabolic systems, and these changes are reflected in altered levels of biomarkers such as interleukin-6, brain-derived neurotrophic factor (BDNF), and plasma d-serine. Notably, the relationship between therapeutic efficacy and ketamine's metabolites, such as (2R,6R)-hydroxynorketamine, highlights the potential for metabolite-guided strategies and reciprocal translational research. In addition, the rapid temporal dynamics of biomarkers, particularly BDNF and inflammatory cytokines, underscore their potential as tools for monitoring treatment response and developing novel therapeutics. Despite these advances, limitations persist, including heterogeneous methodologies and small sample sizes across studies. The field requires a paradigm shift towards integrated biosignatures, combining multi-system biomarkers (i.e., neuroimaging, electrophysiological, and sleep biomarkers) with clinical outcomes. Such an approach has the potential to refine patient stratification, enhance drug development, and improve treatment monitoring.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120016"},"PeriodicalIF":4.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804169","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}