Translational Psychiatry最新文献

{"title":"Associations between sleep quality, plasma neurofilament light, and cognition in older adults without dementia.","authors":"Hai-Hua Guo, Dong-Xin Liang, Qun Zhang, Yan Fu, Liang-Yu Huang, Ze-Hu Sheng, Lan Tan, Zuo-Teng Wang","doi":"10.1038/s41398-025-03389-1","DOIUrl":"10.1038/s41398-025-03389-1","url":null,"abstract":"<p><p>The relationship between sleep quality, neurofilament light chain (NFL), and cognitive impairment, including the potential effect of plasma NFL in this association, remains unclear. Using the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, we excluded individuals with dementia or a history of sleep-related medication use at baseline, including 640 participants with complete sleep assessments and covariates. Sleep quality was assessed using the Neuropsychiatric Inventory sleep subscale, which includes ratings of frequency, severity, and their product, with higher scores indicating poorer sleep quality. Baseline and follow-up demographics, sleep indices, plasma NFL levels, and cognition scores (including Mini-Mental State Examination [MMSE], Montreal Cognitive Assessment [MoCA], Alzheimer's Disease Assessment Scale-Cognitive Subscale [ADAS13], Clinical Dementia Rating Scale-Sum of Boxes [CDRSB], Executive Function [EF], Language [LAN], and Memory [MEM]) were also collected. Multivariable linear regression examined the associations between baseline sleep quality, plasma NFL, and cognition, as well as the relationship between sleep quality and longitudinal cognitive decline, calculated using linear mixed-effects models. Mediation analysis evaluated the role of plasma NFL in the sleep-cognition association. Multiple testing significance was corrected using false discovery rate, with results presented as Q-values. Poor sleep quality scores were associated with elevated plasma NFL levels (β: 0.055 to 2.645, P < 0.05), poorer cognition (ADAS13, CDRSB, EF, LAN, MEM; β: -0.188 to 1.279, Q < 0.05), and accelerated longitudinal cognitive decline (MoCA; β: -0.005, Q < 0.05) in both models, with sensitivity analyses supporting these findings. Furthermore, plasma NFL levels partially mediated the relationship between sleep quality and both baseline cognition (ADAS13, CDRSB, LAN, MEM; P < 0.05) and longitudinal cognitive decline (MoCA; P < 0.05), with mediation proportions ranging from 9.2% to 26.7%. Poorer sleep quality was associated with cognitive impairment and accelerated cognitive decline, suggesting its potential role in Alzheimer's disease. These associations may be partially mediated by neuroaxonal injury.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"169"},"PeriodicalIF":5.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086563","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":"Basic stimulus processing alterations from top-down cognitive control in depression drive independent temporal components of multi-echo naturalistic fMRI data.","authors":"Tengfei Feng, Arnim Johannes Gaebler, Micha Keller, Jana Zweerings, Huanjie Li, Fengyu Cong, Klaus Mathiak","doi":"10.1038/s41398-025-03386-4","DOIUrl":"10.1038/s41398-025-03386-4","url":null,"abstract":"<p><p>Perceptual changes in major depressive disorder (MDD) may extend beyond emotional content and include the processing of basic stimulus features. These alterations may ultimately contribute to perceptual bias and anhedonia. To characterize blood oxygen level-dependent (BOLD) signal of perceptual processing, we investigated temporally independent fMRI signal components related to naturalistic stimulus processing in 39 patients with MDD and 36 healthy subjects. Leveraging the capability of multi-echo data to detect BOLD activity changes, we extracted physiologically meaningful group temporal components. For each component that exhibited a significant correlation with the movie content, we localized its underlying brain network and assessed MDD-associated alterations. Two components exhibited significant group differences; one was associated with auditory features (sound pressure level) and one with visual features (temporal contrast of intensity). Notably, these deficits in MDD localized primarily to higher-order processing areas, such as the dorsal prefrontal cortex and insula, rather than primary sensory cortices. For the visual feature component, additional group differences emerged in non-visual primary sensory cortices (auditory and somatosensory) as well as major hubs of the motor system. Our findings support the hypothesis that basic sensory processing deficits represent an inherent feature of MDD which may contribute to anhedonia and negative perceptual bias. These deficits are primarily confined to higher-order processing units, as well as cross-modal primary sensory cortices indicating predominant dysfunction of top-down control and multisensory integration. Therapeutic effects of interventions targeting the prefrontal cortex may be partially mediated by restoring prefrontal control not only over emotional but also sensory processing hubs.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"171"},"PeriodicalIF":5.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086581","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":"Altered brain network dynamics in motor functional neurological disorders: the role of the right temporo-parietal junction.","authors":"Samantha Weber, Janine Bühler, Thomas A W Bolton, Selma Aybek","doi":"10.1038/s41398-025-03385-5","DOIUrl":"10.1038/s41398-025-03385-5","url":null,"abstract":"<p><p>Functional neurological disorders' (FND) neuropathophysiology has been described as multi-network disturbances including aberrancies in the agency network highlighting the role of the right temporo-parietal junction (rTPJ). Refining the relevance of the rTPJ, we applied a co-activation pattern (CAP) based approach using the rTPJ as a seed in 58 patients with motor FND compared to 58 age- and sex-matched healthy controls (HC). Firstly, CAPs were derived from HC to identify functional alterations in the rTPJ network in FND patients. Secondly, motor subgroup characteristics in patients were examined using CAPs derived from the patient group. Compared to HC, patients were found to enter less frequently a state characterized by salience network and default mode network (DMN) co-activation along with executive control and somatomotor networks co-deactivation. Additionally, patients entered more often a state depicted by somatomotor-salience co-activation and DMN co-deactivation. Comparing motor subgroups, patients with functional weakness (FW) remained longer in a state characterised by salience and dorsal/ventral attention network co-activation and DMN co-deactivation compared to patients with no functional weakness (no-FW). FND patients overall exhibited a reduced coupling of the DMN and an increased coupling of the somatomotor network with the rTPJ compared to controls. Patient subgroups differed regarding coupling between the rTPJ and the attention network and DMN. rTPJ dynamic network alterations might reflect hampered flexibility in brain state switching and altered self-referential processes linked to impaired motor planning and execution, which seem to also differ between symptom types, indicating a potential phenotypic biomarker.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"167"},"PeriodicalIF":5.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080587","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":"COMPASS: Computational mapping of patient-therapist alliance strategies with language modeling.","authors":"Baihan Lin, Djallel Bouneffouf, Yulia Landa, Rachel Jespersen, Cheryl Corcoran, Guillermo Cecchi","doi":"10.1038/s41398-025-03379-3","DOIUrl":"10.1038/s41398-025-03379-3","url":null,"abstract":"<p><p>The therapeutic working alliance is a critical predictor of psychotherapy success. Traditionally, working alliance assessment relies on questionnaires completed by both therapists and patients. In this paper, we present COMPASS, a novel framework to directly infer the therapeutic working alliance from the natural language used in psychotherapy sessions. Our approach leverages advanced large language models (LLMs) to analyze session transcripts and map them to distributed representations. These representations capture the semantic similarities between the dialogues and psychometric instruments, such as the Working Alliance Inventory. Analyzing a dataset of over 950 sessions spanning diverse psychiatric conditions -- including anxiety (N = 498), depression (N = 377), schizophrenia (N = 71), and suicidal tendencies (N = 12) -- collected between 1970 and 2012, we demonstrate the effectiveness of our method in providing fine-grained mapping of patient-therapist alignment trajectories, offering interpretable insights for clinical practice, and identifying emerging patterns related to the condition being treated. By employing various deep learning-based topic modeling techniques in combination with prompting generative language models, we analyze the topical characteristics of different psychiatric conditions and how these topics evolve during each turn of the conversation. This integrated framework enhances the understanding of therapeutic interactions, enables timely feedback for therapists on the quality of therapeutic relationships, and provides clear, actionable insights to improve the effectiveness of psychotherapy.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"166"},"PeriodicalIF":5.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080589","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":"Effects of self-managed lifestyle behavioral changes on cognitive impairment control in Chinese older adults: a population-based prospective study.","authors":"Jingjing Zhang, Dan Liu, Jing Liu, Cheng Cai, Feifei Hu, Guirong Cheng, Lang Xu, Yan Zeng","doi":"10.1038/s41398-025-03365-9","DOIUrl":"10.1038/s41398-025-03365-9","url":null,"abstract":"<p><p>Few studies have examined the effects of self-managed lifestyle behavioral adjustment on cognitive status. This study aimed to explore the association between self-managed behavioral changes and transitions in cognitive status. The Hubei Memory and Aging Cohort Study was a prospective cohort study conducted from 2018-2023 in rural and urban areas. Home-dwelling adults aged ≥65 years completed neuropsychological, lifestyle, clinical, and cognitive assessments. The Cox regressions and cubic splines were used to assess the risk of incident cognitive impairment, and latent class analysis was used to group participants based on behavioral patterns and assess transitions in cognitive status. Among 2477 participants with a mean of 2.02 (SD, 1.25) years of follow-up were included in the study. Participants with low and intermediate compared with high baseline behavioral risk exhibited a reduced risk of incident cognitive impairment. At follow-up, those who maintained stable healthy behaviors or positively adjusted them had a 54% (HR, 0.46 [95% CI, 0.34-0.62]) and 84% (0.16 [0.07-0.35]) lower risk of developing cognitive impairment, respectively, compared with those who maintained unhealthy behaviors. The standard and reinforced behavioral adjustment patterns exhibited a 37% (0.63 [0.22-1.79]) and 77% (0.23 [0.05-0.97]) reduction in the risk of incident cognitive impairment, respectively, compared with the basic pattern. Optimal cognitive gains were attributed to positive adjustments in social networks, physical exercise, cognitive activity, and sleep health. Older adults who maintained healthy behaviors or positively adjusted their unhealthy behaviors exhibited a reduced risk of incident cognitive impairment. Positive behavior modification brought greater cognitive improvement to all participants and more pronounced effects for those with dementia.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"165"},"PeriodicalIF":5.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011620","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":"Role of inflammation in depressive and anxiety disorders, affect, and cognition: genetic and non-genetic findings in the lifelines cohort study.","authors":"Naoise Mac Giollabhui, Chloe Slaney, Gibran Hemani, Éimear M Foley, Peter J van der Most, Ilja M Nolte, Harold Snieder, George Davey Smith, Golam M Khandaker, Catharina A Hartman","doi":"10.1038/s41398-025-03372-w","DOIUrl":"10.1038/s41398-025-03372-w","url":null,"abstract":"<p><p>Inflammation is associated with a range of neuropsychiatric symptoms, but the issue of causality remains unclear. We used complementary non-genetic, genetic risk score (GRS), and Mendelian randomization (MR) analyses to examine whether inflammatory markers are associated with affect, depressive and anxiety disorders, and cognition. We tested in ≈55,098 (59% female) individuals from the Dutch Lifelines cohort the concurrent/prospective associations of C-reactive protein (CRP) with: depressive and anxiety disorders; positive/negative affect; and attention, psychomotor speed, episodic memory, and executive functioning at baseline and a follow-up assessment occurring 3.91 years later (SD = 1.21). Additionally, we examined the association between inflammatory GRSs (CRP, interleukin-6 [IL-6], IL-6 receptor [IL-6R and soluble IL-6R (sIL-6R)], glycoprotein acetyls [GlycA]) on these same outcomes (N_min = 35,300; N_max = 57,946), followed by MR analysis examining evidence of causality of CRP on outcomes (N_min=22,154; N_max = 23,268). In non-genetic analyses, higher CRP was associated with depressive disorder, lower positive/higher negative affect, and worse executive function, attention, and psychomotor speed after adjusting for potential confounders. In genetic analyses, CRP_GRS was associated with any anxiety disorder (β = 0.002, p = 0.037) whereas GlycA_GRS was associated with major depressive disorder (β = 0.001, p = 0.036). Both CRP_GRS (β = 0.006, p = 0.035) and GlycA_GRS (β = 0.006, p = 0.049) were associated with greater negative affect. Inflammatory GRSs were not associated with cognition, except sIL-6R_GRS which was associated with poorer memory (β = -0.009, p = 0.018). There was a non-significant CRP-anxiety association using MR (β = 0.12; p = 0.054). Genetic and non-genetic analyses provide consistent evidence for an association between CRP and negative affect. These results suggest that inflammation may impact a broad range of trans-diagnostic affective symptoms.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"164"},"PeriodicalIF":5.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033665","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":"Antidepressant effects of ershiwei roudoukou pills and its active ingredient Macelignan: Multiple mechanisms involving oxidative stress, neuroinflammation and synaptic plasticity.","authors":"Yan-Li Wang, Lei Chen, Xiao-Lin Zhong, Qing-Shan Liu, Wen-Qiang Li, Yong Cheng, Yang Du","doi":"10.1038/s41398-025-03378-4","DOIUrl":"https://doi.org/10.1038/s41398-025-03378-4","url":null,"abstract":"<p><p>Major depressive disorder (MDD) represents a significant global health burden, with current treatments showing limited efficacy and considerable side effects. While traditional medicines offer promising alternatives, their mechanisms often remain unclear. Here we demonstrate that Ershiwei Roudoukou Pills (ERP) and its active ingredient Macelignan exhibit potent antidepressant effects through multiple interconnected pathways in a chronic unpredictable mild stress (CUMS) mouse model. Both compounds significantly improved depression-like behaviors in forced swimming, tail suspension, and open field tests. Mechanistically, ERP and Macelignan restored oxidative balance by modulating multiple markers including SOD, CAT, and MDA across serum, hippocampus, and prefrontal cortex. They effectively suppressed neuroinflammation by reducing pro-inflammatory cytokines (IL-6, TNF-α) and microglial activation while increasing anti-inflammatory markers (IL-10). Furthermore, both compounds enhanced synaptic plasticity through upregulation of synaptic proteins (PSD-95, MAP2, SYP) and activation of the BDNF-TrkB signaling pathway. Notably, ERP demonstrated differential anti-inflammatory properties compared to Macelignan, with distinct effects on different inflammatory markers, suggesting potential synergistic effects from its multiple components. These findings reveal the multi-target therapeutic potential of ERP and Macelignan in treating depression, providing new insights for developing more effective antidepressant strategies, particularly for treatment-resistant cases.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"163"},"PeriodicalIF":5.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12064756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035783","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":"Transcriptional evidence of reduced BDNF trophic capacity in the post-mortem human midbrain of schizophrenia cases with high inflammation.","authors":"Jessica J Chandra, Yunting Zhu, Alice Petty, Yasmine Kostoglou, William X Haynes, Maree J Webster, Cynthia S Weickert","doi":"10.1038/s41398-025-03359-7","DOIUrl":"https://doi.org/10.1038/s41398-025-03359-7","url":null,"abstract":"<p><p>Elevated inflammation in the midbrain of ~45% of people with schizophrenia may relate to altered trophic support for neurons. Dopamine neurons require trophic support from Brain-Derived Neurotrophic Factor (BDNF), that signals via the full-length Tropomyosin kinase B receptor (TrkB^TK+). The truncated BDNF receptor (TrkB^TK-) and the apoptosis-related p75 receptor may counteract the effects of BDNF. We hypothesised that transcriptional changes in either BDNF, and/or a transcription factor critical for the maintenance of dopamine neurons (Nuclear Receptor Related-1 protein; NURR1), and/or BDNF receptors - TrkB (TK+ or TK-) and p75, would be found in the post-mortem schizophrenia midbrain, particularly in schizophrenia cases defined as \"high inflammation\". The neuroinflammatory status was delineated based on elevated expression levels of a combination of pro-inflammatory transcripts (SERPINA3, IL6, IL1β and TNFα) and defined as a subgroup (46%) by 2-step recursive clustering. Using RT-qPCR, mRNA levels of NURR1, BDNF, TrkB and p75 was quantified in schizophrenia (n = 65) and control (n = 64) ventral mesencephalon. We found significant decreases in BDNF, TrkB^TK+ and NURR1 (14-18%) and increases in TrkB^TK- and p75 (18-35%) mRNA levels in schizophrenia compared to controls (all p < 0.05), with exacerbation of changes identified in high inflammation schizophrenia. To determine whether these changes would be consistent with resulting from chronic antipsychotic treatment, we treated healthy adult rats with antipsychotics (haloperidol and risperidone) for 7 months and found all transcripts to be unaltered compared to control rats. SnRNAseq of human midbrain showed that p75 receptor mRNA is primarily localised in oligodendrocytes and pan-TrkB mRNA is in both neurons and astrocytes. We confirmed that p75 was localised to oligodendrocyte-like cells by immunohistochemistry. Altogether, we find transcriptional evidence of reduced trophic support in schizophrenia midbrain and suggest that this may directly impact dopamine neuron health, particularly when neuroinflammation is also present.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"162"},"PeriodicalIF":5.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987614","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":"Exploring the association between serotonin transporter promoter region methylation levels and depressive symptoms: a systematic review and multi-level meta-analysis.","authors":"F Javelle, G Dao, M Ringleb, W Pulverer, W Bloch","doi":"10.1038/s41398-025-03356-w","DOIUrl":"https://doi.org/10.1038/s41398-025-03356-w","url":null,"abstract":"<p><p>Depressive disorders result from complex interactions among genetic, epigenetic, and environmental factors. DNA methylation, a key epigenetic mechanism, is crucial in understanding depressive symptoms development. The serotonin transporter gene (5-HTT) and its polymorphisms, like 5-HTTLPR, have been extensively studied in relation to depression, yet conflicting findings regarding the association between 5-HTT promoter methylation and depressive symptoms persist, largely due to methodological differences. Thus, this systematic review and meta-analysis aims to assess (1) 5-HTT promoter methylation levels between depressed and non-depressed conditions and (2) the association between 5-HTT methylation and depressive symptoms severity. We searched PubMed, Google Scholar, and Web of Science from inception to January 15th, 2025 (PROSPERO: CRD42023355414) and performed two independent multi-level meta-analyses to answer our aims. Twenty-four trials were included in the systematic review. All reported effects carried potential for bias. The meta-analysis for depression occurrence (12 studies - 2028 subjects - 127 effects) indicated no significant effect (Hedges'g = 0.06) with moderate within- and low between-study heterogeneity. The depression severity analysis (14 studies - 2296 subjects - 116 effects) revealed a null effect size (Fisher's Z = 0.05), with no within- and moderate between-study heterogeneity. Asymmetry was detected for both meta-analyses. Moderator analyses demonstrated no significant effects of depression severity, methylation techniques, single-CpG sites, cell types assessed, age, and female percentage. This comprehensive review provides insights into the intricate interplay between 5-HTT promoter methylation and depressive symptoms. Furthermore, it offers well-considered recommendations for future research endeavors and delineates guidelines for reporting methylation research.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"161"},"PeriodicalIF":5.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043630","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":"Predictive modeling of response to repetitive transcranial magnetic stimulation in treatment-resistant depression.","authors":"Lindsay L Benster, Cory R Weissman, Federico Suprani, Kamryn Toney, Houtan Afshar, Noah Stapper, Vanessa Tello, Louise Stolz, Mohsen Poorganji, Zafiris J Daskalakis, Lawrence G Appelbaum, Jordan N Kohn","doi":"10.1038/s41398-025-03380-w","DOIUrl":"10.1038/s41398-025-03380-w","url":null,"abstract":"<p><p>Identifying predictors of treatment response to repetitive transcranial magnetic stimulation (rTMS) remain elusive in treatment-resistant depression (TRD). Leveraging electronic medical records (EMR), this retrospective cohort study applied supervised machine learning (ML) to sociodemographic, clinical, and treatment-related data to predict depressive symptom response (>50% reduction on PHQ-9) and remission (PHQ-9 < 5) following rTMS in 232 patients with TRD (mean age: 54.5, 63.4% women) treated at the University of California, San Diego Interventional Psychiatry Program between 2017 and 2023. ML models were internally validated using nested cross-validation and Shapley values were calculated to quantify contributions of each feature to response prediction. The best-fit models proved reasonably accurate at discriminating treatment responders (Area under the curve (AUC): 0.689 [0.638, 0.740], p < 0.01) and remitters (AUC 0.745 [0.692, 0.797], p < 0.01), though only the response model was well-calibrated. Both models were associated with significant net benefits, indicating their potential utility for clinical decision-making. Shapley values revealed that patients with comorbid anxiety, obesity, concurrent benzodiazepine or antipsychotic use, and more chronic TRD were less likely to respond or remit following rTMS. Patients with trauma and former tobacco users were more likely to respond. Furthermore, delivery of intermittent theta burst stimulation and more rTMS sessions were associated with superior outcomes. These findings highlight the potential of ML-guided techniques to guide clinical decision-making for rTMS treatment in patients with TRD to optimize therapeutic outcomes.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"160"},"PeriodicalIF":5.8,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020437","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}