Translational Psychiatry最新文献

{"title":"Detecting suicide risk in bipolar disorder patients from lymphoblastoid cell lines genetic signatures.","authors":"Omveer Sharma, Ritu Nayak, Liron Mizrahi, Wote Amelo Rike, Ashwani Choudhary, Hagit Sadis, Yara Hussein, Idan Rosh, Utkarsh Tripathi, Aviram Shemen, Yam Stern, Alessio Squassina, Martin Alda, Shani Stern","doi":"10.1038/s41398-025-03573-3","DOIUrl":"10.1038/s41398-025-03573-3","url":null,"abstract":"<p><p>This research aimed to develop a machine learning algorithm to predict suicide risk in bipolar disorder (BD) patients using RNA sequencing analysis of lymphoblastoid cell lines (LCLs). By identifying differentially expressed genes (DEGs) between high and low risk patients and their enrichment in relevant pathways, we gained insights into the molecular mechanisms underlying suicide risk. LCL gene expression analysis revealed pathway enrichment related to primary immunodeficiency, ion channels, and cardiovascular defects. Notably, genes such as LCK, KCNN2, and GRIA1 emerged as pivotal, suggesting their potential roles as biomarkers. Machine learning algorithms trained on a subset of the patients and tested on others demonstrated high accuracy in distinguishing low and high risk of suicide in BD patients. Additionally, the study explored the genetic overlap between suicide-related genes and several psychiatric disorders. Our study enhances the understanding of the complex interplay between genetics and suicidal behaviour, providing a foundation for prevention strategies.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"339"},"PeriodicalIF":6.2,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993530","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":"Physiological and brain mechanisms contributing to postural tremor in aging with and without alcohol use disorder.","authors":"Edith V Sullivan, Stephanie A Sassoon, Kilian M Pohl, Manojkumar Saranathan, Natalie M Zahr, Adolf Pfefferbaum","doi":"10.1038/s41398-025-03552-8","DOIUrl":"10.1038/s41398-025-03552-8","url":null,"abstract":"<p><p>Postural instability, a concomitant of falls, can persist in people with alcohol use disorder (AUD) even with sustained sobriety. Balance testing using a force plate, which detects micromovements while standing still, can be quantified with spectral analysis and expressed as temporal frequency, an index of truncal (i.e., postural) tremor. Here, we investigated physiological and brain structural factors that may contribute to a mechanistic understanding of postural instability during quiet standing in AUD. This mixed cross-sectional/longitudinal design included 462 observations in 292 participants (age 25-75 years): 120 men and 44 women with DSM-5-determined AUD and 75 control men and 53 control women. All participants completed balance testing on a force plate under two conditions: eyes open and eyes closed, both with feet together. Most participants also underwent two-point discrimination testing on the soles of the feet and structural MRI, typically within the week of balance testing. Linear mixed-effects models revealed greater tremor in all conditions in the AUD than control group with the diagnostic differences attributed to AUD men. Age effects did not differ significantly between AUD and control groups. By contrast, stronger correlations were detected between greater tremor, measured as a 2-5 Hz/0-2 Hz frequency quotient, and smaller regional brain volumes selective to motor centers (frontal supplemental motor cortex, thalamus, pallidum, cerebellar white matter) of the AUD men. The salient signs of postural instability were attributable to AUD men who consumed alcohol exceeding NIAAA guideline limits in the year prior to testing.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"338"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970450","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":"Subjective cognitive decline in major depressive patients is associated with altered entropy and connectivity changes of temporal and insular region.","authors":"Burak Yulug, Ali Yalcinkaya, Shair Shah Safa, Dila Sayman, Seyda Cankaya, Ayse Karakus, Ceyhun Sayman, Abdullah Burak Uygur, Emir Izzet Bircan, Aydogan Dogukan Ucak, Halil Aziz Velioglu, Lutfu Hanoglu, Adil Mardinoglu","doi":"10.1038/s41398-025-03518-w","DOIUrl":"10.1038/s41398-025-03518-w","url":null,"abstract":"<p><p>Depressive cognitive impairment is seen in a significant number of patients with depression. However, it remains challenging to differentiate between patients with amnestic (those with subjective cognitive impairment complaints) and non-amnestic major depressive disorder, highlighting the urgent need for additional objective tools to help classify these patients more accurately. We analyzed cognitive state, alterations in regional entropy and functional connectivity measures of the brain between patients with major depression and healthy controls. The depressed cohort was categorized as either \"amnestic\" or \"non-amnestic,\" depending on self-reported experiences of forgetfulness. The superior temporal region and insula exhibited altered entropy and connectivity measures in individuals with depression and subjective cognitive impairment, which was correlated with impaired executive functions, a pattern not being evident in the control group. Our findings support the notion that insular and superior temporal entropic alterations are linked to subjective cognitive changes in the pathology of depression. These regions also hold potential as biomarkers for determining the underlying objective cognitive deficits in subjective cognitive complaints in patients with major depressive disorder (MDD). This underscores the need for improved diagnostic approaches and the implementation of practical dynamic neuroimaging modalities capable of addressing the current challenges in diagnosing subjective cognitive impairment in MDD, offering promise for the future management of patients with depression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"335"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970465","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":"Dissecting the heterogeneity of autism spectrum disorder with sensory behavior, brain, and epigenetic factors.","authors":"Yongjeon Cheong, Jihyun Bae, Seonkyoung Lee, Jihyeong Ro, Hidehiko Okazawa, Hirotaka Kosaka, Minyoung Jung","doi":"10.1038/s41398-025-03566-2","DOIUrl":"10.1038/s41398-025-03566-2","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD), a disorder with heterogeneous etiology, is characterized by abnormal behavioral responses to sensory inputs. However, there is still limited understanding of how brain and epigenetic factors, along with behavioral abnormality, contribute to ASD. After completing Adolescent-Adult Sensory Profile, a self-report questinnaire, 34 individuals with ASD and 72 controls underwent neuroimaging scans to measure brain structural (cortical and subcortical volume) and functional (thalamo-cortical resting-state functional connectivity) characteristics. For epigenetic measures, we computed DNA methylation values of the oxytocin receptor and arginine vasopressin receptor (AVPR) genes from the participants' saliva. When sensory-related behavior was the default baseline, a machine learning algorithm demonstrated that the neuroimaging-epigenetic model outperformed the neuroimaging model or the epigenetic model. Thalamo-cortical hyperconnectivity and AVPR 1A epigenetic modification were found to be significant contributing factors in these models. By integrating neuroimaging and epigenetic biomarkers with behaviors, a more precise diagnosis of ASD can be achieved.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"337"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970155","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":"[¹⁸F]FDG PET metabolic patterns of the rapid-acting antidepressant effects of NLX-101, a 5-HT_1A receptor biased agonist.","authors":"Sarah Chaib, Elise Levigoureux, Sandrine Bouvard, Caroline Bouillot, Benjamin Vidal, Anthony Fourier, Adrian Newman-Tancredi, Luc Zimmer","doi":"10.1038/s41398-025-03572-4","DOIUrl":"10.1038/s41398-025-03572-4","url":null,"abstract":"<p><p>Rapid-acting antidepressants (RAADs) such as ketamine are currently under development. The aim of this study is to characterize the neural circuits affected by ketamine and NLX-101, a selective 5-HT_1A receptor biased agonist which has shown promising effects, by using [¹⁸F]FDG PET imaging in rats that had received chronic administration of corticosterone (CORT), a model of anxiety-depression. In a longitudinal study, regional changes in brain activity were investigated in 24 selected CORT rats. Each animal underwent PET scans in 3 conditions, i.e. with ketamine (10 mg/kg), NLX-101 (0.16 mg/kg) or saline on day 0 and five days later to assess sustained effects. The anxious-depressive phenotype produced by CORT was supported by behavioural and biological observations. Changes in [¹⁸F]FDG uptake were determined using voxel-based and region of interest analyses. Metabolic connectivity analysis was also performed to investigate the acute and delayed effects of the treatments. Voxel-based and region-of-interest analyses showed marked hypometabolism in regions implicated in depression, particularly cingulate cortex (-7%) and lateral septum (-9%) as well as the striatum (-10%). Acute effects of NLX-101 and ketamine were observed in the lateral septum, resulting in an increase in brain glucose metabolism (p < 0,05). Interestingly, connectivity analyses also showed effects of NLX-101 in the frontal cortex, the thalamus and amygdala (p < 0.05), suggesting that the two molecules converge on common brain regions. This study is the first to show brain activation patterns of RAADs in a CORT rat model by functional PET imaging. NLX-101 appears to exert antidepressant effects by preferentially activating postsynaptic 5-HT_1A heteroreceptors in primary regions common to ketamine. These results support investigation of cortical 5-HT_1A receptors as a target for new generation biased agonist antidepressants.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"336"},"PeriodicalIF":6.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970496","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":"Characterizing replicability in the clustering structure of brain morphology in autism, attention-deficit/hyperactivity disorder, and obsessive compulsive disorder.","authors":"Younes Sadat-Nejad, Marlee M Vandewouw, Jessica Brian, Jennifer Crosbie, Russell J Schachar, Alana Iaboni, Elizabeth Kelley, Jessica Jones, Margot J Taylor, Muhammad Ayub, Robert Nicolson, Bilal Syed, Christopher Hammill, Stelios Georgiades, Paul D Arnold, Jason P Lerch, Evdokia Anagnostou, Azadeh Kushki","doi":"10.1038/s41398-025-03540-y","DOIUrl":"10.1038/s41398-025-03540-y","url":null,"abstract":"<p><p>In neurodevelopmental research, within-diagnosis heterogeneity and across-diagnosis overlap necessitate a shift from case-control designs to data-driven clustering approaches. However, our understanding of the replicability of these clustering structures across independent datasets remains limited. Our objective was to examine the replicability of clustering structure in measures of brain morphology in neurodiverse children across two independent datasets, namely the Province of Ontario Neurodevelopmental Disorder (POND) Network and the Healthy Brain Network (HBN). POND and HBN data were collected across various institutions in Ontario, Canada, and New York, United States, respectively. Participants were 5-19 years old and had diagnoses of autism, attention deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), or were neurotypical. We used measures of cortical volume, surface area, cortical thickness, and subgroup volume from structural MRI data. Principal component analysis (PCA) and clustering were used to examine the replicability of clustering structures across the datasets. Correlations among principle components, measures of clusterability, and alignment between the four brain measures as well as male/female subsets were examined. Brain-behaviour associations were examined using univariate and multivariate approaches. The POND dataset included 747 participants with (autism n = 312, ADHD n = 220, OCD n = 70, neurotypical n = 145). The HBN dataset included 582 participants (autism n = 60, ADHD n = 445, OCD n = 19, neurotypical n = 58). Our results showed significant between-dataset correlations in 82.1% of the principal components derived from brain measures. A two-cluster structure was replicated across datasets, brain measures, and the female/male subsets, however the participant composition of clusters were only aligned between cortical volume and surface area, and cortical thickness and subcortical volume. Regional effect sizes for between-cluster differences were highly correlated across datasets (beta = 0.92+/-0.01, p < 0.0001; adjusted R-squared=0.93). Data-driven clusters did not align with diagnostic labels across datasets. Brain-behaviour associations were only replicated for male subsets and subcortical volume using multivariate analysis. We found evidence of replicability of the clustering structure across two independent datasets; however, caution must be exercised in integrating multiple measures in clustering and interpretation of brain-behaviour associations.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"333"},"PeriodicalIF":6.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970560","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":"Adding to the burden: the tendency to resonate with others' stress is linked to higher PTSD symptom severity in individuals with war-related trauma.","authors":"Christiane Wesarg-Menzel, Mathilde Gallistl, Michael Niconchuk, Veronika Engert","doi":"10.1038/s41398-025-03548-4","DOIUrl":"https://doi.org/10.1038/s41398-025-03548-4","url":null,"abstract":"<p><p>Many refugees experience multiple traumatic events, which set them at increased risk to develop post-traumatic stress disorder (PTSD). To refine interventions aimed at improving refugees' mental health, a better understanding of the factors modulating vulnerability to war-related trauma is needed. In the present study, we focused on stress resonance as a potential vulnerability factor. Stress resonance reflects the empathic sharing of others' subjective and physiological stress experience. Sixty-seven participants who came from Arabic-speaking countries and had entered Germany as refugees or migrants took part in an empathic stress test, in which they observed a native German speaker undergo a psychosocial laboratory stressor. Meanwhile, different stress markers (subjective stress, heart rate, heart rate variability, and cortisol release) were simultaneously captured in the stressed targets and passive observers. Moderation analyses did not support our hypothesis that the extent to which someone resonates with others' stress is a vulnerability factor in the development of PTSD symptoms after trauma exposure. Rather, higher levels of subjective and autonomic stress resonance were directly related to PTSD symptom severity when controlling for sex, age, and trauma exposure. Our findings suggest that heightened stress resonance may constitute a malleable correlate of PTSD symptoms rather than a trait modulating health risk. In the future, efforts should be made to test whether individuals with a history of war-related trauma would benefit from interventions aimed to reduce the tendency to excessively share others' stress.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"331"},"PeriodicalIF":6.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970606","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":"Heightened effective connectivity of DLPFC-mPFC and DLPFC-ACC circuits in major depressive disorder with suicidal ideation: evidence from a TMS-EEG study.","authors":"Meng Chen, Xingxing Li, Wenhao Zhuang, Yongming Xu, Zhenglei Pei, Jimeng Liu, Yuanyuan Zhang, Chang Yu, Yubo Wang, Xiaoli Liu, Junfang Zhang, Guangwei Hou, Yinping Chen, Miaomiao Xu, Yafang Tang, Yan Ding, Jie Zhang, Dongsheng Zhou","doi":"10.1038/s41398-025-03515-z","DOIUrl":"10.1038/s41398-025-03515-z","url":null,"abstract":"<p><p>Major depressive disorder (MDD) with suicidal ideation (SI) significantly impacts global health. Suicidal ideation is associated with alterations in brain network connectivity, yet the effective connectivity from the dorsolateral prefrontal cortex (DLPFC) to functional network nodes remains poorly understood. This study utilizes transcranial magnetic stimulation-electroencephalography (TMS-EEG) to investigate DLPFC connectivity and cortical excitability changes, providing insights into the neurobiological mechanisms and potential treatments for MDD with SI. This study recruited 166 patients with MDD and 61 healthy controls. The TMS-EEG technique was used to assess effective connectivity based on abnormal time-locked TMS evoked potentials (TEPs). Suicidal ideation was assessed using the suicidality module of the Mini International Neuropsychiatric Interview (MINI), and participants were classified into suicidal ideation (SI) and non-SI (NSI) groups based on the presence of active ideation. Subgroup analysis evaluated significant current scattering (SCS) in DLPFC-related circuits through source localization, with multiple functional networks defined as downstream regions of interest. TEP analysis at the F3 electrode revealed no significant differences between the MDD and HC groups across components. However, the SI group exhibited increased N100 amplitudes compared to the NSI group (uncorrected) and healthy controls. Source-level brain network analysis showed that the SCS of the DLPFC-mPFC and DLPFC-ACC circuits was significantly greater in the SI group than in the NSI and control groups. After controlling for age, logistic regression analysis indicated a significant association between these connectivity patterns and the presence of suicidal ideation. MDD patients with suicidal ideation exhibit altered cortical inhibition and enhanced effective connectivity between the DLPFC and key brain regions, such as the ACC and mPFC. These exploratory findings contribute to a deeper understanding of the neural circuitry involved in suicidal ideation.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"332"},"PeriodicalIF":6.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970334","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":"Activity-dependent phosphorylation of CDYL by CDK5 regulates fear memory in mice.","authors":"Na-Yun Lyu, Guo-Guang Xie, Zhi-Wen Hu, Tian-Jie Lyu, Rui Qin, Lu Chen, Yun Wang","doi":"10.1038/s41398-025-03568-0","DOIUrl":"10.1038/s41398-025-03568-0","url":null,"abstract":"<p><p>Fear memory is crucial for animals to effectively respond to dynamic environments and survive dangerous stimuli. However, aberrant fear memory contributes to various psychiatric disorders, such as post-traumatic stress disorder (PTSD). Despite its importance, the precise molecular mechanisms underlying fear memory remain insufficiently understood. In this study, we highlight the pivotal role of the epigenetic factor chromodomain Y-like protein (CDYL) in the regulation of fear memory. We discovered that ablation of CDYL in CaMKIIα⁺ excitatory neurons in the forebrain or hippocampus leads to increased fear memory in mice. CDYL is phosphorylated by cyclin-dependent kinase 5 (CDK5) at Ser147, which facilitates tripartite motif containing 32 (TRIM32)-mediated ubiquitination and degradation of CDYL in response to neural activity. Additionally, we developed an interfering peptide that specifically targets the phosphorylation of CDYL at Ser147, resulting in a decrease in contextual fear memory in mice. Collectively, our findings underscore the essential role of CDYL in fear memory and illustrate the modulatory function of CDK5 and TRIM32 on CDYL, positioning CDYL as a promising target for the modulation of fear memory.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"334"},"PeriodicalIF":6.2,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970559","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":"Psilocybin-assisted therapy for treatment-resistant depression in the US: a model-based cost-effectiveness analysis.","authors":"Anton L V Avanceña, Linh Vuong, James G Kahn, Elliot Marseille","doi":"10.1038/s41398-025-03556-4","DOIUrl":"https://doi.org/10.1038/s41398-025-03556-4","url":null,"abstract":"<p><p>Psilocybin-assisted therapy (PAT) has been shown in early trials to reduce the symptoms of treatment-resistant depression (TRD). This study evaluated the cost-effectiveness of PAT as a third-line treatment for major depressive disorder compared to standard of care (SOC). We used an individual-level, probabilistic simulation model that portrays representative US adults with TRD who receive SOC (pharmacotherapy, psychotherapy, electroconvulsive therapy, and esketamine nasal spray) and PAT over 12 months. We assumed the total cost of PAT was $5000, which we varied in sensitivity analyses ($3000-20,000). We calculated total costs, health effects (in terms of quality-adjusted life years [QALYs] gained), and incremental cost-effectiveness ratio (ICER) from limited healthcare and societal perspectives. PAT leads to an additional 0.031 QALYs and $3639 costs compared to SOC over 12 months, giving an ICER of $117,517 per QALY gained from a limited healthcare perspective. Using a $150,000 cost-effectiveness threshold, PAT had a 75% probability of being the cost-effective choice, and it was associated with a lower expected loss than SOC ($301 vs. $1307). Results were sensitive to uncertainty in model parameters, particularly the cost of PAT. PAT had a 1% probability of being cost-effective when its overall costs were $10,000 and 95% when its costs were $3000. This cost-effectiveness analysis found that when its costs are $5000 or less, PAT may offer economic value compared to available TRD treatments. Future studies can explore ways to reduce the cost of PAT and to understand its long-term effectiveness in maintaining remission and reducing the risk of relapse.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"330"},"PeriodicalIF":6.2,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970484","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}