Translational Psychiatry最新文献

{"title":"Computational modelling and neural correlates of reinforcement learning following three-week escitalopram: a double-blind, placebo-controlled semi-randomised study.","authors":"Christelle Langley, Graham K Murray, Sophia Armand, Franziska Knolle, Rudolf N Cardinal, Annette Johansen, Peter S Jensen, Jianfeng Feng, Dea S Stenbæk, Gitte M Knudsen, Patrick M Fisher, Barbara J Sahakian","doi":"10.1038/s41398-025-03392-6","DOIUrl":"10.1038/s41398-025-03392-6","url":null,"abstract":"<p><p>Reinforcement learning is a fundamental aspect of adaptive behaviour, since it involves the acquisition and updating of associations between actions and their outcomes based on the rewarding or punishing consequences. Acute experimental manipulations of serotonin have provided compelling evidence for its role in reinforcement learning. However, it remains unknown how more chronic manipulation of serotonin, which holds greater clinical relevance, affects reinforcement learning and the underlying neural mechanisms. Consequently, we aimed to investigate the effect of a three-week administration of the SSRI, escitalopram, on a reinforcement learning paradigm during functional magnetic resonance imaging. The study used a double-blind, placebo-controlled design with 64 healthy volunteers. Participants were semi-randomised, ensuring matched groups for age, sex and intelligence quotient (IQ), to receive either 20 mg of escitalopram (n = 32) or placebo (n = 32) for at least 21 days. We analysed group differences in reinforcement learning using both analysis of covariance as well as innovative hierarchical Bayesian modelling of the reinforcement learning task. Escitalopram reduced learning from punishment during punishment trials. A key novel finding was that there was decreased activation of the intraparietal sulcus in the escitalopram group when compared to the placebo group during reward trials. The involvement of the intraparietal sulcus suggests that escitalopram affects the encoding of value outcome, which may lead to reduced reinforcement sensitivity, and thereby impacting adaptive learning from feedback. Understanding these mechanisms may help to optimize SSRI treatment to mitigate clinical symptoms and improve quality of life for neuropsychiatric patients, by elucidating serotonin's effects on affect, cognition, and behaviour.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"175"},"PeriodicalIF":5.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12095678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120936","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":"Investigating the effects of brain stimulation on the neural substrates of inhibition in patients with OCD: A simultaneous tDCS - fMRI study.","authors":"Daniela Rodriguez-Manrique, Hanyang Ruan, Chelsea Winkelmann, Julian Haun, Sandra Gigl, Götz Berberich, Claus Zimmer, Kathrin Koch","doi":"10.1038/s41398-025-03381-9","DOIUrl":"10.1038/s41398-025-03381-9","url":null,"abstract":"<p><p>Inhibition deficits constitute a core characteristic of obsessive-compulsive disorder (OCD). There is evidence in healthy individuals that transcranial direct current stimulation (tDCS) of the pre-supplementary motor area (pre-SMA) leads to a significantly improved inhibition performance. Against this background we investigated the effects of pre-SMA tDCS on inhibition performance and the underlying neural correlates in patients with OCD. Using a double-blind, randomized, sham-controlled, cross-over design (i.e., tDCS sham vs. tDCS stimulation) we investigated the effects of 2 mA anodal tDCS stimulation of the right pre-SMA in a sample of 47 OCD patients. The present study is, to our best knowledge, the first study applying concurrent tDCS-fMRI in patients with OCD. tDCS was applied using the MRI-compatible NeuroConn DC-Stimulator which allowed for a concurrent stimulation, while patients performed an inhibition (i.e., Stroop) task in a 3 T MRI. Imaging data were analysed using a multivariate partial least squares (PLS) approach. tDCS stimulation (vs. sham) was associated with increased activation in a fronto-parieto-cerebellar network comprising, amongst others, the precentral, middle frontal and inferior frontal gyrus, the anterior cingulate and the superior parietal lobe. On the performance level, tDCS stimulation (vs. sham) was linked to an improved inhibition performance in terms of an increased percentage of correct responses in the Stroop task. Present results indicate that tDCS in patients with OCD goes along with an improved inhibition performance as well as activation increases in regions known to be involved in inhibition, motor, and cognitive control. Thus, our findings suggest that tDCS might be a promising method to improve specific impairments in OCD.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"173"},"PeriodicalIF":5.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102759","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":"Personalized prediction of negative affect in individuals with serious mental illness followed using long-term multimodal mobile phenotyping.","authors":"Christian A Webb, Boyu Ren, Habiballah Rahimi-Eichi, Bryce W Gillis, Yoonho Chung, Justin T Baker","doi":"10.1038/s41398-025-03394-4","DOIUrl":"10.1038/s41398-025-03394-4","url":null,"abstract":"<p><p>Heightened negative affect is a core feature of serious mental illness. Over 90% of American adults own a smartphone, equipped with an array of sensors which can continuously and unobtrusively measure behaviors (e.g., activity levels, location, and phone usage patterns) which may predict increases in negative affect in real-time in individuals' daily lives. Sixty-eight adults with a primary mood or psychotic disorder completed daily emotion surveys for over a year, on average (mean 465 days; total surveys = 12,959). At the same time, semi-continuous collection of smartphone accelerometer, GPS location, and screen usage data, along with accelerometer tracking from a wrist-worn wearable device, was conducted for the duration of the study. A range of statistical approaches, including a novel personalized ensemble machine learning algorithm, were compared in their ability to predict states of heightened negative affect. A personalized ensemble machine learning algorithm outperformed other statistical approaches, achieving an area under the receiver operating characteristic curve (AUC) of 0.72 (for irritability) -0.79 (for loneliness) in predicting different negative emotions. Smartphone location (GPS) variables were the most predictive features overall. Critically, there was substantial heterogeneity between individuals in the association between smartphone features and negative emotional states, which highlights the need for a personalized modeling approach. Findings support the use of smartphones coupled with machine learning to detect states of heightened negative emotions. The ability to predict these states in real-time could inform the development and timely delivery of emotionally beneficial smartphone-delivered interventions which could be automatically triggered via a predictive algorithm.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"174"},"PeriodicalIF":5.8,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102760","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":"Stellate ganglion block diminishes consolidation of conditioned fear memory in mice by inhibiting the locus coeruleus to the basolateral amygdala neural circuit.","authors":"Ziheng Wang, Zhouliang Liu, Youjia Yu, Yuning Sun, Yan Zhang, Kailun Gao, Junli Cao, Liwei Wang, Yangzi Zhu","doi":"10.1038/s41398-025-03383-7","DOIUrl":"10.1038/s41398-025-03383-7","url":null,"abstract":"<p><p>Posttraumatic stress disorder (PTSD) is a devastating, prevalent psychological disorder characterized by excessive fear memory because of exposure to severe trauma. Stellate ganglion block (SGB) is traditionally used as a clinical treatment for pain but has been regarded as an innovative therapy for PTSD in recent reports. However, the mechanisms underlying the effect of SGB on PTSD remain unknown. Here, we established a fear conditioning model, which is considered a representative model of traumatic memory, and evaluated the effect of SGB on conditioned fear memory. We found that SGB reduced conditioned fear memory in mice in conjunction with the hypoactivity of locus coeruleus (LC) noradrenergic and basolateral amygdala (BLA) glutamatergic neurons. The norepinephrine concentration in the BLA decreased after SGB. Moreover, conditioned fear memory was re-enforced when the LC NE (LC^NE)-BLA pathway was activated in SGB mice. Our study findings indicated that the hypoactivity of the LC^NE-BLA pathway was the potential mechanism underlying the effects of SGB, which diminished consolidation of fear memory to relieve PTSD symptoms.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"172"},"PeriodicalIF":5.8,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095026","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":"Self-navigating the \"Island of Reil\": a systematic review of real-time fMRI neurofeedback training of insula activity.","authors":"Yuan Zhang, Benjamin Becker, Keith M Kendrick, Qiong Zhang, Shuxia Yao","doi":"10.1038/s41398-025-03382-8","DOIUrl":"10.1038/s41398-025-03382-8","url":null,"abstract":"<p><p>Real-time fMRI (rtfMRI) neurofeedback (NF) is a novel noninvasive technique that permits individuals to voluntarily control brain activity. The crucial role of the insula in emotional and salience processing makes it one of the most commonly targeted regions in previous rtfMRI studies. To provide an overview of progress in the field, the present review identified 25 rtfMRI insula studies and systematically reviewed key characteristics and findings in these studies. We found that rtfMRI-based NF training is efficient for modulating insula activity and its associated behavioral/symptom-related and neural changes. Furthermore, we also observed a maintenance effect of self-regulation ability and sustained symptom improvement, which is of importance for clinical application. However, training success of insula regulation was not consistently paralleled by behavioral/symptom-related changes, suggesting a need for optimizing the NF training protocol enabling more robust training effects. Principles including inclusion of a well-designed control group/condition, statistical analyses and reporting results following common criteria and a priori determination of sample and effect sizes as well as pre-registration are also highly recommended. In summary, we believe our review will inspire and inform both basic research and therapeutic translation of rtfMRI NF training as an intervention in mental disorders particularly those with insula dysfunction.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"170"},"PeriodicalIF":5.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086605","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":"Associations of interpersonal and socioeconomic early life adversity dimensions with adolescents' corticolimbic circuits, cognition, and mental health.","authors":"Yumeng Yang, Tianjiao Kong, Ran Liu, Liang Luo","doi":"10.1038/s41398-025-03384-6","DOIUrl":"10.1038/s41398-025-03384-6","url":null,"abstract":"<p><p>Early life adversity (ELA) is highly prevalent and has significant detrimental effects on children's brain development and behavioral outcomes. However, associations of threat, unpredictability, and deprivation in dimensional models of ELA with corticolimbic circuits were unclear. Previous studies have highlighted the effects of proximity, especially the distinctions between interpersonal and socioeconomic ELA, on children's neurodevelopment. This study first examined the associations between multiple ELA categories (i.e., interpersonal threat, socioeconomic threat, interpersonal unpredictability, socioeconomic unpredictability, interpersonal deprivation, and socioeconomic deprivation) and the developmental changes in resting-state functional connectivity (rsFC) of the frontolimbic and temporal-limbic circuits implicated in cognition and psychopathology, using data from the Adolescent Brain Cognitive Development (ABCD) study, which included four measurements from baseline (mean ± SD age, 119.13 ± 7.51 months; 2815 females) to 3-year follow-up (N = 5885). Controlling for concurrent ELA categories, interpersonal unpredictability and socioeconomic deprivation were associated with accelerated development of rsFC between CON/RTN-amygdala/hippocampus (Cingulo-opercular Network, Retrosplenial Temporal Network). Compared to girls, boys' corticolimbic circuits development was more sensitive to interpersonal threat. Changes in rsFC mediated the associations between interpersonal unpredictability/socioeconomic deprivation with decreased crystallized cognition, fluid cognition, and internalizing problems. Additionally, socioeconomic deprivation was associated with decreased crystallized cognition through interpersonal unpredictability and changes in rsFC between CON and bilateral amygdala/right hippocampus. This study emphasized interpersonal unpredictability and socioeconomic deprivation as key environmental factors affecting corticolimbic circuit development implicated in cognition and psychopathology. Stable family environments and enriched neighborhoods are crucial for supporting optimal neural and behavioral development in children and adolescents.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"168"},"PeriodicalIF":5.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12084605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086570","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":"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}