Translational Psychiatry最新文献

{"title":"Neurocomputational training to boost reward learning and sensitivity in anhedonic individuals: a transdiagnostic proof-of-concept trial.","authors":"Katia M Harlé, Murray B Stein, Alan N Simmons, Charles T Taylor","doi":"10.1038/s41398-026-04355-1","DOIUrl":"https://doi.org/10.1038/s41398-026-04355-1","url":null,"abstract":"<p><p>Anhedonia, which is characterized by a loss of pleasure and engagement in rewarding activities, is prevalent across diagnostic groups and is associated with worse clinical and treatment outcomes. Existing evidence-based treatments have only modest effects on improving anhedonia. Reward learning (RL) is an important driver of reward-responsive behavior, which could be leveraged to improve reward sensitivity - a candidate mechanism underlying anhedonia. Individuals (N = 50) with at least moderate anhedonia and clinical levels of depression and/or anxiety were randomized to either an active RL training (high variance of reward rates to promote reward exploration and maximization) or a sham version. Before and after training, they completed an assessment RL task while undergoing functional neuroimaging as well as ratings of current affect. Computational modeling was used to assess change in reward learning and sensitivity, as well as associated neural activity. Participants assigned to the active condition exhibited greater increases in learning-based reward maximization, i.e., the propensity to choose options predicted to be most rewarding, and reductions in anterior cingulate cortex activation to reward prediction errors (discrepancies between expected and observed rewards), consistent with optimization of reward learning and performance. In exploratory analyses, learning-based reward maximization during training mediated increase in positive affect associated with the active condition. Our results underscore the potential of RL-informed computerized trainings to improve RL and associated goal-directed reward behavior in anhedonic individuals. Future research is needed to determine whether the proposed training can successfully transfer to real-world settings and produce long-term affective and clinical improvements (ClinicalTrials.gov: NCT05383248).</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emotional intensity and visual imagery in trauma nightmares map to posterior hippocampus connectivity.","authors":"Meaghan McKenna, Kevin J Clancy, Christine J So, Yara Pollmann, Boyu Ren, Isabelle M Rosso","doi":"10.1038/s41398-026-04336-4","DOIUrl":"https://doi.org/10.1038/s41398-026-04336-4","url":null,"abstract":"<p><p>Distressing dreams or nightmares about a traumatic experience are common among trauma-exposed individuals and contribute to the maintenance of posttraumatic stress disorder (PTSD) symptoms. Like other intrusive reexperiencing symptoms, trauma-related nightmares are characterized by vivid sensory details and heightened emotional intensity. However, little is known about their underlying neurobiology, and whether it overlaps with that of diurnal reexperiencing symptoms. Therefore, this study aimed to elucidate neurobiological correlates of the phenomenology of trauma-related nightmares. Sixty-six trauma-exposed adults (54 female) completed daily ecological momentary assessments (EMAs) of the phenomenological properties of their trauma-related nightmares for two weeks, as well as resting-state functional magnetic resonance imaging. Pearson correlations examined associations between nightmare properties and functional connectivity within two a priori circuits previously implicated in trauma-related intrusions and episodic memory: 1) an affective circuit between the anterior hippocampus (aHPC) and amygdala (Amyg), and 2) a sensory circuit between the posterior hippocampus (pHPC) and visual cortex (VC). There were no significant associations between nightmare properties and aHPC-Amyg connectivity. In contrast, stronger pHPC-VC connectivity was associated with greater visual detail and emotional intensity of nightmares. These findings align with the established roles of the pHPC and VC in the detailed experience of episodic memory and suggest a novel role for these regions in the affective features of trauma nightmares. Overall, these findings provide support for overlapping neural correlates of the properties of trauma nightmares and diurnal reexperiencing symptoms. They offer additional evidence for a pHPC-VC circuit as a promising neurotherapeutic target for trauma reexperiencing symptoms.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal elements of speech in mania.","authors":"Jeremiah B Joyce, Ivan N Ayala, Sanjeev Mishra, George Chatzisofroniou, Erik Clemens, Hang Yu, Tyler Kendall, Zachi Attia, Baihan Lin, Mark A Frye","doi":"10.1038/s41398-026-04329-3","DOIUrl":"https://doi.org/10.1038/s41398-026-04329-3","url":null,"abstract":"<p><p>Computational analysis of speech enables precise, objective measurements of a behavioral signal closely linked to manic episodes. In a prospective cohort study conducted in Rochester, MN (ClinicalTrials.gov Identifier: NCT05956340), eighteen English-speaking adults voluntarily hospitalized for a manic episode of Bipolar I Disorder between August 2023 and September 2024 were enrolled. Participants completed semi-structured research interviews during both acute episodes and remission, with manic symptom severity assessed at each session using the Young Mania Rating Scale (YMRS). Across 57 recorded interviews, temporal prosodic features were extracted using a novel end-to-end computational pipeline. After adjusting for individual differences and moderating effects, participant articulation rate (β = 0.24, p = 0.0038), speech rate variability (β = 0.23, p = 0.0041), floor transfer offset (β = -0.31, p = 0.007), and speaking duration (β = 0.54, p < 0.001) were significantly associated with manic symptom severity. These exploratory findings were largely independent of medication effects, as well as the presence of psychotic or mixed symptoms. These temporal elements classified manic (CV AUC = 0.85) and remission (CV AUC = 0.83) status, highlighting their potential as monitoring biomarkers for manic episodes.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency of therapeutic drug monitoring in inpatient precision depression care and duration of hospitalization.","authors":"Chantal Hampf, Jürgen Deckert, Sebastian Walther, Heike Weber, Stefan Unterecker, Maike Scherf-Clavel","doi":"10.1038/s41398-026-04316-8","DOIUrl":"10.1038/s41398-026-04316-8","url":null,"abstract":"<p><p>In psychiatry, therapeutic drug monitoring (TDM) is routinely used to improve treatment safety and efficacy, yet its association with hospitalization duration and cost-effectiveness remains unclear. We hypothesized that the frequency of routinely requested TDM is associated with hospitalization duration. In this retrospective study, patients with major depressive disorder receiving TDM of antidepressants between 2015 and 2021 (N = 383) were analyzed. Inclusion criteria were a hospital stay ≥7 days and a first TDM request at admission. Regression analyses assessed associations between TDM frequency and hospitalization duration. Receiver operating characteristic analysis identified a minimum effective TDM frequency of 0.66/week, which was associated with a mean reduction in hospitalization duration of 21 days (p < 2.2*10^-¹⁶). The upper effective threshold was approximated at 1.3/week. Higher TDM frequency was associated with more therapy adjustments within 7 days after TDM, including dose adaptations (p = 3.07*10^-¹⁶) and drug initiation/discontinuation (p = 6.70*10^-6). Drug-specific analyses for amitriptyline, venlafaxine, and mirtazapine confirmed these associations. Cost-effectiveness analysis demonstrated a 37% cost reduction for patients with TDM frequencies ≥0.66/week. In conclusion, frequent, clinically integrated TDM of antidepressants and timely treatment adaptations were associated with shorter hospitalization and reduced hospitalization costs. These findings suggest that at least biweekly TDM combined with subsequent treatment adaptations may represent a previously underappreciated strategy to improve clinical and economic outcomes in a tertiary referral center for severe major depression. Whether these findings are transferable to other inpatient and outpatient settings of depression care requires further studies.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148649312","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":"Cardiac vagal activity during in-vivo threat exposure is associated with within-session inhibition of fear and avoidance.","authors":"Christoph Szeska, Kai Klepzig, Alfons O Hamm, Mathias Weymar","doi":"10.1038/s41398-026-04333-7","DOIUrl":"10.1038/s41398-026-04333-7","url":null,"abstract":"<p><p>Laboratory research suggests that the attenuation of defensive responses during threat exposure relies on the inhibition of subcortical defense circuits orchestrated by the prefrontal cortex. This process may be reflected by increased vagal efferent activity on the autonomic nervous system. Here, we tested whether cardiac vagal efferent activity, indicated by vagally-mediated heart rate variability (vmHRV), is associated with reduced defensive responses during in-vivo threat exposure and whether it may serve as a physiological index of multi-level exposure responding. Thirty-three women with excessive fear of spiders underwent standardized exposure, where they first approached a living tarantula (approach phase) and subsequently progressed through stages of increasingly direct interactions with the spider (threat imminence task). Indices of cardiac vagal activity (vmHRV) and overall cardiac autonomic arousal (heart rate) were measured alongside self-reported fear and avoidance behavior (distance to spider, performance in threat imminence task). During approach, self-reported fear increased until it reached a stable ceiling. Concurrent vmHRV leveled accordingly, with greater activity being related to lower fear and reduced avoidance during the subsequent threat imminence task. From the very first minute, cardiac vagal activity was associated with the participants' ability to physically engage with the fear cue during threat imminence task, irrespective of covariations in self-reported fear. Our results suggest that cardiac vagal activity may represent inhibition of fear and avoidance during exposure to perceived threat. Cardiac vagal activity, indexed by vmHRV, could therefore represent an index of within-session multi-level responding to exposure and a promising target for adjuncts to promote fear reduction.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13428751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654059","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":"Cancer risk among individuals with mental illness - a systematic review and meta-analysis of nordic register-based prospective studies.","authors":"Xue Xiao, Fatemeh Sadeghi, Gillian Murphy, Zhe Zhang, Ole A Andreassen, Unnur Valdimarsdóttir, Fang Fang, Mary M Barker","doi":"10.1038/s41398-026-04351-5","DOIUrl":"https://doi.org/10.1038/s41398-026-04351-5","url":null,"abstract":"<p><p>Although cancer patients have a high burden of mental illness, it is less clear whether patients with mental illness experience a higher-than-expected cancer risk. This systematic review investigated the associations between a wide range of types of mental illness and subsequent cancer risk. Five electronic databases were searched for articles published from database initiation to October 24, 2024. Studies using nationwide Nordic register data to conduct a prospective analysis of the association between mental illness diagnosis and cancer incidence were included. When data from three or more countries were available for a given type of mental illness, random effects meta-analyses were performed; otherwise, narrative syntheses were conducted. A total of 7,767 non-duplicate articles were screened, of which 20 were included. Meta-analyses showed no association between schizophrenia diagnosis and overall cancer risk; however, a high level of heterogeneity was detected between studies. Individuals with schizophrenia appeared to have a higher risk of breast cancer (pooled standardized incidence ratio [SIR]: 1.28, 95% confidence interval [CI]: 1.08-1.52), and lower risks of rectal cancer (pooled SIR: 0.75, 95% CI: 0.59-0.95) and prostate cancer (pooled SIR: 0.53, 95% CI: 0.48-0.59), compared to individuals in the general population. A higher risk of overall cancer was observed for mood, anxiety, and stress-related disorders, as well as autism and intellectual disability, in multiple studies; however, the results differed by cancer types and sex. In summary, these findings suggest an altered risk of cancer among individuals with mental illness living in Nordic countries. Further research is needed to enable the development of targeted cancer prevention strategies to reduce mental health disparities in cancer protection.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-species mapping of acute psychedelic-responsive genes links HTR2A cortical expression, cell-type enrichment, and human cortical expression modules.","authors":"Patrick A McConnell, Jackson Raffety, Andrew Li, Eric Steinberg, Syed Rahim, Christian Valtierra, Adam Gazzaley, Robin L Carhart-Harris, Lorenzo Pasquini","doi":"10.1038/s41398-026-04349-z","DOIUrl":"https://doi.org/10.1038/s41398-026-04349-z","url":null,"abstract":"<p><p>Psychedelic drugs exert rapid and profound effects on human consciousness [1-7] and are increasingly being investigated for their therapeutic potential [8-14]. Yet the transcriptional programs through which they may reshape brain function and structure remain incompletely understood, in part because the available evidence is heterogeneous and largely preclinical [15, 16]. In a structured scoping review of transcriptomic studies in animal models and neural cell cultures, we identified genes reported in the source literature to change within 3 h of classical psychedelic administration and intersected them with the Allen Human Brain Atlas to define an acute expression set. This retained set showed cortex-centered enrichment, a marker-based deep-layer projection-neuron component, and ontology enrichment for neuron projection and related synaptic terms. A smaller subset overlapped with human accelerated region-associated genes and showed greater-than-random spatial alignment with a human cortical-expansion map. The retained cortical-expression maps showed serotonergic spatial alignment in the human cortex, most prominently with HTR2A expression. Clustering identified three cortical spatial-expression modules, including an association/limbic-weighted module enriched for plasticity and synaptic-organization terms. Together, these findings provide a human cortical framework linking acute psychedelic-responsive transcription to cortical cell-type enrichment, HTR2A spatial expression, cortical spatial-expression modules, and cortical-expansion, while leaving receptor-specific, causal, translational, and cell-type-resolved mechanisms for future work.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pharmacogGENEtics in Youth Depression (GENE-YD) study for personalizing antidepressant pharmacotherapy for young Western Australians - A feasibility study.","authors":"Bradley Roberts, Zahra Cooper, Aleksandra Miljevic, Susanne Stanley, Bernadette T Majda, Khan R L Collins, Sarah Woodland, Michael J Kyron, Svetlana Baltic, Suzanna E L Temple, P Anthony Akkari, Sean D Hood, Jennifer Rodger","doi":"10.1038/s41398-026-04321-x","DOIUrl":"10.1038/s41398-026-04321-x","url":null,"abstract":"<p><p>Pharmacogenetic (PGx) testing to guide antidepressant prescribing is becoming increasingly available. However, its uptake into routine psychiatric practice for young people remains limited due to insufficient youth-specific evidence and uncertainty regarding optimal trial design and outcome selection. This pilot study aimed to evaluate the feasibility of implementing a rigorous triple-blind randomized controlled trial to examine PGx-guided antidepressant treatment compared with treatment-as-usual (TAU) in young Australians with depression. The pharmacoGENEtics in Youth Depression (GENE-YD) study recruited young people aged 16-24 years old with major depressive disorder over 13 months, allocating 1:1 to PGx-Guided treatment or TAU. Depressive symptoms and quality-of-life outcomes were measured using rater-administered measures and self-report questionnaires at Baseline and at 6- and 12-weeks follow-up. Feasibility outcomes included recruitment, adherence, attrition, participant satisfaction, and protocol fidelity. Of 73 individuals screened, 55 were eligible and randomized. Baseline data were collected from 39 participants, with 38 completing assessments through Week 12. Adherence to the study protocol and assessment schedule was high, attrition was low, and participant satisfaction was strong. Clinically meaningful improvements were observed, with the PGx-Guided group showing greater reductions in depressive symptom severity, higher rates of treatment response and remission, and improved quality-of-life outcomes compared with TAU. The GENE-YD Study demonstrated that a triple-blind PGx-guided antidepressant trial is feasible and acceptable in young people with depression, with preliminary indications of clinical benefit. These findings support the inclusion of broader patient-centered outcomes beyond symptom change and will inform methodological refinements for future fully powered youth-specific PGx trials.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224812","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":"Adolescent depression and gut microbiota dysbiosis: characteristics, mechanisms, and microbiota-targeted therapeutics.","authors":"Zhuorong Zi, Linwan Liu, Jian Zhou, Yuanbao Sun, Nianjie Wang, Bo Liu, Kezhi Liu, Youguo Tan","doi":"10.1038/s41398-026-04330-w","DOIUrl":"https://doi.org/10.1038/s41398-026-04330-w","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is one of the most prevalent mental disorders, yet its pathogenesis remains incompletely understood. Accumulating evidence indicates that MDD is closely associated with gut microbiota dysbiosis, with bidirectional communication along the microbiota-gut-brain axis playing a pivotal role in disease development. The gut microbiota and its metabolites exert dual influences on MDD, contributing to its pathophysiology while also offering promising therapeutic targets. In recent years, the prevalence of depression, especially in adolescents, has shown a sharp upward trend, increasing the risk of suicide in this population. However, few studies have systematically reviewed the link between gut dysbiosis and MDD in adolescents. This review summarizes current evidence on structural and functional alterations of the gut microbiota in adolescent MDD and explores the underlying mechanisms mediated by the microbiota-gut-brain axis. Furthermore, we also discuss the therapeutic potential of microbiota-targeted interventions, including dietary modification, probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation. Future research should aim to characterize specific microbial alterations in adolescent MDD and clarify the mechanisms underlying gut-brain interactions, thereby advancing the clinical translation of microbiota-targeted therapeutics for adolescent depression.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hippocampal subregion volume alterations at baseline and following antidepressant treatment in youth at high risk for bipolar disorder.","authors":"Biqiu Tang, L Rodrigo Patino, Thomas J Blom, Jeffrey A Welge, Jeffrey R Strawn, Kaitlyn M Bruns, Wenjing Zhang, Su Lui, Manpreet K Singh, Melissa P DelBello","doi":"10.1038/s41398-026-04314-w","DOIUrl":"https://doi.org/10.1038/s41398-026-04314-w","url":null,"abstract":"<p><p>Understanding hippocampal neurostructural alterations at baseline and following antidepressant treatment in high-risk youth, particularly within distinct subregions, is critical for elucidating bipolar disorder (BD) pathophysiology and treatment planning. In this prospective randomized clinical trial, 105 high-risk youth with a first-degree BD-I relative(s) and moderate to severe depression and/or anxiety disorder, along with 51 healthy controls (HCs), were recruited. All participants underwent baseline structural MRI and clinical evaluations for depression, anxiety, and adverse events. High-risk youth were then randomized to receive psychotherapy and with either escitalopram or placebo. After 4 weeks of treatment, high-risk youth underwent repeated structural MRI and clinical assessments. These clinical assessments continued biweekly over the remaining 12 weeks of treatment (up to week 16). Volumetric measurements of hippocampal subregions were analyzed at baseline and 4 weeks. Compared to HCs, high-risk youth had significant baseline volume increases in the right cornu ammonis (CA)3, bilateral CA4, bilateral granule cell and molecular layers of the dentate gyrus (GC-ML-DG), and bilateral molecular layer, but reduced volumes in the bilateral fimbria and left parasubiculum. Volume reduction in the left hippocampal tail after 4 weeks of escitalopram treatment was associated with improvements in disinhibition and impulsivity symptoms from baseline to 4 weeks, and this association remained significant from baseline to 16 weeks. CA3-4 and GC-ML-DG enlargement may reflect adaptive changes, while fimbria and parasubiculum atrophy indicate vulnerabilities in BD-risk youth. Escitalopram-related volume reduction in the left hippocampal tail may reflect neural plasticity associated with emotional symptom improvement in BD high-risk youth. CLINICAL TRIAL REGISTRATION INFORMATION: Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth; https://clinicaltrials.gov/ ; NCT02553161.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":7.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149300437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}