Psychological Medicine最新文献

{"title":"The proportion of people with a first episode of psychosis admitted to hospital at initial presentation: a systematic review and meta-analysis.","authors":"Louisa Gannon, Victoria Teague, Sheri Oduola, Fiona McNicholas, Mary Clarke, Stephen McWilliams, Brian O'Donoghue","doi":"10.1017/S0033291725101256","DOIUrl":"10.1017/S0033291725101256","url":null,"abstract":"<p><strong>Background: </strong>In psychiatry, there is a drive to reduce institutionalization, the risk of which starts with the index admission. In first-episode psychosis (FEP), the proportion of people admitted to hospital at initial presentation is still unknown.</p><p><strong>Methods: </strong>This systematic review aimed to determine the proportion of people with FEP who are admitted at initial presentation (within 30 days from point of first contact with psychiatry) and the influence of individual, clinical, and service factors on admission risk. Four databases were searched from inception until June 2023: PubMed, Embase, PsycINFO, and CINAHL. The pooled proportion of people admitted was calculated using a random-effects model. Analyses were further stratified according to individual, clinical, and service factors.</p><p><strong>Results: </strong>Of 7,455 abstracts screened, 18 studies with 19,854 participants were included. The proportion of people admitted overall was 51% (<i>k</i> = 18, 95% confidence interval [CI]: 37-65%; <i>I</i>²: 99.56%). The proportion admitted involuntarily was 31% (<i>k</i> = 6, 95% CI: 23-40%; <i>I</i>²: 95.26%). Sub-analyses for sex, diagnosis, and early intervention service access did not show significant differences between groups. The proportion of people with a short duration of untreated psychosis (DUP) admitted was 59% (<i>k</i> = 2, 95% CI: 56-63%) vs. 37% (<i>k</i> = 2, 95% CI: 33-41%) for long DUP, which was significant (<i>p</i> < 0.001). High inter-study heterogeneity was observed.</p><p><strong>Conclusions: </strong>Results demonstrate that over half of the people are hospitalized when initially presenting for FEP, a high proportion, with consequences for individuals and health services at large. First, service contact must be prioritized as an opportunity for appropriate intervention, to either avoid unwarranted hospitalizations or if hospitalization is required, to ensure the application of focused therapeutic objectives within intended timeframes.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e228"},"PeriodicalIF":5.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective associations between major depressive disorder, generalized anxiety disorder, fibromyalgia, and myalgic encephalomyelitis/chronic fatigue syndrome.","authors":"Nathaniel Stembridge Thomas, Michael C Neale, Kenneth S Kendler, Hanna M van Loo, Nathan A Gillespie","doi":"10.1017/S0033291725100603","DOIUrl":"10.1017/S0033291725100603","url":null,"abstract":"<p><strong>Background: </strong>Functional disorders (FDs) are associated with internalizing disorders (IDs). Studies investigating the nature of these associations over time are limited. We tested the direction of causation between measures of IDs (major depressive disorder [MDD], generalized anxiety disorder [GAD]) and FDs (fibromyalgia [FM] and myalgic encephalomyelitis/chronic fatigue syndrome [ME/CFS]) measured across two waves of longitudinal data (<i>N</i> = 108,034 and <i>N</i> = 73,590).</p><p><strong>Methods: </strong>The Lifelines Cohort Study is a large prospective population-based cohort study in the northeast of the Netherlands. We tested competing causal models for the longitudinal association between IDs and FDs and, to follow-up results from the model with all IDs and FDs, tested the direction of causation between MDD and FM.</p><p><strong>Results: </strong>FDs were more stable over time than IDs. Initial model comparisons support a bidirectional relationship between most IDs and FDs. Follow-up analyses support a unidirectional model where FM predicts MDD over time (<i>β</i> = 0.14, 95% confidence interval = [0.11, 0.18]), but not vice versa.</p><p><strong>Conclusions: </strong>The cross-time associations between ME/CFS, MDD, and GAD appear bidirectional (causal in both directions). Our results are consistent with, but not demonstrative of, a causal relationship from FM to MDD. The consequences of specific FDs vary, underscoring the value of studying these conditions as distinct constructs.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e232"},"PeriodicalIF":5.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12370297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of childhood trauma and cannabis use on paranoia: a structural equation model approach.","authors":"Giulia Trotta, Edoardo Spinazzola, Hannah Degen, Zhikun Li, Isabelle Austin-Zimmerman, Bok Man Leung, Yifei Lang, Victoria Rodriguez, Monica Aas, Lucia Sideli, Kim Wolff, Tom P Freeman, Robin M Murray, Chloe C Y Wong, Luis Alameda, Marta Di Forti","doi":"10.1017/S0033291725101190","DOIUrl":"10.1017/S0033291725101190","url":null,"abstract":"<p><strong>Background: </strong>Childhood trauma is a well-established risk factor for psychosis, paranoia, and substance use, with cannabis being a modifiable environmental factor that exacerbates these vulnerabilities. This study examines the interplay between childhood trauma, cannabis use, and paranoia using standard tetrahydrocannabinol (THC) units as a comprehensive measure of cannabis exposure.</p><p><strong>Methods: </strong>Data were derived from the Cannabis&Me study, an observational, cross-sectional, online survey of 4,736 participants. Childhood trauma was assessed using a modified Childhood Trauma Screen Questionnaire, while paranoia was measured via the Green Paranoid Thoughts Scale. Cannabis use was quantified using weekly standard THC units. Structural equation modeling (SEM) was employed to evaluate direct and indirect pathways between trauma, cannabis use, and paranoia.</p><p><strong>Results: </strong>Childhood trauma was strongly associated with paranoia, particularly emotional, and physical abuse (<i>β</i> = 16.10, <i>q</i> < 0.001; <i>β</i> = 16.40, <i>q</i> < 0.001). Cannabis use significantly predicted paranoia (<i>β</i> = 0.009, <i>q</i> < 0.001). Interactions emerged between standard THC units and both emotional abuse (<i>β</i> = 0.011, <i>q</i> < 0.001) and household discord (<i>β</i> = 0.011, <i>q</i> < 0.001). SEM revealed a small but significant indirect effect of trauma on paranoia via cannabis use (<i>β</i> = 0.004, <i>p</i> = 0.017).</p><p><strong>Conclusions: </strong>These findings highlight childhood trauma as a primary driver of paranoia, with cannabis use amplifying its effects. While trauma had a strong direct impact, cannabis played a significant mediating role. Integrating standard THC units into psychiatric research and clinical assessments may enhance risk detection and refine intervention strategies, particularly for childhood trauma-exposed individuals.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e220"},"PeriodicalIF":5.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep brain stimulation modulates directional limbic connectivity in major depressive disorder.","authors":"Egill A Fridgeirsson, Isidoor Bergfeld, Bart P de Kwaasteniet, Judy Luigjes, Jan van Laarhoven, Peter Notten, Guus Beute, Pepijn van den Munckhof, Rick Schuurman, Damiaan Denys, Guido van Wingen","doi":"10.1017/S0033291725100767","DOIUrl":"10.1017/S0033291725100767","url":null,"abstract":"<p><strong>Background: </strong>Deep brain stimulation (DBS) is being investigated as a treatment for patients with refractory major depressive disorder (MDD). However, little is known about how DBS exerts its antidepressive effects. Here, we investigated whether ventral anterior limb of the internal capsule stimulation modulates a limbic network centered around the amygdala in patients with treatment-resistant MDD.</p><p><strong>Methods: </strong>Nine patients underwent resting state functional magnetic resonance scans before DBS surgery and after 1 year of treatment. In addition, they were scanned twice within 2 weeks during the subsequent double-blind cross-over phase with active and sham treatment. Twelve matched controls underwent scans at the same time intervals to account for test-retest effects. The imaging data were investigated with functional connectivity (FC) analysis and dynamic causal modelling.</p><p><strong>Results: </strong>Results showed that 1 year of DBS treatment was associated with increased FC of the left amygdala with precentral cortex and left insula, along with decreased bilateral connectivity between nucleus accumbens and ventromedial prefrontal cortex. No changes in FC were observed during the cross-over phase. Effective connectivity analyses using dynamic causal models revealed widespread amygdala-centric changes between presurgery and 1 year follow-up, while the cross-over phase was associated with insula-centric changes between active and sham stimulation.</p><p><strong>Conclusions: </strong>These results suggest that ventral anterior limb of the internal capsule DBS results in complex rebalancing of the limbic network involved in emotion, reward, and interoceptive processing.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e231"},"PeriodicalIF":5.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diazepam modulates hippocampal CA1 functional connectivity in people at clinical high-risk for psychosis.","authors":"Nicholas R Livingston, Amanda Kiemes, Owen O'Daly, Samuel R Knight, Paulina B Lukow, Luke A Jelen, Thomas J Reilly, Aikaterini Dima, Maria A Nettis, Cecilia Casetta, Gabriel A Devenyi, Thomas Spencer, Andrea De Micheli, Paolo Fusar-Poli, Anthony A Grace, Steve C R Williams, Philip McGuire, M Mallar Chakravarty, Alice Egerton, Gemma Modinos","doi":"10.1017/S0033291725101268","DOIUrl":"10.1017/S0033291725101268","url":null,"abstract":"<p><strong>Background: </strong>Preclinical evidence suggests that diazepam enhances hippocampal γ-aminobutyric acid (GABA) signalling and normalises a psychosis-relevant cortico-limbic-striatal circuit. Hippocampal network dysconnectivity, particularly from the CA1 subfield, is evident in people at clinical high-risk for psychosis (CHR-P), representing a potential treatment target. This study aimed to forward-translate this preclinical evidence.</p><p><strong>Methods: </strong>In this randomised, double-blind, placebo-controlled study, 18 CHR-P individuals underwent resting-state functional magnetic resonance imaging twice, once following a 5 mg dose of diazepam and once following a placebo. They were compared to 20 healthy controls (HC) who did not receive diazepam/placebo. Functional connectivity (FC) between the hippocampal CA1 subfield and the nucleus accumbens (NAc), amygdala, and ventromedial prefrontal cortex (vmPFC) was calculated. Mixed-effects models investigated the effect of group (CHR-P placebo/diazepam vs. HC) and condition (CHR-P diazepam vs. placebo) on CA1-to-region FC.</p><p><strong>Results: </strong>In the placebo condition, CHR-P individuals showed significantly lower CA1-vmPFC (<i>Z</i> = 3.17, <i>P</i>_FWE = 0.002) and CA1-NAc (<i>Z</i> = 2.94, <i>P</i>_FWE = 0.005) FC compared to HC. In the diazepam condition, CA1-vmPFC FC was significantly increased (<i>Z</i> = 4.13, <i>P</i>_FWE = 0.008) compared to placebo in CHR-P individuals, and both CA1-vmPFC and CA1-NAc FC were normalised to HC levels. In contrast, compared to HC, CA1-amygdala FC was significantly lower contralaterally and higher ipsilaterally in CHR-P individuals in both the placebo and diazepam conditions (lower: placebo <i>Z</i> = 3.46, <i>P</i>_FWE = 0.002, diazepam <i>Z</i> = 3.33, <i>P</i>_FWE = 0.003; higher: placebo <i>Z</i> = 4.48, <i>P</i>_FWE < 0.001, diazepam <i>Z</i> = 4.22, <i>P</i>_FWE < 0.001).</p><p><strong>Conclusions: </strong>This study demonstrates that diazepam can partially restore hippocampal CA1 dysconnectivity in CHR-P individuals, suggesting that modulation of GABAergic function might be useful in the treatment of this clinical group.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e230"},"PeriodicalIF":5.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofunctional representations of instrumental learning in psychosis: a meta-analysis of neuroimaging studies.","authors":"Yuan Song, Jianguang Zeng, Hengyi Cao, Bochao Cheng, Xun Yang","doi":"10.1017/S0033291725101323","DOIUrl":"10.1017/S0033291725101323","url":null,"abstract":"<p><strong>Background: </strong>Establishing appropriate action-outcome associations can allow animals and humans to control behavior and the environment in a goal-directed manner. Deficits in instrumental learning in psychosis have been widely reported in past studies, but the results remain elusive.</p><p><strong>Study design: </strong>To explore the consistent neural representations of instrumental learning in functional magnetic resonance imaging (fMRI) in individuals with psychosis, a total of 18 studies (458 individuals with psychosis and 454 controls) were included in our coordinate-based meta-analysis.</p><p><strong>Study results: </strong>Patients with psychosis presented increased activation in the left middle occipital gyrus, insula, and lingual and postcentral gyri; decreased activation in cortico-striato-thalamo-cortical (CSTC) networks, including the dorsal striatum, insula, thalamus, middle cingulate cortex, posterior cingulate cortex, dorsolateral, orbital, and medial prefrontal cortices (DLPFC, OFC, and mPFC), cerebellum, and associated sensory areas, during instrumental learning. Moreover, mPFC hypoactivation was negatively associated with the percentage of first-generation antipsychotic users, and insula hyperactivation was negatively associated with the percentage of medicated individuals.</p><p><strong>Conclusions: </strong>Our study revealed that the CSTC circuit could facilitate action-based reward learning in psychosis and may help explain the neuropathological mechanisms underlying these deficits in this disorder.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e229"},"PeriodicalIF":5.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of internet-delivered exposure therapy versus healthy lifestyle promotion for patients with persistent physical symptoms (SOMEX1): a randomized controlled trial with planned moderator analysis.","authors":"Jonna Hybelius, Sandra Af Winklerfelt Hammarberg, Sigrid Salomonsson, Caroline Wachtler, Majken Epstein, Anna Olsson, Emma Strand, Lina Söderström Winter, Tomas Åkerlund, Daniel Björkander, Amanda Kosic, Gabriel Chahin, John Wallert, Eva Toth-Pal, Steven Nordin, Erland Axelsson","doi":"10.1017/S0033291725101244","DOIUrl":"10.1017/S0033291725101244","url":null,"abstract":"<p><strong>Background: </strong>The management of persistent physical symptoms poses a challenge in many healthcare settings, including primary care. Psychological treatments that involve exposure have shown promise for several conditions where patients suffer from persistent physical symptoms and unwanted responses to these. It is unclear, however, to what extent exposure therapy has effects beyond existing routine care interventions and who benefits the most.</p><p><strong>Methods: </strong>A randomized controlled trial at a primary care center in Stockholm, Sweden compared 10 weeks of internet-delivered exposure therapy (<i>n</i> = 80) to healthy lifestyle promotion (HLP; <i>n</i> = 81) for patients bothered by at least one persistent physical symptom. The primary outcome was the mean reduction in subjective somatic symptom burden (Patient Health Questionnaire 15) as measured week-by-week up to the post-treatment assessment. Secondary outcomes included symptom preoccupation, anxiety, depression symptoms, and functional impairment.</p><p><strong>Results: </strong>Patients contributed 1544 datapoints during treatment. The primary analysis showed no significant advantage of exposure therapy versus HLP in the reduction of mean somatic symptom burden (<i>d</i> = 0.14; <i>p</i> = 0.220). In secondary analyses, exposure showed superiority in the reduction of symptom preoccupation (<i>d</i> = 0.31; <i>p</i> = 0.033) but not anxiety, depression symptoms, or functional impairment. A higher somatic symptom burden or symptom preoccupation before treatment was predictive of a larger advantage of exposure versus HLP.</p><p><strong>Conclusions: </strong>Exposure therapy does not appear to show noteworthy average benefit over HLP, with the exception of symptom preoccupation. Substantial benefits are seen in patients with very high symptom burden or symptom preoccupation.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e226"},"PeriodicalIF":5.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the phenotypic expression of ADHD symptoms in middle- and older-aged adults: insights from confirmatory factor analysis of the US Health and Retirement Study.","authors":"Stephen Z Levine, Anat Rotstein, Abraham Reichenberg, Robert B Wallace","doi":"10.1017/S0033291725101347","DOIUrl":"10.1017/S0033291725101347","url":null,"abstract":"<p><strong>Background: </strong>Few studies have examined attention-deficit/hyperactivity disorder (ADHD) symptoms in middle- and older-aged adults. We aim to examine the phenotypic expression of ADHD symptoms in these age groups.</p><p><strong>Methods: </strong>This study comprised a random sample (<i>N</i> = 1,562) from the US Health and Retirement Study 2016, a representative US sample aged 50 years and over. ADHD symptoms were assessed based on the Adult ADHD Self-Report Scale.</p><p><strong>Results: </strong>In the primary analysis, 10 competing confirmatory factor analytic models of ADHD symptoms in middle- and older-aged adults were compared. The best-fitting model was hierarchical with a general ADHD factor at the apex and underneath symptom factors of inattention, hyperactivity, and impulsivity (<i>ꭓ</i>² = 319.34, df = 91.71, <i>P</i> = 0.00, TLI = 0.98, CFI = 0.96, RMSEA = 0.04, 95% CI = 0.04-0.05). In complementary analyses, this model was a satisfactory fit to the data: (1) in individuals without a history of cognitive impairment or dementia, and when the general ADHD factor was specified to load on (2) cognitive function, (3) depressive symptoms (which showed adequate fit), and (4) ADHD polygenic scores, (5) in middle- and older-aged adults, and (6) when weighted to represent the US population.</p><p><strong>Conclusions: </strong>These results imply a hierarchical representation of ADHD symptoms in middle- and older-aged adults consisting of a general factor at the apex with neurocognitive and genetic correlates and underneath symptom factors of inattention, hyperactivity, and impulsivity. Collectively, this model offers a novel framework to study the mechanisms of ADHD symptoms in middle- and older-aged adults and points to treatment targets.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e225"},"PeriodicalIF":5.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic overlap between functional impairment and depression and anxiety symptom severity: evidence from the GLAD Study.","authors":"Megan Skelton, Jessica Mundy, Abigail R Ter Kuile, Brett N Adey, Chérie Armour, Joshua E J Buckman, Jonathan R I Coleman, Molly R Davies, Colette R Hirsch, Matthew Hotopf, Ian R Jones, Gursharan Kalsi, Georgina Krebs, Sang Hyuck Lee, Yuhao Lin, Andrew M McIntosh, Alicia J Peel, Christopher Rayner, Katharine A Rimes, Daniel J Smith, Katherine N Thompson, David Veale, James T R Walters, Christopher Hübel, Gerome Breen, Thalia C Eley","doi":"10.1017/S0033291725101037","DOIUrl":"10.1017/S0033291725101037","url":null,"abstract":"<p><strong>Background: </strong>Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.</p><p><strong>Methods: </strong>In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.</p><p><strong>Results: </strong>The phenotypic correlations were moderate across the three measures (Pearson's <i>r</i> = 0.50-0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [<i>h</i>²_SNP] = 0.11-0.19) with high genetic correlations between them (<i>r_g</i> = 0.79-0.87).</p><p><strong>Conclusions: </strong>Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e224"},"PeriodicalIF":5.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroceutical enhancement of self-compassion training using transcutaneous vagus nerve stimulation: results from a preregistered fully factorial randomized controlled trial.","authors":"Sunjeev K Kamboj, Matthew Peniket, Jessica Norman, Rosalind Robshaw, Amit Soni-Tricker, Caroline Falconer, Paul Gilbert, Louise Simeonov","doi":"10.1017/S0033291725101013","DOIUrl":"10.1017/S0033291725101013","url":null,"abstract":"<p><strong>Background: </strong>Physiological signals conveyed by the vagus nerve may generate quiescent psychological states conducive to contemplative practices. This suggests that vagal neurostimulation could interact with contemplative psychotherapies (e.g. mindfulness and compassion-based interventions) to augment their efficacy.</p><p><strong>Methods: </strong>In a fully factorial experimental trial, healthy adults (<i>n</i> = 120) were randomized to transcutaneous vagus nerve stimulation (tVNS) <i>plus</i> Self-Compassion-Mental-Imagery Training (SC-MIT) <i>or</i> alternative factorial combinations of <i>stimulation</i> (tVNS or sham) plus <i>mental imagery training</i> (MIT: SC-MIT or Control-MIT). Primary outcomes were self-reported state self-compassion, self-criticism, and heart rate variability (HRV). Exploratory outcomes included state mindfulness and oculomotor attentional bias to compassion-expressing faces. Most outcomes were assessed acutely on session 1 at the pre-stimulation (T1), peri-stimulation (T2), and post-MIT + stimulation (T3) timepoints, and after daily stimulation+MIT sessions (eight sessions).</p><p><strong>Results: </strong>During session 1, a significant Timepoint × Stimulation × MIT interaction (<i>p</i> = 0.025) was observed, reflecting a larger acute T1→T3 increase in state self-compassion after tVNS+SC-MIT, with similar rapid effects on state mindfulness. Additionally, significant Session × MIT and Session × Stimulation interactions (<i>p</i> ≤ 0.027) on state mindfulness (but not self-compassion) suggested that tVNS+SC-MIT's effects may accumulate across sessions for some outcomes. By contrast, changes in state self-criticism and compassion-related attentional bias were only moderated by MIT (not stimulation) condition. HRV was unaffected by stimulation or MIT condition.</p><p><strong>Conclusion: </strong>tVNS augmented the effects of SC-MIT and might, therefore, be a useful strategy for enhancing meditation-based psychotherapies. Our findings also highlight the value of oculomotor attentional metrics as responsive markers of self-compassion training and the continued need for sensitive indices of successful vagal stimulation.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e223"},"PeriodicalIF":5.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}