Psychological Medicine最新文献

{"title":"Spurious autobiographical memories of psychosis: a dopamine-gated neuroplasticity account for relapse and treatment-resistant psychosis.","authors":"Yu Hai Eric Chen, Stephanie M Y Wong, Melody M So, Yi Nam Suen, Christy L M Hui","doi":"10.1017/S0033291724003027","DOIUrl":"https://doi.org/10.1017/S0033291724003027","url":null,"abstract":"<p><p>Psychotic disorders are known to be associated with elevated dopamine synthesis; yet, nondopamine factors may underlie the manifestation of some psychotic symptoms that are nonresponsive to dopamine-blocking agents. One under-explored nondopamine mechanism is neuroplasticity. We propose an account of the course of psychotic symptoms based on the extensive evidence for dopamine facilitation of Hebbian synaptic plasticity in cortical and subcortical memory systems. The encoding of psychotic experiences in autobiographical memory (AM) is expected to be facilitated in the hyperdopaminergic state associated with acute psychosis. However, once such 'spurious AM of psychosis' (SAMP) is encoded, its persistence may become dependent more on synaptic factors than dopamine factors. Under this framework, the involuntary retrieval of residual SAMP is postulated to play a key role in mediating the reactivation of symptoms with similar contents, as often observed in patients during relapse. In contrast, with active new learning of normalizing experiences across diverse real-life contexts, supported by intact dopamine-mediated salience, well-integrated SAMP may undergo 'extinction', leading to remission. The key steps to the integration of SAMP across psychotic and nonpsychotic memories may correspond to one's 'recovery style', involving processes similar to the formation of 'non-believed memory' in nonclinical populations. The oversuppression of dopamine can compromise such processes. We synthesize this line of evidence into an updated dopamine-gated memory framework where neuroplasticity processes offer a parsimonious account for the recurrence, persistence, and progression of psychotic symptoms. This framework generates testable hypotheses relevant to clinical interventions.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e14"},"PeriodicalIF":5.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of integrated physical and psychological interventions on PTSD among forcibly displaced persons: a systematic review and meta-analysis.","authors":"Aditi Chaudhari, Apoorwa Chaudhari, Sandra O'Frans, Rohan Jayasuriya, Alvin Kuowei Tay","doi":"10.1017/S0033291725000698","DOIUrl":"https://doi.org/10.1017/S0033291725000698","url":null,"abstract":"<p><p>Forcibly displaced persons (FDPs) exposed to torture and trauma require multidisciplinary therapies to address their complex needs in mental and physical health. In this systematic review and meta-analysis, we explored the efficacy of models of care that integrated psychological and physical interventions for PTSD outcomes. We searched the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, EMBASE, CINAHL, PsychINFO, and Web of Science databases. We performed the meta-analysis on studies with randomized controlled trials and non-randomized controlled trial designs, followed by a subgroup analysis of moderators. In all meta-analyses, a random-effects model was used with standardized mean differences to accommodate for the heterogeneity of studies and outcome measures. In a meta-analysis of a between-group analysis of 11 studies comprising 610 participants, integrated intervention showed a moderate effect size (Hedges' <i>g</i> = -0.46 (95% CI -0.80 to -0.12) in reducing PTSD symptoms. The proportion of variation in observed effects reflects 82% of variation in true effects (<i>I</i>² = 82%). The efficacy of transdisciplinary interventions was higher compared to multidisciplinary models. Moderator analysis found that the type of PTSD measure, format of intervention, and type of personnel providing the intervention were significant predictors of efficacy. Integrated interventions are efficacious in reducing PTSD outcomes for people with FDPs and those exposed to war trauma. Factors such as the type of integration of interventions and service delivery need to be further studied with high-quality designs and larger numbers in future studies.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e109"},"PeriodicalIF":5.9,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143796096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects and costs of an anti-bullying program (KiVa) in UK primary schools: a multicenter cluster randomized controlled trial - CORRIGENDUM.","authors":"Lucy Bowes, Malavika Babu, Julia R Badger, Matthew R Broome, Rebecca Cannings-John, Suzy Clarkson, Elinor Coulman, Rhiannon Tudor Edwards, Tamsin Ford, Richard P Hastings, Rachel Hayes, Fiona Lugg-Widger, Eleri Owen-Jones, Paul Patterson, Jeremy Segrott, Mia Sydenham, Julia Townson, Richard C Watkins, Holly Whiteley, Margiad E Williams, Judy Hutchings","doi":"10.1017/S0033291725000248","DOIUrl":"https://doi.org/10.1017/S0033291725000248","url":null,"abstract":"","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e107"},"PeriodicalIF":5.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do psychotic symptoms predict future psychotic disorders in adolescent psychiatry inpatients? A 17-year cohort study.","authors":"Valentina Kieseppä, Ulla Lång, Colm Healy, Kirstie O'Hare, Covadonga M Díaz-Caneja, Sinan Gülöksüz, Bart P F Rutten, Mary Cannon, Anu-Helmi Halt, Pirkko Riipinen, Ian Kelleher","doi":"10.1017/S003329172500073X","DOIUrl":"10.1017/S003329172500073X","url":null,"abstract":"<p><strong>Background: </strong>Individuals with a psychiatric inpatient admission in adolescence have a high risk of schizophrenia-spectrum disorders (SSDs) when followed to adulthood. Whether psychotic symptoms predict subsequent SSDs in inpatient cohorts, however, is an important unanswered question.</p><p><strong>Methods: </strong>The sample consisted of adolescents (aged 13-17) admitted to psychiatric inpatient care (Oulu, Finland) from April 2001 to March 2006. Psychotic symptoms were assessed with the Schedule for Affective Disorders and Schizophrenia. Specialized health care use and diagnoses were followed up in national health care registers until June 2023. Cox regression was used to predict SSDs by the presence of baseline psychotic symptoms.</p><p><strong>Results: </strong>Of 404 adolescent inpatients admitted with non-psychotic mental disorders, 28% (<i>n</i> = 113) reported psychotic symptoms: 17% (<i>n</i> = 68) subthreshold and 11% (<i>n</i> = 45) full threshold. By the end of follow-up, 23% of the total cohort went on to be diagnosed with an SSD. Subthreshold psychotic symptoms did not differentiate patients who would subsequently develop SSDs (cumulative incidence 24%; HR = 1.42, 95%CI = 0.81-2.50). Full-threshold psychotic symptoms, on the other hand, were associated with an increased risk of subsequent SSDs (cumulative incidence 33%; HR = 2.00, 95%CI = 1.12-3.56). Most subsequent SSDs (83%), however, occurred in individuals who had not reported threshold psychotic symptoms during inpatient admission.</p><p><strong>Conclusions: </strong>There was a high risk of subsequent SSDs among adolescent psychiatry inpatients when followed over time. SSDs were not predicted by subthreshold psychotic symptoms. Full-threshold psychotic symptoms were associated with an increased risk of subsequent SSDs, though with low sensitivity.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e108"},"PeriodicalIF":5.9,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal relationships between social anhedonia and internalizing symptoms in autistic children: results from the Autism Biomarkers Consortium for Clinical Trials.","authors":"Alan H Gerber, Adam Naples, Katarzyna Chawarska, Geraldine Dawson, Natalia Kleinhans, Shafali Jeste, Susan Faja, James Dziura, Sara Webb, Catherine Sugar, Frederick Shic, April R Levin, James C McPartland","doi":"10.1017/S0033291725000650","DOIUrl":"https://doi.org/10.1017/S0033291725000650","url":null,"abstract":"<p><strong>Background: </strong>Social anhedonia, indicating reduced pleasure from social interaction, is heightened in autistic youth and associated with increased internalizing symptoms transdiagnostically. The stability of social anhedonia over time and its longitudinal impact on internalizing symptoms in autism have never been examined.</p><p><strong>Methods: </strong>Participants were 276 autistic children (<i>M</i>_age = 8.60, SD_age = 1.65; 211 male) with IQ ≥ 60 (<i>M</i>_IQ = 96.74, SD_IQ = 18.19). Autism severity was measured using the Autism Diagnostic Observation Schedule, Second Edition. Caregivers completed the Child and Adolescent Symptom Inventory, Fifth Edition (CASI-5) at baseline, 6 weeks, and 6 months. The CASI-5 includes a social anhedonia subscale derived from relevant items across domains. ICC (Intraclass Correlation Coefficient) analysis assessed stability, while cross-lagged panel models examined associations among social anhedonia, depression, and social anxiety across time.</p><p><strong>Results: </strong>At baseline, social anhedonia correlated with autism severity, as well as parent-reported social anxiety and depression. Social anhedonia showed relative stability (ICC = 0.763) over 6 months, with a significant decline between baseline and 6 weeks (<i>β</i> = -0.52, <i>p</i> < .001). Cross-lagged models revealed a bidirectional relationship between social anhedonia and depression over time, while social anxiety displayed concurrent, but not predictive, associations across time.</p><p><strong>Conclusions: </strong>Social anhedonia demonstrated stability over 6 months, suggesting that it may be a relatively stable characteristic in autistic children. Concurrent relationships were observed between social anhedonia and depression, as well as social anxiety and attention-deficit/hyperactivity disorder. Only depression demonstrated a bidirectional longitudinal association with social anhedonia. This bidirectional relationship aligns with developmental models linking early negative social experiences to subsequent internalizing symptoms in autistic children, underscoring the clinical significance of social anhedonia assessment in this population.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e104"},"PeriodicalIF":5.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capitalizing on natural language processing (NLP) to automate the evaluation of coach implementation fidelity in guided digital cognitive-behavioral therapy (GdCBT).","authors":"Nur Hani Zainal, Regina Eckhardt, Gavin N Rackoff, Ellen E Fitzsimmons-Craft, Elsa Rojas-Ashe, Craig Barr Taylor, Burkhardt Funk, Daniel Eisenberg, Denise E Wilfley, Michelle G Newman","doi":"10.1017/S0033291725000340","DOIUrl":"https://doi.org/10.1017/S0033291725000340","url":null,"abstract":"<p><strong>Background: </strong>As the use of guided digitally-delivered cognitive-behavioral therapy (GdCBT) grows, pragmatic analytic tools are needed to evaluate coaches' implementation fidelity.</p><p><strong>Aims: </strong>We evaluated how natural language processing (NLP) and machine learning (ML) methods might automate the monitoring of coaches' implementation fidelity to GdCBT delivered as part of a randomized controlled trial.</p><p><strong>Method: </strong>Coaches served as guides to 6-month GdCBT with 3,381 assigned users with or at risk for anxiety, depression, or eating disorders. CBT-trained and supervised human coders used a rubric to rate the implementation fidelity of 13,529 coach-to-user messages. NLP methods abstracted data from text-based coach-to-user messages, and 11 ML models predicting coach implementation fidelity were evaluated.</p><p><strong>Results: </strong>Inter-rater agreement by human coders was excellent (intra-class correlation coefficient = .980-.992). Coaches achieved behavioral targets at the start of the GdCBT and maintained strong fidelity throughout most subsequent messages. Coaches also avoided prohibited actions (e.g. reinforcing users' avoidance). Sentiment analyses generally indicated a higher frequency of coach-delivered positive than negative sentiment words and predicted coach implementation fidelity with acceptable performance metrics (e.g. area under the receiver operating characteristic curve [AUC] = 74.48%). The final best-performing ML algorithms that included a more comprehensive set of NLP features performed well (e.g. AUC = 76.06%).</p><p><strong>Conclusions: </strong>NLP and ML tools could help clinical supervisors automate monitoring of coaches' implementation fidelity to GdCBT. These tools could maximize allocation of scarce resources by reducing the personnel time needed to measure fidelity, potentially freeing up more time for high-quality clinical care.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e106"},"PeriodicalIF":5.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impulsive adolescents exhibit inefficient processing and a low decision threshold when decoding facial expressions of emotions.","authors":"Alison M Schreiber, Nathan T Hall, Daniel F Parr, Michael N Hallquist","doi":"10.1017/S0033291725000595","DOIUrl":"https://doi.org/10.1017/S0033291725000595","url":null,"abstract":"<p><strong>Background: </strong>Borderline personality disorder (BPD) is a debilitating psychiatric illness whose symptoms frequently emerge during adolescence. Critically, self-injury and suicide attempts in BPD are often precipitated by interpersonal discord. Initial studies in adults suggest that the interpersonal difficulties common in BPD may emerge from disrupted processing of socioemotional stimuli. Less is known about these processes in adolescents with BPD symptoms, despite substantial changes in socioemotional processing during this developmental period.</p><p><strong>Methods: </strong>Eighty-six adolescents and young adults with and without BPD symptoms completed an emotional interference task involving the identification of a facial emotion expression in the presence of a conflicting or congruent emotion word. We used hierarchical drift diffusion modeling to index speed of processing and decision boundary. Using Bayesian multilevel regression, we characterized age-related differences in facial emotion processing. We examined whether BPD symptom dimensions were associated with alterations in facial emotion processing. To determine the specificity of our effects, we analyzed behavioral data from a corresponding nonemotional interference task.</p><p><strong>Results: </strong>Emotion-related impulsivity, but not negative affectivity or interpersonal dysfunction, predicted inefficient processing when presented with conflicting negative emotional stimuli. Across both tasks, emotion-related impulsivity in adolescents, but not young adults, was further associated with a lower decision boundary - resulting in fast but inaccurate decisions.</p><p><strong>Conclusion: </strong>Impulsive adolescents with BPD symptoms are prone to making errors when appraising facial emotion expressions, which may potentiate or worsen interpersonal conflicts. Our findings highlight the role of lower-level social cognitive processes in interpersonal difficulties among vulnerable youth during a sensitive developmental window.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e105"},"PeriodicalIF":5.9,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using machine learning to identify features associated with different types of self-injurious behaviors in autistic youth.","authors":"Ligia Antezana, Caitlin M Conner, Safaa Eldeeb, Samuel Turecki, Matthew Siegel, Helmet T Karim, Carla A Mazefsky","doi":"10.1017/S0033291725000637","DOIUrl":"https://doi.org/10.1017/S0033291725000637","url":null,"abstract":"<p><strong>Background: </strong>Self-injurious behaviors (SIB) are common in autistic people. SIB is mainly studied as a broad category, rather than by specific SIB types. We aimed to determine associations of distinct SIB types with common psychiatric, emotional, medical, and socio-demographic factors.</p><p><strong>Methods: </strong>Participants included 323 autistic youth (~50% non-/minimally-speaking) with high-confidence autism diagnoses ages 4-21 years. Data were collected by the Autism Inpatient Collection during admission to a specialized psychiatric inpatient unit (www.sfari.org/resource/autism-inpatient-collection/). Caregivers completed questionnaires about their child, including SIB type and severity. The youth completed assessments with clinicians. Elastic net regressions identified associations between SIB types and factors.</p><p><strong>Results: </strong>No single factor relates to all SIB types. SIB types have unique sets of associations. Consistent with previous work, more repetitive motor movements and lower adaptive skills are associated with most types of SIB; female sex is associated with hair/skin pulling and self-rubbing/scratching. More attention-deficit/hyperactivity disorder symptoms are associated with self-rubbing/scratching, skin picking, hair/skin pulling, and inserts finger/object. Inserts finger/object has the most medical condition associations. Self-hitting against surface/object has the most emotion dysregulation associations.</p><p><strong>Conclusions: </strong>Specific SIB types have unique sets of associations. Future work can develop clinical likelihood scores for specific SIB types in inpatient settings, which can be tested with large community samples. Current approaches for SIB focus on the behavior functions, but there is an opportunity to further develop interventions by considering the specific SIB type in assessment and treatment. Identifying factors associated with specific SIB types may aid with screening, prevention, and treatment of these often-impairing behaviors.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e98"},"PeriodicalIF":5.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal associations of naturalistic psychedelic use with psychotic and manic symptoms.","authors":"Otto Simonsson, Simon B Goldberg, Walter Osika, Cecilia U D Stenfors, Sankalp Chaturvedi, Caroline M Swords, Jayanth Narayanan, Peter S Hendricks","doi":"10.1017/S0033291725000716","DOIUrl":"https://doi.org/10.1017/S0033291725000716","url":null,"abstract":"<p><strong>Background: </strong>Findings from contemporary clinical trials suggest that psychedelics are generally safe and may be effective in the treatment of various psychiatric disorders. However, less is known about the risks associated with psychedelic use outside of medically supervised contexts, particularly in populations that are typically excluded from participation in clinical trials.</p><p><strong>Methods: </strong>Using a preregistered longitudinal observational research design with a purposive sample of US residents between 18 and 50 years old (<i>N</i>=21,990), we investigated associations between self-reported naturalistic psychedelic use and psychotic and manic symptoms, with emphasis on those with psychiatric histories of schizophrenia or bipolar I disorder.</p><p><strong>Results: </strong>The follow-up survey was completed by 12,345 participants (56% retention), with 505 participants reporting psychedelic use during the 2-month study period. In covariate-adjusted regression models, psychedelic use during the study period was associated with increases in the severity of psychotic and manic symptoms. However, such increases were only observed for those who reported psychedelic use in an illegal context. While increases in the severity of psychotic symptoms appeared to depend on the frequency of use and the intensity of challenging psychedelic experiences, increases in the severity of manic symptoms appeared to be moderated by a personal history of schizophrenia or bipolar I disorder and the subjective experience of insight during a psychedelic experience.</p><p><strong>Conclusions: </strong>The findings suggest that naturalistic psychedelic use specifically in illegal contexts may lead to increases in the severity of psychotic and manic symptoms. Such increases may depend on the frequency of use, the acute subjective psychedelic experience, and psychiatric history.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e99"},"PeriodicalIF":5.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic overlap of substance use behaviors and disorders with externalizing and internalizing problems independent of genetic correlations.","authors":"Laila Al-Soufi, Guy Hindley, Linn Rødevand, Alexey A Shadrin, Piotr Jaholkowski, Vera Fominykh, Romain Icick, Markos Tesfaye, Javier Costas, Ole A Andreassen","doi":"10.1017/S0033291725000108","DOIUrl":"https://doi.org/10.1017/S0033291725000108","url":null,"abstract":"<p><strong>Background: </strong>Externalizing and internalizing pathways may lead to the development of substance use behaviors (SUBs) and substance use disorders (SUDs), which are all heritable phenotypes. Genetic correlation studies have indicated differences in the genetic susceptibility between SUBs and SUDs. We investigated whether these substance use phenotypes are differently related to externalizing and internalizing problems at a genetic level.</p><p><strong>Methods: </strong>We analyzed data from genome-wide association studies (GWAS) of four SUBs and SUDs, five externalizing traits, and five internalizing traits using the bivariate causal mixture model (MiXeR) to estimate genetic overlap beyond genetic correlation.</p><p><strong>Results: </strong>Two distinct patterns were found. SUBs demonstrated high genetic overlap but low genetic correlation of shared variants with internalizing traits, suggesting a pattern of mixed effect directions of shared genetic variants. Conversely, SUDs and externalizing traits exhibited considerable genetic overlap with moderate to high positive genetic correlation of shared variants, suggesting concordant effect direction of shared risk variants.</p><p><strong>Conclusions: </strong>These results highlight the importance of the externalizing pathway in SUDs as well as the limited role of the internalizing pathway in SUBs. As MiXeR is not intended for the identification of specific genes, further studies are needed to reveal the underlying shared mechanisms of these traits.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e100"},"PeriodicalIF":5.9,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}