Psychological Medicine最新文献

{"title":"Characterizing pleiotropy among bipolar disorder, schizophrenia, and major depression: a genome-wide cross-disorder meta-analysis.","authors":"Eleni Friligkou, Gita A Pathak, Daniel S Tylee, Antonella De Lillo, Dora Koller, Brenda Cabrera-Mendoza, Renato Polimanti","doi":"10.1017/S0033291725001217","DOIUrl":"10.1017/S0033291725001217","url":null,"abstract":"<p><strong>Background: </strong>To understand the pathogenetic mechanisms shared among schizophrenia (SCZ), bipolar disorder (BP), and major depression (MDD), we investigated the pleiotropic mechanisms using large-scale genome-wide and brain transcriptomic data.</p><p><strong>Methods: </strong>We analyzed SCZ, BP, and MDD genome-wide association datasets available from the Psychiatric Genomics Consortium using the PLEIO framework and characterized the pleiotropic loci identified using pathway and tissue enrichment analyses. Pleiotropic and disorder-specific loci were also assessed.</p><p><strong>Results: </strong>Our pleiotropy-informed genome-wide analysis identified 553 variants that included 192 loci not reaching genome-wide significance in input datasets. These were enriched for five molecular pathways: cadherin signaling (<i>p</i> = 2.18 × 10^-8), Alzheimer's disease-amyloid secretase (<i>p</i> = 4 × 10^-4), oxytocin receptor-mediated signaling (<i>p</i> = 1.47 × 10^-3), metabotropic glutamate receptor group III (<i>p</i> = 5.82 × 10^-4) and Wnt signaling (<i>p</i> = 1.61 × 10^-11). Pleiotropic loci demonstrated the strongest enrichment in the brain cortex (<i>p</i> = 5.8 × 10^-28), frontal cortex (<i>p</i> = 3 × 10^-31), and cerebellar hemisphere (<i>p</i> = 9.8 × 10^-28). SCZ-BP-MDD pleiotropic variants were also enriched for neurodevelopmental brain transcriptomic profiles related to the second-trimester post-conception (week 21, <i>p</i> = 7.35 × 10^-5; week 17, <i>p</i> = 6.36 × 10^-4) and first year of life (<i>p</i> = 3.25 × 10^-5).</p><p><strong>Conclusions: </strong>Genetic mechanisms shared among SCZ, BP, and MDD appear to be related to early neuronal development. Because the genetic architecture of psychopathology transcends diagnostic boundaries, pleiotropy-focused analyses can lead to increased gene discovery and novel insights into relevant pathogenic mechanisms.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e145"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022250","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":"Adverse childhood experiences, inflammation, and depression: evidence of sex- and stressor specific effects in a nationally representative longitudinal sample of U.S. adolescents.","authors":"Jay D O'Shields, George M Slavich, Orion Mowbray","doi":"10.1017/S0033291725001102","DOIUrl":"10.1017/S0033291725001102","url":null,"abstract":"<p><p>Although adverse childhood experiences (ACEs) are commonly associated with depressive symptoms in adulthood, studies frequently collapse ACEs into a single unitary index, making it difficult to identify specific targets for intervention and prevention. Furthermore, studies rarely explore sex differences in this area despite males and females often differing in the experiences of ACEs, depressive symptoms, and inflammatory activity. To address these issues, we used data from the National Longitudinal Study of Adolescent to Adult Health to model the effects of 10 different ACEs on C-reactive protein (CRP) and depressive symptoms in adulthood. Path modeling was used to measure the effects of ACEs on CRP and depressive symptoms conjointly while also assigning covariances among ACEs to assess their interrelations. Sex-by-ACE interaction terms and sex-disaggregated models were used to test for potential differences. Emotional abuse and parental incarceration were consistently related to both CRP and depressive symptoms for males and females. Childhood maltreatment was associated with depressive symptoms for females, whereas sexual abuse was associated with inflammation for males. Several covariances among ACEs were identified, indicating potential networks through which ACEs are indirectly associated with CRP and depressive symptoms. These data demonstrate that ACEs have differing direct effects on CRP and depressive symptoms - and that they differ with respect to how they cluster - for males versus females. These differences should be considered in theory and clinical workflows aiming to understand, treat, and prevent the long-term impacts of ACEs on depressive symptoms and inflammation-related health conditions in adulthood.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e140"},"PeriodicalIF":5.9,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050836","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":"Integrating HiTOP and RDoC frameworks part II: shared and distinct biological mechanisms of externalizing and internalizing psychopathology.","authors":"Christal N Davis, Yousef Khan, Sylvanus Toikumo, Zeal Jinwala, Dorret I Boomsma, Daniel F Levey, Joel Gelernter, Rachel L Kember, Henry R Kranzler","doi":"10.1017/S0033291725000819","DOIUrl":"10.1017/S0033291725000819","url":null,"abstract":"<p><strong>Background: </strong>The Hierarchical Taxonomy of Psychopathology (HiTOP) and Research Domain Criteria (RDoC) frameworks emphasize transdiagnostic and mechanistic aspects of psychopathology. We used a multi-omics approach to examine how HiTOP's psychopathology spectra (externalizing [EXT], internalizing [INT], and shared EXT + INT) map onto RDoC's units of analysis.</p><p><strong>Methods: </strong>We conducted analyses across five RDoC units of analysis: genes, molecules, cells, circuits, and physiology. Using genome-wide association studies from the companion Part I article, we identified genes and tissue-specific expression patterns. We used drug repurposing analyses that integrate gene annotations to identify potential therapeutic targets and single-cell RNA sequencing data to implicate brain cell types. We then used magnetic resonance imaging data to examine brain regions and circuits associated with psychopathology. Finally, we tested causal relationships between each spectrum and physical health conditions.</p><p><strong>Results: </strong>Using five gene identification methods, EXT was associated with 1,759 genes, INT with 454 genes, and EXT + INT with 1,138 genes. Drug repurposing analyses identified potential therapeutic targets, including those that affect dopamine and serotonin pathways. Expression of EXT genes was enriched in GABAergic, cortical, and hippocampal neurons, while INT genes were more narrowly linked to GABAergic neurons. EXT + INT liability was associated with reduced gray matter volume in the amygdala and subcallosal cortex. INT genetic liability showed stronger causal effects on physical health - including chronic pain and cardiovascular diseases - than EXT.</p><p><strong>Conclusions: </strong>Our findings revealed shared and distinct pathways underlying psychopathology. Integrating genomic insights with the RDoC and HiTOP frameworks advanced our understanding of mechanisms that underlie EXT and INT psychopathology.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e137"},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031017","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":"Smartphone-based text obtained via passive sensing as it relates to direct suicide risk assessment.","authors":"Brooke A Ammerman, Evan M Kleiman, Connor O'Brien, Anne C Knorr, Kerri-Anne Bell, Nilám Ram, Thomas N Robinson, Bryon Reeves, Ross Jacobucci","doi":"10.1017/S0033291725001199","DOIUrl":"10.1017/S0033291725001199","url":null,"abstract":"<p><strong>Background: </strong>Recent research highlights the dynamics of suicide risk, resulting in a shift toward real-time methodologies, such as ecological momentary assessment (EMA), to improve suicide risk identification. However, EMA's reliance on active self-reporting introduces challenges, including participant burden and reduced response rates during crises. This study explores the potential of Screenomics-a passive digital phenotyping method that captures intensive, real-time smartphone screenshots-to detect suicide risk through text-based analysis.</p><p><strong>Method: </strong>Seventy-nine participants with past-month suicidal ideation or behavior completed daily EMA prompts and provided smartphone data over 28 days, resulting in approximately 7.5 million screenshots. Text from screenshots was analyzed using a validated dictionary encompassing suicide-related and general risk language.</p><p><strong>Results: </strong>Results indicated significant associations between passive and active suicidal ideation and suicide planning with specific language patterns. Detection of words related to suicidal thoughts and general risk-related words strongly correlated with self-reported suicide risk, with distinct between- and within-person effects highlighting the dynamic nature of suicide risk factors.</p><p><strong>Conclusions: </strong>This study demonstrates the feasibility of leveraging smartphone text data for real-time suicide risk detection, offering a scalable, low-burden alternative to traditional methods. Findings suggest that dynamic, individualized monitoring via passive data collection could enhance suicide prevention efforts by enabling timely, tailored interventions. Future research should refine language models and explore diverse populations to extend the generalizability of this innovative approach.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e144"},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036367","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":"From genetics and cerebral asymmetry, through motor dysfunction intrinsic to psychosis, to early intervention: elaborating the seminal contributions of Timothy J. Crow.","authors":"John L Waddington","doi":"10.1017/S0033291725001254","DOIUrl":"10.1017/S0033291725001254","url":null,"abstract":"","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e143"},"PeriodicalIF":5.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977042","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":"Integrating HiTOP and RDoC frameworks Part I: Genetic architecture of externalizing and internalizing psychopathology.","authors":"Christal N Davis, Yousef Khan, Sylvanus Toikumo, Zeal Jinwala, Dorret I Boomsma, Daniel F Levey, Joel Gelernter, Rachel L Kember, Henry R Kranzler","doi":"10.1017/S0033291725000856","DOIUrl":"10.1017/S0033291725000856","url":null,"abstract":"<p><strong>Background: </strong>There is considerable comorbidity between externalizing (EXT) and internalizing (INT) psychopathology. Understanding the shared genetic underpinnings of these spectra is crucial for advancing knowledge of their biological bases and informing empirical models like the Research Domain Criteria (RDoC) and Hierarchical Taxonomy of Psychopathology (HiTOP).</p><p><strong>Methods: </strong>We applied genomic structural equation modeling to summary statistics from 16 EXT and INT traits in individuals genetically similar to European reference panels (EUR-like; n = 16,400 to 1,074,629). Traits included clinical (e.g. major depressive disorder, alcohol use disorder) and subclinical measures (e.g. risk tolerance, irritability). We tested five confirmatory factor models to identify the best fitting and most parsimonious genetic architecture and then conducted multivariate genome-wide association studies (GWAS) of the resulting latent factors.</p><p><strong>Results: </strong>A two-factor correlated model, representing EXT and INT spectra, provided the best fit to the data. There was a moderate genetic correlation between EXT and INT (r = 0.37, SE = 0.02), with bivariate causal mixture models showing extensive overlap in causal variants across the two spectra (94.64%, SE = 3.27). Multivariate GWAS identified 409 lead genetic variants for EXT, 85 for INT, and 256 for the shared traits.</p><p><strong>Conclusions: </strong>The shared genetic liabilities for EXT and INT identified here help to characterize the genetic architecture underlying these frequently comorbid forms of psychopathology. The findings provide a framework for future research aimed at understanding the shared and distinct biological mechanisms underlying psychopathology, which will help to refine psychiatric classification systems and potentially inform treatment approaches.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e138"},"PeriodicalIF":5.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977102","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":"A single dose of lamotrigine induces a positive memory bias in healthy volunteers.","authors":"Tarek Zghoul, Pilar Artiach Hortelano, Alexander Kaltenboeck, Lucy Wright, Guy M Goodwin, Liliana P Capitão, Catherine J Harmer","doi":"10.1017/S0033291725000777","DOIUrl":"10.1017/S0033291725000777","url":null,"abstract":"<p><strong>Background: </strong>Lamotrigine has been shown to be effective in the long-term treatment and relapse prevention of depression in bipolar disorder. However, the neuropsychological mechanisms underlying these effects are unclear. We investigated the effects of lamotrigine on a battery of emotional processing tasks in healthy volunteers, previously shown to be sensitive to antidepressant drug action in similar experimental designs.</p><p><strong>Methods: </strong>Healthy volunteers (n = 36) were randomized in a double-blind design to receive a single dose of placebo or 300 mg lamotrigine. Mood and subjective effects were monitored throughout the study period, and emotional processing was assessed using the Oxford Emotional Test Battery (ETB) 3 hours post-administration.</p><p><strong>Results: </strong>Participants receiving lamotrigine showed increased accurate recall of positive versus negative self-descriptors, compared to those in the placebo group. There were no other significant effects on emotional processing in the ETB, and lamotrigine did not affect ratings of mood or subjective experience.</p><p><strong>Conclusions: </strong>Lamotrigine did not induce widespread changes in emotional processing. However, there was increased positive bias in emotional memory, similar to the effects of antidepressants reported in previous studies. Further work is needed to assess whether similar effects are seen in the clinical treatment of patients with bipolar disorder and the extent to which this is associated with its clinical action in relapse prevention.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e139"},"PeriodicalIF":5.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021424","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":"Lifetime suicidal thoughts, attempts, and lethality of attempts as major outcome domains of psychotic disorders: a 21-year prospective cohort study after a first-episode psychosis - CORRIGENDUM.","authors":"Victor Peralta, Lucía Moreno-Izco, Elena García de Jalón, Ana M Sánchez-Torres, David Peralta, Lucía Janda, Manuel J Cuesta","doi":"10.1017/S0033291725001059","DOIUrl":"10.1017/S0033291725001059","url":null,"abstract":"","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e136"},"PeriodicalIF":5.9,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043260","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":"Polygenic risk for schizophrenia and subjective well-being in a general population sample.","authors":"Oona Serimaa, Liisa Keltikangas-Järvinen, Leo-Pekka Lyytikäinen, Jarmo Hietala, Elina Sormunen, Mika Kähönen, Olli Raitakari, Terho Lehtimäki, Aino Saarinen","doi":"10.1017/S0033291725000911","DOIUrl":"10.1017/S0033291725000911","url":null,"abstract":"<p><strong>Background: </strong>Previous evidence has reported associations of a polygenic risk score for schizophrenia (PRS_SCZ) with negative developmental outcomes, such as psychiatric symptoms, adverse health behaviors, and reduced everyday functioning. We now investigated the relationship of PRS_SCZ with subjectively experienced well-being.</p><p><strong>Methods: </strong>Participants (n = 1866) came from the prospective population-based Young Finns Study (YFS). Subjective well-being in adulthood was assessed in terms of life satisfaction, optimism, and self-acceptance (when participants were 20-50 years old). A PRS_SCZ was calculated based on the most recent genome-wide association study on schizophrenia. Covariates included age, sex, early family environment, adulthood socioeconomic factors, and adulthood health behaviors.</p><p><strong>Results: </strong>The PRS_SCZ did not predict any domain of subjective well-being, including life satisfaction, optimism, and self-acceptance. After adding covariates in a stepwise manner or including/excluding participants with diagnosed non-affective psychotic disorders, all the associations remained non-significant. Age- and sex-interaction analyses showed that PRS_SCZ was not associated with subjective well-being in either sex or in any age between 20 and 50 years.</p><p><strong>Conclusions: </strong>While high PRS_SCZ has been linked to multiple adversities in previous studies, we did not find any association between high PRS_SCZ and subjective measures of life satisfaction, optimism, and self-acceptance.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e133"},"PeriodicalIF":5.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026037","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":"Advancing the Personalized Advantage Index (PAI): a Systematic Review and Application in Two Large Multi-Site Samples in Anxiety Disorders - ERRATUM.","authors":"Charlotte Meinke, Silvan Hornstein, Johanna Schmidt, Volker Arolt, Udo Dannlowski, Jürgen Deckert, Katharina Domschke, Lydia Fehm, Thomas Fydrich, Alexander L Gerlach, Alfons O Hamm, Ingmar Heinig, Jürgen Hoyer, Tilo Kircher, Katja Koelkebeck, Thomas Lang, Jürgen Margraf, Peter Neudeck, Paul Pauli, Jan Richter, Winfried Rief, Silvia Schneider, Benjamin Straube, Andreas Ströhle, Hans-Ulrich Wittchen, Peter Zwanzger, Henrik Walter, Ulrike Lueken, Andre Pittig, Kevin Hilbert","doi":"10.1017/S0033291725000431","DOIUrl":"10.1017/S0033291725000431","url":null,"abstract":"","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e135"},"PeriodicalIF":5.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042455","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}