Browsing by Author "Williams, Leanne M"

Filter results by typing the first few letters
Now showing 1 - 3 of 3
  • Thumbnail Image
    ItemOpen Access
    Gender-specific structural abnormalities in major depressive disorder revealed by fixel-based analysis.
    (NeuroImage. Clinical, 2019-01-08) Lyon, Matt; Welton, Thomas; Varda, Adrina; Maller, Jerome J; Broadhouse, Kathryn; Korgaonkar, Mayuresh S; Koslow, Stephen H; Williams, Leanne M; Gordon, Evian; Rush, A John; Grieve, Stuart M

    Background

    Major depressive disorder (MDD) is a chronic disease with a large global impact. There are currently no clinically useful predictors of treatment outcome, and the development of biomarkers to inform clinical treatment decisions is highly desirable.

    Methods

    In this exploratory study we performed fixel-based analysis of diffusion MRI data from the International Study to Predict Optimized Treatment in Depression with the aim of identifying novel biomarkers at baseline that may relate to diagnosis and outcome to treatment with antidepressant medications. Analyses used MR data from individuals with MDD (n = 221) and healthy controls (n = 67).

    Results

    We show focal, gender-specific differences in the anterior limb of the internal capsule (males) and bilaterally in the genu of the corpus callosum (females) associated with diagnosis. Lower fibre cross-section in the tapetum, the conduit between the right and left hippocampi, were also associated with a decreased probability of remission. Analysis of conventional fractional anisotropy showed scattered abnormalities in the corona radiata, cerebral peduncles and mid-brain which were much lower in total volume compared to fixel-based analysis.

    Conclusions

    Fixel-based analysis appeared to identify different underlying abnormalities than conventional tensor-based metrics, with almost no overlap between significant regions. We show that MDD is associated with gender specific abnormalities in the genu of the corpus callosum (females) and in the anterior limb of the internal capsule (males), as well as gender-independent differences in the tapetum that predict remission. Diffusion MRI may play a key role in future guidance of clinical decision-making for MDD.
  • Thumbnail Image
    ItemOpen Access
    GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
    (The American journal of psychiatry, 2023-10) Docherty, Anna R; Mullins, Niamh; Ashley-Koch, Allison E; Qin, Xuejun; Coleman, Jonathan RI; Shabalin, Andrey; Kang, JooEun; Murnyak, Balasz; Wendt, Frank; Adams, Mark; Campos, Adrian I; DiBlasi, Emily; Fullerton, Janice M; Kranzler, Henry R; Bakian, Amanda V; Monson, Eric T; Rentería, Miguel E; Walss-Bass, Consuelo; Andreassen, Ole A; Behera, Chittaranjan; Bulik, Cynthia M; Edenberg, Howard J; Kessler, Ronald C; Mann, J John; Nurnberger, John I; Pistis, Giorgio; Streit, Fabian; Ursano, Robert J; Polimanti, Renato; Dennis, Michelle; Garrett, Melanie; Hair, Lauren; Harvey, Philip; Hauser, Elizabeth R; Hauser, Michael A; Huffman, Jennifer; Jacobson, Daniel; Madduri, Ravi; McMahon, Benjamin; Oslin, David W; Trafton, Jodie; Awasthi, Swapnil; Berrettini, Wade H; Bohus, Martin; Chang, Xiao; Chen, Hsi-Chung; Chen, Wei J; Christensen, Erik D; Crow, Scott; Duriez, Philibert; Edwards, Alexis C; Fernández-Aranda, Fernando; Galfalvy, Hanga; Gandal, Michael; Gorwood, Philip; Guo, Yiran; Hafferty, Jonathan D; Hakonarson, Hakon; Halmi, Katherine A; Hishimoto, Akitoyo; Jain, Sonia; Jamain, Stéphane; Jiménez-Murcia, Susana; Johnson, Craig; Kaplan, Allan S; Kaye, Walter H; Keel, Pamela K; Kennedy, James L; Kim, Minsoo; Klump, Kelly L; Levey, Daniel F; Li, Dong; Liao, Shih-Cheng; Lieb, Klaus; Lilenfeld, Lisa; Marshall, Christian R; Mitchell, James E; Okazaki, Satoshi; Otsuka, Ikuo; Pinto, Dalila; Powers, Abigail; Ramoz, Nicolas; Ripke, Stephan; Roepke, Stefan; Rozanov, Vsevolod; Scherer, Stephen W; Schmahl, Christian; Sokolowski, Marcus; Starnawska, Anna; Strober, Michael; Su, Mei-Hsin; Thornton, Laura M; Treasure, Janet; Ware, Erin B; Watson, Hunna J; Witt, Stephanie H; Woodside, D Blake; Yilmaz, Zeynep; Zillich, Lea; Adolfsson, Rolf; Agartz, Ingrid; Alda, Martin; Alfredsson, Lars; Appadurai, Vivek; Artigas, María Soler; Van der Auwera, Sandra; Azevedo, M Helena; Bass, Nicholas; Bau, Claiton HD; Baune, Bernhard T; Bellivier, Frank; Berger, Klaus; Biernacka, Joanna M; Bigdeli, Tim B; Binder, Elisabeth B; Boehnke, Michael; Boks, Marco P; Braff, David L; Bryant, Richard; Budde, Monika; Byrne, Enda M; Cahn, Wiepke; Castelao, Enrique; Cervilla, Jorge A; Chaumette, Boris; Corvin, Aiden; Craddock, Nicholas; Djurovic, Srdjan; Foo, Jerome C; Forstner, Andreas J; Frye, Mark; Gatt, Justine M; Giegling, Ina; Grabe, Hans J; Green, Melissa J; Grevet, Eugenio H; Grigoroiu-Serbanescu, Maria; Gutierrez, Blanca; Guzman-Parra, Jose; Hamshere, Marian L; Hartmann, Annette M; Hauser, Joanna; Heilmann-Heimbach, Stefanie; Hoffmann, Per; Ising, Marcus; Jones, Ian; Jones, Lisa A; Jonsson, Lina; Kahn, René S; Kelsoe, John R; Kendler, Kenneth S; Kloiber, Stefan; Koenen, Karestan C; Kogevinas, Manolis; Krebs, Marie-Odile; Landén, Mikael; Leboyer, Marion; Lee, Phil H; Levinson, Douglas F; Liao, Calwing; Lissowska, Jolanta; Mayoral, Fermin; McElroy, Susan L; McGrath, Patrick; McGuffin, Peter; McQuillin, Andrew; Mehta, Divya; Melle, Ingrid; Mitchell, Philip B; Molina, Esther; Morken, Gunnar; Nievergelt, Caroline; Nöthen, Markus M; O'Donovan, Michael C; Ophoff, Roel A; Owen, Michael J; Pato, Carlos; Pato, Michele T; Penninx, Brenda WJH; Potash, James B; Power, Robert A; Preisig, Martin; Quested, Digby; Ramos-Quiroga, Josep Antoni; Reif, Andreas; Ribasés, Marta; Richarte, Vanesa; Rietschel, Marcella; Rivera, Margarita; Roberts, Andrea; Roberts, Gloria; Rouleau, Guy A; Rovaris, Diego L; Sanders, Alan R; Schofield, Peter R; Schulze, Thomas G; Scott, Laura J; Serretti, Alessandro; Shi, Jianxin; Sirignano, Lea; Sklar, Pamela; Smeland, Olav B; Smoller, Jordan W; Sonuga-Barke, Edmund JS; Trzaskowski, Maciej; Tsuang, Ming T; Turecki, Gustavo; Vilar-Ribó, Laura; Vincent, John B; Völzke, Henry; Walters, James TR; Weickert, Cynthia Shannon; Weickert, Thomas W; Weissman, Myrna M; Williams, Leanne M; Wray, Naomi R; Zai, Clement C; Agerbo, Esben; Børglum, Anders D; Breen, Gerome; Demontis, Ditte; Erlangsen, Annette; Gelernter, Joel; Glatt, Stephen J; Hougaard, David M; Hwu, Hai-Gwo; Kuo, Po-Hsiu; Lewis, Cathryn M; Li, Qingqin S; Liu, Chih-Min; Martin, Nicholas G; McIntosh, Andrew M; Medland, Sarah E; Mors, Ole; Nordentoft, Merete; Olsen, Catherine M; Porteous, David; Smith, Daniel J; Stahl, Eli A; Stein, Murray B; Wasserman, Danuta; Werge, Thomas; Whiteman, David C; Willour, Virginia; VA Million Veteran Program (MVP); MVP Suicide Exemplar Workgroup; Suicide Working Group of the Psychiatric Genomics Consortium; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium; Bipolar Disorder Working Group of the Psychiatric Genomics Consortium; Schizophrenia Working Group of the Psychiatric Genomics Consortium; Eating Disorder Working Group of the Psychiatric Genomics Consortium; German Borderline Genomics Consortium; Coon, Hilary; Beckham, Jean C; Kimbrel, Nathan A; Ruderfer, Douglas M

    Objective

    Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.

    Methods

    This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.

    Results

    Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.

    Conclusions

    This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
  • Thumbnail Image
    ItemOpen Access
    Sensitivity, specificity, and predictive power of the "Brief Risk-resilience Index for SCreening," a brief pan-diagnostic web screen for emotional health.
    (Brain and behavior, 2012-09) Williams, Leanne M; Cooper, Nicholas J; Wisniewski, Stephen R; Gatt, Justine M; Koslow, Stephen H; Kulkarni, Jayashri; Devarney, Savannah; Gordon, Evian; John Rush, Augustus
    Few standardized tools are available for time-efficient screening of emotional health status across diagnostic categories, especially in primary care. We evaluated the 45-question Brief Risk-resilience Index for SCreening (BRISC) and the 15-question mini-BRISC in identifying poor emotional health and coping capacity across a range of diagnostic groups - compared with a detailed clinical assessment - in a large sample of adult outpatients. Participants 18-60 years of age (n = 1079) recruited from 12 medical research and clinical sites completed the computerized assessments. Three index scores were derived from the full BRISC and the mini-BRISC: one for risk (negativity-positivity bias) and two for coping (resilience and social capacity). Summed answers were converted to standardized z-scores. BRISC scores were compared with detailed health assessment and diagnostic interview (for current psychiatric, psychological, and neurological conditions) by clinicians at each site according to diagnostic criteria. Clinicians were blinded to BRISC scores. Clinical assessment stratified participants as having "clinical" (n = 435) or "healthy" (n = 644) diagnostic status. Receiver operating characteristic analyses showed that a z-score threshold of -1.57 on the full BRISC index of emotional health provided an optimal classification of "clinical" versus "healthy" status (sensitivity: 81.2%, specificity: 92.7%, positive predictive power: 80.2%, and negative predictive power: 93.1%). Comparable findings were revealed for the mini-BRISC. Negativity-positivity bias index scores contributed the most to prediction. The negativity-positivity index of emotional health was most sensitive to classifying major depressive disorder (100%), posttraumatic stress disorder (95.8%), and panic disorder (88.7%). The BRISC and mini-BRISC both offer a brief, clinically useful screen to identify individuals at risk of disorders characterized by poor emotion regulation, from those with good emotional health and coping.