Search

Your search keyword '"Williams, Leanne"' showing total 558 results
Start Over Author "Williams, Leanne" Search Limiters Available in Library Collection
558 results on '"Williams, Leanne"'

3. New and emerging approaches to treat psychiatric disorders.

Author

Scangos, Katherine, State, Matthew, Miller, Andrew, Baker, Justin, and Williams, Leanne

Subjects
Humans, Mental Disorders, Psychiatry, Drug Discovery
Abstract

Psychiatric disorders are highly prevalent, often devastating diseases that negatively impact the lives of millions of people worldwide. Although their etiological and diagnostic heterogeneity has long challenged drug discovery, an emerging circuit-based understanding of psychiatric illness is offering an important alternative to the current reliance on trial and error, both in the development and in the clinical application of treatments. Here we review new and emerging treatment approaches, with a particular emphasis on the revolutionary potential of brain-circuit-based interventions for precision psychiatry. Limitations of circuit models, challenges of bringing precision therapeutics to market and the crucial advances needed to overcome these obstacles are presented.

Published
2023

9. Mediating Effects of Neural Targets on Depression, Weight, and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot Randomized Clinical Trial

Author

Lv, Nan, Ajilore, Olusola A., Xiao, Lan, Venditti, Elizabeth M., Lavori, Philip W., Gerber, Ben S., Snowden, Mark B., Wittels, Nancy E., Ronneberg, Corina R., Stetz, Patrick, Barve, Amruta, Shrestha, Rohit, Dosala, Sushanth, Kumar, Vikas, Eckley, Tessa L., Goldstein-Piekarski, Andrea N., Smyth, Joshua M., Rosas, Lisa G., Kannampallil, Thomas, Zulueta, John, Suppes, Trisha, Williams, Leanne M., and Ma, Jun

Published
2023
Full Text
View/download PDF

10. Development of top-down cortical propagations in youth

Author

Pines, Adam, Keller, Arielle S., Larsen, Bart, Bertolero, Maxwell, Ashourvan, Arian, Bassett, Dani S., Cieslak, Matthew, Covitz, Sydney, Fan, Yong, Feczko, Eric, Houghton, Audrey, Rueter, Amanda R., Saggar, Manish, Shafiei, Golia, Tapera, Tinashe M., Vogel, Jacob, Weinstein, Sarah M., Shinohara, Russell T., Williams, Leanne M., Fair, Damien A., and Satterthwaite, Theodore D.

Published
2023
Full Text
View/download PDF

12. Variability in engagement and progress in efficacious integrated collaborative care for primary care patients with obesity and depression: Within-treatment analysis in the RAINBOW trial

Author

Lv, Nan, Xiao, Lan, Majd, Marzieh, Lavori, Philip W, Smyth, Joshua M, Rosas, Lisa G, Venditti, Elizabeth M, Snowden, Mark B, Lewis, Megan A, Ward, Elizabeth, Lesser, Lenard, Williams, Leanne M, Azar, Kristen MJ, and Ma, Jun

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Nutrition, Behavioral and Social Science, Mental Health, Clinical Research, Health Services, Clinical Trials and Supportive Activities, Brain Disorders, Prevention, Depression, Obesity, Cancer, Stroke, Oral and gastrointestinal, Good Health and Well Being, Adult, Female, Humans, Male, Middle Aged, Patient Participation, Surveys and Questionnaires, Treatment Outcome, General Science & Technology
Abstract

IntroductionThe RAINBOW randomized clinical trial validated the efficacy of an integrated collaborative care intervention for obesity and depression in primary care, although the effect was modest. To inform intervention optimization, this study investigated within-treatment variability in participant engagement and progress.MethodsData were collected in 2014-2017 and analyzed post hoc in 2018. Cluster analysis evaluated patterns of change in weekly self-monitored weight from week 6 up to week 52 and depression scores on the Patient Health Questionnaire-9 (PHQ-9) from up to 15 individual sessions during the 12-month intervention. Chi-square tests and ANOVA compared weight loss and depression outcomes objectively measured by blinded assessors to validate differences among categories of treatment engagement and progress defined based on cluster analysis results.ResultsAmong 204 intervention participants (50.9 [SD, 12.2] years, 71% female, 72% non-Hispanic White, BMI 36.7 [6.9], PHQ-9 14.1 [3.2]), 31% (n = 63) had poor engagement, on average completing self-monitored weight in

Published
2020

13. Correction: Variability in engagement and progress in efficacious integrated collaborative care for primary care patients with obesity and depression: Within-treatment analysis in the RAINBOW trial

Author

Lv, Nan, Xiao, Lan, Majd, Marzieh, Lavori, Philip W, Smyth, Joshua M, Rosas, Lisa G, Venditti, Elizabeth M, Snowden, Mark B, Lewis, Megan A, Ward, Elizabeth, Lesser, Lenard I, Williams, Leanne M, Azar, Kristen MJ, and Ma, Jun

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Good Health and Well Being, General Science & Technology
Abstract

[This corrects the article DOI: 10.1371/journal.pone.0231743.].

Published
2020

15. Sex, Sleep Deprivation, and the Anxious Brain.

Author

Goldstein-Piekarski, Andrea, Greer, Stephanie, Saletin, Jared, Harvey, Allison, Williams, Leanne, and Walker, Matthew

Subjects
Adolescent, Adult, Anxiety, Brain, Cross-Over Studies, Female, Gray Matter, Humans, Magnetic Resonance Imaging, Male, Organ Size, Resilience, Psychological, Sex Characteristics, Sleep Deprivation, Young Adult
Abstract

Insufficient sleep is a known trigger of anxiety. Nevertheless, not everyone experiences these effects to the same extent. One determining factor is sex, wherein women experience a greater anxiogenic impact in response to sleep loss than men. However, the underlying brain mechanism(s) governing this sleep-loss-induced anxiety increase, including the markedly different reaction in women and men, is unclear. Here, we tested the hypothesis that structural brain morphology in a discrete network of emotion-relevant regions represents one such explanatory factor. Healthy participants were assessed across sleep-rested and sleep-deprived conditions, with brain structure quantified using gray matter volume measures. Sleep loss triggered greater levels of anxiety in women compared with men. Reduced gray matter volume in the anterior insula and lateral orbitofrontal cortex predicted the anxiogenic impact of sleep loss in women, yet predicted resilience in men, and did so with high discrimination accuracy. In contrast, gray matter volume in ventromedial prefrontal cortex predicted the anxiogenic impact of sleep loss in both men and women. Structural human brain morphology therefore appears to represent one mechanistic pathway (and possible biomarker) determining anxiety vulnerability to sleep loss-a discovery that may help explain the higher prevalence of sleep disruption and anxiety in women.

Published
2018

20. Problem-solving therapy–induced amygdala engagement mediates lifestyle behavior change in obesity with comorbid depression: a randomized proof-of-mechanism trial

Author

Lv, Nan, Lefferts, Wesley K, Xiao, Lan, Goldstein-Piekarski, Andrea N, Wielgosz, Joseph, Lavori, Philip W, Simmons, Janine M, Smyth, Joshua M, Stetz, Patrick, Venditti, Elizabeth M, Lewis, Megan A, Rosas, Lisa G, Snowden, Mark B, Ajilore, Olusola A, Suppes, Trisha, Williams, Leanne M, and Ma, Jun

Published
2021
Full Text
View/download PDF

22. Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial

Author

Goldstein-Piekarski, Andrea N, Wielgosz, Joseph, Xiao, Lan, Stetz, Patrick, Correa, Carlos G., Chang, Sarah E., Lv, Nan, Rosas, Lisa G., Lavori, Philip W., Snowden, Mark B., Venditti, Elizabeth M., Simmons, Janine M., Smyth, Joshua M., Suppes, Trisha, Lewis, Megan A., Ajilore, Olusola, Ma, Jun, and Williams, Leanne M.

Published
2021
Full Text
View/download PDF

27. Identifying response and predictive biomarkers for Transcranial magnetic stimulation outcomes: protocol and rationale for a mechanistic study of functional neuroimaging and behavioral biomarkers in veterans with Pharmacoresistant depression

Author

Williams, Leanne M., Coman, John T., Stetz, Patrick C., Walker, Nicole C., Kozel, F. Andrew, George, Mark S., Yoon, Jong, Hack, Laura M., Madore, Michelle R., Lim, Kelvin O., Philip, Noah S., and Holtzheimer, Paul E.

Published
2021
Full Text
View/download PDF

29. Features of immunometabolic depression as predictors of antidepressant treatment outcomes: pooled analysis of four clinical trials

Author

Vreijling, Sarah R., primary, Chin Fatt, Cherise R., additional, Williams, Leanne M., additional, Schatzberg, Alan F., additional, Usherwood, Tim, additional, Nemeroff, Charles B., additional, Rush, A. John, additional, Uher, Rudolf, additional, Aitchison, Katherine J., additional, Köhler-Forsberg, Ole, additional, Rietschel, Marcella, additional, Trivedi, Madhukar H., additional, Jha, Manish K., additional, Penninx, Brenda W. J. H., additional, Beekman, Aartjan T. F., additional, Jansen, Rick, additional, and Lamers, Femke, additional

Published
2023
Full Text
View/download PDF

30. The role of aquaporins in the developing ovarian follicle

Author

Williams, Leanne

Subjects
571.864196422, SF Animal culture, QP501 Animal biochemistry
Abstract

The growth of ovarian follicles is well documented in terms of hormonal control, however the fluid dynamics of antral follicle growth is less well understood. Aquaporins (AQP) are transmembrane water channels which facilitate the passive movement of water. In mammals 13 AQPs have been identified in a vast range of tissue types. In terms of ovarian AQPs there is currently a paucity of information. Recent studies in rat, pig and human have revealed the presence of ovarian AQPs, but in doing so have also highlighted a lack of consensus on AQP-type and location. The main aim of this study was to investigate the potential role of AQP in antral follicle growth. The first objective was to identify tissue expression and localisation of AQP proteins in the bovine ovary. This required the characterisation of a panel of polyclonal serum antibodies. Immunohistochemistry (IHC) was then used to identify AQPs and to detect changes in protein expression during follicular growth. Aquaporin 1 was found in most vascular endothelium; it was plentiful in capillaries surrounding antral follicles and increased in abundance as vasculature increased with follicle development. Aquaporin 2 was not found in bovine ovarian tissue and the remaining antibodies were deemed too nonspecific to permit reliable conclusions. The second objective was to investigate, via RT-qPCR, mRNA levels of AQPs in granulosa and theca cells isolated from preantral, through to large preovulatory follicles. Transcripts of AQP 1, -3, -4, -5, -7 and -9 were detected in both the granulosa and theca of antral follicles with expression levels generally higher in theca. The expression of AQP 1, -5, -7 and -9 was initiated in the theca cells of early antral follicles. Finally, swelling assays using bovine and porcine granulosa cells demonstrated the ability of granulosa to swell. This was inhibited by HgCb which is characteristic of AQP function. Porcine granulosa cells incubated with androgen swelled by 27%, this effect was inhibited by hydroxyflutamide. Protein analysis of AQP5 via IHC and Western blotting showed possible up-regulation in porcine follicles. RTqPCR did not reveal AQP5 transcript, the reasons for this currently remain unclear. In conclusion, this study has revealed for the first time the involvement of AQPs in bovine ovarian follicle development, with AQPI, -5, -7 and -9 potentially playing a pivotal role in antrum formation. The AQP system in porcine granulosa cells is androgen sensitive however identification of the AQP/s responsible needs further investigation. The evidence from this investigation suggests a role for AQPs in facilitating follicle growth. The stage-dependent expression of certain AQPs and the androgen sensitive porcine granulosa cells reveals the possibility that AQPs may be modulated by follicle-regulating hormones.

Published
2012

45. GWAS Meta-Analysis of Suicide Attempt:Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Author

Docherty, Anna R., Mullins, Niamh, Ashley-Koch, Allison E., Qin, Xuejun, Coleman, Jonathan R.I., Shabalin, Andrey, Kang, Joo Eun, 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., John Mann, J., 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.M.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., Blake Woodside, D., Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Appadurai, Vivek, Artigas, María Soler, Van Der Auwera, Sandra, Helena Azevedo, M., Bass, Nicholas, Bau, Claiton H.D., 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 W.J.H., 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 J.S., Trzaskowski, MacIej, Tsuang, Ming T., Turecki, Gustavo, Vilar-Ribó, Laura, Vincent, John B., Völzke, Henry, Walters, James T.R., 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, Coon, Hilary, Beckham, Jean C., Kimbrel, Nathan A., Ruderfer, Douglas M., Docherty, Anna R., Mullins, Niamh, Ashley-Koch, Allison E., Qin, Xuejun, Coleman, Jonathan R.I., Shabalin, Andrey, Kang, Joo Eun, 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., John Mann, J., 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.M.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., Blake Woodside, D., Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Appadurai, Vivek, Artigas, María Soler, Van Der Auwera, Sandra, Helena Azevedo, M., Bass, Nicholas, Bau, Claiton H.D., 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 W.J.H., 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 J.S., Trzaskowski, MacIej, Tsuang, Ming T., Turecki, Gustavo, Vilar-Ribó, Laura, Vincent, John B., Völzke, Henry, Walters, James T.R., 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, Coon, Hilary, Beckham, Jean C., Kimbrel, Nathan A., and Ruderfer, Douglas M.

Abstract

Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide asso-ciation studies (GWASs) recently discovered and cross- validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic co-horts 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 ad-mixtures 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 ge-netic 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 en-richment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major de-pressive 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 pheno-types. These findings provide insight into genetic fa, Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis 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 attemp

Published
2023

46. Heritability of cognitive and emotion processing during functional MRI in a twin sample.

Author

Park, Haeme R. P., Chilver, Miranda R., Quidé, Yann, Montalto, Arthur, Schofield, Peter R., Williams, Leanne M., and Gatt, Justine M.

Subjects
FUNCTIONAL magnetic resonance imaging, SELECTIVITY (Psychology), FACIAL expression & emotions (Psychology), HERITABILITY, INDEPENDENT component analysis, EMOTIONS
Abstract

Despite compelling evidence that brain structure is heritable, the evidence for the heritability of task‐evoked brain function is less robust. Findings from previous studies are inconsistent possibly reflecting small samples and methodological variations. In a large national twin sample, we systematically evaluated heritability of task‐evoked brain activity derived from functional magnetic resonance imaging. We used established standardised tasks to engage brain regions involved in cognitive and emotional functions. Heritability was evaluated across a conscious and nonconscious Facial Expressions of Emotion Task (FEET), selective attention Oddball Task, N‐back task of working memory maintenance, and a Go‐NoGo cognitive control task in a sample of Australian adult twins (N ranged from 136 to 226 participants depending on the task and pairs). Two methods for quantifying associations of heritability and brain activity were utilised; a multivariate independent component analysis (ICA) approach and a univariate brain region‐of‐interest (ROI) approach. Using ICA, we observed that a significant proportion of task‐evoked brain activity was heritable, with estimates ranging from 23% to 26% for activity elicited by nonconscious facial emotion stimuli, 27% to 34% for N‐back working memory maintenance and sustained attention, and 32% to 33% for selective attention in the Oddball task. Using the ROI approach, we found that activity of regions specifically implicated in emotion processing and selective attention showed significant heritability for three ROIs, including estimates of 33%–34% for the left and right amygdala in the nonconscious processing of sad faces and 29% in the medial superior prefrontal cortex for the Oddball task. Although both approaches show similar levels of heritability for the Nonconscious Faces and Oddball tasks, ICA results displayed a more extensive network of heritable brain function, including additional regions beyond the ROI analysis. Furthermore, multivariate twin modelling of both ICA networks and ROI activation suggested a mix of common genetic and unique environmental factors that contribute to the associations between networks/regions. Together, the results indicate a complex relationship between genetic factors and environmental interactions that ultimately give rise to neural activation underlying cognition and emotion. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

50. Striatal dopamine deficits predict reductions in striatal functional connectivity in major depression: a concurrent 11C-raclopride positron emission tomography and functional magnetic resonance imaging investigation

Author

Hamilton, J. Paul, Sacchet, Matthew D., Hjørnevik, Trine, Chin, Frederick T., Shen, Bin, Kämpe, Robin, Park, Jun Hyung, Knutson, Brian D., Williams, Leanne M., Borg, Nicholas, Zaharchuk, Greg, Camacho, M. Catalina, Mackey, Sean, Heilig, Markus, Drevets, Wayne C., Glover, Gary H., Gambhir, Sanjiv S., and Gotlib, Ian H.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results