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101. Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice

Author

Abrams, Stephanie, Garner, Donna, Hertel, Paula, Himes, Ryan, Lawson, Alicia, Miloh, Tamir, Triggs, Nicole, Bramlage, Kristin, Carr, April, Cecil, Kim, McNeill, Meghan, Mouzaki, Marialena, Trout, Andrew, Xanthakos, Stavra, Bernstein, Kimberlee, DeVore, Stephanie, Kohli, Rohit, Lake, Kathleen, Podberesky, Daniel, Towbin, Alex, Lavine, Joel E., Mencin, Ali, Reynoso, Elena, Alazraki, Adina, Cleeton, Rebecca, Cordero, Maria, Hernandez, Albert, Karpen, Saul, Munos, Jessica Cruz, Raviele, Nicholas, Vos, Miriam, Bozic, Molly, Carr, Laura, Cummings, Oscar W., Harlow, Kathryn, Klipsch, Ann, Molleston, Jean P., Ragozzino, Emily, Rao, Girish, Kafka, Kimberly, Scheimann, Ann, Fishbein, Mark H., Ito, Joy, Mohammad, Saeed, Whitington, Peter F., Barlow, Sarah, Brunt, Elizabeth M., Carpenter, Danielle, Cattoor, Theresa, Derdoy, Jose, Freebersyser, Janet, Jain, Ajay, King, Debra, Lai, Jinping, Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Angeles, Jorge, Arin, Jennifer, Behling, Cynthia, Bross, Craig, Carrier, Carissa, Collins, Jennifer, De La Pena, Diana, Durelle, Janis, Huckaby, Mary Catherine, Middleton, Michael S., Newton, Kimberly, Schwimmer, Jeffrey B., Sirlin, Claude, Ugalde-Nicalo, Patricia, Courtier, Jesse, Gill, Ryan, Langlois, Camille, Perito, Emily Rothbaum, Rosenthal, Philip, Tsai, Patrika, Blondet, Niviann, Cooper, Kara, Murray, Karen, Otto, Randolph, Yeh, Matthew, Young, Melissa, Fowler, Kathryn, Kleiner, David E., Doo, Edward C., Hall, Sherry, Hoofnagle, Jay H., Robuck, Patricia R., Sherker, Averell H., Torrance, Rebecca, Belt, Patricia, Clark, Jeanne M., Dodge, John, Donithan, Michele, Isaacson, Milana, Lazo, Mariana, Meinert, Jill, Miriel, Laura, Sharkey, Emily P., Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Tonascia, James, Van Natta, Mark L., Wagoner, Annette, Wilson, Laura A., Yamada, Goro, Yates, Katherine P., Xanthakos, Stavra A., Murray, Karen F., Vos, Miriam B., Jain, Ajay K., Scheimann, Ann O., Fishbein, Mark, Behling, Cynthia A., and Sanyal, Arun J.

Published
2020
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102. Neuroendocrine biomarkers of prolonged exposure treatment response in military-related PTSD

Author

Rauch, Sheila A.M., Sripada, Rebecca, Burton, Mark, Michopoulos, Vasiliki, Kerley, Kimberly, Marx, Christine E., Kilts, Jason D., Naylor, Jennifer C., Rothbaum, Barbara O., McLean, Carmen P., Smith, Alicia, Norrholm, Seth D., Jovanovic, Tanja, Liberzon, Israel, Williamson, Douglas E., Yarvis, COL Jeffrey S., Dondanville, Katherine A., Young-McCaughan, Stacey, Keane, Terence M., and Peterson, Alan L.

Published
2020
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105. Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results

Author

Byrd, John C., Wierda, William G., Schuh, Anna, Devereux, Stephen, Chaves, Jorge M., Brown, Jennifer R., Hillmen, Peter, Martin, Peter, Awan, Farrukh T., Stephens, Deborah M., Ghia, Paolo, Barrientos, Jacqueline, Pagel, John M., Woyach, Jennifer A., Burke, Kathleen, Covey, Todd, Gulrajani, Michael, Hamdy, Ahmed, Izumi, Raquel, Frigault, Melanie M., Patel, Priti, Rothbaum, Wayne, Wang, Min Hui, O'Brien, Susan, and Furman, Richard R.

Published
2020
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109. In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores

Author

Schwimmer, Jeffrey B, Lavine, Joel E, Wilson, Laura A, Neuschwander-Tetri, Brent A, Xanthakos, Stavra A, Kohli, Rohit, Barlow, Sarah E, Vos, Miriam B, Karpen, Saul J, Molleston, Jean P, Whitington, Peter F, Rosenthal, Philip, Jain, Ajay K, Murray, Karen F, Brunt, Elizabeth M, Kleiner, David E, Van Natta, Mark L, Clark, Jeanne M, Tonascia, James, Doo, Edward, Abrams, Stephanie H, Barlow, Sarah, Himes, Ryan, Krisnamurthy, Rajesh, Maldonado, Leanel, Mahabir, Rory, Bernstein, Kimberlee, Bramlage, Kristin, Cecil, Kim, DeVore, Stephanie, Lake, Kathleen, Podberesky, Daniel, Towbin, Alex, Xanthakos, Stavra, Behr, Gerald, Lefkowitch, Jay H, Mencin, Ali, Reynoso, Elena, Alazraki, Adina, Cleeton, Rebecca, Karpen, Saul, Munos, Jessica Cruz, Raviele, Nicholas, Vos, Miriam, Bozic, Molly, Cummings, Oscar W, Klipsch, Ann, Munson, Sarah, Sandrasegaran, Kumar, Subbarao, Girish, Kafka, Kimberly, Scheimann, Ann, Amsden, Katie, Fishbein, Mark H, Kirwan, Elizabeth, Mohammad, Saeed, Rigsby, Cynthia, Sharda, Lisa, Derdoy, Jose, Jain, Ajay, King, Debra, Osmack, Pat, Siegner, Joan, Stewart, Susan, Torretta, Susan, Wriston, Kristina, Baker, Susan S, Zhu, Lixin, Africa, Jonathon, Angeles, Jorge, Arroyo, Sandra, Awai, Hannah, Behling, Cynthia, Bross, Craig, Durelle, Janis, Middleton, Michael, Newton, Kimberly, Paiz, Melissa, Sanford, Jennifer, Sirlin, Claude, Ugalde-Nicalo, Patricia, Villarreal, Mariana Dominguez, Aouizerat, Bradley, Courtier, Jesse, Ferrell, Linda D, Fleck, Shannon, Gill, Ryan, Langlois, Camille, Perito, Emily Rothbaum, Tsai, Patrika, Cooper, Kara, Horslen, Simon, and Hsu, Evelyn

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Clinical Trials and Supportive Activities, Chronic Liver Disease and Cirrhosis, Clinical Research, Liver Disease, Hepatitis, 6.1 Pharmaceuticals, Oral and gastrointestinal, Adolescent, Alanine Transaminase, Aspartate Aminotransferases, Biopsy, Body Weight, Child, Cysteamine, Cystine Depleting Agents, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Intention to Treat Analysis, Liver, Liver Cirrhosis, Male, Non-alcoholic Fatty Liver Disease, Severity of Illness Index, Pediatrics, ALT, AST, Obesity, NASH CRN, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract

Background & aimsNo treatment for nonalcoholic fatty liver disease (NAFLD) has been approved by regulatory agencies. We performed a randomized controlled trial to determine whether 52 weeks of cysteamine bitartrate delayed release (CBDR) reduces the severity of liver disease in children with NAFLD.MethodsWe performed a double-masked trial of 169 children with NAFLD activity scores of 4 or higher at 10 centers. From June 2012 to January 2014, the patients were assigned randomly to receive CBDR or placebo twice daily (300 mg for patients weighing ≤65 kg, 375 mg for patients weighing >65 to 80 kg, and 450 mg for patients weighing >80 kg) for 52 weeks. The primary outcome from the intention-to-treat analysis was improvement in liver histology over 52 weeks, defined as a decrease in the NAFLD activity score of 2 points or more without worsening fibrosis; patients without biopsy specimens from week 52 (17 in the CBDR group and 6 in the placebo group) were considered nonresponders. We calculated the relative risks (RR) of improvement using a stratified Cochran-Mantel-Haenszel analysis.ResultsThere was no significant difference between groups in the primary outcome (28% of children in the CBDR group vs 22% in the placebo group; RR, 1.3; 95% confidence interval [CI], 0.8-2.1; P = .34). However, children receiving CBDR had significant changes in prespecified secondary outcomes: reduced mean levels of alanine aminotransferase (reduction, 53 ± 88 U/L vs 8 ± 77 U/L in the placebo group; P = .02) and aspartate aminotransferase (reduction, 31 ± 52 vs 4 ± 36 U/L in the placebo group; P = .008), and a larger proportion had reduced lobular inflammation (36% in the CBDR group vs 21% in the placebo group; RR, 1.8; 95% CI, 1.1-2.9; P = .03). In a post hoc analysis of children weighing 65 kg or less, those taking CBDR had a 4-fold better chance of histologic improvement (observed in 50% of children in the CBDR group vs 13% in the placebo group; RR, 4.0; 95% CI, 1.3-12.3; P = .005).ConclusionsIn a randomized trial, we found that 1 year of CBDR did not reduce overall histologic markers of NAFLD compared with placebo in children. Children receiving CBDR, however, had significant reductions in serum aminotransferase levels and lobular inflammation. ClinicalTrials.gov no: NCT01529268.

Published
2016

110. International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

Author

Caroline M. Nievergelt, Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia-Yen Chen, Karmel W. Choi, Jonathan R. I. Coleman, Shareefa Dalvie, Laramie E. Duncan, Joel Gelernter, Daniel F. Levey, Mark W. Logue, Renato Polimanti, Allison C. Provost, Andrew Ratanatharathorn, Murray B. Stein, Katy Torres, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Søren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Dragan Babić, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Anders D. Børglum, Bekh Bradley, Megan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, José M. Caldas- de- Almeida, Anders M. Dale, Mark J. Daly, Nikolaos P. Daskalakis, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Alma Dzubur-Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Bizu Gelaye, Elbert Geuze, Charles Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Supriya Harnal, Michael A. Hauser, Andrew C. Heath, Sian M. J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Angela G. Junglen, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A. M. Lebois, Catrin E. Lewis, Sarah D. Linnstaedt, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica Maples-Keller, Charles Marmar, Alicia R. Martin, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Sarah McLeay, Divya Mehta, William P. Milberg, Mark W. Miller, Rajendra A. Morey, Charles Phillip Morris, Ole Mors, Preben B. Mortensen, Benjamin M. Neale, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Stephan Ripke, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Ken Ruggiero, Ariane Rung, Bart P. F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Jennifer A. Sumner, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan H. Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Jonathan D. Wolff, Rachel Yehuda, Ross McD. Young, Keith A. Young, Hongyu Zhao, Lori A. Zoellner, Israel Liberzon, Kerry J. Ressler, Magali Haas, and Karestan C. Koenen

Subjects
Science
Abstract

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Published
2019
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111. Examining Individual and Synergistic Contributions of PTSD and Genetics to Blood Pressure: A Trans-Ethnic Meta-Analysis

Author

Jennifer A. Sumner, Adam X. Maihofer, Vasiliki Michopoulos, Alex O. Rothbaum, Lynn M. Almli, Ole A. Andreassen, Allison E. Ashley-Koch, Dewleen G. Baker, Jean C. Beckham, Bekh Bradley, Gerome Breen, Jonathan R. I. Coleman, Anders M. Dale, Michelle F. Dennis, Norah C. Feeny, Carol E. Franz, Melanie E. Garrett, Charles F. Gillespie, Guia Guffanti, Michael A. Hauser, Sian M. J. Hemmings, Tanja Jovanovic, Nathan A. Kimbrel, William S. Kremen, Bruce R. Lawford, Mark W. Logue, Adriana Lori, Michael J. Lyons, Jessica Maples-Keller, Matig R. Mavissakalian, Regina E. McGlinchey, Divya Mehta, Rebecca Mellor, William Milberg, Mark W. Miller, Charles Phillip Morris, Matthew S. Panizzon, Kerry J. Ressler, Victoria B. Risbrough, Barbara O. Rothbaum, Peter Roy-Byrne, Soraya Seedat, Alicia K. Smith, Jennifer S. Stevens, Leigh Luella van den Heuvel, Joanne Voisey, Ross McD Young, Lori A. Zoellner, Caroline M. Nievergelt, and Erika J. Wolf

Subjects
posttraumatic stress disorder, genetics, blood pressure, trans-ethnic, meta-analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study – United Kingdom Biobank – PTSD symptoms were negatively associated with SBP levels (β = −1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.

Published
2021
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114. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia

Author

Byrd, John C, Harrington, Bonnie, O’Brien, Susan, Jones, Jeffrey A, Schuh, Anna, Devereux, Steve, Chaves, Jorge, Wierda, William G, Awan, Farrukh T, Brown, Jennifer R, Hillmen, Peter, Stephens, Deborah M, Ghia, Paolo, Barrientos, Jacqueline C, Pagel, John M, Woyach, Jennifer, Johnson, Dave, Huang, Jane, Wang, Xiaolin, Kaptein, Allard, Lannutti, Brian J, Covey, Todd, Fardis, Maria, McGreivy, Jesse, Hamdy, Ahmed, Rothbaum, Wayne, Izumi, Raquel, Diacovo, Thomas G, Johnson, Amy J, and Furman, Richard R

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Cancer, Lymphatic Research, Clinical Trials and Supportive Activities, Clinical Research, Lymphoma, Rare Diseases, Hematology, Orphan Drug, 6.2 Cellular and gene therapies, 5.1 Pharmaceuticals, Administration, Oral, Agammaglobulinaemia Tyrosine Kinase, Aged, Antineoplastic Agents, Benzamides, Chromosome Deletion, Diarrhea, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Headache, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Protein Kinase Inhibitors, Protein-Tyrosine Kinases, Pyrazines, Recurrence, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundIrreversible inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib represents an important therapeutic advance for the treatment of chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromises its therapeutic index. Acalabrutinib (ACP-196) is a more selective, irreversible BTK inhibitor that is specifically designed to improve on the safety and efficacy of first-generation BTK inhibitors.MethodsIn this uncontrolled, phase 1-2, multicenter study, we administered oral acalabrutinib to 61 patients who had relapsed CLL to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of acalabrutinib. Patients were treated with acalabrutinib at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 mg twice daily in the expansion (phase 2) portion.ResultsThe median age of the patients was 62 years, and patients had received a median of three previous therapies for CLL; 31% had chromosome 17p13.1 deletion, and 75% had unmutated immunoglobulin heavy-chain variable genes. No dose-limiting toxic effects occurred during the dose-escalation portion of the study. The most common adverse events observed were headache (in 43% of the patients), diarrhea (in 39%), and increased weight (in 26%). Most adverse events were of grade 1 or 2. At a median follow-up of 14.3 months, the overall response rate was 95%, including 85% with a partial response and 10% with a partial response with lymphocytosis; the remaining 5% of patients had stable disease. Among patients with chromosome 17p13.1 deletion, the overall response rate was 100%. No cases of Richter's transformation (CLL that has evolved into large-cell lymphoma) and only one case of CLL progression have occurred.ConclusionsIn this study, the selective BTK inhibitor acalabrutinib had promising safety and efficacy profiles in patients with relapsed CLL, including those with chromosome 17p13.1 deletion. (Funded by the Acerta Pharma and others; ClinicalTrials.gov number, NCT02029443.).

Published
2016

117. Virtual Reality as Treatment for Fear of Flying: A Review of Recent Research

Author

Price, Matthew, Anderson, Page, and Rothbaum, Barbara O.

Abstract

Virtual reality exposure has recently emerged as an important tool for exposure therapy in the treatment of fear of flying. There have been numerous empirical studies that have evaluated the effectiveness of virtual reality exposure as compared to other treatments including in vivo exposure, progressive muscle relaxation, cognitive therapy, bibliotherapy, and supportive group therapy. The results of two case studies and eight outcome trials have indicated that virtual reality exposure is comparable or superior to these treatments. However, the best results, as indicated by a reduction in self reported anxiety and fear experienced during an actual flight, were obtained when virtual reality exposure is combined with cognitive interventions. (Contains 1 table.)

Published
2008

119. Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis

Author

Rosenfield, David, Smits, Jasper A.J., Hofmann, Stefan G., Mataix-Cols, David, de la Cruz, Lorena Fernández, Andersson, Erik, Rück, Christian, Monzani, Benedetta, Pérez-Vigil, Ana, Frumento, Paolo, Davis, Michael, de Kleine, Rianne A., Difede, JoAnn, Dunlop, Boadie W., Farrell, Lara J., Geller, Daniel, Gerardi, Maryrose, Guastella, Adam J., Hendriks, Gert-Jan, Kushner, Matt G., Lee, Francis S., Lenze, Eric J., Levinson, Cheri A., McConnell, Harry, Plag, Jens, Pollack, Mark H., Ressler, Kerry J., Rodebaugh, Thomas L., Rothbaum, Barbara O., Storch, Eric A., Ströhle, Andreas, Tart, Candyce D., Tolin, David F., van Minnen, Agnes, Waters, Allison M., Weems, Carl F., Wilhelm, Sabine, Wyka, Katarzyna, Altemus, Margaret, Anderson, Page, Cukor, Judith, Finck, Claudia, Geffken, Gary R., Golfels, Fabian, Goodman, Wayne K., Gutner, Cassidy A., Heyman, Isobel, Jovanovic, Tanja, Lewin, Adam B., McNamara, Joseph P., Murphy, Tanya K., Norrholm, Seth, Thuras, Paul, Turner, Cynthia, and Otto, Michael W.

Published
2019
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122. The Relationship of Attention-Deficit/Hyperactivity Disorder With Posttraumatic Stress Disorder

Author

Frank R. Wendt, Miguel Garcia-Argibay, Brenda Cabrera-Mendoza, Unnur A. Valdimarsdóttir, Joel Gelernter, Murray B. Stein, Michel G. Nivard, Adam X. Maihofer, Caroline M. Nievergelt, Henrik Larsson, Manuel Mattheisen, Renato Polimanti, Sandra M. Meier, Karmel W. Choi, Jonathan R.I. Coleman, Nikolaos P. Daskalakis, Christy A. Denckla, Elizabeth Ketema, Rajendra A. Morey, Andrew Ratanatharathorn, Katy Torres, Aliza P. Wingo, Clement C. Zai, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Soren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Allison E. Ashley-Koch, S. Bryn Austin, Esmina Avdibegovic, Anders D. Borglum, Dragan Babic, Marie Bækvad-Hansen, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan I. Bisson, Marco P. Boks, Elizabeth A. Bolger, Bekh Bradley, Meghan Brashear, Gerome Breen, Richard A. Bryant, Angela C. Bustamante, Jonas Bybjerg-Grauholm, Joseph R. Calabrese, Jose Miguel Caldas-de-Almeida, Chia-Yen Chen, Anders M. Dale, Shareefa Dalvie, Jürgen Deckert, Douglas L. Delahanty, Michelle F. Dennis, Seth G. Disner, Katharina Domschke, Laramie E. Duncan, Alma Dzubur Kulenovic, Christopher R. Erbes, Alexandra Evans, Lindsay A. Farrer, Norah C. Feeny, Janine D. Flory, David Forbes, Carol E. Franz, Sandro Galea, Melanie E. Garrett, Aarti Gautam, Bizu Gelaye, Elbert Geuze, Charles F. Gillespie, Aferdita Goci Uka, Scott D. Gordon, Guia Guffanti, Rasha Hammamieh, Michael A. Hauser, Andrew C. Heath, Sian M.J. Hemmings, David Michael Hougaard, Miro Jakovljevic, Marti Jett, Eric Otto Johnson, Ian Jones, Tanja Jovanovic, Xue-Jun Qin, Karen-Inge Karstoft, Milissa L. Kaufman, Ronald C. Kessler, Alaptagin Khan, Nathan A. Kimbrel, Anthony P. King, Nastassja Koen, Henry R. Kranzler, William S. Kremen, Bruce R. Lawford, Lauren A.M. Lebois, Catrin Lewis, Israel Liberzon, Sarah D. Linnstaedt, Mark W. Logue, Adriana Lori, Bozo Lugonja, Jurjen J. Luykx, Michael J. Lyons, Jessica L. Maples-Keller, Charles Marmar, Nicholas G. Martin, Douglas Maurer, Matig R. Mavissakalian, Alexander McFarlane, Regina E. McGlinchey, Katie A. McLaughlin, Samuel A. McLean, Divya Mehta, Rebecca Mellor, Vasiliki Michopoulos, William Milberg, Mark W. Miller, Charles Phillip Morris, Ole Mors, Preben Bo Mortensen, Elliot C. Nelson, Merete Nordentoft, Sonya B. Norman, Meaghan O’Donnell, Holly K. Orcutt, Matthew S. Panizzon, Edward S. Peters, Alan L. Peterson, Matthew Peverill, Robert H. Pietrzak, Melissa A. Polusny, John P. Rice, Victoria B. Risbrough, Andrea L. Roberts, Alex O. Rothbaum, Barbara O. Rothbaum, Peter Roy-Byrne, Kenneth J. Ruggiero, Ariane Rung, Bart P.F. Rutten, Nancy L. Saccone, Sixto E. Sanchez, Dick Schijven, Soraya Seedat, Antonia V. Seligowski, Julia S. Seng, Christina M. Sheerin, Derrick Silove, Alicia K. Smith, Jordan W. Smoller, Scott R. Sponheim, Dan J. Stein, Jennifer S. Stevens, Martin H. Teicher, Wesley K. Thompson, Edward Trapido, Monica Uddin, Robert J. Ursano, Leigh Luella van den Heuvel, Miranda Van Hooff, Eric Vermetten, Christiaan Vinkers, Joanne Voisey, Yunpeng Wang, Zhewu Wang, Thomas Werge, Michelle A. Williams, Douglas E. Williamson, Sherry Winternitz, Christiane Wolf, Erika J. Wolf, Rachel Yehuda, Keith A. Young, Ross McD. Young, Hongyu Zhao, Lori A. Zoellner, Magali Haas, Heather Lasseter, Allison C. Provost, Rany M. Salem, Jonathan Sebat, Richard Shaffer, Tianying Wu, Stephan Ripke, Mark J. Daly, Kerry J. Ressler, Karestan C. Koenen, Biological Psychology, APH - Mental Health, APH - Methodology, Anatomy and neurosciences, Psychiatry, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
Genome-wide association study, Epidemiology, Siblings, PTSD, Mendelian Randomization Analysis, Comorbidities, SDG 3 - Good Health and Well-being, Humans, ADHD, Attention Deficit Disorder with Hyperactivity/epidemiology, Stress Disorders, Post-Traumatic/genetics, Biological Psychiatry, Causal inference
Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) and posttraumatic stress disorder (PTSD) are associated, but it is unclear if this is a causal relationship or confounding. We used genetic analyses and sibling comparisons to clarify the direction of this relationship. Methods: Linkage disequilibrium score regression and 2-sample Mendelian randomization were used to test for genetic correlation (r g) and bidirectional causal effects using European ancestry genome-wide association studies of ADHD (20,183 cases and 35,191 controls) and 6 PTSD definitions (up to 320,369 individuals). Several additional variables were included in the analysis to verify the independence of the ADHD-PTSD relationship. In a population-based sibling comparison (N = 2,082,118 individuals), Cox regression models were fitted to account for time at risk, a range of sociodemographic factors, and unmeasured familial confounders (via sibling comparisons). Results: ADHD and PTSD had consistent r g (r g range, 0.43–0.52; p < .001). ADHD genetic liability was causally linked with increased risk for PTSD (β = 0.367; 95% CI, 0.186–0.552; p = 7.68 × 10 −5). This result was not affected by heterogeneity, horizontal pleiotropy (Mendelian randomization Egger intercept = 4.34 × 10 −4, p = .961), or other phenotypes and was consistent across PTSD datasets. However, we found no consistent associations between PTSD genetic liability and ADHD risk. Individuals diagnosed with ADHD were at a higher risk for developing PTSD than their undiagnosed sibling (hazard ratio = 2.37; 95% CI, 1.98–3.53). Conclusions: Our findings add novel evidence supporting the need for early and effective treatment of ADHD, as patients with this diagnosis are at significantly higher risk to develop PTSD later in life.

Published
2023
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123. Sex Differences in Peritraumatic Inflammatory Cytokines and Steroid Hormones Contribute to Prospective Risk for Nonremitting Posttraumatic Stress Disorder

Author

Chloe S. Lalonde, Yara Mekawi, Kelly F. Ethun, Eleonore Beurel, Felicia Gould, Firdaus S. Dhabhar, Katharina Schultebraucks, Isaac Galatzer-Levy, Jessica L. Maples-Keller, Barbara O. Rothbaum, Kerry J. Ressler, Charles B. Nemeroff, Jennifer S. Stevens, and Vasiliki Michopoulos

Subjects
Psychiatry, RC435-571
Abstract

Women are at higher risk for developing posttraumatic stress disorder (PTSD) compared to men, yet little is known about the biological contributors to this sex difference. One possible mechanism is differential immunological and neuroendocrine responses to traumatic stress exposure. In the current prospective study, we aimed to identify whether sex is indirectly associated with the probability of developing nonremitting PTSD through pro-inflammatory markers and whether steroid hormone concentrations influence this effect. Female ( n = 179) and male ( n = 197) trauma survivors were recruited from an emergency department and completed clinical assessment within 24 h and blood samples within ∼three hours of trauma exposure. Pro-inflammatory cytokines (IL-6, IL-1 β , TNF, IFNγ), and steroid hormone (estradiol, testosterone, progesterone, cortisol) concentrations were quantified in plasma. Compared to men, women had a higher probability of developing nonremitting PTSD after trauma ( p = 0.04), had lower pro-inflammatory cytokines and testosterone ( p ’ s

Published
2021
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125. Linear crusted papules in an infant

Author

Lauren Langenderfer, BS, Rachel Giesey, DO, Robert Rothbaum, MD, Luisa Christensen, MD, Ari Konheim, MD, and Gregory Delost, DO

Subjects
ATP2A2, autosomal dominant, Darier disease, forward mosaicism, incontinentia pigmenti, inflammatory linear verrucous epidermal nevus, Dermatology, RL1-803
Published
2020
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128. Evaluation of a corticotropin releasing hormone type 1 receptor antagonist in women with posttraumatic stress disorder: Study protocol for a randomized controlled trial

Author

Neylan, Thomas, Dunlop, BW, Rothbaum, BO, Binder, EB, Duncan, E, Harvey, PD, Jovanovic, T, Kelley, ME, Kinkead, B, Kutner, M, and Iosifescu, DV

Abstract

Background: Pharmacologic treatment options for posttraumatic stress disorder (PTSD) are limited in number and effectiveness. Medications currently in use to treat PTSD were originally approved based on their efficacy in other disorders, such as major depr

Published
2014

135. Milestones for neurosurgery sub-interns: a novel evaluation tool to quantitatively differentiate residency applicants

Author

Bowden, Stephen G., primary, Tan, Hao, additional, Rothbaum, Michael G., additional, Cook, Steven H., additional, Hanft, Simon, additional, Heth, Jason, additional, Morgenstern, Peter F., additional, Mullin, Jeffrey P., additional, Orina, Josiah N., additional, Wilson, Jonathan L., additional, Winer, Jesse L., additional, Wolfe, Stacey Q., additional, Chambless, Lola B., additional, and Selden, Nathan R., additional

Published
2023
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136. TP008/#1500 Trial in progress: phase 2/3 study of navtemadlin as maintenance therapy in patients with advanced or recurrent endometrial cancer who responded to chemotherapy (ENGOT-EN21; GOG-3089)

Author

Concin, Nicole, primary, Giorgi, Ugo De, additional, Gorp, Toon Van, additional, Alexandre, Jérôme, additional, Lindemann, Kristina, additional, Marth, Christian, additional, Berger, Regina, additional, Cibula, David, additional, Quindos, Maria, additional, Bologna, Alessandra, additional, Korach, Jacob, additional, Papadimitriou, Christos, additional, Nicum, Shibani, additional, Collins, Dearbhaile, additional, Myers, Reg, additional, Rothbaum, Wayne, additional, Herzog, Thomas, additional, Monk, Bradley, additional, and Cloven, Noelle Gillette, additional

Published
2023
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140. PTSD

Author

Rothbaum, Barbara O., primary and Rauch, Sheila A.M., additional

Published
2020
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144. Afterword

Author

Rothbaum, Barbara O., primary and Rauch, Sheila A. M., additional

Published
2020
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147. Daily Session Schedule

Author

Rauch, Sheila A. M., primary, Rothbaum, Barbara O., additional, Smith, Erin R., additional, and Foa, Edna B., additional

Published
2020
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150. Exposure in PE-IOP

Author

Rauch, Sheila A. M., primary, Rothbaum, Barbara O., additional, Smith, Erin R., additional, and Foa, Edna B., additional

Published
2020
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