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Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study
- Stephanie Haering, Antonia V. Seligowski, Sarah D. Linnstaedt, Vasiliki Michopoulos, Stacey L. House, Francesca L. Beaudoin, Xinming An, Thomas C. Neylan, Gari D. Clifford, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Jr., Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Robert A. Swor, Nina T. Gentile, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Brian J. O'Neil, Leon D. Sanchez, Steven E. Bruce, Steven E. Harte, Samuel A. McLean, Ronald C. Kessler, Karestan C. Koenen, Jennifer S. Stevens, Abigail Powers
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- Journal:
- Psychological Medicine , First View
- Published online by Cambridge University Press:
- 22 May 2024, pp. 1-11
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Background
Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.
MethodsAs part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.
ResultsWomen reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.
ConclusionsOur findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.
41 Examining the independent and additive effects of family history of dementia and apolipoprotein e4 on neurocognitive performance among people with HIV
- Maulika Kohli, Laura M Campbell, Erin Sundermann, Mark W Bondi, Paul Gilbert, Donald Franklin, Scott Letendre, Robert K Heaton, Payal Patel, Susan Morgello, Benjamin Gelman, David Clifford, Raeanne C Moore, David J Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 249-250
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Objective:
Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.
Participants and Methods:283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.
Results:Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).
Conclusions:PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.
3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV
- Laura M Campbell, Maulika Kohli, Erin E Sundermann, Christine Fennema-Notestine, Averi Barrett, Cinnamon Bloss, Mark W Bondi, David B Clifford, Ronald J Ellis, Donald Franklin, Benjamin Gelman, Igor Grant, Robert K Heaton, Scott Letendre, Payal B Patel, David J Moore, Susan Morgello, Raeanne C Moore
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 683-684
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Objective:
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals
- Cecilia A. Hinojosa, Amanda Liew, Xinming An, Jennifer S. Stevens, Archana Basu, Sanne J. H. van Rooij, Stacey L. House, Francesca L. Beaudoin, Donglin Zeng, Thomas C. Neylan, Gari D. Clifford, Tanja Jovanovic, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, John P. Haran, Alan B. Storrow, Christopher Lewandowski, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Michael C. Kurz, Robert A. Swor, Lauren A. Hudak, Jose L. Pascual, Mark J. Seamon, Elizabeth M. Datner, Anna M. Chang, Claire Pearson, David A. Peak, Roland C. Merchant, Robert M. Domeier, Niels K. Rathlev, Paulina Sergot, Leon D. Sanchez, Steven E. Bruce, Mark W. Miller, Robert H. Pietrzak, Jutta Joormann, Diego A. Pizzagalli, John F. Sheridan, Steven E. Harte, James M. Elliott, Ronald C. Kessler, Karestan C. Koenen, Samuel A. McLean, Kerry J. Ressler, Negar Fani
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- Journal:
- Psychological Medicine / Volume 54 / Issue 2 / January 2024
- Published online by Cambridge University Press:
- 13 June 2023, pp. 338-349
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Background
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
MethodsIn total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
ResultsThree trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
ConclusionsOur findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study
- Jutta Joormann, Samuel A. McLean, Francesca L. Beaudoin, Xinming An, Jennifer S. Stevens, Donglin Zeng, Thomas C. Neylan, Gari Clifford, Sarah D. Linnstaedt, Laura T. Germine, Scott L. Rauch, Paul I. Musey, Phyllis L. Hendry, Sophia Sheikh, Christopher W. Jones, Brittany E. Punches, Gregory Fermann, Lauren A. Hudak, Kamran Mohiuddin, Vishnu Murty, Meghan E. McGrath, John P. Haran, Jose Pascual, Mark Seamon, David A. Peak, Claire Pearson, Robert M. Domeier, Paulina Sergot, Roland Merchant, Leon D. Sanchez, Niels K. Rathlev, William F. Peacock, Steven E. Bruce, Deanna Barch, Diego A. Pizzagalli, Beatriz Luna, Steven E. Harte, Irving Hwang, Sue Lee, Nancy Sampson, Karestan C. Koenen, Kerry J. Ressler, Ronald C. Kessler
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- Journal:
- Psychological Medicine / Volume 52 / Issue 10 / July 2022
- Published online by Cambridge University Press:
- 29 October 2020, pp. 1934-1947
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Background
This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.
MethodsWe focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.
ResultsEight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.
ConclusionsThese observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.
Notes on contributors
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- By James Eli Adams, Joseph Bristow, Oliver S. Buckton, Barbara Caine, Richard Cave, David Clifford, Harry Cocks, Matt Cook, Joseph Donohue, Richard Dorment, Sos Eltis, Helen Freshwater, Josephine M. Guy, Ellis Hanson, Merlin Holland, Russell Jackson, Jarlath Killeen, Leon Litvack, Ruth Livesey, Jerusha McCormack, Michèle Mendelssohn, Susan Owens, Kerry Powell, Steven Price, Peter Raby, Mark Ravenhill, John Paul Riquelme, Anthony Roche, Sean Ryder, Jan-Melissa Schramm, Ian Small, Philip E. Smith, Margaret D. Stetz, John Stokes, Mark W. Turner, Lynn Voskuil, Marcus Waithe
- Edited by Kerry Powell, Miami University, Peter Raby, Homerton College, Cambridge
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- Oscar Wilde in Context
- Published online:
- 18 December 2013
- Print publication:
- 12 December 2013, pp xvi-xxii
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Supporting Second Victims of Patient Safety Events: Shouldn't These Communications Be Covered by Legal Privilege?
- Mélanie E. de Wit, Clifford M. Marks, Jeffrey P. Natterman, Albert W. Wu
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- Journal:
- Journal of Law, Medicine & Ethics / Volume 41 / Issue 4 / Winter 2013
- Published online by Cambridge University Press:
- 01 January 2021, pp. 852-858
- Print publication:
- Winter 2013
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The harmful impact of an adverse event ripples beyond injured patients and their families to affect physicians, nurses, and other health care staff that are involved. These “Second Victims” may experience intense feelings of anxiety, guilt, and fear. They may doubt their clinical competence or ability to continue working at all. Some go on to suffer post-traumatic stress disorder and depression.
Medical institutions long ignored this problem, preferring to believe that adverse events, or “errors,” occur due to incompetence — the unfortunate work of a few “bad” practitioners who deserve, if anything, a reprimand for their negligence. Study after study has rejected this attribution and shown that adverse events in health care stem primarily from systemic flaws, not “bad apples.” Devastating errors, in other words, can, do, and always will happen in the care of competent, well-trained, and caring practitioners.
Contributors
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- By Waiel Almoustadi, Brian J. Anderson, David B. Auyong, Michael Avidan, Michael J. Avram, Roland J. Bainton, Jeffrey R. Balser, Juliana Barr, W. Scott Beattie, Manfred Blobner, T. Andrew Bowdle, Walter A. Boyle, Eugene B. Campbell, Laura F. Cavallone, Mario Cibelli, C. Michael Crowder, Ola Dale, M. Frances Davies, Mark Dershwitz, George Despotis, Clifford S. Deutschman, Brian S. Donahue, Marcel E. Durieux, Thomas J. Ebert, Talmage D. Egan, Helge Eilers, E. Wesley Ely, Charles W. Emala, Alex S. Evers, Heidrun Fink, Pierre Foëx, Stuart A. Forman, Helen F. Galley, Josephine M. Garcia-Ferrer, Robert W. Gereau, Tony Gin, David Glick, B. Joseph Guglielmo, Dhanesh K. Gupta, Howard B. Gutstein, Robert G. Hahn, Greg B. Hammer, Brian P. Head, Helen Higham, Laureen Hill, Kirk Hogan, Charles W. Hogue, Christopher G. Hughes, Eric Jacobsohn, Roger A. Johns, Dean R. Jones, Max Kelz, Evan D. Kharasch, Ellen W. King, W. Andrew Kofke, Tom C. Krejcie, Richard M. Langford, H. T. Lee, Isobel Lever, Jerrold H. Levy, J. Lance Lichtor, Larry Lindenbaum, Hung Pin Liu, Geoff Lockwood, Alex Macario, Conan MacDougall, M. B. MacIver, Aman Mahajan, Nándor Marczin, J. A. Jeevendra Martyn, George A. Mashour, Mervyn Maze, Thomas McDowell, Stuart McGrane, Berend Mets, Patrick Meybohm, Charles F. Minto, Jonathan Moss, Mohamed Naguib, Istvan Nagy, Nick Oliver, Paul S. Pagel, Pratik P. Pandharipande, Piyush Patel, Andrew J. Patterson, Robert A. Pearce, Ronald G. Pearl, Misha Perouansky, Kristof Racz, Chinniampalayam Rajamohan, Nilesh Randive, Imre Redai, Stephen Robinson, Richard W. Rosenquist, Carl E. Rosow, Uwe Rudolph, Francis V. Salinas, Robert D. Sanders, Sunita Sastry, Michael Schäfer, Jens Scholz, Thomas W. Schnider, Mark A. Schumacher, John W. Sear, Frédérique S. Servin, Jeffrey H. Silverstein, Tom De Smet, Martin Smith, Joe Henry Steinbach, Markus Steinfath, David F. Stowe, Gary R. Strichartz, Michel M. R. F. Struys, Isao Tsuneyoshi, Robert A. Veselis, Arthur Wallace, Robert P. Walt, David C. Warltier, Nigel R. Webster, Jeanine Wiener-Kronish, Troy Wildes, Paul Wischmeyer, Ling-Gang Wu, Stephen Yang
- Edited by Alex S. Evers, Washington University School of Medicine, St Louis, Mervyn Maze, University of California, San Francisco, Evan D. Kharasch, Washington University School of Medicine, St Louis
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- Anesthetic Pharmacology
- Published online:
- 11 April 2011
- Print publication:
- 10 March 2011, pp viii-xiv
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