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Polygenic contributions to alcohol use and alcohol use disorders across population-based and clinically ascertained samples
- Emma C. Johnson, Sandra Sanchez-Roige, Laura Acion, Mark J. Adams, Kathleen K. Bucholz, Grace Chan, Michael J. Chao, David B. Chorlian, Danielle M. Dick, Howard J. Edenberg, Tatiana Foroud, Caroline Hayward, Jon Heron, Victor Hesselbrock, Matthew Hickman, Kenneth S. Kendler, Sivan Kinreich, John Kramer, Sally I-Chun Kuo, Samuel Kuperman, Dongbing Lai, Andrew M. McIntosh, Jacquelyn L. Meyers, Martin H. Plawecki, Bernice Porjesz, David Porteous, Marc A. Schuckit, Jinni Su, Yong Zang, Abraham A. Palmer, Arpana Agrawal, Toni-Kim Clarke, Alexis C. Edwards
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- Journal:
- Psychological Medicine / Volume 51 / Issue 7 / May 2021
- Published online by Cambridge University Press:
- 20 January 2020, pp. 1147-1156
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Background
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
MethodsWe examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
ResultsIn COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
ConclusionsAUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Violent behaviour and post-traumatic stress disorder in US Iraq and Afghanistan veterans
- Eric B. Elbogen, Sally C. Johnson, H. Ryan Wagner, Connor Sullivan, Casey T. Taft, Jean C. Beckham
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- Journal:
- The British Journal of Psychiatry / Volume 204 / Issue 5 / May 2014
- Published online by Cambridge University Press:
- 02 January 2018, pp. 368-375
- Print publication:
- May 2014
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Background
Violence towards others in the community has been identified as a significant problem for a subset of Iraq and Afghanistan veterans.
AimsTo investigate the extent to which post-traumatic stress disorder (PTSD) and other risk factors predict future violent behaviour in military veterans.
MethodA national, multiwave survey enrolling a random sample of all US veterans who served in the military after 11 September 2001 was conducted. A total of 1090 veterans from 50 US states and all military branches completed two survey waves mailed 1 year apart (retention rate = 79%).
ResultsOverall, 9% endorsed engaging in severe violence and 26% in other physical aggression in the previous year, as measured at Wave 2. Younger age, financial instability, history of violence before military service, higher combat exposure, PTSD, and alcohol misuse at Wave 1 were significantly associated with higher severe violence and other physical aggression in the past year at Wave 2. When combinations of these risk factors were present, predicted probability of violence in veterans rose sharply. Veterans with both PTSD and alcohol misuse had a substantially higher rate of subsequent severe violence (35.9%) compared with veterans with alcohol misuse without PTSD (10.6%), PTSD without alcohol misuse (10.0%) or neither PTSD nor alcohol misuse (5.3%). Using multiple regression, we found that veterans with PTSD and without alcohol misuse were not at significantly higher risk of severe violence than veterans with neither PTSD nor alcohol misuse. There was a trend for other physical aggression to be higher in veterans with PTSD without alcohol misuse.
ConclusionsCo-occurring PTSD and alcohol misuse was associated with a marked increase in violence and aggression in veterans. Compared with veterans with neither PTSD nor alcohol misuse, veterans with PTSD and no alcohol misuse were not significantly more likely to be severely violent and were only marginally more likely to engage in other physical aggression. Attention to cumulative effects of multiple risk factors beyond diagnosis – including demographics, violence history, combat exposure, and veterans' having money to cover basic needs like food, shelter, transportation, and medical care – is crucial for optimising violence risk management.
Contributors
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- By Graham Allan, Donna M. Allen, Irwin Altman, Arthur Aron, Donald H. Baucom, Steven R. H. Beach, Ellen Berscheid, Rosemary Blieszner, Jeffrey Boase, Tyfany M. J. Boettcher, Barbara B. Brown, Abraham P. Buunk, Lorne Campbell, Daniel J. Canary, Rodney Cate, John P. Caughlin, Mahnaz Charania, Jennie Y. Chen, F. Scott Christopher, Jennifer A. Clarke, Marilyn Coleman, W. Andrew Collins, Michael K. Coolsen, Nathan R. Cottle, Carolyn E. Cutrona, Marianne Dainton, Valerian J. Derlega, Lisa M. Diamond, Pieternel Dijkstra, Steve Duck, Pearl A. Dykstra, Norman B. Epstein, Beverley Fehr, Frank D. Fincham, Helen E. Fisher, Julie Fitness, Garth J. O. Fletcher, Myron D. Friesen, Lawrence Ganong, Kelli A. Gardner, Jenny de Jong Gierveld, Robin Goodwin, Christine R. Gray, Kathryn Greene, David W. Harris, Willard W. Hartup, John H. Harvey, Kathi L. Heffner, Ted L. Huston, William J. Ickes, Emily A. Impett, Michael P. Johnson, Deborah J. Jones, Deborah A. Kashy, Janice K. Kiecolt‐Glaser, Jeffrey L. Kirchner, Brighid M. Kleinman, Galena H. Kline, Mark L. Knapp, Ascan Koerner, Jean‐Philippe Laurenceau, Kim Leon, Timothy J. Loving, Stephanie D. Madsen, Howard J. Markman, Alicia Mathews, Mario Mikulincer, Patricia Noller, Nickola C. Overall, Letitia Anne Peplau, Daniel Perlman, Sally Planalp, Urmila Pillay, Nicole D. Pleasant, Caryl E. Rusbult, Barbara R. Sarason, Irwin G. Sarason, Phillip R. Shaver, Alan L. Sillars, Jeffry A. Simpson, Susan Sprecher, Susan Stanton, Greg Strong, Catherine A. Surra, Anita L. Vangelisti, C. Arthur VanLear, Theo van Tilburg, Barry Wellman, Amy Wenzel, Carol M. Werner, Adam R. West, Sarah W. Whitton, Heike A. Winterheld
- Edited by Anita L. Vangelisti, University of Texas, Austin, Daniel Perlman, University of British Columbia, Vancouver
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- Book:
- The Cambridge Handbook of Personal Relationships
- Published online:
- 05 June 2012
- Print publication:
- 05 June 2006, pp xvii-xxii
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Neuroanatomic substrates of semantic memory impairment in Alzheimer's disease: Patterns of functional MRI activation
- ANDREW J. SAYKIN, LAURA A. FLASHMAN, SALLY A. FRUTIGER, STERLING C. JOHNSON, ALEXANDER C. MAMOURIAN, CHAD H. MORITZ, JUDITH R. O'JILE, HENRY J. RIORDAN, ROBERT B. SANTULLI, CYNTHIA A. SMITH, JOHN B. WEAVER
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- Journal:
- Journal of the International Neuropsychological Society / Volume 5 / Issue 5 / July 1999
- Published online by Cambridge University Press:
- 01 July 1999, pp. 377-392
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Impairment in semantic processing occurs early in Alzheimer's disease (AD) and differential impact on subtypes of semantic relations have been reported, yet there is little data on the neuroanatomic basis of these deficits. Patients with mild AD and healthy controls underwent 3 functional MRI auditory stimulation tasks requiring semantic or phonological decisions (match–mismatch) about word pairs (category–exemplar, category–function, pseudoword). Patients showed a significant performance deficit only on the exemplar task. On voxel-based fMRI activation analyses, controls showed a clear activation focus in the left superior temporal gyrus for the phonological task; patients showed additional foci in the left dorsolateral prefrontal and bilateral cingulate areas. On the semantic tasks, predominant activation foci were seen in the inferior and middle frontal gyrus (left greater than right) in both groups but patients showed additional activation suggesting compensatory recruitment of locally expanded foci and remote regions, for example, right frontal activation during the exemplar task. Covariance analyses indicated that exemplar task performance was strongly related to signal increase in bilateral medial prefrontal cortex. The authors conclude that fMRI can reveal similarities and differences in functional neuroanatomical processing of semantic and phonological information in mild AD compared to healthy elderly, and can help to bridge cognitive and neural investigations of the integrity of semantic networks in AD. (JINS, 1999, 5, 377–392.)