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5. Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

Author

Walters, Raymond K, Polimanti, Renato, Johnson, Emma C, McClintick, Jeanette N, Adams, Mark J, Adkins, Amy E, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M, Bigdeli, Tim B, Chen, Li-Shiun, Clarke, Toni-Kim, Chou, Yi-Ling, Degenhardt, Franziska, Docherty, Anna R, Edwards, Alexis C, Fontanillas, Pierre, Foo, Jerome C, Fox, Louis, Frank, Josef, Giegling, Ina, Gordon, Scott, Hack, Laura M, Hartmann, Annette M, Hartz, Sarah M, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hodgkinson, Colin, Hoffmann, Per, Jan Hottenga, Jouke, Kennedy, Martin A, Alanne-Kinnunen, Mervi, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S, Mbarek, Hamdi, McIntosh, Andrew M, McQueen, Matthew B, Meyers, Jacquelyn L, Milaneschi, Yuri, Palviainen, Teemu, Pearson, John F, Peterson, Roseann E, Ripatti, Samuli, Ryu, Euijung, Saccone, Nancy L, Salvatore, Jessica E, Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley T, Wedow, Robbee, Wetherill, Leah, Wills, Amanda G, Boardman, Jason D, Chen, Danfeng, Choi, Doo-Sup, Copeland, William E, Culverhouse, Robert C, Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W, Elson, Sarah L, Frye, Mark A, Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T, Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D, Nurnberger, John I, Palotie, Aarno, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D, Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A, Soyka, Michael, Treutlein, Jens, Witt, Stephanie, and Wodarz, Norbert

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Alcoholism, Alcohol Use and Health, Neurosciences, Brain Disorders, Substance Misuse, Mental Health, Genetics, Behavioral and Social Science, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Mental health, Good Health and Well Being, Alcoholism, Alleles, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Mental Disorders, Phenotype, Polymorphism, Single Nucleotide, 23andMe Research Team, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case-control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10-13) and African ancestries (rs2066702; P = 2.2 × 10-9). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit-hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Published
2018

6. Colocalization analysis of pancreas eQTLs with risk loci from alcoholic and novel non-alcoholic chronic pancreatitis GWAS suggests potential disease causing mechanisms

Author

Schmidt, Andreas W., Kühnapfel, Andreas, Kirsten, Holger, Grallert, Harald, Hellerbrand, Claus, Kiefer, Falk, Mann, Karl, Mueller, Sebastian, Nöthen, Markus M., Peters, Annette, Ridinger, Monika, Frank, Josef, Rietschel, Marcella, Soranzo, Nicole, Soyka, Michael, Wodarz, Norbert, Malerba, Giovanni, Gambaro, Giovanni, Gieger, Christian, Scholz, Markus, Krug, Sebastian, Michl, Patrick, Ewers, Maren, Witt, Heiko, Laumen, Helmut, and Rosendahl, Jonas

Published
2022
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8. Reductions in World Health Organization Risk Drinking Level Are Associated With Reductions in Alcohol Use Disorder Diagnosis and Criteria: Evidence From an Alcohol Pharmacotherapy Trial.

Author

Richards, Dylan K., Tuchman, Felicia R., Hallgren, Kevin A., Kranzler, Henry R., Aubin, Henri-Jean, O'Malley, Stephanie S., Mann, Karl, Aldridge, Arnie, Anton, Raymond F., and Witkiewitz, Katie

Abstract

Objectives: This study aimed to evaluate the validity of World Health Organization (WHO) risk drinking level reductions as meaningful endpoints for clinical practice and research. This study examined whether such reductions were associated with a lower likelihood of a current alcohol use disorder (AUD) diagnosis and fewer AUD criteria. Methods: We conducted a secondary data analysis to address these objectives using data from a multisite randomized controlled trial of gabapentin enacarbil extended release in treating moderate to severe AUD among adults (N = 346). Participants received gabapentin enacarbil extended release or placebo for 6 months. The timeline follow-back was used to assess WHO risk drinking level reductions, and the Mini-International Neuropsychiatric Interview was used to assess Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria at baseline (past year) and end of treatment (past month). Results: Most participants (80.1%) achieved at least a 1-level reduction in the WHO risk drinking levels from baseline to end of treatment, and nearly half of participants (49.8%) achieved at least a 2-level reduction. At least a 1-level reduction or at least a 2-level reduction in WHO risk drinking level predicted lower odds of an active AUD diagnosis (1-level: odds ratio, 0.74 [95% confidence interval (CI), 0.66–0.84]; 2-level: odds ratio, 0.71 [95% CI, 0.64–0.79]) and fewer AUD criteria (1-level: B, −1.66 [95% CI, −2.35 to −0.98]; 2-level: B, −1.76 [95% CI, −2.31 to −1.21]) at end of treatment. Conclusions: World Health Organization risk drinking level reductions correlate with Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) AUD diagnosis and criteria, providing further evidence for their use as endpoints in alcohol intervention trials, which has potential implications for broadening the base of AUD treatment. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Genetic contributions to alcohol use disorder treatment outcomes: a genome-wide pharmacogenomics study

Author

Biernacka, Joanna M., Coombes, Brandon J., Batzler, Anthony, Ho, Ada Man-Choi, Geske, Jennifer R., Frank, Josef, Hodgkinson, Colin, Skime, Michelle, Colby, Colin, Zillich, Lea, Pozsonyiova, Sofia, Ho, Ming-Fen, Kiefer, Falk, Rietschel, Marcella, Weinshilboum, Richard, O’Malley, Stephanie S., Mann, Karl, Anton, Ray, Goldman, David, and Karpyak, Victor M.

Published
2021
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12. Substance Use Initiation, Particularly Alcohol, in Drug-Naive Adolescents: Possible Predictors and Consequences From a Large Cohort Naturalistic Study

Author

Rapp, Michael, Artiges, Eric, Schneider, Sophia, Paus, Tomas, Barbot, Alexis, Barker, Gareth, Bokde, Arun, Vetter, Nora, Büchel, Christian, Cattrell, Anna, Constant, Patrick, Gowland, Penny, Crombag, Hans, Dalley, Jeffrey, Decideur, Benjamin, Spranger, Tade, Ripley, Tamzin, Heym, Nadja, Flor, Herta, Sommer, Wolfgang, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Spanagel, Rainer, Kaviani, Mehri, Heinrichs, Bert, Andreas Heinz, Subramaniam, Naresh, Jia, Tianye, Ihlenfeld, Albrecht, Ireland, James, Ittermann, Bernd, Conrod, Patricia, Banaschewski, Tobias, Jones, Jennifer, Klaassen, Arno, Lalanne, Christophe, Lanzerath, Dirk, Lawrence, Claire, Lemaitre, Hervé, Desrivieres, Sylvane, Mallik, Catherine, Mann, Karl, Mar, Adam, Martinez-Medina, Lourdes, Martinot, Jean-Luc, Mennigen, Eva, Mesquita de Carvahlo, Fabiana, Schwartz, Yannick, Bruehl, Ruediger, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Lathrop, Mark, Robbins, Trevor, Pausova, Zdenka, Pentilla, Jani, Biondo, Francesca, Poline, Jean-Baptiste, Poustka, Luise, Millenet, Sabina, Smolka, Michael, Fröhner, Juliane, Struve, Maren, Williams, Steve, Hübner, Thomas, Bromberg, Uli, Aydin, Semiha, Rogers, John, Romanowski, Alexander, Schmäl, Christine, Schmidt, Dirk, Ripke, Stephan, Arroyo, Mercedes, Schubert, Florian, Pena-Oliver, Yolanda, Fauth-Bühler, Mira, Mignon, Xavier, Whelan, Robert, Speiser, Claudia, Fadai, Tahmine, Stephens, Dai, Ströhle, Andreas, Paillere, Marie-Laure, Strache, Nicole, Theobald, David, Jurk, Sarah, Vulser, Helene, Miranda, Ruben, Yacubilin, Juliana, Frouin, Vincent, Genauck, Alexander, Parchetka, Caroline, Gemmeke, Isabel, Kruschwitz, Johann, WeiB, Katharina, Walter, Henrik, Feng, Jianfeng, Papadopoulos, Dimitri, Filippi, Irina, Ing, Alex, Ruggeri, Barbara, Xu, Bing, Macare, Christine, Chu, Congying, Hanratty, Eanna, Burke Quinlan, Erin, Robert, Gabriel, Schumann, Gunter, Yu, Tao, Ziesch, Veronika, Stedman, Alicia, Ivanov, Iliyan, Parvaz, Muhammad A., Velthorst, Eva, Shaik, Riaz B., Sandin, Sven, Gan, Gabriela, Spechler, Philip, Albaugh, Matthew D., Chaarani, Bader, Mackey, Scott, Bokde, Arun L.W., Quinlan, Erin Burke, Desrivières, Sylvane, Grigis, Antoine, Heinz, Andreas, Paillère Martinot, Marie-Laure, Lemaitre, Herve, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Hohmann, Sarah, Fröhner, Juliane H., and Smolka, Michael N.

Published
2021
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13. A large-scale genome-wide association study meta-analysis of cannabis use disorder

Author

Walters, Raymond, Polimanti, Renato, Johnson, Emma, McClintick, Jeanette, Hatoum, Alexander, He, June, Wendt, Frank, Zhou, Hang, Adams, Mark, Adkins, Amy, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna, Bigdeli, Tim, Chen, Li-Shiun, Clarke, Toni-Kim, Chou, Yi-Ling, Degenhardt, Franziska, Docherty, Anna, Edwards, Alexis, Fontanillas, Pierre, Foo, Jerome, Fox, Louis, Frank, Josef, Giegling, Ina, Gordon, Scott, Hack, Laura, Hartmann, Annette, Hartz, Sarah, Heilmann-Heimbach, Stefanie, Herms, Stefan, Hodgkinson, Colin, Hoffman, Per, Hottenga, Jouke, Kennedy, Martin, Alanne-Kinnunen, Mervi, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion, Mbarek, Hamdi, McIntosh, Andrew, McQueen, Matthew, Meyers, Jacquelyn, Milaneschi, Yuri, Palviainen, Teemu, Pearson, John, Peterson, Roseann, Ripatti, Samuli, Ryu, Euijung, Saccone, Nancy, Salvatore, Jessica, Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley, Wedow, Robbee, Wetherill, Leah, Wills, Amanda, Boardman, Jason, Chen, Danfeng, Choi, Doo-Sup, Copeland, William, Culverhouse, Robert, Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin, Elson, Sarah, Frye, Mark, Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael, Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison, Nurnberger, John, Palotie, Aarno, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen, Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc, Soyka, Michael, Treutlein, Jens, Witt, Stephanie, Wodarz, Norbert, Zill, Peter, Adkins, Daniel, Boden, Joseph, Boomsma, Dorret, Bierut, Laura, Brown, Sandra, Bucholz, Kathleen, Cichon, Sven, Costello, E. Jane, de Wit, Harriet, Diazgranados, Nancy, Dick, Danielle, Eriksson, Johan, Farrer, Lindsay, Foroud, Tatiana, Gillespie, Nathan, Goate, Alison, Goldman, David, Grucza, Richard, Hancock, Dana, Harris, Kathleen Mullan, Heath, Andrew, Hesselbrock, Victor, Hewitt, John, Hopfer, Christian, Horwood, John, Iacono, William, Johnson, Eric, Kaprio, Jaakko, Karpyak, Victor, Kendler, Kenneth, Kranzler, Henry, Krauter, Kenneth, Lichtenstein, Paul, Lind, Penelope, McGue, Matt, MacKillop, James, Madden, Pamela, Maes, Hermine, Magnusson, Patrik, Martin, Nicholas, Medland, Sarah, Montgomery, Grant, Nelson, Elliot, Nöthen, Markus, Palmer, Abraham, Pederson, Nancy, Penninx, Brenda, Porjesz, Bernice, Rice, John, Rietschel, Marcella, Riley, Brien, Rose, Richard, Rujescu, Dan, Shen, Pei-Hong, Silberg, Judy, Stallings, Michael, Tarter, Ralph, Vanyukov, Michael, Vrieze, Scott, Wall, Tamara, Whitfield, John, Zhao, Hongyu, Neale, Benjamin, Gelernter, Joel, Edenberg, Howard, Agrawal, Arpana, Johnson, Emma C, Demontis, Ditte, Thorgeirsson, Thorgeir E, Walters, Raymond K, Hatoum, Alexander S, Paul, Sarah E, Wendt, Frank R, Reginsson, Gunnar W, Baranger, David A A, Gudbjartsson, Daniel F, Adkins, Daniel E, Adkins, Amy E, Alexander, Jeffry, Bigdeli, Tim B, Brown, Sandra A, Bucholz, Kathleen K, Bybjerg-Grauholm, Jonas, Corley, Robin P, Dick, Danielle M, Domingue, Benjamin W, Goate, Alison M, Gordon, Scott D, Hack, Laura M, Hancock, Dana B, Hartz, Sarah M, Hickie, Ian B, Hougaard, David M, Lind, Penelope A, McClintick, Jeanette N, McQueen, Matthew B, Meyers, Jacquelyn L, Montgomery, Grant W, Mors, Ole, Mortensen, Preben B, Nordentoft, Merete, Pearson, John F, Peterson, Roseann E, Reynolds, Maureen D, Rice, John P, Runarsdottir, Valgerdur, Saccone, Nancy L, Silberg, Judy L, Tarter, Ralph E, Tyrfingsson, Thorarinn, Wall, Tamara L, Webb, Bradley T, Werge, Thomas, Wright, Margaret J, Zellers, Stephanie, Adams, Mark J, Bierut, Laura J, Boardman, Jason D, Copeland, William E, Farrer, Lindsay A, Foroud, Tatiana M, Gillespie, Nathan A, Grucza, Richard A, Heath, Andrew C, Hewitt, John K, Hopfer, Christian J, Iacono, William G, Johnson, Eric O, Kendler, Kenneth S, Kennedy, Martin A, Kranzler, Henry R, Madden, Pamela A F, Maes, Hermine H, Maher, Brion S, Martin, Nicholas G, McGue, Matthew, McIntosh, Andrew M, Medland, Sarah E, Nelson, Elliot C, Riley, Brien P, Stallings, Michael C, Vanyukov, Michael M, Davis, Lea K, Bogdan, Ryan, Edenberg, Howard J, Stefansson, Kari, and Børglum, Anders D

Published
2020
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15. Reductions in World Health Organization risk drinking level are associated with improvements in sleep problems among individuals with alcohol use disorder.

Author

Garcia, Christian C, Richards, Dylan K, Tuchman, Felicia R, Hallgren, Kevin A, Kranzler, Henry R, Aubin, Henri-Jean, O'Malley, Stephanie S, Mann, Karl, Aldridge, Arnie, Hoffman, Michaela, Anton, Raymond F, and Witkiewitz, Katie

Subjects
PREVENTION of alcoholism, COMPLICATIONS of alcoholism, RISK assessment, PLACEBOS, RESEARCH funding, STATISTICAL sampling, EMPIRICAL research, QUESTIONNAIRES, TREATMENT effectiveness, RANDOMIZED controlled trials, DESCRIPTIVE statistics, HARM reduction, SLEEP, GABAPENTIN, ALCOHOLISM, ALCOHOL drinking, COMPARATIVE studies, CONFIDENCE intervals, SLEEP disorders
Abstract

Aims Among individuals with alcohol use disorder (AUD), sleep disturbances are pervasive and contribute to the etiology and maintenance of AUD. However, despite increased attention toward the relationship between alcohol use and sleep, limited empirical research has systematically examined whether reductions in drinking during treatment for AUD are associated with improvements in sleep problems. Methods We used data from a multisite, randomized, controlled trial that compared 6 months of treatment with gabapentin enacarbil extended-release with placebo for adults with moderate-to-severe AUD (N  = 346). The Timeline Follow-back was used to assess WHO risk drinking level reductions and the Pittsburgh Sleep Quality Index was used to assess sleep quality over the prior month at baseline and the end of treatment. Results Sleep problem scores in the active medication and placebo groups improved equally. Fewer sleep problems were noted among individuals who achieved at least a 1-level reduction (B  = −0.99, 95% confidence interval (CI) [−1.77, −0.20], P  = .014) or at least a 2-level reduction (B  = −0.80, 95% CI [−1.47, −0.14], P  = .018) in WHO risk drinking levels at the end of treatment. Reductions in drinking, with abstainers excluded from the analysis, also predicted fewer sleep problems at the end of treatment (1-level: B  = −1.01, 95% CI [−1.83, −0.20], P  = .015; 2-level: B  = −0.90, 95% CI [−1.59, −0.22], P  = .010). Conclusions Drinking reductions, including those short of abstinence, are associated with improvements in sleep problems during treatment for AUD. Additional assessment of the causal relationships between harm-reduction approaches to AUD and improvements in sleep is warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Addiction Training and Research: Striking Differences between France and Germany.

Author

Brousse, George, Paille, Francois, and Mann, Karl

Subjects
ADDICTIONS, COLLEGE teachers, ALCOHOLISM, MEDICAL education, NARCOTIC laws
Abstract

The article discusses the differences in addiction training and research between France and Germany. France has a more developed infrastructure for addiction training, with 23 university departments and full professorships in addiction medicine. In contrast, Germany has limited addiction training and little exposure to afflicted patients for medical and psychology students. France has integrated addictology into the academic world, with close collaboration between hospitals and universities, while Germany's approach has focused on creating addiction research centers and professorships. The article highlights the unique characteristics of the French system and suggests that it could serve as inspiration for other countries. [Extracted from the article]

Published
2024
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17. Education and Training in Addiction Medicine and Psychology across Europe: A EUFAS Survey.

Author

Bramness, Jørgen G., Leonhardt, Marja, Dom, Geert, Batalla, Albert, Flórez Menéndez, Gerardo, Mann, Karl, Wurst, Friedrich Martin, Wojnar, Marcin, Drummond, Colin, Scafato, Emanuele, Gual, Antoni, Ribeiro, Cristina Maria, Cottencin, Olivier, Frischknecht, Ulrich, and Rolland, Benjamin

Subjects
BEHAVIORAL medicine, ADDICTIONS, MEDICAL specialties & specialists, EUROPEAN integration, SUBSTANCE abuse, DELPHI method
Abstract

Introduction: Training in addiction medicine and addiction psychology is essential to ensure the quality of treatment for patients with substance use disorders. Some earlier research has shown varying training between countries, but no comprehensive study of addiction training across Europe has been performed. The present study by the European Federation for Addiction Societies (EUFAS) aimed to fill this gap. Methods: A Delphi process was used to develop a questionnaire on specialist training in addiction treatment in 24 European countries. The final questionnaire consisted of 14 questions on either addiction medicine or addiction psychology, covering the nature and content of the training and institutional approval, the number of academic professorial positions, and the estimated number of specialists in each country. Results: Information was not received from all countries, but six (Belgium, Denmark, Ireland, Italy, Poland, and Romania) reported no specialized addiction medicine training, while 17 countries did. Seven countries (Belgium, France, Ireland, Italy, Russia, Switzerland, and the Netherlands) reported no specialized addiction psychology training, while 14 countries did. Training content and evaluation methods varied. Approval was given either by governments, universities, or professional societies. Eighteen countries reported having professorships in addiction medicine and 12 in addiction psychology. The number of specialists in addiction medicine or psychology varied considerably across the countries. Discussion: The survey revealed a large heterogeneity in training in addiction medicine and addiction psychology across Europe. Several countries lacked formal training, and where formal training was present, there was a large variation in the length of the training. Harmonization of training, as is currently the case for other medical and psychology specializations, is warranted to ensure optimal treatment for this under-served patient group. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Cannabis-Associated Psychotic-like Experiences Are Mediated by Developmental Changes in the Parahippocampal Gyrus

Author

Rapp, Michael, Artiges, Eric, Schneider, Sophia, Bach, Christine, Paus, Tomas, Barbot, Alexis, Barker, Gareth, Bokde, Arun, Vetter, Nora, Büchel, Christian, Cattrell, Anna, Constant, Patrick, Gowland, Penny, Crombag, Hans, Czech, Katharina, Dalley, Jeffrey, Decideur, Benjamin, Spranger, Tade, Ripley, Tamzin, Heym, Nadja, Flor, Herta, Sommer, Wolfgang, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Spanagel, Rainer, Kaviani, Mehri, Heinrichs, Bert, Heinz, Andreas, Subramaniam, Naresh, Jia, Tianye, Ihlenfeld, Albrecht, Delosis, James Ireland, Ittermann, Bernd, Conrod, Patricia, Banaschewski, Tobias, Jones, Jennifer, Klaassen, Arno, Lalanne, Christophe, Lanzerath, Dirk, Lawrence, Claire, Lemaitre, Hervé, Desrivieres, Sylvane, Mallik, Catherine, Mann, Karl, Mar, Adam, Martinez-Medina, Lourdes, Martinot, Jean-Luc, Mennigen, Eva, de Carvahlo, Fabiana Mesquita, Schwartz, Yannick, Bruehl, Ruediger, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Lathrop, Mark, Robbins, Trevor, Pausova, Zdenka, Pentilla, Jani, Biondo, Francesca, Poline, Jean-Baptiste, Hohmann, Sarah, Poustka, Luise, Millenet, Sabina, Smolka, Michael, Fröhner, Juliane, Struve, Maren, Williams, Steve, Hübner, Thomas, Bromberg, Uli, Aydin, Semiha, Rogers, John, Romanowski, Alexander, Schmäl, Christine, Schmidt, Dirk, Ripke, Stephan, Arroyo, Mercedes, Schubert, Florian, Pena-Oliver, Yolanda, Fauth-Bühler, Mira, Mignon, Xavier, Whelan, Robert, Speiser, Claudia, Fadai, Tahmine, Stephens, Dai, Ströhle, Andreas, Paillere, Marie-Laure, Strache, Nicole, Theobald, David, Jurk, Sarah, Vulser, Helene, Miranda, Ruben, Yacubilin, Juliana, Frouin, Vincent, Genauck, Alexander, Parchetka, Caroline, Gemmeke, Isabel, Kruschwitz, Johann, WeiB, Katharina, Walter, Henrik, Feng, Jianfeng, Papadopoulos, Dimitri, Filippi, Irina, Ing, Alex, Ruggeri, Barbara, Xu, Bing, Macare, Christine, Chu, Congying, Hanratty, Eanna, Quinlan, Erin Burke, Robert, Gabriel, Schumann, Gunter, Yu, Tao, Ziesch, Veronika, Stedman, Alicia, Zhu, Liping, Desrivières, Sylvane, Bi, Yan, Bokde, Arun L.W., Liu, ChuanXin, Ji, Lei, Ren, Decheng, Du, Li, Hou, Binyin, Paillère Martinot, Marie-Laure, Orfanos, Dimitri Papadopoulos, Luo, Qiang, Smolka, Michael N., Vetter, Nora C., Lei, Cai, Fröhner, Juliane H., He, Guang, and He, Lin

Published
2020
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19. Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Author

Schwantes-An, Tae-Hwi, Zhang, Juan, Chen, Li-Shiun, Hartz, Sarah M, Culverhouse, Robert C, Chen, Xiangning, Coon, Hilary, Frank, Josef, Kamens, Helen M, Konte, Bettina, Kovanen, Leena, Latvala, Antti, Legrand, Lisa N, Maher, Brion S, Melroy, Whitney E, Nelson, Elliot C, Reid, Mark W, Robinson, Jason D, Shen, Pei-Hong, Yang, Bao-Zhu, Andrews, Judy A, Aveyard, Paul, Beltcheva, Olga, Brown, Sandra A, Cannon, Dale S, Cichon, Sven, Corley, Robin P, Dahmen, Norbert, Degenhardt, Louisa, Foroud, Tatiana, Gaebel, Wolfgang, Giegling, Ina, Glatt, Stephen J, Grucza, Richard A, Hardin, Jill, Hartmann, Annette M, Heath, Andrew C, Herms, Stefan, Hodgkinson, Colin A, Hoffmann, Per, Hops, Hyman, Huizinga, David, Ising, Marcus, Johnson, Eric O, Johnstone, Elaine, Kaneva, Radka P, Kendler, Kenneth S, Kiefer, Falk, Kranzler, Henry R, Krauter, Ken S, Levran, Orna, Lucae, Susanne, Lynskey, Michael T, Maier, Wolfgang, Mann, Karl, Martin, Nicholas G, Mattheisen, Manuel, Montgomery, Grant W, Müller-Myhsok, Bertram, Murphy, Michael F, Neale, Michael C, Nikolov, Momchil A, Nishita, Denise, Nöthen, Markus M, Nurnberger, John, Partonen, Timo, Pergadia, Michele L, Reynolds, Maureen, Ridinger, Monika, Rose, Richard J, Rouvinen-Lagerström, Noora, Scherbaum, Norbert, Schmäl, Christine, Soyka, Michael, Stallings, Michael C, Steffens, Michael, Treutlein, Jens, Tsuang, Ming, Wall, Tamara L, Wodarz, Norbert, Yuferov, Vadim, Zill, Peter, Bergen, Andrew W, Chen, Jingchun, Cinciripini, Paul M, Edenberg, Howard J, Ehringer, Marissa A, Ferrell, Robert E, Gelernter, Joel, Goldman, David, Hewitt, John K, Hopfer, Christian J, Iacono, William G, Kaprio, Jaakko, Kreek, Mary Jeanne, Kremensky, Ivo M, Madden, Pamela AF, McGue, Matt, Munafò, Marcus R, and Philibert, Robert A

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Tobacco, Tobacco Smoke and Health, Brain Disorders, Drug Abuse (NIDA only), Substance Misuse, Genetics, Mental health, Good Health and Well Being, Adolescent, Adult, Alleles, Case-Control Studies, Child, Cohort Studies, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Male, Polymorphism, Single Nucleotide, Receptors, Opioid, mu, Sample Size, Substance-Related Disorders, White People, Addiction, Substance dependence, OPRM1, Opioid receptor, Single nucleotide polymorphism, Genetic association, Zoology, Neurosciences, Genetics & Heredity, Biomedical and clinical sciences, Health sciences
Abstract

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.

Published
2016

22. Predictors of Abstinence from Heavy Drinking During Treatment in COMBINE and External Validation in PREDICT

Author

Gueorguieva, Ralitza, Wu, Ran, O'Connor, Patrick G, Weisner, Constance, Fucito, Lisa M, Hoffmann, Sabine, Mann, Karl, and O'Malley, Stephanie S

Subjects
Prevention, Alcoholism, Alcohol Use and Health, Neurosciences, Substance Misuse, Good Health and Well Being, Acamprosate, Age Factors, Alcohol Abstinence, Alcohol Deterrents, Alcohol Drinking, Behavior Therapy, Combined Modality Therapy, Controlled Clinical Trials as Topic, Decision Trees, Germany, Goals, Humans, Logistic Models, Middle Aged, Naltrexone, Predictive Value of Tests, Randomized Controlled Trials as Topic, Reproducibility of Results, Taurine, Time Factors, Treatment Outcome, United States, gamma-Glutamyltransferase, Alcohol Dependence, Clinical Trial, Classification Tree, Deterministic Forest, Logistic Regression, Clinical Sciences, Psychology, Substance Abuse
Abstract

BackgroundThe goal of the current study was to use tree-based methods (Zhang and Singer, 2010, Recursive Partitioning and Applications, 2nd ed. Springer, New York) to identify predictors of abstinence from heavy drinking in COMBINE (Anton et al. JAMA 2006; 295:2003), the largest study of pharmacotherapy for alcoholism in the United States to date, and to validate these results in PREDICT (Mann et al. Addict Biol 2012; 18:937), a parallel study conducted in Germany.MethodsWe compared a classification tree constructed according to purely statistical criteria to a tree constructed according to a combination of statistical criteria and clinical considerations for prediction of no heavy drinking during treatment in COMBINE. We considered over 100 baseline predictors. The tree approach was compared to logistic regression. The trees and a deterministic forest identified the most important predictors of no heavy drinking for direct testing in PREDICT.ResultsThe tree built using both clinical and statistical considerations consisted of 4 splits based on consecutive days of abstinence (CDA) prior to randomization, age, family history of alcoholism, and confidence to resist drinking in response to withdrawal and urges. The tree based on statistical considerations with 4 splits also split on CDA and age but also on gamma-glutamyl transferase level and drinking goal. Deterministic forest identified CDA, age, and drinking goal as the most important predictors. Backward elimination logistic regression among the top 18 predictors identified in the deterministic forest analyses identified only age and CDA as significant main effects. Longer CDA and goal of complete abstinence were associated with better outcomes in both data sets.ConclusionsThe most reliable predictors of abstinence from heavy drinking were CDA and drinking goal. Trees provide binary decision rules and straightforward graphical representations for identification of subgroups based on response and may be easier to implement in clinical settings.

Published
2014

24. Low Smoking Exposure, the Adolescent Brain, and the Modulating Role of CHRNA5 Polymorphisms

Author

Mann, Karl, Struve, Maren, Rietschel, Marcella, Spanagel, Rainer, Fauth-Bühler, Mira, Millenet, Sabina, Grimmer, Yvonne, Ivanov, Nikolay, Strache, Nicole, Rapp, Michael, Ströhle, Andreas, Reuter, Jan, Barbot, Alexis, Thyreau, Benjamin, Schwartz, Yannick, Lalanne, Christophe, Bricaud, Zuleima, Briand, Fanny Gollier, Lemaitre, Hervé, Massicotte, Jessica, Vulser, Helene, Pentillä, Jani, Galinowski, André, Jia, Tianye, Werts, Helen, Topper, Lauren, Reed, Laurence, Andrew, Chris, Mallik, Catherine, Ruggeri, Barbara, Nymberg, Charlotte, Smith, Lindsay, Loth, Eva, Havatzias, Stephanie, Stueber, Kerstin, Stringaris, Argyris, Constant, Patrick, Brühl, Ruediger, Ihlenfeld, Albrecht, Walaszek, Bernadeta, Hübner, Thomas, Müller, Kathrin, Ripke, Stephan, Rodehacke, Sarah, Mennigen, Eva, Schmidt, Dirk, Vetter, Nora, Ziesch, Veronika, Jones, Jennifer, Poline, Jean-Baptiste, Fadai, Tahmine, Yacubian, Juliana, Schneider, Sophia, Lawrence, Claire, Newman, Craig, Head, Kay, Heym, Nadja, Pausova, Zdenka, Tahmasebi, Amir, Chaarani, Bader, Kan, Kees-Jan, Mackey, Scott, Spechler, Philip A., Potter, Alexandra, Orr, Catherine, D’Alberto, Nicholas, Hudson, Kelsey E., Banaschewski, Tobias, Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Cattrell, Anna, Conrod, Patricia J., Desrivières, Sylvane, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Martinot, Jean-Luc, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomáš, Poustka, Luise, Smolka, Michael N., Walter, Henrik, Whelan, Robert, Higgins, Stephen T., Schumann, Gunter, Althoff, Robert R., Stein, Elliot A., and Garavan, Hugh

Published
2019
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26. Reductions in WHO risk drinking levels correlate with alcohol craving among individuals with alcohol use disorder.

Author

Tuchman, Felicia R., Hallgren, Kevin A., Richards, Dylan K., Aldridge, Arnie, Anton, Raymond F., Aubin, Henri‐Jean, Kranzler, Henry R., Mann, Karl, O'Malley, Stephanie S., and Witkiewitz, Katie

Subjects
ALCOHOLISM risk factors, ALCOHOLISM treatment, CONFIDENCE intervals, SELF-evaluation, MULTIPLE regression analysis, DESIRE, REGRESSION analysis, RISK assessment, COMPARATIVE studies, ALCOHOL drinking, RESEARCH funding, QUESTIONNAIRES, SCALE analysis (Psychology), DESCRIPTIVE statistics, SENSITIVITY & specificity (Statistics), SECONDARY analysis, ADULTS
Abstract

Background: Abstinence has historically been considered the preferred goal of alcohol use disorder (AUD) treatment. However, most individuals with AUD do not want to abstain and many are able to reduce their drinking successfully. Craving is often a target of pharmacological and behavioral interventions for AUD, and reductions in craving may signal recovery. Whether reductions in drinking during AUD treatment are associated with reductions in craving has not been well examined. Methods: We conducted secondary analyses of data from three AUD clinical trials (N's= 1327, 346, and 200). Drinking reductions from baseline to the end of treatment were measured as changes in World Health Organization (WHO) risk drinking levels; alcohol craving was measured using validated self‐report measures. Regression analyses tested whether drinking reductions were associated with end‐of‐treatment craving reductions; moderation analyses tested whether associations between drinking reduction and end‐of‐treatment craving differed across AUD severity. Results: Reductions of at least 1 or at least 2 WHO risk drinking levels were associated with lower craving (all p's < 0.05). Results were substantively similar after removing abstainers at the end‐of‐treatment. Associations between drinking reductions and craving were generally not moderated by AUD severity. Conclusions: Individuals with WHO risk drinking level reductions reported significantly lower craving, as compared to those who did not achieve meaningful reductions in drinking. The results demonstrate the utility of WHO risk drinking levels as AUD clinical trial endpoints and provide evidence that drinking reductions mitigate craving. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Consensus paper of the WFSBP task force on biological markers: Biological markers for alcoholism

Author

Hashimoto, Eri, Riederer, Peter Franz, Hesselbrock, Victor M, Hesselbrock, Michie N, Mann, Karl, Ukai, Wataru, Sohma, Hitoshi, Thibaut, Florence, Schuckit, Marc A, and Saito, Toshikazu

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Behavioral and Social Science, Substance Misuse, Genetics, Brain Disorders, Alcoholism, Alcohol Use and Health, Neurosciences, 4.1 Discovery and preclinical testing of markers and technologies, Detection, screening and diagnosis, Mental health, Good Health and Well Being, Alcoholism, Biomarkers, Consensus, Humans, alcohol, biochemical markers, abuse, alcohol dependence, alcohol use disorder, Clinical Sciences, Psychiatry, Clinical sciences, Biological psychology
Abstract

ObjectivesThis article presents an overview of the current literature on biological markers for alcoholism, including markers associated with the pharmacological effects of alcohol and markers related to the clinical course and treatment of alcohol-related problems. Many of these studies are well known, while other studies cited are new and still being evaluated.MethodsIn this paper we first describe known biomarkers of alcohol-related disorders, review their features and the problems involved in their use. We then consider future developments on biomarkers and their possible impact on the field.ResultsMore recent findings cited include the work on type 7 adenylcyclase (AC) polymorphism and its lower expression levels in female alcoholics. Neuroimaging studies involving biomarkers have also reported brain volume reductions of gray and white matter, including amygdala and subcortical regions in alcoholic patients, while a high association between the copy number variations (CNVs) in 6q14.1/5q13.2 and alcohol dependence has more recently been identified in genetic studies.ConclusionsIn addition to their possible importance for diagnosis, biomarkers may have utility for predicting prognosis, progression of the disorder, the development of new treatments, and monitoring treatment effects. Although such findings should be verified in independent studies, the search for new biomarkers is continuing. Several potential candidate biomarkers have been found recently in blood, imaging, and genetic studies with encouraging results.

Published
2013

30. Epidemiological Challenges in the Study of Behavioral Addictions: a Call for High Standard Methodologies

Author

Rumpf, Hans-Jürgen, Brandt, Dominique, Demetrovics, Zsolt, Billieux, Joël, Carragher, Natacha, Brand, Matthias, Bowden-Jones, Henrietta, Rahimi-Movaghar, Afarin, Assanangkornchai, Sawitri, Glavak-Tkalic, Renata, Borges, Guilherme, Lee, Hae-Kook, Rehbein, Florian, Fineberg, Naomi A., Mann, Karl, Potenza, Marc N., Stein, Dan J., Higuchi, Susumu, King, Daniel, Saunders, John B., and Poznyak, Vladimir

Published
2019
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34. Change in non-abstinent WHO drinking risk levels and alcohol dependence: a 3 year follow-up study in the US general population

Author

Fertig, Joanne, Isenberg, Keith, McCann, David, Meulien, Didier, Meyer, Roger, O'Brien, Charles, Ryan, Megan, Silverman, Bernard, Trinquet, Francoise, Wong, Conrad, Zakine, Benjamine, Hasin, Deborah S, Wall, Melanie, Witkiewitz, Katie, Kranzler, Henry R, Falk, Daniel, Litten, Raye, Mann, Karl, O'Malley, Stephanie S, Scodes, Jennifer, Robinson, Rebecca L, and Anton, Raymond

Published
2017
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37. Prediction of alcohol drinking in adolescents: Personality-traits, behavior, brain responses, and genetic variations in the context of reward sensitivity

Author

Heinrich, Angela, Müller, Kathrin U., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Conrod, Patricia, Fauth-Bühler, Mira, Papadopoulos, Dimitri, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Martinot, Jean-Luc, Paus, Tomáš, Pausova, Zdenka, Smolka, Michael, Ströhle, Andreas, Rietschel, Marcella, Flor, Herta, Schumann, Gunter, and Nees, Frauke

Published
2016
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41. Subthreshold Depression and Regional Brain Volumes in Young Community Adolescents

Author

Dalley, J., Subramaniam, N., Theobald, D., Bach, C., Fauth-Bühler, M., Millenet, S., Spanagel, R., Albrecht, L., Ivanov, N., Rapp, M., Reuter, J., Strache, N., Ströhle, A., Lalanne, C., Poline, J.B., Schwartz, Y., Thyreau, B., Lathrop, M., Ireland, J., Rogers, J., Bordas, N., Bricaud, Z., Filippi, I., Galinowski, A., Gollier-Briant, F., Massicotte, J., Andrew, C., Cattrell, A., Desrivieres, S., Hall, D., Havatzias, S., Jia, T., Mallik, C., Nymberg, C., Reed, L., Ruggeri, B., Smith, L., Stueber, K., Topper, L., Werts, H., Brühl, R., Ihlenfeld, A., Walaszek, B., Hübner, T., Müller, K., Ripke, S., Rodehacke, S., Mennigen, E., Schmidt, D., Vetter, N., Ziesch, V., Carter, D., Connolly, C., Nugent, S., Jones, J., Whelan, R., Yacubian, J., Schneider, S., Head, K., Heym, N., Newman, C., Tahmasebi, A., Stephens, D., Vulser, Hélène, Lemaitre, Hervé, Artiges, Eric, Miranda, Ruben, Penttilä, Jani, Struve, Maren, Fadai, Tahmine, Kappel, Viola, Grimmer, Yvonne, Goodman, Robert, Stringaris, Argyris, Poustka, Luise, Conrod, Patricia, Frouin, Vincent, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Flor, Herta, Gallinat, Juergen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Loth, Eva, Mann, Karl, Nees, Frauke, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Schumann, Gunter, Martinot, Jean-Luc, and Paillère-Martinot, Marie-Laure

Published
2015
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42. Glutamate concentration in the anterior cingulate cortex in alcohol dependence: association with alcohol withdrawal and exploration of contribution from glutamatergic candidate genes

Author

Streit, Fabian, Treutlein, Jens, Frischknecht, Ulrich, Hermann, Derik, Mann, Karl, Kiefer, Falk, Sack, Markus, Hall, Alisha S.M., Frank, Josef, Witt, Stephanie H., Foo, Jerome C., Degenhardt, Franziska, Heilmann-Heimbach, Stefanie, Nöthen, Markus M., Sommer, Wolfgang H., Spanagel, Rainer, Rietschel, Marcella, and Ende, Gabriele

Published
2018
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44. Correlated gene expression supports synchronous activity in brain networks

Author

IMAGEN consortium, Richiardi, Jonas, Altmann, Andre, Milazzo, Anna-Clare, Chang, Catie, Chakravarty, M. Mallar, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Conrod, Patricia, Fauth-Bühler, Mira, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Lemaître, Hervé, Mann, Karl F., Martinot, Jean-Luc, Nees, Frauke, Paus, Tomáš, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Spanagel, Rainer, Ströhle, Andreas, Schumann, Gunter, Hawrylycz, Mike, Poline, Jean-Baptiste, and Greicius, Michael D.

Published
2015

45. Reply

Author

Bramness, Jørgen G., Henriksen, Beate, Person, Olle, and Mann, Karl

Published
2015

49. Stratified medicine for mental disorders

Author

Schumann, Gunter, Binder, Elisabeth B., Holte, Arne, de Kloet, E. Ronald, Oedegaard, Ketil J., Robbins, Trevor W., Walker-Tilley, Tom R., Bitter, Istvan, Brown, Verity J., Buitelaar, Jan, Ciccocioppo, Roberto, Cools, Roshan, Escera, Carles, Fleischhacker, Wolfgang, Flor, Herta, Frith, Chris D., Heinz, Andreas, Johnsen, Erik, Kirschbaum, Clemens, Klingberg, Torkel, Lesch, Klaus-Peter, Lewis, Shon, Maier, Wolfgang, Mann, Karl, Martinot, Jean-Luc, Meyer-Lindenberg, Andreas, Müller, Christian P., Müller, Walter E., Nutt, David J., Persico, Antonio, Perugi, Giulio, Pessiglione, Mathias, Preuss, Ulrich W., Roiser, Jonathan P., Rossini, Paolo M., Rybakowski, Janusz K., Sandi, Carmen, Stephan, Klaas E., Undurraga, Juan, Vieta, Eduard, van der Wee, Nic, Wykes, Til, Haro, Josep Maria, and Wittchen, Hans Ulrich

Published
2014
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50. Shared genetic etiology between alcohol dependence and major depressive disorder

Author

Foo, Jerome C., Streit, Fabian, Treutlein, Jens, Ripke, Stephan, Witt, Stephanie H., Strohmaier, Jana, Degenhardt, Franziska, Forstner, Andreas J., Hoffmann, Per, Soyka, Michael, Dahmen, Norbert, Scherbaum, Norbert, Wodarz, Norbert, Heilmann-Heimbach, Stefanie, Herms, Stefan, Cichon, Sven, Preuss, Ulrich, Gaebel, Wolfgang, Ridinger, Monika, Hoffmann, Sabine, Schulze, Thomas G., Maier, Wolfgang, Zill, Peter, Müller-Myhsok, Bertram, Ising, Marcus, Lucae, Susanne, Nöthen, Markus M., Mann, Karl, Kiefer, Falk, Rietschel, Marcella, and Frank, Josef

Published
2018
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