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51. Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis.

Author

Ruggeri, Barbara, Nymberg, Charlotte, Vuoksimaa, Eero, Lourdusamy, Anbarasu, Wong, Cybele P, Carvalho, Fabiana M, Jia, Tianye, Cattrell, Anna, Macare, Christine, Banaschewski, Tobias, Barker, Gareth J, Bokde, Arun L W, Bromberg, Uli, Büchel, Christian, Conrod, Patricia J, Fauth-Bühler, Mira, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, and Garavan, Hugh

Abstract

Objective: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior.Method: The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents.Results: Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task.Conclusions: Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype. [ABSTRACT FROM AUTHOR]

Published
2015
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52. Neural and cognitive correlates of the common and specific variance across externalizing problems in young adolescence.

Author

Castellanos-Ryan, Natalie, Struve, Maren, Whelan, Robert, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Bromberg, Uli, Büchel, Christian, Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Lawrence, Claire, Martinot, Jean-Luc, Nees, Frauke, Paus, Tomas, Pausova, Zdenka, and Rietschel, Marcella

Abstract

Longitudinal and family-based research suggests that conduct disorder, substance misuse, and ADHD involve both unique forms of dysfunction as well as more specific dysfunctions unique to each condition. Using direct measures of brain function, this study also found evidence in both unique and disorder-specific perturbations. [ABSTRACT FROM AUTHOR]

Published
2014
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53. Sex Differences in COMT Polymorphism Effects on Prefrontal Inhibitory Control in Adolescence.

Author

White, Thomas P, Loth, Eva, Rubia, Katya, Krabbendam, Lydia, Whelan, Robert, Banaschewski, Tobias, Barker, Gareth J, Bokde, Arun LW, Büchel, Christian, Conrod, Patricia, Fauth-Bühler, Mira, Flor, Herta, Frouin, Vincent, Gallinat, Jürgen, Garavan, Hugh, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, and Mann, Karl

Subjects
CATECHOLAMINES, OXYGENATORS, GENETIC polymorphisms, PREFRONTAL cortex, TEENAGERS, SEX differences (Biology)
Abstract

Catecholamine-0-methyl-transferase (COMT) gene variation effects on prefrontal blood oxygenation-level-dependent (BOLD) activation are robust; however, despite observations that COMT is estrogenically catabolized, sex differences in its prefrontal repercussions remain unclear. Here, in a large sample of healthy adolescents stratified by sex and Val158Met genotype (n=1133), we examine BOLD responses during performance of the stop-signal task in right-hemispheric prefrontal regions fundamental to inhibitory control. A significant sex-by-genotype interaction was observed in pre-SMA during successful-inhibition trials and in both pre-SMA and inferior frontal cortex during failed-inhibition trials with Val homozygotes displaying elevated activation compared with other genotypes in males but not in females. BOLD activation in the same regions significantly mediated the relationship between COMT genotype and inhibitory proficiency as indexed by stop-signal reaction time in males alone. These sexually dimorphic effects of COMT on inhibitory brain activation have important implications for our understanding of the contrasting patterns of prefrontally governed psychopathology observed in males and females. [ABSTRACT FROM AUTHOR]

Published
2014
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54. Adolescent impulsivity phenotypes characterized by distinct brain networks.

Author

Whelan, Robert, Conrod, Patricia J, Poline, Jean-Baptiste, Lourdusamy, Anbarasu, Banaschewski, Tobias, Barker, Gareth J, Bellgrove, Mark A, Büchel, Christian, Byrne, Mark, Cummins, Tarrant D R, Fauth-Bühler, Mira, Flor, Herta, Gallinat, Jürgen, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Martinot, Jean-Luc, Lalor, Edmund C, Lathrop, Mark, and Loth, Eva

Subjects
IMPULSE (Psychology), ADOLESCENCE, BEHAVIOR disorders in children, ATTENTION-deficit hyperactivity disorder, SUBSTANCE abuse, NORADRENALINE, PHENOTYPES
Abstract

The impulsive behavior that is often characteristic of adolescence may reflect underlying neurodevelopmental processes. Moreover, impulsivity is a multi-dimensional construct, and it is plausible that distinct brain networks contribute to its different cognitive, clinical and behavioral aspects. As these networks have not yet been described, we identified distinct cortical and subcortical networks underlying successful inhibitions and inhibition failures in a large sample (n = 1,896) of 14-year-old adolescents. Different networks were associated with drug use (n = 1,593) and attention-deficit hyperactivity disorder symptoms (n = 342). Hypofunctioning of a specific orbitofrontal cortical network was associated with likelihood of initiating drug use in early adolescence. Right inferior frontal activity was related to the speed of the inhibition process (n = 826) and use of illegal substances and associated with genetic variation in a norepinephrine transporter gene (n = 819). Our results indicate that both neural endophenotypes and genetic variation give rise to the various manifestations of impulsive behavior. [ABSTRACT FROM AUTHOR]

Published
2012
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55. Neuropsychosocial profiles of current and future adolescent alcohol misusers

Author

Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, Ziesch, Veronika, Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, and Ziesch, Veronika

Abstract

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

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56. Structural brain correlates of adolescent resilience

Author

Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, and Garavan, Hugh

Abstract

Background Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity.

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57. 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, Nees, Frauke, 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

Abstract

Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age = 14.37) and again later (mean age = 16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

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58. Neuropsychosocial profiles of current and future adolescent alcohol misusers

Author

Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, Ziesch, Veronika, Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, and Ziesch, Veronika

Abstract

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

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59. 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, Nees, Frauke, 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

Abstract

Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age = 14.37) and again later (mean age = 16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

Full Text
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60. Structural brain correlates of adolescent resilience

Author

Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, and Garavan, Hugh

Abstract

Background Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity.

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61. Neuropsychosocial profiles of current and future adolescent alcohol misusers

Author

Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, Ziesch, Veronika, Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, and Ziesch, Veronika

Abstract

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

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62. Structural brain correlates of adolescent resilience

Author

Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, and Garavan, Hugh

Abstract

Background Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity.

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63. 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, Nees, Frauke, 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

Abstract

Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age = 14.37) and again later (mean age = 16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

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64. Neuropsychosocial profiles of current and future adolescent alcohol misusers

Author

Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, Ziesch, Veronika, Whelan, Robert, Watts, Richard, Orr, Catherine A., Althoff, Robert R., Artiges, Eric, Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L. W., Büchel, Christian, Carvalho, Fabiana M., Conrod, Patricia J., Flor, Herta, Fauth-Bühler, Mira, Frouin, Vincent, Gallinat, Juergen, Gan, Gabriela, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Lawrence, Claire, Mann, Karl, Martinot, Jean-Luc, Nees, Frauke, Ortiz, Nick, Paillère-Martinot, Marie-Laure, Paus, Tomas, Pausova, Zdenka, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Albrecht, Lisa, Arroyo, Mercedes, Aydin, Semiha, Bach, Christine, Barbot, Alexis, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Cattrell, Anna, Czech, Katharina, Dalley, Jeffrey, Desrivieres, Sylvane, Fadai, Tahmine, Fuchs, Birgit, Gollier Briand, Fanny, Head, Kay, Heinrichs, Bert, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ivanov, Nikolay, Jia, Tianye, Jones, Jennifer, Kepa, Agnes, Lanzerath, Dirk, Lathrop, Mark, Lemaitre, Hervé, Lüdemann, Katharina, Martinez-Medina, Lourdes, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nymberg, Charlotte, Pentilla, Jani, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Ripke, Stephan, Rodehacke, Sarah, Rogers, John, Romanowski, Alexander, Ruggeri, Barbara, Schmäl, Christine, Schmidt, Dirk, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Sommer, Wolfgang, Spanagel, Rainer, Stacey, David, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Struve, Maren, Tahmasebi, Amir, Topper, Lauren, Vulser, Helene, Walaszek, Bernadeta, Werts, Helen, Williams, Steve, Peng Wong, C., Yacubian, Juliana, and Ziesch, Veronika

Abstract

A comprehensive account of the causes of alcohol misuse must accommodate individual differences in biology, psychology and environment, and must disentangle cause and effect. Animal models1 can demonstrate the effects of neurotoxic substances; however, they provide limited insight into the psycho-social and higher cognitive factors involved in the initiation of substance use and progression to misuse. One can search for pre-existing risk factors by testing for endophenotypic biomarkers2 in non-using relatives; however, these relatives may have personality or neural resilience factors that protect them from developing dependence3. A longitudinal study has potential to identify predictors of adolescent substance misuse, particularly if it can incorporate a wide range of potential causal factors, both proximal and distal, and their influence on numerous social, psychological and biological mechanisms4. Here we apply machine learning to a wide range of data from a large sample of adolescents (n = 692) to generate models of current and future adolescent alcohol misuse that incorporate brain structure and function, individual personality and cognitive differences, environmental factors (including gestational cigarette and alcohol exposure), life experiences, and candidate genes. These models were accurate and generalized to novel data, and point to life experiences, neurobiological differences and personality as important antecedents of binge drinking. By identifying the vulnerability factors underlying individual differences in alcohol misuse, these models shed light on the aetiology of alcohol misuse and suggest targets for prevention.

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65. Structural brain correlates of adolescent resilience

Author

Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, Garavan, Hugh, Burt, Keith B., Whelan, Robert, Conrod, Patricia J., Banaschewski, Tobias, Barker, Gareth J., Bokde, Arun L.W., Bromberg, Uli, Büchel, Christian, Fauth-Bühler, Mira, Flor, Herta, Galinowski, André, Gallinat, Juergen, Gowland, Penny, Heinz, Andreas, Ittermann, Bernd, Mann, Karl, Nees, Frauke, Papadopoulos-Orfanos, Dimitri, Paus, Tomas, Pausova, Zdenka, Poustka, Luise, Rietschel, Marcella, Robbins, Trevor W., Smolka, Michael N., Ströhle, Andreas, Schumann, Gunter, and Garavan, Hugh

Abstract

Background Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification. Methods 1,870 European adolescents (Mage = 14.56 years, SDage = 0.44 years, 51.5% female) underwent MRI scanning and completed behavioral and psychological measures of stressful life events, academic competence, social competence, rule-abiding conduct, personality, and alcohol use. Results The interaction of competence and adversity identified two regions centered on the right middle and superior frontal gyri; grey matter volumes in these regions were larger in adolescents experiencing adversity who showed positive adaptation. Differences in these regions among competence/adversity subgroups were maintained after controlling for several covariates and were robust to alternative operationalization decisions for key constructs. Conclusions We demonstrate structural brain correlates of adolescent resilience, and suggest that right prefrontal structures are implicated in adaptive functioning for youth who have experienced adversity.

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66. 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, Nees, Frauke, 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

Abstract

Adolescence is a time that can set the course of alcohol abuse later in life. Sensitivity to reward on multiple levels is a major factor in this development. We examined 736 adolescents from the IMAGEN longitudinal study for alcohol drinking during early (mean age = 14.37) and again later (mean age = 16.45) adolescence. Conducting structural equation modeling we evaluated the contribution of reward-related personality traits, behavior, brain responses and candidate genes. Personality seems to be most important in explaining alcohol drinking in early adolescence. However, genetic variations in ANKK1 (rs1800497) and HOMER1 (rs7713917) play an equal role in predicting alcohol drinking two years later and are most important in predicting the increase in alcohol consumption. We hypothesize that the initiation of alcohol use may be driven more strongly by personality while the transition to increased alcohol use is more genetically influenced.

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67. Correlated gene expression supports synchronous activity in brain networks.

Author

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, and Mann, Karl F.

Subjects
*GENE expression, *NEURAL circuitry, *BRAIN research, *FUNCTIONAL magnetic resonance imaging, *ION channels, *GENETIC polymorphisms, *LABORATORY mice, *GENES
Abstract

During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function. [ABSTRACT FROM AUTHOR]

Published
2015
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