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1. Towards precise brain stimulation:Is electric field simulation related to neuromodulation?

Author

Antonenko, Daria, Thielscher, Axel, Saturnino, Guilherme Bicalho, Aydin, Semiha, Ittermann, Bernd, Grittner, Ulrike, Flöel, Agnes, Antonenko, Daria, Thielscher, Axel, Saturnino, Guilherme Bicalho, Aydin, Semiha, Ittermann, Bernd, Grittner, Ulrike, and Flöel, Agnes

Abstract

Background: Recent research on neural and behavioral consequences of transcranial direct current stimulation (tDCS) has highlighted the impact of individual factors, such as brain anatomy which determines current field distribution and may thus significantly impact stimulation effects. Computational modeling approaches may significantly advance our understanding of such factors, but the association of simulation-based tDCS-induced fields and neurophysiological outcomes has not been investigated. Objectives: To provide empirical evidence for the relationship between tDCS-induced neurophysiological outcomes and individually induced electric fields. Methods: We applied tDCS during eyes-closed resting-state functional resonance imaging (rsfMRI) and assessed pre-post magnetic resonance spectroscopy (MRS) in 24 participants. We aimed to quantify effects of 15-min tDCS using the “classical” left SM1-right supraorbital area montage on sensorimotor network (SMN) strength and gamma-aminobutyric acid (GABA) and glutamate concentrations, implementing a cross-over counterbalanced design with three stimulation conditions. Additional structural anatomical MRI sequences and recordings of individual electrode configurations allowed individual electric field simulations based on realistic head models of all participants for both conditions. Results: On a neurophysiological level, we observed the expected reduction of GABA concentrations and increase in SMN strength, both during anodal and cathodal compared to sham tDCS, replicating previous results. The magnitudes of neurophysiological modulations induced by tDCS were significantly associated with simulation-based electric field strengths within the targeted left precentral gyrus. Conclusion: Our findings corroborate previous reports on tDCS-induced neurophysiological modulations and further advance the understanding of underlying mechanisms by providing first empirical evidence for the association of the injected electric field a

Published
2019

2. 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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3. 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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4. 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.

Full Text
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5. 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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