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51. Personality and peer groups in adolescence: Reciprocal associations and shared genetic and environmental influences.

Author

Clark, D. Angus, Durbin, C. Emily, Heitzeg, Mary M., Iacono, William G., McGue, Matt, and Hicks, Brian M.

Subjects
ADOLESCENCE, PEERS, BEHAVIOR genetics, HERITABILITY, PERSONALITY
Abstract

Objective: Peer groups represent a critical developmental context in adolescence, and there are many well‐documented associations between personality and peer behavior at this age. However, the precise nature and direction of these associations are difficult to determine as youth both select into, and are influenced by, their peers. Method: We thus examined the phenotypic, genetic, and environmental links between antisocial and prosocial peer characteristics and several personality traits from middle childhood to late adolescence (ages 11, 14, and 17 years) in a longitudinal twin sample (N = 3762) using teacher ratings of personality and self‐reports of peer characteristics. Results: Less adaptive trait profiles (i.e., high negative emotionality, low conscientiousness, and low agreeableness) were associated with more antisocial and fewer prosocial peer characteristics across time. Associations between personality traits related to emotionality (negative emotionality and extraversion) and peer behavior were largely attributable to shared genetic influences, while associations between personality traits related to behavioral control (conscientiousness and agreeableness) and peer behavior were due to overlapping genetic and shared environmental influences. Conclusions: Overall, results suggest a set of environmental presses that push youth toward both behavioral undercontrol and antisocial peer affiliations, making the identification of such influences and their relative importance a critical avenue of future work. [ABSTRACT FROM AUTHOR]

Published
2023
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53. Genetic imaging consortium for addiction medicine

Author

Mackey, Scott, primary, Kan, Kees-Jan, additional, Chaarani, Bader, additional, Alia-Klein, Nelly, additional, Batalla, Albert, additional, Brooks, Samantha, additional, Cousijn, Janna, additional, Dagher, Alain, additional, de Ruiter, Michiel, additional, Desrivieres, Sylvane, additional, Feldstein Ewing, Sarah W., additional, Goldstein, Rita Z., additional, Goudriaan, Anna E., additional, Heitzeg, Mary M., additional, Hutchison, Kent, additional, Li, Chiang-Shan R., additional, London, Edythe D., additional, Lorenzetti, Valentina, additional, Luijten, Maartje, additional, Martin-Santos, Rocio, additional, Morales, Angelica M., additional, Paulus, Martin P., additional, Paus, Tomas, additional, Pearlson, Godfrey, additional, Schluter, Renée, additional, Momenan, Reza, additional, Schmaal, Lianne, additional, Schumann, Gunter, additional, Sinha, Rajita, additional, Sjoerds, Zsuzsika, additional, Stein, Dan J., additional, Stein, Elliot A., additional, Solowij, Nadia, additional, Tapert, Susan, additional, Uhlmann, Anne, additional, Veltman, Dick, additional, van Holst, Ruth, additional, Walter, Henrik, additional, Wright, Margaret J., additional, Yucel, Murat, additional, Yurgelun-Todd, Deborah, additional, Hibar, Derrek P., additional, Jahanshad, Neda, additional, Thompson, Paul M., additional, Glahn, David C., additional, Garavan, Hugh, additional, and Conrod, Patricia, additional

Published
2016
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57. Charting brain growth and aging at high spatial precision

Author

Rutherford, Saige, primary, Fraza, Charlotte, additional, Dinga, Richard, additional, Kia, Seyed Mostafa, additional, Wolfers, Thomas, additional, Zabihi, Mariam, additional, Berthet, Pierre, additional, Worker, Amanda, additional, Verdi, Serena, additional, Andrews, Derek, additional, Han, Laura KM, additional, Bayer, Johanna MM, additional, Dazzan, Paola, additional, McGuire, Phillip, additional, Mocking, Roel T, additional, Schene, Aart, additional, Sripada, Chandra, additional, Tso, Ivy F, additional, Duval, Elizabeth R, additional, Chang, Soo-Eun, additional, Penninx, Brenda WJH, additional, Heitzeg, Mary M, additional, Burt, S Alexandra, additional, Hyde, Luke W, additional, Amaral, David, additional, Wu Nordahl, Christine, additional, Andreasssen, Ole A, additional, Westlye, Lars T, additional, Zahn, Roland, additional, Ruhe, Henricus G, additional, Beckmann, Christian, additional, and Marquand, Andre F, additional

Published
2022
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58. Author response: Charting brain growth and aging at high spatial precision

Author

Rutherford, Saige, primary, Fraza, Charlotte, additional, Dinga, Richard, additional, Kia, Seyed Mostafa, additional, Wolfers, Thomas, additional, Zabihi, Mariam, additional, Berthet, Pierre, additional, Worker, Amanda, additional, Verdi, Serena, additional, Andrews, Derek, additional, Han, Laura KM, additional, Bayer, Johanna MM, additional, Dazzan, Paola, additional, McGuire, Phillip, additional, Mocking, Roel T, additional, Schene, Aart, additional, Sripada, Chandra, additional, Tso, Ivy F, additional, Duval, Elizabeth R, additional, Chang, Soo-Eun, additional, Penninx, Brenda WJH, additional, Heitzeg, Mary M, additional, Burt, S Alexandra, additional, Hyde, Luke W, additional, Amaral, David, additional, Wu Nordahl, Christine, additional, Andreasssen, Ole A, additional, Westlye, Lars T, additional, Zahn, Roland, additional, Ruhe, Henricus G, additional, Beckmann, Christian, additional, and Marquand, Andre F, additional

Published
2022
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62. Differentiated nomological networks of internalizing, externalizing, and the general factor of psychopathology (' p factor') in emerging adolescence in the ABCD study.

Author

Brislin, Sarah J., Martz, Meghan E., Joshi, Sonalee, Duval, Elizabeth R., Gard, Arianna, Clark, D. Angus, Hyde, Luke W., Hicks, Brian M., Taxali, Aman, Angstadt, Mike, Rutherford, Saige, Heitzeg, Mary M., and Sripada, Chandra

Subjects
RESEARCH, SCHOOL environment, SUBSTANCE abuse, IMPULSIVE personality, FAMILIES, COGNITION, TASK performance, CHILD behavior, FEAR, BEHAVIOR disorders in children, CONCEPTUAL structures, CHILD Behavior Checklist, PATHOLOGICAL psychology, TEMPERAMENT, TEACHERS, SOCIAL skills, PARENTS, PSYCHOLOGICAL stress, PSYCHOSOCIAL factors
Abstract

Background: Structural models of psychopathology consistently identify internalizing (INT) and externalizing (EXT) specific factors as well as a superordinate factor that captures their shared variance, the p factor. Questions remain, however, about the meaning of these data-driven dimensions and the interpretability and distinguishability of the larger nomological networks in which they are embedded. Methods: The sample consisted of 10 645 youth aged 9–10 years participating in the multisite Adolescent Brain and Cognitive Development (ABCD) Study. p , INT, and EXT were modeled using the parent-rated Child Behavior Checklist (CBCL). Patterns of associations were examined with variables drawn from diverse domains including demographics, psychopathology, temperament, family history of substance use and psychopathology, school and family environment, and cognitive ability, using instruments based on youth-, parent-, and teacher-report, and behavioral task performance. Results: p exhibited a broad pattern of statistically significant associations with risk variables across all domains assessed, including temperament, neurocognition, and social adversity. The specific factors exhibited more domain-specific patterns of associations, with INT exhibiting greater fear/distress and EXT exhibiting greater impulsivity. Conclusions: In this largest study of hierarchical models of psychopathology to date, we found that p , INT, and EXT exhibit well-differentiated nomological networks that are interpretable in terms of neurocognition, impulsivity, fear/distress, and social adversity. These networks were, in contrast, obscured when relying on the a priori Internalizing and Externalizing dimensions of the CBCL scales. Our findings add to the evidence for the validity of p , INT, and EXT as theoretically and empirically meaningful broad psychopathology liabilities. [ABSTRACT FROM AUTHOR]

Published
2022
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68. Differential Item Functioning in Reports of Delinquent Behavior between Black and White Youth: Evidence of Measurement Bias in Self-Reports of Arrest in the Adolescent Brain Cognitive Development (ABCD) Study

Author

Brislin, Sarah J, primary, Clark, D. Angus, additional, Clark, Duncan, additional, Durbin, C. Emily, additional, Parr, Ashley C., additional, Ahonen, Lia, additional, Anderson-Carpenter, Kaston D, additional, Heitzeg, Mary M., additional, Luna, Beatriz, additional, Sripada, Chandra, additional, Zucker, Robert A., additional, and Hicks, Brian M., additional

Published
2021
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69. Nucleus Accumbens Response to Reward among Children with a Family History of Alcohol Use Problems: Convergent Findings from the ABCD Study ® and Michigan Longitudinal Study.

Author

Martz, Meghan E., Hardee, Jillian E., Cope, Lora M., McCurry, Katherine L., Soules, Mary, Zucker, Robert A., and Heitzeg, Mary M.

Subjects
ALCOHOLISM, ALCOHOL drinking, NUCLEUS accumbens, REWARD (Psychology), FAMILY history (Sociology)
Abstract

Having a family history of alcohol use problems (FH+) conveys risk for alcohol use in offspring. Reward-related brain functioning may play a role in this vulnerability. The present study investigated brain function in the nucleus accumbens (NAcc) associated with the anticipation of reward in youth with two biological parents with alcohol use problems (FH+2), one biological parent with alcohol use problems (FH+1), and no biological parents with alcohol use problems (FH-). Participants were from the large, national Adolescent Brain Cognitive Development (ABCD) Study (mean age: 9.93; 48% female; FH+2 n = 223, FH+1 n = 1447, FH- n = 9690) and the Michigan Longitudinal Study (MLS), consisting of community-recruited families with high rates of alcohol use disorder (mean age: 10.54; 39.3% female; FH+2 n = 40, FH+1 n = 51, FH- n = 40). Reward anticipation was measured by the monetary incentive delay task. Regression models were used to assess associations between FH status and the anticipation of large rewards in right and left NAcc regions of interest. In both studies, FH+2 youth showed blunted anticipatory reward responding in the right NAcc compared to FH+1 youth. In the MLS, FH+2 youth also had blunted anticipatory reward responding in the right NAcc compared to the FH- group. Convergent results across two separate samples provide insights into a unique vulnerability of FH+2 youth and suggest that binary FH+ versus FH- categorizations may obscure important differences within FH+ youth. [ABSTRACT FROM AUTHOR]

Published
2022
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71. Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study

Author

Herting, Megan M., primary, Uban, Kristina A., additional, Gonzalez, Marybel Robledo, additional, Baker, Fiona C., additional, Kan, Eric C., additional, Thompson, Wesley K., additional, Granger, Douglas A., additional, Albaugh, Matthew D., additional, Anokhin, Andrey P., additional, Bagot, Kara S., additional, Banich, Marie T., additional, Barch, Deanna M., additional, Baskin-Sommers, Arielle, additional, Breslin, Florence J., additional, Casey, B. J., additional, Chaarani, Bader, additional, Chang, Linda, additional, Clark, Duncan B., additional, Cloak, Christine C., additional, Constable, R. Todd, additional, Cottler, Linda B., additional, Dagher, Rada K., additional, Dapretto, Mirella, additional, Dick, Anthony S., additional, Dosenbach, Nico, additional, Dowling, Gayathri J., additional, Dumas, Julie A., additional, Edwards, Sarah, additional, Ernst, Thomas, additional, Fair, Damien A., additional, Feldstein-Ewing, Sarah W., additional, Freedman, Edward G., additional, Fuemmeler, Bernard F., additional, Garavan, Hugh, additional, Gee, Dylan G., additional, Giedd, Jay N., additional, Glaser, Paul E. A., additional, Goldstone, Aimee, additional, Gray, Kevin M., additional, Hawes, Samuel W., additional, Heath, Andrew C., additional, Heitzeg, Mary M., additional, Hewitt, John K., additional, Heyser, Charles J., additional, Hoffman, Elizabeth A., additional, Huber, Rebekah S., additional, Huestis, Marilyn A., additional, Hyde, Luke W., additional, Infante, M. Alejandra, additional, Ivanova, Masha Y., additional, Jacobus, Joanna, additional, Jernigan, Terry L., additional, Karcher, Nicole R., additional, Laird, Angela R., additional, LeBlanc, Kimberly H., additional, Lisdahl, Krista, additional, Luciana, Monica, additional, Luna, Beatriz, additional, Maes, Hermine H., additional, Marshall, Andrew T., additional, Mason, Michael J., additional, McGlade, Erin C., additional, Morris, Amanda S., additional, Nagel, Bonnie J., additional, Neigh, Gretchen N., additional, Palmer, Clare E., additional, Paulus, Martin P., additional, Potter, Alexandra S., additional, Puttler, Leon I., additional, Rajapakse, Nishadi, additional, Rapuano, Kristina, additional, Reeves, Gloria, additional, Renshaw, Perry F., additional, Schirda, Claudiu, additional, Sher, Kenneth J., additional, Sheth, Chandni, additional, Shilling, Paul D., additional, Squeglia, Lindsay M., additional, Sutherland, Matthew T., additional, Tapert, Susan F., additional, Tomko, Rachel L., additional, Yurgelun-Todd, Deborah, additional, Wade, Natasha E., additional, Weiss, Susan R. B., additional, Zucker, Robert A., additional, and Sowell, Elizabeth R., additional

Published
2021
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74. Differentiated nomological networks of internalizing, externalizing, and the general factor of psychopathology (‘p factor’) in emerging adolescence in the ABCD study

Author

Brislin, Sarah J., primary, Martz, Meghan E., additional, Joshi, Sonalee, additional, Duval, Elizabeth R., additional, Gard, Arianna, additional, Clark, D. Angus, additional, Hyde, Luke W., additional, Hicks, Brian M., additional, Taxali, Aman, additional, Angstadt, Mike, additional, Rutherford, Saige, additional, Heitzeg, Mary M., additional, and Sripada, Chandra, additional

Published
2021
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76. COMT [val.sup.158]met genotype affects µ-Opioid neurotransmitter responses to a pain stressor. (Reports)

Author

Zubieta, Jon-Kar, Heitzeg, Mary M., Smith, Yolanda R., Bueller, Joshua A., Xu, Ke, Xu, Yanjun, Koeppe, Robert A., Stohler, Christian S., and Goldman, David

Subjects
Enzymes -- Research, Methyltransferases -- Research, Science and technology, Research
Abstract

Responses to pain and other stressors are regulated by interactions between multiple brain areas and neurochemical systems. We examined the influence of a common functional genetic polymorphism affecting the metabolism of catecholamines on the modulation of responses to sustained pain in humans. Individuals homozygous for the [met.sup.158] allele of the catechot-O-methyltransferase (COMT) polymorphism ([val.sup.158]met) showed diminished regional µ-opioid system responses to pain compared with heterozygotes. These effects were accompanied by higher sensory and affective ratings of pain and a more negative internal affective state. Opposite effects were observed in [val.sup.158] homozygotes. The COMT [val.sup.158]met polymorphism thus influences the human experience of pain and may underlie interindividual differences in the adaptation and responses to pain and other stressful stimuli., Strong interest exists for the discovery of genes that cause individual differences in responses to physical and environmental challenges. In the case of pain, both sensitivity and inhibition are traits [...]

Published
2003

85. Sex Moderates Reward- and Loss-Related Neural Correlates of Triarchic-Model Traits and Antisocial Behavior

Author

Brislin, Sarah J., Weigard, Alexander S., Hardee, Jillian E., Cope, Lora M., Martz, Meghan E., Zucker, Robert A., and Heitzeg, Mary M.

Abstract

Abnormalities in responses to reward and loss are implicated in the etiology of antisocial behavior and psychopathic traits. Although there is evidence for sex differences in neural response to reward and loss, it remains unclear how sex differences may moderate links between these neural responses and the phenotypic expression of antisocial behavior and psychopathic traits. This study examined sex differences in associations of neural response to reward and loss with antisocial personality symptoms and psychopathic traits. Functional neuroimaging data were collected during a monetary incentive delay task from 158 participants. Among males, during loss anticipation, activation in the left nucleus accumbens was negatively associated with antisocial behavior. Among females, during loss feedback, activation in the left nucleus accumbens and left amygdala was negatively associated with antisocial behavior. These results suggest that phenotypic sex differences in psychopathic traits and antisocial behavior may in part be attributable to different etiological pathways.

Published
2022
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89. Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder

Author

Langenecker, Scott A., primary, Mickey, Brian J., additional, Eichhammer, Peter, additional, Sen, Srijan, additional, Elverman, Kathleen H., additional, Kennedy, Susan E., additional, Heitzeg, Mary M., additional, Ribeiro, Saulo M., additional, Love, Tiffany M., additional, Hsu, David T., additional, Koeppe, Robert A., additional, Watson, Stanley J., additional, Akil, Huda, additional, Goldman, David, additional, Burmeister, Margit, additional, and Zubieta, Jon-Kar, additional

Published
2019
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92. Sexual Development in Adolescence: An Examination of Genetic and Environmental Influences.

Author

Clark, D. Angus, Durbin, C. Emily, Heitzeg, Mary M., Iacono, William G., McGue, Matt, and Hicks, Brian M.

Subjects
HUMAN sexuality, HEALTH behavior, SEXUAL intercourse, ADOLESCENCE, DATING violence, ORGASM, FEMALE orgasm
Abstract

Sexual development entails many experiences and is a major feature of adolescence. Most relevant behavioral genetic studies, however, focus primarily on sexual behaviors associated with health risks. We took a more normative, developmental perspective by examining genetic and environmental influences on five sexual behaviors ranging from dating to pregnancy in middle (Mage = 14.90 years) and late adolescence (Mage = 17.85 years) in a sample of twins (N = 3,762). Overall, behaviors that are more common and socially sanctioned (e.g., dating) were more heritable than behaviors that are less common and socially acceptable (e.g., sexual intercourse). That the etiology of different sexual behaviors is tied to their normativeness highlights the importance of considering the broader developmental context when studying sexual development. [ABSTRACT FROM AUTHOR]

Published
2020
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93. Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

Author

Hagler, Donald J, primary, Hatton, Sean N, additional, Makowski, Carolina, additional, Cornejo, M Daniela, additional, Fair, Damien A, additional, Dick, Anthony Steven, additional, Sutherland, Matthew T, additional, Casey, BJ, additional, Barch, Deanna M, additional, Harms, Michael P, additional, Watts, Richard, additional, Bjork, James M, additional, Garavan, Hugh P, additional, Hilmer, Laura, additional, Pung, Christopher J, additional, Sicat, Chelsea S, additional, Kuperman, Joshua, additional, Bartsch, Hauke, additional, Xue, Feng, additional, Heitzeg, Mary M, additional, Laird, Angela R, additional, Trinh, Thanh T, additional, Gonzalez, Raul, additional, Tapert, Susan F, additional, Riedel, Michael C, additional, Squeglia, Lindsay M, additional, Hyde, Luke W, additional, Rosenberg, Monica D, additional, Earl, Eric A, additional, Howlett, Katia D, additional, Baker, Fiona C, additional, Soules, Mary, additional, Diaz, Jazmin, additional, Leon, Octavio Ruiz de, additional, Thompson, Wesley K, additional, Neale, Michael C, additional, Herting, Megan, additional, Sowell, Elizabeth R, additional, Alvarez, Ruben P, additional, Hawes, Samuel W, additional, Sanchez, Mariana, additional, Bodurka, Jerzy, additional, Breslin, Florence J, additional, Morris, Amanda Sheffield, additional, Paulus, Martin P, additional, Simmons, W Kyle, additional, Polimeni, Jonathan R, additional, Kouwe, Andre van der, additional, Nencka, Andrew S, additional, Gray, Kevin M, additional, Pierpaoli, Carlo, additional, Matochik, John A, additional, Noronha, Antonio, additional, Aklin, Will M, additional, Conway, Kevin, additional, Glantz, Meyer, additional, Hoffman, Elizabeth, additional, Little, Roger, additional, Lopez, Marsha, additional, Pariyadath, Vani, additional, Weiss, Susan RB, additional, Wolff-Hughes, Dana L, additional, DelCarmen-Wiggins, Rebecca, additional, Ewing, Sarah W Feldstein, additional, Miranda-Dominguez, Oscar, additional, Nagel, Bonnie J, additional, Perrone, Anders J, additional, Sturgeon, Darrick T, additional, Goldstone, Aimee, additional, Pfefferbaum, Adolf, additional, Pohl, Kilian M, additional, Prouty, Devin, additional, Uban, Kristina, additional, Bookheimer, Susan Y, additional, Dapretto, Mirella, additional, Galvan, Adriana, additional, Bagot, Kara, additional, Giedd, Jay, additional, Infante, M Alejandra, additional, Jacobus, Joanna, additional, Patrick, Kevin, additional, Shilling, Paul D, additional, Desikan, Rahul, additional, Li, Yi, additional, Sugrue, Leo, additional, Banich, Marie T, additional, Friedman, Naomi, additional, Hewitt, John K, additional, Hopfer, Christian, additional, Sakai, Joseph, additional, Tanabe, Jody, additional, Cottler, Linda B, additional, Nixon, Sara Jo, additional, Chang, Linda, additional, Cloak, Christine, additional, Ernst, Thomas, additional, Reeves, Gloria, additional, Kennedy, David N, additional, Heeringa, Steve, additional, Peltier, Scott, additional, Schulenberg, John, additional, Sripada, Chandra, additional, Zucker, Robert A, additional, Iacono, William G, additional, Luciana, Monica, additional, Calabro, Finnegan J, additional, Clark, Duncan B, additional, Lewis, David A, additional, Luna, Beatriz, additional, Schirda, Claudiu, additional, Brima, Tufikameni, additional, Foxe, John J, additional, Freedman, Edward G, additional, Mruzek, Daniel W, additional, Mason, Michael J, additional, Huber, Rebekah, additional, McGlade, Erin, additional, Prescot, Andrew, additional, Renshaw, Perry F, additional, Yurgelun-Todd, Deborah A, additional, Allgaier, Nicholas A, additional, Dumas, Julie A, additional, Ivanova, Masha, additional, Potter, Alexandra, additional, Florsheim, Paul, additional, Larson, Christine, additional, Lisdahl, Krista, additional, Charness, Michael E, additional, Fuemmeler, Bernard, additional, Hettema, John M, additional, Steinberg, Joel, additional, Anokhin, Andrey P, additional, Glaser, Paul, additional, Heath, Andrew C, additional, Madden, Pamela A, additional, Baskin-Sommers, Arielle, additional, Constable, R Todd, additional, Grant, Steven J, additional, Dowling, Gayathri J, additional, Brown, Sandra A, additional, Jernigan, Terry L, additional, and Dale, Anders M, additional

Published
2018
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95. The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites

Author

Casey, B.J., primary, Cannonier, Tariq, additional, Conley, May I., additional, Cohen, Alexandra O., additional, Barch, Deanna M., additional, Heitzeg, Mary M., additional, Soules, Mary E., additional, Teslovich, Theresa, additional, Dellarco, Danielle V., additional, Garavan, Hugh, additional, Orr, Catherine A., additional, Wager, Tor D., additional, Banich, Marie T., additional, Speer, Nicole K., additional, Sutherland, Matthew T., additional, Riedel, Michael C., additional, Dick, Anthony S., additional, Bjork, James M., additional, Thomas, Kathleen M., additional, Chaarani, Bader, additional, Mejia, Margie H., additional, Hagler, Donald J., additional, Daniela Cornejo, M., additional, Sicat, Chelsea S., additional, Harms, Michael P., additional, Dosenbach, Nico U.F., additional, Rosenberg, Monica, additional, Earl, Eric, additional, Bartsch, Hauke, additional, Watts, Richard, additional, Polimeni, Jonathan R., additional, Kuperman, Joshua M., additional, Fair, Damien A., additional, and Dale, Anders M., additional

Published
2018
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96. Functional genetic variants in the vesicular monoamine transporter 1 (VMAT1) modulate emotion processing

Author

Lohoff, Falk W., Hodge, Rachel, Narasimhan, Sneha, Nall, Aleksandra, Ferraro, Thomas N., Mickey, Brian J., Heitzeg, Mary M., Langenecker, Scott A., Zubieta, Jon-Kar, Bogdan, Ryan, Nikolova, Yuliya S., Drabant, Emily, Hariri, Ahmad R., Bevilacqua, Laura, Goldman, David, and Doyle, Glenn A.

Subjects
Male, Polymorphism, Genetic, Adolescent, Genotype, Emotions, Brain, Transfection, Article, Young Adult, Case-Control Studies, Vesicular Monoamine Transport Proteins, Chlorocebus aethiops, Image Processing, Computer-Assisted, Animals, Humans, Biogenic Monoamines, Female, Affective Symptoms, Genetic Association Studies, Cell Line, Transformed
Abstract

SUMMARY Emotional behavior is in part heritable and often disrupted in psychopathology. Identification of specific genetic variants that drive this heritability may provide important new insight into molecular and neurobiological mechanisms involved in emotionality. Our results demonstrate that the presynaptic vesicular monoamine transporter 1 (VMAT1) Thr136Ile (rs1390938) polymorphism is functional in vitro, with the Ile allele leading to increased monoamine transport into presynaptic vesicles. Moreover, we show that the Thr136Ile variant predicts differential responses in emotional brain circuits consistent with its effects in vitro. Lastly, deep sequencing of bipolar disorder (BPD) patients and controls identified several rare novel VMAT1 variants. The variant Phe84Ser was only present in individuals with BPD and leads to marked increase monoamine transport in vitro. Taken together, our data show that VMAT1 polymorphisms influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology.

Published
2013

97. Striatal Dopaminergic Reward Response Relates to Age of First Drunkenness and Feedback Response in At-Risk Youth

Author

Weiland, Barbara J., Zucker, Robert A., Zubieta, Jon-Kar, and Heitzeg, Mary M.

Subjects
Adult, Male, Risk, Adolescent, Dopamine, Functional Neuroimaging, Magnetic Resonance Imaging, Article, Nucleus Accumbens, Feedback, Neostriatum, Alcoholism, Young Adult, Child of Impaired Parents, Delay Discounting, Reward, Raclopride, Positron-Emission Tomography, Ventral Striatum, Dopamine Antagonists, Humans, Age of Onset, Alcoholic Intoxication
Abstract

Dopamine receptor concentrations, primarily in the striatum, are hypothesized to contribute to a developmental imbalance between subcortical and prefrontal control systems in emerging adulthood potentially biasing motivation and increasing risky behaviors. Positron emission tomography (PET) studies have found significant reductions in striatal dopamine D2 receptors, and blunted amphetamine-induced dopamine release, in substance users compared to healthy controls. Extant literature is limited and inconsistent concerning vulnerability associated with having a family history of substance abuse (FH+). Some studies have reported familial liability associated with higher dopamine receptor levels, reduced dopamine response to stimulant challenges and decreased response to oral alcohol. However other reports have failed to find group differences based on family history. We explored the interaction of familial liability and behavioral risk with multi-modal molecular and neural imaging of the dopaminergic system. Forty-four young adult male subjects performed monetary incentive delay tasks during both [11C]raclopride PET and functional magnetic resonance imaging (fMRI) scans. FH+ subjects were identified as Low (n=24) or High Risk (n=9) based on early initiation of drunkenness. FH+ High Risk subjects exhibited heightened striatal dopamine response to monetary reward but did not differ in neural activations compared with FH+ Low Risk subjects and controls with no familial loading (FH-, n=11). Across all subjects, a negative relationship was found between dopamine release and age of first drunkenness and a positive relationship with neural response to reward receipt. These results suggest that in at-risk individuals higher dopamine transmission associated with monetary reward may represent a particularly useful neurobiological phenotype.

Published
2016

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