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2. Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

Author

Huggins, Ashley A, Baird, C Lexi, Briggs, Melvin, Laskowitz, Sarah, Hussain, Ahmed, Fouda, Samar, Haswell, Courtney, Sun, Delin, Salminen, Lauren E, Jahanshad, Neda, Thomopoulos, Sophia I, Veltman, Dick J, Frijling, Jessie L, Olff, Miranda, van Zuiden, Mirjam, Koch, Saskia BJ, Nawjin, Laura, Wang, Li, Zhu, Ye, Li, Gen, Stein, Dan J, Ipser, Jonathan, Seedat, Soraya, du Plessis, Stefan, van den Heuvel, Leigh L, Suarez-Jimenez, Benjamin, Zhu, Xi, Kim, Yoojean, He, Xiaofu, Zilcha-Mano, Sigal, Lazarov, Amit, Neria, Yuval, Stevens, Jennifer S, Ressler, Kerry J, Jovanovic, Tanja, van Rooij, Sanne JH, Fani, Negar, Hudson, Anna R, Mueller, Sven C, Sierk, Anika, Manthey, Antje, Walter, Henrik, Daniels, Judith K, Schmahl, Christian, Herzog, Julia I, Říha, Pavel, Rektor, Ivan, Lebois, Lauren AM, Kaufman, Milissa L, Olson, Elizabeth A, Baker, Justin T, Rosso, Isabelle M, King, Anthony P, Liberzon, Isreal, Angstadt, Mike, Davenport, Nicholas D, Sponheim, Scott R, Disner, Seth G, Straube, Thomas, Hofmann, David, Qi, Rongfeng, Lu, Guang Ming, Baugh, Lee A, Forster, Gina L, Simons, Raluca M, Simons, Jeffrey S, Magnotta, Vincent A, Fercho, Kelene A, Maron-Katz, Adi, Etkin, Amit, Cotton, Andrew S, O’Leary, Erin N, Xie, Hong, Wang, Xin, Quidé, Yann, El-Hage, Wissam, Lissek, Shmuel, Berg, Hannah, Bruce, Steven, Cisler, Josh, Ross, Marisa, Herringa, Ryan J, Grupe, Daniel W, Nitschke, Jack B, Davidson, Richard J, Larson, Christine L, deRoon-Cassini, Terri A, Tomas, Carissa W, Fitzgerald, Jacklynn M, Blackford, Jennifer Urbano, Olatunji, Bunmi O, Kremen, William S, Lyons, Michael J, Franz, Carol E, Gordon, Evan M, May, Geoffrey, Nelson, Steven M, Abdallah, Chadi G, Levy, Ifat, and Harpaz-Rotem, Ilan

Subjects
Clinical and Health Psychology, Psychology, Mind and Body, Mental Illness, Anxiety Disorders, Neurosciences, Brain Disorders, Post-Traumatic Stress Disorder (PTSD), Behavioral and Social Science, Mental Health, Mental health, Humans, Stress Disorders, Post-Traumatic, Cerebellum, Female, Male, Adult, Magnetic Resonance Imaging, Middle Aged, White Matter, Gray Matter, Organ Size, Deep Learning, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum volumes in PTSD compared to healthy controls (88% trauma-exposed). PTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume, as well as reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), vermis (VI, VIII), flocculonodular lobe (lobule X), and corpus medullare (all p-FDR

Published
2024

3. Volume of subcortical brain regions in social anxiety disorder: mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group.

Author

Groenewold, Nynke, Bas-Hoogendam, Janna, Amod, Alyssa, Laansma, Max, Van Velzen, Laura, Aghajani, Moji, Hilbert, Kevin, Oh, Hyuntaek, Salas, Ramiro, Jackowski, Andrea, Pan, Pedro, Salum, Giovanni, Blair, James, Blair, Karina, Hirsch, Joy, Pantazatos, Spiro, Schneier, Franklin, Talati, Ardesheer, Roelofs, Karin, Volman, Inge, Blanco-Hinojo, Laura, Cardoner, Narcís, Pujol, Jesus, Beesdo-Baum, Katja, Ching, Christopher, Thomopoulos, Sophia, Jansen, Andreas, Kircher, Tilo, Krug, Axel, Nenadić, Igor, Stein, Frederike, Dannlowski, Udo, Grotegerd, Dominik, Lemke, Hannah, Meinert, Susanne, Winter, Alexandra, Erb, Michael, Kreifelts, Benjamin, Gong, Qiyong, Lui, Su, Zhu, Fei, Mwangi, Benson, Soares, Jair, Wu, Mon-Ju, Bayram, Ali, Canli, Mesut, Tükel, Raşit, Westenberg, P, Heeren, Alexandre, Cremers, Henk, Hofmann, David, Straube, Thomas, Doruyter, Alexander, Lochner, Christine, Peterburs, Jutta, Van Tol, Marie-José, Gur, Raquel, Kaczkurkin, Antonia, Larsen, Bart, Satterthwaite, Theodore, Filippi, Courtney, Gold, Andrea, Harrewijn, Anita, Zugman, André, Bülow, Robin, Grabe, Hans, Völzke, Henry, Wittfeld, Katharina, Böhnlein, Joscha, Dohm, Katharina, Kugel, Harald, Schrammen, Elisabeth, Zwanzger, Peter, Leehr, Elisabeth, Sindermann, Lisa, Ball, Tali, Fonzo, Gregory, Paulus, Martin, Stein, Murray, Klumpp, Heide, Phan, K, Furmark, Tomas, Månsson, Kristoffer, Manzouri, Amirhossein, Avery, Suzanne, Blackford, Jennifer, Clauss, Jacqueline, Feola, Brandee, Harper, Jennifer, Sylvester, Chad, Lueken, Ulrike, Veltman, Dick, Winkler, Anderson, Jahanshad, Neda, Pine, Daniel, Thompson, Paul, Stein, Dan, Van der Wee, Nic, and Simmons, Alan

Subjects
Adult, Adolescent, Humans, Phobia, Social, Magnetic Resonance Imaging, Brain, Anxiety, Neuroimaging
Abstract

There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE

Published
2023

4. Genetic nurture effects for alcohol use disorder

Author

Thomas, Nathaniel S, Salvatore, Jessica E, Kuo, Sally I-Chun, Aliev, Fazil, McCutcheon, Vivia V, Meyers, Jacquelyn M, Bucholz, Kathleen K, Brislin, Sarah J, Chan, Grace, Edenberg, Howard J, Kamarajan, Chella, Kramer, John R, Kuperman, Samuel, Pandey, Gayathri, Plawecki, Martin H, Schuckit, Marc A, and Dick, Danielle M

Subjects
Prevention, Behavioral and Social Science, Underage Drinking, Genetics, Substance Misuse, Alcoholism, Alcohol Use and Health, Pediatric, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Good Health and Well Being, Child, Adolescent, Humans, Female, Male, Alcoholism, Alcohol Drinking, Alcohol-Related Disorders, Alcoholic Intoxication, Risk Factors, COGA Collaborators, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

We tested whether aspects of the childhood/adolescent home environment mediate genetic risk for alcohol problems within families across generations. Parental relationship discord and parental divorce were the focal environments examined. The sample included participants of European ancestry (N = 4806, 51% female) and African ancestry (N = 1960, 52% female) from the high-risk Collaborative Study on the Genetics of Alcoholism. Alcohol outcomes in the child generation included lifetime criterion counts for DSM-5 Alcohol Use Disorder (AUD), lifetime maximum drinks in 24 h, age at initiation of regular drinking, and age at first alcohol intoxication. Predictors in the parent generation included relationship discord, divorce, alcohol measures parallel to those in the child generation, and polygenic scores for alcohol problems. Parental polygenic scores were partitioned into alleles that were transmitted and non-transmitted to the child. The results from structural equation models were consistent with genetic nurture effects in European ancestry families. Exposure to parental relationship discord and parental divorce mediated, in part, the transmission of genetic risk for alcohol problems from parents to children to predict earlier ages regular drinking (βindirect = -0.018 [-0.026, -0.011]) and intoxication (βindirect = -0.015 [-0.023, -0.008]), greater lifetime maximum drinks (βindirect = 0.006 [0.002, 0.01]) and more lifetime AUD criteria (βindirect = 0.011 [0.006, 0.016]). In contrast, there was no evidence that parental alleles had indirect effects on offspring alcohol outcomes via parental relationship discord or divorce in the smaller number of families of African ancestry. In conclusion, parents transmit genetic risk for alcohol problems to their children not only directly, but also indirectly via genetically influenced aspects of the home environment. Further investigation of genetic nurture in non-European samples is needed.

Published
2023

5. Rare copy number variation in posttraumatic stress disorder

Author

Maihofer, Adam X, Engchuan, Worrawat, Huguet, Guillaume, Klein, Marieke, MacDonald, Jeffrey R, Shanta, Omar, Thiruvahindrapuram, Bhooma, Jean-louis, Martineau, Saci, Zohra, Jacquemont, Sebastien, Scherer, Stephen W, Ketema, Elizabeth, Aiello, Allison E, Amstadter, Ananda B, Avdibegović, Esmina, Babic, Dragan, Baker, Dewleen G, Bisson, Jonathan I, Boks, Marco P, Bolger, Elizabeth A, Bryant, Richard A, Bustamante, Angela C, Caldas-de-Almeida, Jose Miguel, Cardoso, Graça, Deckert, Jurgen, Delahanty, Douglas L, Domschke, Katharina, Dunlop, Boadie W, Dzubur-Kulenovic, Alma, Evans, Alexandra, Feeny, Norah C, Franz, Carol E, Gautam, Aarti, Geuze, Elbert, Goci, Aferdita, Hammamieh, Rasha, Jakovljevic, Miro, Jett, Marti, Jones, Ian, Kaufman, Milissa L, Kessler, Ronald C, King, Anthony P, Kremen, William S, Lawford, Bruce R, Lebois, Lauren AM, Lewis, Catrin, Liberzon, Israel, Linnstaedt, Sarah D, Lugonja, Bozo, Luykx, Jurjen J, Lyons, Michael J, Mavissakalian, Matig R, McLaughlin, Katie A, McLean, Samuel A, Mehta, Divya, Mellor, Rebecca, Morris, Charles Phillip, Muhie, Seid, Orcutt, Holly K, Peverill, Matthew, Ratanatharathorn, Andrew, Risbrough, Victoria B, Rizzo, Albert, Roberts, Andrea L, Rothbaum, Alex O, Rothbaum, Barbara O, Roy-Byrne, Peter, Ruggiero, Kenneth J, Rutten, Bart PF, Schijven, Dick, Seng, Julia S, Sheerin, Christina M, Sorenson, Michael A, Teicher, Martin H, Uddin, Monica, Ursano, Robert J, Vinkers, Christiaan H, Voisey, Joanne, Weber, Heike, Winternitz, Sherry, Xavier, Miguel, Yang, Ruoting, McD Young, Ross, Zoellner, Lori A, Salem, Rany M, Shaffer, Richard A, Wu, Tianying, Ressler, Kerry J, Stein, Murray B, Koenen, Karestan C, Sebat, Jonathan, and Nievergelt, Caroline M

Subjects
Post-Traumatic Stress Disorder (PTSD), Mental Health, Human Genome, Genetics, Neurosciences, Brain Disorders, Mental health, Humans, DNA Copy Number Variations, Stress Disorders, Post-Traumatic, Genome, Brain, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Psychiatric Genomics Consortium PTSD Working Group, Psychiatric Genomics Consortium CNV Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q

Published
2022

7. Clinical, environmental, and genetic risk factors for substance use disorders: characterizing combined effects across multiple cohorts

Author

Barr, Peter B, Driver, Morgan N, Kuo, Sally I-Chun, Stephenson, Mallory, Aliev, Fazil, Linnér, Richard Karlsson, Marks, Jesse, Anokhin, Andrey P, Bucholz, Kathleen, Chan, Grace, Edenberg, Howard J, Edwards, Alexis C, Francis, Meredith W, Hancock, Dana B, Harden, K Paige, Kamarajan, Chella, Kaprio, Jaakko, Kinreich, Sivan, Kramer, John R, Kuperman, Samuel, Latvala, Antti, Meyers, Jacquelyn L, Palmer, Abraham A, Plawecki, Martin H, Porjesz, Bernice, Rose, Richard J, Schuckit, Marc A, Salvatore, Jessica E, and Dick, Danielle M

Subjects
Tobacco, Alcoholism, Alcohol Use and Health, Patient Safety, Drug Abuse (NIDA only), Substance Misuse, Prevention, Brain Disorders, Genetics, Tobacco Smoke and Health, Mental health, Good Health and Well Being, Humans, Young Adult, Adult, Tobacco Use Disorder, Alcoholism, Substance-Related Disorders, Risk Factors, Alcohol Drinking, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Substance use disorders (SUDs) incur serious social and personal costs. The risk for SUDs is complex, with risk factors ranging from social conditions to individual genetic variation. We examined whether models that include a clinical/environmental risk index (CERI) and polygenic scores (PGS) are able to identify individuals at increased risk of SUD in young adulthood across four longitudinal cohorts for a combined sample of N = 15,134. Our analyses included participants of European (NEUR = 12,659) and African (NAFR = 2475) ancestries. SUD outcomes included: (1) alcohol dependence, (2) nicotine dependence; (3) drug dependence, and (4) any substance dependence. In the models containing the PGS and CERI, the CERI was associated with all three outcomes (ORs = 01.37-1.67). PGS for problematic alcohol use, externalizing, and smoking quantity were associated with alcohol dependence, drug dependence, and nicotine dependence, respectively (OR = 1.11-1.33). PGS for problematic alcohol use and externalizing were also associated with any substance dependence (ORs = 1.09-1.18). The full model explained 6-13% of the variance in SUDs. Those in the top 10% of CERI and PGS had relative risk ratios of 3.86-8.04 for each SUD relative to the bottom 90%. Overall, the combined measures of clinical, environmental, and genetic risk demonstrated modest ability to distinguish between affected and unaffected individuals in young adulthood. PGS were significant but added little in addition to the clinical/environmental risk index. Results from our analysis demonstrate there is still considerable work to be done before tools such as these are ready for clinical applications.

Published
2022

9. Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis

Author

Wang, Xin, Xie, Hong, Chen, Tian, Cotton, Andrew S, Salminen, Lauren E, Logue, Mark W, Clarke-Rubright, Emily K, Wall, John, Dennis, Emily L, O’Leary, Brian M, Abdallah, Chadi G, Andrew, Elpiniki, Baugh, Lee A, Bomyea, Jessica, Bruce, Steven E, Bryant, Richard, Choi, Kyle, Daniels, Judith K, Davenport, Nicholas D, Davidson, Richard J, DeBellis, Michael, deRoon-Cassini, Terri, Disner, Seth G, Fani, Negar, Fercho, Kelene A, Fitzgerald, Jacklynn, Forster, Gina L, Frijling, Jessie L, Geuze, Elbert, Gomaa, Hassaan, Gordon, Evan M, Grupe, Dan, Harpaz-Rotem, Ilan, Haswell, Courtney C, Herzog, Julia I, Hofmann, David, Hollifield, Michael, Hosseini, Bobak, Hudson, Anna R, Ipser, Jonathan, Jahanshad, Neda, Jovanovic, Tanja, Kaufman, Milissa L, King, Anthony P, Koch, Saskia BJ, Koerte, Inga K, Korgaonkar, Mayuresh S, Krystal, John H, Larson, Christine, Lebois, Lauren AM, Levy, Ifat, Li, Gen, Magnotta, Vincent A, Manthey, Antje, May, Geoffrey, McLaughlin, Katie A, Mueller, Sven C, Nawijn, Laura, Nelson, Steven M, Neria, Yuval, Nitschke, Jack B, Olff, Miranda, Olson, Elizabeth A, Peverill, Matthew, Phan, K Luan, Rashid, Faisal M, Ressler, Kerry, Rosso, Isabelle M, Sambrook, Kelly, Schmahl, Christian, Shenton, Martha E, Sierk, Anika, Simons, Jeffrey S, Simons, Raluca M, Sponheim, Scott R, Stein, Murray B, Stein, Dan J, Stevens, Jennifer S, Straube, Thomas, Suarez-Jimenez, Benjamin, Tamburrino, Marijo, Thomopoulos, Sophia I, van der Wee, Nic JA, van der Werff, Steven JA, van Erp, Theo GM, van Rooij, Sanne JH, van Zuiden, Mirjam, Varkevisser, Tim, Veltman, Dick J, Vermeiren, Robert RJM, Walter, Henrik, Wang, Li, Zhu, Ye, Zhu, Xi, Thompson, Paul M, Morey, Rajendra A, and Liberzon, Israel

Subjects
Clinical Research, Behavioral and Social Science, Mental Health, Post-Traumatic Stress Disorder (PTSD), Neurosciences, Brain Disorders, Mental health, Cerebral Cortex, Genomics, Humans, Magnetic Resonance Imaging, Stress Disorders, Post-Traumatic, Temporal Lobe, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values

Published
2021

10. Structural brain imaging studies offer clues about the effects of the shared genetic etiology among neuropsychiatric disorders

Author

Radonjić, Nevena V, Hess, Jonathan L, Rovira, Paula, Andreassen, Ole, Buitelaar, Jan K, Ching, Christopher RK, Franke, Barbara, Hoogman, Martine, Jahanshad, Neda, McDonald, Carrie, Schmaal, Lianne, Sisodiya, Sanjay M, Stein, Dan J, van den Heuvel, Odile A, van Erp, Theo GM, van Rooij, Daan, Veltman, Dick J, Thompson, Paul, and Faraone, Stephen V

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Neurosciences, Serious Mental Illness, Genetics, Brain Disorders, Clinical Research, Autism, Intellectual and Developmental Disabilities (IDD), Schizophrenia, Mental Health, Prevention, Aetiology, 2.1 Biological and endogenous factors, Mental health, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Brain, Depressive Disorder, Major, Humans, Neuroimaging, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

Genomewide association studies have found significant genetic correlations among many neuropsychiatric disorders. In contrast, we know much less about the degree to which structural brain alterations are similar among disorders and, if so, the degree to which such similarities have a genetic etiology. From the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium, we acquired standardized mean differences (SMDs) in regional brain volume and cortical thickness between cases and controls. We had data on 41 brain regions for: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), epilepsy, major depressive disorder (MDD), obsessive compulsive disorder (OCD), and schizophrenia (SCZ). These data had been derived from 24,360 patients and 37,425 controls. The SMDs were significantly correlated between SCZ and BD, OCD, MDD, and ASD. MDD was positively correlated with BD and OCD. BD was positively correlated with OCD and negatively correlated with ADHD. These pairwise correlations among disorders were correlated with the corresponding pairwise correlations among disorders derived from genomewide association studies (r = 0.494). Our results show substantial similarities in sMRI phenotypes among neuropsychiatric disorders and suggest that these similarities are accounted for, in part, by corresponding similarities in common genetic variant architectures.

Published
2021

11. Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons

Author

Popova, Dina, Gameiro-Ros, Isabel, Youssef, Mark M., Zalamea, Petronio, Morris, Ayeshia D., Prytkova, Iya, Jadali, Azadeh, Kwan, Kelvin Y., Kamarajan, Chella, Salvatore, Jessica E., Xuei, Xiaoling, Chorlian, David B., Porjesz, Bernice, Kuperman, Samuel, Dick, Danielle M., Goate, Alison, Edenberg, Howard J., Tischfield, Jay A., Pang, Zhiping P., Slesinger, Paul A., and Hart, Ronald P.

Published
2023
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12. Cortical profiles of numerous psychiatric disorders and normal development share a common pattern

Author

Cao, Zhipeng, Cupertino, Renata B., Ottino-Gonzalez, Jonatan, Murphy, Alistair, Pancholi, Devarshi, Juliano, Anthony, Chaarani, Bader, Albaugh, Matthew, Yuan, Dekang, Schwab, Nathan, Stafford, James, Goudriaan, Anna E., Hutchison, Kent, Li, Chiang-Shan R., Luijten, Maartje, Groefsema, Martine, Momenan, Reza, Schmaal, Lianne, Sinha, Rajita, van Holst, Ruth J., Veltman, Dick J., Wiers, Reinout W., Porjesz, Bernice, Lett, Tristram, Banaschewski, Tobias, Bokde, Arun L. W., Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Gowland, Penny, Heinz, Andreas, Brühl, Rüdiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Millenet, Sabina, Fröhner, Juliane H., Robinson, Lauren, Smolka, Michael N., Walter, Henrik, Winterer, Jeanne, Schumann, Gunter, Whelan, Robert, Bhatt, Ravi R., Zhu, Alyssa, Conrod, Patricia, Jahanshad, Neda, Thompson, Paul M., Mackey, Scott, and Garavan, Hugh

Published
2023
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13. Uncovering the genetic architecture of broad antisocial behavior through a genome-wide association study meta-analysis

Author

Tielbeek, Jorim J., Uffelmann, Emil, Williams, Benjamin S., Colodro-Conde, Lucía, Gagnon, Éloi, Mallard, Travis T., Levitt, Brandt E., Jansen, Philip R., Johansson, Ada, Sallis, Hannah M., Pistis, Giorgio, Saunders, Gretchen R. B., Allegrini, Andrea G., Rimfeld, Kaili, Konte, Bettina, Klein, Marieke, Hartmann, Annette M., Salvatore, Jessica E., Nolte, Ilja M., Demontis, Ditte, Malmberg, Anni L. K., Burt, S. Alexandra, Savage, Jeanne E., Sugden, Karen, Poulton, Richie, Harris, Kathleen Mullan, Vrieze, Scott, McGue, Matt, Iacono, William G., Mota, Nina Roth, Mill, Jonathan, Viana, Joana F., Mitchell, Brittany L., Morosoli, Jose J., Andlauer, Till F. M., Ouellet-Morin, Isabelle, Tremblay, Richard E., Côté, Sylvana M., Gouin, Jean-Philippe, Brendgen, Mara R., Dionne, Ginette, Vitaro, Frank, Lupton, Michelle K., Martin, Nicholas G., Castelao, Enrique, Räikkönen, Katri, Eriksson, Johan G., Lahti, Jari, Hartman, Catharina A., Oldehinkel, Albertine J., Snieder, Harold, Liu, Hexuan, Preisig, Martin, Whipp, Alyce, Vuoksimaa, Eero, Lu, Yi, Jern, Patrick, Rujescu, Dan, Giegling, Ina, Palviainen, Teemu, Kaprio, Jaakko, Harden, Kathryn Paige, Munafò, Marcus R., Morneau-Vaillancourt, Geneviève, Plomin, Robert, Viding, Essi, Boutwell, Brian B., Aliev, Fazil, Dick, Danielle M., Popma, Arne, Faraone, Stephen V., Børglum, Anders D., Medland, Sarah E., Franke, Barbara, Boivin, Michel, Pingault, Jean-Baptiste, Glennon, Jeffrey C., Barnes, J. C., Fisher, Simon E., Moffitt, Terrie E., Caspi, Avshalom, Polderman, Tinca J. C., and Posthuma, Danielle

Published
2022
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15. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author

Han, Laura K. M., Dinga, Richard, Hahn, Tim, Ching, Christopher R. K., Eyler, Lisa T., Aftanas, Lyubomir, Aghajani, Moji, Aleman, André, Baune, Bernhard T., Berger, Klaus, Brak, Ivan, Filho, Geraldo Busatto, Carballedo, Angela, Connolly, Colm G., Couvy-Duchesne, Baptiste, Cullen, Kathryn R., Dannlowski, Udo, Davey, Christopher G., Dima, Danai, Duran, Fabio L. S., Enneking, Verena, Filimonova, Elena, Frenzel, Stefan, Frodl, Thomas, Fu, Cynthia H. Y., Godlewska, Beata R., Gotlib, Ian H., Grabe, Hans J., Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Hall, Geoffrey B., Harrison, Ben J., Hatton, Sean N., Hermesdorf, Marco, Hickie, Ian B., Ho, Tiffany C., Hosten, Norbert, Jansen, Andreas, Kähler, Claas, Kircher, Tilo, Klimes-Dougan, Bonnie, Krämer, Bernd, Krug, Axel, Lagopoulos, Jim, Leenings, Ramona, MacMaster, Frank P., MacQueen, Glenda, McIntosh, Andrew, McLellan, Quinn, McMahon, Katie L., Medland, Sarah E., Mueller, Bryon A., Mwangi, Benson, Osipov, Evgeny, Portella, Maria J., Pozzi, Elena, Reneman, Liesbeth, Repple, Jonathan, Rosa, Pedro G. P., Sacchet, Matthew D., Sämann, Philipp G., Schnell, Knut, Schrantee, Anouk, Simulionyte, Egle, Soares, Jair C., Sommer, Jens, Stein, Dan J., Steinsträter, Olaf, Strike, Lachlan T., Thomopoulos, Sophia I., van Tol, Marie-José, Veer, Ilya M., Vermeiren, Robert R. J. M., Walter, Henrik, van der Wee, Nic J. A., van der Werff, Steven J. A., Whalley, Heather, Winter, Nils R., Wittfeld, Katharina, Wright, Margaret J., Wu, Mon-Ju, Völzke, Henry, Yang, Tony T., Zannias, Vasileios, de Zubicaray, Greig I., Zunta-Soares, Giovana B., Abé, Christoph, Alda, Martin, Andreassen, Ole A., Bøen, Erlend, Bonnin, Caterina M., Canales-Rodriguez, Erick J., Cannon, Dara, Caseras, Xavier, Chaim-Avancini, Tiffany M., Elvsåshagen, Torbjørn, Favre, Pauline, Foley, Sonya F., Fullerton, Janice M., Goikolea, Jose M., Haarman, Bartholomeus C. M., Hajek, Tomas, Henry, Chantal, Houenou, Josselin, Howells, Fleur M., Ingvar, Martin, Kuplicki, Rayus, Lafer, Beny, Landén, Mikael, Machado-Vieira, Rodrigo, Malt, Ulrik F., McDonald, Colm, Mitchell, Philip B., Nabulsi, Leila, Otaduy, Maria Concepcion Garcia, Overs, Bronwyn J., Polosan, Mircea, Pomarol-Clotet, Edith, Radua, Joaquim, Rive, Maria M., Roberts, Gloria, Ruhe, Henricus G., Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D., Savitz, Jonathan, Schene, Aart H., Schofield, Peter R., Serpa, Mauricio H., Sim, Kang, Soeiro-de-Souza, Marcio Gerhardt, Sutherland, Ashley N., Temmingh, Henk S., Timmons, Garrett M., Uhlmann, Anne, Vieta, Eduard, Wolf, Daniel H., Zanetti, Marcus V., Jahanshad, Neda, Thompson, Paul M., Veltman, Dick J., Penninx, Brenda W. J. H., Marquand, Andre F., Cole, James H., and Schmaal, Lianne

Published
2021
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16. A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior

Author

Meyers, Jacquelyn L., Zhang, Jian, Chorlian, David B., Pandey, Ashwini K., Kamarajan, Chella, Wang, Jen-Chyong, Wetherill, Leah, Lai, Dongbing, Chao, Michael, Chan, Grace, Kinreich, Sivan, Kapoor, Manav, Bertelsen, Sarah, McClintick, Jeanette, Bauer, Lance, Hesselbrock, Victor, Kuperman, Samuel, Kramer, John, Salvatore, Jessica E., Dick, Danielle M., Agrawal, Arpana, Foroud, Tatiana, Edenberg, Howard J., Goate, Alison, and Porjesz, Bernice

Published
2021
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17. Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders: Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

Author

Opel, Nils, Thalamuthu, Anbupalam, Milaneschi, Yuri, Grotegerd, Dominik, Flint, Claas, Leenings, Ramona, Goltermann, Janik, Richter, Maike, Hahn, Tim, Woditsch, Georg, Berger, Klaus, Hermesdorf, Marco, McIntosh, Andrew, Whalley, Heather C., Harris, Mathew A., MacMaster, Frank P., Walter, Henrik, Veer, Ilya M., Frodl, Thomas, Carballedo, Angela, Krug, Axel, Nenadic, Igor, Kircher, Tilo, Aleman, Andre, Groenewold, Nynke A., Stein, Dan J., Soares, Jair C., Zunta-Soares, Giovana B., Mwangi, Benson, Wu, Mon-Ju, Walter, Martin, Li, Meng, Harrison, Ben J., Davey, Christopher G., Cullen, Kathryn R., Klimes-Dougan, Bonnie, Mueller, Bryon A., Sämann, Philipp G., Penninx, Brenda, Nawijn, Laura, Veltman, Dick J., Aftanas, Lyubomir, Brak, Ivan V., Filimonova, Elena A., Osipov, Evgeniy A., Reneman, Liesbeth, Schrantee, Anouk, Grabe, Hans J., Van der Auwera, Sandra, Wittfeld, Katharina, Hosten, Norbert, Völzke, Henry, Sim, Kang, Gotlib, Ian H., Sacchet, Matthew D., Lagopoulos, Jim, Hatton, Sean N., Hickie, Ian, Pozzi, Elena, Thompson, Paul M., Jahanshad, Neda, Schmaal, Lianne, Baune, Bernhard T., and Dannlowski, Udo

Published
2021
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18. Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium

Author

Dennis, Emily L., Disner, Seth G., Fani, Negar, Salminen, Lauren E., Logue, Mark, Clarke, Emily K., Haswell, Courtney C., Averill, Christopher L., Baugh, Lee A., Bomyea, Jessica, Bruce, Steven E., Cha, Jiook, Choi, Kyle, Davenport, Nicholas D., Densmore, Maria, du Plessis, Stefan, Forster, Gina L., Frijling, Jessie L., Gonenc, Atilla, Gruber, Staci, Grupe, Daniel W., Guenette, Jeffrey P., Hayes, Jasmeet, Hofmann, David, Ipser, Jonathan, Jovanovic, Tanja, Kelly, Sinead, Kennis, Mitzy, Kinzel, Philipp, Koch, Saskia B. J., Koerte, Inga, Koopowitz, Sheri, Korgaonkar, Mayuresh, Krystal, John, Lebois, Lauren A. M., Li, Gen, Magnotta, Vincent A., Manthey, Antje, May, Geoff J., Menefee, Deleene S., Nawijn, Laura, Nelson, Steven M., Neufeld, Richard W. J., Nitschke, Jack B., O’Doherty, Daniel, Peverill, Matthew, Ressler, Kerry J., Roos, Annerine, Sheridan, Margaret A., Sierk, Anika, Simmons, Alan, Simons, Raluca M., Simons, Jeffrey S., Stevens, Jennifer, Suarez-Jimenez, Benjamin, Sullivan, Danielle R., Théberge, Jean, Tran, Jana K., van den Heuvel, Leigh, van der Werff, Steven J. A., van Rooij, Sanne J. H., van Zuiden, Mirjam, Velez, Carmen, Verfaellie, Mieke, Vermeiren, Robert R. J. M., Wade, Benjamin S. C., Wager, Tor, Walter, Henrik, Winternitz, Sherry, Wolff, Jonathan, York, Gerald, Zhu, Ye, Zhu, Xi, Abdallah, Chadi G., Bryant, Richard, Daniels, Judith K, Davidson, Richard J, Fercho, Kelene A, Franz, Carol, Geuze, Elbert, Gordon, Evan M, Kaufman, Milissa L, Kremen, William S., Lagopoulos, Jim, Lanius, Ruth A, Lyons, Michael J., McCauley, Stephen R, McGlinchey, Regina, McLaughlin, Katie A., Milberg, William, Neria, Yuval, Olff, Miranda, Seedat, Soraya, Shenton, Martha, Sponheim, Scott R., Stein, Dan J., Stein, Murray B., Straube, Thomas, Tate, David F., van der Wee, Nic J. A., Veltman, Dick J., Wang, Li., Wilde, Elisabeth A., Thompson, Paul M., Kochunov, Peter, Jahanshad, Neda, and Morey, Rajendra A.

Published
2021
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19. White matter disturbances in major depressive disorder: a coordinated analysis across 20 international cohorts in the ENIGMA MDD working group

Author

van Velzen, Laura S., Kelly, Sinead, Isaev, Dmitry, Aleman, Andre, Aftanas, Lyubomir I., Bauer, Jochen, Baune, Bernhard T., Brak, Ivan V., Carballedo, Angela, Connolly, Colm G., Couvy-Duchesne, Baptiste, Cullen, Kathryn R., Danilenko, Konstantin V., Dannlowski, Udo, Enneking, Verena, Filimonova, Elena, Förster, Katharina, Frodl, Thomas, Gotlib, Ian H., Groenewold, Nynke A., Grotegerd, Dominik, Harris, Mathew A., Hatton, Sean N., Hawkins, Emma L., Hickie, Ian B., Ho, Tiffany C., Jansen, Andreas, Kircher, Tilo, Klimes-Dougan, Bonnie, Kochunov, Peter, Krug, Axel, Lagopoulos, Jim, Lee, Renick, Lett, Tristram A., Li, Meng, MacMaster, Frank P., Martin, Nicholas G., McIntosh, Andrew M., McLellan, Quinn, Meinert, Susanne, Nenadić, Igor, Osipov, Evgeny, Penninx, Brenda W. J. H., Portella, Maria J., Repple, Jonathan, Roos, Annerine, Sacchet, Matthew D., Sämann, Philipp G., Schnell, Knut, Shen, Xueyi, Sim, Kang, Stein, Dan J., van Tol, Marie-Jose, Tomyshev, Alexander S., Tozzi, Leonardo, Veer, Ilya M., Vermeiren, Robert, Vives-Gilabert, Yolanda, Walter, Henrik, Walter, Martin, van der Wee, Nic J. A., van der Werff, Steven J. A., Schreiner, Melinda Westlund, Whalley, Heather C., Wright, Margaret J., Yang, Tony T., Zhu, Alyssa, Veltman, Dick J., Thompson, Paul M., Jahanshad, Neda, and Schmaal, Lianne

Published
2020
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21. Correction: Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders

Author

Opel, Nils, Thalamuthu, Anbupalam, Milaneschi, Yuri, Grotegerd, Dominik, Flint, Claas, Leenings, Ramona, Goltermann, Janik, Richter, Maike, Hahn, Tim, Woditsch, Georg, Berger, Klaus, Hermesdorf, Marco, McIntosh, Andrew, Whalley, Heather C., Harris, Mathew A., MacMaster, Frank P., Walter, Henrik, Veer, Ilya M., Frodl, Thomas, Carballedo, Angela, Krug, Axel, Nenadic, Igor, Kircher, Tilo, Aleman, Andre, Groenewold, Nynke A., Stein, Dan J., Soares, Jair C., Zunta-Soares, Giovana B., Mwangi, Benson, Wu, Mon-Ju, Walter, Martin, Li, Meng, Harrison, Ben J., Davey, Christopher G., Cullen, Kathryn R., Klimes-Dougan, Bonnie, Mueller, Bryon A., Sämann, Philipp G., Penninx, Brenda, Nawijn, Laura, Veltman, Dick J., Aftanas, Lyubomir, Brak, Ivan V., Filimonova, Elena A., Osipov, Evgeniy A., Reneman, Liesbeth, Schrantee, Anouk, Grabe, Hans J., Van der Auwera, Sandra, Wittfeld, Katharina, Hosten, Norbert, Völzke, Henry, Sim, Kang, Gotlib, Ian H., Sacchet, Matthew D., Lagopoulos, Jim, Hatton, Sean N., Hickie, Ian, Pozzi, Elena, Thompson, Paul M., Jahanshad, Neda, Schmaal, Lianne, Baune, Bernhard T., and Dannlowski, Udo

Published
2021
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22. An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry

Author

Meyers, J L, Zhang, J, Wang, J C, Su, J, Kuo, S I, Kapoor, M, Wetherill, L, Bertelsen, S, Lai, D, Salvatore, J E, Kamarajan, C, Chorlian, D, Agrawal, A, Almasy, L, Bauer, L, Bucholz, K K, Chan, G, Hesselbrock, V, Koganti, L, Kramer, J, Kuperman, S, Manz, N, Pandey, A, Seay, M, Scott, D, Taylor, R E, Dick, D M, Edenberg, H J, Goate, A, Foroud, T, and Porjesz, B

Published
2017
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23. A genome-wide association study of anorexia nervosa

Author

Boraska, V, Franklin, C S, Floyd, J A B, Thornton, L M, Huckins, L M, Southam, L, Rayner, N W, Tachmazidou, I, Klump, K L, Treasure, J, Lewis, C M, Schmidt, U, Tozzi, F, Kiezebrink, K, Hebebrand, J, Gorwood, P, Adan, R A H, Kas, M J H, Favaro, A, Santonastaso, P, Fernández-Aranda, F, Gratacos, M, Rybakowski, F, Dmitrzak-Weglarz, M, Kaprio, J, Keski-Rahkonen, A, Raevuori, A, Van Furth, E F, Slof-Op 't Landt, M C T, Hudson, J I, Reichborn-Kjennerud, T, Knudsen, G P S, Monteleone, P, Kaplan, A S, Karwautz, A, Hakonarson, H, Berrettini, W H, Guo, Y, Li, D, Schork, N J, Komaki, G, Ando, T, Inoko, H, Esko, T, Fischer, K, Männik, K, Metspalu, A, Baker, J H, Cone, R D, Dackor, J, DeSocio, J E, Hilliard, C E, O'Toole, J K, Pantel, J, Szatkiewicz, J P, Taico, C, Zerwas, S, Trace, S E, Davis, O S P, Helder, S, Bühren, K, Burghardt, R, de Zwaan, M, Egberts, K, Ehrlich, S, Herpertz-Dahlmann, B, Herzog, W, Imgart, H, Scherag, A, Scherag, S, Zipfel, S, Boni, C, Ramoz, N, Versini, A, Brandys, M K, Danner, U N, de Kovel, C, Hendriks, J, Koeleman, B P C, Ophoff, R A, Strengman, E, van Elburg, A A, Bruson, A, Clementi, M, Degortes, D, Forzan, M, Tenconi, E, Docampo, E, Escaramís, G, Jiménez-Murcia, S, Lissowska, J, Rajewski, A, Szeszenia-Dabrowska, N, Slopien, A, Hauser, J, Karhunen, L, Meulenbelt, I, Slagboom, P E, Tortorella, A, Maj, M, Dedoussis, G, Dikeos, D, Gonidakis, F, Tziouvas, K, Tsitsika, A, Papezova, H, Slachtova, L, Martaskova, D, Kennedy, J L, Levitan, R D, Yilmaz, Z, Huemer, J, Koubek, D, Merl, E, Wagner, G, Lichtenstein, P, Breen, G, Cohen-Woods, S, Farmer, A, McGuffin, P, Cichon, S, Giegling, I, Herms, S, Rujescu, D, Schreiber, S, Wichmann, H-E, Dina, C, Sladek, R, Gambaro, G, Soranzo, N, Julia, A, Marsal, S, Rabionet, R, Gaborieau, V, Dick, D M, Palotie, A, Ripatti, S, Widén, E, Andreassen, O A, Espeseth, T, Lundervold, A, Reinvang, I, Steen, V M, Le Hellard, S, Mattingsdal, M, Ntalla, I, Bencko, V, Foretova, L, Janout, V, Navratilova, M, Gallinger, S, Pinto, D, Scherer, S W, Aschauer, H, Carlberg, L, Schosser, A, Alfredsson, L, Ding, B, Klareskog, L, Padyukov, L, Courtet, P, Guillaume, S, Jaussent, I, Finan, C, Kalsi, G, Roberts, M, Logan, D W, Peltonen, L, Ritchie, G R S, Barrett, J C, Estivill, X, Hinney, A, Sullivan, P F, Collier, D A, Zeggini, E, and Bulik, C M

Published
2014
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24. A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53

Author

Wang, J-C, Foroud, T, Hinrichs, A L, Le, N X H, Bertelsen, S, Budde, J P, Harari, O, Koller, D L, Wetherill, L, Agrawal, A, Almasy, L, Brooks, A I, Bucholz, K, Dick, D, Hesselbrock, V, Johnson, E O, Kang, S, Kapoor, M, Kramer, J, Kuperman, S, Madden, P A F, Manz, N, Martin, N G, McClintick, J N, Montgomery, G W, Nurnberger, Jr, J I, Rangaswamy, M, Rice, J, Schuckit, M, Tischfield, J A, Whitfield, J B, Xuei, X, Porjesz, B, Heath, A C, Edenberg, H J, Bierut, L J, and Goate, A M

Published
2013
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28. Cortical profiles of numerous psychiatric disorders and normal development share a common pattern

Author

Cao, Zhipeng, Cupertino, Renata B., Ottino-Gonzalez, Jonatan, Murphy, Alistair, Pancholi, Devarshi, Juliano, Anthony, Chaarani, Bader, Albaugh, Matthew, Yuan, Dekang, Schwab, Nathan, Stafford, James, Goudriaan, Anna E., Hutchison, Kent, Li, Chiang-Shan R., Luijten, Maartje, Groefsema, Martine, Momenan, Reza, Schmaal, Lianne, Sinha, Rajita, van Holst, Ruth J., Veltman, Dick J., Wiers, Reinout W., Porjesz, Bernice, Lett, Tristram, Banaschewski, Tobias, Bokde, Arun L. W., Desrivières, Sylvane, Flor, Herta, Grigis, Antoine, Gowland, Penny, Heinz, Andreas, Brühl, Rüdiger, Martinot, Jean-Luc, Martinot, Marie-Laure Paillère, Artiges, Eric, Nees, Frauke, Orfanos, Dimitri Papadopoulos, Paus, Tomáš, Poustka, Luise, Hohmann, Sarah, Millenet, Sabina, Fröhner, Juliane H., Robinson, Lauren, Smolka, Michael N., Walter, Henrik, Winterer, Jeanne, Schumann, Gunter, Whelan, Robert, Bhatt, Ravi R., Zhu, Alyssa, Conrod, Patricia, Jahanshad, Neda, Thompson, Paul M., Mackey, Scott, and Garavan, Hugh

Abstract

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1and KCNS2with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.

Published
2022
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29. Alcohol reverses the effects of KCNJ6(GIRK2) noncoding variants on excitability of human glutamatergic neurons

Author

Popova, Dina, Gameiro-Ros, Isabel, Youssef, Mark M., Zalamea, Petronio, Morris, Ayeshia D., Prytkova, Iya, Jadali, Azadeh, Kwan, Kelvin Y., Kamarajan, Chella, Salvatore, Jessica E., Xuei, Xiaoling, Chorlian, David B., Porjesz, Bernice, Kuperman, Samuel, Dick, Danielle M., Goate, Alison, Edenberg, Howard J., Tischfield, Jay A., Pang, Zhiping P., Slesinger, Paul A., and Hart, Ronald P.

Abstract

Synonymous and noncoding single nucleotide polymorphisms (SNPs) in the KCNJ6gene, encoding G protein-gated inwardly rectifying potassium channel subunit 2 (GIRK2), have been linked with increased electroencephalographic frontal theta event-related oscillations (ERO) in subjects diagnosed with alcohol use disorder (AUD). To identify molecular and cellular mechanisms while retaining the appropriate genetic background, we generated induced excitatory glutamatergic neurons (iN) from iPSCs derived from four AUD-diagnosed subjects with KCNJ6variants (“Affected: AF”) and four control subjects without variants (“Unaffected: UN”). Neurons were analyzed for changes in gene expression, morphology, excitability and physiological properties. Single-cell RNA sequencing suggests that KCNJ6AF variant neurons have altered patterns of synaptic transmission and cell projection morphogenesis. Results confirm that AF neurons express lower levels of GIRK2, have greater neurite area, and elevated excitability. Interestingly, exposure to intoxicating concentrations of ethanol induces GIRK2 expression and reverses functional effects in AF neurons. Ectopic overexpression of GIRK2 alone mimics the effect of ethanol to normalize induced excitability. We conclude that KCNJ6variants decrease GIRK2 expression and increase excitability and that this effect can be minimized or reduced with ethanol.

Published
2022
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