Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.

VL - 15 U1 - https://www.ncbi.nlm.nih.gov/pubmed/34177490?dopt=Abstract ER - TY - JOUR T1 - Involvement of the habenula in the pathophysiology of autism spectrum disorder. JF - Sci Rep Y1 - 2021 A1 - Germann, Jürgen A1 - Gouveia, Flavia Venetucci A1 - Brentani, Helena A1 - Bedford, Saashi A A1 - Tullo, Stephanie A1 - Mallar M Chakravarty A1 - Devenyi, Gabriel A AB -The habenula is a small epithalamic structure with widespread connections to multiple cortical, subcortical and brainstem regions. It has been identified as the central structure modulating the reward value of social interactions, behavioral adaptation, sensory integration and circadian rhythm. Autism spectrum disorder (ASD) is characterized by social communication deficits, restricted interests, repetitive behaviors, and is frequently associated with altered sensory perception and mood and sleep disorders. The habenula is implicated in all these behaviors and results of preclinical studies suggest a possible involvement of the habenula in the pathophysiology of this disorder. Using anatomical magnetic resonance imaging and automated segmentation we show that the habenula is significantly enlarged in ASD subjects compared to controls across the entire age range studied (6-30 years). No differences were observed between sexes. Furthermore, support-vector machine modeling classified ASD with 85% accuracy (model using habenula volume, age and sex) and 64% accuracy in cross validation. The Social Responsiveness Scale (SRS) significantly differed between groups, however, it was not related to individual habenula volume. The present study is the first to provide evidence in human subjects of an involvement of the habenula in the pathophysiology of ASD.

VL - 11 CP - 1 U1 - https://www.ncbi.nlm.nih.gov/pubmed/34707133?dopt=Abstract ER - TY - JOUR T1 - Longitudinal Changes After Amygdala Surgery for Intractable Aggressive Behavior: Clinical, Imaging Genetics, and Deformation-Based Morphometry Study-A Case Series. JF - Neurosurgery Y1 - 2020 A1 - Gouveia, Flavia Venetucci A1 - Germann, Jürgen A1 - de Morais, Rosa A1 - Fonoff, Erich Talamoni A1 - Hamani, Clement A1 - Alho, Eduardo Joaquim A1 - Brentani, Helena A1 - Martins, Ana Paula A1 - Devenyi, Gabriel A1 - Patel, Raihaan A1 - Steele, Christopher A1 - Gramer, Robert A1 - Mallar M Chakravarty A1 - Martinez, Raquel Chacon Ruiz AB -**BACKGROUND: **Intractable aggressive behavior (iAB) is a devastating behavioral disorder that may affect psychiatric patients. These patients have reduced quality of life, are more challenging to treat as they impose a high caregiver burden and require specialized care. Neuromodulatory interventions targeting the amygdala, a key hub in the circuitry of aggressive behavior (AB), may provide symptom alleviation.

**OBJECTIVE: **To Report clinical and imaging findings from a case series of iAB patients treated with bilateral amygdala ablation.

**METHODS: **This series included 4 cases (3 males, 19-32 years old) who underwent bilateral amygdala radiofrequency ablation for iAB hallmarked by life-threatening self-injury and social aggression. Pre- and postassessments involved full clinical, psychiatric, and neurosurgical evaluations, including scales quantifying AB, general agitation, quality of life, and magnetic resonance imaging (MRI).

**RESULTS: **Postsurgery assessments revealed decreased aggression and agitation and improved quality of life. AB was correlated with testosterone levels and testosterone/cortisol ratio in males. No clinically significant side effects were observed. Imaging analyses showed preoperative amygdala volumes within normal populational range and confirmed lesion locations. The reductions in aggressive symptoms were accompanied by significant postsurgical volumetric reductions in brain areas classically associated with AB and increases in regions related to somatosensation. The local volumetric reductions are found in areas that in a normal brain show high expression levels of genes related to AB (eg, aminergic transmission) using gene expression data provided by the Allen brain atlas.

**CONCLUSION: **These findings provide new insight into the whole brain neurocircuitry of aggression and suggest a role of altered somatosensation and possible novel neuromodulation targets.

Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.

VL - 6 CP - 5 U1 - https://www.ncbi.nlm.nih.gov/pubmed/32762791?dopt=Abstract ER - TY - JOUR T1 - Analysis of shared heritability in common disorders of the brain. JF - Science Y1 - 2018 A1 - Anttila, Verneri A1 - Bulik-Sullivan, Brendan A1 - Finucane, Hilary K A1 - Walters, Raymond K A1 - Bras, Jose A1 - Duncan, Laramie A1 - Escott-Price, Valentina A1 - Falcone, Guido J A1 - Gormley, Padhraig A1 - Malik, Rainer A1 - Patsopoulos, Nikolaos A A1 - Ripke, Stephan A1 - Wei, Zhi A1 - Yu, Dongmei A1 - Lee, Phil H A1 - Turley, Patrick A1 - Grenier-Boley, Benjamin A1 - Chouraki, Vincent A1 - Kamatani, Yoichiro A1 - Berr, Claudine A1 - Letenneur, Luc A1 - Hannequin, Didier A1 - Amouyel, Philippe A1 - Boland, Anne A1 - Deleuze, Jean-François A1 - Duron, Emmanuelle A1 - Vardarajan, Badri N A1 - Reitz, Christiane A1 - Goate, Alison M A1 - Huentelman, Matthew J A1 - Kamboh, M Ilyas A1 - Larson, Eric B A1 - Rogaeva, Ekaterina A1 - St George-Hyslop, Peter A1 - Hakonarson, Hakon A1 - Kukull, Walter A A1 - Farrer, Lindsay A A1 - Barnes, Lisa L A1 - Beach, Thomas G A1 - Demirci, F Yesim A1 - Head, Elizabeth A1 - Hulette, Christine M A1 - Jicha, Gregory A A1 - Kauwe, John S K A1 - Kaye, Jeffrey A A1 - Leverenz, James B A1 - Levey, Allan I A1 - Lieberman, Andrew P A1 - Pankratz, Vernon S A1 - Poon, Wayne W A1 - Quinn, Joseph F A1 - Saykin, Andrew J A1 - Schneider, Lon S A1 - Smith, Amanda G A1 - Sonnen, Joshua A A1 - Stern, Robert A A1 - Van Deerlin, Vivianna M A1 - Van Eldik, Linda J A1 - Harold, Denise A1 - Russo, Giancarlo A1 - Rubinsztein, David C A1 - Bayer, Anthony A1 - Tsolaki, Magda A1 - Proitsi, Petra A1 - Fox, Nick C A1 - Hampel, Harald A1 - Owen, Michael J A1 - Mead, Simon A1 - Passmore, Peter A1 - Morgan, Kevin A1 - Nöthen, Markus M A1 - Rossor, Martin A1 - Lupton, Michelle K A1 - Hoffmann, Per A1 - Kornhuber, Johannes A1 - Lawlor, Brian A1 - McQuillin, Andrew A1 - Al-Chalabi, Ammar A1 - Bis, Joshua C A1 - Ruiz, Agustin A1 - Boada, Mercè A1 - Seshadri, Sudha A1 - Beiser, Alexa A1 - Rice, Kenneth A1 - van der Lee, Sven J A1 - De Jager, Philip L A1 - Geschwind, Daniel H A1 - Riemenschneider, Matthias A1 - Riedel-Heller, Steffi A1 - Rotter, Jerome I A1 - Ransmayr, Gerhard A1 - Hyman, Bradley T A1 - Cruchaga, Carlos A1 - Alegret, Montserrat A1 - Winsvold, Bendik A1 - Palta, Priit A1 - Farh, Kai-How A1 - Cuenca-Leon, Ester A1 - Furlotte, Nicholas A1 - Kurth, Tobias A1 - Ligthart, Lannie A1 - Terwindt, Gisela M A1 - Freilinger, Tobias A1 - Ran, Caroline A1 - Gordon, Scott D A1 - Borck, Guntram A1 - Adams, Hieab H H A1 - Lehtimäki, Terho A1 - Wedenoja, Juho A1 - Buring, Julie E A1 - Schürks, Markus A1 - Hrafnsdottir, Maria A1 - Hottenga, Jouke-Jan A1 - Penninx, Brenda A1 - Artto, Ville A1 - Kaunisto, Mari A1 - Vepsäläinen, Salli A1 - Martin, Nicholas G A1 - Montgomery, Grant W A1 - Kurki, Mitja I A1 - Hämäläinen, Eija A1 - Huang, Hailiang A1 - Huang, Jie A1 - Sandor, Cynthia A1 - Webber, Caleb A1 - Müller-Myhsok, Bertram A1 - Schreiber, Stefan A1 - Salomaa, Veikko A1 - Loehrer, Elizabeth A1 - Göbel, Hartmut A1 - Macaya, Alfons A1 - Pozo-Rosich, Patricia A1 - Hansen, Thomas A1 - Werge, Thomas A1 - Kaprio, Jaakko A1 - Metspalu, Andres A1 - Kubisch, Christian A1 - Ferrari, Michel D A1 - Belin, Andrea C A1 - van den Maagdenberg, Arn M J M A1 - Zwart, John-Anker A1 - Boomsma, Dorret A1 - Eriksson, Nicholas A1 - Olesen, Jes A1 - Chasman, Daniel I A1 - Nyholt, Dale R A1 - Avbersek, Andreja A1 - Baum, Larry A1 - Berkovic, Samuel A1 - Bradfield, Jonathan A1 - Buono, Russell A1 - Catarino, Claudia B A1 - Cossette, Patrick A1 - De Jonghe, Peter A1 - Depondt, Chantal A1 - Dlugos, Dennis A1 - Ferraro, Thomas N A1 - French, Jacqueline A1 - Hjalgrim, Helle A1 - Jamnadas-Khoda, Jennifer A1 - Kälviäinen, Reetta A1 - Kunz, Wolfram S A1 - Lerche, Holger A1 - Leu, Costin A1 - Lindhout, Dick A1 - Lo, Warren A1 - Lowenstein, Daniel A1 - McCormack, Mark A1 - Møller, Rikke S A1 - Molloy, Anne A1 - Ng, Ping-Wing A1 - Oliver, Karen A1 - Privitera, Michael A1 - Radtke, Rodney A1 - Ruppert, Ann-Kathrin A1 - Sander, Thomas A1 - Schachter, Steven A1 - Schankin, Christoph A1 - Scheffer, Ingrid A1 - Schoch, Susanne A1 - Sisodiya, Sanjay M A1 - Smith, Philip A1 - Sperling, Michael A1 - Striano, Pasquale A1 - Surges, Rainer A1 - Thomas, G Neil A1 - Visscher, Frank A1 - Whelan, Christopher D A1 - Zara, Federico A1 - Heinzen, Erin L A1 - Marson, Anthony A1 - Becker, Felicitas A1 - Stroink, Hans A1 - Zimprich, Fritz A1 - Gasser, Thomas A1 - Gibbs, Raphael A1 - Heutink, Peter A1 - Martinez, Maria A1 - Morris, Huw R A1 - Sharma, Manu A1 - Ryten, Mina A1 - Mok, Kin Y A1 - Pulit, Sara A1 - Bevan, Steve A1 - Holliday, Elizabeth A1 - Attia, John A1 - Battey, Thomas A1 - Boncoraglio, Giorgio A1 - Thijs, Vincent A1 - Chen, Wei-Min A1 - Mitchell, Braxton A1 - Rothwell, Peter A1 - Sharma, Pankaj A1 - Sudlow, Cathie A1 - Vicente, Astrid A1 - Markus, Hugh A1 - Kourkoulis, Christina A1 - Pera, Joana A1 - Raffeld, Miriam A1 - Silliman, Scott A1 - Boraska Perica, Vesna A1 - Thornton, Laura M A1 - Huckins, Laura M A1 - William Rayner, N A1 - Lewis, Cathryn M A1 - Gratacos, Monica A1 - Rybakowski, Filip A1 - Keski-Rahkonen, Anna A1 - Raevuori, Anu A1 - Hudson, James I A1 - Reichborn-Kjennerud, Ted A1 - Monteleone, Palmiero A1 - Karwautz, Andreas A1 - Mannik, Katrin A1 - Baker, Jessica H A1 - O'Toole, Julie K A1 - Trace, Sara E A1 - Davis, Oliver S P A1 - Helder, Sietske G A1 - Ehrlich, Stefan A1 - Herpertz-Dahlmann, Beate A1 - Danner, Unna N A1 - van Elburg, Annemarie A A1 - Clementi, Maurizio A1 - Forzan, Monica A1 - Docampo, Elisa A1 - Lissowska, Jolanta A1 - Hauser, Joanna A1 - Tortorella, Alfonso A1 - Maj, Mario A1 - Gonidakis, Fragiskos A1 - Tziouvas, Konstantinos A1 - Papezova, Hana A1 - Yilmaz, Zeynep A1 - Wagner, Gudrun A1 - Cohen-Woods, Sarah A1 - Herms, Stefan A1 - Julià, Antonio A1 - Rabionet, Raquel A1 - Dick, Danielle M A1 - Ripatti, Samuli A1 - Andreassen, Ole A A1 - Espeseth, Thomas A1 - Lundervold, Astri J A1 - Steen, Vidar M A1 - Pinto, Dalila A1 - Scherer, Stephen W A1 - Aschauer, Harald A1 - Schosser, Alexandra A1 - Alfredsson, Lars A1 - Padyukov, Leonid A1 - Halmi, Katherine A A1 - Mitchell, James A1 - Strober, Michael A1 - Bergen, Andrew W A1 - Kaye, Walter A1 - Szatkiewicz, Jin Peng A1 - Cormand, Bru A1 - Ramos-Quiroga, Josep Antoni A1 - Sánchez-Mora, Cristina A1 - Ribasés, Marta A1 - Casas, Miguel A1 - Hervas, Amaia A1 - Arranz, Maria Jesús A1 - Haavik, Jan A1 - Zayats, Tetyana A1 - Johansson, Stefan A1 - Williams, Nigel A1 - Dempfle, Astrid A1 - Rothenberger, Aribert A1 - Kuntsi, Jonna A1 - Oades, Robert D A1 - Banaschewski, Tobias A1 - Franke, Barbara A1 - Buitelaar, Jan K A1 - Arias Vasquez, Alejandro A1 - Doyle, Alysa E A1 - Reif, Andreas A1 - Lesch, Klaus-Peter A1 - Freitag, Christine A1 - Rivero, Olga A1 - Palmason, Haukur A1 - Romanos, Marcel A1 - Langley, Kate A1 - Rietschel, Marcella A1 - Witt, Stephanie H A1 - Dalsgaard, Soeren A1 - Børglum, Anders D A1 - Waldman, Irwin A1 - Wilmot, Beth A1 - Molly, Nikolas A1 - Bau, Claiton H D A1 - Crosbie, Jennifer A1 - Schachar, Russell A1 - Loo, Sandra K A1 - McGough, James J A1 - Grevet, Eugenio H A1 - Medland, Sarah E A1 - Robinson, Elise A1 - Weiss, Lauren A A1 - Bacchelli, Elena A1 - Bailey, Anthony A1 - Bal, Vanessa A1 - Battaglia, Agatino A1 - Betancur, Catalina A1 - Bolton, Patrick A1 - Cantor, Rita A1 - Celestino-Soper, Patrícia A1 - Dawson, Geraldine A1 - De Rubeis, Silvia A1 - Duque, Frederico A1 - Green, Andrew A1 - Klauck, Sabine M A1 - Leboyer, Marion A1 - Levitt, Pat A1 - Maestrini, Elena A1 - Mane, Shrikant A1 - De-Luca, Daniel Moreno- A1 - Parr, Jeremy A1 - Regan, Regina A1 - Reichenberg, Abraham A1 - Sandin, Sven A1 - Vorstman, Jacob A1 - Wassink, Thomas A1 - Wijsman, Ellen A1 - Cook, Edwin A1 - Santangelo, Susan A1 - Delorme, Richard A1 - Rogé, Bernadette A1 - Magalhaes, Tiago A1 - Arking, Dan A1 - Schulze, Thomas G A1 - Thompson, Robert C A1 - Strohmaier, Jana A1 - Matthews, Keith A1 - Melle, Ingrid A1 - Morris, Derek A1 - Blackwood, Douglas A1 - McIntosh, Andrew A1 - Bergen, Sarah E A1 - Schalling, Martin A1 - Jamain, Stephane A1 - Maaser, Anna A1 - Fischer, Sascha B A1 - Reinbold, Céline S A1 - Fullerton, Janice M A1 - Guzman-Parra, José A1 - Mayoral, Fermin A1 - Schofield, Peter R A1 - Cichon, Sven A1 - Mühleisen, Thomas W A1 - Degenhardt, Franziska A1 - Schumacher, Johannes A1 - Bauer, Michael A1 - Mitchell, Philip B A1 - Gershon, Elliot S A1 - Rice, John A1 - Potash, James B A1 - Zandi, Peter P A1 - Craddock, Nick A1 - Ferrier, I Nicol A1 - Alda, Martin A1 - Rouleau, Guy A A1 - Gustavo Turecki A1 - Ophoff, Roel A1 - Pato, Carlos A1 - Anjorin, Adebayo A1 - Stahl, Eli A1 - Leber, Markus A1 - Czerski, Piotr M A1 - Cruceanu, Cristiana A1 - Jones, Ian R A1 - Posthuma, Danielle A1 - Andlauer, Till F M A1 - Forstner, Andreas J A1 - Streit, Fabian A1 - Baune, Bernhard T A1 - Air, Tracy A1 - Sinnamon, Grant A1 - Wray, Naomi R A1 - MacIntyre, Donald J A1 - Porteous, David A1 - Homuth, Georg A1 - Rivera, Margarita A1 - Grove, Jakob A1 - Middeldorp, Christel M A1 - Hickie, Ian A1 - Pergadia, Michele A1 - Mehta, Divya A1 - Smit, Johannes H A1 - Jansen, Rick A1 - de Geus, Eco A1 - Dunn, Erin A1 - Li, Qingqin S A1 - Nauck, Matthias A1 - Schoevers, Robert A A1 - Beekman, Aartjan Tf A1 - Knowles, James A A1 - Viktorin, Alexander A1 - Arnold, Paul A1 - Barr, Cathy L A1 - Bedoya-Berrio, Gabriel A1 - Bienvenu, O Joseph A1 - Brentani, Helena A1 - Burton, Christie A1 - Camarena, Beatriz A1 - Cappi, Carolina A1 - Cath, Danielle A1 - Cavallini, Maria A1 - Cusi, Daniele A1 - Darrow, Sabrina A1 - Denys, Damiaan A1 - Derks, Eske M A1 - Dietrich, Andrea A1 - Fernandez, Thomas A1 - Figee, Martijn A1 - Freimer, Nelson A1 - Gerber, Gloria A1 - Grados, Marco A1 - Greenberg, Erica A1 - Hanna, Gregory L A1 - Hartmann, Andreas A1 - Hirschtritt, Matthew E A1 - Hoekstra, Pieter J A1 - Huang, Alden A1 - Huyser, Chaim A1 - Illmann, Cornelia A1 - Jenike, Michael A1 - Kuperman, Samuel A1 - Leventhal, Bennett A1 - Lochner, Christine A1 - Lyon, Gholson J A1 - Macciardi, Fabio A1 - Madruga-Garrido, Marcos A1 - Malaty, Irene A A1 - Maras, Athanasios A1 - McGrath, Lauren A1 - Miguel, Eurípedes C A1 - Mir, Pablo A1 - Nestadt, Gerald A1 - Nicolini, Humberto A1 - Okun, Michael S A1 - Pakstis, Andrew A1 - Paschou, Peristera A1 - Piacentini, John A1 - Pittenger, Christopher A1 - Plessen, Kerstin A1 - Ramensky, Vasily A1 - Ramos, Eliana M A1 - Reus, Victor A1 - Richter, Margaret A A1 - Riddle, Mark A A1 - Robertson, Mary M A1 - Roessner, Veit A1 - Rosário, Maria A1 - Samuels, Jack F A1 - Sandor, Paul A1 - Stein, Dan J A1 - Tsetsos, Fotis A1 - Van Nieuwerburgh, Filip A1 - Weatherall, Sarah A1 - Wendland, Jens R A1 - Wolanczyk, Tomasz A1 - Worbe, Yulia A1 - Zai, Gwyneth A1 - Goes, Fernando S A1 - McLaughlin, Nicole A1 - Nestadt, Paul S A1 - Grabe, Hans-Jorgen A1 - Depienne, Christel A1 - Konkashbaev, Anuar A1 - Lanzagorta, Nuria A1 - Valencia-Duarte, Ana A1 - Bramon, Elvira A1 - Buccola, Nancy A1 - Cahn, Wiepke A1 - Cairns, Murray A1 - Chong, Siow A A1 - Cohen, David A1 - Crespo-Facorro, Benedicto A1 - Crowley, James A1 - Davidson, Michael A1 - DeLisi, Lynn A1 - Dinan, Timothy A1 - Donohoe, Gary A1 - Drapeau, Elodie A1 - Duan, Jubao A1 - Haan, Lieuwe A1 - Hougaard, David A1 - Karachanak-Yankova, Sena A1 - Khrunin, Andrey A1 - Klovins, Janis A1 - Kučinskas, Vaidutis A1 - Lee Chee Keong, Jimmy A1 - Limborska, Svetlana A1 - Loughland, Carmel A1 - Lönnqvist, Jouko A1 - Maher, Brion A1 - Mattheisen, Manuel A1 - McDonald, Colm A1 - Murphy, Kieran C A1 - Nenadic, Igor A1 - van Os, Jim A1 - Pantelis, Christos A1 - Pato, Michele A1 - Petryshen, Tracey A1 - Quested, Digby A1 - Roussos, Panos A1 - Sanders, Alan R A1 - Schall, Ulrich A1 - Schwab, Sibylle G A1 - Sim, Kang A1 - So, Hon-Cheong A1 - Stögmann, Elisabeth A1 - Subramaniam, Mythily A1 - Toncheva, Draga A1 - Waddington, John A1 - Walters, James A1 - Weiser, Mark A1 - Cheng, Wei A1 - Cloninger, Robert A1 - Curtis, David A1 - Gejman, Pablo V A1 - Henskens, Frans A1 - Mattingsdal, Morten A1 - Oh, Sang-Yun A1 - Scott, Rodney A1 - Webb, Bradley A1 - Breen, Gerome A1 - Churchhouse, Claire A1 - Bulik, Cynthia M A1 - Daly, Mark A1 - Dichgans, Martin A1 - Faraone, Stephen V A1 - Guerreiro, Rita A1 - Holmans, Peter A1 - Kendler, Kenneth S A1 - Koeleman, Bobby A1 - Mathews, Carol A A1 - Price, Alkes A1 - Scharf, Jeremiah A1 - Sklar, Pamela A1 - Williams, Julie A1 - Wood, Nicholas W A1 - Cotsapas, Chris A1 - Palotie, Aarno A1 - Smoller, Jordan W A1 - Sullivan, Patrick A1 - Rosand, Jonathan A1 - Corvin, Aiden A1 - Neale, Benjamin M AB -Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

VL - 360 CP - 6395 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29930110?dopt=Abstract ER -