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1. Childhood adversity impacts on brain subcortical structures relevant to depression

Author

Frodl, Thomas, Janowitz, Deborah, Schmaal, Lianne, Tozzi, Leonardo, Dobrowolny, Henrik, Stein, Dan J, Veltman, Dick J, Wittfeld, Katharina, van Erp, Theo GM, Jahanshad, Neda, Block, Andrea, Hegenscheid, Katrin, Völzke, Henry, Lagopoulos, Jim, Hatton, Sean N, Hickie, Ian B, Frey, Eva Maria, Carballedo, Angela, Brooks, Samantha J, Vuletic, Daniella, Uhlmann, Anne, Veer, Ilya M, Walter, Henrik, Schnell, Knut, Grotegerd, Dominik, Arolt, Volker, Kugel, Harald, Schramm, Elisabeth, Konrad, Carsten, Zurowski, Bartosz, Baune, Bernhard T, van der Wee, Nic JA, van Tol, Marie-Jose, Penninx, Brenda WJH, Thompson, Paul M, Hibar, Derrek P, Dannlowski, Udo, and Grabe, Hans J

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Mental Health, Violence Research, Serious Mental Illness, Behavioral and Social Science, Depression, Major Depressive Disorder, Brain Disorders, Pediatric, Neurosciences, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Adult, Adult Survivors of Child Adverse Events, Antidepressive Agents, Brain, Depressive Disorder, Major, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Psychiatric Status Rating Scales, Sex Characteristics, Software, Surveys and Questionnaires, Childhood adversity, MRI, Caudate, Hippocampus, ENIGMA, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression.

Published
2017

2. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author

Thompson, Paul M, Stein, Jason L, Medland, Sarah E, Hibar, Derrek P, Vasquez, Alejandro Arias, Renteria, Miguel E, Toro, Roberto, Jahanshad, Neda, Schumann, Gunter, Franke, Barbara, Wright, Margaret J, Martin, Nicholas G, Agartz, Ingrid, Alda, Martin, Alhusaini, Saud, Almasy, Laura, Almeida, Jorge, Alpert, Kathryn, Andreasen, Nancy C, Andreassen, Ole A, Apostolova, Liana G, Appel, Katja, Armstrong, Nicola J, Aribisala, Benjamin, Bastin, Mark E, Bauer, Michael, Bearden, Carrie E, Bergmann, Ørjan, Binder, Elisabeth B, Blangero, John, Bockholt, Henry J, Bøen, Erlend, Bois, Catherine, Boomsma, Dorret I, Booth, Tom, Bowman, Ian J, Bralten, Janita, Brouwer, Rachel M, Brunner, Han G, Brohawn, David G, Buckner, Randy L, Buitelaar, Jan, Bulayeva, Kazima, Bustillo, Juan R, Calhoun, Vince D, Cannon, Dara M, Cantor, Rita M, Carless, Melanie A, Caseras, Xavier, Cavalleri, Gianpiero L, Chakravarty, M Mallar, Chang, Kiki D, Ching, Christopher RK, Christoforou, Andrea, Cichon, Sven, Clark, Vincent P, Conrod, Patricia, Coppola, Giovanni, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Deary, Ian J, de Geus, Eco JC, den Braber, Anouk, Delvecchio, Giuseppe, Depondt, Chantal, de Haan, Lieuwe, de Zubicaray, Greig I, Dima, Danai, Dimitrova, Rali, Djurovic, Srdjan, Dong, Hongwei, Donohoe, Gary, Duggirala, Ravindranath, Dyer, Thomas D, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Emsell, Louise, Erk, Susanne, Espeseth, Thomas, Fagerness, Jesen, Fears, Scott, Fedko, Iryna, Fernández, Guillén, Fisher, Simon E, Foroud, Tatiana, Fox, Peter T, Francks, Clyde, Frangou, Sophia, Frey, Eva Maria, Frodl, Thomas, Frouin, Vincent, Garavan, Hugh, Giddaluru, Sudheer, Glahn, David C, Godlewska, Beata, Goldstein, Rita Z, Gollub, Randy L, and Grabe, Hans J

Subjects
Biological Psychology, Health Sciences, Psychology, Mental Illness, Human Genome, Neurosciences, Brain Disorders, Schizophrenia, Biomedical Imaging, Mental Health, Genetics, 2.1 Biological and endogenous factors, Mental health, Neurological, Good Health and Well Being, Brain Mapping, Cooperative Behavior, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Neuroimaging, MRI, GWAS, Consortium, Meta-analysis, Multi-site, Alzheimer’s Disease Neuroimaging Initiative, EPIGEN Consortium, IMAGEN Consortium, Saguenay Youth Study (SYS) Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology, Biomedical and clinical sciences, Health sciences
Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Published
2014

4. Subkortikale Hirnstrukturen und Hippocampussubfelder in ihrer Assoziation zur Methylierung des Serotonintransportergens bei der depressiven Störung

Author

Frey, Eva-Maria

Subjects
ddc:610, 610 Medizin, MDD, Serotonintransporter, Methylierung
Abstract

Die vorliegende Studie untersuchte 49 Patienten mit Major Depressive Disorder (MDD), die sich beim psychiatrischen Gesundheitsdienst des Adelaide and Meath Hospitals und des National Children’s Hospitals in Dublin in ambulanter Behandlung befanden. Ihnen gegenübergestellt wurde eine Gruppe aus 49 gesunden Kontrollprobanden. Die 98 Studienteilnehmer erhielten eine magnetresonanztomographische zerebrale Bildgebung, anhand derer wir volumetrische Unterschiede in den subkortikalen Strukturen Thalamus, Putamen, Nucleus caudatus, Pallidum, Nucleus accumbens, Hippocampus, Amygdala und der Seitenventrikel sowie der Hippocampussubfelder CA1, CA2/3, CA4/DG, Subiculum, Präsubiculum und Fimbrien analysierten. Die volumetrischen Berechnungen wurden mit dem Segmentierungsprogramm FreeSurfer durchgeführt und mit Matlab sowie manuell überprüft. Die Volumina wurden auf signifikante Unterschiede bezüglich der Diagnose MDD, des Alters und des Geschlechtes untersucht. Das Hippocampusvolumen stellte sich bei Depressiven in beiden Hemisphären signifikant kleiner dar als bei Gesunden, die Volumina der Hippocampussubfelder CA2/3 und CA4/DG zeigten einen gleichartigen Effekt unilateral links. Diese Ergebnisse werden in anderen Studien bestätigt, die Einordnung der Volumenveränderungen in die Chronologie der Major Depressive Disorder bleibt jedoch unklar. So könnte die Depression Folge einer vorausgehenden Volumenverkleinerung in bestimmten Hirnarealen sein oder die morphologischen Veränderungen im Verlauf der Major Depressive Disorder durch krankheitsassoziierte Vorgänge geschehen. Der Hippocampus stellt einen Teil des limbischen Systems dar, der generell in zahlreichen emotionalen Vorgängen sowie in der Gedächtnisfunktion involviert ist. Bezüglich geschlechtlicher Unterschiede wurde ein beidseits signifikant größeres Pallidum- und Fimbrienvolumen bei den männlichen als bei den weiblichen Probanden verzeichnet. Den volumetrischen Veränderungen im Pallidum könnte eine generell größere Rolle in emotionalen und sexuellen Vorgängen bei Männern zugrunde liegen, die Veränderungen im Fimbrienvolumen sind angesichts der aktuellen Studienlage bezüglich dieses noch wenig erforschten Hippocampussubfelds schwer zu interpretieren. Das Alter der Probanden war signifikant mit einer beidseitigen Vergrößerung der Seitenventrikel, sowie einer signifikanten Verkleinerung der Volumina des Putamens, des Nucleus accumbens und des Pallidums assoziiert. Diese Beobachtung wird ebenfalls in zahlreichen vorausgehenden Studien belegt und ist wahrscheinlich durch eine physiologische Atrophie der Hirnsubstanz im Alter und eine fraglich reaktive Vergrößerung der Ventrikel zum intrakraniellen Volumenausgleich bedingt. Weiterhin stellte sich die Frage nach dem Zusammenhang von volumetrischen Veränderungen mit Stresserlebnissen in der Kindheit, die wir bei den Studienteilnehmern anhand des Childhood Trauma Questionnaires anamnestisch erhoben. In diesem Zusammenhang erhielten wir weder signifikante Ergebnisse in den Volumina der subkortikalen Strukturen noch in denen der Hippocampussubfelder, lediglich die Interaktion zwischen kindlichem Stress und Diagnose zeigte eine signifikante Assoziation bezüglich des Pallidumvolumens der rechten Hemisphäre auf. Patienten, die in der Kindheit keinen Missbrauch erfahren hatten, hatten durchschnittlich kleinere Pallidumvolumina, Patienten mit kindlichem Missbrauch zeigten auf der rechten Seite größere und auf der linken Seite kleinere Pallidumvolumina als die Kontrollprobanden. Innerhalb der nach Missbrauchserlebnissen aufgeteilten Probandengruppen erreichten diese Ergebnisse keine Signifikanz mehr, jedoch wird die Bedeutung des Pallidums als stresssensitive zerebrale Struktur hervorgehoben. Den zweiten großen Teil der Studie stellte die Untersuchung einer Untergruppe unserer Studienteilnehmer von insgesamt 69 Probanden (33 Patienten und 36 Kontrollprobanden) dar, die sich zu einer Blutentnahme zur Analyse epigenetischer Methylierung des Serotonintransportergens SLC6A4 in der DNA peripherer Blutzellen bereit erklärt hatten. Hier untersuchten wir die Assoziationen zwischen Methylierung und Alter, Geschlecht, Diagnose, kindlichem Missbrauch und Hippocampusvolumen. Es ergaben sich jeweils unabhängige signifikante Zusammenhänge zwischen Methylierung und Alter, kindlichem Stress und Hippocampusvolumen. Alter und Missbrauch waren positiv korreliert, ältere und Probanden, die kindlichem Missbrauch erfahren hatten, zeigten höhere Methylierungsanteile auf. Mit dem Hippocampusvolumen verhielt es sich umgekehrt, hier lag eine signifikante Assoziation zwischen kleineren Volumina und höherer Methylierung vor. Auch diese Ergebnisse werden durch andere Arbeiten bestätigt und lassen vermuten, dass das Volumen des Hippocampus als hochgradig glukokortikoid- und damit stressempfindliche Region mit der Methylierung des Serotonintransportergens zusammenhängt, die als eventuelle Möglichkeit der Einflussnahme auf die Genetik des Menschen durch äußere Einflüsse wie beispielsweise Stresserlebnisse gehandelt wird. Kindlicher Missbrauch ließ für sich keine signifikante Assoziation mit dem Hippocampusvolumen verzeichnen, was den Mechanismus der Epigenetik als Mittel zur Beeinflussung physiologischer Vorgänge plausibel erscheinen lässt. Zudem untersuchten wir die Methylierung der beiden speziellen Genloki CpG 5_6 und CpG 11_12, die auf dem Gesamtgenabschnitt CpG 5 bis 15 des SLC6A4-Gens liegen und als besonders mit der Serotoninsynthese assoziierte Genabschnitte identifiziert wurden. Hier stellten wir generell einen besonders hohen Methylierungsanteil an CpG 5_6 fest, CpG 11_12 war deutlich weniger häufig signifikant hoch methyliert. Die spezifischen Funktionen der einzelnen Genloki des SLC6A4 sind noch unklar. Die Zusammenschau der vielfältigen Untersuchungen und Ergebnisse unserer Studie zeigen diverse signifikante Zusammenhänge zwischen Depression, kindlichem Stress, Methylierung und volumetrischen Veränderungen zerebraler Strukturen, insbesondere der Hippocampusregion und ihrer Subfelder, auf. Multiple Fragestellungen, insbesondere zur chronologischen Einordnung der volumetrischen und epigenetischen Veränderungen, liegen außerhalb unserer Studie und lassen Spielraum für eventuell darauf aufbauende weitere Studien zum Thema Depression, Missbrauchsereignisse in der Kindheit und Epigenetik., The aim of the present study was to detect volumetric differences between subcortical structures and hippocampal subfields and Major Depression, epigenetic methylation of SLC6A4 and childhood maltreatment. 49 patients with MDD and 49 healthy controls were examined by cerebral magnetic resonance tomography. Significant volumetric differences between patients and controls were detected concerning diagnosis of MDD. Further significant relations were seen between hippocampal volume and epigenetic methylation of SLC6A4, especially hippocampal subfields CA2/3 and CA4/DG. Childhood maltreatment also showed significant association with higher methylation states of SLC6A4.

Published
2017
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5. Childhood adversity impacts on brain subcortical structures relevant to depression

Author

Frodl, Thomas, primary, Janowitz, Deborah, additional, Schmaal, Lianne, additional, Tozzi, Leonardo, additional, Dobrowolny, Henrik, additional, Stein, Dan J., additional, Veltman, Dick J., additional, Wittfeld, Katharina, additional, van Erp, Theo G.M., additional, Jahanshad, Neda, additional, Block, Andrea, additional, Hegenscheid, Katrin, additional, Völzke, Henry, additional, Lagopoulos, Jim, additional, Hatton, Sean N., additional, Hickie, Ian B., additional, Frey, Eva Maria, additional, Carballedo, Angela, additional, Brooks, Samantha J., additional, Vuletic, Daniella, additional, Uhlmann, Anne, additional, Veer, Ilya M., additional, Walter, Henrik, additional, Schnell, Knut, additional, Grotegerd, Dominik, additional, Arolt, Volker, additional, Kugel, Harald, additional, Schramm, Elisabeth, additional, Konrad, Carsten, additional, Zurowski, Bartosz, additional, Baune, Bernhard T., additional, van der Wee, Nic J.A., additional, van Tol, Marie-Jose, additional, Penninx, Brenda W.J.H., additional, Thompson, Paul M., additional, Hibar, Derrek P., additional, Dannlowski, Udo, additional, and Grabe, Hans J., additional

Published
2017
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6. DNA Methylation of the Serotonin Transporter Gene in Peripheral Cells and Stress-Related Changes in Hippocampal Volume: A Study in Depressed Patients and Healthy Controls

Author

Booij, Linda, primary, Szyf, Moshe, additional, Carballedo, Angela, additional, Frey, Eva-Maria, additional, Morris, Derek, additional, Dymov, Sergiy, additional, Vaisheva, Farida, additional, Ly, Victoria, additional, Fahey, Ciara, additional, Meaney, James, additional, Gill, Michael, additional, and Frodl, Thomas, additional

Published
2015
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7. The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data

Author

Thompson, Paul M., Stein, Jason L., Medland, Sarah E., Hibar, Derrek P., Vasquez, Alejandro Arias, Renteria, Miguel E., Toro, Roberto, Jahanshad, Neda, Schumann, Gunter, Franke, Barbara, Wright, Margaret J., Martin, Nicholas G., Agartz, Ingrid, Alda, Martin, Alhusaini, Saud, Almasy, Laura, Almeida, Jorge, Alpert, Kathryn, Andreasen, Nancy C., Andreassen, Ole A., Apostolova, Liana G., Appel, Katja, Armstrong, Nicola J., Aribisala, Benjamin, Bastin, Mark E., Bauer, Michael, Bearden, Carrie E., Bergmann, Orjan, Binder, Elisabeth B., Blangero, John, Bockholt, Henry J., Boen, Erlend, Bois, Catherine, Boomsma, Dorret I., Booth, Tom, Bowman, Ian J., Bralten, Janita, Brouwer, Rachel M., Brunner, Han G., Brohawn, David G., Buckner, Randy L., Buitelaar, Jan, Bulayeva, Kazima, Bustillo, Juan R., Calhoun, Vince D., Cannon, Dara M., Cantor, Rita M., Carless, Melanie A., Caseras, Xavier, Cavalleri, Gianpiero L., Chakravarty, M. Mallar, Chang, Kiki D., Ching, Christopher R. K., Christoforou, Andrea, Cichon, Sven, Clark, Vincent P., Conrod, Patricia, Coppola, Giovanni, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Deary, Ian J., de Geus, Eco J. C., den Braber, Anouk, Delvecchio, Giuseppe, Depondt, Chantal, de Haan, Lieuwe, de Zubicaray, Greig I., Dima, Danai, Dimitrova, Rali, Djurovic, Srdjan, Dong, Hongwei, Donohoe, Gary, Duggirala, Ravindranath, Dyer, Thomas D., Ehrlich, Stefan, Ekman, Carl Johan, Elvsashagen, Torbjorn, Emsell, Louise, Erk, Susanne, Espeseth, Thomas, Fagerness, Jesen, Fears, Scott, Fedko, Iryna, Fernandez, Guillen, Fisher, Simon E., Foroud, Tatiana, Fox, Peter T., Francks, Clyde, Frangou, Sophia, Frey, Eva Maria, Frodl, Thomas, Frouin, Vincent, Garavan, Hugh, Giddaluru, Sudheer, Glahn, David C., Godlewska, Beata, Goldstein, Rita Z., Gollub, Randy L., Grabe, Hans J., Grimm, Oliver, Gruber, Oliver, Guadalupe, Tulio, Gur, Raquel E., Gur, Ruben C., Goering, Harald H. H., Hagenaars, Saskia, Hajek, Tomas, Hall, Geoffrey B., Hall, Jeremy, Hardy, John, Hartman, Catharina A., Hass, Johanna, Hatton, Sean N., Haukvik, Unn K., Hegenscheid, Katrin, Heinz, Andreas, Hickie, Ian B., Ho, Beng-Choon, Hoehn, David, Hoekstra, Pieter J., Hollinshead, Marisa, Holmes, Avram J., Homuth, Georg, Hoogman, Martine, Hong, L. Elliot, Hosten, Norbert, Hottenga, Jouke-Jan, Pol, Hilleke E. Hulshoff, Hwang, Kristy S., Jack, Clifford R., Jr., Jenkinson, Mark, Johnston, Caroline, Joensson, Erik G., Kahn, Rene S., Kasperaviciute, Dalia, Kelly, Sinead, Kim, Sungeun, Kochunov, Peter, Koenders, Laura, Kraemer, Bernd, Kwok, John B. J., Lagopoulos, Jim, Laje, Gonzalo, Landen, Mikael, Landman, Bennett A., Lauriello, John, Lawrie, Stephen M., Lee, Phil H., Le Hellard, Stephanie, Lemaitre, Herve, Leonardo, Cassandra D., Li, Chiang-shan, Liberg, Benny, Liewald, David C., Liu, Xinmin, Lopez, Lorna M., Loth, Eva, Lourdusamy, Anbarasu, Luciano, Michelle, Macciardi, Fabio, Machielsen, Marise W. J., MacQueen, Glenda M., Malt, Ulrik F., Mandl, Rene, Manoach, Dara S., Martinot, Jean-Luc, Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, Mattingsdal, Morten, Meyer-Lindenberg, Andreas, McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Meisenzahl, Eva, Melle, Ingrid, Milaneschi, Yuri, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Moses, Eric K., Mueller, Bryon A., Maniega, Susana Munoz, Muehleisen, Thomas W., Mueller-Myhsok, Bertram, Mwangi, Benson, Nauck, Matthias, Nho, Kwangsik, Nichols, Thomas E., Nilsson, Lars-Goeran, Nugent, Allison C., Nyberg, Lars, Olvera, Rene L., Oosterlaan, Jaap, Ophoff, Roel A., Pandolfo, Massimo, Papalampropoulou-Tsiridou, Melina, Papmeyer, Martina, Paus, Tomas, Pausova, Zdenka, Pearlson, Godfrey D., Penninx, Brenda W., Peterson, Charles P., Pfennig, Andrea, Phillips, Mary, Pike, G. Bruce, Poline, Jean-Baptiste, Potkin, Steven G., Puetz, Benno, Ramasamy, Adaikalavan, Rasmussen, Jerod, Rietschel, Marcella, Rijpkema, Mark, Risacher, Shannon L., Roffman, Joshua L., Roiz-Santianez, Roberto, Romanczuk-Seiferth, Nina, Rose, Emma J., Royle, Natalie A., Rujescu, Dan, Ryten, Mina, Sachdev, Perminder S., Salami, Alireza, Satterthwaite, Theodore D., Savitz, Jonathan, Saykin, Andrew J., Scanlon, Cathy, Schmaal, Lianne, Schnack, Hugo G., Schork, Andrew J., Schulz, S. Charles, Schuer, Remmelt, Seidman, Larry, Shen, Li, Shoemaker, Jody M., Simmons, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soares, Jair C., Sponheim, Scott R., Sprooten, Emma, Starr, John M., Steen, Vidar M., Strakowski, Stephen, Strike, Lachlan, Sussmann, Jessika, Saemann, Philipp G., Teumer, Alexander, Toga, Arthur W., Tordesillas-Gutierrez, Diana, Trabzuni, Daniah, Trost, Sarah, Turner, Jessica, Van den Heuvel, Martijn, van der Wee, Nic J., van Eijk, Kristel, van Erp, Theo G. M., van Haren, Neeltje E. M., van 't Ent, Dennis, van Tol, Marie-Jose, Hernandez, Maria C. Valdes, Veltman, Dick J., Versace, Amelia, Voelzke, Henry, Walker, Robert, Walter, Henrik, Wang, Lei, Wardlaw, Joanna M., Weale, Michael E., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Whalley, Heather C., Whelan, Christopher D., White, Tonya, Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Zilles, David, Zwiers, Marcel P., Thalamuthu, Anbupalam, Schofield, Peter R., Freimer, Nelson B., Lawrence, Natalia S., Drevets, Wayne, Thompson, Paul M., Stein, Jason L., Medland, Sarah E., Hibar, Derrek P., Vasquez, Alejandro Arias, Renteria, Miguel E., Toro, Roberto, Jahanshad, Neda, Schumann, Gunter, Franke, Barbara, Wright, Margaret J., Martin, Nicholas G., Agartz, Ingrid, Alda, Martin, Alhusaini, Saud, Almasy, Laura, Almeida, Jorge, Alpert, Kathryn, Andreasen, Nancy C., Andreassen, Ole A., Apostolova, Liana G., Appel, Katja, Armstrong, Nicola J., Aribisala, Benjamin, Bastin, Mark E., Bauer, Michael, Bearden, Carrie E., Bergmann, Orjan, Binder, Elisabeth B., Blangero, John, Bockholt, Henry J., Boen, Erlend, Bois, Catherine, Boomsma, Dorret I., Booth, Tom, Bowman, Ian J., Bralten, Janita, Brouwer, Rachel M., Brunner, Han G., Brohawn, David G., Buckner, Randy L., Buitelaar, Jan, Bulayeva, Kazima, Bustillo, Juan R., Calhoun, Vince D., Cannon, Dara M., Cantor, Rita M., Carless, Melanie A., Caseras, Xavier, Cavalleri, Gianpiero L., Chakravarty, M. Mallar, Chang, Kiki D., Ching, Christopher R. K., Christoforou, Andrea, Cichon, Sven, Clark, Vincent P., Conrod, Patricia, Coppola, Giovanni, Crespo-Facorro, Benedicto, Curran, Joanne E., Czisch, Michael, Deary, Ian J., de Geus, Eco J. C., den Braber, Anouk, Delvecchio, Giuseppe, Depondt, Chantal, de Haan, Lieuwe, de Zubicaray, Greig I., Dima, Danai, Dimitrova, Rali, Djurovic, Srdjan, Dong, Hongwei, Donohoe, Gary, Duggirala, Ravindranath, Dyer, Thomas D., Ehrlich, Stefan, Ekman, Carl Johan, Elvsashagen, Torbjorn, Emsell, Louise, Erk, Susanne, Espeseth, Thomas, Fagerness, Jesen, Fears, Scott, Fedko, Iryna, Fernandez, Guillen, Fisher, Simon E., Foroud, Tatiana, Fox, Peter T., Francks, Clyde, Frangou, Sophia, Frey, Eva Maria, Frodl, Thomas, Frouin, Vincent, Garavan, Hugh, Giddaluru, Sudheer, Glahn, David C., Godlewska, Beata, Goldstein, Rita Z., Gollub, Randy L., Grabe, Hans J., Grimm, Oliver, Gruber, Oliver, Guadalupe, Tulio, Gur, Raquel E., Gur, Ruben C., Goering, Harald H. H., Hagenaars, Saskia, Hajek, Tomas, Hall, Geoffrey B., Hall, Jeremy, Hardy, John, Hartman, Catharina A., Hass, Johanna, Hatton, Sean N., Haukvik, Unn K., Hegenscheid, Katrin, Heinz, Andreas, Hickie, Ian B., Ho, Beng-Choon, Hoehn, David, Hoekstra, Pieter J., Hollinshead, Marisa, Holmes, Avram J., Homuth, Georg, Hoogman, Martine, Hong, L. Elliot, Hosten, Norbert, Hottenga, Jouke-Jan, Pol, Hilleke E. Hulshoff, Hwang, Kristy S., Jack, Clifford R., Jr., Jenkinson, Mark, Johnston, Caroline, Joensson, Erik G., Kahn, Rene S., Kasperaviciute, Dalia, Kelly, Sinead, Kim, Sungeun, Kochunov, Peter, Koenders, Laura, Kraemer, Bernd, Kwok, John B. J., Lagopoulos, Jim, Laje, Gonzalo, Landen, Mikael, Landman, Bennett A., Lauriello, John, Lawrie, Stephen M., Lee, Phil H., Le Hellard, Stephanie, Lemaitre, Herve, Leonardo, Cassandra D., Li, Chiang-shan, Liberg, Benny, Liewald, David C., Liu, Xinmin, Lopez, Lorna M., Loth, Eva, Lourdusamy, Anbarasu, Luciano, Michelle, Macciardi, Fabio, Machielsen, Marise W. J., MacQueen, Glenda M., Malt, Ulrik F., Mandl, Rene, Manoach, Dara S., Martinot, Jean-Luc, Matarin, Mar, Mather, Karen A., Mattheisen, Manuel, Mattingsdal, Morten, Meyer-Lindenberg, Andreas, McDonald, Colm, McIntosh, Andrew M., McMahon, Francis J., McMahon, Katie L., Meisenzahl, Eva, Melle, Ingrid, Milaneschi, Yuri, Mohnke, Sebastian, Montgomery, Grant W., Morris, Derek W., Moses, Eric K., Mueller, Bryon A., Maniega, Susana Munoz, Muehleisen, Thomas W., Mueller-Myhsok, Bertram, Mwangi, Benson, Nauck, Matthias, Nho, Kwangsik, Nichols, Thomas E., Nilsson, Lars-Goeran, Nugent, Allison C., Nyberg, Lars, Olvera, Rene L., Oosterlaan, Jaap, Ophoff, Roel A., Pandolfo, Massimo, Papalampropoulou-Tsiridou, Melina, Papmeyer, Martina, Paus, Tomas, Pausova, Zdenka, Pearlson, Godfrey D., Penninx, Brenda W., Peterson, Charles P., Pfennig, Andrea, Phillips, Mary, Pike, G. Bruce, Poline, Jean-Baptiste, Potkin, Steven G., Puetz, Benno, Ramasamy, Adaikalavan, Rasmussen, Jerod, Rietschel, Marcella, Rijpkema, Mark, Risacher, Shannon L., Roffman, Joshua L., Roiz-Santianez, Roberto, Romanczuk-Seiferth, Nina, Rose, Emma J., Royle, Natalie A., Rujescu, Dan, Ryten, Mina, Sachdev, Perminder S., Salami, Alireza, Satterthwaite, Theodore D., Savitz, Jonathan, Saykin, Andrew J., Scanlon, Cathy, Schmaal, Lianne, Schnack, Hugo G., Schork, Andrew J., Schulz, S. Charles, Schuer, Remmelt, Seidman, Larry, Shen, Li, Shoemaker, Jody M., Simmons, Andrew, Sisodiya, Sanjay M., Smith, Colin, Smoller, Jordan W., Soares, Jair C., Sponheim, Scott R., Sprooten, Emma, Starr, John M., Steen, Vidar M., Strakowski, Stephen, Strike, Lachlan, Sussmann, Jessika, Saemann, Philipp G., Teumer, Alexander, Toga, Arthur W., Tordesillas-Gutierrez, Diana, Trabzuni, Daniah, Trost, Sarah, Turner, Jessica, Van den Heuvel, Martijn, van der Wee, Nic J., van Eijk, Kristel, van Erp, Theo G. M., van Haren, Neeltje E. M., van 't Ent, Dennis, van Tol, Marie-Jose, Hernandez, Maria C. Valdes, Veltman, Dick J., Versace, Amelia, Voelzke, Henry, Walker, Robert, Walter, Henrik, Wang, Lei, Wardlaw, Joanna M., Weale, Michael E., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Whalley, Heather C., Whelan, Christopher D., White, Tonya, Winkler, Anderson M., Wittfeld, Katharina, Woldehawariat, Girma, Wolf, Christiane, Zilles, David, Zwiers, Marcel P., Thalamuthu, Anbupalam, Schofield, Peter R., Freimer, Nelson B., Lawrence, Natalia S., and Drevets, Wayne

Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Published
2014
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8. Expression of glucocorticoid inducible genes is associated with reductions in cornu ammonis and dentate gyrus volumes in patients with major depressive disorder

Author

Frodl, Thomas, primary, Carballedo, Angela, additional, Frey, Eva-Maria, additional, O'Keane, Veronica, additional, Skokauskas, Norbert, additional, Morris, Derrek, additional, Gill, Michael, additional, Hughes, Martina Mary, additional, Harkin, Andrew, additional, and Connor, Thomas, additional

Published
2014
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10. BDNF Val66 Met genotype interacts with childhood adversity and influences the formation of hippocampal subfields.

Author

Frodl, Thomas, Skokauskas, Norbert, Frey, Eva‐Maria, Morris, Derek, Gill, Michael, and Carballedo, Angela

Abstract

Childhood stress and genetic factors like the Val66MET polymorphism of the brain derived neurotrophic factor (BDNF) gene are associated with a higher risk for developing major depressive disorder (MDD) and might also influence hippocampal changes. The aim of this study was to determine which hippocampal dentate gyrus and cornu ammonis subfields are altered in MDD compared to healthy controls and which subfields are affected by the BDNF Val66Met polymorphism and child adversity. Adult patients with MDD and healthy matched controls underwent high-resolution magnetic resonance imaging. Automatic segmentation using the programme FreeSurfer was used to segment the hippocampal subfields dentate gyrus (DG/CA4), CA1 and CA2/3. The history of possible childhood adversity was assessed using the Childhood Trauma Questionnaire and the Val66Met BDNF SNP (rs6265) genotypes were obtained. Patients with MDD had significantly smaller CA4/DG and CA2/3 volumes compared to healthy controls. Furthermore, there was a significant interactive effect of BDNF allele and childhood adversity on CA2/3 and CA4/DG volumes. Met allele carriers without childhood adversity had larger and with childhood adversity smaller CA4/DG and CA2/3 volumes than Val-allele homozygotes. Our results highlight stress by gene interactions as relevant for hippocampal volume reductions, in particular for the subfield CA2/3 and dentate gyrus. Hum Brain Mapp 35:5776-5783, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2014
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11. Expression of glucocorticoid inducible genes is associated with reductions in cornu ammonis and dentate gyrus volumes in patients with major depressive disorder.

Author

Cicchetti, Dante, Natsuaki, Misaki N., Frodl, Thomas, Carballedo, Angela, Frey, Eva-Maria, O'Keane, Veronica, Skokauskas, Norbert, Morris, Derrek, Gill, Michael, Hughes, Martina Mary, Harkin, Andrew, and Connor, Thomas

Subjects
GENE expression, DENTATE gyrus, GLUCOCORTICOIDS, HIPPOCAMPUS physiology, DEPRESSED persons, MESSENGER RNA, PEOPLE with mental illness, PHYSIOLOGY
Abstract

Alterations of the glucocorticoid system and of hippocampal volumes have consistently been reported in patients with major depressive disorders (MDD). The aim of the present study was to investigate whether the messenger RNA (mRNA) expression of glucocorticoid inducible genes is associated with changes in the cornu ammonis (CA) and dentate gyrus subfields. Forty-three patients with MDD and 43 healthy controls were recruited and investigated with high resolution magnetic resonance imaging. Hippocampal subfields were measured using freesurfer. Measurement of whole blood mRNA expression of glucocorticoid inducible genes serum and glucocorticoid-regulated kinase 1 (SGK1), FK506 binding protein 5 (FKBP5), and glucocorticoid induced leucine zipper (GILZ) was performed. Patients with MDD had significantly smaller volumes of CA1, CA2/3, CA4/DG, and subiculum compared to healthy controls. In the regression analysis, the factor diagnosis had a significant moderating effect on the association of SGK1 and hippocampal volumes. Patients with low expression of SGK1 had significantly smaller CA2/3 and CA4/DG volumes compared to patients with high expression of SGK1 mRNA and to healthy controls with low/high expression of SGK1, respectively. Therefore, a lack of mRNA expression of glucocorticoid inducible genes in patients with MDD that seems to correspond to a blunted cortisol response is associated with smaller hippocampal CA and dentate gyrus volumes. SGK1 seems to be particularly relevant for stress-related mental disorders. [ABSTRACT FROM PUBLISHER]

Published
2014
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