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1. Association of hospitalization with structural brain alterations in patients with affective disorders over nine years

Author

Förster, Katharina, Grotegerd, Dominik, Dohm, Katharina, Lemke, Hannah, Enneking, Verena, Meinert, Susanne, Redlich, Ronny, Heindel, Walter, Bauer, Jochen, Kugel, Harald, Suslow, Thomas, Ohrmann, Patricia, Carballedo, Angela, O’Keane, Veronica, Fagan, Andrew, Doolin, Kelly, McCarthy, Hazel, Kanske, Philipp, Frodl, Thomas, and Dannlowski, Udo

Published
2023
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2. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author

Han, Laura KM, Dinga, Richard, Hahn, Tim, Ching, Christopher RK, 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 LS, Enneking, Verena, Filimonova, Elena, Frenzel, Stefan, Frodl, Thomas, Fu, Cynthia HY, 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 GP, 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 RJM, Walter, Henrik, van der Wee, Nic JA, van der Werff, Steven JA, 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, and Fullerton, Janice M

Subjects
Depression, Aging, Brain Disorders, Biomedical Imaging, Serious Mental Illness, Mental Health, Major Depressive Disorder, Behavioral and Social Science, Clinical Research, Neurosciences, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Adolescent, Adult, Aged, Brain, Depressive Disorder, Major, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

Published
2021

3. Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort

Author

Tozzi, Leonardo, Garczarek, Lisa, Janowitz, Deborah, Stein, Dan J, Wittfeld, Katharina, Dobrowolny, Henrik, Lagopoulos, Jim, Hatton, Sean N, Hickie, Ian B, Carballedo, Angela, Brooks, Samantha J, Vuletic, Daniella, Uhlmann, Anne, Veer, Ilya M, Walter, Henrik, Bülow, Robin, Völzke, Henry, Klinger-König, Johanna, Schnell, Knut, Schoepf, Dieter, Grotegerd, Dominik, Opel, Nils, Dannlowski, Udo, Kugel, Harald, Schramm, Elisabeth, Konrad, Carsten, Kircher, Tilo, Jüksel, Dilara, Nenadić, Igor, Krug, Axel, Hahn, Tim, Steinsträter, Olaf, Redlich, Ronny, Zaremba, Dario, Zurowski, Bartosz, Fu, Cynthia HY, Dima, Danai, Cole, James, Grabe, Hans J, Connolly, Colm G, Yang, Tony T, Ho, Tiffany C, LeWinn, Kaja Z, Li, Meng, Groenewold, Nynke A, Salminen, Lauren E, Walter, Martin, Simmons, Alan N, van Erp, Theo GM, Jahanshad, Neda, Baune, Bernhard T, van der Wee, Nic JA, van Tol, Marie-Jose, Penninx, Brenda WJH, Hibar, Derrek P, Thompson, Paul M, Veltman, Dick J, Schmaal, Lianne, and Frodl, Thomas

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Pediatric, Neurosciences, Clinical Research, Mental Health, Brain Disorders, Depression, Child Abuse and Neglect Research, Behavioral and Social Science, Violence Research, Aetiology, 2.1 Biological and endogenous factors, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Brain Cortical Thickness, Case-Control Studies, Cerebral Cortex, Child, Child Abuse, Cohort Studies, Depressive Disorder, Major, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Parietal Lobe, Prefrontal Cortex, Temporal Lobe, Young Adult, Childhood maltreatment, cortical thickness, ENIGMA, major depressive disorder, ‘for the ENIGMA-MDD Consortium’, Public Health and Health Services, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

BackgroundChildhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.MethodsWithin the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.ResultsCM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.ConclusionsSeverity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Published
2020

5. 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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6. 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

8. 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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10. Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group

Author

Leerssen, Jeanne, Blanken, Tessa F., Pozzi, Elena, Jahanshad, Neda, Aftanas, Lyubomir, Andreassen, Ole A., Baune, Bernhard T., Brack, Ivan, Carballedo, Angela, Ching, Christopher R. K., Dannlowski, Udo, Dohm, Katharina, Enneking, Verena, Filimonova, Elena, Fingas, Stella M., Frodl, Thomas, Godlewska, Beata R., Goltermann, Janik, Gotlib, Ian H., Grotegerd, Dominik, Gruber, Oliver, Harris, Mathew A., Hatton, Sean N., Hawkins, Emma, Hickie, Ian B., Jaworska, Natalia, Kircher, Tilo, Krug, Axel, Lagopoulos, Jim, Lemke, Hannah, Li, Meng, MacMaster, Frank P., McIntosh, Andrew M., McLellan, Quinn, Meinert, Susanne, Mwangi, Benson, Nenadić, Igor, Osipov, Evgeny, Portella, Maria J., Redlich, Ronny, Repple, Jonathan, Sacchet, Matthew D., Sämann, Philipp G., Simulionyte, Egle, Soares, Jair C., Walter, Martin, Watanabe, Norio, Whalley, Heather C., Yüksel, Dilara, Veltman, Dick J., Thompson, Paul M., Schmaal, Lianne, and Van Someren, Eus J. W.

Published
2020
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11. 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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13. Current trends in restrictive interventions in psychiatry: a European perspective.

Author

O'Donovan, David, Boland, Cailín, and Carballedo, Angela

Subjects
PSYCHIATRY, SOLITUDE, EUROPEAN law
Abstract

SUMMARY: This article reviews current evidence on the use of coercive measures, including seclusion and restraint, in psychiatric in-patient settings in Europe. There is a particular focus on evidence regarding the use of mechanical restraint. The review seeks to describe when the use of restrictive interventions such as restraint may be necessary, to explore the use of restraint in certain specialist settings and to investigate current laws and European policies on seclusion and restraint. The current rates of restraint in European psychiatric settings are explored, with a discussion of the limitations of the evidence currently available. The article discusses various consequences of seclusion and restraint, potential alternatives to their use and strategies to minimise their use and harm to patients. The use of coercive measures from an international context is considered, to provide context. [ABSTRACT FROM AUTHOR]

Published
2023
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16. DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli

Author

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

Subjects
Methylation, Depression, Mental, Serotonin, Health, Psychology and mental health
Abstract

Background: The aim of the present study was to investigate the association of fMRI blood oxygen-level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD). Methods: We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyrosequencing. Results: Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation. Limitations: It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn. Conclusion: Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery., Introduction Childhood adversity, such as childhood maltreatment, plays an important role in a number of multifactorial mental disorders. Recent studies reveal that certain aspects of stress-related mental disorders result from [...]

Published
2015
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21. 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

Subjects
Depression, Diagnostic markers, Article
Abstract

Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

Published
2020

23. Effect of childhood maltreatment on brain structure in adult patients with major depressive disorder and healthy participants

Author

Chaney, Aisling, Carballedo, Angela, Amico, Francesco, Fagan, Andrew, Skokauskas, Norbert, Meaney, James, and Frodl, Thomas

Subjects
Brain -- Physiological aspects -- Health aspects, Major depressive disorder -- Care and treatment, Medical personnel -- Malpractice, Child psychology -- Research, Health, Psychology and mental health
Abstract

Background: Childhood maltreatment has been found to play a crucial role in the development of psychiatric disorders. However, whether childhood maltreatment is associated with structural brain changes described for major depressive disorder (MDD) is still a matter of debate. The aim of this study was to investigate whether patients with MDD and a history of childhood maltreatment display more structural changes than patients without childhood maltreatment or healthy controls. Methods: Patients with MDD and healthy controls with and without childhood maltreatment experience were investigated using high- resolution magnetic resonance imaging (MRI), and data were analyzed using voxel-based morphometry. Results: We studied 37 patients with MDD and 46 controls. Grey matter volume was significantly decreased in the hippocampus and significantly increased in the dorsomedial prefrontal cortex (DMPFC) and the orbitofrontal cortex (OFC) in participants who had experienced childhood maltreatment compared with those who had not. Patients displayed smaller left OFC and left DMPFC volumes than controls. No significant difference in hippocampal volume was evident between patients with MDD and healthy controls. In regression analyses, despite effects from depression, age and sex on the DMPFC, OFC and hippocampus, childhood maltreatment was found to independently affect these regions. Limitations: The retrospective assessment of childhood maltreatment; the natural problem that patients experienced more childhood maltreatment than controls; and the restrictions, owing to sample size, to investigating higher order interactions among factors are discussed as limitations. Conclusion: These results suggest that early childhood maltreatment is associated with brain structural changes irrespective of sex, age and a history of depression. Thus, the study highlights the importance of childhood maltreatment when investigating brain structures., Introduction Previous studies have suggested that a relationship exists between childhood maltreatment and an increased risk for a number of mental disorders developing in adulthood, (1,2) including major depressive disorder [...]

Published
2014
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26. 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, Schmaal, Lianne, 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

Abstract

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

Published
2021

27. Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression

Author

Frodl, Thomas, Carballedo, Angela, Fagan, Andrew J., Lisiecka, Danuta, Ferguson, Yolande, and Meaney, James F.

Subjects
Major depressive disorder -- Physiological aspects -- Development and progression, Diagnostic imaging -- Methods, Health, Psychology and mental health
Abstract

Background: Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes. Methods: Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography. Results: Twenty- one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the corpus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts. Limitations: Studying participants' strategies for coping with early-life adversity would have been helpful. Crossing fibres in tracts are a general limitation of the method used. Conclusion: Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive-emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies., Introduction Mental disorders are a major cause of long-term disability and are a direct cause of mortality, with about 800 000 individuals dying from suicide every year worldwide and a [...]

Published
2012
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29. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author

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

Published
2020
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30. No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis

Author

de Kovel, Carolien G.F., primary, Aftanas, Lyubomir, additional, Aleman, André, additional, Alexander-Bloch, Aaron F., additional, Baune, Bernhard T., additional, Brack, Ivan, additional, Bülow, Robin, additional, Busatto Filho, Geraldo, additional, Carballedo, Angela, additional, Connolly, Colm G., additional, Cullen, Kathryn R., additional, Dannlowski, Udo, additional, Davey, Christopher G., additional, Dima, Danai, additional, Dohm, Katharina, additional, Erwin-Grabner, Tracy, additional, Frodl, Thomas, additional, Fu, Cynthia H.Y., additional, Hall, Geoffrey B., additional, Glahn, David C., additional, Godlewska, Beata, additional, Gotlib, Ian H., additional, Goya-Maldonado, Roberto, additional, Grabe, Hans Jörgen, additional, Groenewold, Nynke A., additional, Grotegerd, Dominik, additional, Gruber, Oliver, additional, Harris, Mathew A., additional, Harrison, Ben J., additional, Hatton, Sean N., additional, Hickie, Ian B., additional, Ho, Tiffany C., additional, Jahanshad, Neda, additional, Kircher, Tilo, additional, Krämer, Bernd, additional, Krug, Axel, additional, Lagopoulos, Jim, additional, Leehr, Elisabeth J., additional, Li, Meng, additional, MacMaster, Frank P., additional, MacQueen, Glenda, additional, McIntosh, Andrew M., additional, McLellan, Quinn, additional, Medland, Sarah E., additional, Mueller, Bryon A., additional, Nenadic, Igor, additional, Osipov, Evgeny, additional, Papmeyer, Martina, additional, Portella, Maria J., additional, Reneman, Liesbeth, additional, Rosa, Pedro G.P., additional, Sacchet, Matthew D., additional, Schnell, Knut, additional, Schrantee, Anouk, additional, Sim, Kang, additional, Simulionyte, Egle, additional, Sindermann, Lisa, additional, Singh, Aditya, additional, Stein, Dan J., additional, Ubani, Benjamin N., additional, Van der Wee, Nic J.A., additional, Van der Werff, Steven J.A., additional, Veer, Ilya M., additional, Vives-Gilabert, Yolanda, additional, Völzke, Henry, additional, Walter, Henrik, additional, Walter, Martin, additional, Schreiner, Melinda Westlund, additional, Whalley, Heather, additional, Winter, Nils, additional, Wittfeld, Katharina, additional, Yang, Tony T., additional, Yüksel, Dilara, additional, Zaremba, Dario, additional, Thompson, Paul M., additional, Veltman, Dick J., additional, Schmaal, Lianne, additional, and Francks, Clyde, additional

Published
2019
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31. 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, Schmaal, Lianne, and Universitat Autònoma de Barcelona

Subjects
Depression, Neuroscience
Abstract

Altres ajuts: The ENIGMA-Major Depressive Disorder working group gratefully acknowledges support from the NIH Big Data to Knowledge (BD2K) award (U54 EB020403 to PMT) and NIH grant R01 MH116147 (PMT). LS is supported by an NHMRC MRFF Career Development Fellowship (APP1140764). We wish to acknowledge the patients and control subjects that have particiaped int the study. We thank Rosa Schirmer, Elke Schreiter, Reinhold Borschke and Ines Eidner for image acquisition and data preparation, and Anna Oliynyk for quality checks. We thank Dorothee P. Auer and F. Holsboer for initiation of the RUD study. We wish to acknowledge the patients and control subjects that have particiaped int the study. We thank Rosa Schirmer, Elke Schreiter, Reinhold Borschke and Ines Eidner for image acquisition and data preparation, and Anna Oliynyk for quality checks. We thank Dorothee P. Auer and F. Holsboer for initiation of the RUD study. NESDA: The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen) and mental health care organizations, see www.nesda.nl. M-JvT was supported by a VENI grant (NWO grant number 016.156.077). UCSF: This work was supported by the Brain and Behavior Research Foundation (formerly NARSAD) to TTY; the National Institute of Mental Health (R01MH085734 to TTY; K01MH117442 to TCH) and by the American Foundation for Suicide Prevention (PDF-1-064-13) to TCH. Stanford: This work was supported by NIMH Grants R01MH59259 and R37101495 to IHG. MS is partially supported by an award funded by the Phyllis and Jerome Lyle Rappaport Foundation. Muenster: This work was funded by the German Research Foundation (SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). Marburg: This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to UD; KI 588/ 14-1, KI 588/14-2 to TK; KR 3822/7-1, KR 3822/7-2 to AK; JA 1890/ 7-1, JA 1890/7-2 to AJ). IMH-MDD: This work was supported by the National Healthcare Group Research Grant (SIG/15012) awarded to KS. Barcelona: This study was funded by two grants of the Fondo de Investigación Sanitaria from the Instituto de Salud Carlos III, by the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM). The author is funded through 'Miguel Servet' research contract (CP16-0020), co-financed by the European Regional Development Fund (ERDF) (2016-2019). QTIM: We thank the twins and singleton siblings who gave generously of their time to participate in the QTIM study. We also thank the many research assistants, radiographers, and IT support staff for data acquisition and DNA sample preparation. This study was funded by White matter disturbances in major depressive disorder: a coordinated analysis across 20 international. . . 1521 the National Institute of Child Health & Human Development (RO1 HD050735); National Institute of Biomedical Imaging and Bioengineering (Award 1U54EB020403-01, Subaward 56929223); National Health and Medical Research Council, Australia (Project Grants 496682, 1009064). NIH ENIGMA-BD2K U54 EB020403 (Thompson); R01 MH117601 (Jahanshad/Schmaal). Magdeburg: M.L. and M.W. are funded by SFB 779. Bipolar Family Study: This study has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013). This paper reflects only the author's views and the European Union is not liable for any use that may be made of the information contained therein. This work was also supported by a Wellcome Trust Strategic Award (104036/Z/14/Z). Minnesota Adolescent Depression Study: The study was funded by the National Institute of Mental Health (K23MH090421), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (P41 RR008079 to the Center for Magnetic Resonance Research), University of Minnesota, and the Deborah E. Powell Center for Women's Health Seed Grant, University of Minnesota. Dublin: This study was supported by Science Foundation Ireland through a Stokes Professorhip grant to TF. MPIP: The MPIP Sample comprises patients included in the Recurrent Unipolar Depression (RUD) Case-Control study at the clinic of the Max Planck Institute of Psychiatry, Munich, German. The RUD study was supported by GlaxoSmithKline. Alterations in white matter (WM) microstructure have been implicated in the pathophysiology of major depressive disorder (MDD). However, previous findings have been inconsistent, partially due to low statistical power and the heterogeneity of depression. In the largest multi-site study to date, we examined WM anisotropy and diffusivity in 1305 MDD patients and 1602 healthy controls (age range 12-88 years) from 20 samples worldwide, which included both adults and adolescents, within the MDD Working Group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium. Processing of diffusion tensor imaging (DTI) data and statistical analyses were harmonized across sites and effects were meta-analyzed across studies. We observed subtle, but widespread, lower fractional anisotropy (FA) in adult MDD patients compared with controls in 16 out of 25 WM tracts of interest (Cohen's d between 0.12 and 0.26). The largest differences were observed in the corpus callosum and corona radiata. Widespread higher radial diffusivity (RD) was also observed (all Cohen's d between 0.12 and 0.18). Findings appeared to be driven by patients with recurrent MDD and an adult age of onset of depression. White matter microstructural differences in a smaller sample of adolescent MDD patients and controls did not survive correction for multiple testing. In this coordinated and harmonized multisite DTI study, we showed subtle, but widespread differences in WM microstructure in adult MDD, which may suggest structural disconnectivity in MDD.

Published
2019

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

Published
2019
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34. Brain Aging in Major Depressive Disorder: Results from the ENIGMA Major Depressive Disorder working group

Author

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

Published
2019
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37. 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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38. BDNF Val66Met polymorphism in patterns of neural activation in individuals with MDD and healthy controls

Author

Lisiecka, Danuta M, O'Hanlon, Erik, Fagan, Andrew J, Carballedo, Angela, Morris, Derek, Suckling, John, Frodl, Thomas, Suckling, John [0000-0002-5098-1527], and Apollo - University of Cambridge Repository

Subjects
Adult, Male, Depressive Disorder, Major, Genotype, Brain-Derived Neurotrophic Factor, Functional Neuroimaging, Functional magnetic resonance imaging, Emotions, Brain, Major depressive disorder, Middle Aged, Prefrontal cortex, Magnetic Resonance Imaging, Polymorphism, Single Nucleotide, Striatum, Emotional response, Case-Control Studies, Humans, Female, Alleles
Abstract

BACKGROUND: Rs6265 single nucleotide polymorphism, which influences brain-derived neurotrophic factor (BDNF) levels in the cortical and subcortical brain structures, may result in distinguished patterns of neural activation during a major depressive disorder (MDD) episode. Valine homozygotes with high levels of BDNF and methionine carriers with lower levels of BDNF may present specific neural correlates of MDD. In our study we have tested differences in blood oxygen level dependant (BOLD) signal between individuals with MDD and healthy controls for both allelic variants. METHODS: Individuals with MDD (N = 37) and healthy controls (N = 39) were genotyped for rs6265 and compared separately in each allelic variant for BOLD response in a functional magnetic resonance imaging experiment examining appraisal of emotional scenes. The two allelic variants were also compared separately for both individuals with MDD and healthy controls. RESULTS: In the homozygous valine group MDD was associated with decreased neural activation in areas responsible for cognitive appraisal of emotional scenes. In the methionine group MDD was related to increased activation in subcortical regions responsible for visceral reaction to emotional stimuli. During an MDD episode methionine carriers showed more activation in areas associated with cognitive appraisal of emotional information in comparison to valine homozygotes. LIMITATIONS: Small sample size of healthy controls carrying methionine (N=8). CONCLUSION: Our results suggest that allelic variations in the rs6265 gene lead to specific neural correlates of MDD which may be associated with different mechanisms of MDD in the two allelic groups. This may have potential importance for screening and treatment of patients.

Published
2015

39. Association between single nucleotide polymorphism of the FKBP5 gene and neural correlates of attentional bias towards emotional stimuli in depression

Author

Meaney James, Morris Derek, Wetterling Friedrich, Carballedo Angela, O'Keane Veronica, McCarthy Hazel, Fahey Ciara, Gill Michael, Tozzi Leonardo, and Frodl Thomas

Subjects
Neural correlates of consciousness, General Neuroscience, Emotional stimuli, Single-nucleotide polymorphism, Attentional bias, Association (psychology), Psychology, Neuroscience, Depression (differential diagnoses), FKBP5 Gene, Developmental psychology
Published
2014
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41. Single-Nucleotide Polymorphism of the FKBP5 Gene and Childhood Maltreatment as Predictors of Structural Changes in Brain Areas Involved in Emotional Processing in Depression

Author

Tozzi, Leonardo, primary, Carballedo, Angela, additional, Wetterling, Friedrich, additional, McCarthy, Hazel, additional, O'Keane, Veronica, additional, Gill, Michael, additional, Morris, Derrek, additional, Fahey, Ciara, additional, Meaney, James, additional, and Frodl, Thomas, additional

Published
2015
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42. 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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45. 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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