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1. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, OA, Arango, C, Banaj, N, Bouix, S, Bousman, CA, Brouwer, RM, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-X, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, AS, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, CM, Dickie, EW, Ehrlich, S, Fan, F-M, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, JM, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, DC, Gollub, R, Goudzwaard, ED, Guo, H, Gur, RE, Gur, RC, Gurholt, TP, Hashimoto, R, Hatton, SN, Henskens, FA, Hibar, DP, Hickie, IB, Hong, LE, Horacek, J, Howells, FM, Hulshoff Pol, HE, Hyde, CL, Isaev, D, Jablensky, A, Jansen, PR, Janssen, J, Jönsson, EG, Jung, LA, Kahn, RS, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, RK, Lim, KO, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, RCW, Mathalon, DH, McCarley, RW, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, RI, Michie, PT, Mowry, B, Mueller, BA, Newell, DT, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, SA, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, GR, Pereira, A, and Pineda Zapata, J

Subjects
Neurosciences, Brain Disorders, Mental Health, Serious Mental Illness, Biomedical Imaging, Schizophrenia, Clinical Research, Mental health, Adult, Aged, Aged, 80 and over, Brain, Cohort Studies, Corpus Callosum, Diffusion Magnetic Resonance Imaging, Diffusion Tensor Imaging, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, White Matter, Young Adult, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2018

3. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

Author

Schmaal, L, Hibar, DP, Sämann, PG, Hall, GB, Baune, BT, Jahanshad, N, Cheung, JW, van Erp, TGM, Bos, D, Ikram, MA, Vernooij, MW, Niessen, WJ, Tiemeier, H, Hofman, A, Wittfeld, K, Grabe, HJ, Janowitz, D, Bülow, R, Selonke, M, Völzke, H, Grotegerd, D, Dannlowski, U, Arolt, V, Opel, N, Heindel, W, Kugel, H, Hoehn, D, Czisch, M, Couvy-Duchesne, B, Rentería, ME, Strike, LT, Wright, MJ, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Martin, NG, Gillespie, NA, Goya-Maldonado, R, Gruber, O, Krämer, B, Hatton, SN, Lagopoulos, J, Hickie, IB, Frodl, T, Carballedo, A, Frey, EM, van Velzen, LS, Penninx, BWJH, van Tol, M-J, van der Wee, NJ, Davey, CG, Harrison, BJ, Mwangi, B, Cao, B, Soares, JC, Veer, IM, Walter, H, Schoepf, D, Zurowski, B, Konrad, C, Schramm, E, Normann, C, Schnell, K, Sacchet, MD, Gotlib, IH, MacQueen, GM, Godlewska, BR, Nickson, T, McIntosh, AM, Papmeyer, M, Whalley, HC, Hall, J, Sussmann, JE, Li, M, Walter, M, Aftanas, L, Brack, I, Bokhan, NA, Thompson, PM, and Veltman, DJ

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Major Depressive Disorder, Serious Mental Illness, Neurosciences, Biomedical Imaging, Depression, Basic Behavioral and Social Science, Mental Health, Brain Disorders, Clinical Research, Pediatric, Behavioral and Social Science, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Neurological, Mental health, Adolescent, Adult, Brain, Cerebral Cortex, Depressive Disorder, Major, Female, Frontal Lobe, Gray Matter, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Neuroimaging, Prefrontal Cortex, Temporal Lobe, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.

Published
2017

4. Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

Author

Rentería, ME, Schmaal, L, Hibar, DP, Couvy-Duchesne, B, Strike, LT, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Gillespie, NA, Hatton, SN, Lagopoulos, J, Veltman, DJ, van der Wee, N, van Erp, TGM, Wittfeld, K, Grabe, HJ, Block, A, Hegenscheid, K, Völzke, H, Veer, IM, Walter, H, Schnell, K, Schramm, E, Normann, C, Schoepf, D, Konrad, C, Zurowski, B, Godlewska, BR, Cowen, PJ, Penninx, BWJH, Jahanshad, N, Thompson, PM, Wright, MJ, Martin, NG, Christensen, H, and Hickie, IB

Subjects
Brain, Humans, Magnetic Resonance Imaging, Prevalence, Risk Factors, Suicide, Depressive Disorder, Major, Adult, Aged, Middle Aged, Female, Male, Young Adult, Suicidal Ideation, Neuroimaging, Depressive Disorder, Major, Psychology, Clinical Sciences, Public Health and Health Services
Abstract

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10-3) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Published
2017

6. Response to Dr Fried & Dr Kievit, and Dr Malhi et al.

Author

Schmaal, L, Veltman, DJ, van Erp, TGM, Sämann, PG, Frodl, T, Jahanshad, N, Loehrer, E, Vernooij, MW, Niessen, WJ, Ikram, MA, Wittfeld, K, Grabe, HJ, Block, A, Hegenscheid, K, Hoehn, D, Czisch, M, Lagopoulos, J, Hatton, SN, Hickie, IB, Goya-Maldonado, R, Krämer, B, Gruber, O, Couvy-Duchesne, B, Rentería, ME, Strike, LT, Wright, MJ, de Zubicaray, GI, McMahon, KL, Medland, SE, Gillespie, NA, Hall, GB, van Velzen, LS, van Tol, M-J, van der Wee, NJ, Veer, IM, Walter, H, Schramm, E, Normann, C, Schoepf, D, Konrad, C, Zurowski, B, McIntosh, AM, Whalley, HC, Sussmann, JE, Godlewska, BR, Fischer, FH, Penninx, BWJH, Thompson, PM, and Hibar, DP

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical and Health Psychology, Clinical Sciences, Psychology, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology, Clinical and health psychology
Published
2016

7. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

Author

Schmaal, L, Veltman, DJ, van Erp, TGM, Sämann, PG, Frodl, T, Jahanshad, N, Loehrer, E, Tiemeier, H, Hofman, A, Niessen, WJ, Vernooij, MW, Ikram, MA, Wittfeld, K, Grabe, HJ, Block, A, Hegenscheid, K, Völzke, H, Hoehn, D, Czisch, M, Lagopoulos, J, Hatton, SN, Hickie, IB, Goya-Maldonado, R, Krämer, B, Gruber, O, Couvy-Duchesne, B, Rentería, ME, Strike, LT, Mills, NT, de Zubicaray, GI, McMahon, KL, Medland, SE, Martin, NG, Gillespie, NA, Wright, MJ, Hall, GB, MacQueen, GM, Frey, EM, Carballedo, A, van Velzen, LS, van Tol, MJ, van der Wee, NJ, Veer, IM, Walter, H, Schnell, K, Schramm, E, Normann, C, Schoepf, D, Konrad, C, Zurowski, B, Nickson, T, McIntosh, AM, Papmeyer, M, Whalley, HC, Sussmann, JE, Godlewska, BR, Cowen, PJ, Fischer, FH, Rose, M, Penninx, BWJH, Thompson, PM, and Hibar, DP

Subjects
Brain, Hippocampus, Humans, Magnetic Resonance Imaging, Case-Control Studies, Depressive Disorder, Major, Adult, Middle Aged, Female, Male, Neuroimaging, major depressive disorder, structural volumes, ENIGMA consortium, meta-analysis, hippocampus, Depressive Disorder, Major, Psychiatry, Medical and Health Sciences, Biological Sciences, Psychology and Cognitive Sciences
Abstract

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Published
2016

18. Cerebral vasomotor reactivity testing in head injury: the link between pressure and flow

Author

Lang, EW, Lagopoulos, J, Griffith, J, Yip, K, Yam, A, Mudaliar, Y, Mehdorn, HM, and Dorsch, NWC

Subjects
Blood pressure -- Health aspects -- Research -- Methods, Intracranial pressure -- Health aspects -- Methods -- Research, Patients -- Care and treatment -- Health aspects -- Research -- Methods, Ultrasound imaging -- Methods -- Health aspects -- Research, Cerebral circulation -- Health aspects -- Methods -- Research, Head injuries -- Health aspects -- Care and treatment -- Research -- Complications and side effects, Clinical neuropsychology -- Research -- Health aspects -- Methods, Health, Psychology and mental health, Care and treatment, Complications and side effects, Research, Methods, Health aspects
Abstract

Background: It has been suggested that a moving correlation index between mean arterial blood pressure and intracranial pressure, called PRx, can be used to monitor and quantify cerebral vasomotor reactivity [...]

Published
2003

19. P.3.14 Brain structural correlates of insomnia severity in major depressive disorder: Results from the ENIGMA-MDD consortium

Author

Leerssen, J., Blanken, T.F., Pozzi, E., Jahanshad, N., Aftanas, L., Baune, B.T., Dannlowski, U., Frodl, T., Godlewska, B.R., Gotlib, I.H., Grotegerd, D., Gruber, O., Hatton, S.N., Hickie, I.B., Irungu, B., Jaworska, N., Kircher, T., Krug, A., Lagopoulos, J., Li, M., MacMaster, F.P., McIntosh, A.M., Osipov, E., Portella, M.J., Sacchet, M.D., Saemann, P.G., Simulionyte, E., Soares, J.C., Walter, M., Whalley, H., Veltman, D., Thompson, P.M., Schmaal, L., and Van Someren, E.J.W.

Published
2019
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23. A growth in bipolar disorder?

Author

Xu, J., Rasmussen, I.-A., Berntsen, E. M., Moss, K., Shnier, R., Lagopoulos, J., and Malhi, G. S.

Published
2007

28. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, primary, Jahanshad, N, additional, Zalesky, A, additional, Kochunov, P, additional, Agartz, I, additional, Alloza, C, additional, Andreassen, O A, additional, Arango, C, additional, Banaj, N, additional, Bouix, S, additional, Bousman, C A, additional, Brouwer, R M, additional, Bruggemann, J, additional, Bustillo, J, additional, Cahn, W, additional, Calhoun, V, additional, Cannon, D, additional, Carr, V, additional, Catts, S, additional, Chen, J, additional, Chen, J-x, additional, Chen, X, additional, Chiapponi, C, additional, Cho, Kl K, additional, Ciullo, V, additional, Corvin, A S, additional, Crespo-Facorro, B, additional, Cropley, V, additional, De Rossi, P, additional, Diaz-Caneja, C M, additional, Dickie, E W, additional, Ehrlich, S, additional, Fan, F-m, additional, Faskowitz, J, additional, Fatouros-Bergman, H, additional, Flyckt, L, additional, Ford, J M, additional, Fouche, J-P, additional, Fukunaga, M, additional, Gill, M, additional, Glahn, D C, additional, Gollub, R, additional, Goudzwaard, E D, additional, Guo, H, additional, Gur, R E, additional, Gur, R C, additional, Gurholt, T P, additional, Hashimoto, R, additional, Hatton, S N, additional, Henskens, F A, additional, Hibar, D P, additional, Hickie, I B, additional, Hong, L E, additional, Horacek, J, additional, Howells, F M, additional, Hulshoff Pol, H E, additional, Hyde, C L, additional, Isaev, D, additional, Jablensky, A, additional, Jansen, P R, additional, Janssen, J, additional, Jönsson, E G, additional, Jung, L A, additional, Kahn, R S, additional, Kikinis, Z, additional, Liu, K, additional, Klauser, P, additional, Knöchel, C, additional, Kubicki, M, additional, Lagopoulos, J, additional, Langen, C, additional, Lawrie, S, additional, Lenroot, R K, additional, Lim, K O, additional, Lopez-Jaramillo, C, additional, Lyall, A, additional, Magnotta, V, additional, Mandl, R C W, additional, Mathalon, D H, additional, McCarley, R W, additional, McCarthy-Jones, S, additional, McDonald, C, additional, McEwen, S, additional, McIntosh, A, additional, Melicher, T, additional, Mesholam-Gately, R I, additional, Michie, P T, additional, Mowry, B, additional, Mueller, B A, additional, Newell, D T, additional, O'Donnell, P, additional, Oertel-Knöchel, V, additional, Oestreich, L, additional, Paciga, S A, additional, Pantelis, C, additional, Pasternak, O, additional, Pearlson, G, additional, Pellicano, G R, additional, Pereira, A, additional, Pineda Zapata, J, additional, Piras, F, additional, Potkin, S G, additional, Preda, A, additional, Rasser, P E, additional, Roalf, D R, additional, Roiz, R, additional, Roos, A, additional, Rotenberg, D, additional, Satterthwaite, T D, additional, Savadjiev, P, additional, Schall, U, additional, Scott, R J, additional, Seal, M L, additional, Seidman, L J, additional, Shannon Weickert, C, additional, Whelan, C D, additional, Shenton, M E, additional, Kwon, J S, additional, Spalletta, G, additional, Spaniel, F, additional, Sprooten, E, additional, Stäblein, M, additional, Stein, D J, additional, Sundram, S, additional, Tan, Y, additional, Tan, S, additional, Tang, S, additional, Temmingh, H S, additional, Westlye, L T, additional, Tønnesen, S, additional, Tordesillas-Gutierrez, D, additional, Doan, N T, additional, Vaidya, J, additional, van Haren, N E M, additional, Vargas, C D, additional, Vecchio, D, additional, Velakoulis, D, additional, Voineskos, A, additional, Voyvodic, J Q, additional, Wang, Z, additional, Wan, P, additional, Wei, D, additional, Weickert, T W, additional, Whalley, H, additional, White, T, additional, Whitford, T J, additional, Wojcik, J D, additional, Xiang, H, additional, Xie, Z, additional, Yamamori, H, additional, Yang, F, additional, Yao, N, additional, Zhang, G, additional, Zhao, J, additional, van Erp, T G M, additional, Turner, J, additional, Thompson, P M, additional, and Donohoe, G, additional

Published
2017
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29. Size matters; but so does what you do with it! Response

Author

Schmaal, L., Veltman, D. J., van Erp, T. G. M., Saemann, P. G., Frodl, T., Jahanshad, N., Loehrer, E., Vernooij, M. W., Niessen, W. J., Ikram, M. A., Wittfeld, K., Grabe, H. J., Block, A., Hegenscheid, K., Hoehn, D., Czisch, M., Lagopoulos, J., Hatton, S. N., Hickie, I. B., Goya-Maldonado, R., Kraemer, B., Gruber, O., Couvy-Duchesne, B., Renteria, M. E., Strike, L. T., Wright, M. J., de Zubicaray, G. I., McMahon, K. L., Medland, S. E., Gillespie, N. A., Hall, G. B., van Velzen, L. S., van Tol, M-J, van der Wee, N. J., Veer, I. M., Walter, H., Schramm, E., Normann, C., Schoepf, D., Konrad, C., Zurowski, B., McIntosh, A. M., Whalley, H. C., Sussmann, J. E., Godlewska, B. R., Fischer, F. H., Penninx, B. W. J. H., Thompson, P. M., Hibar, D. P., Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, and Anatomy and neurosciences

Published
2016

30. Response to: Size matters; but so does what you do with it!

Author

Schmaal, L., Veltman, D.J., van Erp, T. G. M., Saemann, P. G., Frodl, T., Jahanshad, N., Loehrer, E., Vernooij, M. W., Niessen, W. J., Ikram, M. A., Wittfeld, K., Grabe, H. J., Block, A., Hegenscheid, K., Hoehn, D., Czisch, M., Lagopoulos, J., Hatton, S. N., Hickie, I. B., Goya-Maldonado, R., Kraemer, B., Gruber, O., Couvy-Duchesne, B., Renteria, M. E., Strike, L. T., Wright, M. J., de Zubicaray, G. I., McMahon, K. L., Medland, S. E., Gillespie, N. A., Hall, G B, van Velzen, L. S., van Tol, M-J., van der Wee, N. J., Veer, I. M., Walter, H., Schramm, E., Normann, C., Schoepf, D., Konrad, C., Zurowski, B., McIntosh, A. M., Whalley, H. C., Sussmann, J. E., Godlewska, B. R., Fischer, F. H., Penninx, B. W. J. H., Thompson, P. M., Hibar, D. P., Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
MAJOR DEPRESSIVE DISORDER, HISTORY, EARLY-ONSET, ANXIETY
Published
2016

31. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

Author

Schmaal, L., Veltman, D.J., Erp, T.G.M. van, Samann, P.G., Frodl, T., Jahanshad, N., Loehrer, E., Tiemeier, H., Hofman, A., Niessen, W.J., Vernooij, M.W., Ikram, M.A., Wittfeld, K., Grabe, H.J., Block, A., Hegenscheid, K., Volzke, H., Hoehn, D., Czisch, M., Lagopoulos, J., Hatton, S.N., Hickie, I.B., Goya-Maldonado, R., Kramer, B., Gruber, O., Couvy-Duchesne, B., Renteria, M.E., Strike, L.T., Mills, N.T., Zubicaray, G.I. de, McMahon, K.L., Medland, S.E., Martin, N.G., Gillespie, N.A., Wright, M.J., Hall, G.B., MacQueen, G.M., Frey, E.M., Carballedo, A., Velzen, L.S. van, Tol, M.J. van, Wee, N.J. van der, Veer, I.M., Walter, H., Schnell, K., Schramm, E., Normann, C., Schoepf, D., Konrad, C., Zurowski, B., Nickson, T., McIntosh, A.M., Papmeyer, M., Whalley, H.C., Sussmann, J.E., Godlewska, B.R., Cowen, P.J., Fischer, F.H., Rose, M., Penninx, B.W.J.H., Thompson, P.M., Hibar, D.P., ENIGMA-Major Depressive Disorder W, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, Epidemiology, Medical Informatics, Radiology & Nuclear Medicine, Neurology, and Erasmus MC other

Subjects
Male, STRESS, hippocampus, SEGMENTATION, Hippocampus, UNIPOLAR DEPRESSION, Medical and Health Sciences, Lateral ventricles, 0302 clinical medicine, pathology [Brain], 2.1 Biological and endogenous factors, Aetiology, Letter to the Editor, First episode, Psychiatry, pathology [Depressive Disorder, Major], ENIGMA consortium, ABNORMALITIES, Depression, Brain, Middle Aged, Biological Sciences, Serious Mental Illness, Magnetic Resonance Imaging, 3. Good health, AMYGDALA VOLUME, Psychiatry and Mental health, structural volumes, Mental Health, VOXEL-BASED MORPHOMETRY, Neurological, Cardiology, Major depressive disorder, Biomedical Imaging, ONSET DEPRESSION, Original Article, Female, Psychology, methods [Neuroimaging], Clinical psychology, Adult, medicine.medical_specialty, Major Depressive Disorder, HIPPOCAMPAL VOLUME, Neuroimaging, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, Clinical Research, Internal medicine, medicine, Subcortical brain alterations, depressive disorder, ENIGMA, Humans, Bipolar disorder, ddc:610, Molecular Biology, METAANALYSIS, Depressive Disorder, Major, Depressive Disorder, Brain morphometry, Psychology and Cognitive Sciences, Neurosciences, Major, Voxel-based morphometry, medicine.disease, 030227 psychiatry, Brain Disorders, meta-analysis, pathology [Hippocampus], Case-Control Studies, Age of onset, MATTER, 030217 neurology & neurosurgery
Abstract

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.Molecular Psychiatry advance online publication, 30 June 2015; doi:10.1038/mp.2015.69. peerReviewed

Published
2016

34. Structural brain alterations in major depression: findings from the ENIGMA Major Depressive Disorder Working Group

Author

Schmaal, L., Veltman, D.J., Erp, T.G. van, Samann, P.G., Frodl, T., Jahanshad, N., Loehrer, E., Tiemeier, H., Hofman, A., Niessen, W.J., Vernooij, M.W., Ikram, M.A., Wittfeld, K., Grabe, H.J., Block, A., Hegenscheid, K., Volzke, H., Hoehn, D., Czisch, M., Lagopoulos, J., Hatton, S.N., Hickie, I.B., Goya-Maldonado, R., Kramer, B., Gruber, O., Couvy-Duchesne, B., Renteria, M.E., Strike, L.T., Mills, N.T., Zubicaray, G.I. de, McMahon, K.L., Medland, S.E., Martin, N.G., Gillespie, N.A., Wright, M.J., Hall, G.B., MacQueen, G.M., Frey, E.M., Carballedo, A., Velzen, L.S. van, Tol, M.J. van, Wee, N.J. van der, Veer, I.M., Walter, H., Schnell, K., Schramm, E., Normann, C., Schoepf, D., Konrad, C., Zurowski, B., Nickson, T., McIntosh, A.M., Papmeyer, M., Whalley, H.C., Sussmann, J.E., Godlewska, B.R., Cowen, P.J., Fischer, F.H., Rose, M., Penninx, B.W., Thompson, P.M., Hibar, D.P., and ENIGMA-Major Depressive Disorder W

Published
2015

36. Neuropsychological and Functional Outcomes in Recent-Onset Major Depression, Bipolar Disorder and Schizophrenia-Spectrum Disorders: A Longitudinal Cohort Study

Author

Lee, R. S.C., Hermens, D. F., Naismith, S. L., Lagopoulos, J., Jones, A., Scott, J., Chitty, K. M., White, D., Robillard, R., Scott, E. M., and Hickie, I. B.

Abstract

Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M=21.5 years old, s.d.=4.8) and returned for follow-up (M=20.6 months later, s.d.=7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n=71), bipolar disorder (BD; n=61), schizophrenia-spectrum disorders (n=35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P>0.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (P

Published
2015

39. P.2.b.017 Structural brain alterations in major depression: findings from the ENIGMA Major Depressive Disorder Working Group

Author

Schmaal, L., primary, Veltman, D.J, additional, Van Erp, T.G, additional, Sämann, P.G, additional, Frodl, T., additional, Jahanshad, N., additional, Loehrer, E., additional, Tiemeier, H., additional, Hofman, A., additional, Niessen, W.J, additional, Vernooij, M.W, additional, Ikram, M.A, additional, Wittfeld, K., additional, Grabe, H.J., additional, Block, A., additional, Hegenscheid, K., additional, Völzke, H., additional, Hoehn, D., additional, Czisch, M., additional, Lagopoulos, J., additional, Hatton, S.N, additional, Hickie, I.B., additional, Goya-Maldonado, R., additional, Krämer, B., additional, Gruber, O., additional, Couvy-Duchesne, B., additional, Rentería, M.E, additional, Strike, L.T, additional, Mills, N.T, additional, De Zubicaray, G.I, additional, McMahon, K.L, additional, Medland, S.E., additional, Martin, N.G, additional, Gillespie, N.A, additional, Wright, M.J, additional, Hall, G.B, additional, MacQueen, G.M, additional, Frey, E.M, additional, Carballedo, A., additional, Van Velzen, L.S., additional, Van Tol, M.J, additional, Van der Wee, N.J, additional, Veer, I.M., additional, Walter, H., additional, Schnell, K., additional, Schramm, E., additional, Normann, C., additional, Schoepf, D., additional, Konrad, C., additional, Zurowski, B., additional, Nickson, T., additional, McIntosh, A.M, additional, Papmeyer, M., additional, Whalley, H.C, additional, Sussmann, J.E, additional, Godlewska, B.R, additional, Cowen, P.J, additional, Fischer, F.H, additional, Rose, M., additional, Penninx, B.W, additional, Thompson, P.M, additional, and Hibar, D.P, additional

Published
2015
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