Structural Brain Changes in remitted Major Depression Andreas Berger unter der Anleitung von Assoc.Prof. Priv.Doz. Dr. Lukas Pezawas Universitätsklinik für Psychiatrie und Psychotherapie Medizinische Universität Wien Juli 2014 Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 1 / 26
Introduction There is no single pathology in MDD that could properly account for the illness. There are subtle alterations in brain structure associated with MDD. Such alterations are the topic of this thesis. Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 2 / 26
Previous studies and brain regions Most reports are of gray matter volume reductions. Prominent brain regions: 1 Hippocampus 2 Basal ganglia 3 Medial prefrontal cortex 1 Subgenual anterior cingulate cortex (sacc) 2 Orbitofrontal cortex (OFC) Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 3 / 26
Regions of interest Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 4 / 26
There are several measures to choose from 1 Gray matter volume 2 Cortical thickness 3 Surface area 4... Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 5 / 26
The radial unit hypothesis Rakic, P. (1988, Jul). Specification of cerebral cortical areas. Science 241 (4862), 170 176. Mountcastle, V. B. (1997, Apr). The columnar organization of the neocortex. Brain 120 ( Pt 4), 701 722. Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 6 / 26
Objective Region-of-interest analysis Is there a group difference in sacc or OFC volume? Cortex-wide analysis Is there a group difference in cortical thickness or surface area anywhere in the cortex? Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 7 / 26
Sample Participants were recruited via ads in Vienna and Dresden. Assessment included SCID-I, SCID-II, HAM-D. n = 216 108 rmdd 108 lifetime-healthy age 19 37 gender 128 female and 88 male MRI scanning was done using a 3 Tesla Siemens TIM Trio scanner with a 12-channel head coil. Anatomical images were acquired using MPRAGE with TR/TE = 2300/4.21ms, flip angle 9 degrees, inversion time 900ms, voxel size 1x1x1.1mm. Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 8 / 26
MRI image processing using FreeSurfer Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 9 / 26
MRI image processing using FreeSurfer Segmentation Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 10 / 26
MRI image processing using FreeSurfer Tesselation Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 11 / 26
MRI image processing using FreeSurfer Tesselation Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 12 / 26
MRI image processing using FreeSurfer Pial surface Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 13 / 26
MRI image processing using FreeSurfer Inflation Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 14 / 26
MRI image processing using FreeSurfer Spherical projection Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 15 / 26
Drawing of ROIs Mapped to each subject via the sphere Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 16 / 26
Statistical Analysis using the General Linear Model y i = β 1 x i1 + β 2 x i2 + β 3 x i3 + ε i Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 17 / 26
Results Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 18 / 26
Result from region-of-interest analysis Group difference in gray matter volume of the left sacc 1100 lh.sacc.label 900 GrayVol (mean + residuals) 700 500 300 lifetime_healthy Clinical.Status remitted_mdd_or_bpii Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 19 / 26
Results from cortex-wide analysis Correlation of cortical thickness with age Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 20 / 26
Results from cortex-wide analysis Correlation of cortical thickness with age vertex 50803 vertex 154600 3.5 3.0 thickness (mean + residuals) 2.5 thickness (mean + residuals) 3.0 2.5 2.0 2.0 20 25 30 35 Age 20 25 30 35 Age Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 21 / 26
Results from cortex-wide analysis Interaction effect between surface area and clinical status Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 22 / 26
Results from cortex-wide analysis Interaction effect between surface area and clinical status vertex 5876 0.6 area (mean + residuals) 0.5 Clinical.Status lifetime_healthy remitted_mdd_or_bpii 0.4 20 25 30 35 Age Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 23 / 26
Summary 1 Former patients have slightly larger left sacc volumes than lifetime-healthy participants. This is unexpected. 2 There is a strong correlation of cortical thickness and age even in relatively young people. This has been documented before. 3 The effect of age on the surface area of a premotor region depends on the clinical status. The meaning of this is unclear. Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 24 / 26
Summary 1 Former patients have slightly larger left sacc volumes than lifetime-healthy participants. This is unexpected. 2 There is a strong correlation of cortical thickness and age even in relatively young people. This has been documented before. 3 The effect of age on the surface area of a premotor region depends on the clinical status. The meaning of this is unclear. Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 24 / 26
Summary 1 Former patients have slightly larger left sacc volumes than lifetime-healthy participants. This is unexpected. 2 There is a strong correlation of cortical thickness and age even in relatively young people. This has been documented before. 3 The effect of age on the surface area of a premotor region depends on the clinical status. The meaning of this is unclear. Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 24 / 26
Summary 1 Former patients have slightly larger left sacc volumes than lifetime-healthy participants. This is unexpected. 2 There is a strong correlation of cortical thickness and age even in relatively young people. This has been documented before. 3 The effect of age on the surface area of a premotor region depends on the clinical status. The meaning of this is unclear. Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 24 / 26
How not to interpret statistics Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 25 / 26
Danke für die Aufmerksamkeit! Andreas Berger (Meduniwien) Structural Brain Changes in rmdd Juli 2014 26 / 26