Enhancing Neuro Imaging Genetics Through Meta Analysis


White matter anisotropy and diffusivity data were collected from 1305 Major Depressive Disorder (MDD) patients and 1602 healthy controls from 20 samples from around the world in the ENIGMA consortium. Effect sizes were meta-analyzed across studies and showed widespread lower fractional anisotropy in adult patients when compared to controls in 16 of 25 regions of interest. The largest differences were seen in the corpus callosum and corona radiata. White matter microstructural differences between adolescent patients and controls were not apparent after correction for multiple testing. These findings may suggest structural disconnectivity in MDD. (Read more; Run the program)


White matter disturbances in major depressive disorder:a coordinated analysis across 20 international cohorts inthe ENIGMA MDD working group

Laura S. van Velzen, Sinead Kelly, Dmitry Isaev, Andre Aleman,


Using the largest bipolar disorder diffusion tensor imaging dataset to date, mega- and meta-analyses were conducted comparing images from bipolar disorder patients with those from healthy controls. The data were gathered from 26 cohorts, resulting in a sample size of N = 3,033. The analyses showed significantly lowered FA in patients in the corpus callosum and cingulum with lithium medication, later onset and short disease duration also related to higher FA in multiple regions. (Read more; Run the program)


Widespread White Matter Microstructural Abnormalities in Bipolar Disorder: Evidence from mega- and meta-analyses across 3,033 individuals

Pauline Favre, Melissa Pauling, Jacques Stout, Franz Hozer,


In this study the diffusion MRI data of 1446 individuals with PTSD and 1603 controls from 28 cohorts in the PGC-ENIGMA PTSF working group were analyzed for differences in white matter tracts. The analysis results showed lower fractional anisotropy in the tapetum region of the corpus callosum, which connects the left and right hippocampus, structures previously implicated in PTSD. These results support an association between PTSD and alterations of the broader hippocampal network. (Read more; run the program.)


Altered White Matter Microstructural Organization in Post-Traumatic Stress Disorder across 3,049 Adults: Results from the PGC-ENIGMA PTSD Consortium

Emily L Dennis, Seth G Disner, Negar Fani, Lauren E Salminen,


Meta- and mega- analyses were performed on DTI scans of 334 22q11.2 deletion carriers and 260 healthy controls in the largest dMRI0-dervied measures of white matter microstructure in 22q11.2 Deletion Syndrome yet. The analyses results indicated major reductions in mean, axial, and radial diffusivities in 22q11DS patients in the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations and sagittal stratum. However, 22q11DS patients showed higher mean fractional anisotropy (FA) in the internal capsule and corona radiata and lower FA in association fibers compared to controls (Read more; run the program.)


Altered White Matter Microstructure in 22q11.2 Deletion Syndrome: A Multisite Diffusion Tensor Imaging Study

Julio E. Villalón-Reina, Kenia Martínez, Xiaoping Qu, Christopher R. K. Ching,


Using T1-weighted MRI scans of 1,905 patients with obsessive-compulsive disorder (OCD) and 1,760 healthy controls from 27 centers worldwide, the authors conducted meta- and mega-analyses to study structural abnormalities of the brain in OCD patients. They found that the inferior parietal cortex was significantly thinner in patients when compared to controls, and that the inferior and superior parietal cortices were thinner in medicated pediatric patients than in non-medicated pediatric patients compared to controls, indicating that these cortical measures may be affected by the different stages of illness and development. (Read more; run the program; download the source code.)


Cortical Abnormalities Associated with Pediatric and Adult Obsessive-Compulsive Disorder: Findings from the ENIGMA Obsessive-Compulsive Disorder Working Group

Premika S.W. Boedhoe, Lianne Schmaal, Yoshinari Abe, Pino Alonso,


The ENIGMA Major Depressive Disorder (MDD) Working Group conducted meta-analyses on the T1-weighted MRI scans of 2,148 MDD patients and 7,957 healthy controls from 20 sites around the world, analyzing adults and adolescents separately. Adults patients were found to have thinner grey matter in the orbitofrontal cortex, anterior and posterior cingulate, insula, and temporal lobes compared to healthy controls. Adolescent patients had lower surface areas, with effects greatest among recurrent patients. These findings indicate consistent cortical alterations in patients compared to controls and imply that MDD may affect brain structure in different ways depending on age. (Read more; run the program; download the source code.)


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

L Schmaal, DP Hibar, PG Sämann, GB Hall,


This study consisted of meta-analyses of data from 474 individuals with the 22q11.2 chromosomal microdeletion (22q11DS) risk factor for psychotic illness and 315 individuals developing typically gathered from 10 sites around the world. Overall, grey matter thickness was greater in the 22q11DS subjects, but there were focal thickness reductions in the temporal and cingulate cortices. There were global reductions of cortical surface area in 22q11DS individuals compared to controls, and there were significant differences in the reduction based on the size of the 22q11DS deletion (1.5 Mb or 3 Mb). The 22q11DS subjects showed brain structure similarities when compared with idiopathic schizophrenia, particularly in the fronto-temporal cortex, which supports the suitability of 22q11DS as a biological model of schizophrenia. (Read more; run the program; download the source code.)


Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size

Daqiang Sun, Christopher R. K. Ching, Amy Lin, Jennifer K. Forsyth,


This study used data from 4,474 patients with schizophrenia and 5,098 healthy controls from 39 centers around the world to conduct a meta-analysis of cortical thickness and surface area abnormalities in patients. Patients with schizophrenia had smaller surface areas especially in the frontal and temporal lobes and had regionally specific thinner cortices. The cortical thickness effect sizes greatly depended on medication, duration of illness, age of onset, indicating that genetic association studies of schizophrenia and cortical thickness should take these variables into account. (Read more; run the program; download the source code.)


Cortical Brain Abnormalities in 4474 Individuals with Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta-Analysis (ENIGMA) Consortium

Theo G.M. van Erp, Esther Walton, Derrek P. Hibar, Lianne Schmaal,


The ENIGMA attention deficit hyperactivity disorder (ADHD) Working Group conducted mega-analyses comparing the T1-weighted MRI scans of 1,713 participants with ADHD with data from 1,529 control participants. They found that the volumes of the accumbens, amygdala, caudate, hippocampus, and putamen in participants with ADHD were significantly smaller than in controls. The analysis also showed a greatest effect sizes in participants under the age of 15 compared to adults. (Read more; run the program in Firefox or Chrome; download the source code.)


Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis

Martine Hoogman, Janita Bralten, Derrek P Hibar, Maarten Mennes,


Mega- and meta- analyses were conducted on the T1-weighted images from 1,830 patients with obsessive-compulsive disorder (OCD) and 1,759 health controls. The results indicated that patients had significantly smaller hippocampal volumes and larger pallidum volumes compared to controls, and that the effects were stronger in medicated patients. Pediatric patients also had significantly larger thalamic volumes. These results indicate a difference in abnormalities of subcortical volumes between adult and pediatric OCD patients. (Read more; run the program in Firefox or Chrome; download the source code.)


Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis

Premika S.W. Boedhoe, Lianne Schmaal, Yoshinari Abe, Stephanie H. Ameis,


Using MRI scans from 2,028 schizophrenia patients and 2,540 healthy controls from 15 sites worldwide, researchers conducted neuroimaging data meta-analyses. They found that schizophrenia patients showed smaller hippocampal, amygdala, thalamic, accumbens, and intracranial volumes, but larger pallidum and lateral ventricle volumes. (Read more; run the program in Firefox or Chrome; download the source code.)


Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium

TGM van Erp, DP Hibar, JM Rasmussen, DC Glahn,


This study consists of meta-analyses of MRI brain scans from 1,728 patients with major depressive disorder (MDD) and 7,199 healthy controls from 15 researcher centers around the world. The results indicate that relative to controls, patients have a smaller volume hippocampus, while later onset MDD was also associated with smaller amygdala and larger lateral ventricles. (Read more; run the program in Firefox or Chrome; download the source code.)


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

L Schmaal, DJ Veltman, TGM van Erp, PG Sämann,


We harmonized the processing of diffusion tensor imaging (DTI) data of 2391 healthy controls and 1,984 schizophrenia patients from 30 studies worldwide and meta-analyzed regional effects. We have observed significantly lower FA values for global and regional FA values. Longer duration of illness was significantly and negativly correlated with FA in subregions of the corpus collosum, external capsule, fornix, posterior thalamic radiation, superior longitudinal fasciculus and sagittal stratum. (Read more; run the program.)


Evidence for Widespread White Matter Microstructural Differences in Schizophrenia Across 4,375 Individuals from 30 International Studies: Results from the ENIGMA Schizophrenia DTI Working Group

Sinead Kelly, Neda Jahanshad, and others.

Alternated brain connectivity has been implicated in the development and clinical burden of schizophrenia. We tested if differences in the trajectories of white matter tract development influenced the patient-control differences observed in FA and if in turn, those tracts show exacerbated decline with aging. (Read more; run the program; download source code on the NITRC website)

Heterochronicity of White Matter Development and Aging and Vulnerability to Schizophrenia

Kochunov Peter, Ganjgahi Halib, Winkler Anderson, Kelly Sinead, Shukla Dinesh, Xiaoming Du, Jahanshad Neda, Rowland Laura, Sampath Hemalatha, Patel Binish, O’Donnell Patricio, Xie Zhiyong, Paciga Sara A, Schubert Christian, Chen Jian, Zhang Guohao, Thompson Paul M., Nichols Thomas E., Hong Elliot L.

Progressive functional decline in the epilepsies is largely unexplained. We formed the ENIGMA-Epilepsy consortium to understand factors that influence brain measures in epilepsy, pooling data from 24 research centres in 14 countries across Europe, North and South America, Asia, and Australia. Structural brain measures were extracted from MRI brain scans across 2149 individuals with epilepsy, divided into four epilepsy subgroups including idiopathic generalized epilepsies (n =367), mesial temporal lobe epilepsies with hippocampal sclerosis (MTLE; left, n = 415; right, n = 339), and all other epilepsies in aggregate (n = 1026), and compared to 1727 matched healthy controls. (Read more; run the program)

Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study

Whelan CD, Altmann A, Botía JA, Jahanshad N, Hibar DP, et al.

Credits: Peter Kochunov, Jian Chen, Guohao Zhang, Elliot Hong, Neda Jahanshad, Paul Thompson