ENIGMA
OCD working group
Teleconference
27th of August 2015
1 PM GMT (Greenwich Mean Time)
Amsterdam/Barcelona/Berlin/Milan/Munich/Rome/Zurich 3 PM
Sao Paulo 10 AM
Tokyo/Kyoto/Seoul 10 PM
Cape Town 3 PM
Los Angeles 6 AM
New York/Toronto/Michigan/Boston 9 AM
Bangalore 6.30 PM
Agenda
1.
Subcortical meta-analysis
1.
2.
3.
4.
2.
3.
Planning cortical meta-analysis
Secondary research proposals
1.
2.
3.
4.
5.
6.
7.
8.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical meta-analysis
DTI
Covariance
other
ENIGMA Lateralization working group
Mega-analysis database
Grants
Presentations
Future meetings
Please, send me (oa.vandenheuvel@vumc.nl) an email as soon as your site
is‘online’, with the name of the person representing the site during the TC.
Take care of the quality of the TC: (un)mute your line by pressing 6!!
Agenda
1.
Subcortical meta-analysis
1.
2.
3.
4.
2.
3.
Planning cortical meta-analysis
Secondary research proposals
1.
2.
3.
4.
5.
6.
7.
8.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical meta-analysis
DTI
Covariance
other
ENIGMA Lateralization working group
Mega-analysis database
Grants
Presentations
Future meetings
Results – adult
OCD vs HC
*
Effect size cohen’s d: 0.16
P-value: 2.1e-3 corrected for multiple comparisons
Analyses controlled for age, gender and ICV
Results – adult
medicated OCD vs HC
*
Effect size d:
P-value:
*
hippocampus -0.28
hippocampus 3.7e-5
pallidum 0.24
pallidum 8.5e-
4
corrected for multiple comparisons
Results – adult
comorbid lifetime depression OCD vs HC
*
Effect size cohen’s d: -0.27
P-value: 6.3e-4 corrected for multiple comparisons
Analyses controlled for age, gender and ICV
Results – paediatric
Unmedicated OCD vs HC
*
Effect size cohen’s d: 0.40
P-value: 9.4e-4 corrected for multiple comparisons
Analyses controlled for age, gender and ICV
Conclusions


Our results clearly indicate a key role of the
thalamus (in children) and the pallidum (in adults)
The hippocampus effect seems to be driven by
OCD patients with comorbid lifetime depression



Different ENIGMA working groups (e.g., Schizophrenia,
MDD, Bipolar) also observed hippocampal abnormalities,
suggesting that these hippocampal abnormalities are
non-specific for OCD
Pallidum finding as in Schizophrenia
Findings suggest a different pattern of subcortical
abnormalities in paediatric and adult OCD patients

This is in line with the developmental nature of the
disease and neuroplastic changes during the course of
the disease
Agenda
1.
2.
3.
4.
5.
6.
7.
8.
Subcortical meta-analysis
1.
2.
3.
4.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical meta-analysis
1.
2.
3.
DTI
Covariance
other
Planning cortical meta-analysis
Secondary research proposals
ENIGMA Lateralization working group
Mega-analysis database
Grants
Presentations
Future meetings
Results – extra analyses
follows (as soon as we have data complete)
 Differences
between child and adult onset
(cut-off 21 years)
 Diagnosis x gender interaction effect
 Age bin analyses
 Effect of different types of medication
(SSRI/antipsychotics)
Results – extra analyses
follows

Sites that still need to send csv files



Gruner
Tolin
Sites that still need to send medication
percentages




Gruner
Kwon
Soriano-Mas
Spalletta
Please, send a.s.a.p. (after holiday)!
Planning meta-analysis for the
subcortical volumes
 Remaining
sites send requested additional
information

September 4th, 2015
 Final

September 11th, 2015
 Draft

run extra analyses
paper
October 2015

Suggested journal: American Journal of Psychiatry
(planning submission end of November?)
Agenda
1.
2.
3.
4.
5.
6.
7.
8.
Subcortical meta-analysis
1.
2.
3.
4.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical meta-analysis
1.
2.
3.
DTI
Covariance
other
Planning cortical meta-analysis
Secondary research proposals
ENIGMA Lateralization working group
Mega-analysis database
Grants
Presentations
Future meetings
Planning cortical meta-analysis
 The
recon-all also included the cortical
segmentations
 First step is to start with the QC

Check outlier/histograms/webpages scripts will
be send mid September

Deadline November 01, 2015
 Statistical
analyses R scripts will be send
on the first of November

Deadline December 01, 2015
Agenda
1.
2.
3.
4.
5.
6.
7.
8.
Subcortical meta-analysis
1.
2.
3.
4.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical metaanalysis
Planning cortical meta-analysis
Secondary research proposals
1.
2.
3.
DTI
Covariance
other
ENIGMA Lateralization working
group
Mega-analysis database
Grants
Presentations
Future meetings
Secondary research proposals

DOMAIN (DTI in OCD Meta-Analytic INvestigation)
 Piras et al. (Italy)


Structural covariance analysis
 Kwon & Yun et al. (South Korea)


approved
Connectomics/graph analysis
 Koch & Reess et al. (Germany)


approved
to be submitted
Resting state
 Soriano-Mas et al. (Spain)

planned
protocol under construction (Piras / Jahanshad)
Meta analyses of DTI data in OCD
Fabrizio Piras, Gianfranco Spalletta, Federica Piras,
Chiara Chiapponi, Tommaso Gili, Mariangela Iorio,
Odile A. van den Heuvel, Premika Boedhoe, Neda
Jahanshad, Dan Stein, Paul Thompson
+ ENIGMA-OCD consortium members contributing
with DTI scans
protocol under construction (Piras / Jahanshad)
Meta analyses of DTI data in OCD
INTRO
Microstructural alterations in the white matter (WM) tracts connecting the
cortical and subcortical regions involved in OCD pathophysiology are relatively
unexplored. Consistently with current frontal-striatal, fronto-parietal and
fronto-limbic models of the disorder, recent studies1 showed altered
functional connectivity among GM matter nodes of the cortico-striatothalamo-cortical circuitry. Moreover, the existence of additional abnormalities
in specific WM tracts (e.g. internal capsule (IC), cingulate bundle (CB), and
corpus callosum (CC)) and in different brain regions (medial frontal and
parietal WM), in the OCD population has been recently suggested2. These WM
abnormalities may be familial3 and responsive to serotonin reuptake inhibitor
treatment (SSRI)4 and vary according to the severity of different symptom
dimensions5 and possibly depending upon therapeutic drugs6. Here we
propose a meta-analytic approach to further study structural brain
architecture abnormalities in the OCD-ENIGMA multisite sample.
1.
2.
3.
4.
5.
6.
Stern, E. R., Fitzgerald, K. D., Welsh, R. C., Abelson, J. L. & Taylor, S. F. PLoS One 7, (2012)
Piras, F., Piras, F., Caltagirone, C. & Spalletta, G. Neuroscience and Biobehavioral Reviews (2013)
Menzies, L. et al. Am. J. Psychiatry 165, 1308–1315 (2008)
Yoo, S. Y. et al. Acta Psychiatr. Scand. 116, 211–219 (2007)
Koch, K. et al. J. Psychiatr. Res. 46, 264–270 (2012).
Radua J et al, Neuropsychopharmacology, 39,1547-57 (2014)
protocol under construction (Piras / Jahanshad)
Meta analyses of DTI data in OCD
METHODS
We plan to perform data aggregation by meta-analytical pooling, where no
raw data are shared between sites.
We took advantage of existent data gathering/analysis protocols within the
ENIGMA consortium (e.g. http://enigma.ini.usc.edu/protocols/dti-protocols/)
for multi-site processing and extraction of DTI values.
Briefly, the protocol includes:
- Preprocessing
- Preprocessing quality control
- Processing (tbss)
- Tbss quality control
- ROIs FA extraction
protocol under construction (Piras / Jahanshad)
Meta analyses of DTI data in OCD
ROIs
Following the extraction of the skeletonized white matter and projection of
individual FA values, ENIGMA-tract-wise regions of interest (ROIs), derived
from the Johns Hopkins University white matter parcellation atlas1 will be
transferred to extract the mean FA across the full skeleton and average FA
values for twelve major white matter tracts, breaking down the corpus
callosum into 3 regions, for a total of 15 regions of interest (ROIs)
1. Kochunov et al, Neuroimage, 95 136-50 (2014)
protocol under construction (Piras / Jahanshad)
Meta analyses of DTI data in OCD
ROIs
Following the extraction of the skeletonized white matter and projection of
individual FA values, ENIGMA-tract-wise regions of interest (ROIs), derived
from the Johns Hopkins University white matter parcellation atlas1 will be
transferred to extract the mean FA across the full skeleton and average FA
values for twelve major white matter tracts, breaking down the corpus
callosum into 3 regions, for a total of 15 regions of interest (ROIs)



Summary statistics (i.e. Cohen’s d), expressing the magnitude of the
potential difference in DTI parameters within ROIs, will be produced.
Possibly, meta-regressions will be performed using age, medication and
symptom severity scores as regressor.
Bonferroni correction (p=0.05/15= 0.0033) will be applied
Secondary research proposals

DOMAIN (DTI in OCD meta-analytic Investigation)
 Piras et al. (Italy)


Structural covariance analysis
 Kwon & Yun et al. (South Korea)


approved
Connectomics/graph analysis
 Koch & Reess et al. (Germany)


approved
to be submitted
Resting state
 Soriano-Mas et al. (Spain)

planned
Cortical Structural Covariance Network
Analysis: meta-analytical approach



Lead by Kwon and Yun et al. (South Korea)
Will be started after the primary cortical thickness
analysis (lead by van den Heuvel et al.)
Requirement for each study sites
 what you need to send to us: 2 kinds of files
(which will be produced during the primary cortical
thickness analysis)
1) ‘LandRthickness.csv’ 2) ‘Covariates.csv’
 we will save your time and working load: by
conducting cortical structural covariance network
analyses & subsequent meta-analytical approach
on our own, using two ‘.csv’ files you prepared
Agenda
1.
2.
3.
4.
5.
6.
7.
8.
Subcortical meta-analysis
1.
2.
3.
4.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical meta-analysis
1.
2.
3.
DTI
Covariance
other
Planning cortical meta-analysis
Secondary research proposals
ENIGMA Lateralization working group
Mega-analysis database
Grants
Presentations
Future meetings
ENIGMA Lateralization
working group (Guadalupe et al.)
Contributing sites within ENIGMA-OCD







Cheng
Van den Heuvel
Kwon
Nakamae
Nakao
Reddy
Stein





Walitza
Mataix-Cols
Menchon
Huyser
Wang
Agenda
1.
2.
3.
4.
5.
6.
7.
8.
Subcortical meta-analysis
1.
2.
3.
4.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical metaanalysis
Planning cortical meta-analysis
Secondary research proposals
1.
2.
3.
DTI
Covariance
other
ENIGMA Lateralization working
group
Mega-analysis database
Grants
Presentations
Future meetings
Agenda
1.
2.
3.
4.
5.
6.
7.
8.
Subcortical meta-analysis
1.
2.
3.
4.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical metaanalysis
Planning cortical meta-analysis
Secondary research proposals
1.
2.
3.
DTI
Covariance
other
ENIGMA Lateralization working
group
Mega-analysis database
Grants
Presentations
Future meetings
Grant proposals

Status grants and new grant opportunities




Pending: Carles Soriano-Mas (OCD foundation)
Planned: Blair Simpson (NIH-grant for LMICs), Dec 2015
Planned: Odile van den Heuvel (vidi), Oct 2015
Note: feel free to submit also personal grants
including ENIGMA-OCD data (but please,
propose/discuss plans prior to submission to
prevent overlap with other analysis plans)
Agenda
1.
2.
3.
4.
5.
6.
7.
8.
Subcortical meta-analysis
1.
2.
3.
4.
Adults
Paediatric
extra-analyses (follows)
Planning final subcortical metaanalysis
Planning cortical meta-analysis
Secondary research proposals
1.
2.
3.
DTI
Covariance
other
ENIGMA Lateralization working
group
Mega-analysis database
Grants
Presentations
Future meetings
Presentations
 Poster
ICOCS 2015 (Boedhoe et al.)
+ Oral presentation ICOCS 2015
(van den Heuvel)
 Symposium SOBP 2016?
 Together with other ENIGMA working groups
 Voorjaarscongres Psychiatry 2016 (NL)
 Together with ENIGMA-MDD (Schmaal), ENIGMA-ADHD
(Franke), ENIGMA-Autism (Buitelaar)
Future meetings
 Options

ECNP - Amsterdam


August 29, 2015 – September 01 2015
ICOCS - Amsterdam

September 02, 2015
 Next

to meet
TC ENIGMA-OCD working group
October 29, 2015