Teleconference November 21 2016 2 PM GMT Greenwich Mean Time AmsterdamBarcelonaBerlinMilanMunichRomeZurich 3 PM OxfordBraga 2 PM Sao Paulo noon TokyoKyotoSeoul 11 PM Cape Town 4 PM ID: 644924
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Slide1
ENIGMA OCD working group
Teleconference
November 21,
2016
2
PM GMT (Greenwich
Mean
Time)
Amsterdam/Barcelona/Berlin/Milan/Munich/Rome/Zurich 3 PM
Oxford/Braga 2 PM
Sao Paulo
noon
Tokyo/Kyoto/Seoul 11 PM
Cape Town 4 PM
Los Angeles 6 AM
New York/Toronto/Michigan/Boston 9 AM
Bangalore 7.30 PMSlide2
Agenda
1
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics
project
Cross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)
Collaboration Lateralization working group (
Francks
et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration Plasticity working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide3
1. Brian Brennan, MD, MMScMedical Director
Obsessive-Compulsive Disorder Institute, McLean Hospital
Associate Director of Translational Neuroscience Research
Biological Psychiatry Laboratory, McLean Hospital
Assistant Professor of Psychiatry
Harvard Medical School
Adult OCD sample (T1, DTI, rs fMRI data)
2Slide4
Agenda
3
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics
project
Cross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)
Collaboration Lateralization working group (
Francks
et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide5
2a. Cortical meTa-analysis Recap main
findings
– adults
Thinner cortices of
frontal
and
temporal
areas
in
medicated
adult OCD patients
versus healthy controls
Frontal and temporal areas (d
≈
- 0.2, P
FDR < 0.05)
4
Confidential results
Please, do not distributeSlide6
Disease Severity Surface Area
Frontal,
temporal, parietal and cingulate
cortex
(d
≈
-
0.1,
P
FDR
< 0.05
)
Lower surface area of
frontal
,
temporal, parietal
and
cingulate
r
egions as disease severity increases in
adult OCD patients
5
Confidential results
Please, do not distribute
2a. Cortical
meTa
-
analysis (adults) Slide7
2a. Cortical meTa-analysisRecap main findings – children
Frontal, parietal, cingulate and occipital regions (d
≈
- 0.3, P
FDR
<
0.05)
Lower surface area of
frontal
,
parietal
and
occipital
regions
in
medicated pediatric OCD patients versus healthy controls
6Confidential resultsPlease, do not distributeSlide8
2b. Cortical meGa AdultsOCD vs HC – Cortical Thickness & Surface Area
↓average cortical thickness (CT)
↓CT bilateral inferior parietal cortices
Also after correction for average thickness (
AvgT
)
↓CT middle temporal cortex, fusiform gyrus, OFC, rostral middle frontal, and
precuneus
(Mean)
Effect size d ≈ - 0.13
↓ surface area (SA) transverse
temporal
cortex (Left)
Also after correction for total surface area (
tSA
) and intracranial volume (ICV)d ≈
- 0.16
all results presented are considered significant if the P-value exceeded a significance threshold determined by the false discovery rate (FDR) procedure q=0.05
7
Confidential results
Please, do not distributeSlide9
2b. Cortical meGa AdultsMedicated patients versus controls
↓
Average thickness
↓CT in almost all regions
Effects disappear after correction for average thickness except for ↓CT
postcentral
gyrus (Right)
d between 0.1 -
0.26
↓ SA transverse temporal lobe (
L)
d
≈
-
0.2
Also after correction for tSA and ICVAfter tSA
correction↑
inferior
parietal surface area
8
Confidential results
Please, do not distributeSlide10
2b. Cortical meGa AdultsMedication analyses
Unmedicated patients versus controls
↓CT of the inferior temporal gyrus (R) after correction for
AvgT
d
≈
-
0.15
Medicated patients versus unmedicated patients
↓CT on average in medicated patients
↓CT caudal middle frontal, inferior frontal, superior frontal, inferior temporal, superior temporal, middle temporal, insula and
supramarginal
gyrus
Effects disappear after correction for
AvgT
d between - 0.13 and – 0.21 9
Confidential results
Please, do not distributeSlide11
2b. Cortical meGa AdultsEarly onset vs HC
↓CT inferior parietal cortex (M) and lateral OFC (M)
Also after correction for
AvgT
↓CT
postcentral
gyrus (R) only after correction for
AvgT
d
≈
-
0.16
10
Confidential results
Please, do not distributeSlide12
2b. Cortical meGa AdultsLate onset vs HC
Cortical thickness
↓average
CT in
late onset patients
↓CT inferior
temporal, middle temporal, fusiform, middle frontal,
mOFC
, operculum, posterior cingulate and lingual
gyrus
d ≈
- 0.15
Effects
disappear when corrected for
AvgT
Surface area
↓SA operculum (L) and transverse temporal cortex (L) d ≈ - 0.16 Also when corrected for tSA and ICV
11
Confidential results
Please, do not distributeSlide13
2b. Cortical meGa AdultsSeverity (YBOCS)
↓average SA
↓SA of cingulate, inferior parietal, superior frontal, middle frontal, OFC,
paracentral
,
precentral
, superior temporal middle temporal
d
between
- 0.06 and - 0.12
Effects disappear when corrected for
tSA
and ICV
12
Confidential resultsPlease, do not distributeSlide14
2b. Cortical meGa Adults Symptom sub dimensions
Cleaning
↓CT middle temporal gyrus and superior frontal gyrus bilaterally
d between - 0.22 and - 0.28
Only when corrected for
AvgT
Aggression/Checking
↑
average SA
↑
SA fusiform, middle temporal, superior temporal, transverse temporal, isthmus cingulate, lateral occipital, inferior parietal, superior parietal,
supramarginal
,
postcentral
,
precuneus, rostral middle frontal and superior frontal gyrus d between 0.16 and 0.27Effects disappear when corrected for tSA/ICV
13Confidential resultsPlease, do not distributeSlide15
2b. Cortical meGa AdultsComorbidities – anxiety
Patients with anxiety versus HC
↓CT
mOFC
, middle temporal, superior frontal
Also when corrected for
AvgT
Additionally
↓CT
paracentral
and
postcentral
gyrus
P
atients without anxiety versus HCOverlapping with OCD vs HC results for CT and SAPatients with versus without a lifetime anxiety comorbidity↓CT superior frontal gyrus
d = - 0.40↑SA lateral occipital, pars orbitalis d ≈ 0.35
14
Confidential results
Please, do not distributeSlide16
2b. Cortical meGa AdultsComorbidities – depression
Patients without depression
vs
HC
Overlapping with OCD
vs
HC
results for CT and SA
Patients with depression
vs
HC
↓CT inferior parietal,
postcentral
, superior parietal, fusiform, inferior temporal, middle temporal, lateral OFC and
paracentral
gyrusAlso after correction for AvgT
15Confidential resultsPlease, do not distributeSlide17
2b. MeGa Summary – Adults Surface area
Overall a lower SA of the transverse temporal cortex in OCD patients
Late onset OCD seem to be associated with a lower SA of the operculum
A global decreased surface area as disease severity increases
A global increased surface area seems to be associated with aggression/checking symptoms
Comorbid anxiety seems to be associated with an increased SA of the lateral occipital cortex
16
Confidential results
Please, do not distributeSlide18
2b. MeGa Summary – Adults Cortical thickness
Overall a thinner inferior parietal cortex in OCD patients
Global thinner cortex seem to be associated with medication status
Late onset patients show overlapping abnormalities as medicated patients
Cleaning symptoms seem associated with a thinner middle temporal cortex and a thicker superior frontal cortex
Comorbid anxiety seems to be associated with a thinner superior frontal cortex
17
Confidential results
Please, do not distributeSlide19
2b. Cortical meGa – childrenOCD vs HC (cortical thickness – CT)
↓CT
inferior parietal, superior parietal and lateral occipital cortex
Inferior parietal and superior parietal cortex maintain after correction for
AvgT
d ≈ - 0.27
↑CT lateral OFC
Also after
AvgT
correction
d ≈ 0.22
Same findings for Medicated OCD versus HC with slightly stronger effect sizes d ~ - 0.3
18
Confidential results
Please, do not distributeSlide20
2b. Cortical meGa – childrenSurface area (SA)
OCD
vs
HC
↓
SA
mOFC
,
paracentral
(R), rostral anterior cingulate
Only after correction for ICV
d ≈ - 0.25
Medicated
vs
HC↓SA
cuneus, mOFC, paracentral, posterior cingulate, rostral middle frontal and superior frontal gyrus
d between - 0.3 and - 0.4Only when corrected for ICV (except for the
mOFC) Medicated versus Unmedicated OCD patients
↓
SA
lingual (only when corrected for ICV) and
pericalcerine
d between - 0.34 and - 0.42
19
Confidential results
Please, do not distributeSlide21
2b. Cortical meGa – childrenClinical variables
Age of onset
↑CT
precentral
gyrus
(M)
Only when corrected for
AvgT
d = 0.20
Ordering/symmetry
↑SA
cuneus
(L)
Only when corrected for ICVd = 0.4920
Confidential resultsPlease, do not distributeSlide22
2b. Cortical meGa – childrenComorbidities
OCD patients without anxiety or depression comorbidities
vs
HC
↓CT inferior
parietal and
superior parietal
cortex d ≈ - 0.3
↑
CT lateral
OFC d = 0.34
Only when corrected for
AvgT
↓SA
mOFC
, paracentral and posterior cingulate d ≈ - 0.25Only when corrected for ICV
With versus without anxiety↑CT of the parahippocampal gyrus (L) d = 0.38
21
Confidential results
Please, do not distributeSlide23
2b. Summary meGa Childrencortical thickness
Cortical thinning of the inferior and superior parietal cortex and lateral occipital cortex
Cortical thinning of the caudal anterior cingulate as disease severity increases
Anxiety in OCD patients seem to be associated with cortical thinning of the
parahippocampal
gyrus
22
Confidential results
Please, do not distributeSlide24
2b. Summary MeGa Childrensurface area
Surface area
Lower surface area of the
mOFC
,
paracentral
and rostral cingulate regions in OCD patientsMore widespread effects in medicated OCD patientsSymmetry symptoms seem to be associated with a greater surface area of the left
cuneus
23
Confidential results
Please, do not distributeSlide25
2b. Overall meTa versus meGa
Consistent
Mega-Analysis is more sensitive
Picks up findings that did not survived FDR correction in the
meTa
-analysis
Subdimensions analyses
24
Confidential results
Please, do not distributeSlide26
2c. Planning cortical meGa analysis
Manuscript writing (Boedhoe / van den Heuvel)
November/December 2016
Draft to co-authors
December 2016 / January 2017
25Slide27
Agenda
26
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics
projectCross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)Collaboration Lateralization working group (Francks
et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide28
Status:
Centrally
processed
data (Rome)
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group
, Rome
Site
PI
HC
DOC
Amsterdam
Odile van den Heuvel
34
38
Bangalore
Reddy Janardhan
131
158
Berlin
Jan-Carl Beucke
15
15
Cape Town
Dan Stein
23
22
Kyoto
Takashi Nakamae
41
35
Milan
Francesco Benedetti
65
63
Munich
Kathrin Koch
60
73
New York
Blair Simpson
28
29
New York
Emily Stern
18
16
Rome
Gianfranco Spalletta
111
77
Sao Paulo
Marcelo Batistuzzo
30
37
Seoul
Jun Soo Kwon
87
98
Shangai
Zhen Wang
45
85
Total
688
746
27Slide29
Available data:TBSS-based FA of 19 bilateral and 5 unilateral white matter labels (plus average FA) based on the John Hopkins University –
ICBM-DTI-81 white matter labels atlas
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group
, Rome
28Slide30
Available data:TBSS-based FA of 19 bilateral and 5 unilateral white matter labels (plus average FA) based on the John Hopkins University –
ICBM-DTI-81 white matter labels atlas
Effect size estimates (Cohen’s d) computed using
a
ge
, sex,
age by sex interaction, age2 and age
2
by sex
interaction
as
covariates since linear and non-linear age and sex interactions have been
reported for FA (Kochunov et al., 2012)3. DOMAIN – OCD DTI meta-analysisFabrizio Piras – Gianfranco
Spalletta’s group, Rome29Slide31
Results: random effects
p<.002 surviving
Bonferroni
correction 0.05/24
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group
, Rome
Groups
Effect size and 95% confidence interval
Test of null (2-Tail)
Heterogeneity
Tau-squared
Tau-squared
Tau-squared
Tau-squared
Group
Point estimate
Standard error
Variance
Lower limit
Upper limit
Z-value
P-value
Q-value
df (Q)
P-value
I-squared
Tau Squared
Standard Error
Variance
Tau
Random effects
ACR
-0,154
0,093
0,009
-0,336
0,029
-1,652
0,099
32,947
12,000
0,001
63,578
0,066
0,046
0,002
0,257
ALIC
-0,046
0,089
0,008
-0,221
0,130
-0,509
0,611
30,482
12,000
0,002
60,632
0,058
0,042
0,002
0,241
AverageFA
-0,209
0,098
0,010
-0,402
-0,017
-2,132
0,033
36,632
12,000
0,000
67,242
0,078
0,051
0,003
0,279
BCC
-0,122
0,097
0,009
-0,313
0,068
-1,261
0,207
35,953
12,000
0,000
66,623
0,076
0,050
0,003
0,275
CC
-0,184
0,097
0,010
-0,375
0,007
-1,889
0,059
36,181
12,000
0,000
66,833
0,076
0,050
0,003
0,276
CGC
-0,001
0,084
0,007
-0,165
0,164
-0,007
0,995
26,901
12,000
0,008
55,392
0,047
0,036
0,001
0,216
CGH
-0,074
0,058
0,003
-0,1880,040-1,2770,20213,80912,0000,31313,0990,0060,0180,0000,075CR-0,1520,0920,008-0,3320,028-1,6540,09832,11212,0000,00162,6300,0630,0440,0020,252CST0,0620,0530,003-0,0410,1661,1830,23711,11712,0000,5190,0000,0000,0150,0000,000EC-0,1080,0770,006-0,2590,044-1,3900,16422,93212,0000,02847,6720,0340,0310,0010,185EC-R-0,1240,0920,008-0,3030,056-1,3480,17832,01912,0000,00162,5230,0630,0440,0020,251FX-0,1190,0680,005-0,2530,015-1,7430,08118,19412,0000,11034,0430,0190,0240,0010,139FXST-0,1120,0900,008-0,2900,065-1,2430,21431,18512,0000,00261,5200,0600,0430,0020,246GCC-0,1990,0800,006-0,356-0,042-2,4850,01324,44112,0000,01850,9020,0390,0330,0010,198IC-0,0110,0800,006-0,1680,145-0,1410,88824,40912,0000,01850,8380,0390,0330,0010,197IFO-0,0200,0700,005-0,1570,117-0,2890,77318,91512,0000,09136,5590,0220,0250,0010,147PCR-0,1650,0660,004-0,295-0,036-2,5080,01217,00012,0000,15029,4130,0160,0220,0000,125PLIC0,0420,0740,006-0,1030,1880,5680,57021,20512,0000,04743,4100,0290,0280,0010,170PTR-0,2550,0540,003-0,361-0,148-4,6950,00012,41012,0000,4133,3010,0010,0160,0000,036RLIC-0,0300,0760,006-0,1780,119-0,3900,69722,01412,0000,03745,4900,0310,0290,0010,177SCC-0,1220,0790,006-0,2770,034-1,5320,12624,13812,0000,01950,2850,0380,0320,0010,195SCR-0,0660,0760,006-0,2150,083-0,8680,38522,11912,0000,03645,7470,0320,0290,0010,178SFO-0,0930,0750,006-0,2410,054-1,2360,21621,73512,0000,04144,7900,0310,0290,0010,175SLF-0,1200,0950,009-0,3070,066-1,2670,20534,41412,0000,00165,1310,0710,0480,0020,266SS-0,1990,0620,004-0,320-0,077-3,1920,00115,37312,0000,22221,9390,0110,0200,0000,103UNC-0,1720,0700,005-0,309-0,035-2,4630,01418,84912,0000,09236,3350,0220,0250,0010,147Total within637,486312,0000,000Total between52,56725,0000,001Overall-0,1020,0150,000-0,131-0,074-6,9610,000690,053337,0000,00051,1630,0380,0060,0000,195
30
Confidential results
Please, do not distributeSlide32
Laterality3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group, Rome
Groups
Effect size and 95% confidence interval
Test of null (2-Tail)
Group
Point estimate
Standard error
Variance
Lower limit
Upper limit
Z-value
P-value
ACR_L
-0,1651
0,0816
0,0067
-0,3250
-0,0051
-2,0223
0,0431
ACR-R
-0,1266
0,1001
0,0100
-0,3228
0,0697
-1,2639
0,2063
ALIC-L
-0,0351
0,0755
0,0057
-0,1832
0,1129
-0,4653
0,6417
ALIC-R
-0,0478
0,0923
0,0085
-0,2287
0,1330
-0,5184
0,6041
CGC-L
-0,0196
0,0676
0,0046
-0,1521
0,1129
-0,2899
0,7719
CGC-R
0,0177
0,0985
0,0097
-0,1753
0,2107
0,1795
0,8576
CGH-L
-0,0828
0,0716
0,0051
-0,2231
0,0576
-1,1559
0,2477
CGH-R
-0,0647
0,0527
0,0028
-0,1680
0,0387
-1,2262
0,2201
CR-L
-0,1656
0,0847
0,0072
-0,3315
0,0003
-1,9559
0,0505
CR-R
-0,1261
0,0954
0,0091
-0,3131
0,0609
-1,3212
0,1864
CST-L
0,0374
0,0527
0,0028
-0,0660
0,1407
0,7088
0,4784
CST-R
0,0731
0,0570
0,0032
-0,0386
0,1848
1,2828
0,1996
EC-L
-0,0832
0,0633
0,0040
-0,2072
0,0408
-1,3154
0,1884
EC-R
-0,1235
0,0917
0,0084
-0,3032
0,0561
-1,3476
0,1778
FX/ST-L
-0,0994
0,0885
0,0078
-0,2728
0,0740
-1,1233
0,2613FX/ST-R-0,10150,08130,0066-0,26090,0579-1,24760,2122IC-L-0,00050,07480,0056-0,14710,1461-0,00690,9945IC-R-0,01640,07940,0063-0,17210,1393-0,20650,8364IFO-L-0,05090,05690,0032-0,16240,0605-0,89560,3705IFO-R0,00810,07280,0053-0,13450,15080,11180,9110PCR-L-0,16380,06740,0045-0,2959-0,0316-2,42850,0152PCR-R-0,14290,05990,0036-0,2603-0,0255-2,38570,0170PLIC-L0,07000,06970,0049-0,06650,20651,00510,3149PLIC-R0,00630,07970,0064-0,15000,16260,07930,9368PTR-L-0,22480,06130,0038-0,3449-0,1048-3,67020,0002PTR-R-0,24400,05290,0028-0,3477-0,1402-4,60910,0000RLIC-L-0,03880,08320,0069-0,20190,1243-0,46630,6410RLIC-R-0,01780,06110,0037-0,13760,1020-0,29150,7707SCR-L-0,07910,07180,0052-0,21980,0616-1,10150,2707SCR-R-0,04120,07760,0060-0,19330,1108-0,53130,5952SFO-L-0,12350,07960,0063-0,27950,0325-1,55170,1207SFO-R-0,03970,06930,0048-0,17560,0961-0,57320,5665SLF-L-0,09670,08560,0073-0,26450,0712-1,12880,2590SLF-R-0,12790,09860,0097-0,32120,0654-1,29680,1947SS-L-0,20290,05700,0032-0,3146-0,0912-3,55950,0004SS-R-0,15970,05800,0034-0,2733-0,0460-2,75400,0059UNC-L-0,13830,06500,0042-0,2657-0,0108-2,12660,0334UNC-R-0,15350,06470,0042-0,2802-0,0267-2,37350,0176Total withinTotal betweenOverall-0,083200,011350,00013-0,10545-0,06096-7,330740,00000p<.0013 surviving Bonferroni correction 0.05/3831Confidential resultsPlease, do not distributeSlide33
Sagittal Striatum - bilateral
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group, Rome
32
Confidential results
Please, do not distributeSlide34
Sagittal Striatum - left
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group
, Rome
33
Confidential results
Please, do not distributeSlide35
Sagittal Striatum - right
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group
, Rome
34
Confidential results
Please, do not distributeSlide36
Posterior Thalamic Radiation
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group, Rome
35
Confidential results
Please, do not distributeSlide37
Posterior Thalamic Radiation - left
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group
, Rome
36
Confidential results
Please, do not distributeSlide38
Posterior Thalamic Radiation - right
3. DOMAIN – OCD DTI meta-analysis
Fabrizio
Piras – Gianfranco
S
palletta’s
group
, Rome
37
Confidential results
Please, do not distributeSlide39
3. DOMAIN – OCD DTI meta-analysisFabrizio Piras – Gianfranco Spalletta’s
group
, Rome
Next Steps:
Analysing diffusivity measures
Please
send the
Investigating moderator variables (
AoO
,
DoI
, Medication, Symptom Severity)
38Slide40
Agenda
39
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics
projectCross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)Collaboration Lateralization working group (Francks
et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide41
4-1. Participants: meta-analytical approach
Comprised of a total of
34 dataset (31+3; 25+9)
4.
ENIGMA
-OCD Structural Covariance
ConfidentialSlide42
4-2. Construction of structural covariance matrix
ROI: 33 CSA
M
+ 33 CT
M
+ 6 subcort_vol
M 72 ROIsExclusion of entorhinal cortices & nucleus accumbens (poor parcellation)
I
nclusion criteria for participants for each study sites (for meta-)
‘or(isnan(ROI
L
)==0, isnan(ROI
R
)==0)==1’ for all of the 72 ROIs, so that computation of ROIM(mean) value availableTo regress-out effect of age, sex and ICV/mean CT/whole CSA
Subcortical vol: Yi = B0 + B1 × age + B2 × sex + B3 × ICV +
rCSA: Yi = B0 + B1 × age + B2 × sex + B3 × ΣCSA + rCT: Yi
= B0 + B1 × age + B2 × sex + B3 × (ΣCT)/Nroi + rZ-score transform the ‘r’ using MHC
/SDHC of given ROIM
Calculation of individualized structural covariance matrix
1./exp((X(i,j)-X(i,k))
^2
)
4.
ENIGMA
-OCD Structural
CovarianceConfidentialSlide43
4-3. Graph theory analysis
For adults & pediatric dataset
Global characteristics (K=0.10-0.25): compare AUC values
Gamma (normalized clustering coefficient)
Lambda (normalized characteristic path length)
Sigma (small-worldness)
Normalized global efficiency
Modularity (mode value of ×500 iterative calculation)
Regional
characteristics (centrality measures) and
community
structure
4. Meta-analytic integration
4-1. Global characteristics in adult (OCD vs. HC
) :4. ENIGMA-OCD Structural Covariance
ConfidentialSlide44
ENIGMA-OCD Structural Covariance
- Normalized clustering coefficient
adult
ConfidentialSlide45
ENIGMA-OCD Structural Covariance
- Normalized characteristic path length
adult
ConfidentialSlide46
ENIGMA-OCD Structural Covariance
- modularity
adult
ConfidentialSlide47
3. Graph theory analysis
4. Meta-analytic integration
4
-2. Regional characteristics
in adult (OCD vs. HC
): -- Eigenvector centrality
4.
ENIGMA
-OCD Structural Covariance
Confidential
Coordinate-based meta-analysis using activation likelihood estimation (ALE)
Eickhoff
SB et al., (2009, 2009, 2014, 2016)
Inclusion as significant per dataset: P < 0.05 (either HC>OCD or HC<OCD)Thresholding: Cluster-level inference method of P < 0.05 with 10,000 permutation; cluster-forming method of uncorrected P < 0.001
MNI coordinates retrieved from brainGraph (CSA >> L; CT>> R; subcort >>L)Slide48
4-2. Group-wise difference of eigenvector centrality: meta-analytic (Adult)
Confidential
4.
ENIGMA
-OCD Structural Covariance
HC>OCD
HC<OCD
subcortical
Caudate, thalamus
-
Cortical surface
area
frontal
Pars opercularis
Pars orbitalis
parietal
-
Paracentral, IPL, PCC
temporal
-
Temporal pole
occipital
-
Cuneus, pericalcarine
Cortical thickness
frontal
mOFC, rMFC
rACC, pars opercularis
parietal
Paracentral, SPL
-
temporal
parahippocampal
-
occipital
-
-
Table 2. Brain regions exhibiting significant difference of eigenvector centrality
value [for the individualized structural covariance network comprised of cortical surface area-cortical thickness-subcortical volume]
between HC and OCD in the meta-analysis
across all adult dataset (23/25)Slide49
4-5. Further plan
Finalize meta-analytic integration for global + regional characteristics using final 34 dataset: (31+3) adult & (9)
ped
. also
Relationship with age of onset/YBOCS/comorbidity/medication status
Writing manuscript to be shared after next TC (2017/JAN)
Confidential
ENIGMA-OCD Structural CovarianceSlide50
Agenda
49
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics project
Cross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)Collaboration Lateralization working group (Francks et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide51
5. Connectomics projectFinished processing of approximately 2000 subjects during the 10kin1day event
See recent email update by Odile
Further processing will be done in Amsterdam
Look at each data set separately to get an impression of the consistency of the output
Quality control steps
Timeline
Coming months/year
50Slide52
Agenda
51
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics project
Cross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)Collaboration Lateralization working group (Francks et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide53
6. Cross disorder meta-analysisOCD/ASD/ADHD (to be coordinated by Boedhoe & van den Heuvel)
Overlap and differences in subcortical volumes, cortical thickness and surface area measures between patients with OCD, patients with autism and patients with ADHD
In collaboration with the ENIGMA-ASD and ENIGMA-ADHD working groups
Daan
van
Rooij
& Jan Buitelaar
(ASD)
Martine
Hoogman
& Barbara
Franke
(ADHD)
Analysis plan in progress To be send around to all members for approval/comments Dec 2016
52Slide54
Agenda
53
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics project
Cross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)Collaboration Lateralization working group (Francks et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide55
7a. ENIGMA lateralization (Francks et al.)in controls only
Subcortical paper (some sites have participated in): Accepted for publication in
Brain Imaging and Behaviour
http://enigma.ini.usc.edu/wp-content/uploads/2015/05/ENIGMA-Laterality-BIB-2016.pdf
Cortical analysis plan: open to participation
(see analysis plan in attachment)
54Slide56
7b. Secondary analysis plan ENIGMA-OCD on lateralization (Francks et al.)
Altered cortical lateralization in people with OCD
In collaboration with the ENIGMA Lateralization working group
Clyde
Francks
& Xiangzhen
Kong
Input from ENIGMA-OCD working group via
Carles
Soriano-Mas (
Menchon’s
group)
Analysis plan for approval/comments, see attachment(Please, approve within 2 weeks time)
55Slide57
Agenda
56
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics project
Cross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)Collaboration Lateralization working group (Francks et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide58
8. Plasticity imaging-GWASAnalysis plan,
see
attached
.
All
sites that would like
to
participate
can
contact Rachel Brouwer: r.m.brouwer-4@umcutrecht.nl
57Slide59
Agenda
58
New collaborator
Cortical
MeTa
- and
MeGa
(Boedhoe / van den Heuvel et al.)
A) Recap main findings cortical
meTa
-analysis
B) Final Cortical
meGa
-analysis findings
C) Planning cortical paper
Status DTI meta analysis (
Fabrizio
Piras
et al. /
Spalletta’s
group)
Status Structural Covariance analysis (Je-
Yeon
Jun et al. /
Kwon’s
group)
Connectomics project
Cross disorder meta-analysis OCD/ASD/ADHD (analysis plan in progress)Collaboration Lateralization working group (Francks et al.)
A) cortical analysis in controls (see analysis plan
Kong&Francks
)
B) secondary analysis plan ENIGMA-OCD: lateralization analysis in OCD (see analysis plan
Francks
)
Collaboration
Plasticity
working
group (
Brouwer
et al.)
(see analysis plan
Brouwer
)
Other issues:
A)
MeGa
database
B) Presentation during
SoBP
symposium (San Diego, May 2016)
C) Am J Psych paper (subcortical
MeTa-MeGa
analysis)
D) Next
telcoSlide60
9a. MeGa database
Copy of IC used in all studies
Highlight permission to share raw MRI/genetic data
Translate important statements on sharing raw data to English
Send it to Odile and Premika
a.s.a.p
Benedetti et al
Beucke et al
Brennan et al
Buitelaar et al
Cheng et al
Denys et al
Fitzgerald et al
Gruner et el
Hoexter et alHuyser et al
James et alKoch et alKwon et alMataix-Cols et alMenchon et alNakao et alNurmi et al
Spalletta et alStein et alStern et alStewart et alTolin et alWalitza et al
59Slide61
9b. Abstract submitted for ENIGMA symposium at SoBP 2017 (May, San Diego)under review
60
Title
:
cerebral
cortex and genetic
vulnerability
in
impulsive-compulsive
spectrum disorders:
Chair: Odile van den Heuvel
co-Chair: Paul Thompson
Speakers:
1: Premika Boedhoe: OCD (
cortical meta- and mega-analysis)2: Patricia Conrod: Addiction
(idem)3: Philip Shaw: ADHD (idem)4: Marieke Klein: imaging-genetics in ADHDSymposium abstract:We present the findings of well-powered
meta- and mega-analyses on cortical thickness and surface area in three disorders within the impulsive-compulsive spectrum, by
bringing together
the
results
of
three
ENIGMA (
Enhancing
Neuroimaging and Genetics
through Meta-Analysis) working groups. We discuss
the findings in obsessive-compulsive disorder (OCD, based on 1905 cases and 1760 controls), addictions, in particular
substance dependence (based
on 1197 cases and 1193 controls), and attention-deficit-hyperactivity-disorder (ADHD, based on 2197 cases and 1926
controls
). In
this
way we are
able
to
give
a most recent update on the disorder-
specific
abnormalities
, the
contribution
of relevant
demographic
and
clinical
factors (
age
at
disease
onset
,
disease
duration
,
medication
status,
comorbidity
,
disease
subtype), and the overlap and
differentiation
across
the disorders
within
the
impulsive-compulsive
spectrum. We
will
present
both
pediatric
and adult data.
Moreover
, we
will
use
ADHD as a model
disease
to
give
some
insight
in the
value
of imaging-genetic analyses.
To
find
out
whether
genetic factors
for
ADHD risk overlap
with
those
influencing
brain volume, the
largest
available
data sets
from
the PGC-ADHD GWAS and the ENIGMA2 GWAS
were
combined
. Slide62
9c. Am J Psychiatry paper (subcortical MeTa/MeGa
)
Authorship consortium members, still work in progress (editor promised to solve it)
Dutch summary will be written for
Tijdschrift
voor
Psychiatrie
, on invitation (only 1 author allowed, but referring to Am J Psychiatry paper)
61Slide63
9d. Next TCProposal: Monday January 16, 2017, 3 PM CET
62