enigma ocd working group teleconference 27 th of august 2015 1 pm gmt (greenwich mean time)...

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 AMTokyo/Kyoto/Seoul 10 PM

Cape Town 3 PMLos Angeles 6 AM

New York/Toronto/Michigan/Boston 9 AMBangalore 6.30 PM

Agenda1. Subcortical meta-analysis

1. Adults2. Paediatric3. extra-analyses (follows)4. Planning final subcortical meta-analysis

2. Planning cortical meta-analysis3. Secondary research proposals

1. DTI2. Covariance3. other

4. ENIGMA Lateralization working group5. Mega-analysis database6. Grants7. Presentations8. Future meetings

Please, send me ([email protected]) 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!!

Results – adultOCD vs HC

Effect size cohen’s d: 0.16P-value: 2.1e-3 corrected for multiple comparisonsAnalyses controlled for age, gender and ICV

*

Results – adultmedicated OCD vs HC

Effect size d: hippocampus -0.28 pallidum 0.24P-value: hippocampus 3.7e-5 pallidum 8.5e-4

corrected for multiple comparisonsAnalyses controlled for age, gender and ICV

**

Results – adultcomorbid lifetime depression OCD vs HC

Effect size cohen’s d: -0.27P-value: 6.3e-4 corrected for multiple comparisonsAnalyses controlled for age, gender and ICV

*

Results – paediatricUnmedicated OCD vs HC

Effect size cohen’s d: 0.40P-value: 9.4e-4 corrected for multiple comparisonsAnalyses 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

Results – extra analysesfollows (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 analysesfollows 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 run extra analyses September 11th, 2015

Draft paper October 2015

Suggested journal: American Journal of Psychiatry (planning submission end of November?)

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


1. Adults2. Paediatric3. extra-analyses (follows)4. Planning final subcortical meta-

analysis



4. ENIGMA Lateralization working group

5. Mega-analysis database6. Grants7. Presentations8. Future meetings

Secondary research proposals DOMAIN (DTI in OCD Meta-Analytic INvestigation)

Piras et al. (Italy) approved

Structural covariance analysis Kwon & Yun et al. (South Korea)

approved Connectomics/graph analysis

Koch & Reess et al. (Germany) to be submitted

Resting state Soriano-Mas et al. (Spain)

planned

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 INTROMicrostructural 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-striato-thalamo-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. Stern, E. R., Fitzgerald, K. D., Welsh, R. C., Abelson, J. L. & Taylor, S. F. PLoS One 7, (2012)2. Piras, F., Piras, F., Caltagirone, C. & Spalletta, G. Neuroscience and Biobehavioral Reviews (2013) 3. Menzies, L. et al. Am. J. Psychiatry 165, 1308–1315 (2008) 4. Yoo, S. Y. et al. Acta Psychiatr. Scand. 116, 211–219 (2007) 5. Koch, K. et al. J. Psychiatr. Res. 46, 264–270 (2012). 6. Radua J et al, Neuropsychopharmacology, 39,1547-57 (2014)


Meta analyses of DTI data in OCD METHODSWe 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


http://enigma.ini.usc.edu/protocols/dti-protocols/

Meta analyses of DTI data in OCD ROIsFollowing 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)


Meta analyses of DTI data in OCD ROIsFollowing 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) approved

Structural covariance analysis Kwon & Yun et al. (South Korea)

approved Connectomics/graph analysis

Koch & Reess et al. (Germany) 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

ENIGMA Lateralization working group (Guadalupe et al.)

Cheng Van den Heuvel Kwon Nakamae Nakao Reddy Stein

Walitza Mataix-Cols Menchon Huyser Wang

Contributing sites within ENIGMA-OCD



analysis





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)



analysis





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 to meet

ECNP - Amsterdam August 29, 2015 – September 01 2015

ICOCS - Amsterdam September 02, 2015

Next TC ENIGMA-OCD working group October 29, 2015

enigma ocd working group teleconference 27 th of august 2015 1 pm gmt (greenwich mean time)...

Documents