Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

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dc.contributor.authorSimpson, Helen B
dc.contributor.authorvan den Heuvel, Odile A
dc.contributor.authorMiguel, Euripedes C
dc.contributor.authorReddy, Y. C J
dc.contributor.authorStein, Dan J
dc.contributor.authorLewis-Fernández, Roberto
dc.contributor.authorShavitt, Roseli G
dc.contributor.authorLochner, Christine
dc.contributor.authorPouwels, Petra J W
dc.contributor.authorNarayanawamy, Janardhanan C
dc.contributor.authorVenkatasubramanian, Ganesan
dc.contributor.authorHezel, Dianne M
dc.contributor.authorVriend, Chris
dc.contributor.authorBatistuzzo, Marcelo C
dc.contributor.authorHoexter, Marcelo Q
dc.contributor.authorde Joode, Niels T
dc.contributor.authorCosta, Daniel L
dc.contributor.authorde Mathis, Maria A
dc.contributor.authorSheshachala, Karthik
dc.contributor.authorNarayan, Madhuri
dc.contributor.authorvan Balkom, Anton J L M
dc.contributor.authorBatelaan, Neeltje M
dc.contributor.authorVenkataram, Shivakumar
dc.contributor.authorCherian, Anish
dc.contributor.authorMarincowitz, Clara
dc.contributor.authorPannekoek, Nienke
dc.contributor.authorStovezky, Yael R
dc.contributor.authorMare, Karen
dc.contributor.authorLiu, Feng
dc.contributor.authorOtaduy, Maria C G
dc.contributor.authorPastorello, Bruno
dc.contributor.authorRao, Rashmi
dc.contributor.authorKatechis, Martha
dc.contributor.authorVan Meter, Page
dc.contributor.authorWall, Melanie
dc.date.accessioned2020-02-18T10:30:27Z
dc.date.available2020-02-18T10:30:27Z
dc.date.issued2020-02-14
dc.date.updated2020-02-16T07:30:33Z
dc.description.abstractBackground Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it.
dc.identifier.apacitationSimpson, H. B., van den Heuvel, O. A., Miguel, E. C., Reddy, Y. C J., Stein, D. J., Lewis-Fernández, R., ... Wall, M. (2020). Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative. <i>BMC Psychiatry</i>, 20(1), 1-14. http://hdl.handle.net/11427/31156en_ZA
dc.identifier.chicagocitationSimpson, Helen B, Odile A van den Heuvel, Euripedes C Miguel, Y. C J Reddy, Dan J Stein, Roberto Lewis-Fernández, Roseli G Shavitt, et al "Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative." <i>BMC Psychiatry</i> 20, 1. (2020): 1-14. http://hdl.handle.net/11427/31156en_ZA
dc.identifier.citationSimpson, H.B., van den Heuvel, O.A., Miguel, E.C., Reddy, Y. C J., Stein, D.J., Lewis-Fernández, R., Shavitt, R.G. & Lochner, C. et al. 2020. Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative. <i>BMC Psychiatry.</i> 20(1):1-14. http://hdl.handle.net/11427/31156en_ZA
dc.identifier.risTY - AU - Simpson, Helen B AU - van den Heuvel, Odile A AU - Miguel, Euripedes C AU - Reddy, Y. C J AU - Stein, Dan J AU - Lewis-Fernández, Roberto AU - Shavitt, Roseli G AU - Lochner, Christine AU - Pouwels, Petra J W AU - Narayanawamy, Janardhanan C AU - Venkatasubramanian, Ganesan AU - Hezel, Dianne M AU - Vriend, Chris AU - Batistuzzo, Marcelo C AU - Hoexter, Marcelo Q AU - de Joode, Niels T AU - Costa, Daniel L AU - de Mathis, Maria A AU - Sheshachala, Karthik AU - Narayan, Madhuri AU - van Balkom, Anton J L M AU - Batelaan, Neeltje M AU - Venkataram, Shivakumar AU - Cherian, Anish AU - Marincowitz, Clara AU - Pannekoek, Nienke AU - Stovezky, Yael R AU - Mare, Karen AU - Liu, Feng AU - Otaduy, Maria C G AU - Pastorello, Bruno AU - Rao, Rashmi AU - Katechis, Martha AU - Van Meter, Page AU - Wall, Melanie AB - Background Obsessive-compulsive disorder (OCD) has a lifetime prevalence of 2–3% and is a leading cause of global disability. Brain circuit abnormalities in individuals with OCD have been identified, but important knowledge gaps remain. The goal of the new global initiative described in this paper is to identify robust and reproducible brain signatures of measurable behaviors and clinical symptoms that are common in individuals with OCD. A global approach was chosen to accelerate discovery, to increase rigor and transparency, and to ensure generalizability of results. Methods We will study 250 medication-free adults with OCD, 100 unaffected adult siblings of individuals with OCD, and 250 healthy control subjects at five expert research sites across five countries (Brazil, India, Netherlands, South Africa, and the U.S.). All participants will receive clinical evaluation, neurocognitive assessment, and magnetic resonance imaging (MRI). The imaging will examine multiple brain circuits hypothesized to underlie OCD behaviors, focusing on morphometry (T1-weighted MRI), structural connectivity (Diffusion Tensor Imaging), and functional connectivity (resting-state fMRI). In addition to analyzing each imaging modality separately, we will also use multi-modal fusion with machine learning statistical methods in an attempt to derive imaging signatures that distinguish individuals with OCD from unaffected siblings and healthy controls (Aim #1). Then we will examine how these imaging signatures link to behavioral performance on neurocognitive tasks that probe these same circuits as well as to clinical profiles (Aim #2). Finally, we will explore how specific environmental features (childhood trauma, socioeconomic status, and religiosity) moderate these brain-behavior associations. Discussion Using harmonized methods for data collection and analysis, we will conduct the largest neurocognitive and multimodal-imaging study in medication-free subjects with OCD to date. By recruiting a large, ethno-culturally diverse sample, we will test whether there are robust biosignatures of core OCD features that transcend countries and cultures. If so, future studies can use these brain signatures to reveal trans-diagnostic disease dimensions, chart when these signatures arise during development, and identify treatments that target these circuit abnormalities directly. The long-term goal of this research is to change not only how we conceptualize OCD but also how we diagnose and treat it. DA - 2020-02-14 DB - OpenUCT DP - University of Cape Town J1 - BMC Psychiatry KW - Obsessive-compulsive disorder KW - Neuroimaging KW - fMRI KW - Unaffected siblings KW - Brain signatures KW - Neurocognitive KW - Global mental health LK - https://open.uct.ac.za PY - 2020 T1 - Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative TI - Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative UR - http://hdl.handle.net/11427/31156 ER -en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12888-020-2439-2
dc.identifier.urihttp://hdl.handle.net/11427/31156
dc.identifier.vancouvercitationSimpson HB, van den Heuvel OA, Miguel EC, Reddy Y C J, Stein DJ, Lewis-Fernández R, et al. Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative. BMC Psychiatry. 2020;20(1):1-14. http://hdl.handle.net/11427/31156.en_ZA
dc.language.rfc3066en
dc.rights.holderThe Author(s).
dc.sourceBMC Psychiatry
dc.sourceBMC Psychiatry
dc.source.journalissue1
dc.source.journalvolume20
dc.source.pagination1-14
dc.source.urihttps://bmcpsychiatry.biomedcentral.com/
dc.source.urihttps://bmcpsychiatry.biomedcentral.com/
dc.subjectObsessive-compulsive disorder
dc.subjectNeuroimaging
dc.subjectfMRI
dc.subjectUnaffected siblings
dc.subjectBrain signatures
dc.subjectNeurocognitive
dc.subjectGlobal mental health
dc.titleToward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative
dc.typeJournal Article
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