Neurogenetics of Dynamic Connectivity Patterns Associated With Obsessive-Compulsive Symptoms in Healthy Children
Suñol, Maria (Institut d'Investigació Biomèdica de Bellvitge)
Alemany, Sílvia (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Bustamante, Mariona (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Diez, Ibai (Gordon Center for Medical Imaging. Department of Radiology and Nuclear Medicine)
Contreras Rodríguez, Oren (Hospital Universitari de Bellvitge)
Laudo, Berta (Hospital Universitari de Bellvitge)
Macià Bros, Dídac (Barcelona Institute for Global Health (ISGlobal))
Martínez-Vilavella, Gerard (Hospital del Mar (Barcelona, Catalunya))
Martínez-Zalacaín, Ignacio (Institut d'Investigació Biomèdica de Bellvitge)
Menchón Magriñá, José Manuel (Hospital Universitari de Bellvitge)
Pujol Nuez, Jesús (Centro de Investigación Biomédica en Red de Salud Mental)
Sunyer, Jordi (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Sepulcre, Jorge (Harvard Medical School. Gordon Center for Medical Imaging)
Soriano-Mas, Carles (Hospital Universitari de Bellvitge)

Fecha:	2021
Resumen:	Obsessive-compulsive symptoms (OCSs) during childhood predispose to obsessive-compulsive disorder and have been associated with changes in brain circuits altered in obsessive-compulsive disorder samples. OCSs may arise from disturbed glutamatergic neurotransmission, impairing cognitive oscillations and promoting overstable functional states. A total of 227 healthy children completed the Obsessive Compulsive Inventory-Child Version and underwent a resting-state functional magnetic resonance imaging examination. Genome-wide data were obtained from 149 of them. We used a graph theory-based approach and characterized associations between OCSs and dynamic functional connectivity (dFC). dFC evaluates fluctuations over time in FC between brain regions, which allows characterizing regions with stable connectivity patterns (attractors). We then compared the spatial similarity between OCS-dFC correlation maps and mappings of genetic expression across brain regions to identify genes potentially associated with connectivity changes. In post hoc analyses, we investigated which specific single nucleotide polymorphisms of these genes moderated the association between OCSs and patterns of dFC. OCSs correlated with decreased attractor properties in the left ventral putamen and increased attractor properties in (pre)motor areas and the left hippocampus. At the specific symptom level, increased attractor properties in the right superior parietal cortex correlated with ordering symptoms. In the hippocampus, we identified two single nucleotide polymorphisms in glutamatergic neurotransmission genes (GRM7, GNAQ) that moderated the association between OCSs and attractor features. We provide evidence that in healthy children, the association between dFC changes and OCSs may be mapped onto brain circuits predicted by prevailing neurobiological models of obsessive-compulsive disorder. Moreover, our findings support the involvement of glutamatergic neurotransmission in such brain network changes.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Brain regional gene expression ; Dynamic functional connectivity ; Neurogenetics ; Obsessive-compulsive disorder ; Subclinical symptoms ; Symptom heterogeneity
Publicado en:	Biological Psychiatry Global Open Science, Vol. 2 (november 2021) , p. 411-420, ISSN 2667-1743

DOI: 10.1016/j.bpsgos.2021.11.009
PMID: 36324658

10 p, 1.2 MB

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