Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder.
Cardoso Saraiva L., Sato JR., Sebenius I., Dzinalija N., Del Río-Torné C., Godinho F., Lopes AC., Fernandez TV., Lima MO., Ramos VR., Iglesio R., Abe Y., Alonso P., Ameis SH., Anticevic A., Araújo A., Arnold PD., Balachander S., Banaj N., Batistuzzo MC., Benedetti F., Bollettini I., Bravi B., Brennan B., Buitelaar J., Castelo-Branco M., Choi S., Costa AD., Dallaspezia S., Denys D., Duarte IC., Echevarria MAN., Eng GK., Fernandes A., Feusner JD., Figee M., Fitzsimmons SMDD., Fontenelle LF., Grazioplene R., Ha M., Hinojosa A., Hoexter MQ., Huijser C., Hu H., James A., Kim M., Kwon JS., Lazaro L., Lochner C., Machado-Sousa M., van Marle H., Martínez-Zalacaín I., Mataix-Cols D., Menchón JM., Minuzzi L., Morgado P., Muñoz-Moreno E., Nakao T., Narayanaswamy JC., Nurmi EL., O'Neill J., Park I., Phillips ML., Piacentini JC., Picó-Pérez M., Piras F., Piras F., Postma TS., Li C-SR., Reddy JYC., van Rooij D., Sakai Y., de Salles Andrade JB., Scheffler F., Shivakumar V., Soreni N., Stern ER., van der Straten A., Thomopoulos SI., Tomiyama H., Tovar-Moll F., Vecchio D., Veltman DJ., Venkatasubramanian G., Vriend C., Wang Z., van der Werf YD., van Wingen G., Zhao Q., ENIGMA-OCD Working Group ., Charney AW., Cho YT., Shavitt RG., Pushkarskaya H., Soriano-Mas C., Romero-Garcia R., Thompson PM., Stein DJ., van den Heuvel OA., Winkler AM., Miguel Filho EC., Pittenger C., Cappi C.
Studies of brain morphology in mental illness often focus on a few neuroimaging phenotypes. Here we present a comprehensive morphological characterization in obsessive-compulsive disorder (OCD) in a large sample (2255 OCD, 2264 controls) using nine cortical and four subcortical phenotypes, including several not previously examined in OCD, among them a subcortical structural similarity network phenotype developed here. Spatially distinct regional alterations emerged across structural phenotypes: cortical curvature alterations in default mode and frontoparietal networks, increased structural similarity network node degree in sensorimotor regions, widespread volume reductions associated with medication use, and localized subcortical shape alterations. In brain-behavior predictive models, curvature phenotypes showed the strongest associations with clinical features. Cortical alterations, especially in structural similarity networks, were associated with specific gene expression patterns, implicating dysregulation of excitatory neurons. RNA-sequencing data from tissue collected during functional neurosurgery revealed that genes downregulated in the dorsolateral prefrontal cortex in OCD contributed to the gene expression patterns linked to cortical alterations. Previously reported differentially expressed genes from postmortem brain studies of OCD also contributed. These findings support the importance of a comprehensive approach to characterizing brain morphology and suggest that cortical curvature and structural similarity alterations reflect key pathophysiological processes in OCD.