Regional cerebellar volumetrics in obsessive-compulsive disorder: An ENIGMA-OCD study.
Although subtle differences in cortico-striato-thalamo-cortical (CTSC) circuit structure and function are critical to the current understanding of the neurocircuitry in obsessive-compulsive disorder (OCD), emerging evidence suggests that the cerebellum may also be involved. However, much of this evidence comes from studies with small samples and notable methodological heterogeneity.
We conducted a mega-analysis of individual participant data on cerebellar sub-regional volumes, comparing individuals with OCD and healthy controls (HC) from the ENIGMA-OCD Working Group. 3D T1-weighted volumetric structural brain magnetic resonance imaging (MRI) scans from 1,954 individuals with OCD and 2,091 HC across 22 sites (40 datasets) were processed using the ACAPULCO (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization) pipeline to extract cerebellar parcellations. We harmonized the volume measures across sites using the ComBat algorithm. Multiple linear regression models were fitted to estimate group differences separately within the pediatric (<12 years), adolescent (12-18 years), and adult (from 18 years) samples, adjusting for age, gender, and intracranial volume (ICV).
In adults with OCD (versus HC), we found significantly smaller volumes of the corpus medullare (d=-0.093, pfdr=0.036), left VIIb (d=-0.085, pfdr=0.039) and right VIIb (d= -0.091, pfdr= 0.036). None of the comparisons between children or adolescents with OCD versus HC remained statistically significant after FDR correction. In all three age groups, cerebellar (subregional) volumes were significantly moderated by medication status.
We report novel findings implicating specific cerebellar sub-regions across developmental stages of OCD, and the key impact of medication status. Further research on the functional significance of these findings may offer new translational leads.
We conducted a mega-analysis of individual participant data on cerebellar sub-regional volumes, comparing individuals with OCD and healthy controls (HC) from the ENIGMA-OCD Working Group. 3D T1-weighted volumetric structural brain magnetic resonance imaging (MRI) scans from 1,954 individuals with OCD and 2,091 HC across 22 sites (40 datasets) were processed using the ACAPULCO (Automatic Cerebellum Anatomical Parcellation using U-Net Locally Constrained Optimization) pipeline to extract cerebellar parcellations. We harmonized the volume measures across sites using the ComBat algorithm. Multiple linear regression models were fitted to estimate group differences separately within the pediatric (<12 years), adolescent (12-18 years), and adult (from 18 years) samples, adjusting for age, gender, and intracranial volume (ICV).
In adults with OCD (versus HC), we found significantly smaller volumes of the corpus medullare (d=-0.093, pfdr=0.036), left VIIb (d=-0.085, pfdr=0.039) and right VIIb (d= -0.091, pfdr= 0.036). None of the comparisons between children or adolescents with OCD versus HC remained statistically significant after FDR correction. In all three age groups, cerebellar (subregional) volumes were significantly moderated by medication status.
We report novel findings implicating specific cerebellar sub-regions across developmental stages of OCD, and the key impact of medication status. Further research on the functional significance of these findings may offer new translational leads.
Authors
Balachander Balachander, Narayanaswamy Narayanaswamy, Shivakumar Shivakumar, Abe Abe, Alonso Alonso, Backhausen Backhausen, Banaj Banaj, Batistuzzo Batistuzzo, Benedetti Benedetti, Bollettini Bollettini, Bravi Bravi, Brem Brem, Cappi Cappi, Chhatkuli Chhatkuli, Choi Choi, Coelho Coelho, Costa Costa, Dallaspezia Dallaspezia, Denys Denys, Diniz Diniz, Dzinalija Dzinalija, Eng Eng, Feusner Feusner, Fiedler Fiedler, Ha Ha, Hirano Hirano, Hoexter Hoexter, Hu Hu, Huijser Huijser, Ipser Ipser, Jahanshad Jahanshad, Jang Jang, Kim Kim, Koch Koch, Kurita Kurita, Kwon Kwon, Lazaro Lazaro, Lochner Lochner, Machado-Sousa Machado-Sousa, Manrique Manrique, van Marle van Marle, Martínez-Zalacaín Martínez-Zalacaín, Mataix-Cols Mataix-Cols, Menchón Menchón, Morgado Morgado, van de Mortel van de Mortel, Muñoz-Moreno Muñoz-Moreno, Nakao Nakao, Nurmi Nurmi, O'Neill O'Neill, Ortiz Ortiz, Ousdal Ousdal, Pascual-Diaz Pascual-Diaz, Pellicano Pellicano, Phillips Phillips, Piacentini Piacentini, Picó-Pérez Picó-Pérez, Piras Piras, Piras Piras, Sakai Sakai, Shavitt Shavitt, Shimizu Shimizu, Soriano-Mas Soriano-Mas, Stern Stern, Thorsen Thorsen, Tomiyama Tomiyama, Vecchio Vecchio, Veltman Veltman, Vetter Vetter, Vriend Vriend, Walitza Walitza, Wang Wang, van der Werf van der Werf, van Wingen van Wingen, Zhao Zhao, , Thomopoulos Thomopoulos, Thompson Thompson, Stein Stein, van den Heuvel van den Heuvel, Venkatasubramanian Venkatasubramanian, Reddy Reddy
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