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Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis

2019; Nature Portfolio; Volume: 9; Issue: 1 Linguagem: Inglês

10.1038/s41598-019-38965-1

2045-2322

Bianca Cristina Garcia Lisbôa, Katia C. Oliveira, Ana Carolina Tahira, Amilton de Lima Barbosa, Arthur Sant’Anna Feltrin, Gisele Rodrigues Gouveia, Luzia Carreira Lima, Ana Cecília Feio dos Santos, David Martins, Renato Puga, Ariane Cristine Moretto, Carlos Alberto de Bragança Pereira, Beny Lafer, Renata Elaine Paraízo Leite, Renata Eloah de Lucena Ferretti‐Rebustini, José Marcelo Farfel, Lea T. Grinberg, Wilson Jacob Filho, Eurípedes C. Miguel, Marcelo Q. Hoexter, Helena Brentani,

Receptor Mechanisms and Signaling

Abstract Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.