LAUSR

Background Obsessive Compulsive Disorder (OCD) is a psychiatric disorder characterized by obsessions and compulsions. The features of OCD are intrusive thoughts (obsessions) and repetitive behavior (compulsions). Functional neuroimaging studies indicate that OCD is a heterogeneous disorder related to the cortical-striatal thalamic circuitry (CSTC) and the areas that compose this circuitry include the nucleus accumbens (NAC), Putamen (PT), Caudate Nucleus (CN), Orbitofrontal Cortex (OFC) and subgenual cingulate gyri (ACC). Each brain area has a relevant role in the affective, dorsal cognitive and ventral cognitive cortico-striatal loops (CSTC). Our proposal is compare the gene expression from transcriptome of post mortem brain from affective and ventral cognitive cortico-striatal circuitry. Methods The brains are part of the psychiatric collection of Brain Bank of Brazilian Aging Brain Study Group (Psy-BBBABSG). All cases and controls were 50 years and older, non-demented and without previous factors that could be cause hypoxia or autolysis of the brain. We analyzed 56 samples sourced from 8 OCD cases and 8 controls aligned by gender, age and hemisphere. The clinical, functional and psychiatric assessment evaluation was made by next-of-kin of the deceased answered a screening with semi-structured questionnaires. The library was constructed with ribosome depletion and the RNA sequencing was performed in automatic sequencer lluminaHiSeq 2500. The reads were evaluated to control quality using FastQC and aligned with genome using TopHat (genome reference hg38). We use Cuffilinks to perform the transcript assembly and HTSeq-count to determine the reads counts to gene in each sample. The gene expression was evaluated using DESeq2 and enrichment analysis was performed with WegGestalt. Results To each circuitry we analyzed Differentially Expressed Genes (DEGs), comparing OCD and controls in each brain area. Were observed 400 DEG in NAC and 512 in the ACC in the affective circuitry, with 16 DEG common to each area. Enrichment analysis showed involvement of the exclusive DEGs from NAC in regulation of synaptic plasticity, glutamatergic and dopaminergic synapses, while exclusive DEGs from ACC enriched to infection disease and metabolic process. To ventral cognitive circuitry, were observed 619 DEG in PT and 444 in the OFC, with 25 DEG common and enrichment analysis showed exclusive DEGs from PT involved with regulation of neurological system process and stimulus responded, whereas exclusive DEGs from OFC involved with gliogenesis, ensheathment of neurons and drug metabolic process. Discussion We analyzed 2 circuitry involved with OCD, the affective and ventral cognitive cortico-striatal circuitry. The Nucleus Accumbens (NAC) in striatum and subgenual cingulate gyri (ACC) in cortex are involved with affective circuitry; and Putamen (PT) in striatum and Orbitofrontal Cortex (OFC) are involved with ventral cognitive circuitry. We found differential gene expression between the areas with different biological functions. The next step will be the evaluation of the coexpression networks between the two circuitry.