How obsessive-compulsive and bipolar disorders meet each other? An integrative gene-based enrichment approach

The novel approaches to psychiatric classification assume that disorders, contrary to what was previously thought, are not completely separate phenomena. In this regard, in addition to symptom-based criteria, disturbances are also considered on the basis of lower level components. With this viewpoint, identifying common biochemical markers would be beneficial in adopting a comprehensive strategy for prevention, diagnosis and treatment.

One of the problematic areas in clinical settings is the coexistence of both obsessive-compulsive disorder (OCD) and bipolar disorder (BD) that is challenging and difficult to manage. In this study, using a system biologic approach we aimed to assess the interconnectedness of OCD and BD at different levels. Gene Set Enrichment Analysis (GSEA) method was used to identify the shared biological network between the two disorders. The results of the analysis revealed 34 common genes between the two disorders, the most important of which were CACNA1C, GRIA1, DRD2, NOS1, SLC18A1, HTR2A and DRD1. Dopaminergic synapse and cAMP signaling pathway as the pathways, dopamine binding and dopamine neurotransmitter receptor activity as the molecular functions, dendrite and axon part as the cellular component and cortex and striatum as the brain regions were the most significant commonalities.

The results of this study highlight the role of multiple systems, especially the dopaminergic system in linking OCD and BD. The results can be used to estimate the disease course, prognosis, and treatment choice, particularly in the cases of comorbidity. Such perspectives, going beyond symptomatic level, help to identify common endophenotypes between the disorders and provide diagnostic and therapeutic approaches based on biological in addition to the symptomatic level.