Understanding the Comorbidities Among Psychiatric Disorders, Chronic Low Back Pain, and Spinal Degenerative Disease Using Observational and Genetically Informed Analyses.

Background: Psychiatric disorders and symptoms are associated with differences in pain perception and sensitivity. These differences can have important implications in treating spinal degenerative disease (SDD) and chronic low back pain (CLBP). Methods: Leveraging UK Biobank (UKB) ( Results: When we compared individuals affected only by SDD, those affected only by CLBP, and those affected by both conditions with control participants, observational and genetically informed analyses highlighted that the strongest effects across the 3 case groups were observed for alcohol use disorder, anxiety, depression, and posttraumatic stress disorder. Additionally, schizophrenia and its polygenic risk score appeared to have an inverse relationship with CLBP, SDD, and their comorbidity. One-sample MR highlighted a potential direct effect of internalizing disorders on the outcomes investigated that was particularly strong on SDD. Our drug repurposing analyses identified histone deacetylase inhibitors as targeting molecular pathways shared by psychiatric disorders, SDD, and CLBP. Conclusions: These findings support that the comorbidity among psychiatric disorders, SDD, and CLBP is due to the contribution of direct effects and shared biology linking these health outcomes. These pleiotropic mechanisms, together with sociocultural factors, play a key role in shaping the SDD-CLBP comorbidity patterns that have been observed across the psychopathology spectrum.