Dr. Zanos has presented new research of our lab at the Hellenic Psychological Society (ΕΛΨΕ) conference in Ioannina, Greece. The presentation, titled “Decoding common molecular pathways affected in opioid use disorder and depression,” explored the complex relationship between these frequently co-occurring conditions. This research was led by our lab members, Drs. Anna Onisiforou and Andrea Georgiou. Opioid use disorder (OUD) often coexists with major depressive disorder (MDD), but the exact underlying molecular and genetic mechanisms are unknown. Our research aimed to investigate the genetic and molecular mechanisms of association between OUD and MDD through Mendelian Randomization (MR), genetic correlation analysis, pathway enrichment analysis, and rodent models. MR analysis was performed to evaluate potential causal relationships, with sensitivity analyses to assess pleiotropy. Additionally, disease-associated protein enrichment analysis was conducted, to explore common molecular mechanisms. Rodent models with behavioral analyses were additionally utilized to identify brain-related biochemical mechanisms. The MR analysis did not provide evidence for a causal relationship, with variance-weighted MR yielding an odds ratio (OR) of 0.99 (95% CI: 0.99–1.00, p = 0.26). Pathway enrichment analysis identified 69 common pathways between OUD and MDD, including key pathways such as calcium signaling and glutamatergic neurotransmission. Direct correlations were also found between cortical neuron activity and synaptic plasticity markers during opioid withdrawal with depressive behaviors in rodent models. Although no evidence for a direct causal relationship between OUD and MDD was observed through MR analysis, the genetic correlation and enrichment analysis highlight common molecular pathways between these disorders. These findings advance our understanding of comorbidity between OUD and MDD and suggest potential targets for therapeutic intervention. The research presented by Dr. Zanos represents a significant contribution to understanding the neurobiological basis of these commonly co-occurring disorders and may help develop more effective treatment strategies.