AQP4-IgG and mood disorders: Case series of neuromyelitis optica spectrum disorder

Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune inflammatory demyelinating conditions primarily affecting the optic nerves and spinal cord. While NMOSD pathogenesis is mediated by aquaporin-4 antibody (AQP4-IgG) autoimmunity, increasing evidence suggests significant comorbidity with affective symptoms. The neuropathological mechanisms underlying this comorbidity, however, remain incompletely understood. We reported two cases of female patients with concurrent NMOSD and mood disorders that illustrate a shared neuroinflammatory etiology. Case 1, a 26-year-old female, presented with a decade-long history of mood instability, diagnosed as bipolar disorder (BD) mixed episode, which coincided with her NMOSD diagnosis. Case 2, a 25-year-old female, initially presented with major depressive disorder (MDD) but was subsequently diagnosed with NMOSD following the acute onset of neurological symptoms. Both patients were, serum AQP4-IgG positive and exhibited demyelinating changes in the frontal lobe. Following immunosuppressive and psychiatric treatment, both patients experienced marked improvement in neurological function, suicidality, and affective symptoms. These case reports suggest a bidirectional relationship between NMOSD and mood disorders, likely mediated by AQP4-IgG-driven neuroinflammatory responses. AQP4-IgG screening may serve as a critical tool to distinguish organic mood disorder from primary psychiatric conditions, particularly in patients with atypical neurological symptoms.