Addressing Psychiatric Symptoms in Wilson's Disease: Translational Overlap with Bipolar Disorder and Emerging...

Background: Wilson's disease (WD) is a rare autosomal recessive disorder characterized by abnormal copper metabolism and accumulation in the liver and brain. While hepatic and neurological manifestations are well-recognized, psychiatric symptoms remain underdiagnosed and frequently precede other clinical signs, leading to delayed diagnosis and poorer outcomes. Objective: This opinion paper aims to explore the emerging understanding of psychiatric features in WD, particularly mood disturbances and their overlap with bipolar spectrum disorders, through a translational lens. Opinion: Psychiatric manifestations-including irritability, aggression, disinhibition, and mood instability-are observed in up to 100% of symptomatic WD patients. Accumulated copper induces oxidative stress and astrocyte dysfunction, which may disrupt neural circuits involved in emotion regulation. There is increasing evidence of shared pathophysiological mechanisms between WD and bipolar disorder, including redox imbalance and circadian rhythm dysregulation. Future Directions: The timely recognition of psychiatric symptoms is essential. Future research should investigate biomarkers of early psychiatric involvement, evaluate psychotropic medication safety in WD, and implement psychoeducational strategies to improve adherence and quality of life. A translational approach can foster individualized interventions and provide insights into broader mood disorders.