Iron dyshomeostasis in neuropsychiatric disorders

Iron is an indispensable element for the normal physiological function of the brain. In terms of neuronal metabolism, iron is involved in multiple critical biological processes such as oxygen transport, energy metabolism, DNA synthesis, neurotransmitter synthesis and myelin formation. Maintaining brain iron homeostasis is crucial for neurodevelopment and function. Iron dyshomeostasis has been associated with the onset and progression of various neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, depression, schizophrenia, attention deficit hyperactivity disorder, and autism spectrum disorder. In neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, abnormally elevated iron levels can be detected in specific brain regions, including the basal ganglia and the prefrontal cortex. These changes are often accompanied by pathological processes such as oxidative stress, neuroinflammation, and pathological protein aggregation. Therefore, brain iron metabolism is an important entry point for understanding the pathophysiological process of neuropsychiatric disorders. Mechanistically, iron overload induces oxidative damage through the Fenton reaction, exacerbating mitochondrial dysfunction and abnormal protein aggregation. The effects of iron deficiency vary across different diseases; its impact on myelination and neurotransmitter synthesis may increase the risk of neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD), while its effects on immune activation and energy metabolism may contribute to the development of mental disorders such as depression. This article systematically reviews the current research progress of the role of cerebral iron metabolism in neuropsychiatric diseases. It focuses on the mechanisms underlying iron homeostasis imbalances in neurodegenerative and psychiatric diseases. Building on this foundation, the article analyzes the therapeutic targets and clinical significance of iron metabolism-related interventions and outlines future research directions in this field.