Myelin Repair as a Novel Mechanism for Ketamine's Sustained Antidepressant Effects.

Depression affects about 300 million people worldwide, and its underlying mechanisms remain unclear. Changes in oligodendrocytes and myelin are implicated in depression pathology. Conventional antidepressants take weeks to work and fail for about one-third of patients. Ketamine provides rapid, sustained antidepressant effects in treatment-resistant patients. Reduced myelination is linked to depression, so repairing myelin damage may be a key mechanism behind ketamine's prolonged effects. This review summarizes the relationship between demyelination and depression and discusses how ketamine might exert antidepressant effects by repairing myelin, offering new insights into the role of myelination in antidepressant mechanisms.

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Abstract

Depression is a prevalent mental disorder, affecting approximately 300 million people worldwide. Despite decades of research into the underlying mechanisms of depression, a consensus remains elusive. Recent studies have implicated changes in oligodendrocytes and myelin in the pathogenesis of depression. Conventional antidepressants may alleviate symptoms within weeks of use, but approximately one-third of patients do not respond to them. Ketamine exhibits rapid and sustained antidepressant effects in treatment-resistant patients with depression. Given the association between reduced myelination and depression pathology, alterations in myelination may be a key mechanism underlying ketamine's prolonged antidepressant effects. However, the exact role of myelination in ketamine's sustained antidepressant effects remains unclear. In this review, we summarize the relationship between demyelination and depression and discuss the potential mechanisms by which ketamine may exert its antidepressant effects by repairing myelin damage, offering new insights into the role of myelination in antidepressant mechanisms.