Neuroglialpharmacology: white matter pathophysiologies and psychiatric treatments

Psychotropic treatments such as second generation or atypical antipsychotics are efficacious in a wide spectrum of psychiatric disorders ranging from schizophrenia to depression, bipolar disorder, and autism. These treatments are associated with peripheral metabolic derangements that are often also present in drug-naive patients. Furthermore, altering lipid composition/levels (with omega 3 fatty acids) and ameliorating oxidative toxicities may treat/prevent disease. The above observations are reexamined from the perspective of a myelin-centered model of the human brain. The model proposes that the human brain's extensive myelination required higher metabolic resources that caused evolutionary adaptations resulting in our quadratic (inverted U) myelination trajectory that peaks in the sixth decade of life. It further proposes that optimal brain function depends on exquisite action potential synchronization that myelin makes possible and that myelin's exceptional vulnerability to subtle metabolic/oxidative abnormalities may promote both developmental and degenerative diseases. Available data are integrated herein to suggest that widely used psychotropic treatments have under-appreciated CNS metabolic and neurotransmitter effects on myelination, its plasticity, and repair that may substantially contribute to their mechanisms of action.