Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments.
Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer's disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and non-invasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases.
Department of Psychiatry, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA. gbar@ucla.edu
George
G
Bartzokis
D000818:Animals; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011619:Psychotropic Drugs / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome
D011619:Psychotropic Drugs