Is There Any Place for Macrolides in Mood Disorders?

Macrolides are protein synthesis inhibitors exerting an action on the bacterial ribosome. The ribosomes coded for by the human mitochondrial deoxyribonucleic acid (DNA) are similar to those from bacteria in size and structure. In addition, mitochondria are thought to have originated from a symbiotic relationship between an anaerobic proto-eukaryotic cell that engulfed an aerobic bacterium. Morphological changes of mitochondria have been observed in bipolar disorder and schizophrenia. Manic episodes associated with the use of antimicrobial agents have been described since the discovery of isoniazid. The oxidative stress induced in the neuronal mitochondria is thought to underlie this effect. The inhibition of GSK-3β in the intra-mitochondrial Akt signaling pathway is thought to convey mood stabilizing properties. Rapamycin is a macrolide that, besides its antiepileptic effect, restores the Akt function and inhibits the mTOR pathway which may have an antidepressant effect. Accordingly, it is hypothesized that rapamycin may have mood stabilizing properties.