Neurotransmitters, Psychotropic Drugs and Microglia: Clinical Implications for Psychiatry

Abstract

Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs such as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin. Recently, microglia, immunological/inflammatory cells in the brain, have been indicated to have positive links to psychiatric disorders. Positron emission tomography (PET) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia, depression and autism. Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. Until now, the relationship between microglia, neurotransmitters and psychiatric disorders has not been well understood. Therefore, in this review, at first, we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine, serotonin, norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date knowledge of the effects of psychotropic drugs such as antipsychotics, antidepressants and antiepileptics on microglial modulation. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further investigations and clinical trials should be conducted to clarify this perspective, using animal in vivo studies and imaging studies with human subjects.

Brain-derived Neurotrophic Factor (BDNF) Induces Sustained Intracellular Ca2+ Elevation through the Up-regulation of Surface Transient Receptor Potential 3 (TRPC3) Channels in Rodent Microglia

“…There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to inflammatory responses mediated by microglial cells (2,3).…”

Analysis of 17 neurotransmitters, metabolites and precursors in zebrafish through the life cycle using ultrahigh performance liquid chromatography–tandem mass spectrometry

“…In fact, changes in neurotransmitter levels produce regional selective changes indirectly via their trophic actions during development [25]. Moreover, neurotransmitter levels are altered in psychiatric disorders [26] and Alzheimer's disease [27][28][29].…”

The Role of Norepinephrine and Its α-Adrenergic Receptors in the Pathophysiology and Treatment of Major Depressive Disorder and Schizophrenia: A Systematic Review

“…Elevated peripheral inflammation may precipitate aberrant CNS inflammatory signaling with subsequent disruption of monoamine and glutamate transmission, in part by inappropriately activating brain microglia (100). Both α- and β-ARs have a key role in regulating macrophage and microglia activity (101, 102). Thus, compromised NE transmission may promote a pro-inflammatory phenotype consistent with depressive psychopathology.…”