Molecular mechanisms of psychiatric diseases

Neurobiol Dis. 2020 Dec:146:105136. doi: 10.1016/j.nbd.2020.105136. Epub 2020 Oct 17.

Abstract

For most psychiatric diseases, pathogenetic concepts as well as paradigms underlying neuropsychopharmacologic approaches currently revolve around neurotransmitters such as dopamine, serotonin, and norepinephrine. However, despite the fact that several generations of neurotransmitter-based psychotropics including atypical antipsychotics, selective serotonin reuptake inhibitors, and serotonin-norepinephrine reuptake inhibitors are available, the effectiveness of these medications is limited, and relapse rates in psychiatric diseases are relatively high, indicating potential involvement of other pathogenetic pathways. Indeed, recent high-throughput studies in genetics and molecular biology have shown that pathogenesis of major psychiatric illnesses involves hundreds of genes and numerous pathways via such fundamental processes as DNA methylation, transcription, and splicing. Current review summarizes these and other molecular mechanisms of such psychiatric illnesses as schizophrenia, major depressive disorder, and alcohol use disorder and suggests a conceptual framework for future studies.

Keywords: Alcohol use disorder; DNA methylation; Histones; Major depressive disorder; Non-coding RNAs; Schizophrenia; Splicing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use*
  • Antipsychotic Agents / therapeutic use*
  • Dopamine / metabolism*
  • Humans
  • Mental Disorders / drug therapy*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Serotonin / metabolism

Substances

  • Antidepressive Agents
  • Antipsychotic Agents
  • Serotonin Uptake Inhibitors
  • Serotonin
  • Dopamine