Dysregulation of adult hippocampal neuroplasticity in major depression: pathogenesis and therapeutic implications

Mol Psychiatry. 2022 Jun;27(6):2689-2699. doi: 10.1038/s41380-022-01520-y. Epub 2022 Mar 30.


Major depressive disorder (MDD) was previously hypothesized to be a disease of monoamine deficiency in which low levels of monoamines in the synaptic cleft were believed to underlie depressive symptoms. More recently, however, there has been a paradigm shift toward a neuroplasticity hypothesis of depression in which downstream effects of antidepressants, such as increased neurogenesis, contribute to improvements in cognition and mood. This review takes a top-down approach to assess how changes in behavior and hippocampal-dependent circuits may be attributed to abnormalities at the molecular, structural, and synaptic level. We conclude with a discussion of how antidepressant treatments share a common effect in modulating neuroplasticity and consider outstanding questions and future perspectives.

Publication types

  • Review

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Depression / therapy
  • Depressive Disorder, Major* / drug therapy
  • Hippocampus
  • Humans
  • Neuronal Plasticity / physiology


  • Antidepressive Agents