The role of serotonin in cognitive function: evidence from recent studies and implications for understanding depression

J Psychopharmacol. 2013 Jul;27(7):575-83. doi: 10.1177/0269881113482531. Epub 2013 Mar 27.


Background: Symptoms of cognitive impairment such as poor concentration, memory loss and difficulty with decision making are prevalent in patients with depression, but currently are not specific targets for treatment. However, patients can continue to demonstrate cognitive impairments even when apparently clinically recovered. Drugs that potentiate serotonin (5-HT) function, such as selective serotonin reuptake inhibitors (SSRIs), are the mainstay of treatment for depression. Nevertheless, our understanding of the effects of SSRIs and other conventional antidepressant therapy on cognitive function in healthy humans and depressed patients remains limited.

Objective: The purpose of this article is to provide a concise overview for clinicians on the impact of pharmacological manipulation of 5-HT on cognitive function in healthy humans with additional reference to animal models where human data are lacking, particularly regarding specific 5-HT receptor subtype modulation.

Findings: The most consistent observation following manipulation of serotonin levels in humans is that low extracellular 5-HT levels are associated with impaired memory consolidation. Preclinical data show that agonism and antagonism at specific 5-HT receptors can exert effects in animal models of cognition.

Conclusions: Larger, consistently designed studies are needed to understand the roles of 5-HT in cognition in healthy and depressed individuals. Efforts to target specific 5-HT receptors to improve cognitive outcomes are warranted.

Keywords: 5-HT receptor; Cognition; antidepressants; serotonin; tryptophan depletion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Cognition Disorders / drug therapy
  • Cognition Disorders / metabolism*
  • Depression / drug therapy
  • Depression / metabolism*
  • Humans
  • Receptors, Serotonin / metabolism
  • Serotonin / administration & dosage
  • Serotonin / metabolism*
  • Serotonin Uptake Inhibitors / administration & dosage*


  • Antidepressive Agents
  • Receptors, Serotonin
  • Serotonin Uptake Inhibitors
  • Serotonin