A novel mechanism of depression: role for connexins

Cong Yuan Xia, Zhen Zhen Wang, Tohru Yamakuni, Nai Hong Chen

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)


Major depressive disorder (MDD) is a chronic and debilitating illness that affects over 350 million people worldwide; however, current treatments have failed to cure or prevent the progress of depression. Increasing evidence suggests a crucial role for connexins in MDD. In this review, we have summarised recent accomplishments regarding the role of connexins, gap junctions, and hemichannels in the aetiology of MDD, and discussed the limitations of current research. A blockage of gap junctions or hemichannels induces depressive behaviour. Possible underlying mechanisms include the regulation of neurosecretory functions and synaptic activity by gap junctions and hemichannels. Gap junctions are functionally inhibited under stress conditions. Conversely, hemichannel permeability is increased. Antidepressants inhibit hemichannel permeability; however, they have contrasting effects on the function of gap junctions under normal conditions and can protect them against stress. In conclusion, the blockage of hemichannels concurrent with improvements in gap junction functionality might be potential targets for depression treatment.

Original languageEnglish
Pages (from-to)483-498
Number of pages16
JournalEuropean Neuropsychopharmacology
Issue number4
Publication statusPublished - 2018 Apr


  • Connexins
  • Depression
  • Gap junction
  • Hemichannels

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)


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