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Decreased expression of synapse-related genes and loss of synapses in major depressive disorder.

Authors
  • Kang, Hyo Jung1
  • Voleti, Bhavya
  • Hajszan, Tibor
  • Rajkowska, Grazyna
  • Stockmeier, Craig A
  • Licznerski, Pawel
  • Lepack, Ashley
  • Majik, Mahesh S
  • Jeong, Lak Shin
  • Banasr, Mounira
  • Son, Hyeon
  • Duman, Ronald S
  • 1 Department of Psychiatry, Yale University, New Haven, Connecticut, USA.
Type
Published Article
Journal
Nature medicine
Publication Date
Sep 01, 2012
Volume
18
Issue
9
Pages
1413–1417
Identifiers
PMID: 22885997
Source
Medline
License
Unknown

Abstract

Previous imaging and postmortem studies have reported a lower brain volume and a smaller size and density of neurons in the dorsolateral prefrontal cortex (dlPFC) of subjects with major depressive disorder (MDD). These findings suggest that synapse number and function are decreased in the dlPFC of patients with MDD. However, there has been no direct evidence reported for synapse loss in MDD, and the gene expression alterations underlying these effects have not been identified. Here we use microarray gene profiling and electron microscopic stereology to reveal lower expression of synaptic-function–related genes (CALM2, SYN1, RAB3A, RAB4B and TUBB4) in the dlPFC of subjects with MDD and a corresponding lower number of synapses. We also identify a transcriptional repressor, GATA1, expression of which is higher in MDD and that, when expressed in PFC neurons, is sufficient to decrease the expression of synapse-related genes, cause loss of dendritic spines and dendrites, and produce depressive behavior in rat models of depression.

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