Decreased Expression of Synapse-Related Genes and Loss of Synapses in Major Depressive Disorder

By H. Kang, B. Voleti, T. Hajszán, G. Rajkowska, C. Stockmeier, P. Licznerski, A. Lepack, M. Majik, L. Jeong, M. Banasr and 2 more. Nature Medicine, 2012

732 citations recorded by the source corpus.

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.

Subfields: Biological Psychiatry, Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/423edbe20f5055e09b2564068c16723eea7aec32

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biological Psychiatry

1. R. Duman
2. G. Sanacora
3. John H. Krystal
4. K. Al-Harbi

In Cellular and Molecular Neuroscience

1. G. Sanacora
2. R. Duman
3. John H. Krystal
4. E. Nestler
5. Bruce S. McEwen
6. L. Monteggia
7. H. Schmidt
8. J. Warner-Schmidt

In Cognitive Neuroscience

1. G. Sanacora
2. R. Duman
3. John H. Krystal

Citations in the corpus

• Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments (2019, background): “These imaging studies point to reductions in glutamate transmission in PFC subregions of MDD patients and are supported by postmortem studies of decreased synapse number and expression of synaptic markers in dlPFC of MDD subjects (Kang et al., 2012).”
• The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain (2017, background): “individuals with depression in postmortem studies have also been observed to have a significantly reduced number of PFC synapses, which thus decreases synaptic functions [18].”