Impaired Synaptic Connections

Research increasingly links impaired synaptic connections with MDD.1

Synaptic connections are constantly remodeled, created, and lost as a result of new experiences, emotions, learning, and memory.1 However, this synaptic plasticity may be impaired in patients with MDD.2

  • In a study published in Nature Medicine, researchers found a significantly lower number of synapses in key regions of post-mortem brains from patients who suffered from MDD compared to healthy subjects3
  • Preclinical studies show that chronic stress not only causes dendritic spines to atrophy and contract, but also reduces the number of synapses2,4
  • The impairment appears to be centered in the prefrontal cortex and hippocampus, which are areas of the brain involved in regulating mood and information processing5
  • Other brain regions that are affected include the amygdala, nucleus accumbens, and orbitofrontal cortex4

Structural and Functional Brain Changes are Associated with MDD

The findings on synaptic impairment add to the evidence that MDD is associated with structural and functional abnormalities in the brain, as previously seen by neuroimaging studies. Again, the most consistent alterations are observed in the prefrontal cortex and hippocampus, where reduced gray matter volume is associated with more severe depression.

Impaired synaptic plasticity within these and other brain regions may reduce the number and strength of synaptic connections, potentially impacting mood regulation. As research advances, scientists hope to answer a key question: What factors play a role in synaptic connections?

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