Post-stroke depression: mechanisms, translation and therapy

J Cell Mol Med. 2012 Sep;16(9):1961-9. doi: 10.1111/j.1582-4934.2012.01555.x.


The interaction between depression and stroke is highly complex. Post-stroke depression (PSD) is among the most frequent neuropsychiatric consequences of stroke. Depression also negatively impacts stroke outcome with increased morbidity, mortality and poorer functional recovery. Antidepressants such as the commonly prescribed selective serotonin reuptake inhibitors improve stroke outcome, an effect that may extend far beyond depression, e.g., to motor recovery. The main biological theory of PSD is the amine hypothesis. Conceivably, ischaemic lesions interrupt the projections ascending from midbrain and brainstem, leading to a decreased bioavailability of the biogenic amines--serotonin (5HT), dopamine (DA) and norepinephrine (NE). Acetylcholine would also be involved. So far, preclinical and translational research on PSD is largely lacking. The implementation and characterization of suitable animal models is clearly a major prerequisite for deeper insights into the biological basis of post-stroke mood disturbances. Equally importantly, experimental models may also pave the way for the discovery of novel therapeutic targets. If we cannot prevent stroke, we shall try to limit its long-term consequences. This review therefore presents animal models of PSD and summarizes potential underlying mechanisms including genomic signatures, neurotransmitter and neurotrophin signalling, hippocampal neurogenesis, cellular plasticity in the ischaemic lesion, secondary degenerative changes, activation of the hypothalamo-pituitary-adrenal (HPA) axis and neuroinflammation. As stroke is a disease of the elderly, great clinical benefit may especially accrue from deciphering and targeting basic mechanisms underlying PSD in aged animals.

Publication types

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

MeSH terms

  • Acetylcholine / therapeutic use
  • Aging*
  • Animals
  • Antidepressive Agents / therapeutic use
  • Depression / complications
  • Depression / diagnosis*
  • Depression / physiopathology*
  • Depression / therapy
  • Disease Models, Animal
  • Dopamine / therapeutic use
  • Hippocampus / drug effects
  • Hippocampus / physiopathology
  • Humans
  • Norepinephrine / therapeutic use
  • Serotonin Uptake Inhibitors / therapeutic use
  • Stroke / complications
  • Stroke / physiopathology*
  • Stroke / psychology*
  • Synaptic Transmission


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Acetylcholine
  • Dopamine
  • Norepinephrine