Serotonin levels and cognitive recovery in patients with subacute stroke after rehabilitation treatment

Mariacristina Siotto, Marco Germanotta, Massimo Santoro, Valeria Cipollini, Giulia Guardati, Dionysia Papadopoulou, Elisa Bray, Alessia Mastrorosa, Irene Aprile

Research output: Contribution to journalArticlepeer-review


Post-stroke depression and cognitive impairment are common conditions affecting patients after stroke. Serotonin is a neurotransmitter involved in modulating, among others, mood, cognition, learning, and memory. Sub-optimal serotonin activity may be in part responsible for cognitive deficits seen in depression. In this pilot study serotonin levels were evaluated in 29 patients with sub-acute stroke before and after a rehabilitation treatment (consisting of a program of upper limb robotic rehabilitation in addition to conventional physical therapy treatment). We employed the Back Depression Inventory scale to evaluate symptoms of depression, and specific tools to evaluate cognitive functions. We found a significant reduction of the serotonin levels after rehabilitation in the whole group (T0: 85.9 ± 92.4 ng/mL; T1: 61.9 ± 58.4 ng/mL; p = 0.0018), as well as in the subgroup of patients untreated with Selective Serotonin Reuptake Inhibitors (SRRI), (mean serotonin at T0: 154.0 ± 102.3 ng/mL; mean serotonin at T1: 92.9. ± 68.7 ng/mL at T1; p = 0.005). We also found a correlation with cognitive assessment: in particular, the change from baseline of the serotonin (∆Serotonin) was correlated with the changes from baseline of the Rey’s Figure (∆ROCF) (r = 0.535; p < 0.05), the Tower of London (∆ToL) (subscore point: r = 0.621; p < 0.005; subscore time: r = −0.619; p < 0.005) meaning that a serotonin levels decrease is associated with a worsening of cognitive functions. Considering patients treated and untreated with SSRIs separately, in patients treated with SSRIs (n = 16) we found only a positive correlation between ∆Serotonin and ∆ToL (subscore point: r= 0.587; p = 0.045), whereas in patients untreated with SSRIs (n = 13) we found a positive correlations between ∆Serotonin and ∆ROCF (r = 0.700; p = 0.036), ∆Stroop (subscore time: r = 0.750; p = 0.020) and ∆Tol (subscore point: r = 0.740; p = 0.023) and a negative correlation between ∆Serotonin and ∆Tol (subscore time: r= −0.833; p = 0.005). These results suggest that variation of serotonin levels should be monitored in patients during a rehabilitation program, not only for their relationship with depression symptoms, but also for the correlation with cognitive performance.

Original languageEnglish
Article number642
JournalBrain Sciences
Issue number5
Publication statusPublished - May 2021


  • 5-HT
  • Cognitive functions
  • Post-stroke cognitive impairment
  • Post-stroke depression
  • Rehabilitation
  • Serotonin
  • SSRIs
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)


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