Plasma polyamines levels and post-stroke depression in ischemic stroke patients: A multicenter prospective study

Background and aims: Polyamines have been suggested to implicated in inflammation, ischemic stroke, and mental disorders, but the associations of polyamines with post-stroke depression (PSD) remain unclear. We aimed to prospectively investigate the associations of plasma putrescine, spermidine and spermine with PSD among ischemic stroke patients in a multicenter cohort study. Methods: We measured plasma putrescine, spermidine and spermine levels at baseline among 635 ischemic stroke patients from a preplanned ancillary study of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The study outcome was depression (Hamilton Depression Rating Scale score >= 8) at 3-month follow-up after ischemic stroke. Results: Plasma putrescine and spermidine were positively associated with the risk of PSD. The adjusted odds ratios of PSD for the highest versus lowest tertile of putrescine and spermidine were 1.77 (95 % CI, 1.13-2.78; ptrend = 0.014) and 1.77 (95 % CI, 1.11-2.82; ptrend = 0.013), respectively. Multivariable-adjusted spline regression analyses showed linear associations of plasma putrescine (p = 0.002 for linearity) and spermidine (p = 0.008 for linearity) with PSD. In addition, plasma putrescine (continuous net reclassification improvement [NRI]: 26.33 %, p = 0.002; integrated discrimination improvement [IDI]: 1.06 %, p = 0.009) and spermidine (continuous NRI: 20.72 %, p = 0.013; IDI: 1.04 %, p = 0.010) could significantly improve the risk reclassification of PSD beyond the established risk factors. Conclusions: High plasma putrescine and spermidine levels were associated with increased risk of PSD among ischemic stroke patients. Our findings suggest that plasma polyamines should be implicated in the pathophysiologic processes of PSD and may be the potential intervention targets for PSD.