Poststroke Depression Biomarkers: A Narrative Review

Abstract

Poststroke depression (PSD) is the most prevalent psychiatric disorder after stroke, which is independently correlated with negative clinical outcome. The identification of specific biomarkers could help to increase the sensitivity of PSD diagnosis and elucidate its pathophysiological mechanisms. The aim of current study was to review and summarize literature exploring potential biomarkers for PSD diagnosis. The PubMed database was searched for papers published in English from October 1977 to December 2017, 90 of which met inclusion criteria for clinical studies related to PSD biomarkers. PSD biomarkers were subdivided into neuroimaging, molecular, and neurophysiological. Some of them could be recommended to support PSD diagnosing. According to the data, lesions affecting the frontal-subcortical circles of mood regulation (prefrontal cortex, basal nuclei, and thalamus) predominantly in the left hemisphere can be considered as neuroimaging markers and predictors for PSD for at least 1 year after stroke. Additional pontine and lobar cerebral microbleeds in acute stroke patients, as well as severe microvascular lesions of the brain, increase the likelihood of PSD. The following molecular candidates can help to differentiate PSD patients from non-depressed stroke subjects: decreased serum BDNF concentrations; increased early markers of inflammation (high-sensitivity C-reactive protein, ferritin, neopterin, and glutamate), serum pro-inflammatory cytokines (TNF-a, IL-1b, IL-6, IL-18, IFN-g), as well as pro-inflammatory/anti-inflammatory ratios (TNF-a/IL-10, IL-1b/IL-10, IL-6/IL-10, IL-18/IL-10, IFN-g/IL-10); lowered complement expression; decreased serum vitamin D levels; hypercortisolemia and blunted cortisol awakening response; S/S 5-HTTLPR, STin2 9/12, and 12/12 genotypes of the serotonin transporter gene SLC6A4, 5-HTR2a 1438 A/A, and BDNF met/met genotypes; higher SLC6A4 promoter and BDNF promoter methylation status. Neurophysiological markers of PSD, that reflect a violation of perception and cognitive processing, are the elongation of the latency of N200, P300, and N400, as well as the decrease in the P300 and N400 amplitude of the event-related potentials. The selected panel of biomarkers may be useful for paraclinical underpinning of PSD diagnosis, clarifying various aspects of its multifactorial pathogenesis, optimizing therapeutic interventions, and assessing treatment effectiveness.