Poststroke Depression Biomarkers: A Narrative Review

If you got survivors 100% recovered you wouldn't have to tackle this secondary problem of depression. Focus on the primary problem and you wouldn't have all these secondary problems to deal with. That is where exact stroke protocols tied to specific objective damage diagnosis comes in. If your doctor and stroke hospital can't see that they need to be fired.
https://www.frontiersin.org/articles/10.3389/fneur.2018.00577/full?

Oleg A. Levada^* and Alexandra S. Troyan

• State Institution “Zaporizhzhia Medical Academy of Postgraduate Education Ministry of Health of Ukraine, ” Zaporizhzhia, Ukraine

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-α, IL-1β, IL-6, IL-18, IFN-γ), as well as pro-inflammatory/anti-inflammatory ratios (TNF-α/IL-10, IL-1β/IL-10, IL-6/IL-10, IL-18/IL-10, IFN-γ/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.

Introduction

Poststroke depression (PSD) is the most prevalent psychiatric disorder after stroke, which affects nearly one-third of the survivors during first 5 years after disease onset (1–3). The diagnosis of PSD includes the following characteristics: (1) presence of major/minor depressive episode according to DSM-III-IV-5 or other valid approaches; (2) evidence of stroke from history, physical examination, and/or neuroimaging data; and (3) onset of PSD is temporally related to the stroke (3). Several epidemiological findings have demonstrated that PSD is independently linked to negative clinical outcomes, such as significantly longer hospitalization; more severe functional disability (3–6); profound diminutions in physical, psycho-social, cognitive, and eco-social domains of quality of life (3, 7); unsatisfactory results of poststroke rehabilitation (8); elevated rates of mortality (3, 9–11); higher risks of recurrent stroke at 1 year (12); as well as considerable strain for caregivers (13). Data mentioned above highlight the importance of identifying PSD among stroke survivors.

The detection of depressive symptoms at early stroke stages and recognition subjects at risk for PSD diagnosis remains challenging. Clinical measures currently used to assess PSD, especially in the acute poststroke patients, may lack the specificity necessary to detect symptoms (14, 15). From this point of view, the identification of specific biomarkers might help to increase the sensitivity of PSD diagnosis. Moreover, it could be helpful for elucidating the pathophysiological mechanisms of PSD and ultimately lead to choosing specific targeted treatment (16).

Thus, we aimed to review and summarize the literature exploring potential biomarkers for PSD diagnosis.