The association between mean platelet volume levels and poststroke depression

Abstract Objective High levels of mean platelet volume (MPV) had been found in depression subjects. We sought to examine the relationship between MPV and poststroke depression (PSD). Methods One hundred and eighty‐five patients with acute ischemic stroke were enrolled in our study. Peripheral venous blood samples were drawn at admission and MPV levels were measured by the automated hematology analyzer. Patients with a HAMD‐17 score >7 were diagnosed as having PSD. Results We found that 60 patients (32.4%) developed PSD, the MPV levels in PSD patients were significantly higher (9.3 ± 1.8 fl) compared to non‐PSD patients (8.5 ± 1.6 fl). High MPV levels (≥9.1 fl) were independently correlated with PSD (OR 2.762, 95% CI 1.138–6.702, p = 0.025). Conclusions Patients with higher levels of MPV at admission were correlated with the development of PSD at 1 month after stroke and might be a predictor of its presence.

Given the relationship between depression and MPV, it would be interesting to investigate whether MPV levels were correlated with the development of depression among patients after ischemic stroke. To date, however, no study has been conducted to examine the relationship between MPV and PSD. Hence, whether MPV levels correlate with PSD at 1 month after ischemic stroke was explored.

| Data collection
The demographic as well as clinical characteristics of our research were obtained through standardized questionnaires interviewed by trained neurological physicians who were blind to the patients' laboratory results at admission. Stroke etiology was classified based on TOAST criteria (Adams, 1993). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the stroke severity on admission. The Barthel Index (BI) as well as modified Rankin Scale (mRS) were applied for assessment of functional outcome at one month after acute ischemic stroke. Besides, The Mini-Mental State Examination (MMSE) was used for evaluation of cognition function at one month after acute ischemic stroke.

| Definition of PSD
Depressive symptoms were evaluated by trained psychiatrists who were blind to the patients' laboratory results using the 17-item F I G U R E 1 Study recruitment profile Hamilton Depression Scale (HAMD-17) (Zimmerman, Martinez, Young, Chelminski, & Dalrymple, 2013). Subjects with a score >7 (Park et al., 2017;Zimmerman, et al., 2013) at one month after acute ischemic stroke were considered PSD according to DSM IV.

| Laboratory tests
The peripheral venous blood samples were drawn on admission and collected in a calcium ethylenediaminetetra-acetic acid tube.
Complete blood count was analyzed by the automated hematology analyzer (Sysmex Company, XE-2100, Japan) within 1 hr after sample collection. Platelet count and MPV levels were recorded. MPV levels were further divided into tertiles (≤7.7 fl, 7.8-9.0 fl, ≥9.1 fl).

| Statistical analysis
The results were expressed as percentages for categorical variables, and continuous variables according to their normal distribution were indicated as median (interquartile range, IQR) or mean standard deviation (SD). Proportions were compared employing the Chi-squared  In the study population, 60 (32.4%) were diagnosed as having PSD. Meanwhile, the average MPV levels for all patients were 8.7 ± 1.7 fl; the levels of MPV in PSD group were significantly higher than that in non-PSD group (9.3 ± 1.8 fl vs. 8.5 ± 1.6 fl; F = 9.64, p = 0.002). Furthermore, a more severe stroke, worse functional outcome as well as worse cognitive function were observed in PSD patients (all p < 0.05). Moreover, the proportion of female gender was higher in PSD than non-PSD (p < 0.05). No association was found between two groups in terms of platelet count, vascular risk factors, stroke etiology, and lesion location (Table 1).

| The association between MPV and PSD
As demonstrated in Table 2, there were significant differences between PSD and non-PSD in MPV tertiles of patients (p = 0.005).
Moreover, in the lowest tertile (≤7.7 fl), PSD group had a lower proportion of patients than that in non-PSD group (p = 0.002), while in the highest tertile (≥9.1 fl), PSD group had a higher proportion of patients than that in non-PSD group (p = 0.010).

| D ISCUSS I ON
To our best knowledge, this was the first report to examine the association between MPV levels and the presence of PSD. Our results indicated that high MPV levels were independently correlated with PSD.
In addition, we found that hyperlipidemia was associated with PSD.
This finding was in accord with previous studies (Armstrong et al., 2017;Lim et al., 2017). However, there was no significant association between PSD and other clinical characteristics, such as lesion location (Guiraud, et al., 2016;Hama et al., 2007;Metoki et al., 2016), although among some of previous studies the results about lesion location remained controversial.
Our results are in line with another study that demonstrated increased MPV levels were associated with depression in a large population (Canan et al., 2012). Likewise, elevated MPV levels were also found in patients with fibromyalgia syndrome as well as bipolar disorder (Vural et al., 2015;Yildirim, Solmaz, Akgol, & Ersoy, 2016).
The relationship between MPV and depression remains not completely understood. However, several mechanisms may explain the depression in patients with higher MPV levels. The regulation of the platelet activity might explain the association between MPV and depression. As a routinely available measure of platelet size at admission, MPV can be considered as a biological indicator of platelet activity (Chu, et al., 2010), which was correlated with depression (Musselman, et al., 1996;Shimbo et al., 2002). This accorded well with one study based on a large population, which reported that elevated MPV levels were associated with major depression (Canan, et al., 2012). Meanwhile, it has been shown that escitalopram effect of inhibiting reuptake of serotonin occurs in neurons as well as platelets, reducing platelet reactivity (Atar et al., 2006). Besides, as mentioned earlier, patients with depression exhibited normalization of platelet activation and significant reduction in MPV levels after escitalopram treatment (Ataoglu & Canan, 2009), indicating that MPV may play a vital role in pathophysiological process of depression. Thus, considering its role in ischemic stroke as well as depression, MPV may participate in the development of PSD.
Our study still has some limitations. First, patients with serious conditions or aphasia were excluded from our study, which may reduce the real PSD prevalence. Second, only MPV levels in the baseline period was measured, which might make us fail to reveal the dynamic change in MPV levels during the development of PSD.
Finally, the application of our conclusion may be limited in those minor stroke subjects, for most of the patients with a higher NIHSS score have been excluded.

| CON CLUS ION
In conclusion, despite these limitations, the findings of this study remained important and demonstrated that high levels of MPV on admission were significantly associated with the development of PSD.
High MPV levels could be considered as an independent prognostic marker of PSD. These findings suggest a potential role of MPV in the pathophysiology of PSD and indicate that patients with acute ischemic stroke should be monitored for high MPV levels. In future, multicenter and randomized controlled trials are critical to determine the causal relationship between MPV levels and PSD.

ACK N OWLED G M ENTS
This study was supported by Wenzhou Municipal Sci-Tech Bureau Program (Y20160002) as well as National Key Technology Research and Development Program of the Ministry of Science and Technology of China (grant number: 2015BAI13B01). We are greatly indebted to the staff and to the patients for their contributions during this study.

CO N FLI C T O F I NTE R E S T
None declared.