Gender differences in platelet brain derived neurotrophic factor in patients with cardiovascular disease and depression

https://doi.org/10.1016/j.jpsychires.2016.03.013Get rights and content

Abstract

Women have a higher prevalence of depression compared to men. Serum levels of Brain-derived neurotrophic factor (BDNF) are decreased in depression. BDNF may also have a protective role in the pathogenesis of coronary artery disease (CAD) or events. We examined whether there are gender differences in BDNF levels in patients with stable CAD and comorbid depression. We enrolled 37 patients (17 women) with stable CAD with and without depression from a single medical center. All patients had depression assessment with the Beck Depression Inventory-II questionnaire. Both plasma and platelet BDNF were measured in all patients using a standard ELISA method. Platelet BDNF levels were higher than plasma BDNF levels in the entire group (5903.9 ± 1915.6 vs 848.5 ± 460.5 pg/ml, p < 0.001). Women had higher platelet BDNF levels than men (6954.2 ± 1685.6 vs. 5011.2 ± 1653.5 pg/ml, p < 0.001). Women without depression (BDI-II < 5, n = 8) had higher platelet BDNF than men without depression (n = 8, 7382.8 ± 1633.1 vs 4811.7 ± 1642.3 pg/ml, p = 0.007). Women with no or minimal depression (BDI < 14, n = 14) had higher platelet BDNF levels than men with no or minimal depression (n = 18, 6900.2 ± 1486.6 vs 4972.9 ± 1568.9 pg/ml, p = 0.001). The plasma BDNF levels were similar between men and women in all categories of depression. In conclusion, women with stable CAD have increased platelet BDNF levels when compared to men with stable CAD regardless of their level of depression. Sex specific differences in BDNF could possibly indicate differences in factors linking platelet activation and depression in men and women.

Introduction

Gender differences in depression have been well documented (Piccinelli and Wilkinson, 2000). The prevalence, incidence and morbidity risk of depressive disorders are higher in women than in men (Kessler et al., 2007). Given this difference, investigators have examined whether gender differences in health are due to risk factors associated with depression. Patients with untreated depression have decreased serum levels of Brain derived neurotrophic factor (BDNF) and increased plasma and platelet levels. BDNF is a member of the nerve growth factor family. It promotes neural and synaptic growth and plays a critical role in the survival, differentiation, neuronal strength, and morphology of neurons (Duman, 1998). BDNF is a neurotransmitter and is also stored in large amounts in platelets. It is thought that stored BDNF is released by platelets in response to neuronal injury, where it plays a role in nerve repair (Fujimura et al., 2002). BDNF also plays a critical role in cardiovascular viability and function and has been suggested to play a protective role in the pathogenesis of CAD or CAD events (Kaess et al., 2015). Serum and platelet BDNF appear to mirror neuronal BDNF, and therefore due to ease of sampling, serum and platelet BDNF levels have been used as a surrogate measure of BDNF levels in the brain (Karege et al., 2002). BDNF levels are increased in platelet-poor plasma and decreased in serum as well as washed platelets in patients with untreated depression (Karege et al., 2002, Yu and Chen, 2011, Serra-Millas et al., 2011). Healthy women have been found to have lower platelet BDNF levels than men (Lommatzsch et al., 2005).

Depression has been correlated with the development of CAD and poor outcomes among patients with an acute coronary syndrome (Ford et al., 1998, Lichtman et al., 2014, Carney et al., 2003). Given that heart disease is the leading cause of death in both men and women (Kochanek et al., 2011), we sought to determine whether men and women with CAD would also have different BDNF levels in platelets and platelet-poor plasma and if levels in individuals without depression differ from those with depression. Understanding sex specific differences in factors such as BDNF that could possibly link platelet activation and depression may lead to novel predictors of CAD disease within women or men with depression.

Section snippets

Materials and methods

We enrolled 37 patients (17 women) with stable CAD from a single out-patient cardiology practice presenting for routine follow-up. CAD was defined as diagnostic cardiac catheterization demonstrating ≥50% obstructive coronary lesion, electrocardiographic evidence of previous myocardial infarction, or stress testing revealing myocardial ischemia or infarction without an acute event in the past year (Lloyd-Jones et al., 2009).

Patients were excluded if they were less than 21 years-old, were

Results

Table 1 shows the demographic and clinical profile of our patient sample. The median BDI for women in the sample was 5 with interquartile range (IQR) of 8 (3–11), for men the median BDI was 5 with IQR of 5.5 (3–8.5). Almost one half (47%) of women had BDI < 5 while 40% of men had BDI < 5. A total of 18% of women had BDI ≥14 compared to 10% of men. All but one patient in each gender group had BDI <20.

Platelet BDNF levels were higher than plasma-BDNF levels in the entire group see Table 2.

Mean

Discussion

This is the first study to show that women with stable CAD have significantly higher platelet BDNF levels when compared to men with stable CAD. Our cohort of these patients without depression (BDI < 5) had gender differences in regard to platelet BDNF as well. There were no statistically significant gender differences found in platelet BDNF levels in patients with CAD who had more than minimal depression (BDI ≥ 14). The levels of platelet BDNF in this subgroup were similar to those in women and

Contributors

Marlene S. Williams, MD- Contributed to research design, data analysis and article preparation Chelsea K. Ngongang, MD - contributed to data analysis Pam Ouyang, MBBS - contributed to research design and article preparation Fabrice Betoudji, MS - contributed to article preparation Christine Harrer, B.Sc- contributed to data analysis Nae-Yuh Wang, PhD - contributed to data analysis and article preparation Roy C. Ziegelstein, MD – contributed to article preparation.

All authors have approved the

Conflicts of interest

none.

Acknowledgments

The current study was funded by the Marianne J. Legato Research Scholar Awards in Gender-Specific Medicine, as well as grant support of NHLBI R01HL096694 and NCATS UL1TR001079 from the National Institutes of Health.

References (30)

  • V. Trajkovska et al.

    Measurements of brain-derived neurotrophic factor: methodological aspects and demographical data

    Brain Res. Bull.

    (2007)
  • A. Appels et al.

    Inflammation, depressive symptomtology, and coronary artery disease

    Psychosom. Med.

    (2000)
  • A. Beck et al.

    Manual for Beck Depression Inventory II (BDI-II)

    (1996)
  • I.M. Cameron et al.

    Measuring depression severity in general practice: discriminatory performance of the PHQ-9, HADS-D, and BDI-II

    Br. J. Gen. Pract.

    (2011)
  • M.J. Donovan et al.

    Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization

    Development

    (2000)
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