Serum brain-derived neurotrophic factor, vascular endothelial growth factor and leptin levels in patients with a diagnosis of severe major depressive disorder with melancholic features

Kotan, Zeynep; Sarandöl, Emre; Kırhan, Emine; Özkaya, Güven; Kırlı, SelcÇuk

doi:10.1177/2045125312436572

Cited by 43 publications

(36 citation statements)

References 76 publications

(116 reference statements)

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“…However, there are considerable discrepancies among studies investigating VEGF in depression. While some studies have reported increased VEGF mRNA (Berent et al, 2014;Iga et al, 2007), serum (Berent et al, 2014;Kahl et al, 2009) or plasma (Lee and Kim, 2012;Takebayashi et al, 2010) levels in patients with MDD, others have found significant decreases in VEGF peripheral levels in depression (Dome et al, 2009;Isung et al, 2012;Katsuura et al, 2011) or no difference between patients with MDD and healthy controls (Kotan et al, 2012;Ventriglia et al, 2009). A recent review assessing clinical studies on VEGF and depression speculated that elevation in VEGF levels in patients with MDD appears to be due to the response to the perceived stress associated with depression resulting in an attempted neuroprotective effect, whereas decreased levels of VEGF seem to be observed in treatment-resistant depressed patients whose brains are less able to undergo neurogenesis processes (Clark-Raymond and Halaris, 2013).…”

Section: Discussionmentioning

confidence: 94%

Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression

Nikkheslat

Zunszain

Horowitz

et al. 2015

Brain, Behavior, and Immunity

127

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Coronary heart disease (CHD) and depression are very common and often co-existing disorders. In addition to psychological and social morbidity, depression exacerbates adverse cardiac outcomes in CHD patients. Inflammation has been proposed as one of the mechanisms involved in the association between these two debilitating diseases. Therefore, the present study aimed to evaluate inflammatory responses as well as to investigate the pathophysiological mechanisms underlying the putative inflammatory activation in CHD patients with and without depression, by assessing the function of two important biological factors regulating inflammation, the hypothalamus-pituitary-adrenal (HPA) axis and the glucocorticoid receptor (GR). Eighty-three CHD patients with (n=28) and without (n=55) comorbid depression were recruited from primary care services in South London. Depression status was assessed by means of Clinical Interview Schedule Revised for diagnosis of depression, and Beck Depression Inventory for the presence of depressive symptoms. Serum C-reactive protein (CRP), plasma vascular endothelial growth factor (VEGF), and plasma and salivary cortisol were measured using commercially available ELISA kits. Gene expression of GR and interleukin-6 (IL-6) were conducted via qPCR. GR sensitivity was evaluated in vitro in isolated peripheral blood mononuclear cells using the dexamethasone inhibition of lipopolysaccharide-stimulated IL-6 levels. Serum levels of kynurenine pathway metabolites were measured using high performance liquid chromatography. Our results show that CHD patients with depression had higher levels of CRP, IL-6 gene expression, and VEGF compared with CHD non-depressed, as well as lower plasma and saliva cortisol levels. The CHD depressed group also exhibited a reduction in GR expression and sensitivity. Finally, tryptophan levels were significantly lower in patients with depression, who also showed an increased kynurenine/tryptophan ratio. In conclusion, CHD patients with depression had elevated levels of inflammation in the context of HPA axis hypoactivity, GR resistance, and increased activation of the kynurenine pathway. Reduced cortisol bioavailability and attenuated glucocorticoid responsiveness due to decreased expression and sensitivity of GR may lead to insufficient glucocorticoid signaling and thus elevation of inflammation in these patients.

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Section: Discussionmentioning

confidence: 94%

Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression

Nikkheslat

Zunszain

Horowitz

et al. 2015

Brain, Behavior, and Immunity

127

View full text Add to dashboard Cite

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“…In one report, the authors found significantly lower VEGF levels in the peripheral blood of MDD patients than in healthy controls (Carvalho et al, 2013). However, other studies have reported no difference between the levels in peripheral blood of MDD patients and healthy controls (Dalby et al, 2013;Dome et al, 2009;Fornaro et al, 2013;Kotan et al, 2012;Ventriglia et al, 2009). These inconsistent findings may be due to many confounding factors, such as different study design, physical illness, age, gender distribution, medical history, length of illness, previous exposure to antidepressants, severity of depression, or sample source (plasma, serum, or whole blood).…”

Section: Introductionmentioning

confidence: 92%

“…In addition, we re-included one article in the meta-analysis of correlations between VEGF and severity of disease (Isung et al, 2012). The results of the literature search are listed in Table 1 (Berent et al, 2014;Carvalho et al, 2014Carvalho et al, , 2013Clark-Raymond et al, 2014;Dalby et al, 2013;Dome et al, 2009;Elfving et al, 2014;Fornaro et al, 2013;Galecki et al, 2013a;Kahl et al, 2009;Kotan et al, 2012;Lee and Kim, 2012;Lu et al, 2013;Schweiger et al, 2008;Takebayashi et al, 2010;Ventriglia et al, 2009). …”

Section: Studies Included In the Current Meta-analysismentioning

confidence: 99%

“…Similarly, during step 3, we subdivided the studies according to the sample source used in the studies into the serum sample subgroup (Berent et al, 2014;Carvalho et al, 2014Carvalho et al, , 2013Elfving et al, 2014;Galecki et al, 2013a;Kahl et al, 2009;Kotan et al, 2012;Schweiger et al, 2008;Ventriglia et al, 2009) and the plasma sample subgroup (ClarkRaymond et al, 2014;Dalby et al, 2013;Dome et al, 2009;Fornaro et al, 2013;Lee and Kim, 2012;Lu et al, 2013;Takebayashi et al, 2010 …”

Section: Meta-analysis Of Vegf Using Serum or Plasma Samplesmentioning

confidence: 99%

“…Berent et al, 2014;Carvalho et al, 2014;Clark-Raymond et al, 2014;Fornaro et al, 2013;Kahl et al, 2009;Kotan et al, 2012;Lee and Kim, 2012;Ventriglia et al, 2009) and non-drug free subgroup(Carvalho et al, 2013;Dalby et al, 2013;Dome et al, 2009;Elfving et al, 2014;Galecki et al, 2013a;Lu et al, 2013;Schweiger et al, 2008;Takebayashi et al, 2010)…”

mentioning

confidence: 97%

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Increased levels of vascular endothelial growth factor in patients with major depressive disorder: A meta-analysis

Tseng¹,

Cheng²,

Chen

et al. 2015

European Neuropsychopharmacology

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Association of peripheral manifestation of brain‐derived neurotrophic factor with depression: A meta‐analysis

Tiwari

Wong

et al. 2022

Brain and Behavior

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Background:The relationship between brain-derived neurotrophic factor (BDNF) and depression is a hot topic in research as several results of preclinical and clinical studies have shown controversial results. Our meta-analysis aims to evaluate and update the current status of peripheral BDNF with depression. Methods:We performed a meta-analysis by comprehensively searching PubMed and Web of Science for English-language literature from inception to 1st of June 2020. The search terms included brain-derived neurotrophic factor or BDNF in combination with depression, without year restriction. Using STATA software, data were pooled using a random-effects model. Results:In our literature search, 24 studies involving 1130 depressed patients and 1378 healthy individuals met our inclusion criteria. The results of our meta-analysis showed that the peripheral levels of BDNF levels significantly decreased in depression than nondepressed healthy controls (SMD = −0.89, 95% CI = −1.41, −0.38, p < .0001); however, the significant heterogeneity among studies (Q = 740.91, I 2 = 96.8; p < .001) was discovered. Trim-and-fill estimations for the adjustment of publication bias indicated that publication bias had no impact on our results. Our sub-group analysis showed that a history of depression and alcohol consumption had an effect on the level of BDNF. In addition, age and gender did not affect the heterogeneity of BDNF in the meta-analysis. Conclusions:Although decreased peripheral expression of BDNF certainly presents a risk of depression, we cannot find a definite relationship between the peripheral level of BDNF with depression to use BDNF as a reliable biomarker to assess the depression in clinical practice. We propose that future research should consider all the factors affecting BDNF and assess the level of proBDNF and mBDNF separately while evaluating the patients with depression objectively.

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Serum brain-derived neurotrophic factor, vascular endothelial growth factor and leptin levels in patients with a diagnosis of severe major depressive disorder with melancholic features

Cited by 43 publications

References 76 publications

Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression

Insufficient glucocorticoid signaling and elevated inflammation in coronary heart disease patients with comorbid depression

Increased levels of vascular endothelial growth factor in patients with major depressive disorder: A meta-analysis

Association of peripheral manifestation of brain‐derived neurotrophic factor with depression: A meta‐analysis

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