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Currently, the diagnosis of major depressive disorder (MDD) mainly relies on clinical examination and subjective evaluation of depressive symptoms. There is no non-invasive, quantitative test available today for the diagnosis of MDD. In MDD, exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment, and predicting the treatment response. In this article, it is aimed to review the findings of suggested biomarkers such as growth factors, cytokines and other inflammatory markers, oxidative stress markers, endocrine markers, energy balance hormones, genetic and epigenetic features, and neuroimaging in MDD and to evaluate how these findings contribute to the pathophysiology of MDD, the prediction of treatment response, severity of the disorder, and identification of subtypes. Among these, the findings related to the brain-derived neurotrophic factor, the hypothalamo-pituitary-adrenal axis, cytokines, and neuroimaging may be strong candidates for being biomarkers MDD, and may provide critical information in understanding biological etiology of depression. Although the findings are not sufficient yet, we think that the results of epigenetic studies will also provide very important contributions to the biomarker research in MDD. The availability of biomarkers in MDD will be an advancement that will facilitate the diagnosis of the disorder, treatment choices in the early stages, and prediction of the course of the disorder. [ABSTRACT FROM AUTHOR]

Aims: The aim of the study is to assess and compare serum C-reactive protein (CRP), brain derived neurotrophic factor (BDNF), and interleukin-2 (IL-2) levels in patients with first-episode depression (FED), recurrent depressive disorder (RDD), and healthy controls (HCs) and to determine the relationship between the above-specified inflammatory markers, severity of depression, and stressful life events. Materials and Methods: Consecutive drug-naive patients with FED and RDD (n = 85) and 50 HCs were studied. Serum concentrations of CRP, brain-derived nerve growth factor (BDNF), and IL-2 were measured. All participants were assessed using Mini-International Neuropsychiatric Interview Plus, Beck's depression inventory, and presumptive stressful life events scale. Results: The FED and RDD groups had statistically significant lower serum concentration of BDNF and higher IL-2 compared to the HC group, whereas no statistically significant difference was observed with regard to CRP level. No statistically significant differences were observed with regard to the severity of depression and serum concentrations of CRP, BDNF, and IL-2 in the FED and RDD groups. No significant correlation was found between severity of depression and serum concentration of CRP, BDNF, and IL-2 in both the groups. Serum CRP concentration was significantly higher in patients with ≥2 stressful life events. No significant difference was observed between number of stressful life events and BDNF and IL-2 in patients with depression. Conclusion: FED and RDD are associated with lower serum concentration of BDNF and higher IL-2 compared to the HCs, whereas there appears no difference with regard to CRP level. Multicentric studies are needed to further elucidate the role of inflammatory markers in depression. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects. [ABSTRACT FROM AUTHOR]

Background: The predictive therapeutic value of brain derived neurotrophic factor (BDNF) and its changes associated with the use of specific antidepressants are still unclear. In this study, we examined BDNF as a peripheral and NAA as a central biomarker over the time course of antidepressant treatment to specify both of their roles in the response to the medication and clinical outcome. Methods: We examined serum BDNF (ELISA kit) in a sample of 76 (47 female and 29 male) depressed patients in a naturalistic setting. BDNF was assessed before medication and subsequently after two, four and six weeks of antidepressant treatment. Additionally, in fifteen patients, N-acetylaspartate (NAA) was measured in the anterior cingulate cortex (ACC) with magnetic resonance spectroscopy (MRS). Over a time course of six weeks BDNF and NAA were also examined in a group of 41 healthy controls. Results: We found significant lower serum BDNF concentrations in depressed patients compared to the sample of healthy volunteers before and after medication. BDNF and clinical symptoms decreased significantly in the patients over the time course of antidepressant treatment. Serum BDNF levels at baseline predicted the symptom outcome after eight weeks. Specifically, responders and remitters had lower serum BDNF at baseline than the nonresponders and nonremitters. NAA was slightly decreased but not significantly lower in depressed patients when compared with healthy controls. During treatment period, NAA showed a tendency to increase. Limitations: A relative high drop-out rate and possibly, a suboptimal observation period for BDNF. Conclusion: Our data confirm serum BDNF as a biomarker of depression with a possible role in response prediction. However, our findings argue against serum BDNF increase being a prerequisite to depressive symptom reduction. [ABSTRACT FROM AUTHOR]

The levels of brain-derived neurotrophic factor (BDNF) are significantly decreased in patients with schizophrenia and correlate with impairments in cognitive function. However, no study has investigated the relationship between the serum BDNF levels and decision-making. We compared patients with schizophrenia to healthy controls with respect to their decision-making ability and serum BDNF levels. Eighty-six chronic schizophrenia patients and 51 healthy controls participated in this study. We controlled for gender, age, and estimated intelligence quotient (IQ), and we investigated the differences in decision-making performance on the Iowa Gambling Task (IGT) between the schizophrenia patient and control groups. We also compared the IGT scores, the serum BDNF levels, and the clinical symptoms between the groups. The IGT scores of the schizophrenia patients were lower than those of the controls. A negative correlation was detected between the mean net scores on the trials in the final two blocks and the serum BDNF levels (p < 0.05). Multiple regression analysis revealed that depressive symptoms and the serum BDNF levels were significantly associated with the mean net scores on the trials in the final two blocks. Based on these results, impaired sensitivity to both reward and punishment is associated with depressive symptoms and reduced serum BDNF levels in chronic schizophrenia patients and may be related to their poor performance on the IGT. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurogenesis, and BDNF plasma and serum levels have been associated with depression, Alzheimer's disease, and other psychiatric and neurodegenerative disorders. In a relatively large community sample, drawn from the Baltimore Longitudinal Study of Aging (BLSA), we examine whether BDNF plasma concentration is associated with the Val66Met functional polymorphism of the BDNF gene ( n = 335) and with depression-related personality traits assessed with the NEO-PI-R ( n = 391). Plasma concentration of BDNF was not associated with the Val66Met variant in either men or women. However, in men, but not in women, BDNF plasma level was associated with personality traits linked to depression. Contrary to the notion that low BDNF is associated with negative outcomes, we found lower plasma levels in men who score lower on depression and vulnerability to stress (two facets of Neuroticism) and higher on Conscientiousness and Extraversion. These findings challenge the prevailing hypothesis that lower peripheral levels of BDNF are a marker of depression. [ABSTRACT FROM AUTHOR]

The search for a biological marker predicting the future failure or success of electroconvulsive therapy (ECT) remains highly challenging for patients with treatment-resistant depression. Evidence suggests that Brain-Derived Neurotrophic Factor (BDNF), a protein known to be involved in brain plasticity mechanisms, can play a key role in both the clinical efficacy of ECT and the pathophysiology of depressive disorders. We hypothesized that mature BDNF (mBDNF), an isoform of BDNF involved in the neural plasticity and survival of neural networks, might be a good candidate for predicting the efficacy of ECT. Total BDNF (tBDNF) and mBDNF levels were measured in 23 patients with severe treatment-resistant depression before (baseline) they received a course of ECT. More precisely, tBDNF and mBDNF measured before ECT were compared between patients who achieved the criteria of remission after the ECT course (remitters, n = 7) and those who did not (non-remitters, n = 16). We found that at baseline, future remitters displayed significantly higher mBDNF levels than future non-remitters (p = 0.04). No differences were observed regarding tBDNF levels at baseline. The multiple logistic regression model controlled for age and sex revealed that having a higher baseline mBDNF level was significantly associated with future remission after ECT sessions (odd ratio = 1.38; 95% confidence interval = 1.07–2.02, p = 0.04). Despite the limitations of the study, current findings provide additional elements regarding the major role of BDNF and especially the mBDNF isoform in the clinical response to ECT in major depression. [ABSTRACT FROM AUTHOR]