Association between major depressive disorder and the -1438A/G polymorphism of the serotonin 2A receptor gene

This study investigated the possible effect of the -1438A/G single-nucleotide polymorphism in the promoter region of the serotonin 2A receptor (5-HTR2A) gene on major depressive disorder (MDD) in a Korean population. This polymorphism was analyzed in 189 patients with MDD and in 148 unrelated healthy controls using a case-control design, which revealed a significant difference in the genotype distributions (chi(2) = 10.78, d.f. = 2, p = 0.005). The frequency of the -1438G allele was also much higher in MDD patients than in normal controls (chi(2) = 7.20, p = 0.007; OR = 1.52, 95% CI 1.12-2.06). We also found significantly more carriers of the G allele (GG+AG genotypes) in MDD patients than in normal controls (chi(2) = 10.18, p = 0.001; OR = 2.46, 95% CI 1.40-4.32). Our results support the hypothesis that the -1438A/G polymorphism of the promoter region of the 5-HTR2A gene is associated with MDD patients in a Korean population.     

Serotonin receptor 2A gene polymorphism (-1438A/G) and short-term treatment response to citalopram

The 5-HTR2A gene is a candidate gene for influencing the clinical response to antidepressant treatment. The purpose of this study was to determine the relationship between the -1438A/G polymorphism in the 5-HTR2A gene and the response to citalopram in a Korean population with major depressive disorder (MDD). Citalopram was administered for 4 weeks to the 71 patients who completed this study. We found significant differences in genotype, allele, and carrier distribution between the normal group and MDD patients (genotypes: chi(2) = 6.473, d.f. = 2, p = 0.039; alleles: chi(2) = 5.589, d.f. = 1, p = 0.018; OR = 0.618, 95% CI = 0.414-0.922; allele carriers: chi(2) = 5.383, d.f. = 1, p = 0.020; OR = 0.473, 95% CI = 0.249-0.879). The frequency of the -1438G allele was much higher in MDD patients than in the normal group (allele carriers: chi(2) = 5.383, d.f. = 1, p = 0.020; OR = 0.473, 95% CI = 0.249-0.879). There were also significant differences in response to citalopram according to the -1438A/G variation of 5-HTR2A in MDD patients. The group of remitters carried a higher frequency of the GG allele than of the AA and AG alleles. More of nonremitters carried the A allele than were without it (genotype: chi(2) = 8.016, p = 0.018; allele carrier: chi(2) = 4.512, p = 0.034; OR = 0.324, 95% CI = 0.112-0.936). The response to citalopram differed with the -1438A/G polymorphism genotype and allele carriers. The -1438G/-1438G genotype appeared to be associated with a better response to citalopram, with especially the G allele being related to core depressive symptoms and psychic anxiety improvement (p<0.05). These results suggest that the G allele of the -1438A/G polymorphism in the 5-HTR2A gene is associated with MDD, and that patients with -1438G/-1438G have a better response to citalopram treatment than patients with -1438A/-1438A or -1438A/-1438G.     

C-reactive protein: A differential biomarker for major depressive disorder and bipolar II disorder

Objectives We aimed to examine whether the C-reactive protein (CRP) level could be used to differentiate between major depressive disorder (MDD) and bipolar II disorder (BD II). Methods Ninety-six healthy controls, 88 BD II and 72 MDD drug-naïve patients in their major depressive episodes were enrolled. The fasting plasma level of high-sensitivity CRP was assessed at baseline and after treatment. Results The BD II patients presented significantly higher 17-item Hamilton Depression Rating Scale (HDRS) scores and CRP levels at baseline when adjustment for age, gender, and body mass index (P?< 0.001 and P?< 0.001, respectively). After treatment the CRP levels remained significantly different (P?< 0.001), although the HDRS score was not significantly different between the BD II and MDD patients. A receiver-operating characteristic analysis showed that a baseline CRP level of 621.6?ng/mL could discriminate between BD II and MDD, with an area under the curve of 0.816 and a sensitivity and specificity of 0.699 and 0.882, respectively. Furthermore, the baseline CRP level greater than 621.6?ng/ml had 28.2 higher odds of a diagnosis of BD II (P?< 0.001, 95% confidence interval: 10.96–72.35). Conclusions The level of CRP plays a role of biomarker to differentiate between MDD and BD II depression in both their depressed and euthymic state.     

Association study between obsessive-compulsive disorder and serotonergic candidate genes

BACKGROUND: To date, research examining the relationship between serotonergic genes and obsessive-compulsive disorder (OCD) has yielded conflicting results. The purpose of this study is to investigate the association between four serotonergic polymorphisms (STin2 VNTR and 5-HTTLPR of the SLC6A4 gene, and A-1438G (rs6311) and T102C (rs6313) of the HTR2A gene) and OCD. METHODS: 99 OCD patients, 456 non-OCD psychiatric patients, and 420 healthy controls from a homogeneous Spanish Caucasian population were genotyped using standard methods. RESULTS: All groups showed Hardy-Weinberg equilibrium for the analyzed genetic variability. A-1438G and T102C polymorphisms were in complete linkage disequilibrium. OCD patients showed an excess of STin2.12 carriers (12/12, 12/10, and 12/9 genotypes) compared with healthy controls (chi(2) (1)=7.21, corrected p=0.021; OR=3.38, 95% CI=1.32-8.62) and non-OCD psychiatric patients (chi(2) (1)=6.70, corrected p=0.030; OR=3.24, 95% CI=1.27-8.26). However, no differences were found between non-OCD patients and healthy controls (chi(2) (1)=0.05, corrected p>1; OR=1.04, 95% CI=0.72-1.51). No significant differences were found with respect to A-1438G and 5-HTTLPR polymorphisms. CONCLUSIONS: Our data provide supporting evidence of an association between the STin2 VNTR polymorphism of the SLC6A4 gene and OCD.     

Association between the DAOA/G72 gene and bipolar disorder and meta-analyses in bipolar disorder and schizophrenia

Müller DJ, Zai CC, Shinkai T, Strauss J, Kennedy JL. Association between the DAOA/G72 gene and bipolar disorder and meta‐analyses in bipolar disorder and schizophrenia.
Bipolar Disord 2011: 13: 198–207. © 2011 The Authors.
Journal compilation © 2011 John Wiley & Sons A/S. Objective: The d ‐amino acid oxidase activator (DAOA, or G72) is involved in the oxidation of d ‐serine, an endogenous modulator of N‐methyl‐d ‐aspartate receptors and thus represents an important candidate in psychotic disorders. Several studies reported the DAOA/G72 gene to be associated with schizophrenia (SZ) and bipolar disorder (BD); however, the associated polymorphisms varied between SZ and BD. This study attempts to replicate the DAOA/G72 findings in BD and to conduct subgroup analyses based on the presence or absence of psychotic symptoms. Methods: Five polymorphisms of the DAOA/G72 gene (rs1341402, rs1935062, rs2391191, rs947267, and rs778294) were analysed for association with BD in a family‐based study design (303 core families including 916 individuals). We also conducted a meta‐analysis of DAOA/G72 polymorphisms in BD and SZ. Results: Marker rs1935062 was significantly associated with BD diagnosis in our sample (Z‐score for C‐allele = ?2.33, p = 0.02, uncorrected for genome‐wide multiple comparisons). When we examined the subset of BD patients with psychotic symptoms (157 families), no significant results were obtained. Our meta‐analysis yielded negative findings for DAOA/G72 markers in BD and positive findings for marker rs2391191 in SZ in East Asians. However, significant heterogeneity across studies limits interpretation. Conclusions: Our results provide evidence that suggests a possible role of the DAOA/G72 gene in BD and SZ. Marker rs1935062 may be specifically associated with BD, while marker rs2391191 may be associated with SZ but not with BD. Together with previous studies, these findings suggest that the DAOA/G72 gene confers susceptibility to both BD and SZ, but that different polymorphisms may potentially differentiate between these two disorders.     

Obesity and the three‐year longitudinal course of bipolar disorder

Goldstein BI, Liu S‐Min, Schaffer A, Sala R, Blanco C. Obesity and the three‐year longitudinal course of bipolar disorder.
Bipolar Disord 2013: 00: 000–000. © 2013 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Despite substantial cross‐sectional evidence that obesity is associated with an increased medical and psychiatric burden in bipolar disorder (BD), few longitudinal studies have examined this topic. Methods: Subjects with BD (n = 1600) who completed both Wave 1 and Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions were included. Analyses examined the association between obesity at Wave 1, and the subsequent course of BD, and of psychiatric and medical comorbidities, between Wave 1 and Wave 2. Results: BD subjects with obesity (n = 506; 29.43%), compared to BD subjects without obesity (n = 1094; 70.57%) were significantly more likely to have a major depressive episode and to receive counseling for depression during follow‐up, more likely to report a lifetime suicide attempt, and less likely to develop new‐onset alcohol use disorders. These differences were no longer significant, however, after controlling for baseline demographic variables. No significant differences in new episodes or treatment of mania/hypomania were observed. After controlling for demographic variables, obese subjects remained significantly more likely to report any new‐onset medical condition [odds ratio (OR) = 2.32, 95% confidence interval (CI): 1.63–3.30], new‐onset hypertension (OR = 1.81, 95% CI: 1.16–2.82) and arthritis (OR = 1.64, 95% CI: 1.07–2.52). Obese subjects were significantly more likely to report physician‐diagnosed diabetes (OR = 6.98, 95% CI: 4.27–11.40) and hyperlipidemia (OR = 2.32, 95% CI: 1.63–3.30) (assessed in Wave 2 only). The incidence of heart attacks was doubled among obese subjects, although this difference was not statistically significant. Conclusions: The association between obesity and increased prospective depressive burden appears to be explained by baseline demographic variables. By contrast, obesity independently predicts the accumulation of medical conditions among adults with BD. Treatment of obesity could potentially mitigate the psychiatric and medical burden of BD.     

Gender differences in bipolar disorder type I and II

Objective: We investigated gender differences in bipolar disorder (BD) type I and II in a representative cohort of secondary care psychiatric in‐ and out‐patients. Method: In the prospective, naturalistic Jorvi Bipolar Study of 191 secondary care psychiatric in‐ and out‐patients, 160 patients (85.1%) could be followed up for 18 months with a life chart. Results: After adjusting for confounders, no marked differences in illness‐related characteristics were found. However, female patients with BD had more lifetime comorbid eating disorders (P < 0.001, OR = 5.99, 95% CI 2.12–16.93) but less substance use disorders (P < 0.001, OR = 0.29, 95% CI 0.16–0.56) than males. Median time to recurrence after remission was 3.1 months longer among men than women, female gender carrying a higher hazard of recurrence (P = 0.006, HR = 2.00, 95% CI 1.22–3.27). Conclusion: Men and women with type I and II BD have fairly similar illness‐related clinical characteristics, but their profile of comorbid disorders may differ significantly, particularly regarding substance use and eating disorders. In medium‐term follow‐up, females appear to have a higher hazard of recurrence than males.     

Self‐esteem in remitted bipolar disorder patients: a meta‐analysis

Nilsson KK, Jørgensen CR, Craig TKJ, Straarup KN, Licht RW. Self‐esteem in remitted bipolar disorder patients: a meta‐analysis.
Bipolar Disord 2010: 12: 585–592. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Low self‐esteem has been found to be a risk factor for depression in major depressive disorder (MDD). In contrast, the role of self‐esteem in bipolar disorder (BD) is still uncertain. In order to examine the characteristics of self‐esteem in BD, we synthesized studies comparing self‐esteem in BD patients with self‐esteem in MDD patients and in normal controls. Methods: Database searches and identification of studies were conducted by two of the authors independently. Remission of BD and MDD was a major selection criterion. The results were generated through meta‐analyses. Results: Random‐effects models of 19 between‐group comparisons (N = 1,838) suggested that the self‐esteem of remitted BD patients was significantly lower than that of normal controls (Cohen’s d = ?0.83), while significantly higher than that of remitted MDD patients (Cohen’s d = 0.54). Fail‐safe numbers and tests for funnel plot asymmetry indicated that the results were robust and unlikely to reflect publication biases. Additional studies indicated that self‐esteem may take a fluctuating course during remission of BD. Conclusions: By revealing that BD patients do experience low self‐esteem, the findings implicate a need for further understanding the causes and therapeutic impact of such abnormality in BD.     

Association analysis of HTR6 and HTR2A polymorphisms in sporadic Alzheimer's disease

Summary. In order to identify gene variants related to the serotonergic neurotransmitter system that possibly represent a hereditary risk factor for sporadic Alzheimer's disease (AD), patients suffering from AD and non-demented psychiatric inpatients without symptoms of dementia were genotyped for polymorphisms of HTR6 (267C/T) and HTR2A (−1438G/A). Although there was a tendency toward an increased number of the genotype TT of the 5-HT₆ receptor polymorphism in AD patients when compared to controls (2.8% vs. 1.3%), neither this nor the 5-HT_2A promoter polymorphism showed significant differences in their genotypic or allelic distribution among patients and controls. These polymorphisms probably do not represent major genetic risk factors of AD. However, further studies including other genetic variants of the serotonergic neurotransmitter system are needed in order to elucidate their role in AD. Received March 1, 2001; accepted June 27, 2001     

HTR2A is Associated with SSRI Response in Major Depressive Disorder in a Japanese Cohort

Several recent investigations reported that the serotonin 2A receptor gene (HTR2A) was associated with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder. There have also been two reported association analyses of HTR2A with SSRI response in Japanese MDD patients, but the results were rather inconsistent and both studies had the problem of small sample sizes. Therefore, we conducted a replication association study using a sample larger than those in the two original Japanese studies (265 MDD patients), and found that four SNPs, two functional SNPs (-A1438G: rs6311 and T102C: rs6313) and two SNPs (rs7997012 and rs1928040) in HTR2A, were associated with the therapeutic response to SSRIs. HTR2A was associated with the therapeutic response SSRIs in Japanese MDD patients in a haplotype-wise analysis (P _{all markers} = 0.0136), and a significant association between rs1928040 in HTR2A and SSRI response was detected in MDD (P _{allele-wise analysis} = 0.0252). However, this significance disappeared after Bonferroni correction (P _{allele-wise analysis} = 0.101). In conclusion, we suggest that HTR2A may play an important role in the pathophysiology of the therapeutic response to SSRIs in Japanese MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples.     

Quantitative separation of the depressive phase of bipolar disorder and major depressive disorder using electrovestibulography

Abstract

Objectives: No electrophysiological, neuroimaging or genetic markers have been established that strongly relate to the diagnostic separation of bipolar disorder (BD) and major depressive disorder (MDD). This paper’s objective is to describe the potential of features, extracted from the recording of electrical activity from the outer ear canal, in a process called electrovestibulography (EVestG), for identifying depressed and partly remitted/remitted MDD and BD patients from each other.

Methods: From EVestG data four sensory vestibulo-acoustic features were extracted from both background (no movement) and using a single supine-vertical translation stimulus to distinguish 27 controls, 39 MDD and 43 BD patients.

Results: Using leave-one-out-cross-validation, unbiased parametric and non-parametric classification routines resulted in 78–83% (2–3 features), 80–81% (1–2 features) and 66–68% (3 features) accuracies for separation of MDD from BD, controls from depressed (BD & MDD) and the 3-way separation of BD from MDD from control groups, respectively. The main limitations of this study were the inability to fully disentangle the impact of prescribed medication from the responses and also the limited sample size.

Conclusions: EVestG features can reliably identify depressed and partly remitted/remitted MDD and BD patients from each other.     

Elevated levels of cerebrospinal fluid neuron-specific enolase (NSE), but not S100B in major depressive disorder

Objectives. Alterations in neuronal and glial integrity are considered to be of pathogenic impact on major depressive disorder (MDD). For MDD, data on cerebrospinal fluid (CSF) levels of neuron-specific enolase (NSE) are lacking and scarce for glial protein S100B. Methods. We measured CSF levels of NSE and S100B in 31 patients with MDD and 32 mentally healthy controls using electrochemiluminescence immunoassays (ECLIA). Results. Adjusted means of NSE were significantly elevated in the MDD patients (11.73 ng/ml (9.95–13.52 95% CI) compared to the controls (6.17 ng/ml (4.55–7.78), F = 9.037, P = 0.004. Effect size for adjusted mean group difference of 5.57 ng/ml was found invariably high (Cohen’s d = 1.23). Differentiating MDD from controls, a NSE cut-off of 7.94 ng/ml showed sensitivity of 81% (95% CI 63.7–90.8) and specificity of 75% (95% CI 57.9–86.7). Adjusted levels of S100B did not differ significantly between the two groups (1.12 ng/ml (0.77–1.48) in MDD, 0.97 ng/ml (0.64–1.30) in controls). Conclusions. Our results of elevated CSF-NSE levels support neuronal pathology in MDD and the potential use of CSF-NSE as marker in clinical diagnostics. Missing group differences in S100B do not promote a specific glial pathology in depressive disorders.     

Interaction of serotonin-related genes affects short-term antidepressant response in major depressive disorder

Background

Four serotonin-related genes including guanine nucleotide binding protein beta polypeptide 3 (GNB3), 5-hydroxytryptamine receptor 1A (HTR1A; serotonin receptor 1A), 5-hydroxytryptamine receptor 2A (HTR2A; serotonin receptor 2A), and solute carrier family 6 member 4 (SLC6A4; serotonin neurotransmitter transporter) have been suggested to be candidate genes for influencing antidepressant treatment outcome. The aim of this study was to explore whether interaction among these genes could contribute to the pharmacogenomics of short-term antidepressant response in a Taiwanese population with major depressive disorder (MDD).

Methods

Included in this study were 101 MDD patients who were treated with antidepressants, 35 of whom were rapid responders and 66 non-responders after 2 weeks of treatment. We genotyped four single nucleotide polymorphisms (SNPs), including GNB3 rs5443 (C825T), HTR1A rs6295 (C-1019G), HTR2A rs6311 (T102C), and SLC6A4 rs25533, and employed the generalized multifactor dimensionality reduction (GMDR) method to investigate gene–gene interactions.

Results

Single-locus analyses showed the GNB3 rs5443 polymorphism to be associated with short-term antidepressant treatment outcome (P-value = 0.029). We did not correct for multiple testing in these multiple exploratory analyses. Finally, the GMDR approach identified a significant gene–gene interaction (P-value = 0.025) involving GNB3 and HTR2A, as well as a significant 3-locus model (P-value = 0.015) among GNB3, HTR2A, and SLC6A4.

Conclusions

These results support the hypothesis that GNB3, HTR2A, and SLC6A4 may play a role in the outcome of short-term antidepressant treatment for MDD in an interactive manner. Future research with independent replication using large sample sizes is needed to confirm the functions of the candidate genes identified in this study as being involved in short-term antidepressant treatment response.     

A psychometric evaluation of the clinician‐rated Quick Inventory of Depressive Symptomatology (QIDS‐C16) in patients with bipolar disorder

The clinician‐rated, 16‐item Quick Inventory of Depressive Symptomatology (QIDS‐C₁₆) has been extensively evaluated in patients with major depressive disorder (MDD). This report assesses the psychometric properties of the QIDS‐C₁₆ in outpatients with bipolar disorder (BD, N = 405) and MDD (N = 547) and in bipolar patients in the depressed phase only (BD‐D) (N = 99) enrolled in the Texas Medication Algorithm Project (TMAP) using classical test theory (CTT) and the Samejima graded item response theory (IRT) model. Values of coefficient alpha were very similar in BD, MDD, and BD‐D groups at baseline (α = 0.80–0.81) and at exit (α = 0.82–0.85). The QIDS‐C₁₆ was unidimensional for all three groups. MDD and BD‐D patients (n = 99) had comparable symptom levels. The BD‐D patients (n = 99) had the most, and bipolar patients in the manic phase had the least depressive symptoms at baseline. IRT analyses indicated that the QIDS‐C₁₆ was most sensitive to the measurement of depression for both MDD patients and for BD‐D patients in the average range. The QIDS‐C₁₆ is suitable for use with patients with BD and can be used as an outcome measure in trials enrolling both BD and MDD patients. Copyright © 2009 John Wiley & Sons, Ltd.     

Higher serum VGF protein levels discriminate bipolar depression from major depressive disorder

Misdiagnosis between major depressive disorder (MDD) and bipolar depression (BD) is quite common. Our previous study found significantly lower serum VGF (non-acronymic) in MDD patients. However, it is unclear whether same changes occur in BD patients. Therefore, we aimed to investigate the relationship between serum VGF levels in BD and MDD patients. General information, scores of 17-item Hamilton Depression Rating Scale (HDRS), and fasting blood samples of all participants including 30 MDD patients, 20 BD patients, and 30 healthy controls (HC) were collected. Serum VGF levels were measured by Enzyme-linked immunosorbent assay kits. Pearson correlation analysis was used to analyze correlations between serum VGF levels and clinical information. Receiver operating characteristic (ROC) curve and likelihood ratios (LRs) were used to analyze the differential potential of serum VGF. Serum VGF levels were significantly lower in MDD patients but higher in BD patients compared with HC (both P_Tukey < 0.01). No correlation was found between serum VGF levels and any data of subjects. The optimal cutoff for serum VGF in discriminating BD patients from MDD patients was ≥1093.85 pg/ml (AUC = 0.990, sensitivity of 95%, specificity of 100% and accuracy of 95%). LRs further confirmed the differential efficiency of serum VGF in distinguishing BD and MDD patients with +LR of infinity and –LR of 0. The results suggest that serum VGF level changed significantly in MDD and BD patients and serum VGF may be an indicator for differentiating BD patients from MDD patients.     

Abnormal fatty acid pattern in the superior temporal gyrus distinguishes bipolar disorder from major depression and schizophrenia and resembles multiple sclerosis

This study investigated the fatty acid composition of the postmortem superior temporal gyrus (STG), a cortical region implicated in emotional processing, from normal controls (n=15) and patients with bipolar disorder (BD, n=15), major depressive disorder (MDD, n=15), and schizophrenia (SZ, n=15). For comparative purposes, STG fatty acid composition was determined in a separate cohort of multiple sclerosis patients (MS, n=15) and normal controls (n=15). Compared with controls, patients with BD, but not MDD or SZ, exhibited abnormal elevations in the saturated fatty acids (SFA) palmitic acid (16:0), stearic acid (18:0), the polyunsaturated fatty acids (PUFA) linoleic acid (18:2n-6), arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3), and reductions in the monounsaturated fatty acid (MUFA) oleic acid (18:1n-9). The total MUFA/SFA and 18:1/18:0 ratios were lower in the STG of BD patients and were inversely correlated with total PUFA composition. MS patients exhibited a pattern of fatty acid abnormalities similar to that observed in BD patients including elevated PUFA and a lower 18:1/18:0 ratio. Collectively, these data demonstrate that BD patients exhibit a pattern of fatty acid abnormalities in the STG that is not observed in MDD and SZ patients and closely resembles MS patients.     

Transdiagnostic time‐varying dysconnectivity across major psychiatric disorders

Dynamic functional connectivity (DFC) analysis can capture time‐varying properties of connectivity. However, studies on large samples using DFC to investigate transdiagnostic dysconnectivity across schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are rare. In this study, we used resting‐state functional magnetic resonance imaging and a sliding‐window method to study DFC in a total of 610 individuals (150 with SZ, 100 with BD, 150 with MDD, and 210 healthy controls [HC]) at a single site. Using k‐means clustering, DFCs were clustered into three functional connectivity states: one was a more frequent state with moderate positive and negative connectivity (State 1), and the other two were less frequent states with stronger positive and negative connectivity (State 2 and State 3). Significant 4‐group differences (SZ, BD, MDD, and HC groups; q < .05, false‐discovery rate [FDR]‐corrected) in DFC were nearly only in State 1. Post hoc analyses (q < .05, FDR‐corrected) in State 1 showed that transdiagnostic dysconnectivity patterns among SZ, BD and MDD featured consistently decreased connectivity within most networks (the visual, somatomotor, salience and frontoparietal networks), which was most obvious in both range and extent for SZ. Our findings suggest that there is more common dysconnectivity across SZ, BD and MDD than we previously expected and that such dysconnectivity is state‐dependent, which provides new insights into the pathophysiological mechanism of major psychiatric disorders.     

Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: A meta-analysis study

ObjectiveWe performed a systematic review and meta-analysis to estimate brain-derived neurotrophic factor (BDNF) level in patients with major depressive disorder (MDD) after electroconvulsive therapy (ECT).MethodA comprehensive search of the Cochrane Library, MEDLINE, LILACS, Grey literature, and EMBASE was performed for papers published from January 1990 to April 2016. The following key terms were searched: “major depressive disorder”, “unipolar depression”, “brain-derived neurotrophic factor”, and “electroconvulsive therapy”.ResultsA total of 252 citations were identified by the search strategy, and nine studies met the inclusion criteria of the meta-analysis. BDNF levels were increased among patients with MDD after ECT (P value = 0.006). The standardized mean difference was 0.56 (95% CI: 0.17–0.96). Additionally, we found significant heterogeneity between studies (I² = 73%).ConclusionOur findings suggest a potential role of BDNF as a marker of treatment response after ECT in patients with MDD.