Jianjun Chen

Left versus right repetitive transcranial magnetic stimulation in treating major depression: a meta-analysis of randomised controlled trials.

Although the majority of randomised controlled trials suggest that major depressive disorder (MDD, major depression) and treatment-resistant depression can be effectively treated by applying either high- (HF) or low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) to the left and right dorsolateral prefrontal cortex (DLPFC), respectively, it is not clear which rTMS approach is more effective or safer. This systematic review and meta-analysis was conducted on randomised controlled trials on HF and LF rTMS applied to the left and right DLPFC, respectively, for the treatment of MDD. Eight randomised controlled trials composed of 249 patients were selected to compare the effects of LF (≤ 1 Hz) rTMS over the right DLPFC to HF (10-20 Hz) rTMS over the left DLPFC. The therapeutic effects of both approaches were similar (odds ratio (OR) = 1.15; 95% confidence interval = 0.65-2.03). Dropout analysis based on only two studies was insufficient to draw a conclusion on the tolerability of LF rTMS. The pooled examination demonstrated that both rTMS methods were equally effective therapies for MDD. However, considering that LF right-sided rTMS produces fewer side effects and is more protective against seizures, its clinical applicability shows greater promise and should be explored further.

Minimally Invasive Surgery for Spontaneous Supratentorial Intracerebral Hemorrhage A Meta-Analysis of Randomized Controlled Trials

Background and Purpose— There has been a nonstandard surgical procedure and extensive international controversy in minimally invasive surgery (MIS) for the management of spontaneous supratentorial intracerebral hemorrhage. This meta-analysis assessed the effectiveness of MIS as compared with other treatment options, including conservative medical treatment and conventional craniotomy, in patients with supratentorial intracerebral hemorrhage. Methods— PubMed, Embase, Cochrane Controlled Trials Register (CCTR), Web of Science, European Association for Grey Literature Exploitation (EAGLE), National Technical Information Service (NTIS), Current Controlled Trials, Clinical Trials, International Clinical Trials Registry, Internet Stroke Center, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI) (last searched December 2011) were searched. Randomized controlled trials on MIS in patients with computed tomography-confirmed supratentorial intracerebral hemorrhage were included. We excluded low-quality randomized controlled trials. The death or dependence at the end of follow-up was defined as the primary outcome, and the death at the end of follow-up was defined as the secondary outcome. Results— The 313 randomized controlled trials met the included criteria. We only analyzed 12 high-quality randomized controlled trials involving 1955 patients. The quality of the included trials was consistently high. OR of the primary outcome and secondary outcome of MIS both showed significant reductions (OR, 0.54, P<0.00001; OR, 0.53, P<0.00001). Conclusions— Patients with supratentorial intracerebral hemorrhage may benefit more from MIS than other treatment options. The most likely candidates to benefit from MIS are both sexes, age of 30 to 80 years with superficial hematoma, Glasgow Coma Scale score of ≥9, hematoma volume between 25 and 40mL, and within 72 hours after onset of symptoms. Our study could help select appropriate patients for MIS and guide clinicians to optimize treatment strategies in supratentorial intracerebral hemorrhage.

Blend Sign on Computed Tomography Novel and Reliable Predictor for Early Hematoma Growth in Patients With Intracerebral Hemorrhage

Background and Purpose— Early hematoma growth is not uncommon in patients with intracerebral hemorrhage and is an independent predictor of poor functional outcome. The purpose of our study was to report and validate the use of our newly identified computed tomographic (CT) blend sign in predicting early hematoma growth. Methods— Patients with intracerebral hemorrhage who underwent baseline CT scan within 6 hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Significant hematoma growth was defined as an increase in hematoma volume of >33% or an absolute increase of hematoma volume of >12.5 mL. The blend sign on admission nonenhanced CT was defined as blending of hypoattenuating area and hyperattenuating region with a well-defined margin. Univariate and multivariable logistic regression analyses were performed to assess the relationship between the presence of the blend sign on nonenhanced admission CT and early hematoma growth. Results— A total of 172 patients were included in our study. Blend sign was observed in 29 of 172 (16.9%) patients with intracerebral hemorrhage on baseline nonenhanced CT scan. Of the 61 patients with hematoma growth, 24 (39.3%) had blend sign on admission CT scan. Interobserver agreement for identifying blend sign was excellent between the 2 readers (&kgr;=0.957). The multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and presence of blend sign on baseline CT scan to be independent predictors of early hematoma growth. The sensitivity, specificity, positive and negative predictive values of blend sign for predicting hematoma growth were 39.3%, 95.5%, 82.7%, and 74.1%, respectively. Conclusions— The CT blend sign could be easily identified on regular nonenhanced CT and is highly specific for predicting hematoma growth.

A novel urinary metabolite signature for diagnosing major depressive disorder.

Major depressive disorder (MDD) is a prevalent and debilitating mental disorder. Yet, there are no objective biomarkers available to support diagnostic laboratory testing for this disease. Here, gas chromatography-mass spectrometry was applied to urine metabolic profiling of 126 MDD and 134 control subjects. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to identify the differential metabolites in MDD subjects relative to healthy controls. The OPLS-DA analysis of data from training samples (82 first-episode, drug-naïve MDD subjects and 82 well-matched healthy controls) showed that the depressed group was significantly distinguishable from the control group. Totally, 23 differential urinary metabolites responsible for the discrimination between the two groups were identified. Postanalysis, 6 of the 23 metabolites (sorbitol, uric acid, azelaic acid, quinolinic acid, hippuric acid, and tyrosine) were defined as candidate diagnostic biomarkers for MDD. Receiver operating characteristic analysis of combined levels of these six biomarkers yielded an area under the receiver operating characteristic curve (AUC) of 0.905 in distinguishing training samples; this simplified metabolite signature classified blinded test samples (44 MDD subjects and 52 healthy controls) with an AUC of 0.837. Furthermore, a composite panel by the addition of previously identified urine biomarker (N-methylnicotinamide) to this biomarker panel achieved a more satisfactory accuracy, yielding an AUC of 0.909 in the training samples and 0.917 in the test samples. Taken together, these results suggest this composite urinary metabolite signature should facilitate development of a urine-based diagnostic test for MDD.

Metabolomic identification of molecular changes associated with stress resilience in the chronic mild stress rat model of depression

Chronic stressful events are key risk factors for major depressive disorder (MDD), yet some individuals exposed to stressful events do not develop MDD. This disparity suggests the significance of resilience to deleterious stress effects. However, the underlying molecular mechanisms of stress resilience are poorly understood. In the present study, the chronic mild stress (CMS) rat model of depression was used to reveal the individual differences in stress response. Employing a gas chromatography/mass spectrometry metabolomic approach, the molecular changes associated with stress resilience in rat cerebellum were characterized by comparing anhedonic, CMS resilient and control groups. The results showed that four cerebellar metabolites—proline, lysine, glutamine, and dihydroxyacetone phosphate—were identified as the key differential metabolites associated with stress resilience. These metabolites may play a potential role in rendering individuals less vulnerable to CMS exposure. These findings provide insight into the molecular mechanisms underlying stress resilience and shed light on novel therapeutic opportunities to augment stress resiliency.

Combined Application of NMR- and GC-MS-Based Metabonomics Yields a Superior Urinary Biomarker Panel for Bipolar Disorder

Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any single metabonomic platform alone. Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that generated a panel of five metabolite biomarkers for BD-four GC-MS-derived metabolites and one NMR-derived metabolite. This composite biomarker panel could effectively discriminate BD subjects from HC, achieving an area under receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set. Moreover, the diagnostic performance of this panel was significantly superior to the previous single platform-derived metabolite panels. Thus, the urinary biomarker panel identified here shows promise as an effective diagnostic tool for BD. These findings also demonstrate the complementary nature of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the combination of NMR spectroscopy and GC-MS can identify a more comprehensive metabolite panel than applying each platform in isolation.

Bilateral vs. unilateral repetitive transcranial magnetic stimulation in treating major depression: A meta-analysis of randomized controlled trials

Previous studies have demonstrated inconsistent findings regarding the efficacy of bilateral vs. unilateral repetitive transcranial magnetic stimulation (rTMS) in treating major depressive disorder (MDD). Therefore, this meta-analysis was conducted to compare the efficacy of these two rTMS modalities. Data were obtained from seven randomized controlled trials (RCTs) consisting of 509 subjects. Bilateral and unilateral rTMS displayed comparable efficacy in treating MDD with a pooled odds ratios of 1.06 (95% confidence interval (CI)=0.58-1.91) for response rates and 1.05 (95% CI=0.52-2.11) for remission rates. Subgroup analysis found that bilateral rTMS was equally effective in comparison with both left and right unilateral rTMS. No significant differences in drop-out rates were found. No publication bias was detected. In conclusion, the pooled examination demonstrated that bilateral rTMS displays comparable anti-depressant efficacy and acceptability to unilateral rTMS in treating MDD. These findings suggest that simultaneous rTMS of the right and left dorsolateral prefrontal cortices in MDD patients does not provide marginal benefits in terms of efficacy or acceptability. As the number of RCTs included here was limited, further large-scale multi-center RCTs are required to validate our conclusions.

Meta-analyses of comparative efficacy of antidepressant medications on peripheral BDNF concentration in patients with depression

Background Brain derived neurotrophic factor (BDNF) is one of the most important regulatory proteins in the pathophysiology of major depressive disorder (MDD). Increasing numbers of studies have reported the relationship between serum/plasma BDNF and antidepressants (ADs). However, the potential effects of several classes of antidepressants on BDNF concentrations are not well known. Hence, our meta-analyses aims to review the effects of differential antidepressant drugs on peripheral BDNF levels in MDD and make some recommendations for future research. Methods Electronic databases including PubMed, EMBASE, the Cochrane Library, Web of Science, and PsycINFO were searched from 1980 to June 2016. The change in BDNF levels were compared between baseline and post-antidepressants treatment by use of the standardized mean difference (SMD) with 95% confidence intervals (CIs). All statistical tests were two-sided. Results We identified 20 eligible trials of antidepressants treatments for BDNF in MDD. The overall effect size for all drug classes showed that BDNF levels were elevated following a course of antidepressants use. For between-study heterogeneity by stratification analyses, we detect that length of treatment and blood samples are significant effect modifiers for BDNF levels during antidepressants treatment. While both SSRIs and SNRIs could increase the BDNF levels after a period of antidepressant medication treatment, sertraline was superior to other three drugs (venlafaxine, paroxetine or escitalopram) in the early increase of BDNF concentrations with SMD 0.53(95% CI = 0.13–0.93; P = 0.009). Conclusions There is some evidence that treatment of antidepressants appears to be effective in the increase of peripheral BDNF levels. More robust evidence indicates that different types of antidepressants appear to induce differential effects on the BDNF levels. Since sertraline makes a particular effect on BDNF concentration within a short amount of time, there is potential value in exploring its relationship with BDNF and its pharmacological mechanism concerning peripheral blood BDNF. Further confirmatory trials are required for both observations.

Potential clinical utility of plasma amino acid profiling in the detection of major depressive disorder

Plasma amino acids levels were measured in first-onset treatment-naïve depressed patients (n=26) and healthy controls (n=25) using a mass spectrometry-based method. One of the major findings was that a logistic regression model constructed from tryptophan, glutamine and cysteine discriminated depressed subjects from controls with a receiver-operating-characteristic curve integral of 0.90.

Combined Metabolomics and Proteomics Analysis of Major Depression in an Animal Model: Perturbed Energy Metabolism in the Chronic Mild Stressed Rat Cerebellum

Major depressive disorder (MDD) is a highly prevalent, debilitating mental illness of importance for global health. However, its molecular pathophysiology remains poorly understood. Combined proteomics and metabolomics approaches should provide a comprehensive understanding of MDDs etiology. The present study reports novel -omics insights from a rodent model of MDD. Cerebellar samples from chronic mild stressed (CMS)-treated depressed rats and controls were compared with a focus on the differentially expressed proteins and metabolites using isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and gas chromotography/mass spectrometry (GC-MS) metabolomics techniques, respectively. The combined analyses found significant alterations associated with cerebellar energy metabolism, as indicated by (1) abnormal amino acid metabolism accompanied by corresponding metabolic enzymatic alterations and disturbed protein turnover, (2) increased glycolytic and tricarboxylic acid (TCA) cycle enzyme levels paralleled by changes in the concentrations of associated metabolites, and (3) perturbation of ATP biosynthesis through adenosine accompanied by perturbation of the mitochondrial respiratory chain. To the best of our knowledge, this study is the first to integrate proteomics and metabolomics analyses to examine the pathophysiological mechanism(s) underlying MDD in a CMS rodent model of depression. These results can offer important insights into the pathogenesis of MDD.