Neurotransmitter system aberrations in patients with drug addiction.

Drug dependence may affect the neurotransmitter system levels in the human body. This study recruited 113 healthy control subjects, 118 heroin-dependent patients and 118 methamphetamine-dependent patients and examined the serum 5-HT, dopamine, glutamate and norepinephrine levels in the 349 volunteers. ELISA assays demonstrated that the serum 5-HT levels were significantly reduced in the drug-dependent patients, whereas the serum dopamine and glutamate levels were both significantly increased in the drug-dependent patients when compared with control subjects. In contrast, the norepinephrine levels did not exhibit a significant difference between the drug-dependent and control subjects. We also used qRT-PCR to analyze the transcriptional expression levels of 5-HT1A, 5-HT1B, dopmaine-D1 and dopamine-D2 receptors in the blood of drug-dependent patients and controls, and the results show that only 5-HT1B receptor levels were dysfunctional in the heroin abusers. In addition, our results suggest that serum 5-HT, dopamine, and glutamate levels had the potential to differ between drug abusers and controls, and combining those three potential biomarkers provided an accurate means to differentiate between the drug-dependent and control subjects. Taken together, our study reveals a differential profile of neurotransmitters in the heroin-dependent patients and methamphetamine-dependent patients, and this revelation may contribute to understanding the pathophysiology of drug addiction.

Real time three-dimensional transthoracic echocardiography evaluation in a patient with congenital pulmonary vein stenosis.

Although real time three-dimensional transthoracic echocardiography (RD-3DTTE) has been used in children with complex congenital heart diseases, the benefit of RD-3DTTE as a vision of the pulmonary veins still requires further evaluation. We present here, a 3-year-old girl with a stenosis of the left upper pulmonary vein (LUPV). Excellent images were obtained rapidly by RD-3DTTE that successfully visualized the narrowing at the junction of the LUPV. The result was demonstrated by MRI, cardiac catheterization, and operation. RD-3DTTE is a feasible and promising technique in evaluating pulmonary veins in children.

Aberrations in peripheral inflammatory cytokine levels in substance use disorders: a meta-analysis of 74 studies.

AIMS: To characterize the peripheral inflammatory cytokine profile in people with substance use disorders (SUDs). DESIGN: Systematic review and meta-analysis. SETTING: Clinical studies that evaluated peripheral blood inflammatory cytokine levels in patients with SUDs and healthy controls PARTICIPANTS: SUD patients and healthy controls. MEASUREMENTS: PubMed and Web of Science were systematically searched for relevant studies. Two investigators independently selected studies and extracted data. A total of 77 articles were included in the meta-analysis, containing 5649 patients with SUDs and 4643 healthy controls. Data were pooled using a random-effects model by the Comprehensive Meta-Analysis version 2 software. FINDINGS: Concentrations of interleukin (IL)-6) in 32 studies, tumor necrosis factor (TNF)-α in 28 studies, IL-10 in 20 studies, IL-8 in 17 studies, C-reactive protein in 14 studies, IL-4 in 10 studies, IL-12 in seven studies, monocyte chemoattractant protein (MCP)-1 in 6 studies, TNF-receptor 2 (TNF-R2) in four studies and granulocyte-macrophage colony-stimulating factor (GM-CSF) in three studies were significantly higher in patients with SUDs compared with healthy controls, while concentrations of leptin in 14 studies were significantly lower in patients with SUDs compared with healthy controls. The findings were inconclusive for the associations between interferon-γ, IL-1ß, IL-2, IL-1 receptor antagonist (IL-1RA), transforming growth factor (TGF)-ß1, G-CSF, C-C motif chemokine 11, TGF-α and SUDs. CONCLUSIONS: People with substance use disorders (SUDs) appear to have higher peripheral concentrations of IL-4, IL-6, IL-8, IL-10, IL-12, TNF-α, C-reactive protein, MCP-1, TNF-R2 and GM-CSF and lower peripheral concentrations of leptin than people without SUDs. This strengthens the view that SUD is accompanied by an inflammatory response.

Serum Exosome-Derived miR-139-5p as a Potential Biomarker for Major Depressive Disorder.

BACKGROUND: MicroRNAs (miRs) have been suggested to be biomarkers to inform the diagnosis of major depressive disorder (MDD). We have previously shown that exosome-derived miR-139-5p had potential in differentiating between patients with MDD and healthy control (HC) subjects. MATERIALS AND METHODS: To validate the potential of exosome-derived miR-139-5p as a biomarker for MDD, here we recruited 30 patients with MDD and 30 HC subjects, and used TaqMan probes to detect serum exosomal miR-139-5p levels. RESULTS: The data showed that patients with MDD had significantly increased exosomal miR-139-5p levels when compared with controls. Correlation analysis suggested that sex, age, and body mass index did not significantly affect blood exosomal miR-139-5p levels in the tested subjects. The ROC curve showed that serum-derived miR-139-5p had reasonable performance in discriminating patients with MDD and HC subjects, with a sensitivity of 0.867 and specificity of 0.767, and the AUC was 0.807. DISCUSSION: Taken together, these results demonstrated that patients with MDD were accompanied by significantly increased blood exosomal miR-139-5p levels, and exosomal miR-139-5p is a promising biomarker for the diagnosis of MDD.

The Effect of Estrogen Replacement Therapy on Alzheimer's Disease and Parkinson's Disease in Postmenopausal Women: A Meta-Analysis.

Background: Estrogen replacement therapy (ERT) is a common treatment method for menopausal syndrome; however, its therapeutic value for the treatment of neurological diseases is still unclear. Epidemiological studies were performed, and the effect of postmenopausal ERT on treating neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), was summarized through a meta-analysis. Methods: Twenty-one articles were selected using a systematic searching of the contents listed on PubMed and Web of Science before June 1, 2019. Epidemiological studies were extracted, and relevant research data were obtained from the original articles based on the predefined inclusion criteria and data screening principles. The Comprehensive Meta-Analysis Version 2 software was used to pool effective size, test heterogeneity, conduct meta-regression and subgroup analysis, and to calculate publication bias. Results: Our results showed that ERT significantly decreased the risk of onset and/or development of AD [odds ratio (OR): 0.672; 95% CI: 0.581-0.779; P < 0.001] and PD (OR: 0.470; 95% CI: 0.368-0.600; P < 0.001) compared with the control group. A subgroup and meta-regression analysis showed that study design and measure of effect were the source of heterogeneity. Age, sample size, hormone therapy ascertainment, duration of the treatment, or route of administration did not play a significant role in affecting the outcome of the meta-analysis. Conclusion: We presented evidence here to support the use of estrogen therapy for the treatment of AD and PD.

Exosomes from patients with major depression cause depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis.

Exosomal microRNAs (miRNAs) have been suggested to participate in the pathogenesis of neuropsychiatric diseases, but their role in major depressive disorder (MDD) is unknown. We performed a genome-wide miRNA expression profiling of blood-derived exosomes from MDD patients and control subjects and revealed the top differentially expressed exosomal miRNA, i.e. hsa-miR-139-5p (upregulation), had good performance to differentiate between MDD patients and controls. Tail vein injection of blood exosomes isolated from MDD patients into normal mice caused their depressive-like behaviors as determined by the forced swimming, tail suspension, and novelty suppressed feeding tests, and injection of blood exosomes isolated from healthy volunteers into unpredictable mild stress (CUMS)-treated mice alleviated their depressive-like behaviors. CUMS mice also showed significantly increased blood and brain levels of exosomal miR-139-5p. Furthermore, the depressive-like behaviors in CUMS-treated mice were rescued by intranasal injection of miR-139-5p antagomir, suggesting that increased exosomal miR-139-5p levels may mediate stress-induced depression-like behavior in mice. Both exosome treatment and miR-139-5p antagomir treatment increased hippocampal neurogenesis in the CUMS-treated mice, and treatment of exosome from MDD patients decreased hippocampal neurogenesis in the normal mice. The role of miR-139-5p in neurogenesis was validated by in vitro experiments, demonstrating that miR-139-5p is a negative regulator for neural stem cell proliferation and neuronal differentiation. Our findings together suggest that exosomes from patients with major depression caused depressive-like behaviors in mice with involvement of miR-139-5p-regulated neurogenesis. Therefore, exosomal miRNAs are promising targets for the diagnosis and treatment of MDD.

Genome-Wide, Integrative Analysis Implicates Exosome-Derived MicroRNA Dysregulation in Schizophrenia.

Genetic variants conferring risk for schizophrenia (SCZ) have been extensively studied, but the role of posttranscriptional mechanisms in SCZ is not well studied. Here we performed the first genome-wide microRNA (miRNA) expression profiling in serum-derived exosome from 49 first-episode, drug-free SCZ patients and 46 controls and identified miRNAs and co-regulated modules that were perturbed in SCZ. Putative targets of these SCZ-affected miRNAs were enriched strongly for genes that have been implicated in protein glycosylation and were also related to neurotransmitter receptor and dendrite (spine) development. We validated several differentially expressed blood exosomal miRNAs in 100 SCZ patients as compared with 100 controls by quantitative reverse transcription-polymerase chain reaction. The potential regulatory relationships between several SCZ-affected miRNAs and their putative target genes were also validated. These include hsa-miR-206, which is the most upregulated miRNA in the blood exosomes of SCZ patients and that previously reported to regulate brain-derived neurotrophic factor expression, which we showed reduced mRNA and protein levels in the blood of SCZ patients. In addition, we found 11 miRNAs in blood exosomes from the miRNA sequence data that can be used to classify samples from SCZ patients and control subjects with close to 90% accuracy in the training samples, and approximately 75% accuracy in the testing samples. Our findings support a role for exosomal miRNA dysregulation in SCZ pathophysiology and provide a rich data set and framework for future analyses of miRNAs in the disease, and our data also suggest that blood exosomal miRNAs are promising biomarkers for SCZ.

Serum Oxidative Stress Marker Levels in Unmedicated and Medicated Patients with Schizophrenia.

Oxidative stress has been suggested to be involved in schizophrenia, but studies have demonstrated inconsistent results on oxidative stress marker level/activity in patients with schizophrenia. In order to clarify the circulating oxidative stress marker level/activity in patients with schizophrenia, this study recruited 80 schizophrenia patients (40 first-episode, drug-free and 40 chronically medicated patients) and 80 controls to analyze serum activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), and levels of lipid peroxidation marker malondialdehyde (MDA) in schizophrenia patients, and whether they associate with the severity of the disease. We showed that only serum GSH-Px activity was significantly reduced in unmedicated patients with schizophrenia when compared with control subjects, whereas the other three analyzed oxidative stress markers did not show significant differences between cases and controls. Moreover, our results demonstrated that chronic medication increased GSH-Px activity and MDA levels in patients with schizophrenia, but reduced SOD activity in the patients. We also found that short-term antipsychotic treatments on the patients with schizophrenia reduced the SOD activity. Correlation analyses indicated that the oxidative stress marker activity/level is not significantly associated with the severity of schizophrenia, except that SOD level correlated with PANSS positive score significantly. Taken together, the data from the present study suggested that the dysfunctions of oxidative stress markers in patients with schizophrenia were mainly caused by antipsychotics, emphasizing increased oxidative stress as a potential side effect of antipsychotics on the patients.