Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial.

BACKGROUND: Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression. METHODS: A total of 71 adolescents with depression (aged 13-24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR. RESULTS: Significant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline. LIMITATIONS: The trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect. CONCLUSIONS: Our results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.

Low-frequency repetitive transcranial magnetic stimulation over the right orbitofrontal cortex for patients with first-episode schizophrenia: A randomized, double-blind, sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) has been used in the treatment of patients with schizophrenia. The conventional targets of rTMS treatment are the dorsolateral prefrontal cortex (DLPFC) and temporoparietal cortex (TPC). However, the efficacy of these two treatment strategies was quite heterogeneous. Structural and functional abnormalities of the orbitofrontal cortex (OFC) in schizophrenia are closely related to negative symptoms. We sought to determine whether 1 Hz rTMS over the right OFC is effective in treating patients with first-episode schizophrenia. In this study, eighty-nine patients with drug-naïve, first-episode schizophrenia were randomly divided into the rTMS (n = 47) or sham stimulation (n = 42) groups, with both groups receiving twenty sessions of 1 Hz rTMS treatment. The PANSS was assessed at baseline, day 10, and day 20, and MATRICS Consensus Cognitive Battery (MCCB) was implemented to assess the cognitive impairment at baseline and day 20. Results showed that patients in the active rTMS group had more improvement in clinical symptoms and cognitive deficits than patients in sham group at day 20. In conclusion, 1 Hz rTMS over OFC can improve psychotic symptoms and cognitive functions in schizophrenic patients. Our study provides a new alternative for the treatment of negative symptoms and cognitive deficits in schizophrenia.

CCRT and aerobic exercise: a randomised controlled study of processing speed, cognitive flexibility, and serum BDNF expression in schizophrenia.

Computerised cognitive remediation therapy (CCRT) and aerobic exercise are often used to rehabilitate social functioning in patients with schizophrenia. However, there is limited knowledge regarding the effects of CCRT combined with aerobic exercise on cognitive function and brain-derived neurotrophic factor (BDNF) levels in patients with schizophrenia and cognitive impairment. Ninety-six patients with schizophrenia and cognitive impairment were included in this study and randomly divided into control, aerobic exercise (AE), and CCRT combined with aerobic exercise (CAE) groups. Changes in processing speed and cognitive flexibility at week 8 were evaluated as primary and secondary cognitive outcomes using the Trail Making Test: Part A, the Brief Assessment of Cognition in Schizophrenia: Symbol Coding Test, and the Stroop Colour-Word Test. Positive and Negative Syndrome Scale (PANSS) scores and serum BDNF expression were determined as other secondary outcomes. The CAE group showed significantly better performance in terms of changes in processing speed and cognitive flexibility than the control and AE groups at week 8 (p < 0.05); however, no significant improvements in processing speed and cognitive flexibility were found between the control and AE groups. The CAE group showed significant improvements in the PANSS negative symptoms than the control group at week 8 (p < 0.05), but the AE group showed no significant difference in the changes of PANSS negative symptoms when compared with the other two groups. The CAE group and AE group showed a greater increase in serum BDNF levels than the control group (p < 0.01), but there was no significant difference in serum BDNF expression between the CAE group and AE group. In conclusion, 8-week CCRT combined with aerobic exercise may improve some cognitive performance and negative symptoms in patients with schizophrenia. Aerobic exercise may have an immediate effect on serum BDNF levels rather than cognitive function.

Multi-omics analysis identifies rare variation in leptin/PPAR gene sets and hypermethylation of ABCG1 contribute to antipsychotics-induced metabolic syndromes.

Antipsychotic-induced metabolic syndrome (APs-induced Mets) is the most common adverse drug reaction, which affects more than 60% of the psychiatric patients. Although the etiology of APs-induced Mets has been extensively investigated, there is a lack of integrated analysis of the genetic and epigenetic factors. In this study, we performed genome-wide, whole-exome sequencing (WES) and epigenome-wide association studies in schizophrenia (SCZ) patients with or without APs-induced Mets to find the underlying mechanisms, followed by in vitro and in vivo functional validations. By population-based omics analysis, we revealed that rare functional variants across in the leptin and peroxisome proliferator-activated receptors (PPARs) gene sets were imbalanced with rare functional variants across the APs-induced Mets and Non-Mets cohort. Besides, we discovered that APs-induced Mets are hypermethylated in ABCG1 (chr21:43642166-43642366, adjusted P < 0.05) than Non-Mets, and hypermethylation of this area was associated with higher TC (total cholesterol) and TG (triglycerides) levels in HepG2 cells. Candidate genes from omics studies were furtherly screened in C. elegans and 17 gene have been verified to associated with olanzapine (OLA) induced fat deposit. Among them, several genes were expressed differentially in Mets cohort and APs-induced in vitro/in vivo models compared to controls, demonstrating the validity of omics study. Overexpression one of the most significant gene, PTPN11, exhibited compromised glucose responses and insulin resistance. Pharmacologic inhibition of PTPN11 protected HepG2 cell from APs-induced insulin resistance. These findings provide important insights into our understanding of the mechanism of the APs-induced Mets.

miR143-3p-Mediated NRG-1-Dependent Mitochondrial Dysfunction Contributes to Olanzapine Resistance in Refractory Schizophrenia.

BACKGROUND: Olanzapine is an effective antipsychotic medication for treatment-resistant schizophrenia (TRS); however, the therapeutic effectiveness of olanzapine has been found to vary in individual patients. It is imperative to unravel its resistance mechanisms and find reliable targets to develop novel precise therapeutic strategies. METHODS: Unbiased RNA sequencing analysis was performed using homogeneous populations of neural stem cells derived from induced pluripotent stem cells in 3 olanzapine responder (reduction of Positive and Negative Syndrome Scale score ≥25%) and 4 nonresponder (reduction of Positive and Negative Syndrome Scale score <25%) inpatients with TRS. We also used a genotyping study from patients with TRS to assess the candidate genes associated with the olanzapine response. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9-mediated genome editing, neurologic behavioral tests, RNA silencing, and microRNA sequencing were used to investigate the phenotypic mechanisms of an olanzapine resistance gene in patients with TRS. RESULTS: Neuregulin-1 (NRG-1) deficiency-induced mitochondrial dysfunction is associated with olanzapine treatment outcomes in TRS. NRG-1 knockout mice showed schizophrenia-relevant behavioral deficits and yielded olanzapine resistance. Notably, miR143-3p is a critical NRG-1 target related to mitochondrial dysfunction, and miR143-3p levels in neural stem cells associate with severity to olanzapine resistance in TRS. Meanwhile, olanzapine resistance in NRG-1 knockout mice could be rescued by treatment with miR143-3p agomir via intracerebral injection. CONCLUSIONS: Our findings provide direct evidence of olanzapine resistance resulting from NRG-1 deficiency-induced mitochondrial dysfunction, and they link olanzapine resistance and NRG-1 deficiency-induced mitochondrial dysfunction to an NRG-1/miR143-3p axis, which constitutes a novel biomarker and target for TRS.

Efficient removal of aqueous Cr(VI) with ferrous sulfide/N-doped biochar composites: Facile, in-situ preparation and Cr(VI) uptake performance and mechanism.

FeS nanoparticles loaded on nitrogen-doped biochar (FeS/BNC) were fabricated by pyrolyzing coffee husks pretreated with Mohr's salt. The nitrogen doping and FeS loading of biochar are simultaneously achieved in one-pot pyrolysis. The elemental analysis, SEM, TEM, XRD, XPS, Raman, FTIR and N2 adsorption-desorption technologies were used to characterize the composition and structure of FeS/NBC. The appraisement for removing aqueous Cr(VI) testified that FeS/NBC offered a synergistic scavenging effect of Cr(VI) by FeS and NBC. The effect of crucial experimental conditions (FeS/NBC dosage, foreign ions, initial pH and concentration of Cr(VI) solution) were investigated. The Cr(VI) removal capacity was as high as 211.3 ± 26 mg g-1 under the optimized condition. The practicability of FeS/NBC was examined by using simulated actual samples from tap water and lake water. The mechanism examination showed that surface adsorption/reduction and solution reduction were implicated in the removal of Cr(VI). The current work introduces a novel FeS/NBC composite prepared by an in situ pyrolysis method with excellent potential for chromium pollution remediation.

The association between polymorphism of norepinephrine transporter G1287A and major depressive disorder, antidepressant response: a meta-analysis.

OBJECTIVES: Massive research has examined the cause of major depressive disorder (MDD) and accumulating evidence has revealed that the gene for the norepinephrine transporter (NET) is involved in MDDs etiology as well as the antidepressant response. The G1287A (rs5569, GRCh38, Chromosome 16, 55697923) is located in the exon 9 region of the SLC6A2 gene. It was found to be connected with MDD and antidepressant response in people of different genetic ancestries. However, the results are still inconsistent. METHODS: A meta-analysis was conducted to evaluate the overall association of rs5569 polymorphisms with MDD and the antidepressant response. RESULTS: Sixteen articles that studied the connection between the G1287A polymorphism and MDD or antidepressant response were identified, and their outcomes revealed there was a significant connection between the polymorphisms and MDD and antidepressant response. Our study indicated that the GG genotype may be a protection factor against the development of MDD [odds ratio (OR = 0.78, 95% confidence interval (CI) = 0.64-0.96, P = 0.02 for Asian population; OR = 0.79, 95% CI = 0.63-0.98, P = 0.03 for Han Chinese population] while the GG genotype had a worse antidepressant response (OR = 0.49, 95% CI = 0.25-0.94, P = 0.03). CONCLUSIONS: NET G1287A polymorphisms are involved in the etiology of MDD and antidepressant response.