Gender differences in brain region activation during verbal fluency task as detected by fNIRS in patients with depression.

BACKGROUND: Gender plays a role in the mechanisms of depression, but fewer studies have focused on gender differences in the abnormal activation of brain regions when patients perform specific cognitive tasks. METHODS: A total of 110 major depressive disorder (MDD) patients and 106 healthy controls were recruited. The relative change in oxygen-haemoglobin (oxy-Hb) concentration during the verbal fluency task were measured by a 52-channel near-infra-red spectroscopy (NIRS) system. Differences in brain region activation between patients and healthy controls and between genders of depression patients were compared. RESULTS: MDD patients demonstrated significantly decreased [oxy-Hb] changes in the right inferior frontal gyrus (p = 0.043) compared to healthy controls. A marked increase in leftward functional language lateralisation in the inferior frontal gyrus was observed in the MDD group in contrast to the HC group (p = 0.039). Furthermore, female patients in the MDD group exhibited significant reductions in [oxy-Hb] changes in the right frontal region (specifically, the superior and middle frontal gyrus; p = 0.037) compared with male patients. CONCLUSIONS: Gender impacts depression-related brain activation during cognitive tasks, potentially influencing depression's pathogenesis.

Comparisons of Accelerated Continuous and Intermittent Theta Burst Stimulation for Treatment-Resistant Depression and Suicidal Ideation.

BACKGROUND: Suicidal ideation is a substantial clinical challenge in treatment-resistant depression (TRD). Recent work demonstrated promising antidepressant effects in TRD patients with no or mild suicidal ideation using a specific protocol termed intermittent theta burst stimulation (iTBS). Here, we examined the clinical effects of accelerated schedules of iTBS and continuous TBS (cTBS) in patients with moderate to severe suicidal ideation. METHODS: Patients with TRD and moderate to severe suicidal ideation (n = 44) were randomly assigned to receive accelerated iTBS or cTBS treatment. Treatments were delivered in 10 daily TBS sessions (1800 pulses/session) for 5 consecutive days (total of 90,000 pulses). Neuronavigation was employed to target accelerated iTBS and cTBS to the left and right dorsolateral prefrontal cortex (DLPFC), respectively. Clinical outcomes were evaluated in a 4-week follow-up period. RESULTS: Accelerated cTBS was superior to iTBS in the management of suicidal ideation (pweek 1 = .027) and anxiety symptoms (pweek 1 = .01). Accelerated iTBS and cTBS were comparable in antidepressant effects (p < .001; accelerated cTBS: mean change at weeks 1, 3, 5 = 49.55%, 54.99%, 53.11%; accelerated iTBS: mean change at weeks 1, 3, 5 = 44.52%, 48.04%, 51.74%). No serious adverse events occurred during the trial. One patient withdrew due to hypomania. The most common adverse event was discomfort at the treatment site (22.73% in both groups). CONCLUSIONS: These findings provide the first evidence that accelerated schedules of left DLPFC iTBS and right DLPFC cTBS are comparably effective in managing antidepressant symptoms and indicate that right DLPFC cTBS is potentially superior in reducing suicidal ideation and anxiety symptoms.

Elevated Plasma Levels of Mature Brain-Derived Neurotrophic Factor in Major Depressive Disorder Patients with Higher Suicidal Ideation.

Several pieces of evidence show that signaling via brain-derived neurotrophic factor (BDNF) and its receptor, tropomycin receptor kinase B (TrkB), as well as inflammation, play a crucial part in the pathophysiology of depression. The purpose of our study was to evaluate plasma levels of BDNF-TrkB signaling, which are inflammatory factors in major depressive disorder (MDD) patients, and assess their associations with clinical performance. This study recruited a total sample of 83 MDD patients and 93 healthy controls (CON). All the participants were tested with the Hamilton Depression Scale (HAMD), the Beck Scale for Suicide Ideation, and the NEO Five-Factor Inventory. The plasma level of selected BDNF-TrkB signaling components (mature BDNF (mBDNF), precursor BDNF (proBDNF), tyrosine kinase B (TrkB), and tissue plasminogen activator (tPA)) and selected inflammatory factors (interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) were measured using an enzyme-linked immunosorbent assay (ELISA). Further, we performed correlation analysis to indicate the relationship between the plasma levels of the factors and clinical characteristics. Results: (i) A higher level of mBDNF and lower openness were observed in MDD patients with higher suicidal ideation than patients with lower suicidal ideation. (ii) In MDD patients, mBDNF was positively correlated with the sum score of the Beck Scale for Suicide Ideation (BSS). (iii) The levels of mBDNF, tPA, IL-1 ß and IL-6 were significantly higher in all MDD subjects compared to the healthy controls, while the levels of TrkB and proBDNF were lower in MDD subjects. Conclusion: Our study provides novel insights regarding the potential role of mBDNF in the neurobiology of the association between depression and suicidal ideation and, in particular, the relationship between BDNF-TrkB signaling, inflammatory factors, and clinical characteristics in MDD.

The roles of extracellular vesicles in major depressive disorder.

Major depressive disorder (MDD) is a serious mental disease characterized by depressed mood, loss of interest and suicidal ideation. Its rising prevalence has rendered MDD one of the largest contributors to the global disease burden. However, its pathophysiological mechanism is still unclear, and reliable biomarkers are lacking. Extracellular vesicles (EVs) are widely considered important mediators of intercellular communication, playing an important role in many physiological and pathological processes. Most preclinical studies focus on the related proteins and microRNAs in EVs, which can regulate energy metabolism, neurogenesis, neuro-inflammation and other pathophysiological processes in the development of MDD. The purpose of this review is to describe the current research progress of EVs in MDD and highlight their potential roles as biomarkers, therapeutic indicators and drug delivery carriers for the treatment of MDD.

Self-management and illness perception among cervical cancer patients: A cross-sectional study.

AIM: This study aimed to describe self-management among cervical cancer patients and to elucidate the relationship between illness perception and self-management in patients with cervical cancer. METHODS: This was a cross-sectional study. A convenience sample of 220 cervical cancer patients was recruited from the gynaecology outpatient department of a cancer hospital. Data were collected from September 2018 to February 2019. Self-management and illness perception were assessed using the Cancer Self-Management Assessment Scale and the Revised Illness Perception Questionnaire for cervical cancer, respectively. Data were analysed using Pearson correlation analysis, univariate analysis and hierarchical linear regression analysis. RESULTS: The mean score of self-management was 3.87 ± 0.53, and daily life management showed the highest score (4.18 ± 0.58), while symptom management was the lowest (3.11 ± 082). Hierarchical linear regression analysis showed that family monthly income per person, types of surgery and personal control were factors that significantly influenced self-management. CONCLUSIONS: The results demonstrate that self-management among patients with cervical cancer needs to be improved. The significant influence of illness perception offers an opportunity for nurses to improve self-management behaviours of patients with cervical cancer.

YY1 (Yin-Yang 1), a transcription factor regulating systemic inflammation, is involved in cognitive impairment of depression.

AIM: Clinical and preclinical studies suggest that alterations in the peripheral and brain immune system are associated with the pathophysiology of depression, also leading to changes in local glucose metabolism in the brain. Here, the authors identified Yin-Yang 1 (YY1), a transcription factor closely associated with central and peripheral inflammation. METHODS: Plasma levels of YY1, interleukin (IL) 6, and IL-1ß in major depressive disorder (MDD) were collected before and after treatment with vortioxetine, and correlation with clinical and cognitive scores was studied. Chronic unpredictable mild stress was treated with vortioxetine. Micropositron emission tomography (microPET) was used to analyze glucose metabolism and mRNA, and the protein level of the YY1-nuclear factor κB (NF-κB)-IL-1ß inflammatory pathway were measured in related brain regions. RESULTS: Plasma levels of YY1 and IL-1ß were significantly increased in MDD and decreased after treatment with vortioxetine. Meanwhile, the level of YY1 in plasma was negatively correlated with cognitive functions in patients with MDD and positively correlated with the level of IL-1ß in plasma. Compared with the control group, in chronic unpredictable mild stress rats, (microPET) analysis showed that the decrease of glucose metabolism in the hippocampus, entorhinal cortex, amygdala, striatum, and medial prefrontal cortex was reversed after treatment. mRNA and protein level of related molecular in YY1-NF-κB-IL-1ß inflammatory pathway decreased in the hippocampus and was reversed by vortioxetine. CONCLUSION: The current study suggests that the YY1-NF-κB-IL-1ß inflammatory pathway may play an essential role in both mood changes and cognitive impairment in depression, and may be associated with changes in glucose metabolism in emotion regulation and cognition. These findings provide new evidence for the inflammatory mechanisms of depression.

Fatalism and metaphor in Confucianism: A qualitative study of barriers to genetic testing among first-degree relatives of hereditary cancer patients from China.

OBJECTIVE: Despite the benefits, the rate of genetic testing among first-degree relatives (FDRs; parents, children, and siblings) remains low, and the barriers to undergoing testing among FDRs in China are not clear. We explored the reasons why FDRs refused genetic testing. METHODS: Semi-structured face-to-face interviews were conducted with 22 patients and 27 FDRs. Participants were recruited at an urban tertiary hospital in Guangzhou, South China. We used qualitative content analysis to analyse the transcripts of audio recordings and identify major themes and subthemes. RESULTS: Three major themes emerged related to FDRs' low rate of participation in genetic testing. First, there is cognitive distance from genetic testing/cancer and a lack of knowledge of preventive medicine that deepens the 'fatalistic' attitude towards cancer among FDRs, which leads to an enormous gap between their knowledge and understanding of genetic testing. Second, medical consultation is not valued in Confucianism, and the view of cancer as 'bad news' and the risk of cancer as a curse makes cancer a metaphor, which leads to exhausting arguments when persuading FDRs to undergo genetic testing. Third, physical distance from the hospital, loss of privacy, possible discrimination in many social activities and genetic testing as a source of stress and anxiety lead FDRs to fear the disruption of their daily lives. CONCLUSIONS: There are many barriers to genetic testing among the FDRs of hereditary cancer patients originating from the national social and cultural context. Healthcare professionals should develop interventions rooted in culture and promote cancer risk communication between hereditary cancer patients and FDRs.

Effects of neuronavigation-guided rTMS on serum BDNF, TrkB and VGF levels in depressive patients with suicidal ideation.

BACKGROUND: Neuronavigation-guided high-dose repetitive transcranial magnetic stimulation (rTMS) could rapidly treat depressive patients with suicidal ideation. But the mechanism of rTMS still needs to be elucidated. This study aims to investigate if rTMS improves suicidal ideation and depressive symptoms by influencing brain-derived neurotrophic factor (BDNF), tropomysin receptor kinase B (TrkB) and VGF levels. METHODS: In the present 1-week study, 59 treatment-naive depressive patients with suicidal ideation were randomly assigned to the active (n = 31) or sham (n = 28) rTMS group. The severity of suicidal ideation and depression were measured by the Beck Scale for Suicide Ideation, the Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale. Fasting venous blood samples were collected at baseline and after treatment. Serum protein concentrations of BDNF, TrkB and VGF were measured by enzyme linked immunosorbent assay. RESULTS: We found after treatment the levels of BDNF in the active rTMS group were higher than the sham group (p = 0.011), TrkB levels were decreased in the active group (p < 0.001), VGF levels were increased in the active group (p = 0.005). Post-treatment VGF levels in the active group were higher than the sham group (p = 0.008). However, there were no significant correlation between changes in BDNF, TrkB and VGF levels and the changes in clinical variables. LIMITATIONS: Participants taking medication may affect the results. CONCLUSIONS: Our results suggest that the BDNF-TrkB pathway and VGF may be implicated in the mechanisms underlying neuronavigation-guided rTMS for treating depressive patients with suicidal ideation.

The role of reelin in the pathological mechanism of depression from clinical to rodents.

Major depressive disorder (MDD) is a devastating mental illness and the leading cause of disability worldwide. Previous studies have suggested that synaptic plasticity in the hippocampus plays an important role in depression pathogenesis. Reelin is expressed mainly in the frontal lobe and hippocampus, and is closely associated with neurodevelopment and synaptic plasticity. However, few studies have investigated its role in MDD combining clinical trials and animal experiments. We show that in a clinical trial, plasma reelin levels decreased in patients with first-episode drug-naïve MDD and increased after treatment; further, plasma reelin levels allowed to distinguish drug-naïve patients with first-episode MDD from healthy individuals. In rats, chronic mild and unpredictable stress led to a decrease in both reelin mRNA and protein levels in the hippocampus, which could be reversed by vortioxetine. Subsequent experiments confirmed that the reelin-ApoER2-NR2A /NR2B pathway regulates hippocampal synaptic plasticity and may be involved in depression or antidepressant responses. Our work contributes to a deeper understanding of MDD pathogenesis and provides new evidence that reelin should be considered a potential therapeutic target for MDD.

A pilot exploration of multi-omics research of gut microbiome in major depressive disorders.

The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis's role in MDD has an increasing attention. However, the specific mechanism of the multi-level effects of gut microbiota on host metabolism, immunity, and brain structure is unclear. Multi-omics approaches based on the analysis of different body fluids and tissues using a variety of analytical platforms have the potential to provide a deeper understanding of MGB axis disorders. Therefore, the data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naïve MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1ß concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1ß and lipids (as an example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial.

Roles of calcium-dependent protein kinases mediated reactive oxygen species homeostasis in inducing resistance of apples by acibenzolar-S-methyl.

This study was carried out to investigate the effect of acibenzolar-S-methyl (ASM) and ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA) treatments on calcium-dependent protein kinases (CDPKs) and reactive oxygen species (ROS) metabolism in apples. Postharvest ASM treatment increased H2O2 content, reduced glutathione and ascorbic acid contents, and NADPH oxidase, peroxidase, ascorbate peroxidase, superoxide dismutase and glutathione reductase activities and retarded catalase activity and MdCAT expression in apples. ASM treatment enhanced MdSOD, MdPOD, MdAPX, MdGR, MdCDPK1, MdCDPK4, MdCDPK5, MdCDPK7, and MdCDPK21 expressions in apples. However, EGTA + ASM treatments suppressed H2O2, glutathione and ascorbic acid contents, NADPH oxidase, peroxidase, superoxide dismutase, ascorbate peroxidase and glutathione reductase activities. EGTA + ASM treatments suppressed the selected genes expressions in ROS metabolism and CDPKs, but up-regulated MdCAT expression in apples. These findings suggest that CDPKs play a vital role in regulating ROS metabolism and involve in inducing resistance in apples by ASM.

Mitogen-Activated Protein Kinase Cascade and Reactive Oxygen Species Metabolism are Involved in Acibenzolar-S-Methyl-Induced Disease Resistance in Apples.

Apple fruits were subjected to dipping treatment to explore the effects of acibenzolar-S-methyl (ASM) and the mitogen-activated protein kinase (MAPK) inhibitor PD98059 on lesion growth in fruits inoculated with Penicillium expansum. We investigated the roles of the MAPK cascade and reactive oxygen species metabolism in disease resistance in apples. ASM treatment inhibited lesion growth; suppressed catalase (CAT) activity; increased H2O2 content; reduced glutathione and ascorbic acid contents; and increased glutathione reductase, ascorbate peroxidase, peroxidase, superoxide dismutase, and NADPH oxidase activities. Moreover, ASM upregulated MdSOD, MdPOD, MdGR, MdAPX, MdMAPK4, MdMAPK2, and MdMAPKK1 expressions and downregulated MdCAT and MdMAPK3 expressions. PD98059 + ASM treatment increased CAT activity and MdCAT and MdMAPK3 expressions; inhibited MdSOD, MdPOD, MdGR, MdAPX, MdMAPK4, MdMAPK2, and MdMAPKK1 expressions; reduced superoxide dismutase, peroxidase, ascorbate peroxidase, and glutathione reductase activities; and reduced glutathione content in apples. These findings indicate that ASM induces disease resistance in apples by regulating the expressions of key genes involved in reactive oxygen species metabolism and the MAPK cascade.

Influences of postharvest ATP treatment on storage quality and enzyme activity in sucrose metabolism of Malus domestica.

The respiratory metabolism of apples remains vigorous after harvest, which can accelerate the consumption of sugar, organic acid, and other substances, thus leading to a decline in quality. The influence of postharvest ATP treatment on the changes of quality parameters and sucrose metabolism-related enzyme activity in apples was investigated in this study. The results showed that applying ATP effectively repressed the respiratory rate and weight loss and maintained higher levels of soluble solids content and flesh firmness in apples. In addition, ATP treatment enhanced succinate dehydrogenase, cytochrome oxidase, sucrose phosphate synthase, and sucrose synthase synthesis activities and reduced neutral invertase, acid invertase, and sucrose synthase cleavage activities in apples. These findings suggest that applying ATP after harvest could improve the internal quality of apples by suppressing the respiratory rate and modulating sucrose metabolism.

Diagnostic performance of individual characteristics and anthropometric measurements in detecting elevated serum alanine aminotransferase among children and adolescents.

BACKGROUND: Screening for elevated serum alanine aminotransferase (ALAT) can help identifying individuals at the risks of chronic and metabolic diseases, but blood collection is invasive and cannot be widely used for investigations. Considered as simple and inexpensive screening indices, individual characteristics and anthropometric measurements can be measured in a large crowd and may be important surrogate markers for ALAT levels. This study aimed to examine the diagnostic performance of individual characteristics and anthropometric parameters as predictive factors for discerning an elevated ALAT activity among Shenzhen children and adolescents. METHODS: A school-based screening study was performed from 9 high schools in Shenzhen during February 2017 and June 2018. Receiver operating characteristic curve was used to examine the diagnostic performance of each variable for detecting elevated ALAT. RESULTS: Altogether 7271 students aged 9-17 years were involved. The proportion of elevated ALAT greatly increased with increasing classification of BMI-z. By the sex-specific cut-offs for elevated ALAT (30 U/L boys; 19 U/L girls), BMI showed the highest area under the curve of 0.789 (95% CI 0.765-0.812) and followed by weight (0.779 [0.755-0.802]), BMI-z (0.747 [0.722-0.772]), height (0.622 [0.597-0.647]), and age (0.608 [0.584-0.632]), while height-z was not capable. With the cut-off of 67.8 kg for weight and 22.6 kg/m2 for BMI, the accuracy to identify elevated ALAT was 87.1% for weight and 82.9% for BMI. CONCLUSIONS: The presence of elevated ALAT was more common in overweight or obese children and adolescents. BMI and weight had the superiority of detecting elevated ALAT, followed by BMI-z, height, and age.

The prevalence and correlates of symptom distress and quality of life in Chinese oesophageal cancer patients undergoing chemotherapy after radical oesophagectomy.

PURPOSE: The current study was designed to describe the symptom distress and quality of life (QoL) in Chinese oesophageal cancer patients undergoing chemotherapy after radical oesophagectomy and to identify the factors that influenced symptom distress and the relationship between symptom distress and QoL. METHODS: The sample consisted of 102 oesophageal cancer patients undergoing chemotherapy after radical oesophagectomy. The patients completed the Chinese versions of the M.D. Anderson Symptom Inventory (MDASI, an instrument that measures symptom distress), the Hospital Anxiety and Depression Scale (HADS), the Medical Coping Modes Questionnaire (MCMQ) and the Functional Assessment of Cancer Treatment-General (FACT-G, an instrument that measures QoL). RESULTS: The symptoms and symptom interference scores of the patients in the current research were 3.62 (SD 1.66) and 2.94 (SD 1.76), respectively. Occupation after illness, anxiety, types of surgery, whether chemotherapy was on schedule and confrontation coping strategies were factors that influenced symptom distress. There was a negative relationship between symptom distress and QoL scores. CONCLUSION: Oesophageal cancer patients receiving chemotherapy suffer many limitations due to symptom distress and disruptions in their QoL. Oesophageal cancer patients should be assessed regularly and should be supported on an ongoing basis.