Association between the frontoparietal network, clinical symptoms and treatment response in individuals with untreated anorexia nervosa.

Background: Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN. Aims: The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN. Methods: In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline. Results: Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN. Conclusions: Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

New media facilitate adolescents' body dissatisfaction and eating disorders in Mainland China.

New media play a significant role in adolescents' body dissatisfaction and eating disorders in Mainland China, through shaping social standards, peers, and family dynamics. How to mitigate their adverse effects on adolescents, reduce body dissatisfaction, and prevent eating disorders is a significant social issue that demands serious consideration.

Microbiota-gut-brain axis drives overeating disorders.

Overeating disorders (ODs), usually stemming from dieting history and stress, remain a pervasive issue in contemporary society, with the pathological mechanisms largely unresolved. Here, we show that alterations in intestinal microbiota are responsible for the excessive intake of palatable foods in OD mice and patients with bulimia nervosa (BN). Stress combined with a history of dieting causes significant changes in the microbiota and the intestinal metabolism, which disinhibit the vagus nerve terminals in the gut and thereby lead to a subsequent hyperactivation of the gut-brain axis passing through the vagus, the solitary tract nucleus, and the paraventricular nucleus of the thalamus. The transplantation of a probiotic Faecalibacterium prausnitzii or dietary supplement of key metabolites restores the activity of the gut-to-brain pathway and thereby alleviates the OD symptoms. Thus, our study delineates how the microbiota-gut-brain axis mediates energy balance, unveils the underlying pathogenesis of the OD, and provides potential therapeutic strategies.

Chinese university students showed less disordered eating during the COVID-19 campus lockdown.

OBJECTIVE: The rapid spread of the Omicron variant of COVID-19 in China had resulted in campus lockdown in many universities since February 2022, profoundly affecting students' daily lives. Campus lockdown conditions differ considerably from home quarantine, so that the eating patterns of university students may be different. Thus, the current study aimed to: (1) investigate university students' eating patterns during campus lockdown; (2) identify factors associated with their disordered eating. METHOD: An online survey about recent life changes, disordered eating, stress, depression, and anxiety was carried out from April 8th to May 16th, 2022. A total of 2541 responses from 29 provinces/cities of China were received. RESULTS: 2213 participants were included in the main analysis, and other 86 participants were analyzed separately as a subgroup due to their diagnosis of eating disorder. Participants who were undergoing campus lockdown (the lockdown group) showed less disordered eating than those who had never been in campus lockdown (the never-lockdown group), as well as those who had experienced campus lockdown before (the once-lockdown group). However, they perceived more stress and felt more depressed. Being female, higher BMI, gaining weight, increasing exercise, spending more time on social media, higher level of depression and anxiety were all related to disordered eating in the lockdown group. CONCLUSIONS: Disordered eating among Chinese university students was less prevalent during campus lockdown due to the strict and regular diet. However, there is a potential risk of "revenge eating" after campus lockdown ends. Thus, there should be further tracking and related prevention. LEVEL OF EVIDENCE: IV, uncontrolled trials without any interventions.

Identification of two key UDP-glycosyltransferases responsible for the ocotillol-type ginsenoside majonside-R2 biosynthesis in Panax vietnamensis var. fuscidiscus.

MAIN CONCLUSION: Two UDP-glycosyltransferases from Panax vienamensis var. fuscidiscus involved in ocotillol-type ginsenoside MR2 (majonside-R2) biosynthesis were identified. PvfUGT1 and PvfUGT2 sequentially catalyzes 20S,24S-Protopanxatriol Oxide II and 20S,24R-Protopanxatriol Oxide I to pseudoginsenoside RT4/RT5 and RT4/RT5 to 20S, 24S-MR2/20S, 24S-MR2. Ocotilol type saponin MR2 (majonside-R2) is the main active component of Panax vietnamensis var. fuscidiscus (commonly known as 'jinping ginseng') and is well known for its diverse pharmacological activities. The use of MR2 in the pharmaceutical industry currently depends on its extraction from Panax species. Metabolic engineering provides an opportunity to produce high-value MR2 by expressing it in heterologous hosts. However, the metabolic pathways of MR2 remain enigmatic, and the two-step glycosylation involved in MR2 biosynthesis has not been reported. In this study, we used quantitative real-time PCR to investigate the regulation of the entire ginsenoside pathway by MeJA (methyl jasmonate), which facilitated our pathway elucidation. We found six candidate glycosyltransferases by comparing transcriptome analysis and network co-expression analysis. In addition, we identified two UGTs (PvfUGT1 and PvfUGT2) through in vitro enzymatic reactions involved in the biosynthesis of MR2 which were not reported in previous studies. Our results show that PvfUGT1 can transfer UDP-glucose to the C6-OH of 20S, 24S-protopanaxatriol oxide II and 20S, 24R-protopanaxatriol oxide I to form pseudoginsenoside RT4 and pseudoginsenoside RT5, respectively. PvfUGT2 can transfer UDP-xylose to pseudoginsenoside RT4 and pseudoginsenoside RT5 to form 20S, 24S-MR2 and 20S, 24S-MR2. Our study paves the way for elucidating the biosynthesis of MR2 and producing MR2 by synthetic biological methods.

Comparative genomics reveals the diversification of triterpenoid biosynthesis and origin of ocotillol-type triterpenes in Panax.

Gene duplication is assumed to be the major force driving the evolution of metabolite biosynthesis in plants. Freed from functional burdens, duplicated genes can mutate toward novelties until fixed due to selective fitness. However, the extent to which this mechanism has driven the diversification of metabolite biosynthesis remains to be tested. Here we performed comparative genomics analysis and functional characterization to evaluate the impact of gene duplication on the evolution of triterpenoid biosynthesis using Panax species as models. We found that whole-genome duplications (WGDs) occurred independently in Araliaceae and Apiaceae lineages. Comparative genomics revealed the evolutionary trajectories of triterpenoid biosynthesis in plants, which was mainly promoted by WGDs and tandem duplication. Lanosterol synthase (LAS) was likely derived from a tandem duplicate of cycloartenol synthase that predated the emergence of Nymphaeales. Under episodic diversifying selection, the LAS gene duplicates produced by γ whole-genome triplication have given rise to triterpene biosynthesis in core eudicots through neofunctionalization. Moreover, functional characterization revealed that oxidosqualene cyclases (OSCs) responsible for synthesizing dammarane-type triterpenes in Panax species were also capable of producing ocotillol-type triterpenes. Genomic and biochemical evidence suggested that Panax genes encoding the above OSCs originated from the specialization of one OSC gene duplicate produced from a recent WGD shared by Araliaceae (Pg-ß). Our results reveal the crucial role of gene duplication in diversification of triterpenoid biosynthesis in plants and provide insight into the origin of ocotillol-type triterpenes in Panax species.

Hypermethylation of the serotonin transporter gene and paternal parenting styles in untreated anorexia nervosa patients: A pilot study.

Purpose: It has been reported that serotonergic systems and parenting styles are involved in the pathogenesis of anorexia nervosa (AN). The present study made attempts to examine the DNA methylation profiles in the promoter region of serotonin transporter (5-HTT) encoding gene SLC6A4, and explore the association between the methylation level and severity of symptoms, 5-HTT linked polymorphic region (5-HTTLPR) genotypes and parenting styles in untreated Chinese Han AN patients. Methods: Ninety-one untreated female AN patients (ANs) and eighty-seven matched healthy controls (HCs) were analyzed for DNA methylation status at CpG islands in the promoter region of SLC6A4 using MassARRY EpiTYPER, and genotypes of 5-HTTLPR using PCR-RFLP. The severity of eating disorder (ED) symptoms was evaluated by body mass index (BMI) and Questionnaire Version of the Eating Disorders Examination (EDE-Q 6.0), and part of participants were assessed parenting styles using the short Chinese Egna Minnen av Barndoms Uppfostra (s-EMBU-C). Results: ANs had greater methylation levels at CpG26.27.28, CpG 31.32, and CpG 37 than HCs (P = 0.039, 0.042, 0.018 respectively). A positive association of methylation level at CpG26.27.28 with ED symptoms detected by EDEQ-6.0 was discovered in AN group (r = 0.216, P = 0.047). Methylation level at CpG26.27.28 was showed to be or tend to be positively correlated with the parenting styles of paternal rejection (r = 0.425, P = 0.038) and paternal overprotection (r = 0.362, P = 0.062) in ANs. No significant differences were found in SLC6A4 promoter region methylation levels among 5-HTTLPR genotypes in our samples (P > 0.05) and no interaction effect between 5-HTTLPR genotypes and parenting styles on SLC6A4 promoter region methylation was observed (P > 0.05). Conclusions: This study suggested that hypermethylation of SLC6A4 promoter region may be implicated in the pathological mechanisms of untreated Chinese Han female ANs, which is possibly associated with poor parenting styles. This finding may provide a direction for the epigenetic and family treatments for ANs and further investigation with larger samples is warranted.

Anorexia nervosa and gut microbiome: implications for weight change and novel treatments.

INTRODUCTION: Host-microbiota interactions may be involved in many physical and psychological functions ranging from the digestion of food, maintenance of immune homeostasis, to the regulation of mood and cognition. Microbiome dysbiosis has been consistently described in many diseases. The pathogenesis and weight regulation mechanism in anorexia nervosa (AN) also seem to be implicated in the dynamic bidirectional adjustment of the microbiota-gut-brain axis. This review aims at elucidating this relationship. AREA COVERED: This review starts with a description of pathogenic gut-brain pathways. Next, we focus on the latest research on the associations between gut microbiota and weight change in the condition of AN. The strategies to alter the intestinal microbiome for the treatment of this disorder are discussed, including dietary, probiotics, prebiotics, synbiotics, and fecal microbiota transplantation. EXPERT OPINION: Gut microbiome is inextricably linked to AN. It may regulate weight gain in the process of refeeding via the microbiota-gut-brain axis, while the specific mechanism has yet to be clearly established. In the future, a better understanding of gut microbiome could have implications for developing microbiome-based prevention, diagnostics and therapies.

Metabolomics changes after rTMS intervention reveal potential peripheral biomarkers in methamphetamine dependence.

Methamphetamine is one of the most commonly used drugs around the world, leading to serious public health and psychiatric problems. Due to the lackness of objective laboratory evaluation indicators, the molecular mechanisms of methamphetamine dependence still remain unclear. Previous evidence demonstrated that repetitive transcranial magnetic stimulation (rTMS) may be useful in treating drug addiction. The aim of this study was to identify and validate plasma metabolomics biomarkers in patients with methamphetamine use disorder before and after rTMS intervention. An untargeted gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) based metabolomics approach was applied to characterize the metabolic profile of forty methamphetamine dependent subjects and thirty-eight healthy controls in peripheral blood mononuclear cells (PBMCs). Patients were randomized to receive either rTMS or sham over the DLPFC for four weeks (20 daily sessions, 900 pulses per day). Cognitive function were assessed before and after rTMS intervention. Eight PBMC metabolites responsible for distinguishing real rTMS from sham treatment were identified. These metabolites were mainly involved in energy metabolism and oxidative stress. Compared with baseline, the expression of three metabolites was reversed after rTMS intervention: alpha-tocopherol, glyceric acid and fumaric acid. Changes of the alpha-tocopherol were associated with cognitive function improvement following rTMS. These findings suggest that energy metabolism and oxidative stress system may be associated with the effect of rTMS on cognitive function in methamphetamine dependence, and warrant further investigation.

Identification of two UDP-glycosyltransferases involved in the main oleanane-type ginsenosides in Panax japonicus var. major.

MAIN CONCLUSION: Two UDP-glycosyltransferases from Panax japonicus var. major were identified, and the biosynthetic pathways of three oleanane-type ginsenosides (chikusetsusaponin IVa, ginsenoside Ro, zingibroside R1) were elucidated. Chikusetsusaponin IVa and ginsenoside Ro are primary active components formed by stepwise glycosylation of oleanolic acid in five medicinal plants of the genus Panax. However, the key UDP-glycosyltransferases (UGTs) in the biosynthetic pathway of chikusetsusaponin IVa and ginsenoside Ro are still unclear. In this study, two UGTs (PjmUGT1 and PjmUGT2) from Panax japonicus var. major involved in the biosynthesis of chikusetsusaponin IVa and ginsenoside Ro were identified based on bioinformatics analysis, heterologous expression and enzyme assays. The results show that PjmUGT1 can transfer a glucose moiety to the C-28 carboxyl groups of oleanolic acid 3-O-ß-D-glucuronide and zingibroside R1 to form chikusetsusaponin IVa and ginsenoside Ro, respectively. Meanwhile, PjmUGT2 can transfer a glucose moiety to oleanolic acid 3-O-ß-D-glucuronide and chikusetsusaponin IVa to form zingibroside R1 and ginsenoside Ro. This work uncovered the biosynthetic mechanism of chikusetsusaponin IVa and ginsenoside Ro, providing the rational production of valuable saponins through synthetic biology strategy.

The Potential Regulatory Network of Glutamate Metabolic Pathway Disturbance in Chinese Han Withdrawal Methamphetamine Abusers.

OBJECTS: To explore the long-term influence of methamphetamine abuse on metabolomics character, with gas chromatography-mass spectrometry (GS-MS) technology, and the potential regulatory network using the bioinformatics method. METHODS: Forty withdrawal methamphetamine abusers (WMA) were recruited from Shanghai Gaojing Forced Isolation Detoxification Institute. Forty healthy controls (HC) were recruited from society. GS-MS technology was used to detect metabolic products in serum. A bioinformatics method was used to build a regulatory network. Q-PCR was used to detect the candidate gene expressions, and ELISA was used to detect the regulatory enzyme expressions. RESULTS: Four pathways were significantly changed in the MA compared to the HC: (1) the arginine synthesis pathway, (2) alanine, aspartic acid and glutamate metabolic pathway, (3) cysteine and methionine metabolic pathway, and (4) the ascorbate and aldarate pathway (enrichment analysis p < 0.05, Impactor factor > 0.2). When focusing on the 'Alanine, aspartate, and glutamate metabolism' pathway, a regulatory network was established, and the expression of candidate regulatory genes and enzymes was verified. It was found that the expression of DLG2 (Discs large MAGUK scaffold protein 2), PLA2G4 (Phospholipase A2 group IVE), PDE4D (Phosphodiesterase 4D), PDE4B (Phosphodiesterase 4B), and EPHB2 (Ephrin type-B receptor 2) were significantly different between the two groups (p < 0.05), However, after adjusting for age and BMI, only DLG2, PLA2G4, and EPHB2 remained significant (p < 0.05). The expression of enzymes was not significantly different (p > 0.05). CONCLUSION: Methamphetamine abuse influences the metabolic process in the long term, and DLG2, PLA2G4, and EPHB2 may regulate the glutamate metabolism pathway.

Effectiveness and influencing factors of online education for caregivers of patients with eating disorders during COVID-19 pandemic in China.

OBJECTIVE: The goals were twofold: To estimate the depression and anxiety levels among caregivers of patients with eating disorders (ED) in China during the COVID-19 pandemic when compared with a control group, and to assess whether an online education program was effective in decreasing the anxiety and depression of the caregivers of patients with ED, and associated factors. METHOD: Caregivers of patients with ED (n = 254) and a comparison group of non-ED caregivers (N = 254) were recruited at baseline. Additionally, caregivers of patients with ED were invited into a free 4-week online education program, with an additional online group as support. Depression and anxiety levels were assessed at baseline and after the intervention. RESULTS: Caregivers of patients with ED showed significantly higher levels of depression and anxiety than the comparison group of non-ED caregivers. The online education program showed no significant effect on decreasing depression and anxiety levels of caregivers of patients with ED overall. Caregivers who had older loved ones and not living with them were more likely to decrease their depression levels. Caregivers of patients with longer illness duration were less likely to decrease their anxiety levels. DISCUSSION: These results showed that caregivers of ED patients suffered more serious psychological distress during the pandemic. A more structured and intensive online intervention with a limited number of participants might be required to address caregivers' distress in post-COVID-19 China.

Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats.

BACKGROUND: Nucleus Accumbens (NAc) is a vital brain region for the process of reward and stress, whereas microRNA plays a crucial role in depression pathology. However, the abnormality of NAc miRNA expression during the stress-induced depression and antidepressant treatment, as well as its biological significance, are still unknown. METHODS: We performed the small RNA-sequencing in NAc of rats from three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with an antidepressant, Escitalopram. We applied an integrative pipeline for analyzing the miRNA expression alternation in different model groups, including differential expression analysis, co-expression analysis, as well as a subsequent pathway/network analysis to discover both miRNA alteration pattern and its biological significance. RESULT: A total of 423 miRNAs were included in analysis.18/8 differential expressing (DE) miRNA (adjusted p < 0.05, |log2FC| > 1) were observed in controls Vs. depression/depression Vs. treatment, 2 of which are overlapping. 78% (14/18) of these miRNAs showed opposite trends of alteration in stress and treatment. Two micro RNA, miR-10b-5p and miR-214-3p, appeared to be hubs in the regulation networks and also among the top findings in both differential analyses. Using co-expression analysis, we found a functional module that strongly correlated with stress (R = 0.96, P = 0.003), and another functional module with a moderate correlation with anhedonia (R = 0.89, P = 0.02). We also found that predicted targets of these miRNAs were significantly enriched in the Ras signaling pathway, which is associated with both depression, anhedonia, and antidepressant treatment. CONCLUSION: Escitalopram treatment can significantly reverse NAc miRNA abnormality induced by chronic stress. However, the novel miRNA alteration that is absent in stress pathology also emerges, which means that antidepressant treatment is unlikely to bring miRNA expression back to the same level as the controls. Also, the Ras-signaling pathway may be involved in explaining the depression disease etiology, the clinical symptom, and treatment response of stress-induced depression.

Methadone Dosage and Plasma Levels, SNPs of OPRM1 Gene and Age of First Drug Use Were Associated With Outcomes of Methadone Maintenance Treatment.

Objective: To explore the association between methadone dosage, plasma drug concentration, SNPs of µ-opioid receptor gene (OPRM1), ATP-binding cassette subfamily B member 1 gene (ABCB1), and methadone maintenance treatment (MMT) response. Method: A total of 240 Chinese Han participants receiving MMT were recruited from Shanghai. Nine single nucleotide polymorphisms (SNPs) of the OPRM1 gene and three SNPs of the ABCB1 gene were genotyped, plasma methadone concentration was detected, and a morphine urine test was taken from all subjects. Results: Methadone dosage, plasma methadone concentration, and negative rate of morphine urine test of retention participants were significantly higher, although the addiction severity index (ASI) was not significantly different between the two groups. A allele and AA genotype carriers of rs562859 (OPRM1 gene) had better compliance of MMT, and AA genotype carriers had a higher negative rate of morphine urine test. However, the difference was not significant after adjusting influence factors (age, sex, and methadone dosage). GG genotype carriers of rs3192723 (OPRM1 gene) had a significantly lower negative rate of morphine urine test, and the difference was still significant after adjusting influence factors. Logistic regression analysis showed that methadone-free trough concentration (OR = 0.910, p = 0.023) and AA genotype of rs526859 (OR = 0.580, p = 0.037) were associated with better compliance of MMT. After Bonferroni correction, only free trough concentration of methadone was negatively correlated with MMT compliance. The SNPs rs6912029 (OR = 0.021, p = 0.066) and rs6902403 (OR = 0.910, p = 0.007) of the OPRM1 gene, age at first use (OR = 1.118, p = 0.005), and average methadone dosage (OR = 1.033, p = 0.045) were associated with MMT effect. After Bonferroni correction, average methadone dosage was no longer correlated with MMT effect. Conclusion: Dosage of methadone, plasma methadone concentration, several SNPs (rs3192723, rs6912029, rs6902403) of the OPRM1 gene, and age of first drug use were associated with better MMT outcomes.

Variants in GABBR1 Gene Are Associated with Methamphetamine Dependence and Two Years' Relapse after Drug Rehabilitation.

Methamphetamine (MA) use disorder is a growing global health challenge marked by a steady increase worldwide. GABAergic system plays an important role in the mechanism of drug dependence, however few studies about the association between methamphetamine use disorder and genes in GABAergic system. Concerning GABBR1 gene which encoding the GABAB receptor subunit 1 is an important regulator in the GABAergic system. The aim of the study is to explore whether GABBR1 gene play a role in methamphetamine dependence and relapse after rehabilitation. Three single nucleotide polymorphisms (SNPs, rs2076483, rs29221, rs715044) of the GABBR1 gene were genotyped in 791 participants with MA use disorder and 448 healthy controls. The distribution of genotypes and alleles of the three SNPs between the two groups and their subgroups (dependence and abuse) was been analyzed. The multivariate logistic model was used to identify factors associate with relapse of MA use disorder during the following 2 years after drug rehabilitation. It was found that the C allele frequency of rs715044 of the GABBR1 gene was associated with MA use disorder and MA dependence. The CGA (rs2076483- rs29221- rs715044) was negatively associated with MA use disorder. The drug use years and rs29221 GG genotype were associated with relapse during the following 2 years after drug rehabilitation. GABBR1 gene may be associated with the susceptibility for MA use disorder and relapse and it indicates that the GABAergic system may play a role in the MA use disorder. Graphical Abstract GABBR1 gene may be associated with the susceptibility for MA use disorder and relapse and it indicates that the GABAergic system may play a role in the MA use disorder.

Dopamine receptor D2 and catechol-O-methyltransferase gene polymorphisms associated with anorexia nervosa in Chinese Han population: DRD2 and COMT gene polymorphisms were associated with AN.

Dopamine receptor D2 (DRD2) and catechol-O-methyltransferase (COMT) are important in dopamine system which is proved to be associated with food-anticipatory behavior, food restriction, reward and motivation. This has made them good candidates for anorexia nervosa (AN). The aim of this work is to explore the roles of DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) gene polymorphisms in the susceptibility of AN within the Chinese Han population. We recruited 260AN patients with DSM-IV diagnosis criteria, and 247 unrelated, normal weight controls. DRD2 (rs1800497) and COMT (rs4680, rs4633, rs4818) were genotyped in all subjects. We found rs1800497 and rs4633 were associated with the susceptibility of AN within the Chinese Han sample, and allele C of rs1800497 was a protective factor. There was a gene-gene interaction between rs1800497 of DRD2 gene and rs4633 of COMT gene. We concluded that rs1800497 and rs4633 play important roles in the AN susceptibility with respect to the Chinese Han population. The gene-gene interaction between DRD2 and COMT contributes to the risk of AN.

Decreased platelet 5-hydroxytryptamin (5-HT) levels: a response to antidepressants.

BACKGROUND: Platelet 5-hydroxytryptamin (serotonin, 5-HT) has been examined for its use as a peripheral biomarker for depression or other mental disorders; however, it remains unclear whether blood 5-HT levels can reflect the brain's levels of serotonin. METHODS: Platelet 5-HT levels in 45 drug-naïve, 32 citalopram-treated patients with major depression and 32 healthy control were assayed, Hamilton Depression scale (HAMD) and Hamilton Anxiety Scale (HAMA) were assessed. We then measured 5-HT in platelet, in platelet-poor plasma and in the nuclei of brain tissues obtained from chronic unpredictable mild stress (CUMS) rats with or without citalopram treatment, and from the controls rats that were treated with vehicle. Toward this end, we analyzed whether correlations exist between platelet and brain. RESULTS: No differences were observed among drug-naïve patients, citalopram-treated patients and health control according to gender and age (p>0.05). Drug-naïve depressed patients had highest scores in HAMD and HAMA among the three groups (F=223.3, p<0.01; F=70.7, p<0.01, respectively) Citalopram-treated patients had significantly lower platelet 5-HT levels,compared to control subjects (Mean 58.1±36.8ng/10(9) versus 558.0±199.4ng/10(9), p<0.01) and compared to drug-naïve patients (Mean 58.1 ±36.8ng/10(9) versus 646.4±259.0ng/10(9), p<0.01), while drug-naïve patients had similar 5-HT platelet concentrations as controls(p>0.05). Consistent with clinical results, in comparison with control (1473.4±391.0ng/10(9)) and drug-naive CUMS rats (1559.0±424.4ng/10(9)), the citalopram-treated CUMS rats (684.2±335.6ng/10(9)) demonstrated a significant reduction in platelet 5-HT levels (p<0.01), but there were no difference among the three groups in platelet-poor plasma 5-HT(F=0.11, p>0.05). Hippocampal 5-HT levels were higher among CUMS rats treated with saline (98.2±59.0ng/g) than vehicle animals (31.9±18.3ng/g, p<0.01) or citalopram-treated rats (42.1±33.9ng/g, p<0.05); however, 5-HT concentrations in prefrontal cortex and Raphe Nuclei were consistent among citalopram-treated or saline-treated CUMS rats(p>0.05). Furthermore, the levels of platelet 5-HT did not correlate with neuronal 5-HT levels (p>0.05). LIMITATIONS: Dosages was fix for citalopram-treat rats, and the citalopram-treated vehicle arm did not set up. CONCLUSIONS: Our study suggests that platelet 5-HT levels might respond to SSRI treatment, but this peripheral index is not a direct reflector of central 5-HT levels.

The dopamine receptor D1 gene is associated with the length of interval between first heroin use and onset of dependence in Chinese Han heroin addicts.

Previous researches showed that the dopamine receptor D1 (DRD1) may play a critical role in drug dependence. This research aimed to determine whether DRD1 played a role in development of heroin dependence in Chinese heroin-dependent patients. 465 Chinese Han heroin-dependent subjects and 379 healthy controls were recruited in the Shanghai region. Five single-nucleotide-polymorphisms (SNPs) of the DRD1 gene were genotyped in all subjects. The results found that the frequencies of DRD1 SNP genotypes or haplotypes were not different between heroin-dependent patients and controls. Among heroin-dependent patients, subjects with rs5326CC and/or rs6882300AA genotypes develop to heroin-dependent more rapidly than those without rs5326CC and/or rs6882300AA genotypes. The results indicated that DRD1 gene polymorphism may not play an important role in the susceptibility of heroin dependence in the Chinese Han population, but it may be associated with the rapidity of heroin dependence development from first drug use.

Stress-induced depressive behaviors are correlated with Par-4 and DRD2 expression in rat striatum.

Depression is a common mental disorder; however, its molecular mechanism has not been fully elucidated. In this study, we investigated the role of maternal deprivation (MD) and chronic mild stress (CMS) in the pathogenesis of depression in rat models. The mRNA levels of prostate apoptosis response-4 (Par-4) and dopamine receptor D2 (DRD2) genes in the striatum were measured by real-time PCR. Methylation level in the promoter of Par-4 gene was detected by bisulfite sequencing. Correlation between gene expression and depression-like behaviors were analyzed. Our results demonstrated that MD and CMS alone or their combination (dual stresses: DS) caused depression-like behaviors in rats. The mRNA levels of Par-4 and DRD2 genes in the striatum were significantly lower in MD-, CMS-, and DS-treated rats than in control rats. Importantly, Par-4 and DRD2 mRNA levels significantly correlated with depression-like behaviors. However, no significant differences in total methylation levels in the promoter of Par-4 gene were found between four groups. Our study suggested that either maternal deprivation or chronic mild stress plays a crucial role in the development of depression-like behaviors in rats. This process is associated with down-regulated Par-4 and DRD2 gene expression in the striatum through a non-methylation mechanism.

[Detection and significance of transcription factors and cytokines of Th17/Treg cells in peripheral blood in the gastric cancer patients].

OBJECTIVE: To detect the expression levels of transcription factors and associated cytokines of Th17 and Treg cells in peripheral blood mononuclear cells (PBMC) of patients with gastric cancer, and explore the possible pathological mechanism of these cells involved in the development of gastric cancer. METHODS: The mRNA levels of RORgammat, FoxP3 in PBMC were determined by quantitative real-time PCR (QRT-PCR) from 57 patients with gastric cancer, 31 patients with benign gastric illness and 40 healthy people. The concentration of IL-17, IL-23, TGF-beta, IL-10 in plasma were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with healthy volunteers, patients with gastric cancer showed higher levels of RORgammat and FoxP3 in PBMC (P < 0.05). The ratio of FoxP3/RORgammat in gastric cancer group was higher than that in the volunteer group and benign gastric illness group (P < 0.05). The ratio of FoxP3/RORgammat was higher in advanced disease than early disease (P < 0.05). The expressions of IL-17, IL-23, TGF-beta and IL-10 were higher in patients with gastric cancer than that in healthy volunteers (P < 0.05). In addition, The expression of TGF-beta and IL-10 were significantly increased in the advanced disease group than that in the early group (P < 0.05), but IL-17 and IL-23 was not significantly changed between the two groups (P > 0.05). CONCLUSION: There are higher levels of Th17 and Treg cells in gastric cancer patients, and it also shows a persistent predominant tendency of Treg cells and a reduced tendency of Th17 cells in advanced disease. Detecting the expression of Th17/Treg transcription factor and related cytokines would contribute to the diagnosis and prediction of the disease development and prognosis.