A randomized, prospective, active-controlled study comparing intramuscular long-acting paliperidone palmitate versus oral antipsychotics in patients with schizophrenia at risk of violent behavior.

OBJECTIVE: Paliperidone palmitate (PP) is an effective long-acting antipsychotic injection, but its impact on the behavior of schizophrenia patients with dangerous tendencies requires further investigation. This study aims to explore the effects of long-term antipsychotic treatment on this population in the community. METHODS: This 49-week, randomized controlled trial was conducted across 21 communities in Wuhan and enrolled 134 schizophrenia patients at risk for violent behavior. With a fixed block size of 10, participants were randomly assigned to receive either intramuscular PP 1-month formulation (PP1M) or oral antipsychotic medication (OAP) at a 1:1 ratio. Changes in patients' risk for violent/aggressive behavior, family burden, social, and cognitive functioning were measured using VRAPP, MOAS, PANSS, FBS, PSP, and RBANS scales from baseline to endpoint. Longitudinal data from multiple repeated measures were analyzed using linear mixed-effects models. RESULTS: The study protocol was completed by 77.6% of the patients overall. Significant improvements were observed in the risk assessment scores, MOAS total score, PANSS total score, PSP total score, and FBS total score of patients in the PP1M group from baseline to the end of treatment (all P < 0.05). Importantly, compared to patients in the OAP group, the improvements in these measures were also significantly greater in the PP1M group. Commonly observed AEs, such as hyperprolactinemia (70.3% vs. 62.65%) and muscle tension (45.3% vs. 57.8%), were considered to be the PP-related AEs. Nonetheless, the differences between the two groups did not reach statistical significance, and no new safety concerns emerged. CONCLUSIONS: Our study suggests that PP long-acting injection (LAI) is a safe and effective treatment option for community-dwelling schizophrenia patients with impulsive violence and risky behaviors.

Prebiotics for depression: how does the gut microbiota play a role?

Depression, a mood disorder characterized by persistent feelings of sadness and aversion to activity that can interfere with daily life, is a condition of great concern. Prebiotics, which are non-digestible substances selectively utilized by host microorganisms for health benefits, have gained attention for their potential to improve overall wellness and alleviate various disorders including depression. This study aims to review clinical trials utilizing carbohydrate-type prebiotics such as inulin-type fructans, galactooligosaccharides (GOS), human milk oligosaccharides, resistant starch, prebiotic phytochemicals including epigallocatechin gallate (EGCG), chlorogenic acids, resveratrol, and prebiotic lipids (n-3 polysaturated fatty acids) to determine their effects on depression. Our findings suggest that GOS at a daily dosage of 5 g and eicosapentaenoic acid at or less than 1 g can effectively mitigate depressive symptoms. While EGCG exhibits potential antidepressant properties, a higher dosage of 3 g/d may be necessary to elicit significant effects. The plausible mechanisms underlying the impact of prebiotics on depression include the synthesis of neurotransmitters, production of short-chain fatty acids, and regulation of inflammation.

Corrigendum: Gut microbiota: Linking nutrition and perinatal depression.

[This corrects the article DOI: 10.3389/fcimb.2022.932309.].

Gut microbiota: Linking nutrition and perinatal depression.

Perinatal depression is a mood disorder that is reported in women during pregnancy (prenatal) and after childbirth (postnatal). The onset of perinatal depression is associated with changes in reproductive hormones, stress hormones and neurosteroids. These chemical compounds can be modulated by the gut microbiota, which may affect maternal mental health during the perinatal period via the gut-brain-axis. Recent studies suggest that nutritional and dietary interventions (vitamin D, ω-3 fatty acids, iron, and fiber) effectively prevent or mitigate maternal depression and anxiety, but their efficacy is confounded by various factors, including the gut microbiota. Probiotics are efficacious in maintaining microbiota homeostasis, and thus, have the potential to modulate the development of perinatal mood disorders, despite no evidence in human. Therefore, clinical trials are warranted to investigate the role of probiotic supplementation in perinatal depression and behavioral changes. This article reviews the interplay between nutrition, gut microbiota and mood and cognition, and the evidence suggesting that probiotics affect the onset and development of perinatal depression.

Oral Microbiota Profile of Individuals Who Abuse Methamphetamine.

The poor oral health condition of individuals who abuse methamphetamine (MA) is well known. The roles of the oral and fecal microbiomes in addiction and nervous system diseases have been the focus of many studies. However, changes in the microbiota composition of MA users have not been reported. This was addressed in the present study in 20 MA users and 14 sex-matched healthy subjects. Saliva samples were collected and high-throughput 16S rRNA sequencing and bioinformatic analysis were performed to evaluate oral microbiome profiles. The results showed that species richness was significantly lower in the MA group than in the control group. Bacterial taxa that are known to be related to oral diseases such as Negativicutes, Veillonellaceae, Veillonella, and Selenomonadales had higher relative abundance in the MA group than in the control group, and the relative abundance of Prevotella melaninogenica-a putative etiologic agent of periodontal disease-was also higher. Avoiding MA use and improving oral hygiene practices over a short term (i.e., during hospitalization for 2 weeks) did not alter the oral microbiota composition of MA users. Although the causal relationship between changes in oral microbiome profile and MA abuse remains to be determined, our results suggest that oral disease prevention and treatment strategies are important for MA users.

Altered fecal microbiota composition in individuals who abuse methamphetamine.

As a severe public health problem, methamphetamine (METH) abuse places a heavy burden on families and society. A growing amount of evidence has indicated communication between gut microbiota and the CNS in drug addiction, with associations to neural, endocrine and immune pathways. Thus, we searched for alterations in the gut microbiota and their potential effects in METH users through 16S rRNA gene sequencing. A decreased Shannon index indicated lower bacterial diversity in the METH users than in the age-matched control group. The gut microbial community composition in the METH users was also altered, including reductions in Deltaproteobacteria and Bacteroidaceae abundances and increases in Sphingomonadales, Xanthomonadales, Romboutsia and Lachnospiraceae abundances. Moreover, the Fusobacteria abundance was correlated with the duration of METH use. Enterobacteriaceae, Ruminococcaceae, Bacteroides, and Faecalibacterium had statistically significant correlations with items related to the positive and negative symptoms of schizophrenia and to general psychopathology in the METH users, and all have previously been reported to be altered in individuals with psychotic syndromes, especially depression. Abstraction, one of the items of the cognitive assessment, was positively related to Blautia. These findings revealed alterations in the gut microbiota of METH users, and these alterations may play a role in psychotic syndrome and cognitive impairment. Although the mechanisms behind the links between these disorders and METH abuse are unknown, the relationships may indicate similarities in the pathogenesis of psychosis induced by METH abuse and other causes, providing a new paradigm for addiction and METH use disorder treatment.

Transcriptome Analysis Reveals MFGE8-HAPLN3 Fusion as a Novel Biomarker in Triple-Negative Breast Cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly aggressive cancer with poor prognosis. The lack of effective targeted therapies for TNBC remains a profound clinical challenge. Fusion transcripts play critical roles in carcinogenesis and serve as valuable diagnostic and therapeutic targets in cancer. The present study aimed to identify novel fusion transcripts in TNBC. METHODS: We analyzed the RNA sequencing data of 360 TNBC samples to identify and filter fusion candidates through SOAPfuse and ChimeraScan analysis. The characteristics, including recurrence, fusion type, chromosomal localization, TNBC subgroup distribution, and clinicopathological correlations, were analyzed in all candidates. Furthermore, we selected the promising fusion transcript and predicted its fusion type and protein coding capacity. RESULTS: Using the RNA sequencing data, we identified 189 fusion transcripts in TNBC, among which 22 were recurrent fusions. Compared to para-tumor tissues, TNBC tumor tissues accumulated more fusion events, especially in high-grade tumors. Interestingly, these events were enriched at specific chromosomal loci, and the distribution pattern varied in different TNBC subtypes. The vast majority of fusion partners were discovered on chromosomes 1p, 11q, 19p, and 19q. Besides, fusion events mainly clustered on chromosome 11 in the immunomodulatory subtype and chromosome 19 in the luminal androgen receptor subtype of TNBC. Considering the tumor specificity and frameshift mutation, we selected MFGE8-HAPLN3 as a novel biomarker and further validated it in TNBC samples using PCR and Sanger sequencing. Further, we successfully identified three types of MFGE8-HAPLN3 (E6-E2, E5-E3, and E6-E3) and predicted the ORF of E6-E2, which could encode a protein of 712 amino acids, suggesting its critical role in TNBC. CONCLUSIONS: Improved bioinformatic stratification and comprehensive analysis identified the fusion transcript MFGE8-HAPLN3 as a novel biomarker with promising clinical application in the future.

The Role of Diet, Eating Behavior, and Nutrition Intervention in Seasonal Affective Disorder: A Systematic Review.

Background: Seasonal affective disorder (SAD) is a biological and mood disorder with a seasonal pattern. Dietary intervention and nutritional status have been reported to affect SAD severity. The objective of this study was to systematically review the evidence of associations between SAD and diet, eating behavior, and nutrition intervention. Methods: We performed a comprehensive search of MEDLINE, EMBASE, Web of Science, and Google Scholar from inception up to July 1, 2019. Studies that examined diet and eating behaviors in SAD patients and tests of nutrition interventions for SAD were included. Two independent investigators extracted data based on study designs, participants, outcomes, exposures, and association measures. Results: Eleven studies were included: six studies examined distinctive dietary patterns and eating behaviors in SAD patients and five studies explored the efficacy of nutrition interventions for SAD. Vegetarianism and alcoholism were associated with higher SAD prevalence, but normal alcohol intake was not correlated with SAD severity. Compared with non-clinical subjects, SAD patients tended to consume significantly larger dinners and more evening snacks during weekdays and weekends and exhibit a higher frequency of binge eating, external eating, and emotional eating. Additionally, compared to healthy controls, SAD patients presented more cravings for starch-rich food and food with high fiber. However, neither the ingestion of carbohydrate-loaded meals nor Vitamin D/B12 supplementation showed benefit for SAD. Conclusion: Studies suggest that SAD patients may exhibit distinctive diet preferences and eating behaviors, but no current nutrition intervention has demonstrated efficacy for ameliorating SAD symptoms. Further evidence is needed from randomized controlled trials with larger sample sizes and longer durations.

Paliperidone Extended-Release Tablets for the Treatment of Methamphetamine Use Disorder in Chinese Patients After Acute Treatment: A Randomized, Double-Blind, Placebo-Controlled Exploratory Study.

Background: To test paliperidone extended-release (ER) for efficacy in decreasing methamphetamine (METH) use and reducing psychotic symptoms in METH-dependent patients after detoxification. Rates of adverse events with paliperidone ER versus placebo were also compared. Methods: After discharge and 7 days without medication, 80 treatment-seeking METH-dependent participants were randomly assigned to paliperidone ER (3 mg once daily; n = 40) or placebo (once daily; n = 40) for 84 days under double-blind conditions. The participants attended clinics weekly to provide urine samples that were analyzed for METH metabolites, to complete research assessments, and to receive substance use and medication counseling. Results: Fifty-six percent of follow-up visits and final visits were completed. The placebo group had a significantly lower retention [51.5 days; 95% confidence interval (CI), 41.6-61.4] than the paliperidone ER group (69.4 days,; 95% CI, 61.9-76.9; p = 0.016). Paliperidone ER was a protective factor against psychotic symptom relapse [hazard ratio (HR) = 0.15, p = 0.003]. Moreover, there were statistically significant effects of paliperidone ER on psychosis severity and METH craving, assessed by mean changes in Positive and Negative Syndrome Scale (PANSS) total scores, Clinical Global Impression-Severity (CGI-S) scores, and METH craving scores over time (p = 0.006, p = 0.002, and p = 0.03 for the medication-by-time interaction effect, respectively). There were no statistically significant differences between the two groups in METH use. There were no serious adverse events related to the study drug. Conclusion: Compared with placebo, paliperidone ER administration resulted in a better retention rate and lower psychotic symptom relapse, but we did not find significantly reduced METH use among adults after acute METH detoxification treatment.

ALG3 Is Activated by Heat Shock Factor 2 and Promotes Breast Cancer Growth.

BACKGROUND Previous research found that ALG3 is associated with cervical cancer, but the role of ALG3 in breast cancer was still unknown. MATERIAL AND METHODS The expression of ALG3 in breast carcinoma tissues was determined by immunochemistry. The ability of cellular proliferation, migration, and invasion was determined by CCK-8 assay, wound healing migration assay, and cell invasion assays, respectively. The binding between HSF2 and promoter of ALG3 was determined by ChIP assay. RESULTS There was an increased expression of ALG3 in breast cancer tissues compared to normal breast tissues (p<0.05). High expression of ALG3 was significantly correlated with poor OS (p<0.05). ALG3 expression was significantly increased in cancer samples with advanced stages (stage III/IV) compared with those in the early stages of disease (stage I/II) (p<0.05). The staining intensity of ALG3 was significantly correlated to the tumor grade (grades 2-3 versus 1, p<0.05). Silencing ALG3 or HSF2 inhibited the proliferation, migration, and invasion abilities of MCF-7 cells. Silencing ALG3 retarded the growth of MCF-7 cells in vivo. CONCLUSIONS Silencing ALG3 inhibited MCF-7 cells growth in vitro and in vivo. HSF2 activated ALG3 and promoted the growth of breast carcinoma.