Resident gut microbiota community determines the efficacy of soluble fiber in reducing adiposity.

Consumption of dietary fiber has been linked to several health benefits. Among these, dietary fiber breakdown through the process of anaerobic fermentation by the colonic microbiota leads to the production of beneficial metabolites, mainly short-chain fatty acids (acetate, propionate, and butyrate), which have been implicated in reduced calorie intake. Nevertheless, the link between gut microbiota and obesity remains unclear. We investigated the effects of dietary fibers on food intake and body weight gain in two independent but similarly designed studies in rats. In the first study, the inclusion of 10% w/w pectin, fructooligosaccharides or beta-glucan (n = 10/group) in the diets each significantly reduced body weight gain ('responders') compared to the cellulose control whereas, in a closely matched, but not fully identical study (n = 8/group), no effect of dietary fiber on body weight ('non-responders') was observed. The aim of this work was to explore the basis of this differential response between the two similarly designed and comparable studies, with a focus on the potential role of the gut microbiota in the control of food intake and body weight.

Ketamine induces multiple individually distinct whole-brain functional connectivity signatures.

Background: Ketamine has emerged as one of the most promising therapies for treatment-resistant depression. However, inter-individual variability in response to ketamine is still not well understood and it is unclear how ketamine's molecular mechanisms connect to its neural and behavioral effects. Methods: We conducted a single-blind placebo-controlled study, with participants blinded to their treatment condition. 40 healthy participants received acute ketamine (initial bolus 0.23 mg/kg, continuous infusion 0.58 mg/kg/hr). We quantified resting-state functional connectivity via data-driven global brain connectivity and related it to individual ketamine-induced symptom variation and cortical gene expression targets. Results: We found that: (i) both the neural and behavioral effects of acute ketamine are multi-dimensional, reflecting robust inter-individual variability; (ii) ketamine's data-driven principal neural gradient effect matched somatostatin (SST) and parvalbumin (PVALB) cortical gene expression patterns in humans, while the mean effect did not; and (iii) behavioral data-driven individual symptom variation mapped onto distinct neural gradients of ketamine, which were resolvable at the single-subject level. Conclusions: These results highlight the importance of considering individual behavioral and neural variation in response to ketamine. They also have implications for the development of individually precise pharmacological biomarkers for treatment selection in psychiatry. Funding: This study was supported by NIH grants DP5OD012109-01 (A.A.), 1U01MH121766 (A.A.), R01MH112746 (J.D.M.), 5R01MH112189 (A.A.), 5R01MH108590 (A.A.), NIAAA grant 2P50AA012870-11 (A.A.); NSF NeuroNex grant 2015276 (J.D.M.); Brain and Behavior Research Foundation Young Investigator Award (A.A.); SFARI Pilot Award (J.D.M., A.A.); Heffter Research Institute (Grant No. 1-190420) (FXV, KHP); Swiss Neuromatrix Foundation (Grant No. 2016-0111) (FXV, KHP); Swiss National Science Foundation under the framework of Neuron Cofund (Grant No. 01EW1908) (KHP); Usona Institute (2015 - 2056) (FXV). Clinical trial number: NCT03842800.

Ketamine is a widely used anesthetic as well as a popular illegal recreational drug. Recently, it has also gained attention as a potential treatment for depression, particularly in cases that don't respond to conventional therapies. However, individuals can vary in their response to ketamine. For example, the drug can alter some people's perception, such as seeing objects as larger or small than they are, while other individuals are unaffected. Although a single dose of ketamine was shown to improve depression symptoms in approximately 65% of patients, the treatment does not work for a significant portion of patients. Understanding why ketamine does not work for everyone could help to identify which patients would benefit most from the treatment. Previous studies investigating ketamine as a treatment for depression have typically included a group of individuals given ketamine and a group given a placebo drug. Assuming people respond similarly to ketamine, the responses in each group were averaged and compared to one another. However, this averaging of results may have masked any individual differences in response to ketamine. As a result, Moujaes et al. set out to investigate whether individuals show differences in brain activity and behavior in response to ketamine. Moujaes et al. monitored the brain activity and behavior of 40 healthy individuals that were first given a placebo drug and then ketamine. The results showed that brain activity and behavior varied significantly between individuals after ketamine administration. Genetic analysis revealed that different gene expression patterns paired with differences in ketamine response in individuals ­ an effect that was hidden when the results were averaged. Ketamine also caused greater differences in brain activity and behavior between individuals than other drugs, such as psychedelics, suggesting ketamine generates a particularly complex response in people. In the future, extending these findings in healthy individuals to those with depression will be crucial for determining whether differences in response to ketamine align with how effective ketamine treatment is for an individual.

Alcohol prices, the April effect, and the environment, in violence-related injury in England and Wales.

Violent injury varies widely across England and Wales as does the price of alcohol. While the links between alcohol consumption and violence are well established in the medical and epidemiological literature, a causal link is questionable. This paper cuts through the causative argument by reporting a link between the general price of alcohol and violence-related injury across the economic regions of England and Wales. It examines the influence of the real price of alcohol and identifies an 'April effect' that coincides with the annual uprating of alcohol prices for excise duties, on violence-related injuries recorded at Emergency Department attendance. The data are monthly frequency of violent injury rates covering the period 2005-2014 across the economic regions. The principal finding is that a one-way relationship between the real price of alcohol and violent injury is established, and tax policy can be used to reduce the incidence of violent injury and the associated health costs.

Control by the brain of vitamin A homeostasis.

Vitamin A is a micronutrient essential for vertebrate animals maintained in homeostatic balance in the body; however, little is known about the control of this balance. This study investigated whether the hypothalamus, a key integrative brain region, regulates vitamin A levels in the liver and circulation. Vitamin A in the form of retinol or retinoic acid was stereotactically injected into the 3rd ventricle of the rat brain. Alternatively, retinoids in the mouse hypothalamus were altered through retinol-binding protein 4 (Rbp4) gene knockdown. This led to rapid change in the liver proteins controlling vitamin A homeostasis as well as vitamin A itself in liver and the circulation. Prolonged disruption of Rbp4 in the region of the arcuate nucleus of the mouse hypothalamus altered retinol levels in the liver. This supports the concept that the brain may sense retinoids and influence whole-body vitamin A homeostasis with a possible "vitaminostatic" role.

Financial literacy, behavioral traits, and ePayment adoption and usage in Japan.

This study investigates how financial literacy and behavioral traits affect the adoption of electronic payment (ePayment) services in Japan. We construct a financial literacy index using a representative sample of 25,000 individuals from the Bank of Japan's 2019 Financial Literacy Survey. We then analyze the relationship between this index and the extensive and intensive usage of two types of payment services: electronic money (e-money) and mobile payment apps. Using an instrumental variable approach, we find that higher financial literacy is positively associated with a higher likelihood of adopting ePayment services. The empirical results suggest that individuals with higher financial literacy use payment services more frequently. We also find that risk-averse people are less likely to adopt and use ePayment services, whereas people with herd behavior tend to adopt and use ePayment services more. Our empirical results also suggest that the effects of financial literacy on the adoption and use of ePayment differ among people with different behavioral traits. Supplementary Information: The online version contains supplementary material available at 10.1186/s40854-023-00504-3.

Brain glutamate and sleep efficiency associations following a ketogenic diet intervention in individuals with Alcohol Use Disorder.

Background: We previously showed that ketogenic diet (KD) was effective in curbing alcohol withdrawal and craving in individuals with alcohol use disorder (AUD). We hypothesized that the clinical benefits were due to improvements in sleep. To test this, we performed a secondary analysis on the KD trial data to (1) examine the effects of KD on total sleep time (TST) and sleep quality and (2) investigate the association between KD-induced alterations in cingulate glutamate concentration and changes in TST and sleep quality. Methods: AUD individuals undergoing alcohol detoxification were randomized to receive KD (n=19) or standard American diet (SA; n=14) for three weeks. TST was measured weekly by self-report, GENEActive sleep accelerometer, and X4 Sleep Profiler ambulatory device. Sleep quality was assessed using subjectively ratings of sleep depth and restedness and Sleep Profiler (Sleep Efficiency [%]). Weekly 1H magnetic resonance spectroscopy scans measured cingulate glutamate levels. Results: TST was lower in KD than SA and increased with effect of time. Sleep depth, restedness, and Sleep Efficiency improved with time, but exhibited no effect of diet. In KD and SA combined, week 1 cingulate glutamate levels correlated positively with Sleep Efficiency, but not with TST. Conclusions: Although cingulate glutamate levels correlated positively with Sleep Efficiency in week 1, KD-induced glutamate elevation did not produce significant sleep improvements. Rather, KD was associated with lower TST than SA. Given the well-established associations between sleep and alcohol relapse, longer follow up assessment of KD's impact on sleep in AUD is warranted.

Timing of daily calorie loading affects appetite and hunger responses without changes in energy metabolism in healthy subjects with obesity.

Morning loaded calorie intake in humans has been advocated as a dietary strategy to improve weight loss. This is also supported by animal studies suggesting time of eating can prevent weight gain. However, the underlying mechanisms through which timing of eating could promote weight loss in humans are unclear. In a randomized crossover trial (NCT03305237), 30 subjects with obesity/overweight underwent two 4-week calorie-restricted but isoenergetic weight loss diets, with morning loaded or evening loaded calories (45%:35%:20% versus 20%:35%:45% calories at breakfast, lunch, and dinner, respectively). We demonstrate no differences in total daily energy expenditure or resting metabolic rate related to the timing of calorie distribution, and no difference in weight loss. Participants consuming the morning loaded diet reported significantly lower hunger. Thus, morning loaded intake (big breakfast) may assist with compliance to weight loss regime through a greater suppression of appetite.

The all-Wales forensic adolescent consultation and treatment service (FACTS): A 5-year referral cohort study.

BACKGROUND: FACTS is a Wales-wide mental health service for 10-17-year-olds with needs beyond the remit of mainstream child and adolescent mental health services (CAMHS). As a purely consultation-liaison service, it differs from other UK services in the field. AIMS: To describe a complete cohort of referrals to FACTS 2013-2017 with service exit by June 2018. METHODS: Clinical, social and offending data were extracted from FACTS records. RESULTS: 80 young people completed a FACTS episode, averaging nearly a year (309 days; range 13-859 days). Mostly boys (65, 81%) of mean age 15.4 years (range 9-18), two-thirds (n = 53) had three or more referral reasons, one invariably being threatened/actual harm to others; only half were criminal-justice involved. Half (41, 51%) were committing sexually harmful acts. Half were self-harming (41, 51%). All but seven had had at least one adverse childhood experience (ACE), nearly half (35, 44%) four or more. Nevertheless, post-traumatic stress disorder (PTSD) was rarely diagnosed (7, 9%); just over one-quarter (23, 29%) had no diagnosis at all. Correspondence analyses endorsed two distinct Attention deficit hyperactivity disorder groups, distinguished by presence/absence of evidenced brain damage or dysfunction. Suicide-related behaviours clustered with the other diagnoses, flashbacks and psychotic symptoms with no diagnosis. Change in home circumstances during a FACTS episode was slight. CONCLUSIONS: The complexity of presenting problems and service involvement evidences need for FACTS. The extent of persistently harmful sexual behaviours is a novel finding, suggesting need for more expert input for this at other service levels. Rarity of PTSD diagnoses was surprising given the extent of ACEs. This raises concerns that services focus on disorder signs rather than the child's inner life. Given the extent of problems, minimal change may be a positive outcome - especially when remaining in the community. Further development of this service should include explicit case-by-case goals and indicative outcome markers.

Oral Warty Dyskeratoma-A Systematic Review of the Literature.

OBJECTIVE: To systematically review the clinicopathological features of oral warty keratoma based on published literature. MATERIALS AND METHODS: PubMed and Scopus databases were searched for reports of oral warty dyskeratoma. Of the 52 identified articles, only 25 articles (43 cases) satisfied the selection criteria (case report/series in the English language reporting clinicopathologically diagnosed oral warty dyskeratoma/oral focal acantholytic keratosis/oral isolated dyskeratosis follicularis in humans). Risk of bias was assessed using the Joanna Briggs institute critical appraisal checklist for case reports and case series. RESULTS: Most cases had well-circumscribed, white, nodular verruco-papillary lesions with a central depressed/crater-like area. Alveolar ridges were the most frequent sites of occurrence and tobacco was the most commonly associated risk factor. Histopathologically, the most pathognomonic feature was the supra-basal clefting. The cleft had dyskeratotic acantholytic cells (corps ronds, and grains). Below the cleft were projections of the connective tissue villi lined by basal cells. The basal cells in a few cases exhibited hyperplasia in the form of budding into the stroma, but epithelial dysplasia was not reported. The surface epithelium had crypts filled with keratin debris. CONCLUSION: Oral warty dyskeratoma is a rare solitary self-limiting benign entity, which due to its clinical and histopathological resemblance and associated habit history could be misdiagnosed as leukoplakia or carcinoma. None of the assessed articles provided molecular data, which in turn could be the reason for the lack of insight into the etiopathogenesis of this enigmatic lesion.

Short- and long-term effects of a community-based suicide prevention program: A Hong Kong experience.

BACKGROUND: A multidisciplinary, multilayer, community-based suicide prevention program (2008-2012) was implemented in the Eastern District, Hong Kong. This article documents the program and reports on short- and longer-term program evaluation. METHODS: Characteristics and rates of self-harm/suicidal behaviors and suicide deaths by age group and gender in the Eastern District before, during, and after the intervention were calculated and compared with the rest of Hong Kong, using Kruskal-Wallis and chi-squared tests, and Jonckheere-Terpstra and Cochran-Mantel-Haenszel tests for trend analyses. RESULTS: The program impacts varied by age and gender subgroups. Suicide rates in the Eastern District were lower compared to the rest of Hong Kong during the intervention period. They slowly rebounded after the intervention ceased; nevertheless, they remained lower than the rest of Hong Kong until 2016. The rates of self-harm continuously dropped and remained lower than the rest of Hong Kong. During the intervention period in the Eastern District, the age of people who died by suicide increased; more deaths occurred from jumping and fewer by charcoal burning. CONCLUSIONS: The program coincided with the lowered self-harm and suicide rates after the implementation. Some of the strategies need to be rebooted or routinely and continuously implemented to ensure the sustainability.

Circadian Rhythms in Resting Metabolic Rate Account for Apparent Daily Rhythms in the Thermic Effect of Food.

CONTEXT: Daily variation in the thermic effect of food (TEF) is commonly reported and proposed as a contributing factor to weight gain with late eating. However, underlying circadian variability in resting metabolic rate (RMR) is an overlooked factor when calculating TEF associated with eating at different times of the day. OBJECTIVE: This work aimed to determine whether methodological approaches to calculating TEF contribute to the reported phenomena of daily variation in TEF. METHODS: Fourteen overweight to obese but otherwise healthy individuals had their resting and postprandial energy expenditure (EE) measured over 15.5 hours at a clinical research unit. TEF was calculated for breakfast, lunch, and dinner using standard methods (above a baseline and premeal RMR measure) and compared to a method incorporating a circadian RMR by which RMR was derived from a sinusoid curve model and TEF was calculated over and above the continuously changing RMR. Main outcome measures were TEF at breakfast, lunch, and dinner calculated by different methods. RESULTS: Standard methods of calculating TEF above a premeal measured RMR showed that morning TEF (60.8 kcal ±â€…5.6) (mean ±â€…SEM) was 1.6 times greater than TEF at lunch (36.3 kcal ±â€…8.4) and 2.4 times greater than dinner TEF (25.2 kcal ±â€…9.6) (P = .022). However, adjusting for modeled circadian RMR nullified any differences between breakfast (54.1 kcal ±â€…30.8), lunch (49.5 kcal ±â€…29.4), and dinner (49.1 kcal ±â€…25.7) (P = .680). CONCLUSION: Differences in TEF between morning and evening can be explained by the underlying circadian resting EE, which is independent of an acute effect of eating.

RAF1-MEK/ERK pathway-dependent ARL4C expression promotes ameloblastoma cell proliferation and osteoclast formation.

Ameloblastoma is an odontogenic neoplasm characterized by slow intraosseous growth with progressive jaw resorption. Recent reports have revealed that ameloblastoma harbours an oncogenic BRAFV600E mutation with mitogen-activated protein kinase (MAPK) pathway activation and described cases of ameloblastoma harbouring a BRAFV600E mutation in which patients were successfully treated with a BRAF inhibitor. Therefore, the MAPK pathway may be involved in the development of ameloblastoma; however, the precise mechanism by which it induces ameloblastoma is unclear. The expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C), induced by a combination of the EGF-MAPK pathway and Wnt/ß-catenin signalling, has been shown to induce epithelial morphogenesis. It was also reported that the overexpression of ARL4C, due to alterations in the EGF/RAS-MAPK pathway and Wnt/ß-catenin signalling, promotes tumourigenesis. However, the roles of ARL4C in ameloblastoma are unknown. We investigated the involvement of ARL4C in the development of ameloblastoma. In immunohistochemical analyses of tissue specimens obtained from 38 ameloblastoma patients, ARL4C was hardly detected in non-tumour regions but tumours frequently showed strong expression of ARL4C, along with the expression of both BRAFV600E and RAF1 (also known as C-RAF). Loss-of-function experiments using inhibitors or siRNAs revealed that ARL4C elevation depended on the RAF1-MEK/ERK pathway in ameloblastoma cells. It was also shown that the RAF1-ARL4C and BRAFV600E-MEK/ERK pathways promoted cell proliferation independently. ARL4C-depleted tumour cells (generated by knockdown or knockout) exhibited decreased proliferation and migration capabilities. Finally, when ameloblastoma cells were co-cultured with mouse bone marrow cells and primary osteoblasts, ameloblastoma cells induced osteoclast formation. ARL4C elevation in ameloblastoma further promoted its formation capabilities through the increased RANKL expression of mouse bone marrow cells and/or primary osteoblasts. These results suggest that the RAF1-MEK/ERK-ARL4C axis, which may function in cooperation with the BRAFV600E-MEK/ERK pathway, promotes ameloblastoma development. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Synaptic dysregulation and hyperexcitability induced by intracellular amyloid beta oligomers.

Intracellular amyloid beta oligomer (iAßo) accumulation and neuronal hyperexcitability are two crucial events at early stages of Alzheimer's disease (AD). However, to date, no mechanism linking iAßo with an increase in neuronal excitability has been reported. Here, the effects of human AD brain-derived (h-iAßo) and synthetic (iAßo) peptides on synaptic currents and action potential firing were investigated in hippocampal neurons. Starting from 500 pM, iAßo rapidly increased the frequency of synaptic currents and higher concentrations potentiated the AMPA receptor-mediated current. Both effects were PKC-dependent. Parallel recordings of synaptic currents and nitric oxide (NO)-associated fluorescence showed that the increased frequency, related to pre-synaptic release, was dependent on a NO-mediated retrograde signaling. Moreover, increased synchronization in NO production was also observed in neurons neighboring those dialyzed with iAßo, indicating that iAßo can increase network excitability at a distance. Current-clamp recordings suggested that iAßo increased neuronal excitability via AMPA-driven synaptic activity without altering membrane intrinsic properties. These results strongly indicate that iAßo causes functional spreading of hyperexcitability through a synaptic-driven mechanism and offers an important neuropathological significance to intracellular species in the initial stages of AD, which include brain hyperexcitability and seizures.

Serial step sections at narrow intervals with immunohistochemistry are required for accurate histological assessment of sentinel lymph node biopsy in oral squamous cell carcinoma.

BACKGROUND: Sentinel lymph node (SLN) biopsy is an accurate staging modality in early oral squamous cell carcinoma (OSCC), but its accuracy relies on labor-intensive histopathology protocols. We sought to determine whether serial step sections with immunohistochemistry (SSSIHC) at narrow intervals of the entire SLN are required to accurately exclude metastasis. METHODS: Consecutive SLN biopsies over a 13-year period were retrospectively evaluated. If the index section was negative for carcinoma, the entire SLN was subjected to SSSIHC at 150 µm intervals. The first section level and total number of section levels to contain carcinoma were recorded. RESULTS: One hundred and eighteen SLN+ from 90 patients were included. SSSIHC upstaged the nodal status in 19.5% of patients. Metastasis was identified in 16.7% and 10.2% beyond section levels 4 and 6, respectively. Among SLNs requiring SSSIHC, 47.5% contained carcinoma in a single section level. CONCLUSION: SSSIHC of the entire SLN at 150 µm intervals are required to identify occult metastasis in OSCC.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

PURPOSE: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. MATERIAL AND METHODS: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. RESULTS: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. CONCLUSION: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.

Moderation of Prazosin's Efficacy by Alcohol Withdrawal Symptoms.

OBJECTIVE: Alcohol use disorder (AUD) is a leading cause of global disease burden. Chronic, heavy use increases the likelihood of alcohol withdrawal symptoms and associated secondary outcomes of alcohol craving and mood, anxiety, and sleep disturbances, which are predictive of poor treatment outcomes. The authors examined whether alcohol withdrawal symptoms moderate the efficacy of prazosin in reducing alcohol intake and associated secondary outcomes. METHODS: A 12-week, double-blind, randomized, controlled proof-of-concept trial of prazosin (16 mg/day, with a 2-week titration) was conducted in community-recruited adults with current alcohol dependence (N=100) with varying levels of alcohol withdrawal symptoms assessed at treatment entry. Primary outcomes were daily self-reported drinking days and heavy drinking days, and secondary outcomes were average drinks/day and mood, anxiety, craving, and sleep quality ratings. RESULTS: Modified intent-to-treat analyses indicated a significant interaction of alcohol withdrawal symptom score by treatment by full-dose treatment period (weeks 3-12) for drinking days, heavy drinking days, and average drinks/day. By week 12, participants with high alcohol withdrawal symptoms on prazosin reported 7.07% heavy drinking days and 27.46% drinking days, while those on placebo had 35.58% heavy drinking days and 58.47% drinking days (heavy drinking days: odds ratio=0.14, 95% CI=0.058, 0.333; drinking days: odds ratio=0.265, 95% CI=0.146, 0.481). No such benefit of prazosin was observed in those reporting low or no alcohol withdrawal symptoms. Individuals with high alcohol withdrawal symptoms on prazosin compared with placebo also showed significantly improved anxiety, depression, and alcohol craving over the course of the trial. CONCLUSIONS: The findings indicate that alcohol withdrawal symptoms are a significant moderator of prazosin treatment response for alcohol use outcomes and for associated symptoms of alcohol craving, anxiety, and mood symptoms. These data support further evaluation of alcohol withdrawal symptoms as a prognostic indicator of prazosin's efficacy in the treatment of AUD.

Naltrexone + Bupropion Combination for the Treatment of Binge-eating Disorder with Obesity: A Randomized, Controlled Pilot Study.

PURPOSE: Binge-eating disorder (BED), the most prevalent eating disorder, is associated strongly with obesity and functional impairments. Few evidence-based treatments for BED exist; a pharmacotherapy effective in reducing both binge eating and weight needs to be identified. This placebo-controlled double-blind pilot RCT evaluated the acute effects of naltrexone + bupropion (NB) on BED with obesity and examined the longer-term effects through 6-month follow-up after the discontinuation of medication. METHODS: Twenty-two adult patients with BED were randomized to receive 12 weeks of double-blind treatment with fixed-dose NB (naltrexone + bupropion XL 50/300 mg) or placebo. Independent (blinded) researcher-clinicians evaluated patients at major outcome time points (baseline, posttreatment, and 6-month follow-up after the treatment period); patients were also evaluated for the tracking of course/tolerability throughout treatments and at 3-month follow-up. Primary outcomes were changes from baseline in binge-eating frequency and percentage weight. Secondary outcomes were changes in eating-disorder psychopathology and depression. FINDINGS: A total of 22 patients were enrolled (86.4% women; mean age, 50.4 years), with 77.3% of patients completing treatments; completion rates (NB, 83.3%; placebo, 70.0%) and adverse events did not differ significantly between NB and placebo. Analyses revealed significant reductions from baseline in binge-eating, eating-disorder psychopathology, depression, and weight during treatment, but these changes with NB did not differ significantly from those with placebo. The percentage of patients who attained 3% weight loss was significantly greater with NB than with placebo (45.5% vs 0%); weight-loss and binge-eating reductions were significantly correlated in the group that received NB. At 6-month follow-up, outcomes remained improved relative to baseline, with no significant differences between NB and placebo. IMPLICATIONS: The findings from this pilot RCT suggest that NB was well-tolerated in these patients with BED and comorbid obesity. Most outcomes were not statistically different between NB and placebo. A larger-scale, adequately powered RCT is needed for determining the efficacy of NB in the treatment of BED. ClinicalTrials.gov identifier: NCT02317744.