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The aim of this article is to summarize the pathways connecting the gut and the brain and to highlight their role in the development of depression as well as their potential use as therapeutic targets. A literature search was conducted in PubMed using relevant keywords and their combinations up to the end of March 2020. Previously seen as a disease pertaining solely to the central nervous system, depression is now perceived as a multifactorial condition that extends beyond neurotransmitter depletion. Central to our understanding of the disease is our current knowledge of the communication between the gut and the brain, which is bidirectional and involves neural, endocrine, and immune pathways. This communication is facilitated via stress-mediated activation of the HPA axis, which stimulates the immune system and causes a decrease in microbial diversity, also known as dysbiosis. This change in the intestinal flora leads, in turn, to bacterial production of various substances which stimulate both the enteric nervous system and the vagal afferents and contribute to additional activation of the HPA axis. Concomitantly, these substances are associated with an increase in intestinal permeability, namely, the leaky gut phenomenon. The bidirectional link between the gut and the brain is of great importance for a more inclusive approach to the management of depression. It can thus be deployed for the development of novel therapeutic strategies against depression, offering promising alternatives to limited efficacy antidepressants, while combination therapy also remains a potential treatment option.

Although high protein and low glycemic index (GI) foods are thought to promote satiety, little is known about the effects of GI, protein, and their interaction on hunger and energy intake several hours following a mixed meal. This study investigated the long term effects of GI, protein, and their combined effects on glucose, insulin, hunger, and energy intake in healthy, sedentary, overweight, and obese adults (BMI of 30.9 ± 3.7 kg/m(2)). Sixteen individuals participated separately in four testing sessions after an overnight fast. The majority (75%) were non-Hispanic Blacks. Each consumed one of four breakfast meals (high GI/low protein, high GI/high protein, low GI/low protein, low GI/high protein) in random order. Visual analog scales (VAS) and blood samples were taken at baseline, 15 min, and at 30 min intervals over 4 h following the meal. After 4 h, participants were given the opportunity to consume food ad libitum from a buffet style lunch. Meals containing low GI foods produced a smaller glucose (P < 0.002) and insulin (P = 0.0001) response than meals containing high GI foods. No main effects for protein or interactions between GI and protein were observed in glucose or insulin responses, respectively. The four meals had no differential effect on observed energy intake or self-reported hunger, satiety, and prospective energy intake. Low GI meals produced the smallest postprandial increases in glucose and insulin. There were no effects for GI, protein, or their interaction on appetite or energy intake 4 h after breakfast.

Background: Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss., Objective: To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program., Design: Randomized parallel-group trial. (ClinicalTrials.gov registration number: NCT00143936), Setting: 3 academic medical centers., Patients: 307 participants with a mean age of 45.5 years (SD, 9.7 years) and mean body mass index of 36.1 kg/m(2) (SD, 3.5 kg/m(2))., Intervention: A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low-glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d;

Given the increased prevalence of obesity in the United States (and its associated cardiovascular risk) despite reduced fat intake, there has been increasing interest in the effect of low-carbohydrate diets on obesity. Recent prospective trials have demonstrated equivalent weight loss on low-carbohydrate versus low-fat diets, but with significantly different effects on metabolic risk factors for cardiovascular disease. Low-carbohydrate diets have more favorable effects on metabolic abnormalities found in insulin resistance syndromes, including serum triglyceride levels, high-density lipoprotein cholesterol levels, and small, dense low-density lipoprotein particles. The translation of these different metabolic effects on cardiovascular disease and events requires future studies. These studies should take into consideration that patients with insulin resistance syndromes would be the most likely group to benefit from carbohydrate restriction.

Modafinil is indicated for the management of excessive daytime sleepiness; however, recent studies have examined a broad range of potential uses. Given that clinical uses of modafinil may be expanding, this study compared modafinil and d-amphetamine effects on subjective and performance measures. Across 11 sessions, 11 healthy adults were tested after oral doses of placebo (5 sessions), modafinil (1.75 mg/kg, 3.50 mg/kg, or 7.00 mg/kg), and d-amphetamine (0.035 mg/kg, 0.070 mg/kg, 0.140 mg/kg) under double-blind, randomized conditions. Assessments of cognitive performance and subjective effects were completed before drug administration, 30 min after drug administration, and at hourly intervals after drug administration for 5 hr. Modafinil increased ratings on the Amphetamine and Morphine Benzedrine Group scales of the Addiction Research Center Inventory (ARCI) and increased ratings on the Vigor and Total Positive scales of the Profile of Mood States. d-Amphetamine increased visual analog ratings of feeling stimulated and liking the drug and increased ratings on the Morphine Benzedrine Group scale of the ARCI. Both medications significantly reduced visual analog scale ratings of feeling sleepy, and modafinil decreased ratings on the ARCI Pentobarbital-Chlorpromazine-Alcohol Group scale. Both medications sustained performance that deteriorated across time on the Sternberg Number Recognition Test. Modafinil also enhanced performance rate on the Digit-Symbol Substitution Task above baseline levels and increased response rate on the Repeated Acquisition of Response Sequences Task. These results suggest that modafinil engenders alerting effects and increases performance in healthy non-sleep-deprived individuals comparable with that of d-amphetamine.

Behavioral treatment is an approach used to help individuals develop a set of skills to achieve a healthier weight. It is more than helping people to decide what to change; it is helping them identify how to change. The behavior change process is facilitated through the use of self-monitoring, goal setting, and problem solving. Studies suggest that behavioral treatment produces weight loss of 8-10% during the first 6 mo of treatment. Structured approaches such as meal replacements and food provision have been shown to increase the magnitude of weight loss. Most research on behavioral treatment has been conducted in university-based clinic programs. Although such studies are important, they tell us little about the effectiveness of these approaches in settings outside of specialized clinics. Future research might focus more on determining how these behavioral techniques can be best applied in a real-world setting.

Despite efforts to achieve a desirable weight, two-thirds of the population has an elevated body weight. Medications are useful in supporting weight loss, but produce adverse effects. This study compared the effects of amphetamine and modafinil on food intake and cardiovascular activity in healthy men and women. Participants (n = 11) completed 11 sessions. In random order, participants received placebo on five separate sessions and single oral doses of modafinil (1.75, 3.5, or 7.0 mg/kg) and amphetamine (0.035, 0.07, 0.14 mg/kg). Free time between hourly performance testing intervals gave participants the opportunity to eat. Like amphetamine, modafinil reduced the amount of food consumed and decreased energy intake, without altering the proportion of macronutrients consumed. Although both medications significantly increase heart rate and blood pressure at higher doses, the dose of modafinil that was efficacious in decreasing food intake did not significantly increase heart rate. Modafinil may be well suited for the treatment of obesity, although further studies with repeated dosing in overweight populations are warranted. Modafinil may have less adverse health consequences than some anorectic agents and greater treatment efficacy.

Objective: This study was designed to assess physicians' attitudes toward obese patients and the causes and treatment of obesity., Research Methods and Procedures: A questionnaire assessed attitudes in 2 geographically representative national random samples of 5000 primary care physicians. In one sample (N = 2500), obesity was defined as a BMI of 30 to 40 kg/m(2), and in the other (N = 2500), obesity was defined as a BMI > 40., Results: Six hundred twenty physicians responded. They rated physical inactivity as significantly more important than any other cause of obesity (p < 0.0009). Two other behavioral factors-overeating and a high-fat diet-received the next highest mean ratings. More than 50% of physicians viewed obese patients as awkward, unattractive, ugly, and noncompliant. The treatment of obesity was rated as significantly less effective (p < 0.001) than therapies for 9 of 10 chronic conditions. Most respondents (75%), however, agreed with the consensus recommendations that a 10% reduction in weight is sufficient to improve obesity-related health complications and viewed a 14% weight loss (i.e., 78 +/- 5 kg from an initial weight of 91 kg) as an acceptable treatment outcome. More than one-half (54%) would spend more time working on weight management issues if their time was reimbursed appropriately., Discussion: Primary care physicians view obesity as largely a behavioral problem and share our broader society's negative stereotypes about the personal attributes of obese persons. Practitioners are realistic about treatment outcomes but view obesity treatment as less effective than treatment of most other chronic conditions.