A specific gut microbiota signature is associated with an enhanced GLP-1 and GLP-2 secretion and improved metabolic control in patients with type 2 diabetes after metabolic Roux-en-Y gastric bypass.

Objective: To determine changes in incretins, systemic inflammation, intestinal permeability and microbiome modifications 12 months after metabolic RYGB (mRYGB) in patients with type 2 diabetes (T2D) and their relationship with metabolic improvement. Materials and methods: Prospective single-center non-randomized controlled study, including patients with class II-III obesity and T2D undergoing mRYGB. At baseline and one year after surgery we performed body composition measurements, biochemical analysis, a meal tolerance test (MTT) and lipid test (LT) with determination of the area under the curve (AUC) for insulin, C-peptide, GLP-1, GLP-2, and fasting determinations of succinate, zonulin, IL-6 and study of gut microbiota. Results: Thirteen patients aged 52.6 ± 6.5 years, BMI 39.3 ± 1.4 kg/m2, HbA1c 7.62 ± 1.5% were evaluated. After mRYGB, zonulin decreased and an increase in AUC after MTT was observed for GLP-1 (pre 9371 ± 5973 vs post 15788 ± 8021 pM, P<0.05), GLP-2 (pre 732 ± 182 vs post 1190 ± 447 ng/ml, P<0.001) and C- peptide, as well as after LT. Species belonging to Streptococaceae, Akkermansiacea, Rickenellaceae, Sutterellaceae, Enterobacteriaceae, Oscillospiraceae, Veillonellaceae, Enterobacterales_uc, and Fusobacteriaceae families increased after intervention and correlated positively with AUC of GLP-1 and GLP-2, and negatively with glucose, HbA1c, triglycerides and adiposity markers. Clostridium perfringens and Roseburia sp. 40_7 behaved similarly. In contrast, some species belonging to Lachnospiraceae, Erysipelotricaceae, and Rumnicocaceae families decreased and showed opposite correlations. Higher initial C-peptide was the only predictor for T2D remission, which was achieved in 69% of patients. Conclusions: Patients with obesity and T2D submitted to mRYGB show an enhanced incretin response, a reduced gut permeability and a metabolic improvement, associated with a specific microbiota signature.

Perceived stress, social functioning and quality of life in first-episode psychosis: A 1-year follow-up study.

AIM: Quality of life (QoL) has been widely studied in people with schizophrenia. In the early phases of psychosis, it remains often impaired even after the remission of psychotic symptoms. The aim of this study was to explore QoL and social functioning during the first year after a first-episode psychosis (FEP), and to study potential moderating effects of stress measures. METHODS: Here, 61 FEP subjects and 55 healthy controls (HCs) were included. Sociodemographic data and clinical variables were collected through a semi-structured interview. Stress measures, social functioning and QoL were assessed with the Holmes-Rahe Social Readjustment Rating Scale, the Perceived Stress Scale, the Social Adaptation Self-Scale and the Euro-QoL-5D, respectively. Analysis of variance was employed with repeated measures and a mediation analysis at baseline and at 1-year follow-up was carried out. RESULTS: Patients reported lower QoL, poorer social functioning and more stress than HC. FEP patients significantly improved in QoL and stress measures over time, but not in social functioning. Perceived stress mediated the association between poorer social functioning and lower QoL. CONCLUSIONS: Social functioning at baseline may determine QoL over a 1-year follow-up period. Despite the improvement in most measures, patients do not achieve the level of well-being as the healthy group.

Perceived stress mediates the relationship between social adaptation and quality of life in individuals at ultra high risk of psychosis.

AIM: Quality of life (QoL) and social functioning have emerged as good predictors of the outcome of psychotic disorders. Poor QoL and social functioning are usually present before the onset of the first episode of psychosis. Our study aimed to explore the relationship between social adaptation and QoL in young people at risk of psychosis (ultra-high-risk, UHR) and healthy controls (HCs), and to investigate potential mediating effects of stress measures (perceived stress, stressful life events). METHODS: The study included 55 UHR subjects and 40 HC. Social functioning was assessed with the Social Adaptation Self-evaluation Scale (SASS). Stress measures included the assessment of stressful life events and perceived stress. We compared stress and QoL measures between UHR and HC, and also compared UHR with low or normal social adaptation. A mediation analysis was performed to explore whether stress measures mediated the relationship between social adaptation and QoL. RESULTS: UHR were less frequently employed and reported more stress, poorer QoL and lower social adaptation than HC. QoL and social adaptation were associated with stress measures. UHR with low social adaptation reported more perceived stress and less QoL than UHR with normal social adaptation and HC. Perceived stress mediated the relationship between social adaptation and QoL. CONCLUSIONS: Social adaptation is less developed in UHR subjects than in healthy subjects and has a negative impact on quality of life. This association is mediated by perceived stress.

Increased levels of serum leptin in the early stages of psychosis.

BACKGROUND: Studies evaluating leptin levels in patients with first-episode psychoses (FEP) have been inconclusive, and apparently, the high levels of leptin reported in patients with schizophrenia may be associated with weight gain. The aim of this study was to evaluate leptin levels at the early stages of the disease and the relationship between leptin and lifestyle habits, stress-related variables and metabolic parameters. METHODS: In total, 14 at-risk mental state (ARMS) patients, 39 FEP patients, 32 psychotic patients in the critical period (CP) and 21 healthy controls (HCs) were assessed. Anthropometric and biochemical parameters, as well as dietary intake, physical activity, stress-related variables and symptomatology, were collected. RESULTS: Leptin levels were higher in the ARMS, FEP and CP patients than in the HCs. After controlling for age, sex, BMI, physical exercise, tobacco use and dietary intake, the highest differences in leptin levels were observed between the ARMS patients and HCs (p = 0.025). In the whole sample, leptin levels were positively correlated with BMI (p < 0.001), waist circumference (p < 0.001), insulin levels (p = 0.020), levels of the inflammatory marker IL-6 (p = 0.007) and energy intake (p = 0.043) and negatively correlated with HDL cholesterol (p = 0.018). Interestingly, energy intake and food craving scores were positively correlated with levels of leptin only in females (p = 0.022 and p = 0.036, respectively). DISCUSSION: The present study detected increased leptin levels in the early stages of psychosis and significant correlations between leptin levels and anthropometric, lipid, hormone, and cytokine parameters. We found higher leptin levels in women, and we identified dietary intake habits associated with leptin exclusively in females that advocate considering sex in future studies.

Food addiction and preoperative weight loss achievement in patients seeking bariatric surgery.

INTRODUCTION: Evidence suggests that food addiction (FA) is prevalent among individuals with obesity seeking bariatric surgery (BS), but there is no evidence about whether FA is a predictor of weight loss (WL). We aimed to analyse the prevalence of FA in patients with obesity seeking BS and to examine whether FA could predict WL following dietary intervention before surgery. METHOD: The study included 110 patients with obesity who underwent a dietetic intervention. Assessment included endocrinological variables, a semistructured interview to rule out mental disorders, and Yale Food Addiction Scale version 2.0 (YFAS 2.0). RESULTS: In our sample, the prevalence of FA was 26.4%. Those who met YFAS 2.0 criteria showed less WL after dietetic intervention and regain weight during dietary intervention. CONCLUSIONS: FA appears to be prevalent in obesity. Our findings confirmed a lower WL throughout dietary intervention before surgery in patients who fulfilled baseline criteria for FA. Future interventions should include multidisciplinary intervention to maximize WL before and after BS.

Gene-environment interaction between the brain-derived neurotrophic factor Val66Met polymorphism, psychosocial stress and dietary intake in early psychosis.

AIM: The brain-derived neurotrophic factor (BDNF) is a major participant in the regulation of food intake and may play a role in the regulation of the stress response. We aimed to investigate whether there is a gene-environment interaction in the relationship between stress and BDNF Val66Met polymorphism in relation to dietary patterns in a sample of subjects with early psychosis. METHODS: We studied 124 early psychotic disorder (PD) patients, 36 At-Risk Mental States (ARMS) and 62 healthy subjects (HS). Dietary patterns were examined by a dietician. Physical activity, life stress and perceived stress were assessed by validated questionnaires. BDNF Val66Met polymorphism (rs6265) was genotyped. A gene-environment interaction was tested with multiple linear regression analysis while adjusting for covariates. RESULTS: Perceived stress was not associated with calorie intake in HS. In ARMS subjects, Met-carriers who presented low-perceived stress were associated with increased caloric intake. Conversely, those who presented high-perceived stress were associated with reduced caloric intake. In PD, perceived stress was neither associated with increased calorie intake without an effect by BDNF genotype nor a gene-environment interaction. Perceived stress was associated with food craving in PD patients, independent of genotype, and in ARMS or HS who were Val homozygous. CONCLUSIONS: This study suggests that the common Val66Met polymorphism of the BDNF gene may modulate the relationship between life stress and calorie intake in subjects at risk for psychosis.

Is Trabecular Bone Score Valuable in Bone Microstructure Assessment after Gastric Bypass in Women with Morbid Obesity?

INTRODUCTION: The effects of bariatric surgery on skeletal health raise many concerns. Trabecular bone score (TBS) is obtained through the analysis of lumbar spine dual X-ray absorptiometry (DXA) images and allows an indirect assessment of skeletal microarchitecture (MA). The aim of our study was to evaluate the changes in bone mineral density (BMD) and alterations in bone microarchitecture assessed by TBS in morbidly obese women undergoing Roux-en-Y gastric bypass (RYGB), over a three-year follow-up. MATERIAL/METHODS: A prospective study of 38 morbidly obese white women, aged 46.3 ± 8.2 years, undergoing RYGB was conducted. Biochemical analyses and DXA scans with TBS evaluation were performed before and at one year and three years after surgery. RESULTS: Patients showed normal calcium and phosphorus plasma concentrations throughout the study. However, 25-hydroxyvitamin D (25(OH)D3) decreased, and 71% of patients had a vitamin D deficiency at three years. BMD at femoral neck and lumbar spine (LSBMD) significantly decreased 13.53 ± 5.42% and 6.03 ± 6.79%, respectively, during the three-year follow-up; however Z-score values remained above those for women of the same age. TBS was within normal ranges at one and three years (1.431 ± 106 and 1.413 ± 85, respectively), and at the end of the study, 73.7% of patients had normal bone MA. TBS at three years correlated inversely with age (r = -0.41, p = 0.010), body fat (r = -0.465, p = 0.004) and greater body fat deposited in trunk (r = -0.48, p = 0.004), and positively with LSBMD (r = 0.433, p = 0.007), fat mass loss (r = 0.438, p = 0.007) and lean mass loss (r = 0.432, p = 0.008). In the regression analysis, TBS remained associated with body fat (ß = -0.625, p = 0.031; R² = 0.47). The fracture risk, calculated by FRAX® (University of Sheffield, Sheffield, UK), with and without adjustment by TBS, was low. CONCLUSION: Women undergoing RYGB in the mid-term have a preserved bone MA, assessed by TBS.

Weight Loss Trajectories in Bariatric Surgery Patients and Psychopathological Correlates.

This study aimed to explore the empirical trajectories of body mass index (BMI) 1 year following bariatric surgery (BS) and to identify the risk factors for each trajectory. The study included 115 patients with severe obesity who underwent BS. Assessment included metabolic variables, psychopathological and personality measures. Growth mixture modelling identified four separated trajectories for the percentage of total weight loss course shape (namely, T1 'good-fast', T2 'good', T3 'low' and T4 'low-slow'). After adjusting for BS subtype and metabolic baseline state, T1 and T2 registered less eating and general psychopathology. T1 was characterized by the lowest scores in novelty seeking and self-transcendence, whereas T4 was defined by the highest scores in novelty seeking and the lowest scores in persistence. Our findings suggest that psychological state prior to BS is predictive of BMI trajectories during the 12 months following BS. These results could be useful in developing more efficient interventions for these patients. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Increased prolactin levels are associated with impaired processing speed in subjects with early psychosis.

Hyperprolactinaemia, a common side effect of some antipsychotic drugs, is also present in drug-naïve psychotic patients and subjects at risk for psychosis. Recent studies in non-psychiatric populations suggest that increased prolactin may have negative effects on cognition. The aim of our study was to explore whether high plasma prolactin levels are associated with poorer cognitive functioning in subjects with early psychoses. We studied 107 participants: 29 healthy subjects and 78 subjects with an early psychosis (55 psychotic disorders with <3 years of illness, 23 high-risk subjects). Cognitive assessment was performed with the MATRICS Cognitive Consensus Cognitive Battery, and prolactin levels were determined as well as total cortisol levels in plasma. Psychopathological status was assessed and the use of psychopharmacological treatments (antipsychotics, antidepressants, benzodiazepines) recorded. Prolactin levels were negatively associated with cognitive performance in processing speed, in patients with a psychotic disorder and high-risk subjects. In the latter group, increased prolactin levels were also associated with impaired reasoning and problem solving and poorer general cognition. In a multiple linear regression analysis conducted in both high-risk and psychotic patients, controlling for potential confounders, prolactin and benzodiazepines were independently related to poorer cognitive performance in the speed of processing domain. A mediation analysis showed that both prolactin and benzodiazepine treatment act as mediators of the relationship between risperidone/paliperidone treatment and speed of processing. These results suggest that increased prolactin levels are associated with impaired processing speed in early psychosis. If these results are confirmed in future studies, strategies targeting reduction of prolactin levels may improve cognition in this population.

Increased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms.

Schizophrenia patients experience activated inflammatory responses, but little is known about the presence of such inflammatory processes at or prior to disease onset. We measured interleukin-6 (IL-6) and C-reactive protein (CRP) serum levels and plasma fibrinogen in 17 at-risk mental state (ARMS) subjects, 77 patients with psychotic disorder (PD) and 25 healthy control subjects (HC). ARMS subjects were followed-up, and transition to psychosis was registered. IL6 rs1800795 SNP was genotyped, as IL-6 levels may be influenced by this genetic variant. We did not observe significant differences in the IL6 rs1800795 SNP genotype frequencies between the groups. ARMS subjects exhibited significantly higher IL-6 levels than did controls (p=0.019). In subjects not taking cannabis, we found that patients diagnosed with ARMS or PD exhibited increased IL-6 levels when compared with HC (p=0.004). In both ARMS and PD subjects, IL-6 levels were positively associated with negative symptoms. However, with respect to positive psychotic symptoms, a different relationship was observed in the ARMS and PD groups (positive relationship in ARMS; negative relationship in PD). These findings could not be attributed to confounding variables, including gender, body mass index (BMI), tobacco consumption or the rs1800795 genotype. Six of 17 ARMS subjects (35%) exhibited a transition to psychosis during the follow-up period of 26 months. ARMS subjects who developed psychosis exhibited increased median IL-6 levels compared with those who did not transition (0.61 vs. 0.35pg/mL). However, this difference was not statistically significant, which could be explained by a lack of statistical power due to the small sample size. Our results suggest that IL-6 may be a biomarker for early psychotic symptoms; however, further studies in larger samples are needed to confirm this result.

Unhealthy lifestyle in early psychoses: the role of life stress and the hypothalamic-pituitary-adrenal axis.

An unhealthy lifestyle is thought to contribute to the metabolic syndrome in subjects with psychoses. In the present study we aimed to study whether life stress or cortisol measures may influence dietary patterns in subjects with early stages of psychoses. We studied 81 subjects with early psychoses (65 subjects with a psychotic disorder [PD] and <5 years of illness; 16 subjects at risk for psychosis [high-risk, HR]) and a control group of 25 healthy subjects (HS). Dietary habits were examined by a dietician, who registered food intake (24h recall). Physical activity was assessed by validated questionnaire. Life stress was assessed with Holmes-Rahe Social Readjustment Scale. Fasting morning salivary and plasma cortisol levels were determined. We found that PD and HR reported an unhealthier lifestyle with more smoking, reduced physical activity and poorer dietary habits. HR reported increased intake of calories and saturated fatty acids and reduced protein consumption, when compared to HS. Life stress was a predictor of these adverse behaviours, although we found opposite associations in HR and PD. Life stress was associated with increased intake of refined sugar in PD and decreased intake in HR and HS. Salivary cortisol was related to increased intake of saturated fat only in HR subjects, but cortisol levels in plasma or saliva were not associated with other dietary habits or obesity measures (BMI, waist circumference). Our study suggests that unhealthy diet in early psychoses is influenced by stress, but our data do not support this effect being mediated by hypercortisolism. Future preventive interventions in psychosis may target dietary habits, particularly for those who are at risk for psychosis.

Changes in prolactin levels and sexual function in young psychotic patients after switching from long-acting injectable risperidone to paliperidone palmitate.

Hyperprolactinaemia is a significant side effect of antipsychotic medications and may cause sexual dysfunction. The aim of our study was to assess the effect of switching from long-acting injectable (LAI) risperidone to paliperidone palmitate (PP) on sexual function and prolactin levels in patients with psychosis. We carried out a prospective observational study during a 3-month period that involved 11 patients with psychosis treated with risperidone-LAI who suffered from hyperprolactinaemia and who were then switched to PP. Two assessments were completed: the first one before the switch and the second one 3 months after the switch. These assessments measured sexual function using the Arizona Sexual Experience Scale and assessed prolactin levels. Our results showed a significant decrease in serum prolactin levels (P=0.041). We observed a four-fold reduction in clinically significant sexual dysfunction that is suggestive of benefit, although the sample size is too small to be sure. Our study suggests that prolactin levels seem to decrease after switching from risperidone-LAI to PP in patients with a psychotic disorder.