A lifestyle score in childhood and adolescence was positively associated with subsequently measured fluid intelligence in the DONALD cohort study.

PURPOSE: Lifestyle scores which combine single factors such as diet, activity, or sleep duration showed associations with cognitive decline in adults. However, the role of a favourable lifestyle in younger age and the build-up of cognitive reserve is less clear, which is why we investigated longitudinal associations between a lifestyle score in childhood and adolescence and fluid intelligence obtained on average 6 years later. METHODS: In the DONALD cohort, a lifestyle score of 0 to 4 points including healthy diet and duration of moderate-to-vigorous physical activity, sedentary behaviour and sleep was repeatedly assessed in participants aged 5 and 19 years. Data on fluid intelligence were assessed via a German version of the culture fair intelligence test (CFT), using CFT 1-R in children 8.5 years of age or younger (n = 62) or CFT 20-R in participants older than 8.5 years (n = 192). Multivariable linear regression models were used to investigate prospective associations between the lifestyle score and the fluid intelligence score. RESULTS: Mean lifestyle score of all participants was 2.2 (0.7-4) points. A one-point increase in the lifestyle score was associated with a higher fluid intelligence score (4.8 points [0.3-7.3], p = 0.0343) for participants completing the CFT 20-R. Furthermore, each additional hour of sedentary behaviour was associated with a lower fluid intelligence score (- 3.0 points [- 5.7 to - 0.3], p = 0.0313). For younger participants (CFT 1-R), no association was found in any analysis (p > 0.05). CONCLUSION: A healthy lifestyle was positively associated with fluid intelligence, whereby sedentary behaviour itself seemed to play a prominent role.

Changes in patterns of eating habits and food intake during the first German COVID-19 lockdown: results of a cross-sectional online survey.

PURPOSE: The COVID-19 pandemic and public measures have a direct impact on the nutrition situation; studies show changes in food consumption, eating behavior or body weight but complex pattern analyses of changes rarely exist. METHODS: During the first German lockdown, a web-based survey was conducted among adults. It included 33 questions about changes in food intake, eating habits and physical activity, as well as anthropometrics and sociodemographic factors. Patterns of change were calculated based on changes in food intake and eating habits using two-step cluster analysis. To identify influencing factors for assignment to the patterns of change, binary logistic regression analyses were performed. RESULTS: Data from 2103 participants (81% female, 40 ± 14 years) were considered for analysis. Increased stockpiling, cooking, and variation in preparation was reported by 50-70%. The constant pattern (C-P, 36%) reported little change besides the above. The health-oriented pattern (HO-P; 37%) reported eating more healthy foods, avoiding unhealthy foods, and eating less and less frequently. The emotional-driven pattern (ED-P; 28%) exhibits higher influence of emotions on eating behavior, less avoidance of unhealthy foods, and increased consumption of sweets, pastries, and alcohol. The odds of changing eating behavior either to HO-P or ED-P were higher in women, people with migration background, younger participants, and increased with BMI categories. CONCLUSION: Both, the ED-P and HO-P, exhibit distinctive reactions in eating habits and food intake when dealing with a distressing experience. In subgroups, these may lead to disturbances in eating behavior and increase the risk for eating disorders and obesity.

Low leptin levels are associated with elevated physical activity among lean school children in rural Tanzania.

BACKGROUND: In Sub-Saharan African countries, rapid urbanization and increasing socio-economic status are associated with a transition to decreased physical activity (PA). A more sedentary lifestyle is linked to increased body fat leading to increments in leptin levels. Since rodent and human studies in high-income countries have shown that starvation-induced hypoleptinemia triggers high PA, efforts are warranted to pursue the hypothesis that low leptin levels in lean children of low- and middle-income countries (LMIC) are also associated with high PA. METHODS: In this cross-sectional study, we assessed seven-day PA with triaxial accelerometry (ActiGraph GT3X) among 223 primary school children (9 to 12 years of age) in rural Tanzania. Moderate-to-vigorous PA (MVPA) and total accelerometer counts per day were outcome variables. Leptin was determined using enzyme linked immunosorbent assay tests from dried blood spots. Anthropometric assessments were conducted and food insecurity and socio-demographic data were gathered using semi-structured interviews. RESULTS: In this sample of school children in rural Tanzania, leptin concentrations (median: 0.91 ng/mL, P25: 0.55, P75: 1.69), body mass index z-scores (median: -1.35, P25: -1.93, P75: -0.82), and height-for-age-z-scores (median: -1.16, P25: -1.96, P75: -0.61) were low. In contrast, PA levels were high with a median MVPA time of 119 min/day. Linear regression confirmed that leptin levels were negatively associated with MVPA (beta: -18.1; 95%CI: -29.7; -6.5; p = 0.002) and total accelerometer counts (beta: -90,256; 95%CI: -154,146; -26,365; p = 0.006). Children residing in areas with better infrastructure had lower MVPA levels (p < 0.001) and tended to have higher leptin levels (p = 0.062) than children residing in areas only reachable via dirt roads. CONCLUSION: Our cross-sectional field study is the first that supports the hypothesis of low leptin levels as a potential endocrine trigger of high PA in lean children of a LMIC. We observed early signs of a PA transition towards a less active lifestyle in a subgroup residing in areas with better infrastructure that concomitantly tended to have higher leptin concentrations. Considering that area-dependent PA differences were more pronounced among girls than boys, whereas differences in leptin levels were less pronounced, not only biological, but also external factors explain PA transition.

Rapid amelioration of anorexia nervosa in a male adolescent during metreleptin treatment including recovery from hypogonadotropic hypogonadism.

With this case report we support our medical hypothesis that metreleptin treatment ameliorates starvation related emotional, cognitive and behavioral symptomatology of anorexia nervosa (AN) and show for the first time strong effects in a male patient with AN. A 15.9 year old adolescent with severe AN of eight-month duration was treated off-label with metreleptin. Hyperactivity was assessed with accelerometry. Visual analogue scales (VAS), validated self- and clinician rating scales and lab results tracked changes from baseline to end of the 24-day dosing period and a five-month follow-up. Substantial improvements of mood and eating disorder related cognitions and hyperactivity set in after two days of treatment. During dosing, sub-physiological testosterone and TT3 levels normalized; clinically libido reemerged. Weight did not increase substantially during the dosing period. During follow-up target weight was attained; mood did not deteriorate; hyperactivity ceased. The results substantiate the strong effects seen in female cases and underscore the need for a double-blind placebo-controlled trial to confirm the observed strong, multiple and rapid onset beneficial effects of metreleptin in AN.

A mendelian randomization study on causal effects of 25(OH)vitamin D levels on attention deficit/hyperactivity disorder.

BACKGROUND: While observational studies revealed an inverse association between serum 25(OH)vitamin D (25(OH)D) and the risk of attention deficit/hyperactivity disorder (ADHD), the causality of this relationship remains unclear. METHODS: We conducted a bidirectional two-sample Mendelian Randomization (MR) study to examine whether 25(OH)D has an effect on the risk to develop ADHD or vice versa. Information on single nucleotide polymorphisms (SNP) associated with serum 25(OH)D was obtained from a genome-wide association study (GWAS) considering phenotype data from 79,366 individuals of European ancestry. Data on risk for ADHD were derived from a GWAS analysis with 20,183 individuals diagnosed with ADHD and 35,191 controls. For our analysis, we considered effect sizes based on the European participants (19,099 cases and 34,194 controls). RESULTS: Single SNP analyses showed a causal effect of vitamin D on ADHD risk for only one SNP (rs12785878, p = 0.024). The overall MR estimates did not reveal a causal effect of 25(OH)D on risk for ADHD. In the reverse analysis, neither any single nor the multi-SNP MR analyses showed a causal effect of ADHD on 25(OH)D. CONCLUSION: Results from this two-sample MR study did not confirm a causal effect of 25(OH)D on ADHD or vice versa. Accordingly, our study does not provide evidence that improving 25(OH)D via supplementation could reduce the risk of developing ADHD.

Clinical Trials Required to Assess Potential Benefits and Side Effects of Treatment of Patients With Anorexia Nervosa With Recombinant Human Leptin.

The core phenotype of anorexia nervosa (AN) comprises the age and stage dependent intertwining of both its primary and secondary (i.e., starvation induced) somatic and mental symptoms. Hypoleptinemia acts as a key trigger for the adaptation to starvation by affecting diverse brain regions including the reward system and by induction of alterations of the hypothalamus-pituitary-"target-organ" axes, e.g., resulting in amenorrhea as a characteristic symptom of AN. Particularly, the rat model activity-based anorexia (ABA) convincingly demonstrates the pivotal role of hypoleptinemia in the development of starvation-induced hyperactivity. STAT3 signaling in dopaminergic neurons in the ventral tegmental area (VTA) plays a crucial role in the transmission of the leptin signal in ABA. In patients with AN, an inverted U-shaped relationship has been observed between their serum leptin levels and physical activity. Albeit obese and therewith of a very different phenotype, humans diagnosed with rare congenital leptin deficiency have starvation like symptoms including hypothalamic amenorrhea in females. Over the past 20 years, such patients have been successfully treated with recombinant human (rh) leptin (metreleptin) within a compassionate use program. The extreme hunger of these patients subsides within hours upon initiation of treatment; substantial weight loss and menarche in females ensue after medium term treatment. In contrast, metreleptin had little effect in patients with multifactorial obesity. Small clinical trials have been conducted for hypothalamic amenorrhea and to increase bone mineral density, in which metreleptin proved beneficial. Up to now, metreleptin has not yet been used to treat patients with AN. Metreleptin has been approved by the FDA under strict regulations solely for the treatment of generalized lipodystrophy. The recent approval by the EMA may offer, for the first time, the possibility to treat extremely hyperactive patients with AN off-label. Furthermore, a potential dissection of hypoleptinemia-induced AN symptoms from the primary cognitions and behaviors of these patients could ensue. Accordingly, the aim of this article is to review the current state of the art of leptin in relation to AN to provide the theoretical basis for the initiation of clinical trials for treatment of this eating disorder.

Vitamin D and the Risk of Depression: A Causal Relationship? Findings from a Mendelian Randomization Study.

While observational studies show an association between 25(OH)vitamin D concentrations and depressive symptoms, intervention studies, which examine the preventive effects of vitamin D supplementation on the development of depression, are lacking. To estimate the role of lowered 25(OH)vitamin D concentrations in the etiology of depressive disorders, we conducted a two-sample Mendelian randomization (MR) study on depression, i.e., "depressive symptoms" (DS, n = 161,460) and "broad depression" (BD, n = 113,769 cases and 208,811 controls). Six single nucleotide polymorphisms (SNPs), which were genome-wide significantly associated with 25(OH)vitamin D concentrations in 79,366 subjects from the SUNLIGHT genome-wide association study (GWAS), were used as an instrumental variable. None of the six SNPs was associated with DS or BD (all p > 0.05). MR analysis revealed no causal effects of 25(OH)vitamin D concentration, either on DS (inverse variance weighted (IVW); b = 0.025, SE = 0.038, p = 0.52) or on BD (IVW; b = 0.020, SE = 0.012, p = 0.10). Sensitivity analyses confirmed that 25(OH)vitamin D concentrations were not significantly associated with DS or BD. The findings from this MR study indicate no causal relationship between vitamin D concentrations and depressive symptoms, or broad depression. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

High CRP Levels After Critical Illness are Associated With an Increased Risk of Rehospitalization.

PURPOSE: Chronic inflammation, even at subclinical levels, is associated with adverse long-term outcome. PATIENTS AND METHODS: In this prospective, observational study, 66 critically ill patients surviving to hospital discharge were included. C-reactive protein (CRP) levels were determined at hospital discharge, 1, 2, and 6 weeks after hospital discharge. All the patients were repeatedly screened for adverse events resulting in rehospitalization or death for 1.5 years. RESULTS: After hospital discharge, over two-thirds of the patients exhibited elevated CRP levels (>2.0 mg/L). During the first week, CRP decreased compared with hospital discharge (P < 0.001) but did not change after week 1 (P = 0.67). Age (P = 0.24), surgical status (P = 0.95), or sepsis (P = 0.77) did not influence the CRP course. The latter differed between patients with (n = 15) and without (n = 51) adverse events (P = 0.003). CRP levels of patients without adverse events persistently decreased after hospital discharge (P = 0.03), whereas those of patients with adverse events did not (P = 0.86) but rebounded early. CONCLUSIONS: Plasma CRP levels in critically ill patients decreased during the first week after hospital discharge but remained unchanged during the subsequent 5 weeks. Over two-thirds of the patients exhibited elevated CRP levels compatible with chronic sub-clinical inflammation. Persistently elevated CRP levels after hospital discharge are associated with higher risk of rehospitalization.