Adiposity is Associated with Regional Cortical Thinning

BACKGROUND: Although obesity is associated with structural changes in brain grey matter, findings have been inconsistent and the precise nature of these changes is unclear. Inconsistencies may partly be due to the use of different volumetric morphometry methods, and the inclusion of participants with comorbidities that exert independent effects on brain structure. The latter concern is particularly critical when sample sizes are modest. The purpose of the current study was to examine the relationship between cortical grey matter and body mass index (BMI), in healthy participants, excluding confounding comorbidities and using a large sample size. SUBJECTS: A total of 202 self-reported healthy volunteers were studied using surface-based morphometry, which permits the measurement of cortical thickness, surface area and cortical folding, independent of each other. RESULTS: Although increasing BMI was not associated with global cortical changes, a more precise, region-based analysis revealed significant thinning of the cortex in two areas: left lateral occipital cortex (LOC) and right ventromedial prefrontal cortex (vmPFC). An analogous region-based analysis failed to find an association between BMI and regional surface area or folding. Participants' age was also found to be negatively associated with cortical thickness of several brain regions; however, there was no overlap between the age- and BMI-related effects on cortical thinning. CONCLUSIONS: Our data suggest that the key effect of increasing BMI on cortical grey matter is a focal thinning in the left LOC and right vmPFC. Consistent implications of the latter region in reward valuation, and goal control of decision and action suggest a possible shift in these processes with increasing BMI.We thank all the participants and the staff of the Wolfson Brain Imaging Centre. This work was supported by the Bernard Wolfe Health Neuroscience Fund (NM, HZ, ISF, PCF), the Wellcome Trust (RGAG/144 to N.M, RGAG/188 to ISF, RNAG/259 to PCF) and the Medical Research Council (G0701497 to KDE).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ijo.2016.42

Identification of blood-based molecular signatures for prediction of response and relapse in schizophrenia patients

The current inability of psychiatric medicine to objectively select the most appropriate treatment or to predict imminent relapse are major factors contributing to the severity and clinical burden of schizophrenia. We have previously used multiplexed immunoassays to show that schizophrenia patients have a distinctive molecular signature in serum compared with healthy control subjects. In the present study, we used the same approach to measure biomarkers in a population of 77 schizophrenia patients who were followed up over 25 months with four aims: (1) to identify molecules associated with symptom severity in antipsychotic naive and unmedicated patients, (2) to determine biomarker signatures that could predict response over a 6-week treatment period, (3) to identify molecular panels that could predict the time to relapse in a cross-sectional population of patients in remission and (4) to investigate how the biological relapse signature changed throughout the treatment course. This led to identification of molecular signatures that could predict symptom improvement over the first 6 weeks of treatment as well as predict time to relapse in a subset of 18 patients who experienced recurrence of symptoms. This study provides the groundwork for the development of novel objective clinical tests that can help psychiatrists in the clinical management of schizophrenia

Increased carotid IMT in overweight and obese women affected by Hashimoto's thyroiditis: an adiposity and autoimmune linkage?

<p>Abstract</p> <p>Background</p> <p>Hashimoto's thyroiditis is the most important cause of hypothyroidism. It is a systemic disease that can even affect the cardiovascular system, by accelerating the atherosclerotic process. Aim of this study was to examine whether autoimmune thyroiditis has an effect on the intima-media thickness of the common carotid artery (IMT-CCT), independently of the thyroid function and well-known cardiovascular risk factors. Hashimoto's thyroiditis is a systemic disease. The aim is to examine whether autoimmune thyroiditis and adiposity can effect carotid IMT independently of thyroid hormones and cardiovascular risk factors.</p> <p>Methods</p> <p>A total of 104 obese women (BMI ≥ 25.0 kg/m^-2), with FT3 and FT4 serum levels in the normal range and TSH levels < 4.5 μU/ml, were investigated. None of these patients was taking any kind of drug influencing thyroid function. Measurements were made of the IMT-CCT, BMI, waist circumference, blood pressure levels, as well as fasting TSH, FT3, FT4, anti-thyroid antibodies, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol serum concentrations.</p> <p>Results</p> <p>Of the 104 women, 30 (28.8%) were affected by autoimmune thyroiditis. Significantly higher values of IMT-CCT (p < 0.05), TSH (p < 0.05), and triglycerides (p < 0.05) were obtained, and significantly lower values of FT4 (p < 0.05), in patients with Hashimoto's thyroiditis as compared to those with a normal thyroid function. When examining the whole group together, at multiple regression analysis Hashimoto's thyroiditis maintained a positive association with the IMT (p < 0.001), independently of age, hypertension, BMI, and the fasting serum levels of TSH, FT3, FT4, insulin, fasting glycemia, triglycerides, total and HDL-cholesterol levels.</p> <p>Conclusions</p> <p>The present study shows that Hashimoto's thyroiditis is associated to an increased IMT only in overweight and obese, independently of the thyroid function, BMI and cardiovascular risk factors. These results suggest that Hashimoto's thyroiditis is a marker of evolution of the atherosclerosis if combined to adiposity.</p

Evidence for energy conservation during pubertal growth. A 10-year longitudinal study (EarlyBird 71)

BACKGROUND: Diabetes is closely linked to obesity, and obesity rates climb during adolescence for reasons that are not clear. Energy efficiency is important to obesity, and we describe a temporary but substantial fall in absolute energy expenditure, compatible with improved energy efficiency, during the rapid growth phase of puberty. METHODS: In a longitudinal cohort study lasting 10 years, we measured voluntary energy expenditure as physical activity (PA) by accelerometry, involuntary energy expenditure as resting energy expenditure (REE) by oxygen consumption, body mass index (BMI) and body composition by dual energy X-ray absorptiometry annually on 10 occasions from 7 to 16 years in the 347 children of the EarlyBird study. We used mixed effects modelling to analyse the trends in REE and their relationship to BMI, lean mass (LM), fat mass (FM), age, PA and pubertal stage. RESULTS: Relative REE and total PA fell during puberty, as previously described, but the longitudinal data and narrow age-range of the cohort (s.d.±4m) revealed for the first time a substantial fall in absolute REE during the period of maximum growth. The fall became clearer still when adjusted for FM and LM. The fall could not be explained by fasting insulin, adiponectin, leptin, luteinising hormone or follicle stimulating hormone. CONCLUSIONS: There appears to be a temporary but substantial reduction in energy expenditure during puberty, which is unrelated to changes in body composition. If it means higher energy efficiency, the fall in REE could be advantageous in an evolutionary context to delivering the extra energy needed for pubertal growth, but unfavourable to weight gain in a contemporary environment.International Journal of Obesity advance online publication, 4 October 2016; doi:10.1038/ijo.2016.158.We are grateful to the Bright futures trust, Fountain Foundation, BUPA Foundation, EarlyBird Diabetes Trust and countless individual donors who made this study possible

Correlations among Brain Gray Matter Volumes, Age, Gender, and Hemisphere in Healthy Individuals

To determine the relationship between age and gray matter structure and how interactions between gender and hemisphere impact this relationship, we examined correlations between global or regional gray matter volume and age, including interactions of gender and hemisphere, using a general linear model with voxel-based and region-of-interest analyses. Brain magnetic resonance images were collected from 1460 healthy individuals aged 20–69 years; the images were linearly normalized and segmented and restored to native space for analysis of global gray matter volume. Linearly normalized images were then non-linearly normalized and smoothed for analysis of regional gray matter volume. Analysis of global gray matter volume revealed a significant negative correlation between gray matter ratio (gray matter volume divided by intracranial volume) and age in both genders, and a significant interaction effect of age × gender on the gray matter ratio. In analyzing regional gray matter volume, the gray matter volume of all regions showed significant main effects of age, and most regions, with the exception of several including the inferior parietal lobule, showed a significant age × gender interaction. Additionally, the inferior temporal gyrus showed a significant age × gender × hemisphere interaction. No regional volumes showed significant age × hemisphere interactions. Our study may contribute to clarifying the mechanism(s) of normal brain aging in each brain region

A Nutrition and Conditioning Intervention for Natural Bodybuilding Contest Preparation: Case Study.

Bodybuilding competitions are becoming increasingly popular. Competitors are judged on their aesthetic appearance and usually exhibit a high level of muscularity and symmetry and low levels of body fat. Commonly used techniques to improve physique during the preparation phase before competitions include dehydration, periods of prolonged fasting, severe caloric restriction, excessive cardiovascular exercise and inappropriate use of diuretics and anabolic steroids. In contrast, this case study documents a structured nutrition and conditioning intervention followed by a 21 year-old amateur bodybuilding competitor to improve body composition, resting and exercise fat oxidation, and muscular strength that does not involve use of any of the above mentioned methods. Over a 14-week period, the Athlete was provided with a scientifically designed nutrition and conditioning plan that encouraged him to (i) consume a variety of foods; (ii) not neglect any macronutrient groups; (iii) exercise regularly but not excessively and; (iv) incorporate rest days into his conditioning regime. This strategy resulted in a body mass loss of 11.7 kg’s, corresponding to a 6.7 kg reduction in fat mass and a 5.0 kg reduction in fat-free mass. Resting metabolic rate decreased from 1993 kcal/d to 1814 kcal/d, whereas resting fat oxidation increased from 0.04 g/min to 0.06 g/min. His capacity to oxidize fat during exercise increased more than two-fold from 0.24 g/min to 0.59 g/min, while there was a near 3-fold increase in the corresponding exercise intensity that elicited the maximal rate of fat oxidation; 21% V̇ O2max to 60% V̇ O2max. Hamstring concentric peak torque decreased (1.7 to 1.5 Nm/kg), whereas hamstring eccentric (2.0 Nm/kg to 2.9 Nm/kg), quadriceps concentric (3.4 Nm/kg to 3.7 Nm/kg) and quadriceps eccentric (4.9 Nm/kg to 5.7 Nm/kg) peak torque all increased. Psychological mood-state (BRUMS scale) was not negatively influenced by the intervention and all values relating to the Athlete’s mood-state remained below average over the course of study. This intervention shows that a structured and scientifically supported nutrition strategy can be implemented to improve parameters relevant to bodybuilding competition and importantly the health of competitors, therefore questioning the conventional practices of bodybuilding preparation

Elimination Therapy for the Endemic Malarias

Most malaria diagnosed outside endemic zones occurs in patients experiencing the consequences of what was likely a single infectious bite by an anopheline mosquito. A single species of parasite is nearly always involved and expert opinion on malaria chemotherapy uniformly prescribes species- and stage-specific treatments. However the vast majority of people experiencing malaria, those resident in endemic zones, do so repeatedly and very often with the involvement of two or more species and stages of parasite. Silent forms of these infections—asymptomatic and beyond the reach of diagnostics—may accumulate to form substantial and unchallenged reservoirs of infection. In such settings treating only the species and stage of malaria revealed by diagnosis and not others may not be sensible or appropriate. Developing therapeutic strategies that address all species and stages independently of diagnostic evidence may substantially improve the effectiveness of the control and elimination of endemic malaria

Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III), 1991-1994

<p>Abstract</p> <p>Background</p> <p>Albuminuria, a common marker of kidney damage, serves as an important predictive factor for the progression of kidney disease and for the development of cardiovascular disease. While the underlying etiology is unclear, chronic, low-grade inflammation is a suspected key factor. Genetic variants within genes involved in inflammatory processes may, therefore, contribute to the development of albuminuria.</p> <p>Methods</p> <p>We evaluated 60 polymorphisms within 27 inflammatory response genes in participants from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a population-based and nationally representative survey of the United States. Albuminuria was evaluated as logarithm-transformed albumin-to-creatinine ratio (ACR), as ACR ≥ 30 mg/g, and as ACR above sex-specific thresholds. Multivariable linear regression and haplotype trend analyses were conducted to test for genetic associations in 5321 participants aged 20 years or older. Differences in allele and genotype distributions among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans were tested in additive and codominant genetic models.</p> <p>Results</p> <p>Variants in several genes were found to be marginally associated (uncorrected P value < 0.05) with log(ACR) in at least one race/ethnic group, but none remained significant in crude or fully-adjusted models when correcting for the false-discovery rate (FDR). In analyses of sex-specific albuminuria, <it>IL1B </it>(rs1143623) among Mexican Americans remained significantly associated with increased odds, while <it>IL1B </it>(rs1143623), <it>CRP </it>(rs1800947) and <it>NOS3 </it>(rs2070744) were significantly associated with ACR ≥ 30 mg/g in this population (additive models, FDR-P < 0.05). In contrast, no variants were found to be associated with albuminuria among non-Hispanic blacks after adjustment for multiple testing. The only variant among non-Hispanic whites significantly associated with any outcome was <it>TNF </it>rs1800750, which failed the test for Hardy-Weinberg proportions in this population. Haplotypes within <it>MBL2</it>, <it>CRP</it>, <it>ADRB2, IL4R</it>, <it>NOS3</it>, and <it>VDR </it>were significantly associated (FDR-P < 0.05) with log(ACR) or albuminuria in at least one race/ethnic group.</p> <p>Conclusions</p> <p>Our findings suggest a small role for genetic variation within inflammation-related genes to the susceptibility to albuminuria. Additional studies are needed to further assess whether genetic variation in these, and untested, inflammation genes alter the susceptibility to kidney damage.</p