Neurobiological and metabolic mechanisms of binge-eating in anorexia and bulimia nervosa

Binge-eating is characterised by the recurrent consumption of large amounts of food, which co-occurs with a subjective loss of control over intake. This transdiagnostic syndrome results in significant distress, functional impairment and comorbidity. However, precise characterisation of the physiological and neurobiological mechanisms that give rise to, or maintain, this behaviour is lacking. This thesis integrates observations across metabolic, neural and behavioural levels in women with and without eating disorders, providing novel insights into how perturbations across each strata interact with one another in illness and in health to shape eating behaviour. In Chapter 1, I review the classification of binge-eating disorders prior to summarising the extant literature on homeostatic and non-homeostatic mechanisms that influence (ab)normal eating behaviour. This introductory chapter also reviews current perspectives on how psychological stress influences disordered eating, outlining the motivation for the multimodal neuroimaging protocol detailed in Chapter 2. Chapter 2 focuses on the specific methodology of this neuroimaging study, which examined the impact of acute, psychological stress on gut hormones, endocrine responses, and inhibitory control in women acutely ill with the binge-eating and purging subtype of anorexia nervosa, bulimia nervosa and matched controls. Chapters 3 through 5 report the results of this study. Chapter 3 focuses on findings of dissociable hormonal responses to stress in anorexia and bulimia nervosa, presenting novel evidence that links acute changes in mental state to altered gut hormone signalling in anorexia nervosa. Chapter 4 is dedicated to the functional magnetic resonance imaging arm of the protocol, which rigorously examined the impact of diagnosis and induced stress on two forms of response inhibition: proactive and reactive control. Chapter 5 provides insight into associations between peripheral metabolic markers and neural integrity of the cerebral cortex in patients and controls. Finally, Chapter 6 provides a brief summary, discusses the implications of these findings and presents some ongoing and future research that extends this original work. In summary, this thesis represents, to my knowledge, the first attempt to generate a multi-level framework for understanding the physiological and psychological mechanisms of illnesses characterised by binge-eating. Findings identify important metabolic and neurobiological distinctions between two eating disorders with shared symptomatology, demonstrating the need for, and value in, integrative models of mental illness.Cambridge International Trust; NIH Oxford Cambridge Scholars Progra

Brightness temperature and attenuation diversity statistics at 20.6 and 31.65 GHz for the Colorado Research Network

A limited network of four dual-channel microwave radiometers, with frequencies of 20.6 and 31.65 GHz, was operated in the front range of eastern Colorado from 1985 to 1988. Data, from November 1987 through October 1988 are analyzed to determine both single-station and joint-station brightness temperature and attenuation statistics. Only zenith observations were made. The spatial separations of the stations varied from 50 km to 190 km. Before the statistics were developed, the data were screened by rigorous quality control methods. One such method, that of 20.6 vs. 31.65 GHz scatter plots, is analyzed in detail, and comparisons are made of measured vs calculated data. At 20.6 and 31.65 GHz, vertical attenuations of 5 and 8 dB are exceeded 0.01 percent of the time. For these four stations and at the same 0.01 percent level, diversity gains from 6 to 8 dB are possible with the 50 to 190 km separations

Tuberculosis in relation to measles and other infectious diseases: a study of the intra-dermal tuberculin test

Medicine being an Art as well as a Science, it is liable to reflect numan ta.ilins and foibles, one. of whicn is the weakness for a "fashion'. it may be said that of the various tuberculin tests, the one associated with von Pirquet's name has been the fashionable one. Recently, however, the intra-dermal method or Mendel and Mantoux has bid fair to supplant the scarification test in popularity. If it is going to prove fashionable, it occurred to one that it might be of service to investigate its possible fallacies, particularly in relation to the acute infectious diseases. Although the physician may be prone to "fashion" in technique, he is also a slave to dogma. A positive statement in medicine often acquires the authority of an established principle. One such principle has been that tuberculosis is particularly liable to ensue after certain acute infectious diseases. Accordingly adopting the latest "fashion" in tuberculin tests, I set out as a devout believer to assess the value or the test in mitigating this grave sequel of events

Suprarenal insufficiency in tuberculous patients, with special reference to the sodium level in the blood serum

#1. Evidence of suprarenal insufficiency has been sought in 174 patients with tuberculosis. Clinical features have been examined and the level of sodium in the blood serum investigated. #2. Serial sections of glands obtained at autopsy showed suprarenal abnormality in eleven patients. • Serum sodium above 315. • • Three autopsies. • • • One positive inoculation for tubercle bacilli. • Serum sodium below 315. • • twenty -two autopsies. • • • Seven positive on inoculation for tubercle bacilli. • Serial sections. • • Two definite tuberculous lesions. • • Pour small tuberculous foci. • • One amyloid degeneration. #3. Suprarenal insufficiency was diagnosed in four patients, two showed tuberculous lesions of the suprarenals, in one there was no evidence of disease in the glands, while the other is untraced. #4. The normal range of sodium has been assessed as 315 to 350 mgms per 100c.cm. of serum. #5. In 114 cases the level of serum sodium was normal. • In 60 cases the level of serum sodium was low. #6. A low serum sodium indicates a bad prognosis. #7. Such suprarenal lesions as were found, occurred with one exception, in Group with low serum sodium. #8. Pigmentation of the skin was present only in the group with a low serum sodium. #9. Cases with pyrexia, sweating, diarrhoea or vomiting did not have of necessity a low serum sodium. #10. There is no proof that serous effusions or purulent discharges can drain away sufficient sodium to account for the low level, nor that they upset the sodium balance. #11. There is no evidence that cases with a low serum sodium had a low enough sodium intake to explain the decreased serum level. #12. Even with a low sodium intake there is an appreciable loss of sodium in the urine. #13. In the presence of a low serum sodium continued excretion of sodium in the urine suggests suprarenal damage, even'with a low intake. #14. In the absence of factors such as severe vomiting or diarrhoea a low serum sodium is suspicious evidence of suprarenal insufficiency

Radiometric observations at 20.6, 31.65, and 90.0 GHz: Continuing studies

Ground based radiometer measurements at 20.6, 31.65, and 90.0 GHz were analyzed to provide attenuation statistics, thus extending the data base of previous NAPEX studies. Using data from colocated radiosondes, comparisons of measurements and calculations of brightness temperatures are presented. The oxygen absorption model of Rosenkranz and the water vapor absorption models of Liebe and of Waters are used. Data from July 1987 at San Nicolas Island, California and from December 1987, August and November 1988 at Denver, Colorado, are included. Joint attenuation statistics at 20.6 and 31.65 GHz are presented for two locations of the Colorado Research Network for December 1987 and August 1988

Development Of An Engineered Bioluminescent Reporter Phage For Detection Of Bacterial Blight Of Crucifers

Bacterial blight, caused by the phytopathogen Pseudomonas cannabina pv. alisalensis, is an emerging disease afflicting important members of the Brassicaceae family. The disease is often misdiagnosed as pepper spot, a much less severe disease caused by the related pathogen Pseudomonas syringae pv. maculicola. We have developed a phage-based diagnostic that can both identify and detect the causative agent of bacterial blight and differentiate the two pathogens. A recombinant >light>-tagged reporter phage was generated by integrating bacterial luxAB genes encoding luciferase into the genome of P. cannabina pv. alisalensis phage PBSPCA1. The PBSPCA1::luxAB reporter phage is viable and stable and retains properties similar to those of the wildtype phage. PBSPCA1::luxAB rapidly and sensitively detects P. cannabina pv. alisalensis by conferring a bioluminescent signal response to cultured cells. Detection is dependent on cell viability. Other bacterial pathogens of Brassica species such as P. syringae pv. maculicola, Pseudomonas marginalis, Pectobacterium carotovorum, Xanthomonas campestris pv. campestris, and X. campestris pv. raphani either do not produce a response or produce significantly attenuated signals with the reporter phage. Importantly, the reporter phage detects P. cannabina pv. alisalensis on diseased plant specimens, indicating its potential for disease diagnosis.National Science Foundation Small Business Innovative Research 1012059U.S. Department of EducationU.S. Department of AgricultureCellular and Molecular Biolog

Combined effects of age and BMI are related to altered cortical thickness in adolescence and adulthood

Overweight and obesity are associated with functional and structural alterations in the brain, but how these associations change across critical developmental periods remains unknown. Here, we examined the relationship between age, body mass index (BMI) and cortical thickness (CT) in healthy adolescents (n = 70; 14–19 y) and adults (n = 75; 25–45 y). We also examined the relationship between adiposity, impulsivity, measured by delay discounting (DD), and CT of the inferior frontal gyrus (IFG), a region key to impulse control. A significant age-by- BMI interaction was observed in both adolescents and adults; however, the direction of this relationship differed between age groups. In adolescents, increased age-adjusted BMI Z-score attenuated age-related CT reductions globally and in frontal, temporal and occipital regions. In adults, increased BMI augmented age-related CT reductions, both globally and in bilateral parietal cortex. Although DD was unrelated to adiposity in both groups, increased DD and adiposity were both associated with reduced IFG thickness in adolescents and adults. Our findings suggest that the known age effects on CT in adolescence and adulthood are moderated by adiposity. The association between weight, cortical development and its functional implications would suggest that future studies of adolescent and adult brain development take adiposity into account.This work was supported by Wellcome Trust [project grant 206368/ Z/17/Z] (PCF), the Bernard Wolfe Health Neuroscience Fund (HZ, PCF) and the Andalusian Health Service (Consejeria de Salud) [project grant P-10-HUM-6635 (NEUROECOBE)] (AVG). MLW was supported by the Cambridge Trust and NIH-Oxford Cambridge Scholars Program

Sugar addiction: the state of the science.

PURPOSE: As obesity rates continue to climb, the notion that overconsumption reflects an underlying 'food addiction' (FA) has become increasingly influential. An increasingly popular theory is that sugar acts as an addictive agent, eliciting neurobiological changes similar to those seen in drug addiction. In this paper, we review the evidence in support of sugar addiction. METHODS: We reviewed the literature on food and sugar addiction and considered the evidence suggesting the addictiveness of highly processed foods, particularly those with high sugar content. We then examined the addictive potential of sugar by contrasting evidence from the animal and human neuroscience literature on drug and sugar addiction. RESULTS: We find little evidence to support sugar addiction in humans, and findings from the animal literature suggest that addiction-like behaviours, such as bingeing, occur only in the context of intermittent access to sugar. These behaviours likely arise from intermittent access to sweet tasting or highly palatable foods, not the neurochemical effects of sugar. CONCLUSION: Given the lack of evidence supporting it, we argue against a premature incorporation of sugar addiction into the scientific literature and public policy recommendations.Wellcome Trust (Senior Fellowship award)This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00394-016-1229-