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Food restriction paradigms are widely used in animal studies to investigate systems involved in energy regulation. We have observed behavioral, physiological, and molecular differences in response to food restriction in three inbred mouse strains, C57BL/6J, A/J, and DBA/2J. These are the progenitors of chromosome substitution and recombinant inbred mouse strains used for mapping complex traits. DBA/2J and A/J mice increased their locomotor activity during food restriction, and both displayed a decrease in body temperature, but the decrease was significantly larger in DBA/2J compared with A/J mice. C57BL/6J mice did not increase their locomotor activity and displayed a large decrease in their body temperature. The large decline in body temperature during food restriction in DBA/2J and C57BL/6J strains was associated with a robust reduction in plasma leptin levels. DBA/2J mice showed a marked decrease in white and brown adipose tissue masses and an upregulation of the antithermogenic hypothalamic neuropeptide Y [Y.sub.1] receptor. In contrast, A/J mice showed a reduction in body temperature to a lesser extent that may be explained by downregulation of the thermogenic melanocortin 3 receptor and by behavioral thermoregulation as a consequence of their increased locomotor activity. These data indicate that genetic background is an important parameter in controlling an animal's adaptation strategy in response to food restriction. Therefore, mouse genetic mapping populations based on these progenitor lines are highly valuable for investigating mechanisms underlying strain-dependent differences in behavioral physiology that are seen during reduced food availability. locomotor activity; body temperature; food intake; neuropeptide Y; melanocortin doi:10.1152/ajpendo.00068.2005

Abstract Background Previous Magnetic Resonance Imaging (MRI) studies of people with anorexia nervosa (AN) have shown differences in brain structure. This study aimed to provide preliminary extensions of this data by examining how different levels of appetitive restraint impact on brain volume. Methods Voxel based morphometry (VBM), corrected for total intracranial volume, age, BMI, years of education in 14 women with AN (8 RAN and 6 BPAN) and 21 women (HC) was performed. Correlations between brain volume and dietary restraint were done using Statistical Package for the Social Sciences (SPSS). Results Increased right dorsolateral prefrontal cortex (DLPFC) and reduced right anterior insular cortex, bilateral parahippocampal gyrus, left fusiform gyrus, left cerebellum and right posterior cingulate volumes in AN compared to HC. RAN compared to BPAN had reduced left orbitofrontal cortex, right anterior insular cortex, bilateral parahippocampal gyrus and left cerebellum. Age negatively correlated with right DLPFC volume in HC but not in AN; dietary restraint and BMI predicted 57% of variance in right DLPFC volume in AN. Conclusions In AN, brain volume differences were found in appetitive, somatosensory and top-down control brain regions. Differences in regional GMV may be linked to levels of appetitive restraint, but whether they are state or trait is unclear. Nevertheless, these discrete brain volume differences provide candidate brain regions for further structural and functional study in people with eating disorders.

Abstract Background Set-shifting is impaired in people with anorexia nervosa (AN), but the underlying physiological and biochemical processes are unclear. Animal studies have established that glutamatergic pathways in the prefrontal cortex play an important role in set-shifting ability. However, it is not yet understood whether levels of serum glutamatergic amino acids are associated with set-shifting performance in humans. The aim of this study was to determine whether serum concentrations of amino acids related to glutamatergic neurotransmission (glutamine, glutamate, glycine, l-serine, d-serine) are associated with set-shifting ability in people with acute AN and those after recovery. Methods Serum concentrations of glutamatergic amino acids were measured in 27 women with current AN (AN group), 18 women recovered from AN (ANRec group) and 28 age-matched healthy controls (HC group). Set-shifting was measured using the Wisconsin Card Sorting Test (WCST) and the Trail Making Task (TMT). Dimensional measures of psychopathology were used, including the Eating Disorder Examination Questionnaire (EDEQ), the Maudsley Obsessive-Compulsive Inventory (MOCI) and the Hospital Anxiety and Depression Scale (HADS). Results Serum glutamine concentrations in the AN group (1,310.2 ± 265.6 μM, mean ± SD) were significantly higher (by approximately 20%) than those in the HC group (1,102.9 ± 152.7 μM, mean ± SD) (F(2, 70) = 6.3, P = 0.003, 95% CI 61.2 to 353.4). Concentrations of serum glutamine were positively associated with markers of the illness severity: a negative correlation was present between serum glutamine concentrations and body mass index (BMI) and lowest BMI and a positive correlation was found between duration of illness and EDEQ. The AN group showed significantly impaired set shifting in the WCST, both total errors, and perseverative errors. In the AN group, there were no correlations between serum glutamine concentrations and set shifting. Conclusions Serum concentrations of glutamine may be a biomarker of illness severity in people with AN. It does not appear to be directly associated with changes in executive function.

Abstract Background Anorexia nervosa (AN) is a severe mental illness. Drug treatments are not effective and there is no established first choice psychological treatment for adults with AN. Neuropsychological studies have shown that patients with AN have difficulties in cognitive flexibility: these laboratory based findings have been used to develop a clinical intervention based on Cognitive Remediation Therapy (CRT) which aims to use cognitive exercises to strengthen thinking skills. Aims 1) To conduct a preliminary investigation of CRT in patients with AN 2) to explore whether cognitive training improves performance in set shifting tasks 3) to explore whether CRT exercises are appropriate and acceptable to AN patients 4) to use the data to improve a CRT module for AN patients. Methods Intervention was comprised of ten 45 minute sessions of CRT. Four patients with AN were assessed before and after the ten sessions using five set shifting tests and clinical assessments. At the end, each patient wrote a letter providing feedback on the intervention. Results Post intervention, three of the five set shifting assessments showed a moderate to large effect size in performance and two showed a large effect size in performance, both indicative of improved flexibility. Patients were aware of an improvement in their cognitive flexibility qualitative feedback was generally positive towards CRT. Discussion This preliminary study suggests that CRT changed performance on flexibility tasks and may be beneficial for acute, treatment resistant patients with AN. Feedback gathered from this small case series has enabled modification of the intervention for a future larger study, for example, by linking exercises with real life behavioural tasks and including exercises that encourage global thinking. Conclusion This exploratory study has produced encouraging data supporting the use of CRT in patients with AN: it has also provided insight into how the module should be tailored to maximise its effectiveness for people with acute AN.