Franziska P. Busse

Obesity-Related Differences between Women and Men in Brain Structure and Goal-Directed Behavior

Gender differences in the regulation of body-weight are well documented. Here, we assessed obesity-related influences of gender on brain structure as well as performance in the Iowa Gambling Task. This task requires evaluation of both immediate rewards and long-term outcomes and thus mirrors the trade-off between immediate reward from eating and the long-term effect of overeating on body-weight. In women, but not in men, we show that the preference for salient immediate rewards in the face of negative long-term consequences is higher in obese than in lean subjects. In addition, we report structural differences in the left dorsal striatum (i.e., putamen) and right dorsolateral prefrontal cortex for women only. Functionally, both regions are known to play complimentary roles in habitual and goal-directed control of behavior in motivational contexts. For women as well as men, gray matter volume correlates positively with measures of obesity in regions coding the value and saliency of food (i.e., nucleus accumbens, orbitofrontal cortex) as well as in the hypothalamus (i.e., the brains central homeostatic center). These differences between lean and obese subjects in hedonic and homeostatic control systems may reflect a bias in eating behavior toward energy-intake exceeding the actual homeostatic demand. Although we cannot infer from our results the etiology of the observed structural differences, our results resemble neural and behavioral differences well known from other forms of addiction, however, with marked differences between women and men. These findings are important for designing gender-appropriate treatments of obesity and possibly its recognition as a form of addiction.

Sex-Dependent Influences of Obesity on Cerebral White Matter Investigated by Diffusion-Tensor Imaging

Several studies have shown that obesity is associated with changes in human brain function and structure. Since women are more susceptible to obesity than men, it seems plausible that neural correlates may also be different. However, this has not been demonstrated so far. To address this issue, we systematically investigated the brains white matter (WM) structure in 23 lean to obese women (mean age 25.5 y, std 5.1 y; mean body mass index (BMI) 29.5 kg/m2, std 7.3 kg/m2) and 26 lean to obese men (mean age 27.1 y, std 5.0 y; mean BMI 28.8 kg/m2, std 6.8 kg/m2) with diffusion-weighted magnetic resonance imaging (MRI). There was no significant age (p>0.2) or BMI (p>0.7) difference between female and male participants. Using tract-based spatial statistics, we correlated several diffusion parameters including the apparent diffusion coefficient, fractional anisotropy (FA), as well as axial (λ∥) and radial diffusivity (λ⊥) with BMI and serum leptin levels. In female and male subjects, the putative axon marker λ∥ was consistently reduced throughout the corpus callosum, particularly in the splenium (r = −0.62, p<0.005). This suggests that obesity may be associated with axonal degeneration. Only in women, the putative myelin marker λ⊥ significantly increased with increasing BMI (r = 0.57, p<0.005) and serum leptin levels (r = 0.62, p<0.005) predominantly in the genu of the corpus callosum, suggesting additional myelin degeneration. Comparable structural changes were reported for the aging brain, which may point to accelerated aging of WM structure in obese subjects. In conclusion, we demonstrate structural WM changes related to an elevated body weight, but with differences between men and women. Future studies on obesity-related functional and structural brain changes should therefore account for sex-related differences.

Lead poisoning due to adulterated marijuana.

Recently, 29 patients were admitted to four different hospitals in the greater Leipzig area with classic signs and symptoms of lead intoxication. Despite great efforts, the source of lead could not be identified. The patients eventually conceded that they were regular users of marijuana.

Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity

Previous cross-sectional studies on body-weight-related alterations in brain structure revealed profound changes in the gray matter (GM) and white matter (WM) that resemble findings obtained from individuals with advancing age. This suggests that obesity may lead to structural brain changes that are comparable with brain aging. Here, we asked whether weight-loss-dependent improved metabolic and neurotrophic functioning parallels the reversal of obesity-related alterations in brain structure. To this end we applied magnetic resonance imaging (MRI) together with voxel-based morphometry and diffusion-tensor imaging in overweight to obese individuals who participated in a fitness course with intensive physical training twice a week over a period of 3 months. After the fitness course, participants presented, with inter-individual heterogeneity, a reduced body mass index (BMI), reduced serum leptin concentrations, elevated high-density lipoprotein-cholesterol (HDL-C), and alterations of serum brain-derived neurotrophic factor (BDNF) concentrations suggesting changes of metabolic and neurotrophic function. Exercise-dependent changes in BMI and serum concentration of BDNF, leptin, and HDL-C were related to an increase in GM density in the left hippocampus, the insular cortex, and the left cerebellar lobule. We also observed exercise-dependent changes of diffusivity parameters in surrounding WM structures as well as in the corpus callosum. These findings suggest that weight-loss due to physical exercise in overweight to obese participants induces profound structural brain plasticity, not primarily of sensorimotor brain regions involved in physical exercise, but of regions previously reported to be structurally affected by an increased body weight and functionally implemented in gustation and cognitive processing.

Lead poisoning due to adulterated marijuana in Leipzig

BACKGROUND Between August and December 2007, a mass poisoning due to adulterated marijuana was uncovered in the area of Leipzig, Germany. METHODS Retrospective reports of patients with lead poisoning who were treated at Leipzig University Hospital. Analysis of data from the local health office, where marijuana consumers could have their blood lead concentration determined. RESULTS At Leipzig University Hospital, 35 patients (7 female; age 24.2 +/- 4.4 years) had to be treated for lead poisoning (blood lead levels 1063.3 +/- 864.0 microg/L). Five hundred ninety-seven marijuana consumers (439 men, 158 women; age 26.9 +/- 4.8 years) had their blood lead levels measured at the local health office. Among them, 27.3% had lead levels above the HBM-II threshold, 12.2% had concentrations that required monitoring, and 60.5% had levels below the HBM-I threshold. CONCLUSION Drug consumption should be considered in otherwise unexplained anemia and abdominal colic. Several hundred people suffered lead poisoning presumably resulting from the desire of drug dealers to maximize profits.

Investigating the relationship between body weight and brain connectivity using diffusion tensor imaging

Alkan A 2008. Diffusion-weighted imaging features of brain in obesity. Magnetic Resonance Imaging, vol. 26, no. 4, pp. 446-450. Anwander A 2007. Connectivity-based parcellation of Brocas area. Cerebral Cortex, vol. 17, no. 4, pp. 816-825.Haltia LT 2007. Brain white matter expansion in human obesity and the recovering effect of dieting. Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 8, pp. 3278-3284. Jenkinson P 2002. Improved optimization for the robust and accurate linear registration and motion correction of brain images. NeuroImage, vol. 17, no. 2, pp. 825-841. Lohmann G 2001. Lipsia A new software system for the evaluation of functional magnetic resonance images of the human brain. Computerized Medical Imaging and Graphics, vol. 25, no. 6, pp. 449-457.Smith SM 2006. Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data. NeuroImage, vol. 31, no. 4, pp. 1487-1505. Thirion J-P 1998. Image matching as a diffusion process: an analogy with Maxwells demons, Medical Image Analysis. vol. 2, no. 3, pp. 243-260. Connectivity of voxels related to the negative BMI/FA-correlation overlaid onto a shrunken brain surface (based on a representative individual subject). The tractography indicates that the detected areas in the corpus callosum project to cortical regions in the frontal lobe. Voxel-wise GLM analysis of the FA values. The red dots show the fitted parameters for the factor BMI. There is a negative correlation between FA and BMI (adjusted for subjects age and gender) in anterior regions of the corpus callosum. TBSS analysis of FA maps of 53 subjects with a BMI between 18.9 and 50.7. The results (color-coded in red/yellow) show the negative correlation between BMI and FA (p<0.05 corrected for multiple comparisons). Thus, the greater the BMI, the smaller the FA in anterior regions of the corpus callosum.

Metastasis of Neuroendocrine Colon Carcinoma Mimicking Graves' Ophthalmopathy

We report about a 75-year-old man, who presented to the department of ophthalmology with progressive left-sided exophthalmus and acute loss of vision. Previously, prednisolone had been administered for clinical suspicion of thyroid eye disease without effect. On physical examination, unilateral chemosis and marked proptosis with visual acuity reduced to light perception were present. There were no clinical signs of hyperthyroidism. Thyroid function tests were normal and thyroid autoantibodies negative. Magnetic resonance imaging revealed a nonhomogeneous mass of 3.5 2.2 1.8 cm within the rectus inferior muscle with invasion of the posterior orbita and causing compression of the optic nerve (Fig. 1a). Emergency endonasal decompression was performed and the infiltrated muscle was biopsied. Histopathology showed neuroendocrine tumor cells. Serum chromogranin A levels were elevated (1340 mmol=L, normal <110 mmol=L). Enhanced somatostatin receptor expression was detected in the left orbit and the right colon in an indium In 111 octreoscan (Fig. 1b). An ulcerating tumor was found in the ascending colon on colonoscopy causing subtotal colon stenosis. No other primary was found on extensive imaging. Contrast-enhanced computed tomographic scan and fluorodeoxyglucose positron emission tomography revealed metastatic disease to the liver and mediastinal and abdominal lymph nodes. Subsequently, the patient underwent a hemicolectomy (histology: low-grade malignant well-differentiated neuroendocrine tumor, Ki-67 labelling index: 3%; Fig. 2). A palliative radiotherapy of the orbit and a biotherapy with a long-acting somatostatin-analogue was initiated. Clinicians should be aware that in the absence of clear-cut Graves’ disease, monolateral proptosis and eye muscle dysfunction require urgent imaging to exclude neoplasm. Almost every malignancy may metastasize to the orbit, and orbital metastases are associated with a very poor outcome.

Nichtoperative Therapiemöglichkeiten gastroenteropankreatischer neuroendokriner Tumoren

Gastroenteropancreatic neuroendocrine tumors (NET) are an extremely heterogeneous entity with respect to their biological behavior and functionality. Considering the diversity of NET, therapeutic approaches should be chosen carefully. Besides surgical resection or tumor debulking, various palliative options including medical, locally ablative and radiotherapeutical interventions are available. In functionally active tumors biotherapy with either somatostatin analogues or interferon alpha is indicated. The results of chemotherapy are often unsatisfactory, and its use is mostly restricted to pancreatic neuroendocrine carcinomas. Here, streptozotocin and 5-fluorouracil or doxorubicin are considered standard first-line therapy. In slowly progressing disease, however, chemotherapy is not effective. In rapidly growing carcinomas etoposide and cisplatin are mostly applied. In the treatment of hepatic metastases, embolization therapy with or without chemotherapy is frequently used when surgery is not an option. Radiofrequency ablation is another alternative. In tumors with strong somatostatin receptor expression, radionuclide therapy is an approach that enables internal radiation therapy. Bearing in mind actually running active clinical trials, we here present a therapeutic algorithm which we hope will facilitate therapeutical decision making.

ADOPT: evidence for early use of thiazolidinediones

‘...β-cell dysfunction preceeds diabetes manifestation and underlies any glycemic increase, even within the ranges of normal glucose tolerance.’ Franziska Philomena Busse and Michael Stumvoll † Author for correspondence University of Leipzig, Third Medical Department, Philipp-Rosenthal-Str. 27 04103 Leipzig, Germany Tel.: +49 341 971 3380 Fax: +49 341 971 3389 michael.stumvoll@medizin. uni-leipzig.de