Increased anticipatory but decreased consummatory brain responses to food in sisters of Anorexia Nervosa patients

Background We have previously shown increased anticipatory and consummatory neural responses to rewarding and aversive food stimuli in women recovered from anorexia nervosa (AN). Aims To determine if these differences are trait markers for anorexia nervosa we examined the neural response in those with a familial history but no personal history of AN. Method 36 volunteers were recruited, 15 who had a sister with anorexia nervosa (FH) and 21 control participants. Using fMRI we examined the neural response during an anticipatory phase (food cues, rewarding and aversive), an effort phase and a consummatory phase (rewarding and aversive tastes). Results FH volunteers showed increased activity in the caudate during the anticipation of both reward and aversive food and in the thalamus and amygdala during anticipation of aversive only. FH had decreased activity in the dorsal anterior cingulate cortex, the pallidum and the superior frontal gyrus during taste consumption. Conclusions Increased neural anticipatory but decreased consummatory responses to food might be a biomarker for AN. Interventions that could normalize these differences may help to prevent disorder onset

Enhanced neural response to anticipation, effort and consummation of reward and aversion during Bupropion treatment

Background We have previously shown that the selective serotonergic re-uptake inhibitor, citalopram, reduces the neural response to reward and aversion in healthy volunteers. We suggest that this inhibitory effect might underlie the emotional blunting reported by patients on these medications. Bupropion is a dopaminergic and noradrenergic re-uptake inhibitor and has been suggested to have more therapeutic effects on reward-related deficits. However, how bupropion affects the neural responses to reward and aversion is unclear. Methods 17 healthy volunteers (9 female, 8 male) received 7 days of bupropion (150 mg/day) and 7 days of placebo treatment, in a double-blind crossover design. Our functional Magnetic Resonance Imaging task consisted of 3 phases; an anticipatory phase (pleasant or unpleasant cue), an effort phase (button presses to achieve a pleasant taste or to avoid an unpleasant taste) and a consummatory phase (pleasant or unpleasant tastes). Volunteers also rated wanting, pleasantness and intensity of the tastes. Results Relative to placebo, bupropion increased activity during the anticipation phase in the ventral medial prefrontal cortex (vmPFC) and caudate. During the effort phase, bupropion increased activity in the vmPFC, striatum, dorsal anterior cingulate cortex and primary motor cortex. Bupropion also increased medial orbitofrontal cortex, amygdala and ventral striatum activity during the consummatory phase. Conclusions Our results are the first to show that bupropion can increase neural responses during the anticipation, effort and consummation of rewarding and aversive stimuli. This supports the notion that bupropion might be beneficial for depressed patients with reward-related deficits and blunted affect

Resveratrol Suppresses Constitutive Activation of AKT via Generation of ROS and Induces Apoptosis in Diffuse Large B Cell Lymphoma Cell Lines

BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway

Women gaze behaviour in assessing female bodies: the effects of clothing, body size, own body composition and body satisfaction

Often with minimally clothed figures depicting extreme body sizes, previous studies have shown women tend to gaze at evolutionary determinants of attractiveness when viewing female bodies, possibly for self-evaluation purposes, and their gaze distribution is modulated by own body dissatisfaction level. To explore to what extent women’s body-viewing gaze behaviour is affected by clothing type, dress size, subjective measurements of regional body satisfaction and objective measurements of own body composition (e.g., chest size, body mass index, waist-to-hip ratio), in this self-paced body attractiveness and body size judgement experiment, we compared healthy, young women’s gaze distributions when viewing female bodies in tight and loose clothing of different dress sizes. In contrast to tight clothing, loose clothing biased gaze away from the waist-hip to the leg region, and subsequently led to enhanced body attractiveness ratings and body size underestimation for larger female bodies, indicating the important role of clothing in mediating women’s body perception. When viewing preferred female bodies, women’s higher satisfaction of a specific body region was associated with an increased gaze towards neighbouring body areas, implying satisfaction might reduce the need for comparison of confident body parts; furthermore undesirable body composition measurements were correlated with a gaze avoidance process if the construct was less changeable (i.e. chest size) but a gaze comparison process if the region was more changeable (i.e. body mass index, dress size). Clearly, own body satisfaction and body composition measurements had an evident impact on women’s body-viewing gaze allocation, possibly through different cognitive processes

Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: the role of somatosensory and salience networks.

Atypical anorexia nervosa (AN) usually occurs during adolescence. Patients are often in the normal-weight range at diagnosis; however, they often present with signs of medical complications and severe restraint over eating, body dissatisfaction, and low self-esteem. We investigated functional circuitry underlying the hedonic response in 28 female adolescent patients diagnosed with atypical AN and 33 healthy controls. Participants were shown images of food with high (HC) or low (LC) caloric content in alternating blocks during functional MRI. The HC > LC contrast was calculated. Based on the previous literature on full-threshold AN, we hypothesized that patients would exhibit increased connectivity in areas involved in sensory processing and bottom-up responses, coupled to increased connectivity from areas related to top-down inhibitory control, compared with controls. Patients showed increased connectivity in pathways related to multimodal somatosensory processing and memory retrieval. The connectivity was on the other hand decreased in patients in salience and attentional networks, and in a wide cerebello-occipital network. Our study was the first investigation of food-related neural response in atypical AN. Our findings support higher somatosensory processing in patients in response to HC food images compared with controls, however HC food was less efficient than LC food in engaging patients' bottom-up salient responses, and was not associated with connectivity increases in inhibitory control regions. These findings suggest that the psychopathological mechanisms underlying food restriction in atypical AN differ from full-threshold AN. Elucidating the mechanisms underlying the development and maintenance of eating behavior in atypical AN might help designing specific treatment strategies

Erfolgreiche Pembrolizumab-Therapie bei metastasiertem adenosquamösem Karzinom des Kolons

Adenosquamous carcinoma (ASqC) is an exceedingly rare subtype of colorectal cancer without any known special guidelines for treatment. The biological behaviour and molecular background are widely unknown, although a few case studies report a worse prognosis compared to ordinary colorectal adenocarcinoma. We herein report for the first time the successful immune checkpoint inhibitor therapy in a 40-year-old patient suffering from metastasized right-sided colonic ASqC with unique molecular features, after having previously progressed under standard chemotherapy