Sinirbiliminden son on yil icinde elde edilen bulgular, psikiyatrik hastaliklarin algilanis bicimiyle ilgili anlayisimizi sekillendirdi. Psikiyatrik bozukluklari aciklamada, psikolojik ve sosyokulturel faktorlere dayanan daha geleneksel teorilere ek olarak, genetik ve norolojik bilesenleri de iceren cok yonlu bir etyolojiyi destekleyen kanitlar her gecen gun artmaktadir. Kendini ac birakma ve asiri derecede dusuk vucut agirligi ile tanimlanan ve olumcul olma riski yuksek bir psikiyatrik bozukluk olan anoreksiya nervoza, bu bulgular isiginda, bir beyin bozuklugu olarak siniflandirilabilir. Birbirinden farkli sonuclar mevcut olmakla birlikte, anoreksiya nervoza hastalarinin beyinlerindeki yapisal ve norokimyasal degisiklik ve anomalileri ve bunlarin islevsel onemi ve bilissel sonuclarini arastiran bircok calisma bulunmaktadir. Bu derlemenin amaci, anoreksiya nervozada saptanan anomali ve degisiklikleri ve bunlari hedef alan birtakim tedavi yaklasimlari ile ilgili guncel literaturu bir araya getirmektir.

In its most basic form impulsivity, a heritable trait, is defined as a tendency to act without control and has been implicated in the onset, symptomatic expression, and maintenance of overeating.Specifically, high impulsivity and its related constructs such as poor inhibitory control and high sensitivity for reward and environmental cues have been shown to perpetuate binging and overeating.Thus, several studies have been conducted to investigate the possible common genetic etiologies for high impulsivity and overeating.The purpose of this review is to summarize the genetic findings indicating an association between impulsivity and overeating.

Anorexia nervosa (AN) is an eating disorder that is thought to emerge through biological predisposition(s) within sociocultural context(s). Practical and ethical concerns limit study of the etiology of this disorder in humans, and in particular the biological aspects. Laboratory animal models have a pivotal role in advancing our understanding of the neurobiological, physiological and behavioral aspects of this disorder, and developing new treatment strategies. One shortcoming of animal models, including activity based anorexia (ABA) in rodents, is that they cannot fully capture the contextual aspects of AN. In this article we discuss the merits of an alternate approach, cost-based anorexia (CBA). CBA is conceptually founded in behavioral economics and its magnitude is influenced by several relevant contextual aspects of feeding.

The findings from neuroscience have shaped our understanding in the past decade regarding the way we perceive psychiatric illness. In addition to the more conventional theories that are based solely on the psychological and sociocultural factors to explain psychiatric disorders, there is growing evidence supporting a multifactorial etiology with genetic and neurological components. Anorexia nervosa, a life-threatening psychiatric disorder with relentless restrictive eating resulting in extremely low body weight, is one such illness that may be categorized as a brain disorder based on the recent findings. Although inconsistencies exist, several studies investigated the structural and the neurochemical alterations in the brain as well as the functional significance and the cognitive manifestations of these abnormalities in anorexia nervosa patient. This review aims to summarize the current literature on the neural aberrations and several treatment approaches targeting these abnormalities in anorexia nervosa.

CONTEXT:Hypothalamic proopiomelanocortin (POMC) is processed to α-melanocyte-stimulating hormone, which interacts with the melanocortin antagonist agouti-related protein (AgRP), to regulate energy balance. The POMC-derived opioid peptide β-endorphin (β-EP) also affects feeding behavior via interactions with brain µ-opioid receptors (MORs), including autoinhibitory interactions with MOR expressed by POMC neurons. The opioid antagonist naltrexone (NTX) stimulates POMC neurons in rodents and decreases food intake.OBJECTIVE AND DESIGN:The effect of NTX on brain POMC in humans was assessed by measuring POMC peptide concentrations in lumbar cerebrospinal fluid (CSF). AgRP and cortisol levels were also measured because both are inhibited by opioids. In a double-blinded crossover study, 14 healthy subjects were given NTX (50 mg daily) or placebo for either 2 or 7 days.RESULTS:CSF β-EP levels increased after 2 and 7 days of NTX treatment; CSF POMC levels did not change, but the β-EP-to-POMC ratio increased. CSF AgRP levels did not change, but plasma AgRP levels tended to increase after NTX (P = 0.06). Cortisol increased in plasma and CSF after NTX treatment; these changes correlated positively with changes in AgRP levels.CONCLUSION:Opioid antagonism stimulates POMC peptide release into CSF in humans. The increase in the CSF β-EP-to-POMC ratio could indicate selective release of processed peptides or an effect on POMC processing. Furthermore, AgRP and cortisol stimulation by NTX may mitigate POMC-induced decrease in food intake. It remains to be determined if biomarkers in CSF and plasma could be used to predict responses to pharmacotherapy targeting the melanocortin system.

In most basic terms impulsivity is defined as a tendency to act without control. Impulsivity has been implicated in the onset, symptomatic expression, and maintenance of overeating. Specifically, high impulsivity and associated poor inhibitory control, along with sensation seeking and reward sensitivity, as well as negative affect have been found to have an interaction effect on emotional eating, which may lead to binge eating and obesity. Moreover, associations between overeating and impulsive behaviors such as difficulty in response inhibition, planning, attention, addiction, or risk taking etc. have been previously shown. The purpose of this review is to summarize the evidence from psychology regarding the potential role of the impulsivity trait in overeating, with implications on the treatments for obesity and binge eating.

The melanocortin neuronal system, which consists of hypothalamic proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, is a leptin target that regulates energy balance and metabolism, but studies in humans are limited by a lack of reliable biomarkers to assess brain melanocortin activity. The objective of this study was to measure the POMC prohormone and its processed peptide, β-endorphin (β-EP), in cerebrospinal fluid (CSF) and AgRP in CSF and plasma after calorie restriction to validate their utility as biomarkers of brain melanocortin activity. CSF and plasma were obtained from 10 lean and obese subjects after fasting (40 h) and refeeding (24 h), and from 8 obese subjects before and after 6 wk of dieting (800 kcal/day) to assess changes in neuropeptide and hormone levels. After fasting, plasma leptin decreased to 35%, and AgRP increased to 153% of baseline. During refeeding, AgRP declined as leptin increased; CSF β-EP increased, but POMC did not change. Relative changes in plasma and CSF leptin were blunted in obese subjects. After dieting, plasma and CSF leptin decreased to 46% and 70% of baseline, CSF POMC and β-EP decreased, and plasma AgRP increased. At baseline, AgRP correlated negatively with insulin and homeostasis model assessment (HOMA-IR), and positively with the Matsuda index. Thus, following chronic calorie restriction, POMC and β-EP declined in CSF, whereas acutely, only β-EP changed. Plasma AgRP, however, increased after both acute and chronic calorie restriction. These results support the use of CSF POMC and plasma AgRP as biomarkers of hypothalamic melanocortin activity and provide evidence linking AgRP to insulin sensitivity.

In the face of worldwide obesity epidemics that is associated with a myriad of adverse health consequences, numerous dietary regimens have been designed to prevent weight gain by modifying the amount and type of the calorie intake. Dietary protein is the least studied macronutrient regarding the nutritional manipulations recommended for weight loss however, despite the initial skepticism of many investigators, high-protein (HP) diets have received attention as a strategy for weight control and obesity management. From the thermodynamics point of view, a calorie is a calorie is a calorie, regardless of the macronutrient composition of the diet. However, not opposing but adding to this; a weight loss diet that is also increasing energy expenditure would result in a greater negative energy balance than the mere effects of hypocaloric intake, leading to a greater weight loss. In support; it has been shown that individuals given (HP) diets accompanied by carbohydrate restriction, increased energy expenditure, attenuating muscle loss, and improving blood lipids. Within this review, we present evidence from well designed randomized control trials showing that an HP diet regimen can lead to a greater feeling of satiety, decreased caloric intake during and at a subsequent meal, increased resting energy expenditure and greater overall weight loss especially from fat depots as well as less weight regain following weight loss than an isocaloric low-protein (LP) diet regimen. We will also discuss the safety concerns raised against protein-laden food intake for the general public; current research on the safety issues have mostly been regarded as inconclusive, and the associated harmful effects seem to be contingent upon the former health status (e.g. existing kidney dysfunction), the specific content of the overall diet, and possibly the type of dietary protein. Finally, a calorie is a calorie, however this comprises one half of the energy balance equation; thus the effects of dietary protein on energy expenditure may lead to greater weight loss benefits of a hypocaloric HP diet than the other macronutrients.

Sexually-dimorphic behavioral and biological aspects of human eating have been described. Using psychophysiological interaction (PPI) analysis, we investigated sex-based differences in functional connectivity with a key emotion-processing region (amygdala, AMG) and a key reward-processing area (ventral striatum, VS) in response to high vs. low energy-dense (ED) food images using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in obese persons in fasted and fed states. When fed, in response to high vs. low-ED food cues, obese men (vs. women) had greater functional connectivity with AMG in right subgenual anterior cingulate, whereas obese women had greater functional connectivity with AMG in left angular gyrus and right primary motor areas. In addition, when fed, AMG functional connectivity with pre/post-central gyrus was more associated with BMI in women (vs. men). When fasted, obese men (vs. women) had greater functional connectivity with AMG in bilateral supplementary frontal and primary motor areas, left precuneus, and right cuneus, whereas obese women had greater functional connectivity with AMG in left inferior frontal gyrus, right thalamus, and dorsomedial prefrontal cortex. When fed, greater functional connectivity with VS was observed in men in bilateral supplementary and primary motor areas, left postcentral gyrus, and left precuneus. These sex-based differences in functional connectivity in response to visual food cues may help partly explain differential eating behavior, pathology prevalence, and outcomes in men and women.

BACKGROUND: Addiction is characterized by an inability to stop using drugs, despite adverse consequences. One contributing factor to this compulsive drug taking could be the impact of drug use on the ability to extinguish drug seeking after changes in expected outcomes. Here, we compared effects of cocaine, morphine, and heroin self-administration on two forms of extinction learning: standard extinction driven by reward omission and extinction driven by reward overexpectation.METHODS: In experiment 1, we trained rats to self-administer cocaine, morphine, or sucrose for 3 hours per day (limited access). In experiment 2, we trained rats to self-administer heroin or sucrose for 12 hours per day (extended access). Three weeks later, we trained the rats to associate several cues with palatable food reward, after which we assessed extinction of the learned Pavlovian response, first by pairing two cues together in the overexpectation procedure and later by omitting the food reward.RESULTS: Rats trained under limited access conditions to self-administer sucrose or morphine demonstrated normal extinction in response to both overexpectation and reward omission, whereas cocaine-experienced rats or rats trained to self-administer heroin under extended access conditions exhibited normal extinction in response to reward omission but failed to show extinction in response to overexpectation.CONCLUSIONS: Here we show that cocaine and heroin can induce long-lasting deficits in the ability to extinguish reward seeking. These deficits were not observed in a standard extinction procedure but instead only affected extinction learning driven by a more complex phenomenon of overexpectation.

Objective: Body adiposity index (BAI), a new surrogate measure of body fat (hip circumference/(height(1.5) - 18)), has been proposed as an alternative to body mass index (BMI). We compared BAI with BMI, and each of them with laboratory measures of body fat-derived from bioimpedance analysis (BIA), air displacement plethysmography (ADP), and dual-energy X-ray absorptiometry (DXA) in clinically severe obese (CSO) participants.Design and Methods: Nineteen prebariatric surgery CSO, nondiabetic women were recruited (age = 32.6 +/- 7.7 SD; BMI = 46.5 +/- 9.0 kg/m(2)). Anthropometrics and body fat percentage (% fat) were determined from BIA, ADP, and DXA. Scatter plots with lines of equality and Bland-Altman plots were used to compare BAI and BMI with % fat derived from BIA, ADP, and DXA. BAI and BMI correlated highly with each other (r = 0.90, P < 0.001).Results: Both BAI and BMI correlated significantly with % fat from BIA and ADP. BAI, however, did not correlate significantly with % fat from DXA (r = 0.42, P = 0.08) whereas BMI did (r = 0.65, P = 0.003). BMI was also the single best predictor of % fat from both BIA (r(2) = 0.80, P < 0.001) and ADP (r(2) = 0.65, P < 0.001). The regression analysis showed that the standard error of the estimate (SEE), or residual error around the regression lines, was greater for BAI comparisons than for BMI comparisons with BIA, ADP, and DXA. Consistent with this, the Bland and Altman plots indicated wider 95% confidence intervals for BAI difference comparisons than for BMI difference comparisons for their respective means for BIA, ADP, and DXA.Conclusions: Thus, BAI does not appear to be an appropriate proxy for BMI in CSO women.

Gender specific effects on human eating have been previously reported. Here we investigated sex-based differences in neural activation via whole-brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in response to high energy-dense (high-ED) vs. low-ED visual and auditory food cues in obese men vs. women in both fed and fasted states. The results show that in response to high vs. low ED foods in the fed state, obese men (vs. women) had greater activation in brain areas associated with motor control regions (e.g. supplementary motor areas) whereas women showed greater activation in cognitive-related regions. In the fasted state, obese men had greater activation in a visual-attention region whereas obese women showed greater activation in affective and reward related processing regions (e.g. caudate). Overall the results support our a priori hypothesis that obese women (vs. men) have greater neural activation in regions associated with cognition and emotion-related brain regions. These findings may improve our understanding of sex specific differences among obese individuals in eating behavior.

We are expected to live longer than if we had been born 100 years ago however, the additional years are not necessarily spent in good health or free from disability. Body composition changes dramatically over the course of life. There is a gradual increase in body weight throughout adult life until the age of about 60-65 years. In contrast, body weight appears to decrease with age after the age of 65-75 years, even in those demonstrating a previous healthy body weight. This age related decrease in body weight, often called unintentional weight loss or involuntary weight loss can be a significant problem for the elderly. This has been shown to be related to decline in appetite and food intake is common amongst the elderly and is often referred to the anorexia of aging. Underlying mechanisms regulate energy homeostasis and appetite may change as people age. In this review, peripheral factors regulating appetite have been summarized in regards to their age-dependent changes and role in the etiology of anorexia of aging. Understanding the alterations in the mechanisms regulating appetite and food intake in conjunction with aging may help inform strategies that promote healthy aging and promote health and wellbeing in the elderly years, with the end goal to add life to the years and not just years to our lives.

There is growing evidence supporting a multifactorial etiology that includes genetic, neurochemical, and physiological components for eating disorders above and beyond the more conventional theories based on psychological and sociocultural factors. Ghrelin is one of the key gut signals associated with appetite, and the only known circulating hormone that triggers a positive energy balance by stimulating food intake. This review summarizes recent findings and several conflicting reports on ghrelin in eating disorders. Understanding these findings and inconsistencies may help in developing new methods to prevent and treat patients with these disorders.

Reductions in mesolimbic responsivity have been noted following Roux-en-Y gastric bypass (RYGB; Ochner et al., 2011a). Given potential for postoperative increases in postprandial gut (satiety) peptides to affect mesolimbic neural responsivity, we hypothesized that: (1) post RYGB changes in mesolimbic responsivity would be greater in the fed relative to the fasted state and; (2) fasted vs. fed state differences in mesolimbic responsivity would be greater post-relative to pre-surgery. fMRI was used to asses neural responsivity to high- and low-calorie food cues in five women 1 mo pre- and 1 mo post-RYGB. Scans were repeated in fasted and fed states. Significant post RYGB decreases in the insula, ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) responsivity were found in the fasted state. These changes were larger than neural changes in the fed state, which were non-significant. Preoperatively, fasted vs. fed differences in neural responsivity were greater in the precuneus, with large but nonsignificant clusters in the vmPFC and dlPFC. Postoperatively, however, no fasted vs. fed differences in neural responsivity were noted. Results were opposite to that predicted and appear inconsistent with the initial hypothesis that postoperative increases in postprandial gut peptides are the primary driver of postoperative changes in neural responsivity.

OBJECTIVE: Body Adiposity Index (BAI), a new surrogate measure of body fat (hip circumference/[height 1.5-18]), has been proposed as a more accurate alternative to BMI. We compared BAI with BMI and their correlations with measures of body fat, waist circumference (WC), and indirect indices of fat pre- and post-Roux-en-Y gastric bypass (RYGB). METHODS: Sixteen clinically severe obese (CSO) non-diabetic women (age = 33.9± 7.9 SD; BMI = 46.5±9.5 kg/m(2)) were assessed pre-surgery, and at 2 (n=9) and 5 mo (n=8) post-surgery. Body fat percentage (% fat) was estimated with bioimpedance analysis (BIA), air displacement plethysmography (ADP), and dual-energy x-ray absorptiometry (DXA). WC, an indicator of central fat, and both plasma leptin (ng/ml) and insulin (mU/l) concentrations were measured as indirect body fat indices. Pre- and post-surgery values were analyzed with Pearson correlations and linear regressions. RESULTS: BAI and BMI correlated significantly with each other pre-surgery and at each time point post surgery. BAI and BMI also correlated significantly with % fat from BIA and ADP; however, only BMI correlated significantly with % fat from DXA pre- and post-RYGB. BMI was the single best predictor of WC and leptin at 2 and 5 mo post-surgery and had significant longitudinal changes correlating with % fat from BIA and DXA as well as with leptin. DISCUSSION: Both BAI and BMI were good surrogates of % fat as estimated from BIA and ADP, but only BMI was a good surrogate of % fat from DXA in CSO women. Thus, BAI may not be a better alternative to BMI.

Heightened cortisol response to stress due to hyperactivation of the hypothalamic-pituitary-adrenal (HPA) axis may stimulate appetite and food intake. In this study, we assessed cortisol responsivity to a cold pressor test (CPT) as well as appetite ratings and subsequent test meal intake (TMI) in obese women. Following an overnight fast on two counterbalanced days, 20 obese women immersed their non-dominant hand for 2min in ice water (CPT) or warm water (WW) as a control. Plasma cortisol (ng/ml), heart rate, and blood pressure, as well as ratings of stress, pain, and appetite, were serially acquired. An ad libitum liquid meal was offered at 45min and intake measured covertly. Fasting cortisol was higher at 15min (mean peak cortisol) following the CPT compared to WW. Higher stress was reported at 2 and 15min for the CPT compared to WW. Pain, an indirect marker of the acute stress, systolic and diastolic blood pressure increased following the CPT at 2min compared to WW. Hunger decreased after the CPT at 2 and 15min, and desire to eat ratings were lower following CPT compared to WW. Subjects did not have greater test meal intake (TMI) following CPT compared to WW. There was also no significant relationship between cortisol levels following stress and TMI, indicating that cortisol did not predict subsequent intake in obese women.