Predictors of weight loss in participants with obesity following bariatric surgery - A prospective longitudinal fMRI study.

Prevalence rates of overweight and obesity are increasing worldwide and are amongst the leading causes of death. Participants with obesity also suffer from poorer mental health with a concomitant reduced quality of life. Bariatric surgery outperforms other existing weight optimization approaches. However, hitherto, it was not possible to identify factors predicting weight loss following surgery. Therefore, we aimed at investigating neural and behavioral predictors of weight loss, as well as the neurological underpinnings of food cue-induced craving before and after bariatric surgery. The total sample consisted of 26 participants with obesity (17 females and 9 males, mean age 41 ± 12 years, mean BMI 46 ± 6 kg/m2, 21 received Roux-en-Y gastric bypass and 5 sleeve gastrectomy). Participants with obesity were prospectively assessed using functional magnetic resonance imaging two weeks before, as well as eight and 24 weeks after surgery. Imaging data were available for 11 individuals; 10 received Roux-en-Y gastric bypass and one sleeve gastrectomy. Subjective cue-induced food craving correlated positively with brain activation in the amygdala, the parahippocampal gyrus, and hippocampus, and negatively with brain activation in frontal brain regions. In the total sample (N = 26), perceived feeling of hunger and YFAS sum score explained 50.6% of the variance (R2 = 0.506, F(1,23) = 10.759, p < 0.001) and in the imaging sample, cue-induced food craving at baseline before surgery explained 49.6% of the variance (R2 = 0.496, F(1,23) = 7.862, p = 0.023) of % total weight loss (%TWL). In other words, with respect to %TWL, bariatric surgery was most efficient in candidates characterized by high cue-induced food craving, high-perceived feeling of hunger and a low YFAS sum score.

Reliability of neural food cue-reactivity in participants with obesity undergoing bariatric surgery: a 26-week longitudinal fMRI study.

Obesity is highly prevalent worldwide and results in a high disease burden. The efforts to monitor and predict treatment outcome in participants with obesity using functional magnetic resonance imaging (fMRI) depends on the reliability of the investigated task-fMRI brain activation. To date, no study has investigated whole-brain reliability of neural food cue-reactivity. To close this gap, we analyzed the longitudinal reliability of an established food cue-reactivity task. Longitudinal reliability of neural food-cue-induced brain activation and subjective food craving ratings over three fMRI sessions (T0: 2 weeks before surgery, T1: 8 weeks and T2: 24 weeks after surgery) were investigated in N = 11 participants with obesity. We computed an array of established reliability estimates, including the intraclass correlation (ICC), the Dice and Jaccard coefficients and similarity of brain activation maps. The data indicated good reliability (ICC > 0.6) of subjective food craving ratings over 26 weeks and excellent reliability (ICC > 0.75) of brain activation signals for the contrast of interest (food > neutral) in the caudate, putamen, thalamus, middle cingulum, inferior, middle and superior occipital gyri, and middle and superior temporal gyri and cunei. Using similarity estimates, it was possible to re-identify individuals based on their neural activation maps (73%) with a fading degree of accuracy, when comparing fMRI sessions further apart. The results show excellent reliability of task-fMRI neural brain activation in several brain regions. Current data suggest that fMRI-based measures might indeed be suitable to monitor and predict treatment outcome in participants with obesity undergoing bariatric surgery.

[Substance abuse in older adults]. / Sucht im Alter.

In respect of demographic change, the number of older patients with substance abuse and addiction is on the raise. In this review we present important clinical and therapeutic aspects of substance abuse and addiction in the elderly and focus on alcohol, benzodiazepines and opioids. Daily and risky alcohol consumption is common among older people. They also have an increased risk getting alcohol-related complications. For early detection, laboratory parameters and questionnaires such as the AUDIT-C are suitable. Therapeutically brief interventions have been proved successful. Also, abuse of benzodiazepines, especially low-dose addiction, is widespread among older persons, although often overlooked, and patients often do not recognize their addiction. The physician has to know the correct indication, adequate dosage and pharmacological interactions. A slow-dose reduction is recommended in case of addiction. Thanks to opioid substitution therapy, patients with an opioidaddiction can reach a higher age. Age influences the effects of the substitute, which may require an adjustment of the dosage. Treatment of elderly patients should be based on their needs and resources and is usually very effective.

Sur le plan démographique le nombre de personnes âgées abusant ou dépendant de substances est en augmentation. Dans cette revue seront présentés des aspects cliniques et thérapeutiques de l'abus et de la dépendance de substances dans cette classe de la population, en particulier en ce qui concerne l'alcool, les benzodiazépines et les opioïdes. La consommation d'alcool quotidienne est fréquente chez les personnes âgées et augmente chez elles le risque de complications. Pour la détection précoce d'un abus d'alcool des paramètres de laboratoire et des questionnaires comme le AUDIT-C sont appropriés. Des interventions thérapeutiques brèves se sont avérées efficaces. L'abus de benzodiazépines, en particulier la dépendance à ces substances à petites doses, est aussi très répandu et souvent négligé chez les personnes âgées, de telle sorte que ces dernières n'en ont pas conscience. Le médecin doit connaître l'indication correcte, le dosage adéquat et les interactions des benzodiazépines. Une réduction lente des doses est recommandée en cas de dépendance. Les patients présentant une dépendance aux opioïdes ont leur vie prolongée grâce à un traitement substitutif. L'âge influence les effets des substances substitutives, ce qui peut nécessiter des adaptations de dosage. Le traitement des personnes âgées devrait être basé sur leurs besoins et leurs ressources. Il est généralement très efficace.

Oleoylethanolamide and human neural responses to food stimuli in obesity.

IMPORTANCE: Obesity has emerged as a leading health threat but its biological basis remains insufficiently known, hampering the search for novel treatments. Here, we study oleoylethanolamide, a naturally occurring lipid that has been clearly implicated in weight regulation in animals. However, its role for weight regulation and obesity in humans is still unclear. OBJECTIVE: To investigate associations between plasma oleoylethanolamide levels and body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) and functional magnetic resonance imaging response to food stimuli in obese patients and matched control participants. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 21 obese patients and 24 matched control participants. Obesity was defined as having a BMI of at least 30. The mean age of participants was 40.8 years and BMIs ranged from 18.2 to 47.5. MAIN OUTCOMES AND MEASURES: Interactions between plasma oleoylethanolamide levels and obesity on BMI and functional magnetic resonance imaging response to food stimuli. RESULTS: Associations between oleoylethanolamide and BMI differed significantly depending on whether individuals were obese or not (P = .02). In obese individuals, oleoylethanolamide showed a trend toward a positive correlation with BMI (P = .06, ρ = 0.42), while this relationship was inverse for nonobese control participants (P = .07, ρ = -0.34). Similarly, we found significant interactions between oleoylethanolamide levels and obesity on food-related brain activation in cortical areas associated with reward processing and interoceptive signaling (P = .009). Specifically, nonobese individuals with higher oleoylethanolamide levels had higher insular brain activity (P < .001, ρ = 0.70); again, the relationship trended to be inverse for obese patients (P = .11, ρ = -0.36). These effects were not associated with plasma levels of leptin and anandamide, suggesting an independent role of oleoylethanolamide in hunger-associated interoceptive signaling. Analysis of food craving during the functional magnetic resonance imaging task suggested that the identified brain areas may be involved in suppressing food-liking reactions in nonobese individuals. CONCLUSIONS AND RELEVANCE: This study suggests that oleoylethanolamide-mediated signaling plays an important role for hedonic regulation of food craving and obesity in humans and thus may be a valuable target for developing novel antiobesity drugs.

Hunger modulates behavioral disinhibition and attention allocation to food-associated cues in normal-weight controls.

Overeating, weight gain and obesity are considered as a major health problem in Western societies. At present, an impairment of response inhibition and a biased salience attribution to food-associated stimuli are considered as important factors associated with weight gain. However, recent findings suggest that the association between an impaired response inhibition and salience attribution and weight gain might be modulated by other factors. Thus, hunger might cause food-associated cues to be perceived as more salient and rewarding and might be associated with an impairment of response inhibition. However, at present, little is known how hunger interacts with these processes. Thus, the aim of the present study was to investigate whether hunger modulates response inhibition and attention allocation towards food-associated stimuli in normal-weight controls. A go-/nogo task with food-associated and control words and a visual dot-probe task with food-associated and control pictures were administered to 48 normal-weight participants (mean age 24.5 years, range 19-40; mean BMI 21.6, range 18.5-25.4). Hunger was assessed twofold using a self-reported measure of hunger and a measurement of the blood glucose level. Our results indicated that self-reported hunger affected behavioral response inhibition in the go-/nogo task. Thus, hungry participants committed significantly more commission errors when food-associated stimuli served as distractors compared to when control stimuli were the distractors. This effect was not observed in sated participants. In addition, we found that self-reported hunger was associated with a lower number of omission errors in response to food-associated stimuli indicating a higher salience of these stimuli. Low blood glucose level was not associated with an impairment of response inhibition. However, our results indicated that the blood glucose level was associated with an attentional bias towards food-associated cues in the visual dot probe task. In conclusion our results suggest that hunger induces an approach bias and is associated with an impairment of response inhibition when normal-weight participants are confronted with food-associated cues. These findings are important as these processes play a crucial role with regard to the control of food-intake and weight gain and are assumed to contribute to obesity. Thus, individualized treatment approaches taking into account the experience of hunger in everyday-life situations should be considered in addition to a training of response inhibition.

Insula-specific H magnetic resonance spectroscopy reactions in heavy smokers under acute nicotine withdrawal and after oral nicotine substitution.

The aim of this study was to clarify whether addiction-specific neurometabolic reaction patterns occur in the insular cortex during acute nicotine withdrawal in tobacco smokers in comparison to nonsmokers. Fourteen male smokers and 10 male nonsmokers were included. Neurometabolites of the right and the left insular cortices were quantified by magnetic resonance spectroscopy (MRS) on a 3-Tesla scanner. Three separate MRS measurements were performed in each subject: among the smokers, the first measurement was done during normal smoking behavior, the second measurement during acute withdrawal (after 24 h of smoking abstinence), and the third shortly after administration of an oral nicotine substitute. Simultaneously, craving, withdrawal symptoms, and CO levels in exhaled air were determined during the three phases. The participants in the control group underwent the same MR protocol. In the smokers, during withdrawal, the insular cortex showed a significant increase in glutamine (Gln; p = 0.023) as well as a slight increase not reaching significance for glutamine/glutamate (Glx; p = 0.085) and a nonsignificant drop in myoinositol (mI; p = 0.381). These values tended to normalize after oral nicotine substitution treatment, even though differences were not significant: Gln (p = 0.225), Glx (p = 0.107) and mI (p = 0.810). Overall, the nonsmokers (control group) did not show any metabolic changes over all three phases (p > 0.05). In smokers, acute nicotine withdrawal produces a neurometabolic reaction pattern that is partly reversed by the administration of an oral nicotine substitute. The results are consistent with the expression of an addiction-specific neurometabolic shift in the brain and confirm the fact that the insular cortex seems to play a possible role in nicotine dependence.

[Pregabalin for the reduction of opiate withdrawal symptoms]. / Pregabalin zur Reduktion von Opiatentzugssymptomen.

Pregabalin is a substance which modulates monoamine release in "hyper-excited" neurons. It binds potently to the α2-δ subunit of calcium channels. Pilotstudies on alcohol- and benzodiazepine dependent patients reported a reduction of withdrawal symptoms through Pregabalin. To our knowledge, no studies have been conducted so far assessing this effect in opiate dependent patients. We report the case of a 43-year-old patient with Pregabalin intake during opiate withdrawal. Multiple inpatient and outpatient detoxifications from maintenance replacement therapy with Buprenorphine in order to reach complete abstinence did not show success because of extended withdrawal symptoms and repeated drug intake. Finally he disrupted his heroine intake with a simultaneously self administration of 300  mg Pregabaline per day and was able to control the withdrawal symptoms. In this time we did control the Pregabalin level in serum and urine in our outpatient clinic. In the course the patient reported that he could treat further relapse with opiate or opioids with Pregabalin successful. This case shows first details for Pregabalin to relief withdrawal symptoms in opiate withdrawal.

Psychological and hormonal features of smokers at risk to gain weight after smoking cessation--results of a multicenter study.

Preclinical and clinical data suggest modulating effects of appetite-regulating hormones and stress perception on food intake. Nicotine intake also interferes with regulation of body weight. Especially following smoking cessation gaining weight is a common but only partially understood consequence. The aim of this study was to examine the interaction between smoking habits, the appetite regulating hormone leptin, negative affectivity, and stress vulnerability on eating behavior in a clinical case-control study under standardized conditions. In a large population-based study sample, we compared leptin and cortisol plasma concentrations (radioimmunoassay) between current tobacco smokers with high cognitive restraint and disinhibition in eating behavior and smokers scoring low in both categories as assessed with the Three Factor Eating Questionnaire (TFEQ; Stunkard & Messick, 1985). As a measure for smoking effects on the stress axis, the saliva cortisol concentrations were compared before and after nicotine smoking. Additionally, stress perception was assessed with the Perceived Stress Scale (PSS), symptoms of depression and anxiety with the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). In smokers showing high cognitive restraint and disinhibition we found significantly higher leptin concentrations than in the group of smokers scoring low in both categories. Furthermore there was a significant group difference in saliva cortisol concentrations after nicotine intake. Smokers showing high cognitive restraint and disinhibition were also characterized by significantly higher scores in the STAI, the PSS and the BDI. Our results suggest that smokers with a pathological eating behavior show an impaired neuroendocrine regulation of appetite and are prone to experience higher levels of stress and negative affectivity. This interaction of behavioral and neuroendocrinological factors may constitute a high risk condition for gaining weight following smoking cessation.

Urinary ethylglucuronide assessment in patients treated with disulfiram: a tool to improve verification of abstention and safety.

AIM: Disulfiram has been shown to be efficacious and safe in the treatment of alcohol relapse prevention. However, drinking alcohol while taking disulfiram can be harmful because of the resulting alcohol-disulfiram reaction/acetaldehyde reaction. Alcohol consumption of patients receiving a low disulfiram dose or low alcohol consumption in normal disulfiram dose can result in subclinical alcohol-disulfiram reactions. This undermines the learning of alcohol-associated punishment, might increase the risk to raise alcohol consumption, and can result in chronic acetaldehyde exposure, which has carcinogenic, neurotoxic, and cardiotoxic properties. Therefore, the use of an alcohol marker monitoring retrospective alcohol use is tested in this study. METHOD: A total of 51 patients being treated with supervised disulfiram were unheralded measured for ethylglucuronide (EtG) if they attended at least for 2 weeks in the outpatient treatment program. Ethylglucuronide was measured with liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS). Detection limit was 0.1 mg/L. RESULTS: Urinary EtG was found positive in 5.9% (3/51) of the patients. Regularly conducted breathalyzer tests had been continuously negative in these patients. Moreover, vegetative withdrawal symptoms had not been found in these patients. Two of the positive EtG tests could be classified as covered relapses, whereas the third remained unclear but showed a negative EtG in a repetition of the test few days later. CONCLUSIONS: Unheralded urinary EtG monitoring improved verification of abstinence in patients treated with disulfiram, was helpful in detecting covered consumption of alcoholic beverages or hidden alcohol exposition (eg, fruit juice or personal care products), and thereby improved safety by preventing chronic acetaldehyde reaction.

Orexin and leptin are associated with nicotine craving: a link between smoking, appetite and reward.

OBJECTIVE: Preclinical data suggest modulating effects of both orexin/hypocretin and leptin on dopaminergic transmission in mesolimbic reward pathways. This indicates a possible role of both peptides in reward function and motivation, and thus in addictive diseases. The aim of this study was to examine the possible association between orexin and leptin, and nicotine craving in smokers in a clinical case-control study under standardized conditions. METHODS: We compared orexin and leptin, ACTH and cortisol plasma concentrations (RIA) between tobacco smokers (n=60) during early nicotine withdrawal and healthy controls (n=64). Motivational aspects of nicotine craving were additionally assessed in the smoking participants using the Questionnaire of Smoking Urges (QSU). RESULTS: As main results we detected a significant negative correlation between orexin plasma concentration and nicotine craving (r=-0.28; p<.05), and a positive association between craving and leptin plasma concentration (r=0.29; p<.05). CONCLUSIONS: Our results show an association between craving for nicotine and plasma concentrations of orexin and leptin suggesting that both peptides interfere with the dopaminergic transmission during nicotine withdrawal in a bidirectional manner and, thus, modulate craving for nicotine.

Reduced affective symptoms during tobacco dependence treatment with varenicline.

BACKGROUND: The nicotinic acetylcholine receptor partial agonist varenicline has been shown to be effective in the treatment of tobacco dependence, but has been reported to induce exacerbations of psychiatric symptoms in subjects with pre-existing psychiatric disorders. CASE DESCRIPTION: We report a tobacco-dependent patient who developed depression and suicidal tendencies during several cessation attempts, but was finally able to stay nicotine-abstinent by taking varenicline. CONCLUSION: In this case varenicline did not lead to exacerbation but appeared to improve the affective symptoms.