When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

BACKGROUND: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. METHODS: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. OUTCOMES: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. INTERPRETATION: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

Inhibitory control mediates the effect of high intensity interval exercise on food choice.

Exercise is associated with changes in food consumption and cognitive function. The aim of this study was to examine the immediate effects of acute exercise on appetite, food choices, and cognitive processes, and the mediating role of cognitive functioning, namely inhibitory control, working memory, cognitive flexibility and decision making. We compared the effects of high-intensity interval exercise (HIIE) to a resting condition on appetite and food choices, using visual analogue rating scales and a computerised portion selection task. Mediation analysis was performed with exercise/rest condition as a predictor variable and cognitive measures were entered as mediating variables and food choice measures as outcomes. Young women with low activity levels, aged between 18 and 35 years with a body mass index (BMI) between 18 and 25 kg/m², were recruited. Participants (n = 30) demonstrated improved performance on a Stroop task following HIIE compared to the rest session, indicating enhanced attentional inhibition. Accuracy on an N-back task was significantly higher after HIIE, indicating an improvement in working memory and response times on the N-back task were shorter after HIIE, suggesting increased processing speed. Delay discounting for food (but not money) was reduced after HIEE but there were no significant effects on go/no-go task performance. On the trail-making task (a measure of cognitive flexibility), the time difference between trail B and A was significantly lower after HIIE, compared to rest. HIIE reduced rated enjoyment and ideal portion size selection for high energy dense foods. The relationship between exercise and food choices was mediated by inhibition as assessed by the Stoop task. These results suggest that HIIE leads to cognitive benefits and a reduced preference for high-calorie foods and that an enhancement of attentional inhibition may underlie this relationship.

The effect of intranasal insulin on appetite and mood in women with and without obesity: an experimental medicine study.

BACKGROUND/OBJECTIVES: Intranasal (IN) administration of insulin decreases appetite in humans, but the underlying mechanisms are unclear, and it is unknown whether IN insulin affects the food intake of women with obesity. SUBJECTS/METHODS: In a double-blind, placebo-controlled, crossover design, participants (35 lean women and 17 women with obesity) were randomized to receive 160 IU/1.6 mL of IN insulin or placebo in a counterbalanced order in the post prandial state. The effects of IN insulin on cookie intake, appetite, mood, food reward, cognition and neural activity were assessed. RESULTS: IN insulin in the post prandial state reduced cookie intake, appetite and food reward relative to placebo and these effects were more pronounced for women with obesity compared with lean women. IN insulin also improved mood in women with obesity. In both BMI groups, IN insulin increased neural activity in the insula when viewing food pictures. IN insulin did not affect cognitive function. CONCLUSIONS: These results suggest that IN insulin decreases palatable food intake when satiated by reducing food reward and that women with obesity may be more sensitive to this effect than lean women. Further investigation of the therapeutic potential of IN insulin for weight management in women with obesity is warranted.

Utility of an experimental medicine model to evaluate efficacy, side-effects and mechanism of action of novel treatments for obesity and binge-eating disorder.

Obesity and Binge-Eating Disorder (BED) are prevalent conditions that are associated with increased risk of morbidity and mortality. There is evidence that the use of pharmacotherapy alongside behavioural treatments can improve quality of life and reduce disease risk for patients with these disorders. However, there are few approved drug therapies for obesity, and these are limited by poor efficacy and/or side effects and only one drug has been approved for the treatment of BED. There is considerable potential to use experimental medicine models to identify new drug treatments for obesity and BED, with greater efficacy and an improved side effect profile, at an early stage of development. Here, we present a model developed in our laboratory that incorporates both behavioural and neuroimaging measures which can be used to facilitate drug development for obesity and BED. The results from validation studies conducted to date using our model suggest that it is sensitive to the effects of agents with behavioural, neurophysiological and neuropharmacological mechanisms of action known to be associated with weight loss and reductions in binge eating. Future studies using the model will be valuable to evaluate the potential efficacy and side-effects of new candidate drugs at an early stage in the development pipeline for both obesity and BED.

Top-down guidance of attention to food cues is enhanced in individuals with overweight/obesity and predicts change in weight at one-year follow up.

BACKGROUND: Changing eating behaviour may be challenging for individuals with obesity and this may be related to attentional bias towards food. Previous paradigms used to assess attentional bias to food stimuli have not distinguished between bottom-up processes related to assessment of rewarding stimuli versus top-down processes related to effects of mind-set on attention. We investigated whether attentional bias for food cues varies between individuals with overweight/obesity and healthy weight individuals, due to differential top-down control of attention. We also determined whether top-down biases predict food consumption in the lab and weight change in our sample over one-year. METHODS: Forty-three participants with overweight/obesity and 49 healthy weight participants between the ages of 18 and 58 participated. Participants completed two attention tasks in a counterbalanced order: (i) a priming task assessing bottom-up control of attention and (ii) a working memory task assessing top-down control of attention. Eating behaviour was assessed by a taste test. At one-year follow-up participants returned to the laboratory to assess changes in their body mass index (BMI). RESULTS: The healthy weight and overweight/obese groups did not differ in demographics and baseline measures (appetite, food liking, taste test food intake). Participants with overweight/obesity showed greater top-down attentional bias towards food cues than did healthy weight participants but had no difference in bottom-up attentional bias. Top down attentional bias towards food cues predicted weight change over one-year but did not predict food intake in the taste test. CONCLUSIONS: The present findings illustrate that the relationship between attentional bias for food, food intake, and body weight is complex. Top-down effects of mind-set on attention, rather than bottom-up control of attention to food may contribute to patterns of eating that result in development and/or maintenance of overweight/obesity. Interventions targeted at top down biases could be effective in facilitating prevention of weight gain.

Changes in cardiovascular function after venlafaxine but not pregabalin in healthy volunteers: a double-blind, placebo-controlled study of orthostatic challenge, blood pressure and heart rate.

It is generally thought that venlafaxine raises blood pressure at higher doses; however, some studies have found no effect or a decrease in blood pressure. The aim of this study was to evaluate the cardiovascular (CV) effects of 3 weeks of dosing with venlafaxine, pregabalin and placebo on young healthy adults. Fifty-four participants, of mean age 23.1 years (sd 4.68), 29 male, were randomised into three parallel groups. Each group received one of the three drugs, dosed incrementally over a 3-week period to reach daily doses of 150 mg/day venlafaxine and 200 mg/day pregabalin. Blood pressure sphygmomanometer measurements, heart rate measurements, and orthostatic challenges recorded continuously beat-to-beat were performed weekly over this period and 5 days after treatment cessation. Results showed resting systolic blood pressure (SBP) and resting and standing diastolic blood pressure (DBP) and heart rate (HR) were significantly raised by venlafaxine compared with the pregabalin and placebo groups. SBP drop on standing was larger, the resulting overshoot was smaller, and recovery was slower on venlafaxine. HR recovery was significantly impaired by venlafaxine. CV changes were observed after only 1 week of dosing at 112.5 mg/day. These effects of venlafaxine are likely to be due to its action of noradrenergic reuptake inhibition.

Interoceptive accuracy mediates the longitudinal relationship between attention deficit hyperactivity disorder (ADHD) inattentive symptoms and disordered eating in a community sample.

Attention deficit hyperactivity disorder (ADHD) symptoms are associated with disordered eating and interoceptive deficits (as assessed by reliance on hunger/satiety cues) have been suggested as a potential mediating influence. The aim of this longitudinal study was to examine whether the association between ADHD symptoms and disordered eating is explained by deficits in specific facets of interoception. We also aimed to provide further evidence on the previously reported association between ADHD symptoms, negative mood and disordered eating. A community-based sample of 345 adult men and women (M age = 33.9, 72.5% women) completed questionnaires assessing disordered eating (restrictive and binge-type), ADHD symptoms, reliance on hunger/ satiety cues, specific facets of interoception (interoceptive accuracy and interoceptive sensibility) and negative mood at two timepoints over a 6-month period. We tested the mediating influence of reliance on hunger/satiety cues, facets of interoception and negative mood on the relationship between ADHD symptoms and disordered eating. Reliance on hunger/satiety cues mediated the relationship between inattentive symptoms of ADHD and both restrictive and binge-type eating. Interoceptive accuracy, but not sensibility mediated the relationship between inattentive ADHD symptoms and binge-type eating. Negative mood mediated the relationship between both ADHD symptom types and restrictive and binge-type eating. The results from this longitudinal study confirm that deficits in interoception and negative mood contribute to the relationship between ADHD symptoms and disordered eating and extend knowledge by highlighting interoceptive accuracy specifically as the most important facet of interoception in the relationship between inattentive symptoms and binge-type eating.

The effect of a clinically effective and non-effective dose of lorazepam on 7.5% CO2-induced anxiety.

Symptoms of anxiety induced by 7.5% CO2 inhalation can be attenuated by acute administration of GABA(A) receptor anxiolytics such as lorazepam and alprazolam. This study investigated if these effects are dose-related, by comparing a 0.5 mg dose (considered non-clinically effective) and a 2 mg dose of lorazepam (clinically effective) on 7.5% CO2 inhalation. Eighteen healthy males (mean age 20.6 years, SD 1.29), judged physically and mentally fit, attended three visits, each one week apart, to take each treatment in a randomised double-blind crossover design. Drugs were given 60 min prior to 20 min air inhalation, followed by 20 min 7.5% CO2 inhalation. The order of gas presentation was single blind. Subjective ratings using visual analogue scales (VAS) and questionnaires were recorded before and after each inhalation. Blood pressure (BP), heart rate (HR), respiration rate (RR) and expired CO2 were recorded during each inhalation. Inhalation of 7.5% CO2 significantly raised BP, HR, RR and expired CO2. Ratings of feeling like leaving the room were significantly lower on 2 mg compared with 0.5 mg and placebo, and dose-dependent trends were seen in scores for VAS fearful, anxious, stressed, tense, and worried. Results may be indicative of dose-dependent effects of lorazepam in a CO2 model of anxiety.

Validation of the P1vital® Faces Set for Use as Stimuli in Tests of Facial Emotion Recognition.

BACKGROUND: Negative bias in facial emotion recognition is a well-established concept in mental disorders such as depression. However, existing face sets of emotion recognition tests may be of limited use in international research, which could benefit from more contemporary and diverse alternatives. Here, we developed and provide initial validation for the P1vital® Affective Faces set (PAFs) as a contemporary alternative to the widely-used Pictures of Facial Affect (PoFA). METHODS: The PAFs was constructed of 133 color photographs of facial expressions of ethnically-diverse trained actors and compared with the PoFA, comprised of 110 black and white photographs of facial expressions of generally Caucasian actors. Sixty-one recruits were asked to classify faces from both sets over six emotions (happy, sad, fear, anger, disgust, surprise) varying in intensity in 10% increments from 0 to 100%. RESULTS: Participants were significantly more accurate in identifying correct emotions viewing faces from the PAFs. In both sets, participants identified happy faces more accurately than fearful faces, were least likely to misclassify facial expressions as happy and most likely to misclassify all emotions at low intensity as neutral. Accuracy in identifying facial expressions improved with increasing emotion intensity for both sets, reaching peaks at 60 and 80% intensity for the PAFs and PoFA, respectively. The study was limited by small sizes and age-range of participants and ethnic diversity of actors. CONCLUSIONS: The PAFs successfully depicted a range of emotional expressions with improved performance over the PoFA and may be used as a contemporary set in facial expression recognition tests.

The effects of lisdexamfetamine dimesylate on eating behaviour and homeostatic, reward and cognitive processes in women with binge-eating symptoms: an experimental medicine study.

Lisdexamfetamine dimesylate (LDX) is the only drug currently approved by the FDA for the treatment of Binge-Eating Disorder (BED), but little is known about the behavioural mechanisms that underpin the efficacy of LDX in treating BED. We examined the behavioural and neural effects of an acute dose of LDX (50 mg) in 22 women with binge-eating symptomatology using a randomised, crossover, double-blind, placebo-controlled experimental medicine design. LDX reduced self-reported appetite ratings and intake of both a pasta meal and a palatable cookie snack. LDX also decreased the eating rate of pasta but not of cookies and reduced self-reported liking ratings for pasta at the end of the meal. When viewing food pictures during an fMRI scan, LDX reduced activity bilaterally in the thalamus. LDX enhanced sustained attention and reduced impulsive responding in a continuous performance task but had no effect on emotional bias or working memory. These results suggest the observed effects of LDX on food intake (and by implication the efficacy of LDX in treating BED) may be related to the actions of the drug to enhance satiety, reduce food-related reward responding when full and/or increase cognitive control. Novel pharmacotherapies for BED might be most effective if they have a broad spectrum of effects on appetite, reward and cognition.

Lisdexamfetamine and binge-eating disorder: A systematic review and meta-analysis of the preclinical and clinical data with a focus on mechanism of drug action in treating the disorder.

Binge-Eating Disorder (BED) is the most common eating disorder in the United States. Lisdexamfetamine (LDX) was approved in 2015 by the FDA for treatment of BED and is the only drug approved for treating the disorder. There has been no systematic evaluation of the published clinical and preclinical evidence for efficacy of LDX in treating BED and the mechanisms responsible for the therapeutic action of the drug. To address this gap, we conducted a systematic review and meta-analysis using PRISMA guidelines. Fourteen clinical and seven preclinical articles were included. There is consistent evidence from clinical studies that LDX is an effective treatment for BED and that the drug reduces the BED symptoms and body weight of patients with the disorder. There is also consistent evidence from preclinical studies that LDX reduces food intake but no consistent evidence for a preferential reduction of palatable food consumption by the drug in rodents. The evidence on mechanism of action is more limited and suggests LDX may reduce binge eating by a combination of effects on appetite/satiety, reward, and cognitive processes, including attention and impulsivity/inhibition, that are mediated by catecholamine and serotonin mechanisms in the brain. There is an urgent need for adequately powered, placebo-controlled, behavioural and neuroimaging studies with LDX (recruiting patients and/or individuals with subclinical BED symptoms) to further investigate the mechanism of action of the drug in treating BED. An improved understanding of the behavioural and neurochemical mechanisms of action of LDX could lead to the development of improved drug therapies to treat BED.

The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial.

Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment. We conducted a multicentre, open-label, randomised controlled trial in 913 medication-free depressed patients. Patients were randomly assigned to have their antidepressant treatment guided by a predictive algorithm or treatment as usual (TaU). The primary outcome was the response of depression symptoms, defined as a 50% or greater reduction in baseline score of the QIDS-SR-16 scale, at week 8. Additional prespecified outcomes included symptoms of anxiety at week 8, and symptoms of depression and functional outcome at weeks 8, 24 and 48. The response rate of depressive symptoms at week 8 in the PReDicT (55.9%) and TaU (51.8%) arms did not differ significantly (odds ratio: 1.18 (95% CI: 0.89-1.56), P = 0.25). However, there was a significantly greater reduction of anxiety in week 8 and a greater improvement in functional outcome at week 24 in the PReDicT arm. Use of the PReDicT test did not increase the rate of response to antidepressant treatment estimated by depressive symptoms but did improve symptoms of anxiety at week 8 and functional outcome at week 24. Our findings indicate that personalisation of antidepressant treatment may improve outcomes in depressed patients.

Value of monitoring negative emotional bias in primary care in England for personalised antidepressant treatment: a modelling study.

BACKGROUND: Depressed patients often focus on negative life events. Effective antidepressant therapy reverses this negative emotional bias (NEB) within 1 week. Clinical therapeutic effect usually requires 4-6 weeks. The value of implementing NEB monitoring for the personalisation of antidepressant therapy is unknown. OBJECTIVE: To estimate the likely outcome and cost consequences of adopting the P1vital Oxford Emotional Test Battery (ETB) for this purpose in routine primary care in England. METHODS: A hybrid decision analytic model (decision tree plus Markov model) was developed to estimate the cost-effectiveness of ETB monitoring versus no ETB over 52 weeks using quality-adjusted life years (QALYs). Differences in depression severity, episode type and analytical perspectives were considered. Input data were derived from relevant guidelines, literature, national databases, expert opinion and the developers for the year 2013. Multiple sensitivity analyses addressed uncertainty. FINDINGS: The mean number of ETB tests is 2.162 per newly diagnosed patient and 2.166 per patient with recurrent depression. The incremental cost-effectiveness of ETB versus 'no ETB' is £4355/QALY from the healthcare perspective. From the broader societal perspective, ETB is more effective and cost saving. CONCLUSIONS: Monitoring negative emotional bias in primary care in England for personalised antidepressant treatment using ETB seems as an effective and cost-effective option under all considered scenarios (including worst case). Its main economic value seems to lie in reduced productivity loss as opposed to healthcare savings. CLINICAL IMPLICATIONS: The test supports accelerated application of evidence-based depression care. Further optimisation and implementation in the ongoing European PReDicT trial is ongoing.

Predicting treatment response to antidepressant medication using early changes in emotional processing.

Antidepressants must be taken for weeks before response can be assessed with many patients not responding to the first medication prescribed. This often results in long delays before effective treatment is started. Antidepressants induce changes in the processing of emotional stimuli early in the course of treatment. In the current study we assessed whether changes in emotional processing and subjective symptoms over the first week of antidepressant treatment predicted clinical response after 4-8 weeks of treatment. Such a predictive test may shorten the time taken to initiate effective treatment in depressed patients. Seventy-four depressed primary care patients completed measures of emotional bias and subjective symptoms before starting antidepressant treatment and then again 1 week later. Response to treatment was assessed after 4-6 weeks. The performance of classifiers based on these measures was assessed using a leave-one-out validation procedure with the best classifier then tested in an independent sample from a second study of 239 patients. The combination of a facial emotion recognition task and subjective symptoms predicted response with 77% accuracy in the training sample and 60% accuracy in the independent study, significantly better than possible using baseline response rates. The face based measure of emotional bias provided good quality data with high acceptability ratings. Changes in emotional processing can provide a sensitive early measure of antidepressant efficacy for individual patients. Early treatment induced changes in emotional processing may be used to guide antidepressant therapy and reduce the time taken for depressed patients to return to good mental health.

Antagonists of the human adenosine A2A receptor. Part 3: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyrrolo[2,3-d]pyrimidines and 6-arylpurines.

A series of pyrazolo[3,4-d]pyrimidine, pyrrolo[2,3-d]pyrimidine and 6-arylpurine adenosine A(2A) antagonists is described. Many examples were highly selective against the human A(1) receptor sub-type and were active in an in vivo model of Parkinson's disease.

Antagonists of the human adenosine A2A receptor. Part 2: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives.

We describe herein the discovery and development of a series of 4-arylthieno[3,2-d]pyrimidines which are potent adenosine A(2A) receptor antagonists. These novel compounds show high degrees of selectivity against the human A(1), A(2B) and A(3) receptor sub-types. Moreover, a number of these compounds show promising activity in vivo, suggesting potential utility in the treatment of Parkinson's disease.

Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives.

The (-)-(11R,2'S)-enantiomer of the antimalarial drug mefloquine has been found to be a reasonably potent and moderately selective adenosine A(2A) receptor antagonist. Further investigation of this compound has led to the discovery of a series of keto-aryl thieno[3,2-d]pyrimidine derivatives, which are potent and selective antagonists of the adenosine A(2A) receptor. These derivatives show selectivity against the A(1) receptor. Furthermore, some of these compounds have been shown to have in vivo activity in a commonly used model, suggesting the potential for the treatment of Parkinson's disease.

Associations Between Core Symptoms of Attention Deficit Hyperactivity Disorder and Both Binge and Restrictive Eating.

INTRODUCTION: It is unclear whether core symptoms of attention deficit hyperactivity disorder (ADHD) relate to specific types of disordered eating and little is known about the mediating mechanisms. We investigated associations between core symptoms of ADHD and binge/disinhibited eating and restrictive eating behavior and assessed whether negative mood and/or deficits in awareness and reliance on internal hunger/satiety cues mediate these relationships. METHODS: In two independent studies, we used a dimensional approach to study ADHD and disordered eating. In Study 1, a community-based sample of 237 adults (72.6% female, 18-60 years [M = 26.8, SE = 0.6]) completed an online questionnaire, assessing eating attitudes/behaviors, negative mood, awareness, and reliance on internal hunger/satiety cues and ADHD symptomatology. In Study 2, 142 students (80.3% female, 18-32 years [M = 19.3, SE = 0.1]) were recruited to complete the same questionnaires and complete tasks assessing interoceptive sensitivity and impulsivity in the laboratory. RESULTS: In each study, core symptoms of ADHD correlated positively with both binge/disinhibited and restrictive eating and negative mood mediated the relationships. Deficits in awareness and reliance on internal hunger/satiety signals also mediated the association between inattentive symptoms of ADHD and disordered eating, especially binge/disinhibited eating. The results from both studies demonstrated that inattentive symptoms of ADHD were also directly related to binge/disinhibited eating behavior, while accounting for the indirect pathways of association via negative mood and awareness and reliance on internal hunger/satiety signals. CONCLUSION: This research provides evidence that core symptoms of ADHD are associated with both binge/disinhibited eating and restrictive eating behavior. Further investigation of the role of inattentive symptoms of ADHD in disordered eating may be helpful in developing novel treatments for both ADHD and binge eating.

The 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) reduces palatable food consumption and BOLD fMRI responses to food images in healthy female volunteers.

RATIONALE: Brain 5-HT2C receptors form part of a neural network that controls eating behaviour. 5-HT2C receptor agonists decrease food intake by activating proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus, but recent research in rodents has suggested that 5-HT2C receptor agonists may also act via dopaminergic circuitry to reduce the rewarding value of food and other reinforcers. No mechanistic studies on the effects of 5-HT2C agonists on food intake in humans have been conducted to date. OBJECTIVES: The present study examined the effects of the 5-HT2C receptor agonist meta-chlorophenylpiperazine (mCPP) on food consumption, eating microstructure and blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to food pictures in healthy female volunteers. METHODS: In a double-blind, placebo-controlled, crossover design, participants were randomized immediately after screening to receive oral mCPP (30mg) in a single morning dose, or placebo, in a counterbalanced order. Test foods were served from a Universal Eating Monitor (UEM) that measured eating rate and fMRI BOLD signals to the sight of food and non-food images were recorded. RESULTS: mCPP decreased rated appetite and intake of a palatable snack eaten in the absence of hunger but had no significant effect on the consumption of a pasta lunch (although pasta eating rate was reduced). mCPP also decreased BOLD fMRI responses to the sight of food pictures in areas of reward-associated circuitry. A post hoc analysis identified individual variability in the response to mCPP (exploratory responder-non-responder analysis). Some participants did not reduce their cookie intake after treatment with mCPP and this lack of response was associated with enhanced ratings of cookie pleasantness and enhanced baseline BOLD responses to food images in key reward and appetite circuitry. CONCLUSIONS: These results suggest that 5-HT2C receptor activation in humans inhibits food reward-related responding and that further investigation of stratification of responding to mCPP and other 5-HT2C receptor agonists is warranted.

Attention Deficit Hyperactivity Disorder (ADHD) and disordered eating behaviour: A systematic review and a framework for future research.

Preliminary findings suggest that Attention Deficit Hyperactivity Disorder (ADHD) may be associated with disordered eating behaviour, but whether there is sufficient evidence to suggest an association between ADHD and specific types of disordered eating behaviour is unclear. Furthermore, it is uncertain whether specific features associated with ADHD are differentially associated with disordered eating behaviour. A systematic review of seventy-five studies was conducted to evaluate the potential association between ADHD symptomatology and disordered eating behaviour and to provide an estimate of the strength of evidence for any association. Overall, a moderate strength of evidence exists for a positive association between ADHD and disordered eating and with specific types of disordered-eating behaviour, in particular, overeating behaviour. There is consistent evidence that impulsivity symptoms of ADHD are positively associated with overeating and bulimia nervosa and more limited evidence for an association between hyperactivity symptoms and restrictive eating in males but not females. Further research is required to assess the potential direction of the relationship between ADHD and disordered eating, the underlying mechanisms and the role of specific ADHD symptoms in the development and/or maintenance of disordered eating behaviour. We propose a framework that could be used to guide the design of future studies.