Hisham Ziauddeen

Obesity and the brain: how convincing is the addiction model?

An increasingly influential perspective conceptualizes both obesity and overeating as a food addiction accompanied by corresponding brain changes. Because there are far-reaching implications for clinical practice and social policy if it becomes widely accepted, a critical evaluation of this model is important. We examine the current evidence for the link between addiction and obesity, identifying several fundamental shortcomings in the model, as well as weaknesses and inconsistencies in the empirical support for it from human neuroscientific research.

Is food addiction a valid and useful concept

In this paper, we consider the concept of food addiction from a clinical and neuroscientific perspective. Food addiction has an established and growing currency in the context of models of overeating and obesity, and its acceptance shapes debate and research. However, we argue that the evidence for its existence in humans is actually rather limited and, in addition, there are fundamental theoretical difficulties that require consideration.

The relevance of reward pathways for schizophrenia.

Purpose of review There has been a resurgence of interest in the field of reward processing in schizophrenia in recent years, aided by insights from functional neuroimaging. We examine how disturbances in reward-related processes relate to the pathophysiology and symptomatology of this disorder. Recent findings Behavioural and functional neuroimaging studies in psychosis demonstrate impairments in the representation of reward value and in reward-related learning and a failure to motivate behaviour for incentives. These impairments are linked to abnormal mesocorticolimbic and mesostriatal function. Summary Abnormalities in reward processing offer insights into the symptomatology of schizophrenia and its underlying neurobiology. Further investigation is required into the specificity of these deficits to particular symptom expression and to what extent they are improved by antipsychotic treatment.

Effects of the mu-opioid receptor antagonist GSK1521498 on hedonic and consummatory eating behaviour: a proof of mechanism study in binge-eating obese subjects

The opioid system is implicated in the hedonic and motivational processing of food, and in binge eating, a behaviour strongly linked to obesity. The aim of this study was to evaluate the effects of 4 weeks of treatment with the mu-opioid receptor antagonist GSK1521498 on eating behaviour in binge-eating obese subjects. Adults with body mass index ⩾30 kg m−2 and binge eating scale scores ⩾19 received 1-week single-blind placebo run-in, and were then randomized to 28 days with either 2 mg day−1 GSK1521498, 5 mg day−1 GSK1521498 or placebo (N=21 per arm) in a double-blind parallel group design. The outcome measures were body weight, fat mass, hedonic and consummatory eating behaviour during inpatient food challenges, safety and pharmacokinetics. The primary analysis was the comparison of change scores in the higher-dose treatment group versus placebo using analysis of covariance at each relevant time point. GSK1521498 (2 mg and 5 mg) was not different from placebo in its effects on weight, fat mass and binge eating scores. However, compared with placebo, GSK1521498 5 mg day−1 caused a significant reduction in hedonic responses to sweetened dairy products and reduced calorific intake, particularly of high-fat foods during ad libitum buffet meals, with some of these effects correlating with systemic exposure of GSK1521498. There were no significant effects of GSK1521498 2 mg day−1 on eating behaviour, indicating dose dependency of pharmacodynamics. GSK1521498 was generally well tolerated and no previously unidentified safety signals were detected. The potential for these findings to translate into clinically significant effects in the context of binge eating and weight regain prevention requires further investigation.

Neural and Behavioral Effects of a Novel Mu Opioid Receptor Antagonist in Binge-Eating Obese People

Background Binge eating is associated with obesity and has been conceptualized as “food addiction.” However, this view has received only inconsistent support in humans, and limited evidence relates key neurocircuitry to the disorder. Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors. Methods In a double-blind, placebo-controlled, parallel group study, we explored the effects of a potent mu-opioid receptor antagonist, GSK1521498, in obese individuals with moderate binge eating. Subjects were tested during a baseline placebo run-in period and retested after 28-days of drug (n = 21) or placebo (n = 21) treatment. Using functional magnetic resonance imaging and behavioral measures, we determined the drug’s effects on brain responses to food images and, separately, on motivation to expend energy to view comparable images. Results Compared with placebo, GSK1521498 was associated with a significant reduction in pallidum/putamen responses to pictures of high-calorie food and a reduction in motivation to view images of high-calorie food. Intriguingly, although motivational responding was reduced, subjective liking for the same images actually increased following drug treatment. Conclusions Stimulus-specific putamen/pallidal responses in obese people with binge eating are sensitive to altered mu-opioid function. This neuromodulation was accompanied by reductions in motivational responding, as measured by grip force, although subjective liking responses to the same stimuli actually increased. As well as providing evidence for a link between the opioid system and food-related behavior in binge-eating obese individuals, these results support a dissociation across measures of motivation and liking associated with food-related stimuli in these individuals.

Obesity and the Neurocognitive Basis of Food Reward and the Control of Intake

With the rising prevalence of obesity, hedonic eating has become an important theme in obesity research. Hedonic eating is thought to be that driven by the reward of food consumption and not metabolic need, and this has focused attention on the brain reward system and how its dysregulation may cause overeating and obesity. Here, we begin by examining the brain reward system and the evidence for its dysregulation in human obesity. We then consider the issue of how individuals are able to control their hedonic eating in the present obesogenic environment and compare 2 contrasting perspectives on the control of hedonic eating, specifically, enhanced control of intake via higher cognitive control and loss of control over intake as captured by the food addiction model. We conclude by considering what these perspectives offer in terms of directions for future research and for potential interventions to improve control over food intake at the population and the individual levels.

Reduction in ventral striatal activity when anticipating a reward in depression and schizophrenia: a replicated cross-diagnostic finding

In the research domain framework (RDoC), dysfunctional reward expectation has been proposed to be a cross-diagnostic domain in psychiatry, which may contribute to symptoms common to various neuropsychiatric conditions, such as anhedonia or apathy/avolition. We used a modified version of the Monetary Incentive Delay (MID) paradigm to obtain functional MRI images from 22 patients with schizophrenia, 24 with depression and 21 controls. Anhedonia and other symptoms of depression, and overall positive and negative symptomatology were also measured. We hypothesized that the two clinical groups would have a reduced activity in the ventral striatum when anticipating reward (compared to anticipation of a neutral outcome) and that striatal activation would correlate with clinical measures of motivational problems and anhedonia. Results were consistent with the first hypothesis: two clusters in both the left and right ventral striatum were found to differ between the groups in reward anticipation. Post-hoc analysis showed that this was due to higher activation in the controls compared to the schizophrenia and the depression groups in the right ventral striatum, with activation differences between depression and controls also seen in the left ventral striatum. No differences were found between the two patient groups, and there were no areas of abnormal cortical activation in either group that survived correction for multiple comparisons. Reduced ventral striatal activity was related to greater anhedonia and overall depressive symptoms in the schizophrenia group, but not in the participants with depression. Findings are discussed in relation to previous literature but overall are supporting evidence of reward system dysfunction across the neuropsychiatric continuum, even if the specific clinical relevance is still not fully understood. We also discuss how the RDoC approach may help to solve some of the replication problems in psychiatric fMRI research.

Negative schizophrenic symptoms and the frontal lobe syndrome: one and the same?

The negative symptoms of schizophrenia have been considered to be a psychiatric form of the frontal lobe syndrome. However, no studies have compared these two disorders at the clinical level. In this study, 12 negative symptom schizophrenic patients and 11 patients with behavioural variant frontotemporal dementia (bv-FTD) were rated for negative symptoms and for occurrence of frontal lobe behaviours in everyday life. They were also rated for speech disorder and were given a series of executive tests. Both patient groups showed positive ratings on negative symptoms and frontal lobe behaviours in daily life; however, the schizophrenic patients had higher negative symptom scores and the bv-FTD patients had higher carer ratings on frontal behaviours in daily life. Both groups were impaired on the executive tests, but the bv-FTD patients showed significantly greater impairment on verbal fluency and a test requiring inhibition of prepotent responses. A minority of the bv-FTD patients unexpectedly showed speech abnormalities typically associated with schizophrenia. The findings indicate that the negative syndrome in schizophrenia and the frontal lobe syndrome resemble each other clinically in important respects. Some of the differences may be attributable to the additional presence of disinhibition in the frontal lobe syndrome.

A study of psychotic symptoms in borderline personality disorder.

Abstract Patients with borderline personality disorder (BPD) report psychotic symptoms, but it has been questioned whether they are intrinsic to BPD. Thirty patients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for BPD were drawn from a specialist personality disorder service. Exclusion criteria included a preexisting clinical diagnosis of nonaffective psychotic disorder. Participants underwent structured psychiatric interview using the Present State Examination (PSE), lifetime version. Approximately 60% of the patients reported psychotic symptoms unrelated to drugs or affective disorder. Auditory hallucinations were the most common symptom (50%), which were persistent in the majority of cases. A fifth of the patients reported delusions, half of whom (three patients) also met DSM-IV criteria for schizophrenia, who were previously undiagnosed. The form of auditory hallucinations was similar to that in schizophrenia; the content was predominantly negative and critical. Persistent auditory hallucinations are intrinsic symptoms of BPD. This may inform current diagnostic criteria and have implications for approaches to treatment, both pharmacological and psychological. The presence of delusions may indicate a comorbid axis I disorder.

Sugar addiction: the state of the science

PurposeAs obesity rates continue to climb, the notion that overconsumption reflects an underlying ‘food addiction’ (FA) has become increasingly influential. An increasingly popular theory is that sugar acts as an addictive agent, eliciting neurobiological changes similar to those seen in drug addiction. In this paper, we review the evidence in support of sugar addiction.MethodsWe reviewed the literature on food and sugar addiction and considered the evidence suggesting the addictiveness of highly processed foods, particularly those with high sugar content. We then examined the addictive potential of sugar by contrasting evidence from the animal and human neuroscience literature on drug and sugar addiction.ResultsWe find little evidence to support sugar addiction in humans, and findings from the animal literature suggest that addiction-like behaviours, such as bingeing, occur only in the context of intermittent access to sugar. These behaviours likely arise from intermittent access to sweet tasting or highly palatable foods, not the neurochemical effects of sugar.ConclusionGiven the lack of evidence supporting it, we argue against a premature incorporation of sugar addiction into the scientific literature and public policy recommendations.