Iain C. Campbell

A neurodevelopmental model for anorexia nervosa

This paper integrates genetic and biological data on aetiological risk for anorexia nervosa (AN) with cognitive and psychosocial explanatory models. We have reviewed clinical and basic science data from each of these domains and then used a developmental perspective to formulate a multifactorial threshold model. By positioning interpersonal stress as a central component of this model, psychological, social and biological conceptualisations of AN can be used to generate a data driven, neurodevelopmental hypothesis for the aetiology of this complex disorder.

Functional Neuroanatomy of Body Shape Perception in Healthy and Eating-Disordered Women

BACKGROUND Abnormalities in perception and evaluation of body shape are a hallmark of eating disorders. METHODS Brain responses to line drawings of underweight, normal weight, and overweight female bodies were measured with functional magnetic resonance imaging in 9 women with bulimia nervosa, 13 with anorexia nervosa, and 18 healthy women. Participants rated the stimuli for fear and disgust. RESULTS In the three groups, the lateral fusiform gyrus, inferior parietal cortex, and lateral prefrontal cortex were activated in response to body shapes compared with the control condition (drawings of houses). The responses in the lateral fusiform gyrus and in the parietal cortex were less strong in patients with eating disorders compared with healthy control subjects. Patients with eating disorders rated the body shapes in all weight categories as more aversive than did healthy women. In the group with eating disorders, the aversion ratings correlated positively with activity in the right medial apical prefrontal cortex. CONCLUSIONS Processing of female body shapes engages a distributed neural network, parts of which are underactive in women with eating disorders. The considerable variability in subjective emotional reaction to body shapes in patients with eating disorders is associated with differential activity in the prefrontal cortex.

Cerebral processing of food-related stimuli: effects of fasting and gender.

To maintain nutritional homeostasis, external food-related stimuli have to be evaluated in relation to the internal states of hunger or satiety. To examine the neural circuitry responsible for integration of internal and external determinants of human eating behaviour, brain responses to visual and complex gustatory food-related stimuli were measured using functional magnetic resonance imaging in 18 healthy non-smokers (10 women, 8 men). Each individual was studied on two occasions, the order of which was counterbalanced; after eating as usual and after 24 h fasting. Raised plasma free fatty acids and lower insulin and leptin concentrations confirmed that participants fasted as requested. When fasted, participants reported more hunger, nervousness and worse mood and rated the visual (but not gustatory) food-related stimuli as more pleasant. The effect of fasting on hunger was stronger in women than in men. No circuitry was identified as differentially responsive in fasting compared to satiety to both visual and gustatory food-related stimuli. The left insula response to the gustatory stimuli was stronger during fasting. The inferior occipito-temporal response to visual food-related stimuli also tended to be stronger during fasting. The responses in the occipito-temporal cortex to visual and in the insula to gustatory stimuli were stronger in women than in men. There was no interaction between gender and fasting. In conclusion, food reactivity in modality-specific sensory cortical areas is modulated by internal motivational states. The stronger reactivity to external food-related stimuli in women may be explored as a marker of gender-related susceptibility to eating disorders.

Recovery and chronicity in anorexia nervosa: brain activity associated with differential outcomes

BACKGROUND The course of anorexia nervosa varies from rapid recovery to a chronic debilitating illness. This study aimed to identify functional neural correlates associated with differential outcomes. METHODS Brain reactions to food and emotional visual stimuli were measured with functional magnetic resonance imaging in nine women who had long-term recovery from restricting anorexia nervosa. These were compared with age- and education-matched groups of eight women chronically ill with restricting anorexia nervosa and nine healthy control women. RESULTS In response to food stimuli, increased medial prefrontal and anterior cingulate activation, as well as a lack of activity in the inferior parietal lobule, differentiated the recovered group from the healthy control subjects. Increased activation of the right lateral prefrontal, apical prefrontal, and dorsal anterior cingulate cortices differentiated these recovered subjects from chronically ill patients. Group differences were specific to food stimuli, whereas processing of emotional stimuli did not differ between groups. CONCLUSIONS Separate neural correlates underlie trait and state characteristics of anorexia nervosa. The medial prefrontal response to disease-specific stimuli may be related to trait vulnerability. Lateral and apical prefrontal involvement is associated with a good outcome.

A systematic review and meta-analysis of cognitive bias to food stimuli in people with disordered eating behaviour

AIM Maladaptive cognitions about food, weight and shape bias attention, memory and judgment and may be linked to disordered eating behaviour. This paper reviews information processing of food stimuli (words, pictures) in people with eating disorders (ED). METHOD PubMed, Ovid, ScienceDirect, PsychInfo, Web of Science, Cochrane Library and Google Scholar were searched to December 2009. 63 studies measured attention, memory and judgment bias towards food stimuli in women with ED. RESULTS Stroop tasks had sufficient sample size for a meta-analyses and effects ranged from small to medium. Other studies of attention bias had variable effects (e.g. the Dot-Probe task, distracter tasks and Startle Eyeblink Modulation). A meta-analysis of memory bias studies in ED and RE yielded insignificant effect. Effect sizes for judgment bias ranged from negligible to large. CONCLUSIONS People with ED have greater attentional bias to food stimuli than healthy controls (HC). Evidence for a memory and judgment bias in ED is limited.

Differential neural responses to food images in women with bulimia versus anorexia nervosa

Background Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. Methods We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). Results In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. Conclusions Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.

Effect of Left Prefrontal Repetitive Transcranial Magnetic Stimulation on Food Craving

BACKGROUND Dysfunction of the prefrontal cortex is implicated in craving for drugs and food. This study explores the effect of prefrontal cortex stimulation on food craving. METHODS In a randomized double-blind parallel group study, 28 women, who reported frequent cravings for food were exposed to foods that typically elicit strong cravings before and after a single session of real or sham 10-Hz repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex at an intensity of 110% individual motor threshold. RESULTS Self-reported food craving during exposure to the experimental foods remained stable before and after real stimulation compared with sham stimulation in which cravings increased over the experimental session. Consumption of snack foods within a 5-min period after stimulation did not differ between groups. CONCLUSIONS Prefrontal stimulation inhibits the development of craving. A longer period of observation is necessary to establish whether there is an effect on food consumption.

An investigation of decision making in anorexia nervosa using the Iowa Gambling Task and skin conductance measurements

The objective of this study is to determine (a) if decision making ability is impaired in patients with anorexia nervosa (AN) and in people with good recovery from AN and (b) whether any impairment in decision making is associated with alterations in skin conductance responses (SCR). Patients with AN (n = 29), healthy controls comparable in age and IQ (HC, n = 29), and women long term recovered from AN (n = 14), completed the Iowa Gambling Task (IGT) while their SCR were measured. AN patients performed poorly in the IGT compared to the HC and to the recovered AN participants. AN patients had decreased anticipatory SCR prior to choosing cards and reduced SCR after losses compared to HC. IGT performance and the SCR of recovered AN participants did not differ from the HC. Decision making ability is impaired in AN. It is associated with a significantly attenuated SCR. Neither of these features are found in recovered AN. The association between impaired decision making ability and a decreased autonomic response is consistent with the predictions of the Somatic Marker Hypothesis.

Cognitive remediation therapy for patients with anorexia nervosa: preliminary findings.

BackgroundAnorexia nervosa (AN) is a severe mental illness. Drug treatments are not effective and there is no established first choice psychological treatment for adults with AN. Neuropsychological studies have shown that patients with AN have difficulties in cognitive flexibility: these laboratory based findings have been used to develop a clinical intervention based on Cognitive Remediation Therapy (CRT) which aims to use cognitive exercises to strengthen thinking skills.Aims1) To conduct a preliminary investigation of CRT in patients with AN 2) to explore whether cognitive training improves performance in set shifting tasks 3) to explore whether CRT exercises are appropriate and acceptable to AN patients 4) to use the data to improve a CRT module for AN patients.MethodsIntervention was comprised of ten 45 minute sessions of CRT. Four patients with AN were assessed before and after the ten sessions using five set shifting tests and clinical assessments. At the end, each patient wrote a letter providing feedback on the intervention.ResultsPost intervention, three of the five set shifting assessments showed a moderate to large effect size in performance and two showed a large effect size in performance, both indicative of improved flexibility. Patients were aware of an improvement in their cognitive flexibility qualitative feedback was generally positive towards CRT.DiscussionThis preliminary study suggests that CRT changed performance on flexibility tasks and may be beneficial for acute, treatment resistant patients with AN. Feedback gathered from this small case series has enabled modification of the intervention for a future larger study, for example, by linking exercises with real life behavioural tasks and including exercises that encourage global thinking.ConclusionThis exploratory study has produced encouraging data supporting the use of CRT in patients with AN: it has also provided insight into how the module should be tailored to maximise its effectiveness for people with acute AN.

Blood Platelets Contain a Neuron-Specific Enolase Subunit

Abstract: Neuron‐specific enolase (NSE) is a cell‐specific isoenzyme of the glycolytic enzyme enolase that is present only in neurons and selected neuroendocrine cells. We now report the presence of this neuronal marker in blood platelets. The level of NSE found in human blood platelets is much lower than that found in brain tissue (0.045% of the total soluble protein for platelets versus 1.5% for cortical tissue), but is 20‐30 times higher than NSE levels found in peripheral non‐nervous tissues. Chromatographic analysis indicates that the majority of the NSE γ‐subunit in platelets is present as the hybrid αγ isoenzyme. This, coupled with the high level of non‐neuronal enolase (NNE) found in platelets, indicates that blood platelets contain both the α‐ and γ‐ subunit.