Therapeutic Impact of Dysfunction in Reward Processing in Anorexia Nervosa - A Mini Review

Special Article - Eating Disorders

Ann Nutr Disord & Ther. 2017; 4(2): 1045.

Therapeutic Impact of Dysfunction in Reward Processing in Anorexia Nervosa - A Mini Review

Kulvinder Kochar Kaur¹*, Allahbadia G² and Singh M³

¹Centre for Human Reproduction, India

²Rotunda - A Centre for Human Reproduction, India

³Swami Satyanand Hospital, India

*Corresponding author: Kulvinder Kochar Kaur, Centre for Human Reproduction, Scientific Director, 721, G.T.B. Nagar, Jalandhar-144001, Punjab, India

Received: May 05, 2017; Accepted: May 25, 2017; Published: June 01, 2017


Anorexia Nervosa (AN) is a disorder having a chronic course which is refractory to treatment in many patients and is one psychiatric disorder where greatest mortality rate exists. Hence understanding the basic pathophysiology is essential. Recently the dysfunction of reward processing has been highlighted in many reviews along with aberrant appetite motivators like leptin, ghrelin, BDNF and endocannabonoids signal is believed to affect not only homeostatic food systems but also hedonic circuits, just like importance of dopamine, acetylcholine, serotonin in reward processing is emphasized. This minireview tries to emphasize on the altered reward processing in such ED’s and in formulating newer therapies in a disorder not having any specific treatment till date.


Cultural influences, psychological, biologic, genetic and social factors likely contribute to the development of eating disorders. Several have been associated with their development including a history of dieting, preoccupation with weight, athletic and artistic pursuits that favour leanness or involve subjective judging and possibly sexual abuse. Young women having a first degree relative with an eating or affective disorder or alcoholism are at an increased risk for developing an eating disorder. Linkage analysis has identified possible susceptibility loci for Anorexia Nervosa (AN) on chromosome1 and for Bulimia Nervosa (BN) on chromosome 10. Affective, anxiety And Obsessive Compulsive Disorders (OCD), personality disorders substance abuse are common in women with eating disorders. Family stresses referred to high perceived parental expectations (for success, achievement) poor communication and marital tension also may play a role.

The clinical spectrum of eating disorders varies on a limited period of amenorrhea associated with a crash diet in otherwise normal women to the grossly underweight anorexic having a distorted body image and the bulimic who cycle regularly between binge eating and purging behavior. The specific diagnostic criteria for AN and BN are defined in the Diagnostic &Statistical Manual of Mental Disorders (DSM IV) and are briefly summarized here. DSMIV categorizes those with clearly abnormal eating patterns and weight control habits which do not meet the specific criteria for AN or BN as having an eating disorder not otherwise specified.

Anorexia Nervosa (AN)

Clinical features: Restrictive AN include weight loss, which frequently dates from a specific event like an illness, insensitive comments, rebuke or loss. Amenorrhea typically precedes weight loss which begins with dieting and specific restriction of fat intake. Affected women often admit fatigue, nausea, early satiety or bloating after meals. They exhibit a distorted body image, denial &disordered thinking and frequently use exercise as an additional weight control strategy. In women with AN the physical examination may reveal hypotension, bradycardia, low body temperature, dry skin [5] and lanugo (fine soft hair on the back ,buttocks and extremities).Thus while BN exhibits impulsive and addictive qualities on their behaviors, an inability to control binge eating and purging and frequently used cigarettes, alcohol and other drugs. Many have irregular menses, but not amenorrhea, and in most, weight fluctuates but is not abnormally low. Those with BN have parotid gland hypertrophy and erosion of their teeth enamel from frequent vomiting. Metabolic abnormalities associated with AN reflect dysfunctional hypothalamic regulation of appetite thirst, temperature, sleep, autonomic balance and endocrine secretion. Clinical consequences can be severe and even life threatening. The associated endocrine abnormalities include low FSH/LH/E2/IGF1, leptin concentrations and increased cortisol levels, prolactin, TSH and T4 levels are normal but the T3 levels low and Reverse T3 (r T3) high (r T3 is an isomer of T3 derived from T4 which binds but does not activate thyroid hormone receptors). With a gain all of metabolic abnormalities resolve [6]. Even though normal gonadotropin secretion may be restored with appropriate wt gain approximately 1/3rd remain amenorrheic likely reflecting persistent hypothalamic dysfunction [7].

Response Inhibition in ED’s

Behavior and personality characteristics vary in Eating Disorder (ED) patients depending on subtypes. Patients binge eating or purging behavior like AN, binge eating/purging type & or BN often show compulsive and disinhibited personality characteristics. While those with AN restricting type [8-10] often show a restrictive or overly controlled behavior style.

BN Is characterized by disinhibition & impulsivity related to eating behaviors [11,12]. Because of this vital hallmark of BN, DSMIV diagnostic description includes the disinhibited (out of control) characteristic [13]. Impulsitivity may also extend into other areas of life besides binge eating or purging [9]. Like patients with BN also show alcohol and drug abuse, self harm, sexual disinhibition and shoplifting [12]. Few data suggest that basis of cognitive and behavioral disinhibition in BN may also be related to serotonin dysregulation [14], while neuropsychiatric studies have found evidence of disinhibition at neurocognitive level in affected individuals. As compared to healthy subjects individuals with BN who used laxatives were seen to make greater errors of commissioning go/no go task for impulsive behaviors on a self report assessment [11]. Cognitive research in inhibition processing using a motor stop signal paradigm and a motor stroop task found that patients with a restrictive type AN displayed superior response inhibition. Overall fewer impulsive errors occur in patients with the binge eating/purging type [15]. AN patients with binge eating/purging behavior also made more response errors on a modified version of the Hayling sentence completion task relative to patients with restrictive subtype [15,16]. Thus behavior of similarities in impulsive cognitive styles between AN, binge eating/ purging type and BN they were grouped together as a single category of binge eating /purging type eating disorder in order to compare these patients with individuals in a restrictive type AN group and a healthy comparison group for this study of cognitive inhibitory control. Neural difference in the executive functioning related to inhibitory control maybe associated with the cognitive and clinical symptoms in BN [17-19]. Only few functional imaging studies have examined inhibition and disinhibition in BN till date. Marsh et al. studied response inhibition in adult patients with BN. They found that adult patients with BN responded more impulsively and made more errors on a response inhibition task (Simon task) [20], as compared to healthy comparison subjects and patients with the most severe symptoms made the most errors. Correct responding on incongruent trials, patients failed to activate frontostriatal circuits to the same degree as healthy comparison subjects including the bilateral inferior frontal gyrus, lenticular, caudate nuclei and the Anterior Cingulate Cortex (ACC). Marsh et al. concluded that diminished activity in these regions may contribute to the loss of control in eating behaviors of patients with BN. In contrast to patients with BN, clinical report show preservative, obsessive and rigid thinking styles in patients with AN. Patients with AN are commonly perfectionist and report obsessive compulsory personality traits and Obsessive Compulsive Disorders (OCD) in childhood [8]. Also studies show that patients who had AN but though recovered still showed traits of anxiety, perfectionism, inflexible thinking and over concern support/the likely importance of examining inhibition/disinhibition in adolescents with eating disorders. More work showed abnormal functioning of the inferior frontal and anterior cingulate gyrus is likely to be associated with impulsitivity and disinhibition in AN pts who binge eat and purge but not in those with the restrictive subtype [11]. Examination of response inhibition using the functional MRI in adolescents with ED’s specifically comparing those with restrictive type AN with those who had B Nor AN, Binge eating/purging type gives an opportunity to explore these processes in the developing brain and to distinguish patients with those subtypes from each other on a neural basis as well as from healthy comparison subjects. Examining neural correlates of inhibitory control in an adolescent population which is not severely emaciated and not chronically ill may help to distinguish these features associated with the onset of ED’s as opposed to the secondary effects associated with starvation and prolonged disease. Hence Lock et al. conducted a first study regarding brain activation associated with response inhibition in adolescents with ED’S and compared 13 female adolescents with binge eating and purging behavior (i.e. BN or AN binge eating /purging type). 14 with AN restricting type & 13 healthy normal controls who performed a rapid jittered event related go/nogo task. fMRI images were collected using a 3 Tesla GE scanner and a spiral pulse sequence. A whole brain 3 group analysis of variance in SPMS was used to identify significant activation associated with the main effect of group for the comparison of correct no go versus go trial. The mean activation in these clusters was extracted for further comparison in SPSS. They found that the binge eating/ purging group showed a markedly greater activation than the healthy comparison group in the bilateral precentral gyrus, ACC, middle and superior temporal gyrus as well as greater activation relative to both comparison and restrictive AN subjects in the hypothalamus and right dorsolateral prefrontal cortex. Within group analysis found that only the restrictive type AN group showed a positive correlation between the percent correct on go trials and activation in post visual and inferior parietal cortex regions. Thus they concluded that the study provided initial evidence that during adolescence, ED subtypes maybe distinguishable in terms of neural correlates of inhibitory control. This distinction is consistent with difference in behavior or impulsivity in this patient groups [21].

Altered Reward Processing in AN

Wagner et al. based on previous findings of altered striatal dopamine binding in AN tried to assess the response of the anterior ventral striatum to reward and loss in this disorder. They studied striatal responses to a simple monetary reward task using event related functional MRI. They compared 13normal women &13 women who had recovered from resting type AN and had 1 year of normal weight and regular menstrual cycles without binge eating or purging. They found that recovered women showed a significant positive relationship between trait anxiety and the percentage changes in haemodynamic signal in the caudate during either wins or loses .In contrast in the anterior ventral striatum comparison women distinguished positive and negative feedback whereas recovered women had similar responses to both conditions. Thus they concluded that individuals who have recovered from AN may have difficulties in differentiating positive and negative feedback. The exaggerated activation of the caudate, a region involved in linking action to outcome may constitute an attempt at ‘’strategic’’ (as opposed to hedonic) means of responding to reward stimuli. Thus they hypothesized that individuals of AN have an imbalance in information processing with impaired ability to identify the emotional significance of a stimulus but increased traffic in neurocircuits concerned with planning and consequences [22]. Figure 1 for neurocircuits associated with hedonic and goal directed behaviors.

Citation: Kulvinder Kochar Kaur, Allahbadia G and Singh M. Therapeutic Impact of Dysfunction in Reward Processing in Anorexia Nervosa - A Mini Review. Ann Nutr Disord & Ther. 2017; 4(2): 1045.