Kaye W. Neurobiology of anorexia and bulimia nervosa. Physiol Behav 94: 121-135

University of California, San Diego, 8950 Villa La Jolla Drive, Suite C207, La Jolla, CA 92037, United States.
Physiology & Behavior (Impact Factor: 2.98). 05/2008; 94(1):121-35. DOI: 10.1016/j.physbeh.2007.11.037
Source: PubMed


Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by which they can modulate brain 5-HT functional activity and anxious mood. People with AN enter a vicious cycle which accounts for the chronicity of this disorder because caloric restriction results in a brief respite from dysphoric mood. However, malnutrition and weight loss, in turn, produce alterations in many neuropeptides and monoamine function, perhaps in the service of conserving energy, but which also exaggerates dysphoric mood. In summary, this article reviews findings in brain chemistry and neuroimaging that shed new light on understanding the psychopathology of these difficult and frustrating disorders.

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Available from: Walter H Kaye, Jul 14, 2014
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    • "The extremely low weight characteristic of anorexia nervosa may also decrease feelings of anxiety by having a direct effect on serotonin levels and the HPA axis (Connan et al., 2003). Perhaps due to the wealth of evidence highlighting the importance of social cognition in ED, several theoretical models have implicated social and emotional difficulties as playing a key role in the development and maintenance of ED (Connan et al., 2003; Kaye, 2008; Hatch et al., 2010; Treasure et al., 2012). "
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    ABSTRACT: Diagnosis of an eating disorder (ED) has been associated with differences in social cognition. To date research investigating social cognition and ED has mainly employed patient and recovered samples. It is therefore unclear whether differences in social cognition are present prior to onset of ED, potentially contributing to development, or whether differences observed are a consequence of the disorder. We aimed to further explore whether individuals at high-risk for ED present social cognition characteristics previously found in ED groups. Our sample was drawn from a population-based cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Data on maternal ED behaviors over the lifetime were collected through in-depth clinical interviews (n = 1128) conducted using the Structured Clinical Interview for DSM disorders (SCID), and were used to categorize mothers according to ED behaviors over the lifetime: Restricting and Excessive Exercising (n = 58), Purging (n = 70), Binge-eating (n = 72), Binging and Purging (n = 66), no ED (n = 862). High-risk status of children was determined using these maternal lifetime behavioral phenotypes. Children at high-risk (maternal ED exposure) were compared to children at low-risk (born to mothers with no ED) on three measures of social cognition: the Social Communication Disorders Checklist (SCDC) (n = 922), the faces subtest of the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) (n = 722), and the Emotional Triangles Task (n = 750). Children at high-risk for ED showed poorer performance on measures of social cognition compared to children at low-risk. Maternal lifetime binge-eating, and maternal lifetime binging and purging were associated with poorer social communication in children (OR: 2.4, 95% CI: 1.0, 5.7, p = 0.05; and OR: 2.7, 95% CI: 1.1, 6.5, p = 0.03 respectively). Maternal binging and purging was also found to be associated with differential facial emotion processing and poorer recognition of fear from social motion cues (B: -0.7, 95% CI: -1.1, -0.2, p = 0.004). Children at high-risk for ED showed slight differences in some areas of social cognition when compared to children at low-risk. Characteristic patterns in social cognition are present in children at high-risk for ED, particularly among children whose mothers have binge-eating and purging behaviors over the lifetime. Our findings support the hypothesis that these differences may be part of an intermediate phenotype for ED: perhaps contributing to development, or perhaps indexing a shared liability with psychiatric disorders characterized by abnormal social cognition.
    Full-text · Article · Aug 2015 · Frontiers in Behavioral Neuroscience
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    • "Multiple mental disorders like anxiety, depression, and obsessive-compulsive disorder (OCD) are associated with binge eating (McElroy et al. 1994; Peterson et al. 2012). Binge eating may be triggered by anxiety, but bingeing reduces anxiety and increases reward sensation during and after the episode (Kaye 2008). Similarly, anxiety is triggered in individuals with OCD during the obsessive phase and is reduced/ released when the compulsive act is executed. "
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    ABSTRACT: Obsessive-compulsive disorder (OCD) gradually emerges and reaches clinical significance during early adulthood. Whether a predisposition for OCD manifests as binge eating disorder earlier during adolescence is proposed. To further characterize how OCD-like behaviors increase across maturation and to determine whether an OCD-like predisposition increases the likelihood of binge eating during adolescence. Male and female Sprague-Dawley rats were injected with the tricyclic antidepressant clomipramine (CMI, 15 mg/kg) or saline vehicle twice daily between postnatal days 9-15. Both groups were tested for perseverative (spontaneous alternation) and anxiety-like (elevated plus maze; marble burying) behaviors during juvenility (day 28), adolescence (day 60), and adulthood (day 90). Both motivations to eat sucrose pellets and binge eating on fat were investigated. Sex- and age-dependent increases in anxiety-like and perseverative behavior were observed in CMI subjects. Differences in consummatory behaviors emerged during late adolescence, while no significant differences in alternation or anxiety-like behaviors were detected between CMI and vehicle animals until adulthood. Adolescent CMI females consumed more sucrose pellets in 30 min relative to vehicle females, whereas adolescent CMI males consumed approximately half as much as vehicle males. Sucrose consumption did not differ between groups in adulthood. Adolescent CMI rats demonstrated more fat bingeing than vehicles, independent of sex. OCD-like behaviors are emerging during adolescence, but sucrose consumption and fat bingeing in CMI-treated animals significantly precedes the appearance of anxiety and perseveration. This OCD-like phenotype emerges fully during adulthood, suggesting that eating may likely serve as a coping strategy in these animals.
    Full-text · Article · May 2015 · Psychopharmacology
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    • "Furthermore, this objectified body (see Riva et al., 2015) may be refused by AN patients, who look for a more genuine and subjective body that is not immediately given to others. This philosophical perspective recalls neuropsychiatric models' (Kaye, 2008) viewing of AN symptoms as an expression of a pathological need to control, which finds in an individual's body the most available and, apparently, personal object. That social relations are crucial in EDs is also indicated by the empirical evidence reviewed by Martijn, Alleva, and Jansen (2015), which shows that positive social feedback may attenuate dissatisfaction with one's own body. "

    Full-text · Article · Jan 2015 · European Psychologist
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