The Neurobiology of Anorexia Nervosa

Timothy D Brewerton, Ian Frampton, Bryan Lask
US Psychiatry, 2009;2(1):57-60
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Abstract

This article provides an overview of research findings on the neurobiology of anorexia nervosa (AN), including studies of monoamine neurotransmitter function, genetics, brain imaging, and neuropsychology. Such studies are designed to reveal the underlying neuroanatomical and pathophysiological bases of this potentially lethal condition. Notwithstanding commonly held misconceptions, there is no compelling evidence that sociocultural factors alone cause AN. Over the previous two decades, research into the role of the brain in eating disorders has been very productive and informative. Sorting out what is trait- and what is state-related has been a challenging focus of neurobiological research in AN. Many of the earlier identified abnormalities have been shown to be directly due to the effects of semi-starvation, weight loss, and/or maladaptive behaviors of AN. Results in AN patients who have been weight-recovered for at least one year indicate persistent alterations in serotonin function, set shifting, and visuo-spatial processing.
Keywords
Anorexia nervosa, neurobiology, serotonin, brain imaging, neuropsychology
Disclosure The authors have no conflicts of interest to declare.
Received: April 17, 2008 Accepted November 06, 2008
Correspondence: Timothy D Brewerton, MD, 216 Scott Street; Mt. Pleasant, SC 29464. E: tbrewerton1@comcast.net

This article will provide an overview of research findings on the neurobiology of anorexia nervosa (AN), including studies of neurotransmitter function, genetics, brain imaging, and neuropsychology. Such studies are aimed at elucidating the underlying neuroanatomical and pathophysiological bases of AN. Despite widely held beliefs, there is no convincing evidence that cultural factors alone cause AN. Indeed, over the past few years research into the role of the brain in eating disorders has been very fruitful. This is despite the clear realization that many earlier identified abnormalities have been found to be directly due to the effects of semi-starvation and/or the extreme eating practices of AN. Sorting out what is trait- and what is state-related has been a challenging focus of neurobiological research in AN.

Monoamine Neurotransmitters

The monoamine neurotransmitters (norepinephrine [NE]), dopamine [DA]), and serotonin [5-HT]) have been extensively studied during all phases of AN (actively ill, short-term weight-recovered, and long-term weight-recovered) using existing technologies. Dieting and/or semi-starvation deplete all central monoamines and lead to altered neurotransmitter levels and receptor sensitivity in animals and humans, the results of which have been reviewed in detail elsewhere.1,2 In order to minimize these starvation-state- related effects and to reveal potential trait-related disturbances or vulnerabilities, investigators have more recently studied ‘recovered’ patients, i.e. those AN patients who have attained (for at least one year) normalization of eating and weight, resumption of menses and/or normalization of gonadal hormone levels, and abatement of typical cognitive features to subclinical levels. However, the long-term effects of chronic malnutrition and disordered eating behaviors on the brain (similar to substance use disorders) cannot be dismissed. For the purposes of this article, studies of recovered AN patients will be the major focus.

Norepinephrine

The role of NE in the modulation of feeding, mood, anxiety, neuroendocrine control, metabolic rate, sympathetic tone, and temperature has made it a likely candidate for study in AN.3–12 Low-weight AN patients have been shown to have reduced measures of plasma, urinary, and cerebrospinal fluid (CSF) 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), the major metabolite of NE.6–9 However, these levels completely normalize upon full weight restoration.12 In contrast, AN patients tend to have higher plasma NE levels at admission, which then decrease as treatment and weight gain progress.4,11

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