Biological Psychiatry - Vol. 2

By Hugo D'Haenen; J.A. Den Boer et al. | Go to book overview


Frances Connan


Although over a single day food intake is poorly matched to energy expenditure, longer term food intake and energy expenditure can be extremely well balanced such that weight may remain remarkably stable over time (Edholm, 1977). However, the systems governing energy homeostasis appear to function more effectively to defend against starvation than they do in defence of overweight. Indeed, it has been argued that the capacity of the system to maintain healthy weight in the face of high availability of energy dense food and low physical activity levels is poor: there is a marked tendency to over consume, resulting in a high prevalence of obesity (Pinel et al., 2000). In addition to the significant morbidity associated with obesity in its own right, a tendency toward overweight may be a vulnerability factor for the most common of the eating disorders, bulimia nervosa (BN) and binge-eating disorder (BED). These disorders are associated with elevated subjective reward value of food (Karhunen et al., 1997a; Wisniewski et al., 1997), reduced subjective sense of satiety (Kissileff et al., 1996) and premorbid or family history of obesity (Fairburn et al., 1997, 1998).

At the other end of the weight spectrum, anorexia nervosa (AN) is characterized by reduced food intake, but the question of whether appetite is impaired remains controversial and poorly researched. Studies employing subjective assessment have consistently reported reduced hunger and desire to eat and enhanced satiety and sensation of fullness in people with AN (e.g., Halmi and Sunday, 1991; Robinson, 1989). Furthermore, the subjective reward value of food is reduced (Drewnowski et al., 1987; Sunday and Halmi, 1990), and the rate of eating is slow (Halmi and Sunday, 1991). Some authors argue that these findings reflect tight cognitive control of normal appetite (Palmer, 2000). However, relative to healthy comparison women, those with AN show reduced salivation (LeGoff et al., 1988) and a heightened autonomic response to food (Leonard et al., 1998). Images of food elicit fear and disgust (Ellison et al., 1998). These objective data suggest that appetite may indeed be impaired in AN (Pinel et al., 2000), although some capacity to respond to hunger and satiety cues clearly remains (Cugini et al., 1998; Rolls et al., 1992). A predisposition to leanness may be a risk factor for AN (Hebebrand and Remschmidt, 1995), supporting the notion that heritable risk for the disorder may be exerted through the biological systems regulating appetite and weight.

If we are to understand the neuroendocrinology of appetite and weight regulation in eating disorders, we must first understand the normal function of these systems and their responses to changes in body weight. It is well recognized that starvation causes profound changes in neuroendocrine systems and thus many of the findings associated particularly with AN, are liable to be consequence rather than cause of the disorder. Accordingly, the first section provides an overview of current models for understanding the neuroendocrine regulation of appetite and weight. Subsequent sections examine neuroendocrine data relating to each of the eating disorders in turn before presenting a synthesis and considering the implications for treatment and future research.


Leptin—A Peripheral Energy Sensor

The discovery of leptin in 1995 led to dramatic advances in the understanding of central pathways regulating appetite and weight. Leptin is a 146 amino acid protein that is synthesized and secreted by fat cells. When energy balance is stable, leptin concentration is proportional to fat mass (Considine et al., 1996). However, acute changes in energy balance modulate leptin expression, such that fasting is associated with a greater fall in leptin than might be expected for the change in fat mass and conversely, overeating results in an enhanced postprandial rise in circulating leptin (Ahima et al., 1996; Kolaczynski et al., 1996a). The leptin system therefore responds to potential weight change before fat mass actually changes.

The importance of leptin as a signal of energy balance is demonstrated by genetic strains of mice lacking functional leptin (ob/ob mice) or its receptor (db/db mice). These animals are hyperphagic, hypothermic, hyperinsulinaemic and obese (Chua-SC et al., 1996; Lee et al., 1996; Zhang et al., 1994). Although rare, genetic deficits of leptin signalling in humans are associated with a similar phenotype (Clement et al., 1998; Montague et al., 1997). Exogenous leptin administration reduces food intake and weight in normal and leptin deficient individuals (Farooqi et al., 1999; Halaas et al., 1997; Pelleymounter et al., 1995). Thus, despite the obese phenotype, genetic leptin deficiency is actually a model of starvation: reduced leptin levels signal reduced fat mass and appetite is appropriately elevated.

Leptin enters the brain via an active transport mechanism and its functional long-arm receptors are located in areas of the hypothalamus, such as the arcuate, ventromedial, paraventricular and dorsomedial nuclei (Elmquist et al., 1998): areas important for the function of neuroendocrine systems, including those regulating appetite and weight. The leptin system is therefore an excellent candidate for a peripheral signal of energy homeostasis and adequacy of fat stores to central systems coordinating the adaptive response to starvation.

Other Peripheral Signals of Energy Homeostasis

Several other peripheral hormones play a significant role in the central regulation of appetite. Insulin was one of the first hormonal signals known to be secreted in proportion to adipose mass. Insulin is actively transported across the blood-brain barrier and both insulin receptor mRNA and specific insulin binding sites


Notes for this page

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this book

This book has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this book

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Cite this page

Cited page

Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited page

Bookmark this page
Biological Psychiatry - Vol. 2
Table of contents

Table of contents



Text size Smaller Larger Reset View mode
Search within

Search within this book

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Full screen
/ 730

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25,

    New feature

    It is estimated that 1 in 10 people have dyslexia, and in an effort to make Questia easier to use for those people, we have added a new choice of font to the Reader. That font is called OpenDyslexic, and has been designed to help with some of the symptoms of dyslexia. For more information on this font, please visit

    To use OpenDyslexic, choose it from the Typeface list in Font settings.

    OK, got it!

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Author Advanced search


    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.