Several lines of evidence suggest that women with anorexia nervosa have a disturbance of se rotonin (5-hydroxytryptamine [5-HT]) neuronal transmission. Serotonin function in the brain is involved in the regulation of both mood and behavior, including eating behavior. Increased 5-HT activity may contribute to core emotional and attitudinal factors, such as anxiety, perfectionism, harm avoidance, and body image distortions, which, when coupled with psychosocial influences, may increase an individual's risk for developing anorexia nervosa (Kaye et al., submitted). Disturbances of 5-HT activity and anxious, obsessive symptoms persist after recovery from anorexia nervosa, and recovered women have increased levels of the major serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) (Kaye, Gwirtsman, George, & Ebert, 1991). Moreover, the antidepressant medication fluoxetine, which affects the serotonergic system, may reduce the rate of relapse among anorexia nervosa patients (Kaye et al., 2001).

A series of family studies have demonstrated a significantly greater lifetime prevalence of eating disorders among relatives of eating disordered individuals than among relatives of controls (Gershon et al., 1983; Hudson, Pope, Jonas, Yurgelun-Todd, & Frankenburg, 1987; Kassett et al., 1989; Lilenfeld et al., 1998; Strober et al., 1990; Strober, Freeman, Lampert, Diamond, & Kaye, 2000). Relatives of individuals with anorexia nervosa and bulimia nervosa also have significantly increased rates of eating disorders that do not meet full diagnostic criteria, compared to relatives of controls (Lilenfeld et al., 1998; Strober et al., 2000), which suggests a broad spectrum of eating-related pathology in families. Thus, anorexia nervosa appears to be familial (see Lilenfeld, Kaye, & Strober, 1997, for a review). In addition, twin studies (Klump, Miller, Keel, McGue, & Iacono, 2001; Kortegaard, Hoerder, Joergensen, Gillberg, & Kyvik, 2001; Wade et al., 2000) suggest that the observed familial links may be accounted for by genetic effects.

Linkage studies have begun to identify areas of the human genome that may harbor suscep

tibility genes for anorexia nervosa, with the most promising areas being identified on chromosome 1 (Devlin et al., 2002; Grice et al., 2002). Several groups have investigated the relation between a variety of candidate genes and eating disorders (for a review, see Tozzi, Bergen, & Bulik, 2002). These studies have chosen candidate genes based on systems and functions associated with food intake, body weight, regulation of feeding behavior, motor activity, energy expenditure, metabolic adaptation to fasting, and other related characteristics and symptoms of eating disorders. Although a number of positive findings have been documented, no single gene or set of genes has consistently emerged as being strongly associated with either anorexia nervosa or bulimia nervosa. As anorexia nervosa is a complex disorder whose etiology is influenced by multiple genes and multiple environmental factors, ultimate understanding of risk will have to include the elucidation of Gene × Environment, Gene × Gene, and Environment × Environment interactions.

Numerous studies have been conducted to identify risk factors that predict the onset of anorexia nervosa, but enhanced efforts are needed to identify true risk and protective factors for anorexia nervosa. Studies of recovered individuals, while valuable, are not sufficient to discriminate between risk factors for anorexia nervosa and residual effects of anorexia nervosa. The identification of protective factors is equally critical, as the identification of factors that are associated with both the emergence of anorexia nervosa and the failure to develop the disorder has implications for both detection and prevention of the disorder.

As with anorexia nervosa, the cultural emphasis on thinness has been implicated as a risk factor for the development of bulimia nervosa. Pressure to be thin has been shown to predict increases in body dissatisfaction, dieting, and negative affect (Cattarin & Thompson, 1994; Field et al., 2001; Stice, 2001; Stice & Bearman, 2001; Stice & Whitenton, 2002; Wertheim, Koerner, & Paxton, 2001) and to contribute to bulimic symptom onset (Field, Camargo, Taylor, Berkey, & Colditz, 1999; Stice & Agras, 1998; Stice, Presnell, & Spangler, 2002). Experiments have found that acute and long-term exposure to ultraslender media images and peers produces increased body dissatisfaction, negative affect, dieting, and bulimic symptoms, but that these effects are stronger for girls with preexisting body image disturbances and social support deficits (Cattarin, Thompson, Thomas, & Williams, 2000; Groesz, Levine, & Murnen, 2002; Irving, 1990). Thus, perceived pressure to be thin appears to be a risk factor for body dissatisfaction, dieting, negative affect, and bulimic symptoms, and these effects may be amplified for at-risk individuals.

Several studies have examined the extent to which early problems with feeding constitute risk factors for the later development of broadly

defined eating disorder symptoms. In data obtained from a long-term prospective study, Marchi and Cohen (1990) found that symptoms of bulimia nervosa in later adolescence were related to both digestive problems and pica in early childhood and to efforts at weight loss in early adolescence. Stice, Agras, and Hammer (1999) found that a higher infant body mass index (BMI) predicted the emergence of overeating and that longer duration of infant sucking predicted overeating-induced vomiting in children; however, the relationship of these phenomena to the development of bulimia nervosa is unknown.

Early menarche is thought to produce increased adipose tissue, which may result in a perceived deviation from the thin ideal and decreased body dissatisfaction and could, in turn, lead to dieting, negative affect, and bulimic symptoms. Early sexual development can also lead to increased sexual attention and unwanted comments and teasing. However, early menarche did not predict future increases in body dissatisfaction, dieting, negative affect, or bulimic symptoms (Cooley & Toray, 2001a; Hayward et al., 1997; Stice & Whitenton, 2002). Therefore, the currently available research does not support early pubertal development as a risk factor for these symptoms.

Perfectionism has been evaluated as a risk factor for eating pathology because this personality trait may promote a relentless pursuit of the thin ideal. Three studies have found that perfectionism did not predict future bulimic symptomatology (Killen et al., 1996; Vohs, Bardone, Joiner, Abramson, & Heatherton, 1999; Vohs et al., 2001), although neither study used DSM-IV criteria for bulimia nervosa as an outcome. Another personality characteristic, a deficit in impulse control, has also been considered a risk factor for bulimic pathology, as deficits in impulse control might increase the propensity for episodes of uncontrollable binge eating. Data from three pro spective studies indicate that impulsivity does not predict subsequent increases in bulimic symptoms (Wonderlich, Connolly, & Stice, in press). Thus, while there is currently no empirical evidence for a role of perfectionism or impulsivity as risk factors for bulimic pathology, additional studies are required to determine whether these traits influence risk for threshold bulimia nervosa.

Negative affect has been shown to predict increases in bulimic symptoms and subthreshold/threshold bulimic pathology among adolescents (Cooley & Toray, 2001a; Killen et al., 1996; Stice, 2001; Stice & Agras, 1998), and experimentally induced negative affect produced increases in body dissatisfaction in one study (Taylor & Cooper, 1992). One prevention trial found that an intervention that reduced negative affect produced decreases in bulimic pathology (Burton, Stice, Bearman, & Rohde, submitted). These results are consistent in suggesting that negative affect is a risk factor for bulimic pathology.

Elevated body mass, or being at a higher weight, has been shown to predict increases in perceived pressure to be thin, in body dissatisfaction, and in attempted dieting (Cattarin & Thompson, 1994; Field et al., 2001; Patton, Johnson-Sabine, Wood, Mann, & Wakeling, 1990; Stice & Whitenton, 2002; Vogeltanz-Holm et al., 2000), but not increases in depression (Lewinsohn et al., 1994; Stice & Bearman, 2001; Stice, Hayward Cameron, Killen, & Taylor, 2000). Therefore, individuals at a higher weight may experience pressure to be thin from family or peers, which could result in increased drive for thinness or body dissatisfaction, and increased risk for bulimic symptoms. Increased BMI predicted the onset of bulimic symptoms in several studies (Killen et al., 1994; Stice, Presnell, & Spangler, 2002; Vogeltanz-Holm et al., 2000), but other studies found no association (Cattarin & Thompson, 1994; Cooley & Toray, 2001b; Killen et al.,

1996; Stice & Agras, 1998). Thus, while increased weight is a risk factor for pressure to be thin, body dissatisfaction, and attempted dieting, it may play a more important role in promoting other risk factors for bulimia nervosa than in directly fostering bulimic symptoms.

Self-report dietary restraint measures predicted increases in negative affect (Stice & Bearman, 2001; Stice et al., 2000) and onset of bulimic pathology (Field, Camargo, Taylor, Berkey, & Colditz, 1999; Killen et al., 1994, 1996; Stice, 2001; Stice & Agras, 1998). However, experiments manipulating dietary restriction have not supported dietary restriction as a risk factor for bulimic symptoms. Random assignment to a low-calorie diet (Goodrick, Poston, Kimball, Reeves & Foreyt, 1998; Presnell & Stice, 2003; Reeves et al., 2001) or a weight-maintenance diet (Klem, Wing, Simkin-Silverman, & Kuller, 1997; Stice, Presnell, Groesz, & Shaw, submitted), relative to a waiting-list condition, resulted in reduced negative affect and bulimic symptoms among obese and nonobese samples. Although these findings appear contradictory, it has been reported that self-report dietary restraint scales do not measure actual caloric restriction (Stice, Fisher, & Lowe, 2004), which indicates that these scales may not be valid measures of dietary restriction. Thus, although prospective studies suggest that dieting is a risk factor for negative affect and bulimic pathology, experimental studies suggest that prescribed dietary restriction is not a causal risk factor for bulimic pathology. It is important to note that caloric restriction as implemented in experimental situations may not mimic the types of dysfunctional dieting behavior that occur among individuals prone to eating disorders.

Body dissatisfaction predicts increases in attempted dieting (Cooley & Toray, 2001a; Patton et al., 1990; Stice, 2001; Wertheim, Koerner, & Paxton 2001), negative affect (Rierdan, Koff, & Stubbs, 1989; Stice & Bearman, 2001; Stice et al., 2000), bulimic symptom onset (Field et al., 1999; Killen et al., 1994, 1996; Stice & Agras, 1998), and bulimic symptoms (Cooley & Toray, 2001a; Stice, 2001). An intervention that reduced body dissatisfaction produced decreases in negative affect and bulimic symptoms (Bearman, Stice, & Chase, 2003).

The societal ideal for thinness is very difficult to attain, and may promote dieting in the absence of body dissatisfaction. Body dissatisfaction and attempted dieting, in turn, are thought to increase the risk for negative affect and bulimic pathology. Thin-ideal internalization predicts increases in body dissatisfaction, attempted dieting, negative affect (Stice, 2001; Stice & Whitenton, 2002) and is associated with bulimic symptom onset (Field et al., 1999; Stice & Agras, 1998; Stice et al., 2002). The effects of thin-ideal internalization appear to be stronger for heavier girls (Stice et al., 2002; Stice & Whitenton, 2002). Interventions that reduce thin-ideal internalization result in decreased body dissatisfaction, dieting, negative affect, and bulimic symptoms (Stice & Shaw, 2004). Thus, the thin-ideal internalization may be a risk factor for body dissatisfaction, dieting, negative affect, and bulimic symptoms, and these effects are potentiated by elevated body weight.

Twin studies have yielded heritability estimates ranging from 31% to 83% for bulimia nervosa (e.g., Bulik, Sullivan, & Kendler, 1998; Kendler et al., 1991; Wade et al., 1999). Significant linkage has been reported on chromosome 10p, which suggests that this is an area of the genome worthy of further investigation for containing genes that may influence risk for bulimia nervosa (Bulik, Devlin, et al., 2003). However, researchers have been unable to identify specific genes that may influence the risk of developing bulimia nervosa. It may be that bulimia nervosa is a complex syndrome with both genetic and environmental underpinnings.

Although it is likely that risk factors for bulimia are interactive and multiplicative, the prospective evidence examining this issue is mini