Being female is perhaps the most reliable risk factor for anorexia nervosa. The female-to-male ratio for anorexia nervosa has been consistently estimated to be approximately 10:1 in both clinical and epidemiological samples (Garfinkel et al., 1995; Hoek, 1991; Jones, Fox, Babigan, & Hutton, 1980; Lucas, Beard, O'Fallon, & Kurland, 1988; Lucas, Beard, O'Fallon, & Kurland, 1991; Rand & Kuldau, 1992; Rastam, Gillberg, & Garton, 1989; Soundy, Lucas, Suman, & Melton, 1995; Wells, Bushnell, Hornblow, Joyce, & Oakley-Browne, 1989). The uneven gender distribution cannot yet be explained, and although theories ranging from sociocultural to bi ological (Garner & Garfinkel, 1980) factors exist, no definitive answer has been found as to why a differential risk for gender is so consistently observed across cultures.

The onset of anorexia nervosa typically occurs during the peripubertal or postpubertal period (Lucas et al., 1988, 1991). Prepubertal anorexia nervosa exists (Cooper, Watkins, Bryant-Waugh, & Lask, 2002), but is uncommon (Stein, Chalhoub, & Hodes, 1998). Disturbances in eating and weight-related behaviors are clearly present, however, in preadolescent girls (Graber, Brooks-Gunn, Paikoff, & Warren, 1994; Killen et al., 1994; Leon, Fulkerson, Perry, & Cudeck, 1993;

Sands, Tricker, Sherman, Armatas, & Maschette, 1997). The extent to which these disturbances overlap with anorexia nervosa is not entirely known (Kotler et al., 2001). Onset of anorexia nervosa can occur throughout the life span (Beck, Casper, & Andersen, 1996; Inagaki et al., 2002), but the highest risk period for onset is around puberty (Lucas et al., 1988, 1991). As is true with gender, there is no definitive answer as to why puberty increases risk, and theories range from sociocultural (during puberty girls become more vulnerable to social pressures to be thin, especially in the context of their changing bodies; Gowers & Shore, 2001) to biological (hormonal changes during puberty trigger other relevant biological processes; see Muñoz & Argente, 2002, for a review). In contrast to binge eating disorder (Reichborn-Kjennerud, Bulik, Tambs, Harris, & Sullivan, submitted) early menarche has not been associated with risk for anorexia nervosa (Fairburn, Cooper, Doll, & Welch, 1999; Stice et al., 2001).

Weight concerns and dieting are normative in developed countries (Rodin, Silberstein, & Striegel-Moore, 1985; Striegel-Moore, Silberstein, & Rodin, 1986), a cultural phenomenon thought to be a necessary but not sufficient precondition for the development of eating disorders (Brownell, 1991; Garner & Garfinkel, 1980). The incidence of anorexia nervosa on Curaçao suggests, however, that anorexia nervosa is not confined to areas embracing the Western ideal of slimness (Hoek, van Harten, van Hoeken, & Susser, 1998). The precise role of sociocultural factors in increasing risk for anorexia nervosa is unclear, as exposure to thin ideals and dieting are nearly universal in industrialized countries, but only a very small number of young women actually develop clinically significant eating disorders. Individuals may be susceptible to the cultural pressures toward dieting and body dissatisfaction in proportion to their degree of genetic predisposition (Bulik, 2003). Thus, although all individuals are exposed to these forces, those at greater genetic risk may be more adversely affected. Immigration and the rapid introduction of Western body ideals have been shown to af fect the incidence of eating disorder–related behaviors (Becker, Burwell, Gilman, Herzog, & Hamburg, 2002; Bulik, 1987; Fichter, Weyerer, Sourdi, & Sourdi, 1983; Katzman, Nasser, & Gordon, 2001). It is unclear whether exposure to Western ideals or major nonspecific life stress (i.e., immigration) is associated with the emergence of eating pathology.

Traditionally, anorexia nervosa was considered to be a disorder confined to the white upper-middle class. This perception may result from the failure of many community-based studies to include non-white participants or from sampling highly homogeneous populations (Bushnell, Wells, Hornblow, Oakley-Browne, & Joyce, 1990; Götestam & Agras, 1995; Hoek et al., 1995; Kendler et al., 1991). Anorexia nervosa occurs across races and cultures (Hoek et al., 1998; Katzman et al., 2001). In terms of socioeconomic status, in a large population-based study of female twins, Walters and Kendler (1995) found that a greater number of years of parental education (a proxy variable for SES) was associated with anorexia nervosa. In addition, Striegel-Moore, Dohm, et al. (2003) found that 15 white (1.5%) and no black women in a geographically and economically diverse community sample of young women who had previously participated in the 10-year National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study met lifetime criteria for anorexia nervosa.

Cnattingius, Hultman, Dahl, and Sparen (1999), using the link between the Swedish birth registry and the Swedish psychiatric inpatient registry, found that girls born prematurely (especially if they were small for gestational age) and those born with cephalhematoma (a collection of blood under the scalp of a newborn) were at increased risk for developing anorexia nervosa. This study employed a design capable of identifying true prospective risk factors. The authors hypothesized that subtle brain damage at birth could result in early feeding difficulties and increase risk for anorexia nervosa. It is also possible

that prematurity and small size for gestational age of infants were secondary effects of lingering eating disorders in the mother. Shoebridge and Gowers (2000) also noted higher rates of perinatal or infant loss in mothers of a clinical sample of individuals with anorexia nervosa, and greater maternal anxiety and concern during pregnancy. Emerging data in animals suggest that even moderate maternal undernutrition around the time of conception can produce a precocious fetal cortisol surge and preterm birth (Bloomfield et al., 2003), a phenomenon which could occur in women with anorexia nervosa symptoms around the time of conception. Additional data indicate that individuals with current or past anorexia nervosa have a higher risk of birth complications, cesarean deliveries, and postpartum depression (Bulik, Sullivan, Fear, Pickering, & Dawn, 1999; Franko & Walton, 1993; Franko et al., 2001). Perinatal adverse events may therefore increase the risk of developing anorexia nervosa, and a past history of anorexia nervosa may increase the risk of experiencing adverse perinatal events, thus perpetuating a cycle of risk.

Psychometric studies have consistently linked anorexia nervosa to a cluster of personality and temperamental traits—specifically, negative self-evaluation, low self-esteem, extreme compliance, obsessionality, perfectionism, neuroticism, and harm avoidance (Anderluh, Tchanturia, Rabe-Hesketh, & Treasure, 2003; Brewerton, Dorn, & Bishop, 1992; Bulik, Sullivan, Weltzin, & Kaye, 1995; Bulik, Tozzi, et al., 2003; Fairburn, Cooper, et al., 1999; Gual et al., 2002; Karwautz et al., 2001; Kleifield, Sunday, Hurt, & Halmi, 1994; Srinivasagam et al., 1995; Strober, 1990; Tyrka, Waldron, Graber, & Brooks-Gunn, 2002; Vitousek & Manke, 1994; Waller et al., 1993; Walters & Kendler, 1995). These traits continue to characterize individuals with anorexia nervosa even after recovery (Bulik, Sullivan, Fear, & Pickering, 2000; Casper, 1990; Kaye, Weltzin, & Hsu, 1993; Srinivasagam et al., 1995). In the absence of premorbid personality data on large samples of individuals who later develop anorexia nervosa, some studies have used a “recovery” design, in which traits that persist after recovery are assumed to represent enduring traits that preceded the onset of the disorder and are thought to represent vulnerability factors. The potential weakness of this design is that these traits may not have existed premorbidly and instead could represent personality or trait “scars” from having had anorexia nervosa.

Parental obesity is less frequently associated with risk for anorexia nervosa than for bulimia nervosa, and familial obesity appears to be more common in family members of women with bulimia nervosa than women with anorexia nervosa (Garfinkel, Moldofsky, & Garner, 1980; Grace, Jacobson, & Fullager, 1985; Vieselman & Roig, 1985). Fairburn, Welch, Doll, Davies, and O'Connor (1997) also found a differential obesity risk between individuals with anorexia nervosa and bulimia nervosa, with anorexia nervosa women having lower familial risk of obesity. Only one study explored the opposite phenomenon, whether parents of individuals with anorexia nervosa tend to be thinner than parents of healthy controls (Halmi, Struss, & Goldberg, 1978), and there was no evidence to suggest that either mothers or fathers weighed less than parents of controls.

The prevalence of dieting has been estimated to be between 14% and 77% and is highest in young women (French, Perry, Leon, & Fulkerson, 1994). In most of these studies dieting was simply defined as whether individuals had ever restricted their intake to lose weight, and therefore may have captured both successful and unsuccessful dieters. In a study of 36,320 public school students, dieting frequency was strongly related to poor body image, fears of being unable to control eating, and more prevalent history of binge eating. Dieting was also related in a “dose–re

sponse” fashion to a range of psychosocial and health behavior variables (French, Story, Downes, Resnick, & Blum, 1995). Walters and Kendler (1995) found dieting status to be associated with anorexia nervosa in a population-based sample of twins; however, dieting was not measured prior to the onset of anorexia nervosa. In contrast, in a series of studies of anorexia nervosa, bulimia nervosa, and binge eating disorder in which subjects were asked to report on the premorbid presence of potential risk factors, Fairburn, Cooper, et al. (1999) found that although dieting dimensions were relevant to the emergence of both bulimia nervosa and binge eating disorder, they were not associated with anorexia nervosa. Dieting was not elevated in a study of affected sisters of discordant sister pairs (Karwautz et al., 2001). Thus, the data from clinical and epidemiological studies do not resolve whether dieting should be considered a risk factor for anorexia nervosa.

Dissatisfaction with the size or shape of one's body is often thought to be the psychological motivator for dieting behavior (Stice, 1994) and a key contributor to the gender differential in prevalence of eating disorders. In puberty, body satisfaction begins to decrease in young girls, and this dissatisfaction may be secondary to the increase in body fat percentage associated with female pubertal development (Marino & King, 1980). Dissatisfaction with body shape or size is thought to be the driving force for the onset of dieting behavior (Cash & Henry, 1995; Hawkins & Clement, 1984; Rodin et al., 1985; Tiggemann, 1994; Van Strien, 1989).

As previously discussed in Chapter 13, other significant psychiatric disorders, especially major depression and anxiety disorders, commonly co-occur with anorexia nervosa (Braun, Sunday, & Halmi, 1994; Bulik, 2001; Bulik, Sullivan, Fear, & Joyce, 1997; Deep, Nagy, Weltzin, Rao, & Kaye, 1995; Halmi et al., 1991). Well over half of women with anorexia nervosa report a lifetime presence of an anxiety disorder—most commonly, overanxious disorder, obsessive-compulsive disorder, or social phobia. In many cases, onset of the anxiety disorder precedes the onset of anorexia nervosa (Bulik et al., 1997; Deep et al., 1995). Retrospective accounts of premorbid symptoms among children who later develop anorexia nervosa often emphasize the presence of pervasive anxiety (Bruch, 1973; Lask & Bryant-Waugh, 2000). This pattern of onset may reflect the natural course of the two disorders (i.e., the average age of onset of many anxiety disorders is younger than the average age of onset of anorexia nervosa), but it may also indicate that childhood anxiety is a significant risk factor for the development of anorexia nervosa. In a population-based sample of over 2,000 female twins, odds ratios for generalized anxiety disorder, phobias, and panic disorder were significantly elevated among women with varying definitions of anorexia nervosa (Walters & Kendler, 1995).

In addition, several outcome studies suggest that depression and anxiety commonly persist after recovery from anorexia nervosa (Löwe et al., 2001; Sullivan, Bulik, Fear, & Pickering, 1998). Significantly elevated relative risks for mood disorders have been reported among relatives of probands with anorexia nervosa (Gershon et al., 1984; Hudson, Pope, Jonas, & Yurgelun-Todd, 1983; Logue, Crowe, & Bean, 1989; Rivinus et al., 1984), although these rates may be highest among relatives of individuals with anorexia nervosa who are themselves depressed (Strober, Lampert, Morrell, Burroughs, & Jacobs, 1990). Twin studies have shown that the genetic risk factors for anorexia nervosa and depression are correlated (Wade, Bulik, Neale, & Kendler, 2000), and there appears to be a unique genetic factor that influences the emergence of both early eating and early anxiety disorder symptoms (Silberg & Bulik, submitted).

Early family theories of the etiology of anorexia nervosa posited dysfunctional family patterns marked by enmeshment and rigidity (Minuchin, Rosman, & Baker, 1978). Studies have generally