اضطراب دوران کودکی مرتبط با شاخص توده بدنی در زنان با بی اشتهایی عصبی

Objective Extremely low body mass index (BMI) values are associated with increased risk for death and poor long-term prognosis in individuals with anorexia nervosa (AN). The present study explores childhood personality characteristics that could be associated with the ability to attain an extremely low BMI. Methods Participants were 326 women from the Genetics of Anorexia Nervosa (GAN) Study who completed the Structured Interview for Anorexia Nervosa and Bulimic Syndromes and whose mother completed the Child Behavioral Checklist and/or Revised Dimensions of Temperament Survey. Results Children who were described as having greater fear or anxiety by their mothers attained lower BMIs during AN (p < 0.02). Path analysis in the GAN and a validation sample, Price Foundation Anorexia Nervosa Trios Study, confirmed the relation between early childhood anxiety, caloric restriction, qualitative food item restriction, excessive exercise, and low BMI. Path analysis also confirmed a relation between childhood anxiety and caloric restriction, which mediated the relation between childhood anxiety and low BMI in the GAN sample only. Conclusion Fearful or anxious behavior as a child was associated with the attainment of low BMI in AN and childhood anxiety was associated with caloric restriction. Measures of anxiety and factors associated with anxiety-proneness in childhood may index children at risk for restrictive behaviors and extremely low BMIs in AN.

Anorexia nervosa (AN) is a debilitating and potentially lethal disorder (Berkman et al., 2007, Fichter et al., 2006, Papadopoulos et al., 2009, Sullivan, 1995 and Sullivan et al., 1998) in which compulsive and unrelenting food avoidance results in dangerously low body mass index (BMI). Low BMI is associated with elevated mortality in the general population (Engeland et al., 2003, Kivimaki et al., 2008, Reis et al., 2009, Troiano et al., 1996 and Whitlock et al., 2009) and individuals with AN are at significantly increased risk of sudden cardiac death (Lesinskiene, Barkus, Ranceva, & Dembinskas, 2008). Low BMI also has therapeutic and prognostic implications, has been associated with longer time to remission (Clausen, 2008), persistence of lower BMI following initiation of treatment (Pinter, Probst, Vandereycken, Pieters, & Goris, 2004), overall poorer prognosis (Steinhausen, Grigoroiu-Serbanescu, Boyadjieva, Neumarker, & Metzke, 2009), increased risk of relapse in the year following hospital discharge (Walsh et al., 2006), and increased likelihood for re-hospitalization (Steinhausen, Grigoroiu-Serbanescu, Boyadjieva, Neumarker, & Winkler Metzke, 2008). Food intake in the weeks prior to treatment and shortly following treatment termination is also related to long-term prognosis. Caloric restriction and qualitative food item restriction, avoidance of certain food items or macronutrients (i.e., fat), are associated with a less favorable treatment outcome in those with eating disorders. Individuals with greater caloric restriction prior to treatment have higher rates of relapse following treatment (McFarlane, Olmsted, & Trottier, 2008). Following hospitalization for AN, women with limited dietary variety have a poorer prognosis than women who eat a wider range of food items (Schebendach et al., 2008). As it is well known that anxiety is present in a substantial majority of individuals with AN prior to any signs of abnormal eating or distortions of body image (Godart et al., 2000, Raney et al., 2008 and Salbach-Andrae et al., 2008), the identification of early developmental factors that confer risk of restrictive eating behaviors and attaining low BMI among those with AN has theoretical and clinical importance. One factor of potential significance is anxiety, which has been linked in cross-sectional studies of AN to elevations in resting energy expenditure (Van Wymelbeke, Brondel, Marcel Brun, & Rigaud, 2004), more extreme exercise (Penas-Lledo et al., 2002 and Shroff et al., 2006), and generally higher physical activity (Brewerton, Stellefson, Hibbs, Hodges, & Cochrane, 1995). Given how often anxiety phenotypes are present in women with AN (Godart et al., 2000, Raney et al., 2008 and Salbach-Andrae et al., 2008), and that anxiety disorders tend to predate the onset of AN (Godart et al., 2000, Kaye et al., 2004 and Raney et al., 2008), and considering that persisting, morbid fear of weight gain and its avoidance is central to its descriptive psychopathology, an intuitive hypothesis is that caloric restriction is anxiolytic. This hypothesis is partially supported by neurobiological processes. Increased extracellular levels of serotonin in AN may lead to increased anxiety and decreased appetite; serotonin levels are reduced during starvation and could thereby reduce anxiety. Refeeding is associated with increased serotonin levels and increased anxiety (Kaye, Fudge, & Paulus, 2009). Reductions in dietary tryptophan, the dietary precursor to serotonin, has been shown to reduce anxiety in individuals with and recovered from AN (Kaye et al., 2003). This effect could account, at least in part, for the reinforcing nature of starvation in the ill state (Kaye, 2008 and Kaye et al., 2003), accentuated further by the inherent, general anxiolytic properties of physical activity (Norris et al., 1992 and Sexton et al., 1989). Thus, a biologically and psychologically plausible speculation is that more extreme anxiety indexes greater disease liability to AN and is associated with greater caloric restriction, consequent lower BMI, and perhaps a poorer long-term prognosis. Other related personality and temperamental factors that may be associated with attainment of low BMI are timidity (Wilbur & Colligan, 1981) and low self-esteem (Halvorsen and Heyerdahl, 2006 and Wilksch and Wade, 2004). Personality and temperamental characteristics, such as timidity and low self-esteem are related to anxiety-proneness and captured by constructs such as harm avoidance (Cloninger, 1986, Cloninger and Svrakic, 1992 and Joyce et al., 2003), often exhibited in individuals with AN (Fassino, Abbate-Daga, et al., 2002 and Fassino, Svrakic, et al., 2002), and associated with chronic AN (Bulik, Sullivan, Fear, & Pickering, 2000). One study has identified neurotrophic tyrosine kinase receptor type 2 that may be associated with eating disorders, harm avoidance, and low BMI in those with eating disorders (Ribases et al., 2005). An additional trait of interest in attainment of low BMI is early display of a rigid and unvarying schedule. Elevated rhythmicity could be associated with more severe eating disorder symptomatology. Teens with AN have less variation (greater rhythmicity) in their daily eating and sleep routines than teens with bulimia nervosa (BN) and adolescents with AN had less daily variation overall than adolescents with BN or depression (Shaw & Steiner, 1997). Childhood rhythmicity in those who develop AN needs to be explored to determine if early rhythmicity could serve as an early indication that a child may be prone to develop a low BMI. In children, high sleep activity (more restlessness during sleep) is associated with later development of anxiety disorders (Gregory et al., 2005). Childhood rhythmicity could be an early harbinger of later obessionality and sleep activity could index underlying anxious temperament. Early identification of at risk individuals could allow for tailored, targeted prevention and early intervention for AN. In this study, we examined childhood measures of temperament that index anxiety-proneness to determine their association with lifetime lowest BMI (lowest BMI) in a cohort of individuals with AN. We further hypothesized that the relation between childhood anxiety and low BMI is mediated by illness related behavioral factors, specifically caloric restriction (Fig. 1). Full-size image (24 K) Fig. 1. Path diagram.

Anxiety may play a prominent role in the attainment of low BMI in individuals with AN and caloric restriction may have anxiolytic properties (Kaye et al., 2009). Certain behaviors associated with childhood anxiety may index individuals who may attain a low BMI if AN develops. The present study elucidates a relation between childhood anxiety and caloric restriction. Although the mechanisms underlying this association remain obscure, the association is intriguing in light of mounting developmental translational evidence linking anxiety early in life to behavioral and neurobiological sequelae which confer later risk to abnormal coping, alterations in hedonic motivation and locomotor activity, elevated stress reactivity, and elevated anxiety sensitivity. These factors may be mediated by abnormalities in stress related fronto-limbic structures now implicated in a broad range of neuropsychiatric phenotypes (see Pine, 2007). High levels of serotonin have been associated with increased anxiety, decreased appetite, and present in individuals with active AN and recovered from AN (Kaye et al., 2009). Although possibly a sequela of illness, elevated serotonin levels in recovered individuals may suggest that high premorbid serotonin levels presage illness (Kaye et al., 2009) and could index an underlying biological factor influencing the relation among childhood anxiety, caloric restriction, and lowest attained BMI. Of related potential significance is evidence of common neurotransmitter signaling and molecular variations in the central control of emotion arousal, exploratory behavior, and body weight regulation under conditions of stress (Domschke and Zwanzger, 2008 and Smith et al., 2009). These works suggest the potential application of novel behavioral and neurodevelopmental strategies for exploring the mechanisms underlying clinically important phenotypic associations in AN and related eating disorders.