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Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by which they can modulate brain 5-HT functional activity and anxious mood. People with AN enter a vicious cycle which accounts for the chronicity of this disorder because caloric restriction results in a brief respite from dysphoric mood. However, malnutrition and weight loss, in turn, produce alterations in many neuropeptides and monoamine function, perhaps in the service of conserving energy, but which also exaggerates dysphoric mood. In summary, this article reviews findings in brain chemistry and neuroimaging that shed new light on understanding the psychopathology of these difficult and frustrating disorders.

Objective: Limited data suggest that eating-related concerns and behaviors, disturbances in mood, and altered temperament persist following recovery from bulimia nervosa (BN)., Method: In order to replicate and extend such findings, 11 women who were long-term recovered from BN (>1 year with no binging, purging, or restricting behaviors, normal weight, and regular menstrual cycles) were compared with 15 healthy volunteer women on the Eating Disorders Invertory-2 (EDI-2), the Beck Depression Inventory, the State Trait Anxiety Inventory, and the Multidimensional Personality Questionnaire (MPQ)., Results: Compared with the control women, the recovered BN women showed elevated levels of the EDI-2 subscales of Drive for Thinness, Body Dissatisfaction, Ineffectiveness, Perfectionism, and Social Insecurity, greater depression and anxiety, elevated levels of the MPQ Stress Reaction dimension and the higher-order factor of Negative Emotionality, and lower levels of the MPQ Well Being and Closeness dimensions., Discussion: Core eating and weight-related concerns, dysphoric affect, social discomfort, and personality traits indicative of perfectionism persist following long-term recovery from BN., (Copyright 2002 by Wiley Periodicals, Inc.)

People with anorexia (AN) and bulimia nervosa (BN) have altered patterns of eating. It is possible that alterations of the neuropeptide gastrin releasing peptide (GRP), a bombesin (BBS) -like peptide with potent central anorexigenic activity, could contribute to disturbed eating behavior. To avoid the confounding effects of pathologic eating behavior, we measured cerebrospinal fluid (CSF) GRP concentrations in women who were long-term recovered (>1 year, normal weight, and regular menstrual cycles, no binging or purging) from AN (REC AN, N=12) or BN (REC BN, N=21) compared to healthy control women (NC, N=15). CSF GRP was significantly lower (chi(2)=9.41(3), p<0.01) in REC BN (9.6+/-3.1 pg/ml) compared to NC (13.4+/-5.5 pg/ml) and REC AN (11.6+/-2.9 pg/ml). Persistent GRP abnormalities after recovery from BN raise the possibility that this alteration might be trait-related and contribute to episodic hyperphagia in BN., (Copyright 2000 Academic Press.)

Physical and sexual abuse among patients with eating disorders has been a focus of attention in Western countries, however, there is no study comparing the incidence of these factors in Western and Asian countries. Japanese subjects consisted of 38 patients with anorexia nervosa restricting type (AN-R), 46 patients with anorexia nervosa binge eating/purging type (AN-BP), 76 patients with bulimia nervosa purging type (BN) and 99 controls. Subjects from the USA consisted of 29 AN-R, 34 AN-BP and 16 BN. The Physical and Sexual Abuse Questionnaire was administered to all subjects. Minor sexual abuse such as confronting exhibitionism or being fondled by a stranger tended to be more prevalent among Japanese subjects, while victimization by rape or incest was more prevalent among USA subjects. Conversely, physical abuse history was similarly distributed across each diagnostic subgroup in both countries. Events related to physical abuse, such as an abusive family background, may contribute whether eating disorder patients are restricting or bulimic and regardless of culture.

Objective: The authors' goal was to confirm that brain serotonin (5-HT) alterations are present in patients who have recovered from bulimia nervosa. Positron emission tomography imaging with [(18)F]altanserin was used to characterize binding of the 5-HT(2A) receptor, which might contribute to altered feeding, mood, or impulse control., Method: Nine women who had recovered from bulimia nervosa (they had no episodes of binge eating or purging, were at normal weight, and had regular menstrual cycles for more than 1 year) were compared with 12 female volunteers who had never had bulimia., Results: The healthy volunteers, but not the women who had recovered from bulimia nervosa, had an age-related decline in 5-HT(2A) binding. Women who had recovered from bulimia nervosa had a reduction of medial orbital frontal cortex 5-HT(2A) binding., Conclusions: The lack of age-related changes in 5-HT activity is further evidence of 5-HT alterations in subjects who have recovered from bulimia nervosa. In addition, vulnerabilities for eating disorders, impulse dyscontrol, and mood disturbances may involve 5-HT and frontal lobe activity.

Background: This study compared the effectiveness of cognitive therapy (CT), nutritional therapy (NT), the combination of cognitive and nutritional therapy (CNT), against a control condition of support group (SG) in the treatment of bulimia nervosa., Methods: One hundred female out-patients who fulfilled DSM-III-R criteria for bulimia nervosa were randomized to the four treatment groups. NT and CT were designed to cover different areas with minimal overlap, and CNT provided all of the features of both of these treatments. The control condition was conducted in a group self-help format. Each of the treatments lasted 14 weeks., Results: All three active treatments as well as SG produced significant decreases in binge/vomit episodes. Intent-to-treat analysis found CNT and CT to be significantly more effective than SG in retaining subjects in treatment and completion of study, as well as in producing greater improvements in dysfunctional attitudes and self-control. CNT was superior to SG in achieving abstinence from bulimic behaviour. NT was superior to SG only in increase of self-control. Logistic regression found that the cognitive component, whether given alone or in conjunction with NT, and higher pre-treatment self-control scores were significant predictors for both completion of study and abstinence., Conclusion: CT (either alone, or in combination with nutritional therapy) remains the treatment of choice for bulimia nervosa. A treatment escalation approach should be tested for the treatment of bulimia with the more intensive and less widely available CT (with or without nutritional counselling) offered after patients have failed the less intensive and more widely available support group treatment.

Discussion: Control trials show that antidepressants are efficacious in eating disorders. Although selective serotonin reuptake inhibitors (SSRIs) are used in clinical practice, there are relatively few controlled or open trials demonstrating that SSRIs are effective. We report five cases of underweight women with binge eating/purging-type eating disorders who gained weight and had reduced core eating disorder behaviors in response to sertraline., (Copyright 2001 by John Wiley & Sons, Inc.)

When ill, women with bulimia nervosa (BN) show alterations of regional cerebral blood flow (rCBF). In this study we investigated rCBF in nine women in long-term recovery from BN (RBN, n=9), i.e. more than 1 year without bingeing/purging behavior, normal weight, stable food intake, and regular menses, and compared them with age-matched healthy control women (CW, n=13). Positron emission tomography (PET) was used for the assessment of rCBF. There were no significant differences in rCBF between groups. However, rCBF was significantly inversely related to length of recovery in RBN for the left and right prefrontal cortex (BA 10), right medial orbital frontal cortex (BA 11), left subgenual cingulate (BA 25), right anterior cingulate (BA 32), left sensory motor cortex (BA 1,2,3,4), left and right lateral temporal (BA 21), and left occipital cortex (BA 17), as well as left thalamus. This finding suggests that previously reported alterations in rCBF during the ill state of BN may be a state-related phenomenon that remits with recovery. It is also possible that reductions in rCBF occur in a later stage of recovery from BN.

Background: A combined family study and recovered study design was utilized to examine several hypothesized relationships between personality and bulimia nervosa (BN)., Methods: We studied 47 women with a lifetime history of DSM-III-R BN (31 currently ill and 16 recovered), 44 matched control women (CW) with no history of an eating disorder (ED), and their first-degree female relatives (N = 89 and N = 100, respectively), some of whom had current or previous EDs., Results: BN probands' relatives with no ED history had significantly elevated levels of perfectionism, ineffectiveness, and interpersonal distrust compared to CW probands' relatives with no ED history. In contrast, diminished interoceptive awareness, heightened stress reactivity and perfectionistic doubting of actions were found among the previously eating disordered relatives of bulimic probands compared to their never ill relatives. Finally, a sense of alienation and emotional responsivity to the environment were elevated among currently ill compared to recovered bulimic probands., Conclusions: The fact that perfectionism, ineffectiveness and interpersonal distrust are transmitted independently of an ED in relatives suggests that they may be of potential aetiological relevance for BN. In contrast, diminished interoceptive awareness, heightened stress reactivity and perfectionistic doubting of actions are more likely consequent to, or exacerbated by, previously having experienced the illness. Finally, a sense of alienation and emotional responsivity to the environment are more likely to be associated with currently having BN.

Background: When ill, people with eating disorders have disturbances of the neuropeptides vasopressin and oxytocin., Methods: To avoid the confounding effects of the ill state, we studied women who were recovered (more than 1 year, normal weight, and regular menstrual cycles, no bingeing or purging) from bulimia nervosa (rBN) or binge eating/purging-type anorexia nervosa (rAN-BN), and matched healthy control women., Results: Vasopressin was elevated in rAN-BN and showed a trend towards elevation in rBN. In rBN, elevated cerebrospinal fluid vasopressin may be related to having a lifetime history of major depression. In comparison, cerebrospinal fluid oxytocin was normal in recovered subjects, but elevated levels in some rBN might be related to birth control pill use., Conclusions: These data confirm and extend the possibility that elevated cerebrospinal fluid vasopressin may be related to the pathophysiology of eating disorders, and/or a lifetime history of major depression.

Objective: Studies in Western world patients suggest the possible existence of a subgroup of patients with bulimia nervosa (BN) who display multiple problems with impulsivity, such as suicidal attempts. We assessed impulsive behaviors among BN patients in Japan to discuss them crossculturally., Method: Impulsive behaviors in 64 BN patients were assessed and multi-impulsivity (MI) was defined according to the definition proposed by Fichter, Quadflieg, and Rief (Psychological Medicine, 24, 591-604,1994)., Results: Nineteen patients (30%) met the definition of MI. BN patients with MI had more severe clinical features, such as concurrent depressive and anxious symptoms, global functioning, and higher prevalence of borderline personality disorder than BN patients without MI., Discussion: These results showed the similarities between BN patients with MI in Japan and those patients in the Western world in clinical and psychopathological characteristics and a life-time incidence of each impulsive behavior. These findings may suggest culturally free bases for linkage between BN and MI., (Copyright 2000 by John Wiley & Sons, Inc.)

Objective: Lifetime rates of full and partial anorexia nervosa and bulimia nervosa were determined in first-degree relatives of diagnostically pure proband groups and relatives of matched, never-ill comparison subjects., Method: Rates of each eating disorder were obtained for 1,831 relatives of 504 probands on the basis of personal structured clinical interviews and family history. Best-estimate diagnoses based on all available information were rendered without knowledge of proband status and pedigree identity. Only definite and probable diagnoses were considered., Results: Whereas anorexia nervosa was rare in families of the comparison subjects, full and partial syndromes of anorexia nervosa aggregated in female relatives of both anorexic and bulimic probands. For the full syndrome of anorexia nervosa, the relative risks were 11.3 and 12.3 in female relatives of anorexic and bulimic probands, respectively. Bulimia nervosa was more common than anorexia nervosa in female relatives of comparison subjects, but it, too, aggregated in the families of ill probands; the corresponding relative risks for bulimia nervosa were 4.2 and 4.4 for female relatives of anorexic and bulimic probands, respectively. When partial syndromes of anorexia nervosa and bulimia nervosa were considered, relative risks fell by one-half in each group of ill probands., Conclusions: Both anorexia nervosa and bulimia nervosa are familial. Their cross-transmission in families suggests a common, or shared, familial diathesis. The additional observation that familial aggregation and cross-transmission extend to milder phenotypes suggests the validity of their inclusion in a continuum of familial liability.

Background: The present study investigated the role of serotonin in the pathophysiology of bulimia nervosa (BN) by studying the affective and appetitive responses of women ill with BN to an acute tryptophan depletion (ATD) paradigm., Methods: Twenty-two women with BN and 16 healthy control women (CW) were studied on 2 separate days during the follicular stage of the menstrual cycle. Participants drank a control mix of essential amino acids (100 g + 4.6 g tryptophan) on one day and a tryptophan deficient (100 g - 4.6 g tryptophan) mixture (ATD) on the other in a double-blind fashion. Mood/appetite ratings and blood samples were taken at baseline and at intervals up to 420 minutes. Participants were then presented with an array of foods and were allowed to binge and vomit if they desired., Results: CW and BN women had a similar and significant reduction in plasma tryptophan levels and the tryptophan: LNAA ratio after ATD. After ATD, the BN women had a significantly greater increase in peak (minus baseline) depression, mood lability, sadness and desire to binge compared to the CW. BN subjects and CW had similar peak changes in mood after the control amino acid mixture. BN subjects and CW consumed similar amounts of food after the two amino acid treatments., Conclusions: Women with BN seem more vulnerable to the mood lowering effects of ATD, suggesting they have altered modulation of central 5-HT neuronal systems.

Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by abnormal patterns of weight regulation and eating behavior and by disturbances in attitudes and perceptions toward weight and body shape. Etiologic research has indicated substantial genetic influence on these disorders, suggesting significant biological contributions to their development. Obsessional, perfectionistic, and anxious personality styles may be premorbid traits that contribute to this pathogenesis. Studies of neuroendocrine, neuropeptide, and neurotransmitter functioning in patients with AN and BN indicate that disturbances of these systems may contribute to the maintenance as well as the etiology of these sometimes fatal disorders. The efficacy of psychological treatments and pharmacotherapy has been more clearly established for BN than for AN.

This study sought to assess the prevalence and symptomatology of comorbid obsessive-compulsive disorder (OCD) among Japanese subjects who met the DSM-III-R criteria for bulimia nervosa (BN). The Structured Clinical Interview for DSM-III-R Patient Version was used to distinguish 26 BN patients with concurrent OCD from 52 BN patients without OCD. Obsessive-compulsive symptoms in BN subjects with concurrent OCD were evaluated using the Japanese version of the Yale-Brown Obsessive-Compulsive Scale. There were no differences in the prevalence of concurrent OCD between BN subjects with and without a lifetime history of anorexia nervosa. Among BN subjects with concurrent OCD, symptoms related to symmetry and order were most frequently identified, followed by contamination and aggressive obsessions, and checking and cleaning/washing compulsions. Bulimia nervosa subjects with concurrent OCD were more likely than subjects without OCD to have more severe mood and core eating disorder psychopathology. Comorbid OCD is a common phenomenon in Japanese bulimics (33%) similar to that suggested in BN subjects in the Western countries. Obsessive-compulsive symptoms related to symmetry and order were most frequently observed in BN subjects with concurrent OCD, which was a similar finding to that reported among restricting anorexic subjects.

Objective: Obsessive-compulsive disorder (OCD) symptoms are common in people who are ill with bulimia nervosa. However, little is known about whether OCD symptoms persist after long-term recovery from bulimia., Method: Thirty-one female patients with bulimia nervosa, 29 women who had been recovered from bulimia for more than 1 year, and 19 healthy female comparison subjects completed the Yale-Brown Obsessive Compulsive Scale, which measures OCD-like symptoms. Items related to symptoms of core eating disorders were omitted from the Yale-Brown scale., Results: The Yale-Brown scale scores of the women with bulimia (mean = 13.1, SD = 10.6) and those who had recovered from bulimia (mean = 7.9, SD = 7.0) were significantly higher than the scores of the normal comparison subjects (mean = 1.9, SD = 2.6). Women with bulimia and those who had recovered from bulimia had similar Yale-Brown scale scores and endorsed similar Yale-Brown scale target symptoms, such as obsessions related to symmetry and exactness., Conclusions: OCD symptoms persist after recovery from bulimia. Moreover, the types of OCD symptoms experienced by bulimia patients do not vary dramatically with improvement in bulimic symptoms. Persistent OCD symptoms after recovery from bulimia raise the possibility that these behaviors are trait-related and contribute to the pathogenesis of bulimia.

Objective: While familial aggregation of bulimia nervosa (BN) is known to occur, the extent to which aggregation of a broader spectrum of eating disorders (ED) occurs in the families of individuals with BN is less certain., Method: Direct interviews and blind best-estimate diagnostic procedures were used to assess lifetime histories of EDs among first-degree relatives (n = 177) of probands with BN (n = 47) and first-degree relatives (n = 190) of non-ED control probands (n = 44)., Results: Forty-three percent of sisters and 26% of mothers of BN probands had a lifetime ED diagnosis, with eating disorder not otherwise specified (ED-NOS) diagnoses being most common. These rates were significantly higher than among sisters (5%) and mothers (5%) of controls. Few male relatives of either cohort had an ED., Conclusions: Diagnostic assessment using contemporary family-epidemiology methodology revealed very strong familial aggregation of a broad spectrum of EDs among female relatives of women with BN.

We sought to clarify the influence of a history of sexual or physical abuse on a variety of psychopathologies in subjects with bulimia nervosa (BN). To avoid confounding effects, the presence of a history of sexual or physical abuse, lifetime axis I disorders, and personality disorders were assessed through direct structured interviews in 44 subjects recovered from BN for at least 1 year. Twenty abused subjects (45%) were significantly more likely than 24 subjects without abuse to have severe general psychopathology and eating disturbance. Compared with nonabused subjects, abused subjects showed a trend toward more frequent lifetime diagnoses of posttraumatic stress disorder and substance dependence. These results suggest that abusive experiences may be associated with some psychopathology of BN, particularly related to anxiety, substance abuse, and more severe core eating disorder pathology.

Background: Disturbances of leptin, neuropeptide Y (NPY), and peptide YY (PYY) have been found in women who are ill with anorexia or bulimia nervosa. It is not certain whether peptide disturbances are cause or consequence of eating disorders., Methods: Plasma leptin and cerebrospinal fluid leptin, NPY, and PYY concentrations were measured in women who were recovered from anorexia or bulimia nervosa to determine whether alterations persisted after recovery., Results: NPY, PYY, and leptin concentrations were similar across all diagnostic groups., Conclusions: Alterations in NPY, PYY, and serum leptin concentrations are probably secondary to pathological eating behaviors. Alterations of these peptides are unlikely to be trait-related disturbances that contribute to the etiology of eating disorders.

Although considerable progress has been made in the understanding and treatment of anorexia and bulimia nervosa, a substantial proportion of people with these disorders have a limited response to treatment. Treatment strategies used in eating disorders have tended to be adopted from therapies that were devised to treat other psychiatric illnesses. Recent studies suggest that eating disorders are independently transmitted familial liabilities with a unique pathophysiology. These new findings raise the possibility that an improved understanding of the pathogenesis of eating disorders will generate more specific and effective psychotherapies and pharmacologic interventions.

Objectives: Psychotherapy and antidepressant medication are helpful to many patients with bulimia nervosa (BN). However, a substantial number of bulimics respond poorly to such treatments. Recent studies suggest that many of the poor responders have cluster B personality disorders. In some ways, the symptomatology of bulimics who have a comorbid cluster B disorder resembles that of patients with attention deficit hyperactivity disorder (ADHD). In particular, individuals in both groups frequently have a high level of impulsivity. Such a resemblance raised the question of whether administration of methylphenidate (MPH), a drug used to treat ADHD, would have therapeutic effects in this subgroup of BN patients., Methods: In a pilot study, we administered MPH to 2 patients with BN and cluster B traits and found beneficial effects. These patients had not responded to adequate trials of psychotherapy and selective serotonin reuptake inhibitors (SSRIs)., Results: MPH treatment was effective. Both Patients had decreased binging and purging., Discussion: MPH may be useful for bulimics with cluster B personality disorder who respond poorly to conventional treatment. Further studies of MPH administration may be worthwhile. Due to the potential risks, however, clinical treatment with this agent is not recommended at this time.

Anorexia nervosa (AN) and bulimia nervosa (BN) are disorders characterized by aberrant patterns of feeding behavior and weight regulation, and disturbances in attitudes toward weight and shape and the perception of body shape. Emerging data support the possibility that substantial biologic and genetic vulnerabilities contribute to the pathogenesis of AN and BN. Multiple neuroendocrine and neurotransmitter abnormalities have been documented in AN and BN, but for the most part, these disturbances are state-related and tend to normalize after symptom remission and weight restoration; however, elevated concentrations of 5-hydroxyindoleacetic acid in the cerebrospinal fluid after recovery suggest that altered serotonin activity in AN and BN is a trait-related characteristic. Elevated serotonin activity is consistent with behaviors found after recovery from AN and BN, such as obsessionality with symmetry and exactness, harm avoidance, perfectionism, and behavioral over control. In BN, serotonergic modulating antidepressant medications suppress symptoms independently of their antidepressant effects. Selective serotonin reuptake inhibitors (SSRIs) are not useful when AN subjects are malnourished and under-weight; however, when given after weight restoration, fluoxetine may significantly reduce the extremely high rate of relapse normally seen in AN. Nonresponse to SSRI medication in ill AN subjects could be a consequence of an inadequate supply of nutrients, which are essential to normal serotonin synthesis and function. These data raise the possibility that a disturbance of serotonin activity may create a vulnerability for the expression of a cluster of symptoms that are common to both AN and BN and that nutritional factors may affect SSRI response in depression, obsessive-compulsive disorder, or other conditions characterized by disturbances in serotonergic pathways.

Background: Women with bulimia nervosa (BN) have disturbances of mood and behavior and alterations of monoamine activity when they are bingeing and purging. It is not known whether these alterations are secondary to pathological eating behavior or traits that could contribute to the pathogenesis of BN., Methods: To avoid the confounding effects of pathological eating behavior, we studied 30 women after long-term recovery (>1 year with no bingeing or purging, normal weight, and regular menstrual cycles) from BN. Subjects were compared with 31 healthy volunteer women. We assessed psychiatric diagnoses and symptoms to determine whether there was any persistent disturbance of behavior after recovery. We measured cerebrospinal fluid (CSF) levels of the major metabolites of serotonin (5-hydroxyindoleacetic acid [5-HIAA]), dopamine (homovanillic acid [HVA]), and norepinephrine (3-methoxy-4-hydroxyphenylglycol [MHPG]) as well as hormonal and behavioral response to m-chlorophenylpiperazine (m-CPP), a serotonin-specific agent., Results: Women who were recovered from BN had mild to moderate negative moods and obsessions with perfectionism and exactness and exaggerated core eating disorder symptoms compared with healthy volunteer women. Recovered BN women had increased levels of CSF 5-HIAA compared with control women (117 +/- 33 vs 73 +/- 15 pmol/mL; P< or =.001) but normal CSF HVA and MHPG concentrations. Recovered BN women had an anxious and disorganized behavioral response to m-CPP but a normal hormonal response., Conclusions: Persistent serotonergic and behavioral abnormalities after recovery raise the possibility that these psychobiological alterations might be trait-related and contribute to the pathogenesis of BN.

Background: We used contemporary family-epidemiological methods to examine patterns of comorbidity and familial aggregation of psychiatric disorders for anorexia and bulimia nervosa., Methods: Direct interviews and blind best-estimate diagnostic procedures were used with diagnostically "pure" groups of probands with eating disorders and a matched control group. Lifetime prevalence rates of eating disorders, mood disorders, substance use disorders, anxiety disorders, and selected personality disorders were determined in female probands with restricting anorexia nervosa (n=26) or bulimia nervosa (n=47), control women (n=44), and first-degree biological relatives (n=460)., Results: Relatives of anorexic and bulimic probands had increased risk of clinically subthreshold forms of an eating disorder, major depressive disorder, and obsessive-compulsive disorder. Familial aggregation of major depressive disorder and obsessive-compulsive disorder was independent of that of anorexia nervosa and bulimia nervosa. These relatives also had increased risk of other anxiety disorders, but the mode of familial transmission was not clear-cut. The risk of substance dependence was elevated among relatives of bulimic probands compared with relatives of anorexic probands, and familial aggregation was independent of that of bulimia nervosa. The risk of obsessive-compulsive personality disorder was elevated only among relatives of anorexic probands, and there was evidence that these 2 disorders may have shared familial risk factors., Conclusions: There may be a common familial vulnerability for anorexia nervosa and bulimia nervosa. Major depressive disorder, obsessive-compulsive disorder, and substance dependence are not likely to share a common cause with eating disorders. However, obsessional personality traits may be a specific familial risk factor for anorexia nervosa.

It has been well-recognized that starvation in anorexia and bulimia nervosa causes endocrine disturbances. Such disturbances may help understand why many people with eating disorders cannot easily reverse their illness since people with eating disorders often enter a downward spiraling circle with malnutrition sustaining and perpetuating the desire for more weight loss and dieting. Symptoms, such as obsessions and dysphoric mood, and altered appetitive behavior, may be exaggerated by neuropeptide alterations and thus contribute to this downward spiral. While neuropeptide disturbances do not appear to be a permanent feature or cause or anorexia nervosa, these disturbances are strongly entrenched, and are not easily corrected by improved nutrition or short-term weight normalization. This suggests that therapy should be sustained for months after nutritional normalization.

Objective: Women with bulimia nervosa (BN) and comorbid substance dependence often display impulsive behaviors. We assessed Axis I and II psychiatric diagnoses in their first-degree relatives in order to understand the etiological factors that may contribute to this subtype of BN., Method: We used contemporary family-epidemiological methodology to compare the lifetime prevalence of psychiatric disorders among 47 women with BN and 44 non-eating-disordered community control women, and their first-degree relatives (177 and 190, respectively). BN probands were stratified by the presence (n = 20) or absence (n = 27) of a lifetime history of alcohol and/or drug dependence., Results: Social phobia, conduct disorder, and clusters B and C personality disorders were significantly more prevalent among BN probands with substance dependence than among BN probands without substance dependence or control women probands. Substance use disorders, social phobia, panic disorder, and cluster B personality disorders were significantly more prevalent among the relatives of BN probands with substance dependence than the relatives of the other two groups., Discussion: Women with BN and substance dependence have problems with social anxiety, antisocial behavior, and a variety of personality disturbances, and come from families where there are problems with substance use disorders, anxiety, impulsivity, and affective instability. These data raise the possibility that a familial vulnerability for impulsivity and affective instability may contribute to the development of substance dependence in a subgroup of women with BN.

Objective: Bulimia nervosa (BN) patients have been shown to experience anomalous responses to food and food cues. We investigated the response to food over time by presenting repeated food cues and measuring changes in physiological (ie, salivation) and subjective responses., Method: Subjects were 18 BN women and 18 matched control women. Two palatable food stimuli, regular or frozen yogurt, that varied in macronutrient composition but had similar sensory characteristics, were presented to subjects repeatedly during a laboratory session. After two baseline salivation measures, subjects were presented with eight trials of one of the two yogurts. On Trial 9 a lemon juice dishabituator was presented, with the yogurt stimulus presented again at Trial 10., Results: We found that control subjects had decreased salivation after repeated food presentations. In comparison, BN subjects failed to show a decrease in salivation. The desire to binge increased over trials for the BN subjects, but remained stable for normals., Conclusions: These data suggest that salivary habituation may be abnormal in BN patients.

This article addresses the effect of managed care on the treatment of eating disorders. We review strategies for negotiating limitations that managed care reviewers place on treatment. Finally, this article reviews the experiences of a Canadian program that has 10 years of experience in providing low-cost day treatment. While change is frustrating and difficult, it is inevitable and can be rejuvenating. These changes offer opportunities for creative development of quality low-cost care. If we do not adjust to these conditions, patients will not get treatment that they need.

Alcohol and drug use disorders are common among women with bulimia nervosa (BN) and their family members. However, it is not known whether there is a familial relationship between BN and substance use disorders. We compared 47 women with BN and 44 non-eating-disordered community control women, and their first-degree relatives (177 and 190, respectively). BN probands were stratified by the presence (43%) or absence (57%) of lifetime alcohol and/or drug dependence. The first-degree relatives of substance-dependent BN probands had significantly higher lifetime rates of alcohol/drug dependence (38%), compared with relatives of nonsubstance-dependent BN probands (10%) or relatives of community controls (18%). These data suggest that BN and substance dependence are transmitted independently in families.

Objective: Data suggest that serotonin activity is reduced in women at normal weight who have bulimia nervosa. The authors tested whether acute perturbations in serotonin activity could alter short-term eating behavior and mood., Method: They examined the effect of acute tryptophan depletion in 10 women with and 10 women without bulimia nervosa., Results: Women with bulimia nervosa exhibited an increase in caloric intake and mood irritability after acute tryptophan depletion., Conclusions: These results indicate that women with bulimia nervosa have an exaggerated or pathological response to transient alterations in serotonin activity.

Nine female patients with anorexia nervosa and 7 female patients with bulimia nervosa were assessed on the Matching Familiar Figures Test (MFFT). This study found that subjects with bulimia nervosa responded more quickly than did the anorexic subjects. Results such as these suggest that not only are bulimic patients more behaviorally impulsive than anorexic patients, they are also more cognitively impulsive. Patients with anorexia nervosa in contrast seemed to display a reflective cognitive style. Extreme cognitive styles may contribute to resistance in treatment and/or relapse in anorexia or bulimia nervosa.

After admission for weight restoration, restrictor anorectics (n = 17) gained significantly less weight than bulimic anorectics (n = 17) in a 30-day period. However, these groups had similar caloric intake. Severity of illness was found to be a predictor of rate of weight gain for restrictor anorectics, but not for bulimic anorectics.

This study examined dimensional personality and temperamental characteristics in women with eating disorders. Clinical symptoms, personality, and temperament were examined in 30 women with anorexia nervosa (AN), 32 women with bulimia nervosa with no history of anorexia nervosa (BN), and 20 women with comorbid anorexia and bulimia nervosa (AB). Temperament differed markedly across the groups on the Tridimensional Personality Questionnaire (TPQ) with AN women showing greater reward dependence, BN women scoring higher on novelty seeking subscales, and AB women showing high harm avoidance. The TPQ subscales also displayed higher classification accuracy than other personality and symptom measures. Temperamental features are distinct across eating disorder subtypes. Temperament could reflect differential vulnerabilities for the development of specific eating disorder symptom clusters.

Symptoms of anxiety can be prominent during treatment of bulimia nervosa. Our experience is that bulimics who abuse laxatives have the most prominent symptoms of anxiety. We conducted ratings of anxiety in 23 bulimics who purge with laxatives and 17 who purge by vomiting. We found that the laxative-abusing group had higher levels of state but not trait anxiety and that they were more likely to be treated with medication for anxiety during hospitalization. These data suggest an association between laxatives and anxiety in bulimia nervosa.

Serotonin (5HT) is one of several neuromodulators of feeding. Experimentally reducing 5HT activity in animals increases food intake, while increasing 5HT activity has the opposite effect. Studies suggest that women with bulimia nervosa show signs of reduced 5HT activity, which may be related to binge eating. Data supporting the theory that reduced central nervous system 5HT activity may play a role in the pathophysiology of bulimia nervosa is reviewed. Disturbances of 5HT activity and the relationship to other psychopathology in bulimia nervosa, such as depression, substance abuse, and impulsivity, are also reviewed.

A relatively new instrument, the Defense Style Questionnaire (DSQ), represents an efficient method by which to quantify an individual's psychological defense style. We administered the DSQ to 66 women hospitalized for anorexia nervosa, bulimia nervosa, or concurrent anorexia and bulimia nervosa. Contrary to our expectations, there were no consistent patterns of identifiable defense styles specific to these groups in qualitative, univariate, and multivariate analyses. The failure of the DSQ to demonstrate specificity across eating disorder subgroups suggests it is not informative in regard to the pathogenesis of these specific syndromes. In contrast, in a previous study, we found temperamental measures to be informative.

Acute tryptophan depletion, which may reduce brain serotonin synthesis in humans, was evaluated in bulimic and normal subjects assessing its effects on the plasma ratio of tryptophan to the sum of the other large, neutral amino acids (TRP/sigma LNAA). Thirteen bulimic and 9 control women ingested an amino acid mixture containing either 2.3 g (control mixture) or 0 g of tryptophan (active mixture), in combination with 100 g of the other amino acids. Six healthy male volunteers were also studied, using a similar mixture containing 4.6 g of tryptophan. Bulimic and control women both experienced sizable reductions in the plasma TRP/sigma LNAA ratio, compared to baseline values, for both the active mixture (10% of baseline) or the control mixture (45% of baseline). For bulimic women, the active mixture produced a significant increase in fatigue and a trend toward increased anxiety and indecisiveness. The control mixture did not maintain baseline TRP/sigma LNAA ratios so we identified a control amino acid mixture that does not cause a drop in the plasma TRP/sigma LNAA ratio when ingested (4.6 g tryptophan in combination with 100 g of other amino acids). An oral, tryptophan-deficient amino acid mixture produced acute, substantial reductions in the plasma TRP/sigma LNAA ratio in all subjects, suggesting that the treatment should reduce brain tryptophan uptake and serotonin synthesis. A control mixture containing tryptophan was also identified that maintains the plasma TRP/sigma LNAA ratio at pretreatment values.

We compared the characteristics of hospitalized women with bulimia nervosa alone (N = 19) and with bulimia nervosa plus alcohol abuse (N = 13) using standard measures of depression, eating disorders, general psychiatric symptomatology, and temperament. Bulimic women with alcohol abuse had significantly higher lowest past weight, but did not differ from women with bulimia alone on age, age of onset of bulimia, current weight, and highest past weight. There were no differences in clinical symptoms of bulimia, depression, or general psychiatric symptomatology. On Cloninger's Tridimensional Personality Questionnaire (TPQ), bulimic women with alcohol abuse scored significantly higher on Total Novelty Seeking, on the Novelty Seeking Subscale Disorderliness, and on the Reward Dependence Subscale Attachment. Implications for understanding the relation between bulimia and substance abuse are discussed.

It is not understood why disturbed menstrual function occurs in as many as 50% of women with bulimia nervosa who are at normal weight. The authors measured luteinizing hormone (LH), estradiol, and progesterone in 13 women with bulimia nervosa who were at normal weight and six normal comparison subjects. They found that the women with bulimia nervosa were likely to have abnormal 24-hour luteinizing hormone (LH) secretion if their current weight was less than 85% of their past high weight.

While caloric consumption during binge eating has been measured, it is not known how many of the calories are retained in the gastrointestinal tract after vomiting. In 17 normal weight bulimic patients, there appeared to be a ceiling on the number of calories retained after vomiting. That is, whether or not bulimic patients had small (mean = 1,549 kcal, SD = 505) or large (mean = 3,530 kcal, SD = 438) binges, they retained similar amounts of kilocalories (mean = 1,128, SD = 497, versus mean = 1,209, SD = 574, respectively) after vomiting.

Twenty women with bulimia nervosa (BN) and 20 women with obsessive-compulsive disorder (OCD) were compared on responses to the Minnesota Multiphasic Personality Inventory (MMPI), Symptom Checklist-90-Revised (SCL-90-R), and the Beck Depression Inventory (BDI). Multivariate analyses showed no significant differences between bulimic and OCD women on the MMPI, although a greater number of bulimic women showed significant elevations on several of the clinical scales. Analyses of SCL-90-R profiles indicated higher scores on somatization, interpersonal sensitivity, and psychoticism in the BN sample. Bulimic women did not differ significantly from OCD women on either obsessive-compulsive measures or other measures of anxiety. Similarities and differences in symptom profiles between these two groups are discussed, as well as their implications for alternative treatment approaches for BN.

Cerebrospinal fluid neurotransmitter metabolite levels were studied to assess whether measures of central serotonin, dopamine, or norepinephrine function are associated with severity of abnormal eating patterns in patients with bulimia nervosa. In comparison with healthy controls (N = 17), hospitalized bulimic patients with a history of binge eating more frequently than twice daily (N = 11) had significantly lower CSF concentrations of 5-hydroxyindoleacetic acid and homovanillic acid. For the total patient group (N = 29), levels of both metabolites were significantly inversely correlated with binge frequency. On the basis of preclinical studies, these results were examined in the context of speculative models in which low central serotonin function might contribute to blunted satiety responses in bulimic patients, while low central dopamine activity might play a role in abnormal hedonic responses to food.

We have designed a human-feeding laboratory to be used to study feeding behavior in patients with eating disorders. Twenty-one normal-weight bulimic subjects consumed 29.711 +/- 39.940 MJ (range 0.862-178.632 MJ; 7101 +/- 9546 kcal, range 206 to 42,694 kcal) in 24 h. In comparison, 11 healthy volunteer women, when instructed to eat ad lib for 48 h, ate 7.715 +/- 2.590 MJ (1844 +/- 619 kcal) during the first 24 h and 7665 +/- 1828 MJ (1832 +/- 437 kcal) during the second 24 h. Bulimics and control subjects had a similar number of eating intervals (6.6 +/- 2.6 vs 5.0 +/- 1.7); 72% of the bulimic subjects' meals were similar in size to the meals of the controls [167-4100 kJ (40-980 kcal)] but these meals were higher in carbohydrate and lower in fat in bulemic patients. Excessive caloric intake by bulimic subjects was because 28% of their meals were very large [range 4.427-28.150 MJ (1058-6728 kcal)]. Data gathered in a laboratory setting appears to be a reasonable replication of naturalistic feeding and suggest that such a laboratory may prove useful for future studies of feeding behaviors in humans.

Brain serotonin activity contributes to satiety. Theoretically, binging behavior is consistent with reduced serotonin function, whereas anorexia nervosa is consistent with increased serotonin activity. Brain serotonin abnormalities could also contribute to psychopathologic behaviors such as dysphoric mood, disturbance of impulse control, and obsessionality, as well as neuroendocrine disturbances. In fact, disturbances of serotonin have been found in acutely ill anorexia nervosa patients. Tryptophan, an essential amino acid found in the diet, is the precursor of serotonin. Thus serotonin disturbances could be secondary to dietary abnormalities. However, disturbances of serotonin activity appear to persist after long-term weight recovery from anorexia nervosa. While speculative, it is possible that increased serotonin activity could contribute to the pathogenesis of restricted eating and obsessional behaviors in this illness. Physiologic and pharmacologic evidence suggest that patients with normal weight bulimia have reduced serotonin activity when acutely ill. Such disturbances, even if secondary to dietary abnormalities, may still contribute to dysphoric mood and binging behavior.

We characterized the naturalistic feeding patterns of 54 women with bulimia nervosa and 11 matched controls over a continuous 24-hr period in a feeding laboratory. Overall, bulimic women consumed more calories in 24 hr (4446 +/- 584 kcal) than did controls (1845 +/- 649 kcal). Bulimic women consumed a wide range of caloric intake, with 44% overeating and 19% undereating in comparison to the range of controls. In addition, bulimics showed a disruption of circadian feeding patterns. For overeating bulimic women, the majority of meals were of normal size and frequency. Increased caloric intake in the group of overeating bulimic women was mainly due to the fact that 37% of their meals were greater than 1000 calories. Large meals occurred predominantly during the afternoon and evening and consisted primarily of dessert and snack foods. Importantly, the percentage of fat, but not carbohydrates, consumed increased as meal size, and 24-hr caloric intake increased. This study is the first to describe the naturalistic feeding characteristics of a large number of bulimics by direct observation. These findings are consistent with previous self-reports and extend and replicate previous laboratory studies. We think that laboratory studies are a reasonable replica of naturalistic feeding and should facilitate further investigation of the psychological and physiological correlates of feeding behavior in eating disorders.