Biomedical subjects

Walter H Kaye

Publications and source records attributed to Walter H Kaye.

At least 37 records · Page 2Linked to original sources

PubMed2005

Association of multiple DRD2 polymorphisms with anorexia nervosa.

To investigate whether the dopaminergic system plays a role in the etiology of anorexia nervosa (AN) via the dopamine D2 receptor, we investigated association and transmission disequilibrium at seven single-nucleotide polymorphisms (SNPs) spanning about 75 kbp of the gene DRD2. We studied 191 probands with a DSM-IV diagnosis of AN, 457 parents and affected relatives with a DSM-IV eating disorder diagnosis, and 98 unrelated, female, normal weight controls. The -141 C/- insertion/deletion (-141 Indel), previously shown to affect DRD2 transcription efficiency, and multiple exon seven polymorphisms, one of which has previously been shown to affect DRD2 transcript stability, exhibited statistically significant association with diagnosis in haplotype transmission disequilibrium and in haplotype case : control analyses. Significant linkage disequilibrium between the -141 Indel and two exon seven SNPs (939Y and 957Y) was observed over a distance of >50 kbp in the AN probands but not in the controls. Genetically transmitted variation in D2 dopamine receptor expression mediated by functional polymorphisms affecting transcription and translation efficiency may play a role in vulnerability to AN.

Adolescent↗

PubMed2005

Symptom fluctuation in eating disorders: correlates of diagnostic crossover.

OBJECTIVE: The course of anorexia nervosa often includes the emergence of bulimic symptoms and a crossover to the full syndrome of bulimia nervosa. However, clinicians' ability to predict who will develop bulimia nervosa is limited. The converse phenomenon, crossover from bulimia nervosa to anorexia nervosa, has not been investigated as thoroughly. The authors identified factors that are associated with crossover from anorexia nervosa to bulimia nervosa and from bulimia nervosa to anorexia nervosa. METHOD: All participants were from the International Price Foundation Genetic Study. Two groups were studied. The first comprised 88 individuals with an initial diagnosis of anorexia nervosa, of whom 32 developed bulimia nervosa. The second included 350 individuals with bulimia nervosa, of whom 93 developed anorexia nervosa. Several variables, including DSM-IV axis I and II disorders and personality traits, were evaluated as potential predictors of crossover. RESULTS: For the majority of affected individuals, crossover occurred by the fifth year of illness. A low level of self-directedness was associated with crossover in both directions. Other factors differed by diagnosis: high parental criticism was associated with crossover from anorexia nervosa to bulimia nervosa, whereas alcohol abuse/dependence and a low level of novelty seeking were associated with crossover from bulimia nervosa to anorexia nervosa. CONCLUSIONS: Low self-directedness may be associated with diagnostic instability in general, whereas other specific factors are related to the direction of diagnostic crossover. These results indicate that personality and family characteristics may influence the course of eating disorders and may be informative for planning interventions.

Adolescent↗

PubMed2004

Application of a latent class analysis to empirically define eating disorder phenotypes.

CONTEXT: Diagnostic criteria for eating disorders influence how we recognize, research, and treat eating disorders, and empirically valid phenotypes are required for revealing their genetic bases. OBJECTIVE: To empirically define eating disorder phenotypes. DESIGN: Data regarding eating disorder symptoms and features from 1179 individuals with clinically significant eating disorders were submitted to a latent class analysis. The resulting latent classes were compared on non-eating disorder variables in a series of validation analyses. SETTING: Multinational, collaborative study with cases ascertained through diverse clinical settings (inpatient, outpatient, and community). PARTICIPANTS: Members of affected relative pairs recruited for participation in genetic studies of eating disorders in which probands met DSM-IV-TR criteria for anorexia nervosa (AN) or bulimia nervosa and had at least 1 biological relative with a clinically significant eating disorder. Main Outcome Measure Number and clinical characterization of latent classes. RESULTS: A 4-class solution provided the best fit. Latent class 1 (LC1) resembled restricting AN; LC2, AN and bulimia nervosa with the use of multiple methods of purging; LC3, restricting AN without obsessive-compulsive features; and LC4, bulimia nervosa with self-induced vomiting as the sole form of purging. Biological relatives were significantly likely to belong to the same latent class. Across validation analyses, LC2 demonstrated the highest levels of psychological disturbance, and LC3 demonstrated the lowest. CONCLUSIONS: The presence of obsessive-compulsive features differentiates among individuals with restricting AN. Similarly, the combination of low weight and multiple methods of purging distinguishes among individuals with binge eating and purging behaviors. These results support some of the distinctions drawn within the DSM-IV-TR among eating disorder subtypes, while introducing new features to define phenotypes.

Adolescent↗

PubMed2004

Use of nutritional supplements to increase the efficacy of fluoxetine in the treatment of anorexia nervosa.

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) medication does not appear to be effective in ill, malnourished anorexia nervosa (AN) patients. However, it may be effective in preventing relapse after weight restoration. The purpose of this study was to determine whether nutritional supplements could potentiate the effects of fluoxetine in underweight AN subjects. METHOD: Twenty-six subjects with AN participated in a trial of fluoxetine. In a double-blind, placebo-controlled manner, subjects received either nutritional supplements or a nutritional placebo. The nutritional supplement included tryptophan (the precursor of serotonin), vitamins, minerals, and essential fatty acids believed to influence serotonin pathway function. RESULTS: There was no significant difference in weight gain between subjects treated with fluoxetine plus nutritional supplements versus fluoxetine plus a nutritional placebo. Moreover, there were no significant differences between groups on mean changes in anxiety or obsessive and compulsive symptoms. DISCUSSION: The results of this study suggest that supplement strategies are not a substitute for adequate nutrition and are ineffective in increasing the efficacy of fluoxetine in underweight AN subjects.

Adult↗

PubMed2004

Report of the National Institutes of Health workshop on overcoming barriers to treatment research in anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is associated with serious medical morbidity and has the highest mortality rate of all psychiatric disorders. The National Institutes of Health (NIH) Workshop on Overcoming Barriers to Treatment Research in Anorexia Nervosa convened on September 26-27, 2002 to address the dearth of treatment research in this area. The goals of this workshop were to discuss the stages of illness and illness severity, pharmacologic interventions, psychological interventions, and methodologic considerations. METHOD: The program consisted of a series of brief presentations by moderators, each followed by a discussion of the topic by workshop participants, facilitated by the session chair. RESULTS: This report summarizes the major discussions of these sessions and concludes with a set of recommendations related to the development of treatment research in AN based on these findings. DISCUSSION: It is crucial that treatment research in this area be prioritized.

Anorexia Nervosa↗

PubMed2004

Genetic analysis of bulimia nervosa: methods and sample description.

OBJECTIVE: Twin and family studies suggest that genetic variants contribute to the pathogenesis of bulimia nervosa (BN) and anorexia nervosa (AN). The Price Foundation has supported an international, multisite study of families with these disorders to identify these genetic variations. The current study presents the clinical characteristics of this sample as well as a description of the study methodology. METHOD: All probands met modified criteria for BN or bulimia nervosa with a history of AN (BAN) as defined in the 4th ed. of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV; American Psychiatric Association, 1994). All affected relatives met DSM-IV criteria for BN, AN, BAN, or eating disorders not otherwise specified (EDNOS). Probands and affected relatives were assessed diagnostically using both trained-rater and self-report assessments. DNA samples were collected from probands, affected relatives, and available biologic parents. RESULTS: Assessments were obtained from 163 BN probands and 165 BAN probands. Overall, there were 365 relative pairs available for linkage analysis. Of the affected relatives of BN probands, 62 were diagnosed as BN (34.8%), 49 as BAN (27.5%), 35 as AN (19.7%), and 32 as EDNOS (18.0%). For the relatives of BAN probands, 42 were diagnosed as BN (22.5%), 67 as BAN (35.8%), 48 as AN (25.7%), and 30 as EDNOS (16.0%). DISCUSSION: This study represents the largest genetic study of eating disorders to date. Clinical data indicate that although there are a large number of individuals with BN disorders, a range of eating pathology is represented in the sample, allowing for the examination of several different phenotypes in molecular genetic analyses.

Anxiety↗

PubMed2004

Personality in men with eating disorders.

OBJECTIVE: This study compares personality variables of men with eating disorders to women with eating disorders. METHOD: Data were obtained from an international study of the genetics of eating disorders. Forty-two male participants were age-band matched at 1:2 ratio to females from the same study. Personality features were compared between males and females controlling for diagnostic subgroup. RESULTS: Males with eating disorders appear to be slightly less at risk for perfectionism, harm avoidance, reward dependence, and cooperativeness than females. Few differences were found when diagnostic subgroup was considered. CONCLUSION: Observed differences in personality variables may help explain the difference in incidence and prevalence of eating disorders in men and women.

Adult↗

PubMed2004

Personality characteristics of women before and after recovery from an eating disorder.

BACKGROUND: Previous studies of personality characteristics in women with eating disorders primarily have focused on women who are acutely ill. This study compares personality characteristics among women who are ill with eating disorders, recovered from eating disorders, and those without eating or other Axis I disorder pathology. METHOD: Female participants were assessed for personality characteristics using the Temperament and Character Inventory (TCI): 122 with anorexia nervosa (AN; 77 ill, 45 recovered), 279 with bulimia nervosa (BN; 194 ill, 85 recovered), 267 with lifetime histories of both anorexia and bulimia nervosa (AN + BN; 194 ill, 73 recovered), 63 with eating disorder not otherwise specified (EDNOS; 31 ill, 32 recovered), and 507 without eating or Axis I disorder pathology. RESULTS: Women ill with all types of eating disorders exhibited several TCI score differences from control women, particularly in the areas of novelty-seeking, harm avoidance, self-directedness, and cooperativeness. Interestingly, women recovered from eating disorders reported higher levels of harm avoidance and lower self-directedness and cooperativeness scores than did normal control women. CONCLUSIONS: Women with eating disorders in both the ill and recovered state show higher levels of harm avoidance and lower self-directedness and cooperativeness scores than normal control women. Although findings suggest that disturbances may be trait-related and contribute to the disorders' pathogenesis, additional research with more representative community controls, rather than our pre-screened, normal controls, is needed to confirm these impressions.

Adult↗

PubMed2004

Neuroimaging studies in eating disorders.

The understanding of the eating disorders (EDs) anorexia (AN) and bulimia nervosa (BN) has undergone remarkable advancements in the past decade. Most studies that have been done in AN show brain gray and white matter volume loss during the ill state that, at least in part, remit with recovery. Similar patterns occur for brain phospholipids assessed using magnet resonance spectroscopy (MRS). Imaging studies have been used to provide functional information regarding serotonin neuroreceptor dynamics, regional cerebral blood flow, or cerebral glucose metabolism. Such studies have implicated cingulate, frontal, temporal, and parietal regions in AN. Investigators have found that challenges such as food and body image distortions may activate some of these regions, raising the possibility that such studies may shed light on puzzling AN symptoms, such as body image distortions or extremes of appetitive behaviors. Emerging data suggest these disturbances persist after recovery from AN, suggesting the possibility that these are traits that may create a vulnerability to develop an ED. While fewer studies have been done in BN or binge eating disorder, there may be disturbances of serotonin metabolism in similar brain regions. Taken together, these findings give promise for future investigations with the hope of delineating brain pathways that contribute to the etiology of EDs

Anorexia Nervosa↗

PubMed2004

Altered 5-HT(2A) receptor binding after recovery from bulimia-type anorexia nervosa: relationships to harm avoidance and drive for thinness.

Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN) and bulimia nervosa (BN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5-HT(2A)) receptor, which could contribute to disturbances of appetite and behavior in AN and BN. To avoid the confounding effects of malnutrition, we studied 10 women recovered from bulimia-type AN (REC AN-BN, > 1 year normal weight, regular menstrual cycles, no binging, or purging) compared with 16 healthy control women (CW) using PET imaging and a specific 5-HT(2A) receptor antagonist, [18F]altanserin. REC AN-BN women had significantly reduced [18F]altanserin binding potential relative to CW in the left subgenual cingulate, the left parietal cortex, and the right occipital cortex. [18F]altanserin binding potential was positively related to harm avoidance and negatively related to novelty seeking in cingulate and temporal regions only in REC AN-BN subjects. In addition, REC AN-BN had negative relationships between [18F]altanserin binding potential and drive for thinness in several cortical regions. In conclusion, this study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from bulimia-type AN, particularly in subgenual cingulate regions. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of eating disorders. It is possible that subgenual cingulate findings are not specific for AN-BN, but may be related to the high incidence of lifetime major depressive disorder diagnosis in these subjects.

Adult↗

PubMed2004

Comorbidity of anxiety disorders with anorexia and bulimia nervosa.

OBJECTIVE: A large and well-characterized sample of individuals with anorexia nervosa and bulimia nervosa from the Price Foundation collaborative genetics study was used to determine the frequency of anxiety disorders and to understand how anxiety disorders are related to state of eating disorder illness and age at onset. METHOD: Ninety-seven individuals with anorexia nervosa, 282 with bulimia nervosa, and 293 with anorexia nervosa and bulimia were given the Structured Clinical Interview for DSM-IV Axis I Disorders and standardized measures of anxiety, perfectionism, and obsessionality. Their ratings on these measures were compared with those of a nonclinical group of women in the community. RESULTS: The rates of most anxiety disorders were similar in all three subtypes of eating disorders. About two-thirds of the individuals with eating disorders had one or more lifetime anxiety disorder; the most common were obsessive-compulsive disorder (OCD) (N=277 [41%]) and social phobia (N=134 [20%]). A majority of the participants reported the onset of OCD, social phobia, specific phobia, and generalized anxiety disorder in childhood, before they developed an eating disorder. People with a history of an eating disorder who were not currently ill and never had a lifetime anxiety disorder diagnosis still tended to be anxious, perfectionistic, and harm avoidant. The presence of either an anxiety disorder or an eating disorder tended to exacerbate these symptoms. CONCLUSIONS: The prevalence of anxiety disorders in general and OCD in particular was much higher in people with anorexia nervosa and bulimia nervosa than in a nonclinical group of women in the community. Anxiety disorders commonly had their onset in childhood before the onset of an eating disorder, supporting the possibility they are a vulnerability factor for developing anorexia nervosa or bulimia nervosa.

Adolescent↗

PubMed2004

Alcohol use disorder comorbidity in eating disorders: a multicenter study.

BACKGROUND: Eating disorders and alcohol use disorders (AUDs) commonly co-occur, although the patterns of comorbidity differ by eating disorder subtype. Our aim was to explore the nature of the co-morbid relation between AUDs and eating disorders in a large and phenotypically well-characterized group of individuals. METHOD: We compared diagnostic and personality profiles of 97 women with lifetime anorexia nervosa only, 282 women with lifetime bulimia nervosa only, and 293 women with a lifetime history of both anorexia nervosa and bulimia nervosa or anorexia nervosa with binge eating (ANBN) (DSM-IV criteria). All individuals were participants in a multicenter study of the genetics of anorexia nervosa and bulimia nervosa. We explored pattern of onset, Axis I and II comorbidity, and personality characteristics of individuals with and without AUDs by eating disorder subtype. Personality characteristics were assessed with the Multidimensional Perfectionism Scale, the Temperament and Character Inventory, and the Barratt Impulsivity Scale. RESULTS: Alcohol use disorders were significantly more prevalent in women with ANBN and bulimia nervosa than in women with anorexia nervosa (p =.0001). The majority of individuals reported primary onset of the eating disorder, with only one third reporting the onset of the AUD first. After eating disorder subtype was controlled for, AUDs were associated with the presence of major depressive disorder, a range of anxiety disorders, and cluster B personality disorder symptoms. In addition, individuals with AUDs presented with personality profiles marked by impulsivity and perfectionism. CONCLUSIONS: Individuals with eating disorders and AUDs exhibit phenotypic profiles characterized by both anxious, perfectionistic traits and impulsive, dramatic dispositions. These traits mirror the pattern of control and dyscontrol seen in individuals with this comorbid profile and suggest that anxiety modulation may be related to alcohol use in this group.

Age of Onset↗

PubMed2004

An open trial of olanzapine in anorexia nervosa.

BACKGROUND: Recent reports raise the possibility that olanzapine can assist weight gain and improve behavioral symptoms during refeeding in anorexia nervosa. METHOD: Seventeen DSM-IV anorexia nervosa subjects hospitalized between May 1999 and October 2000 were enrolled in open-label treatment with olanzapine for up to 6 weeks. Baseline weight and symptoms were compared to patients' status at the end of treatment. RESULTS: Olanzapine administration was associated with a significant reduction in depression, anxiety, and core eating disorder symptoms, and a significant increase in weight. A comparison with our historical data suggests that subjects in this study had a significantly greater decrease in depression. CONCLUSION: These data lend support to the possibility that olanzapine may be useful in treating anorexia nervosa. However, a controlled trial is necessary to demonstrate that olanzapine is efficacious.

Adult↗

PubMed2003

The evaluation of brain activity in response to taste stimuli--a pilot study and method for central taste activation as assessed by event-related fMRI.

BACKGROUND: Brain pathways contribute to the regulation of appetite behaviors, and advancements in brain imaging offer new opportunities in determining whether disturbances of these pathways play a role in pathological feeding behaviors in humans. We developed a standardized method for the assessment of brain activation in response to taste stimuli. METHODS: Five healthy control women were positioned in a 1.5 T GE magnet resonance (MR) scanner for functional MR imaging (fMRI). They received 1.0 cm3 samples of 1 M glucose solution or artificial saliva (25 mM KCl, 2 mM NaHCO3). Fluid challenges were delivered by a programmable syringe pump (J-Kem Scientific, St. Louis, MO). E-Prime software (Psychology Software Tools Inc., Pittsburgh, PA) coordinated taste stimulation with MR scanning. Data were analyzed using NeuroImaging software (NIS). RESULTS: Healthy women showed increased orbitofrontal cortex activation when glucose was compared to artificial saliva. In addition, mesial and lateral temporal cortical regions contrasted glucose from artificial saliva. CONCLUSIONS: This study demonstrates a design for the systematic study of brain activation after taste stimulation using fMRI and computer controlled stimulus delivery. The results are consistent with previous studies, showing activation in higher order brain centers that are involved in emotional coding of taste experience.

Adult↗

PubMed2003

Olanzapine treatment of anorexia nervosa: a retrospective study.

BACKGROUND: Recent reports raise the possibility that olanzapine, which commonly causes weight gain in non-eating-disordered subjects, assisted weight gain and mood during refeeding in anorexia nervosa (AN) patients. METHODS: Eighteen AN subjects who engaged in open treatment with olanzapine were retrospectively questioned about their response. RESULTS: Subjects reported a significant reduction in anxiety, difficulty eating, and core eating disorder symptoms after taking olanzapine. DISCUSSION: These data lend support to the possibility that olanzapine may be useful in AN patients. CONCLUSION: A controlled trial is necessary to prove that olanzapine is efficacious.

Adolescent↗

PubMed2003

Anxiolytic effects of acute tryptophan depletion in anorexia nervosa.

OBJECTIVE: Recent studies have raised the question as to whether a dysregulation of the neurotransmitter serotonin may contribute to the alterations in mood seen in anorexia nervosa (AN). People with AN tend to be anxious, obsessional, perfectionistic, and harm avoidant. These traits are premorbid and persist after recovery. It has been suggested that increased activity of brain serotonin systems could contribute to this pathologic condition. Dieting in AN, which serves to reduce plasma levels of tryptophan (TRP), may serve to reduce symptoms of dysphoric mood. METHOD: Fourteen women currently symptomatic with AN (ILL AN), 14 women recovered from AN (REC AN), and 15 healthy control women (CW) underwent acute tryptophan depletion (ATD). Measures of psychological state were self-assessed at baseline and hourly after ATD to determine whether ATD would reduce negative mood. RESULTS: ILL AN and REC AN had significantly higher mean baseline TRP/LNAA (tryptophan/large neutral amino acids) ratios compared with CW. In contrast to placebo, the ATD challenge demonstrated a significantly greater reduction in the TRP/LNAA ratio for ILL AN (-95%) and REC AN (-84%) compared with CW (-70 %). Both the ILL AN and REC AN had a significant reduction in anxiety on the ATD day compared with the placebo day. DISCUSSION: These data demonstrate that a dietary-induced reduction of TRP, the precursor of serotonin, is associated with decreased anxiety in people with AN. Restricting dietary intake may represent a mechanism through which individuals with AN modulate a dysphoric mood.

Adolescent↗

PubMed2003

Obsessions and compulsions in anorexia nervosa subtypes.

OBJECTIVE: Obsession and compulsions in anorexia nervosa (AN) patients are often confused with the preoccupations and rituals that are characteristic of obsessive-compulsive disorder (OCD). We examined the type and frequency of characteristic OCD obsessions and compulsions in a large sample of AN patients. METHOD: In personal interviews with 324 AN patients, we assessed lifetime histories of eating disorder symptomatology and obsessive-compulsive behaviors with valid semistructured interviews. Checklist category sums on the Yale-Brown Obsessive Compulsive Scale were compared between AN and OCD subjects using generalized estimating equations. RESULTS: Lifetime obsessions and compulsions occurred in 68% of the AN restricting type and in 79.1% of the AN binge/purge type. The AN subgroups did not differ from OCD controls in frequency of obsessions in the symmetry and somatic categories or in the compulsion categories of ordering and hoarding. In all other categories, the AN subgroups had a significantly lower frequency compared with the OCD controls. DISCUSSION: Some common phenotype characteristics shared by most AN and OCD patients suggest these disorders may share common brain behavioral pathways. However, the lack of complete overlap indicates they most likely have different loci of pathology within those pathways.

Adult↗

PubMed2003

Pain perception in recovered bulimia nervosa patients.

OBJECTIVE: Decreased pain sensitivity is found in individuals who are ill with bulimia nervosa (BN). The purpose of this study is to determine whether altered pain perception persists after recovery from bulimia nervosa (RBN). METHODS: Eleven women who were recovered from BN for more than 1 year were compared with 15 healthy volunteer women. The participants received two pain evaluations--thermal pain stimulation (TPS), which evaluates threshold and tolerance to heat, and the submaximal effort tourniquet test (SETT), which assesses threshold and tolerance to ischemic pain induced by inflation of a blood pressure cuff. RESULTS: Compared with the controls, the RBN women showed elevated pain threshold as measured with the SETT and a tendency to elevated pain threshold on the TPS. DISCUSSION: Decreased pain sensitivity persists after recovery from BN and may reflect altered modulatory function in this illness.

Adult↗