Biomedical subjects

Walter H Kaye

Publications and source records attributed to Walter H Kaye.

At least 19 recordsLinked to original sources

PubMed2026

Eating Disorders and Parkinson's Disease-2: Genetic Epidemiology and Shared Genomics.

OBJECTIVE: Individuals with anorexia nervosa (AN) share premorbid traits with Parkinson's Disease (PD) (e.g., anxiety) and exhibit a two-fold relative risk of a reported family history of PD. Published estimates of intra- and inter-disorder genetic architecture were extracted and compared prior to conducting novel analyses to provide evidence for cross-disorder genetic risk. METHODS: National register or meta-analytic familial, twin, and common variant genome-wide studies were searched; estimates and findings were extracted and compared. Novel cross-disorder conditional and conjunctional false discovery rate analyses were performed. RESULTS: Sibling relative risks and additive genetic estimates of the two disorders were similar. AN had greater common variant heritability than PD whether measured via infinitesimal model (linkage disequilibrium score regression, LDSC) or causal mixture model (MiXeR). AN had greater polygenicity than PD (mean (SD) 2.50E-03 (1.64E-04) versus 2.72E-4 (1.47E-05), p < 0.001), but lower discoverability than PD (4.20E-05 (2.69E-06) versus 1.40E-04 (6.95E-06), p < 0.001). Global genetic correlation was significant (e.g., bivariate LDSC rg = 0.10, p = 0.0033). Novel analyses identified cross-disorder enrichment, and cross-disorder risk at chr3p21.31. CONCLUSIONS: Cross-disorder AN and PD research identified shared risk variants at chr3p21.31, genes and mechanisms (e.g., conditioning, fear, and reward) linked to a shared endophenotype.

Parkinson's disease↗

PubMed2024

Genome-wide copy number variation association study in anorexia nervosa.

This study represents the first large-scale investigation of rare (<1% population frequency) copy number variants (CNVs) in anorexia nervosa (AN). Large, rare CNVs are reported to be causally associated with anthropometric traits, neurodevelopmental disorders, and schizophrenia, yet their role in the genetic basis of AN is unclear. Using genome-wide association study (GWAS) array data from the Anorexia Nervosa Genetics Initiative (ANGI), which included 7414 AN case and 5044 controls, we investigated the association of 67 well-established syndromic CNVs and 178 pleiotropic disease-risk dosage-sensitive CNVs with AN. To identify novel CNV regions (CNVRs) that increase the risk of AN, we conducted genome-wide association studies with a focus on rare CNV-breakpoints (CNV-GWAS). We found no net enrichment of rare CNVs, either deletions or duplications, in AN, and none of the well-established syndromic or pleiotropic CNVs had a significant association with AN status. However, the CNV-GWAS found 21 nominally associated CNVRs that contribute to AN risk, covering protein-coding genes implicated in synaptic function, metabolic/mitochondrial factors, and lipid characteristics, like the CD36 (7q21.11) gene, which transports long-chain fatty acids into cells. CNVRs intersecting genes previously related to neurodevelopmental traits include deletions of NRXN1 intron 5 (2p16.3), IMMP2L (7q31.1), and PTPRD (9p23). Overall, given that our study is well powered to detect the CNV burden level reported for schizophrenia, we can conclude that rare CNVs have a limited role in the etiology of AN, as reported for bipolar disorder. Our nominal associations for the 21 discovered CNVRs are consistent with AN being a metabo-psychiatric trait, as demonstrated by the common genetic architecture of AN, and we provide association results to allow for replication in future research.

Humans↗

PubMed2006

Smoking in eating disorders.

OBJECTIVE: Smoking has been reported as an appetite and weight control method in eating disorders; however, few studies have explored patterns of smoking across subtypes of eating disorders. The aim of this paper was to explore the patterns and prevalence of smoking behavior in 1,524 women from two of the multisite Price Foundation Genetic studies. METHOD: Smoking behavior was assessed in 306 individuals with anorexia nervosa-restricting type (RAN), 186 with anorexia nervosa-purging type (PAN), 180 with anorexia nervosa and bulimia nervosa (ANBN), 107 with anorexia nervosa-binging type (BAN), 71 individuals with purging type-bulimia nervosa (PBN), and 674 female community controls. We compared smoking prevalence and smoking behaviors across eating disorder (ED) subtypes and in comparison to controls using the Fagerstrom Test of Nicotine Dependence (FTND). RESULTS: Overall, women with eating disorders reported higher rates of smoking and greater nicotine dependence than controls. Women with binge/purge subtypes of eating disorders reported the highest rates of smoking of all of the subtypes. Smoking in eating disorders was related to impulsive personality traits. CONCLUSIONS: Women with eating disorders appear to be at increased risk for smoking, particularly those who binge eat and/or purge and display impulsive personality characteristics. Given the high prevalence, the impact of ongoing smoking on maintenance of eating disorders symptoms is worthy of both clinical and research attention.

Adult↗

PubMed2006

Neural correlates of habituation to taste stimuli in healthy women.

Recent studies show that specific regions of the cortex contribute to modulation of appetitive behaviors. The purpose of this study was to determine whether neural response in these regions changes over time when a taste stimulus is administered repeatedly. Such a paradigm may be useful for determining whether altered habituation contributes to disturbed eating behavior. This study used a programmable syringe pump to compare administration of a 10% sucrose solution to distilled water in 11 healthy female subjects using functional magnetic resonance imaging. The stimuli were presented in either a sequential or pseudorandom order. An a priori 'Region of Interest' (ROI) based analysis method was used, with ROIs defined in the prefrontal cortex, insula, amygdala, and hippocampus. To test habituation, activation during the first half of each block was compared with activation during the second half. For the pseudorandom blocks, subjects showed habituation in almost all ROIs to water, but in none to sucrose. By contrast, for sequential blocks, both stimuli produced habituation in taste-related brain regions. These data suggest that habituation patterns in healthy subjects may depend on frequency and regularity of stimulus administration.

Adult↗

PubMed2006

Altered brain activity in women recovered from bulimic-type eating disorders after a glucose challenge: a pilot study.

OBJECTIVE: It is not known whether individuals with bulimic-type eating disorders have a dysregulation of brain pathways that modulate appetite. Taste plays a role in the regulation of appetite and the purpose of the current study was to determine whether bulimic women have alterations in the physiologic response to the blind administration of glucose. METHOD: To avoid the confounding effects of a current eating disorder, and to assess possibly trait-related disturbances, we studied 10 subjects recovered (> or = 1 year) from a bulimic-type eating disorder and 6 control women. Subjects were administered a solution of glucose or artificial saliva (control solution) in alternating blocks during a functional magnet resonance imaging scan. RESULTS: Individuals who recovered from a bulimic-type eating disorder had significantly lower activation in the right anterior cingulate cortex (ACC; Montreal Neurological Institute [MNI] coordinates x = 8, y = 22, z = 28; cluster size = 18 voxels, T = 5.11, Z-score = 3.78) and in the left cuneus (occipital cortex; MNI coordinates x = -12, y = -78, z = 10; cluster size = 21 voxels, T = 4.27, Z-score = 3.36), when glucose was compared with artificial saliva. CONCLUSION: The ACC plays a role in the anticipation of reward. Individuals with bulimic-type eating disorders may have a reduced reward response to nutrients, and thus may be vulnerable to overeating. However, this is a small sample and the current study will need replication in a larger sample size with investigation of additional regions of interest.

Adult↗

PubMed2006

Features associated with excessive exercise in women with eating disorders.

OBJECTIVE: Excessive exercise and motor restlessness are observed in a substantial number of patients with eating disorders. This trait has been studied extensively among animal models of activity anorexia nervosa (AN) and may hold particular interest as an endophenotype for AN. We explored features associated with excessive exercise across subtypes of eating disorders. METHOD: Participants were female probands and affected female relatives from the multi-site international Price Foundation Genetic Studies with diagnoses of AN, bulimia nervosa (BN), and both AN and BN or eating disorder not otherwise specified (ED-NOS) (N=1,857). Excessive exercise was defined based on responses to the Structured Interview for Anorexic and Bulimic Disorders (SIAB). RESULTS: Among the eating disorder diagnostic groups, excessive exercise was most common among the purging subtype of AN. Individuals who reported excessive exercise also reported lower minimum BMI, younger age at interview, higher scores on anxiety, perfectionism, and eating disorder symptom measures, more obsessions and compulsions, and greater persistence. CONCLUSION: Excessive exercise may be associated particularly with the purging subtype of AN as well as with a constellation of anxious/obsessional temperament and personality characteristics among women with eating disorders.

Adult↗

PubMed2006

Personality traits after recovery from eating disorders: do subtypes differ?

OBJECTIVE: We compared individuals recovered from anorexia (AN) and bulimia nervosa (BN) to determine characteristics that are shared by or distinguish eating disorder (ED) subtypes. METHOD: Sixty women recovered for > or = 1 year from AN or BN were compared with 47 control women (CW). Assessments included the Yale-Brown-Cornell Eating Disorder Scale, the Spielberger State-Trait Anxiety Inventory, the Beck Depression Inventory, the Yale-Brown Obsessive Compulsive Scale, the Temperament and Character Inventory, and Structured Clinical Interviews for DSM-IV. RESULTS: Individuals recovered from an ED had similar scores for mood and personality variables that were significantly higher than the scores for CW. Few recovered subjects had Cluster B personality disorder. Most individuals recovered within 6 years of their ED onset. A latent profile analysis identified an "inhibited" and "disinhibited" cluster based on personality traits. CONCLUSION: A wide range of symptoms persist after recovery and do not differ between subtypes of ED. These findings may aid in identifying traits that create vulnerabilities for developing an ED.

Adult↗

PubMed2005

Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates.

To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR), and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum body mass index (BMI), concern over mistakes (CM), and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.3]; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals.

Anorexia Nervosa↗

PubMed2005

Selection of eating-disorder phenotypes for linkage analysis.

Vulnerability to anorexia nervosa (AN) and bulimia nervosa (BN) arise from the interplay of genetic and environmental factors. To explore the genetic contribution, we measured over 100 psychiatric, personality, and temperament phenotypes of individuals with eating disorders from 154 multiplex families accessed through an AN proband (AN cohort) and 244 multiplex families accessed through a BN proband (BN cohort). To select a parsimonious subset of these attributes for linkage analysis, we subjected the variables to a multilayer decision process based on expert evaluation and statistical analysis. Criteria for trait choice included relevance to eating disorders pathology, published evidence for heritability, and results from our data. Based on these criteria, we chose six traits to analyze for linkage. Obsessionality, Age-at-Menarche, and a composite Anxiety measure displayed features of heritable quantitative traits, such as normal distribution and familial correlation, and thus appeared ideal for quantitative trait locus (QTL) linkage analysis. By contrast, some families showed highly concordant and extreme values for three variables-lifetime minimum Body Mass Index (lowest BMI attained during the course of illness), concern over mistakes, and food-related obsessions-whereas others did not. These distributions are consistent with a mixture of populations, and thus the variables were matched with covariate linkage analysis. Linkage results appear in a subsequent report. Our report lays out a systematic roadmap for utilizing a rich set of phenotypes for genetic analyses, including the selection of linkage methods paired to those phenotypes.

Algorithms↗

PubMed2005

Brain imaging of serotonin after recovery from anorexia and bulimia nervosa.

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with relatively homogenous presentations such as age of onset and gender distribution. In addition, they share symptoms, such as extremes of food consumption, body image distortion, anxiety and obsessions, and ego-syntonic neglect. Taken together, these observations raise the possibility that these symptoms reflect disturbed brain function, which contributes to the pathophysiology of these illnesses. Several lines of evidence suggest that disturbances of serotonin (5-HT) pathways play a role. First, 5-HT pathways contribute to the modulation of feeding, mood, and impulse control. Second, medications that act on 5-HT pathways have some degree of efficacy in individuals with AN and BN. Third, such disturbances are present when subjects are ill and persist after recovery, suggesting that 5-HT alterations may be traits that are independent of the state of the illness. Positron emission tomography (PET) with radioligands offers an opportunity to directly characterize brain 5-HT pathways and their relationship with behavior. For example, reduced 5-HT(2A) receptor function occurs in AN whereas increased 5-HT(1A) receptor function occurs in BN. Moreover, imaging studies correlate altered 5-HT(1A) and 5-HT(2A) receptor function with traits often found in individuals with AN and BN, such as harm avoidance. Finally, alteration of these receptors tends to implicate pathways involving frontal, cingulate, temporal, and parietal regions. Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.

Animals↗

PubMed2005

Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa.

BACKGROUND: Individuals who are ill with anorexia (AN) and bulimia nervosa (BN) often have increased cerebrospinal fluid (CSF) volumes and decreased total gray and white matter volumes. It is unclear whether such disturbances persist after recovery from an eating disorder. METHODS: Magnetic resonance imaging was performed on 40 women who were long-term recovered (>1 year no binging, purging, or restricting behaviors, normal weight, and menstrual cycles, not on medication) from restricting or binge/purging type AN or BN and 31 healthy control women (CW). Voxel-based morphometry (VBM) was used for data analysis. RESULTS: Recovered AN and BN subgroups were similar to CW in terms of cerebrospinal fluid (CSF) volume as well as total or regional gray or white matter volume. CONCLUSIONS: These findings suggest that structural brain abnormalities are reversible in individuals with eating disorders after long-term recovery.

Adolescent↗

PubMed2005

Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [11c]raclopride.

BACKGROUND: Several lines of evidence support the possibility that disturbances of dopamine (DA) function could contribute to alterations of weight, feeding, motor activity, and reward in anorexia nervosa (AN). METHODS: To assess possibly trait-related disturbances but avoid confounding effects of malnutrition, 10 women who were recovered from AN (REC AN) were compared with 12 healthy control women (CW). Positron emission tomography with [(11)C]raclopride was used to assess DA D2/D3 receptor binding. RESULTS: The women who were recovered from AN had significantly higher [(11)C]raclopride binding potential in the antero-ventral striatum than CW. For REC AN, [(11)C]raclopride binding potential was positively related to harm avoidance in the dorsal caudate and dorsal putamen. CONCLUSIONS: These data lend support for the possibility that decreased intrasynaptic DA concentration or increased D2/D3 receptor density or affinity is associated with AN and might contribute to the characteristic harm avoidance or increased physical activity found in AN. Most intriguing is the possibility that individuals with AN might have a DA related disturbance of reward mechanisms contributing to altered hedonics of feeding behavior and their ascetic, anhedonic temperament.

Adult↗

PubMed2005

Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging studies.

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders with relatively homogenous presentations such as age of onset and gender distribution. In addition, they share symptoms, such as extremes of food consumption, body image distortion, anxiety and obsessions, and ego-syntonic neglect, raises the possibility that these symptoms reflect disturbed brain function that contributes to the pathophysiology of this illness. Recent brain imaging studies have identified altered activity in frontal, cingulate, temporal, and parietal cortical regions in AN and BN. Importantly, such disturbances are present when subjects are ill and persist after recovery, suggesting that these may be traits that are independent of the state of the illness. Emerging data point to a dysregulation of serotonin pathways in cortical and limbic structures that may be related to anxiety, behavioral inhibition, and body image distortions. In specific, recent studies using PET with serotonin specific radioligands implicate alterations of 5-HT1A and 5-HT2A receptors and the 5-HT transporter. Alterations of these circuits may affect mood and impulse control as well as the motivating and hedonic aspects of feeding behavior. Such imaging studies may offer insights into new pharmacology and psychotherapy approaches.

Animals↗

PubMed2005

Altered brain serotonin 5-HT1A receptor binding after recovery from anorexia nervosa measured by positron emission tomography and [carbonyl11C]WAY-100635.

CONTEXT: Previous studies have shown that women with anorexia nervosa (AN), when ill and after recovery, have alterations of serotonin (5-HT) neuronal activity and core eating disorder symptoms, such as anxiety. OBJECTIVE: To further characterize the 5-HT system in AN, we investigated 5-HT1A receptor activity using positron emission tomography imaging because this receptor is implicated in anxiety and feeding behavior. DESIGN, SETTING, AND PARTICIPANTS: To avoid the confounding effects of malnutrition, we studied 13 women who had recovered from restricting-type AN (mean age, 23.3 +/- 5.2 years) and 12 women who had recovered from bulimia-type AN (mean age, 28.6 +/- 7.3 years) (>1 year normal weight, regular menstrual cycles, no bingeing or purging). These subjects were compared with 18 healthy control women (mean age, 25.1 +/- 5.8 years). Intervention The 5-HT1A receptor binding was measured using positron emission tomography imaging and a specific 5-HT1A receptor antagonist, [carbonyl-11C]WAY-100635. MAIN OUTCOME MEASURE: Specific 5-HT1A receptor binding was assessed using the binding potential measure. Binding potential values were derived using both the Logan graphical method and compartmental modeling. The binding potential in a region of interest was calculated with the formula: binding potential = distribution volume of the region of interest minus distribution volume of the cerebellum. RESULTS: Women recovered from bulimia-type AN had significantly (P<.05) increased [11C]WAY-100635 binding potential in cingulate, lateral and mesial temporal, lateral and medial orbital frontal, parietal, and prefrontal cortical regions and in the dorsal raphe compared with control women. No differences were found for women recovered from restricting-type AN relative to controls. For women recovered from restricting-type AN, the 5-HT1A postsynaptic receptor binding in mesial temporal and subgenual cingulate regions was positively correlated with harm avoidance. CONCLUSIONS: We observed increased 5-HT1A receptor binding in women who had recovered from bulimia-type AN but not restricting-type AN. However, 5-HT1A receptor binding was associated with a measure of anxiety in women recovered from restricting-type AN. These data add to a growing body of evidence showing that altered serotonergic function and anxiety symptoms persist after recovery from AN. These psychobiological alterations may be trait related and may contribute to the pathogenesis of AN.

Adult↗

PubMed2005

Neurobiology of anorexia nervosa: clinical implications of alterations of the function of serotonin and other neuronal systems.

Recent evidence suggests that genetic and neurobiologically mediated mechanisms contribute to the etiology of anorexia nervosa (AN). Serotonin neuronal systems, in particular, may create vulnerabilities related to pathological feeding, anxiety and obsessions, and extremes of impulse control, that make individuals susceptible to developing an eating disorder, perhaps in combination with environmental stressors.

Age Factors↗

PubMed2005

Relationships between features associated with vomiting in purging-type eating disorders.

OBJECTIVE: Vomiting is a pernicious symptom of eating disorders. We explored the relation between the symptom of vomiting and features of eating disorder course and severity, personality traits, and Axis I and II comorbidity in individuals with purging-type eating disorders. METHOD: The sample included participants from the multisite, international Price Foundation Genetic Studies, who had an eating disorder diagnosis (anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified) and had data available for the frequency of purging behaviors (n = 1,048). Axis I disorders, personality disorders, trait anxiety, perfectionism, and temperament and character dimensions were included as possible correlates. RESULTS: The presence of vomiting was associated with less regular laxative use, lower self-directedness, organization, personal standards, and higher novelty seeking. CONCLUSION: Vomiting remains a prevalent and potentially destructive symptom of eating disorders, with significant dental and medical morbidity. Our findings suggest that certain clinical and personality variables distinguish individuals with purging-type eating disorders who vomit from those who do not, although there were no marked differences in Axis I or II comorbidity. Specifically targeting treatment to decrease duration of exposure to this dangerous symptom continues to be an important clinical objective.

Adolescent↗

PubMed2005

The relation among perfectionism, obsessive-compulsive personality disorder and obsessive-compulsive disorder in individuals with eating disorders.

OBJECTIVE: Perfectionism and obsessionality are core features of eating disorders (ED), yet the nature of their relation remains unknown. Understanding the relation between these traits may enhance our ability to identify relevant behavioral endophenotypes for ED. METHOD: Six-hundred seven individuals with anorexia and bulimia nervosa from the International Price Foundation Genetic Study were assessed for perfectionism, obsessive-compulsive personality disorder (OCPD), and obsessive-compulsive disorder (OCD). RESULTS: No differences were found across ED subtypes in the prevalence of OCPD and OCD, nor with the association between OCD and OCPD. Perfectionism scores were highest in individuals with OCPD whether alone or in combination with OCD. CONCLUSION: Perfectionism appears to be more closely associated with obsessive-compulsive personality symptoms rather than OCD. The pairing of perfectionism with OCPD may be a relevant core behavioral feature underlying vulnerability to ED.

Adolescent↗

PubMed2005

Positron emission tomography studies in eating disorders: multireceptor brain imaging, correlates with behavior and implications for pharmacotherapy.

Modern imaging techniques that visualize disease-specific organ neurotransmitter or protein receptor sites are increasingly able to define pathological processes on a molecular level. One of those imaging modalities, positron emission tomography (PET), for the assessment of brain neuroreceptor binding has revolutionized the in vivo assessment of biologic markers that may be related to human behavior. Such studies may help identify chemical targets that may be directly related to psychiatric pathology and, thus, opportunities for pharmacological intervention. In this review, we describe results from PET studies in eating disorders (EDs). Eating disorders are frequently debilitating illnesses that are quite homogeneous in their presentation. Those studies that identified particular serotonin and dopamine receptor alterations can distinguish recovered ED subjects from controls as well as ED subgroups. Furthermore, correlations of receptor binding with behavioral constructs, such as harm avoidance or novelty seeking, could be found. These recognized receptors may now help us to move away from rather nonspecific treatment approaches in psychiatric research and clinic to the possibility of more syndrome- and symptom-specific treatment approaches.

Brain↗