Biomedical subjects

Guido K Frank

Publications and source records attributed to Guido K Frank.

17 recordsLinked to original sources

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

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

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

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↗

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

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

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↗

PubMed2002

Reduced 5-HT2A receptor binding after recovery from anorexia nervosa.

BACKGROUND: Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5HT2A) receptor, which could contribute to disturbances of appetite and behavior in AN. METHODS: To avoid the confounding effects of malnutrition, we studied 16 women recovered from AN (REC AN, >1 year normal weight, regular menstrual cycles, no bingeing or purging) compared with 23 healthy control women (CW) using [18F]altanserin, a specific 5-HT2A receptor antagonist on PET imaging. RESULTS: REC AN women had significantly reduced [18F]altanserin binding relative to CW in mesial temporal (amygdala and hippocampus), as well as cingulate cortical regions. In a subset of subjects (11 CW and 16 REC AN), statistical parametric mapping (SPM) confirmed reduced mesial temporal cortex 5HT2A receptor binding and, in addition, showed reduced occipital and parietal cortex binding. CONCLUSIONS: This study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from AN and may be related to disturbances of mesial temporal lobe function. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of AN.

Adult↗