Brain morphology and regional cerebral blood flow in anorexia nervosa

Cranial computed tomography (CT) was performed in 12 patients with anorexia nervosa, revealing that the majority of the patients displayed ventricular dilatation and/or sulcal widening. In addition, regional cerebral blood flow (rCBF) was measured at admission and once again after weight gain, using xenon-133 dynamic single-photon emission tomography (dSPECT). The mean flow rates assessed at the first examination did not significantly differ from those assessed at the second examination and from those of a control group. There was a significant inverse relationship between the size of the cerebrospinal fluid spaces and the cerebral blood flow in the anorectics; a decrease in ventricular size after weight gain was associated with an increase in cerebral blood flow in this area. This finding, however, has to be interpreted with caution, as partial volume effects render the flow rates ambiguous in brain areas, which, in addition to neuronal tissue, also include ventricular and sulcal structures.     

Comparison of regional cerebral blood flow in patients with anorexia nervosa before and after weight gain

We investigated changes in regional cerebral blood flow (rCBF) before and after weight gain in patients with restrictive anorexia nervosa (AN-R) in comparison with findings in normal subjects. We assessed resting rCBF using single photon emission computed tomography with technetium-99m hexamethylpropylene amine oxime in 12 AN-R patients and 11 controls. Each patient was examined at two time points, at the beginning of treatment and after weight gain (average examination interval = 88 ± 26 days). Control subjects were examined only once. Before treatment, the AN-R group had lower rCBF in the bilateral anterior lobes, including the anterior cingulate cortex (ACC), and in the right parietal lobe, the insula, and the occipital lobes. After weight gain, the patients showed significant increases in the right parietal lobe and decreases in the basal ganglia and cerebellum in accordance with significant improvement in body weight and eating attitudes. However, they showed persistent decreases in the ACC area even after weight gain compared with findings in the controls. A significant positive correlation was observed between body mass index and rCBF in the occipital lobes in the patients. These results suggest that weight gain is associated with a normalization of rCBF in a number of brain areas, but that the low level of rCBF in the ACC at baseline is unaffected by treatment in AN-R.     

No differences are seen in the regional cerebral blood flow in the restricting type of anorexia nervosa compared with the binge eating/purging type

Aims:  Anorexia nervosa (AN) is subdivided into the restricting type (AN-R) and the binge-eating/purging type (AN-BP), but differences in cerebral blood flow between patients with these types of AN and healthy controls have not been investigated.
Methods:  The present study was designed to elucidate any such differences using resting single photon emission computed tomography (SPECT) studies to compare the differences in cerebral perfusion among both types of AN and a healthy control group. Resting regional cerebral blood flow was assessed using SPECT with technetium-99 m hexamethylpropyleneamine oxime in 13 female AN-R patients, 13 female AN-BP patients, and 10 healthy women as controls with 3-D stereotactic surface projections.
Results:  The analytic program of the SPECT images showed bilateral decreased perfusion of the subcallosal gyrus (SCG), midbrain and posterior cingulate gyrus (PCG) in both AN-R and AN-BP patients, as compared with the controls. There were no clear differences between the AN-R and AN-BP groups. There were no significant differences in cerebral blood flow between patients with AN-R and AN-BP.
Conclusions:  Abnormalities of the neuronal circuits containing the SCG, midbrain and PCG are possibly relevant to trait-related AN.     

Evidence of complex involvement of serotonergic genes with restrictive and binge purge subtypes of anorexia nervosa

Abstract

Objectives. There is mixed evidence of association of serotoninergic genes with anorexia nervosa (AN), but substantial evidence for the involvement of serotonergic mechanisms in appetite control. This study was designed to investigate possible associations between the two subtypes of AN (Restricting-RAN, and Binge-purging–BPAN) and polymorphisms within five genes encoding for proteins involved in the serotoninergic system. Methods. In order to carry out this investigation we have conducted a case–control association study on 226 females meeting the criteria for AN, and 678 matched healthy females. Results. Our data show a significant association between polymorphisms with the gene encoding HTR2A with both AN subtypes, an association between polymorphisms within the genes encoding HTR1D and HTR1B with RAN, and an association between polymorphisms within the gene encoding HTR2C with BPAN. No associations were found for any polymorphisms of the serotonin transporter gene. This outcome indicates a substantial and complex inter-relationship between serotoninergic genes and AN. Conclusions. Given these data we hypothesis that the expression or control of expression of several genes of the serotoninergic system, and interactions between these genes, could exert considerable influence over the specific symptomatology of the subtypes of AN.     

Associations between negative affect and binge/purge behaviors in women with anorexia nervosa: Considering the role of negative urgency

ObjectiveEvidence implicates negative affect in the occurrence of binge/purge behaviors, although the extent to which theoretically relevant individual difference variables may impact this association remains unclear. Negative urgency, the dispositional tendency to engage in rash action when experiencing negative affect, is a unique facet of impulsivity that may play a key role. Moreover, it was hypothesized that women with anorexia nervosa (AN) who are higher on measures of negative urgency, relative to those lower on negative urgency, would exhibit: 1) greater binge eating and purging frequencies on high negative affect days, and 2) a greater change in negative affect prior to and following binge eating and purging episodes.MethodWomen with AN (n = 82) completed a self-report measure of negative urgency and a 2-week ecological momentary assessment protocol in which they recorded binge eating, purging, and negative affect ratings.ResultsWomen with higher levels of negative urgency exhibited a greater frequency of binge eating and purging; however, in comparison to women low on negative urgency, they: 1) were more likely to binge eat on days corresponding with low-to-moderate negative affect (similar rates of binge eating were observed on high negative affect days), and 2) displayed substantially elevated levels of negative affect across time, and thus, smaller degrees of change in negative affect prior to and following binge eating and purging episodes.DiscussionNegative urgency underlies individual differences in the daily experience of negative affect. Women with AN who are high on negative urgency may have an increased propensity for binge eating and purging via a relatively persistent and heightened state of negative emotions.     

Regional cerebral blood flow in weight-restored anorexia nervosa: a preliminary study

Twenty-one individuals (19 females, two males) with teenage-onset anorexia nervosa (AN), 19 of whom were weight restored, were assessed using single-photon emission computed tomography (SPECT) 7 years after onset of AN, at a mean age of 22 years. For comparison we recruited a younger group without neuropsychiatric disorder (mean age 9:8 years; five females, four males) who underwent SPECT at follow-up after an operation for coarctation of the aorta or because of lymphatic leukaemia. Ethical considerations precluded the study of regional cerebral blood flow (rCBF) in participants with completely normal development. The group with AN showed marked hypoperfusion of temporal, parietal, occipital, and orbitofrontal lobes compared to the contrast group. rCBF was not correlated to body mass index in any of the groups. Results suggest that, even long after re-feeding has occurred, AN may be associated with moderate to severe cerebral blood flow hypoperfusion in the temporoparietal (or temporoparietooccipital) region and in the orbitofrontal region. A limitation of the study is that the young contrast group in this study could be expected to have a higher global rCBF than the group with AN. However, this should not significantly affect the relative values used in this study.     

Predictors of binge eating in restrictive anorexia nervosa patients in Italy

The aim of the present study was to investigate the predictive factors for the development of binge eating in restricting anorexia nervosa patients who underwent an outpatient treatment. The sample was a group of 168 patients with restricting anorexia nervosa, consecutively admitted to an outpatient unit. All the patients underwent a routine baseline assessment. Information regarding binge eating onset and duration of treatment was prospectively recorded in clinical records. Twenty-three patients developed binge episodes during outpatient treatment. High scores on the Eating Disorders Inventory body dissatisfaction subscale and early age at menarche significantly predict the risk of developing binge eating. High levels of ineffectiveness, as measured by the Eating Disorders Inventory, and early age at menarche are significant predictors of a shortened time to develop binge eating. The identification of subjects at risk for developing binge eating should be considered an important step for a successful treatment of restricting anorexic patients.     

Effect of age on regional cerebral blood flow patterns in Alzheimer's disease patients

The purpose of this study was to explore the influence of age on regional cerebral blood flow (rCBF) patterns in patients with Alzheimer's disease (AD). Single photon emission computed tomography (SPECT) was performed in 79 patients with AD, including 31 younger and 48 older patients divided according to age at examination (<70 and > or = 70 years), and the SPECT data were analyzed using three-dimensional stereotactic surface projection. Although no significant differences in severity and duration of disease between the two groups were found, there were some differences in rCBF patterns. Patients with younger AD had a more severe decrease of rCBF in the parietotemporal and posterior cingulate cortex, while patients with older AD had a more severe decrease of rCBF in the medial temporal region and medial frontal lobe. This observer-independent analysis of SPECT data provides an objective assessment of cortical rCBF abnormalities in patients with AD and is useful in demonstrating the differences in rCBF patterns between younger and older patients with AD.     

Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa

BACKGROUND: An abnormality in regional cerebral blood flow (rCBF) in anorexia nervosa (AN) patients has been reported. There are very few studies that have investigated the rCBF changes in the recovery process of AN. METHODS: For eight female AN patients, we performed (123)I-IMP single photon emission computed tomography (SPECT) and four psychological assessments (Eating Disorder Inventory (EDI), Eating Attitude Test (EAT), Self-Rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI)) both before and after inpatient-behavioral therapy. SPECT images were analyzed using statistical parametric mapping software. We also performed correlational analysis between rCBF and clinical variables. RESULTS: Following treatment, the patients showed significant body weight recovery. They showed significant improvement in EAT, SDS, STAI and a subscale of EDI - interoceptive awareness (IA) - but not in total EDI or other EDI subscales. Significant rCBF increases were observed in the precuneus, posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC) by the treatment. Significant correlation was observed between rCBF of right DLPFC and IA score before treatment. CONCLUSIONS: Changes of rCBF in right DLPFC, ACC, MPFC, PCC and precuneus were related to the AN recovery process and might be associated with improvement of IA following treatment.     

Regional cerebral blood flow changes in early-onset anorexia nervosa before and after weight gain

To investigate the changes of regional cerebral blood flow (rCBF) in early-onset anorexia nervosa (AN) before and after weight gain, we examined resting rCBF using single photon emission computed tomography (SPECT) with [¹²³I]iodoamphetamine (¹²³I-IMP). Ten female children with AN (mean age 13.2 years old) participated in this study. SPECT examinations were performed in all patients twice at the beginning of treatment and after weight gain. The mean body mass index (BMI) was changed from 13.1 to 16.6 during 4 months treatment period. Automatic voxel-based analysis of the images was carried out using statistical parametric mapping (SPM) software. Relatively increased rCBF in the bilateral parietal lobe and limbic lobe including the posterior cingulate cortex (PCC) were observed after weight gain in early-onset AN. There was no significant decrease in the rCBF after weight gain. A significant positive correlation was observed between BMI and rCBF in the right thalamus, right parietal lobe, and right cerebellum. These results suggested that weight gain during the process of recovery from early-onset AN might activate specific brain regions which are possibly relevant to the pathophysiological aspects of the disorder.     

Self-injurious behavior in anorexia nervosa

Recent reports have postulated the existence of two different types of self-injurious behavior: impulsive and compulsive. The aim of the present study is to analyze the dimensionality of self-injurious behavior and to study the link between self-injurious behavior and clinical features in anorexia nervosa. The study involved 236 consecutive patients with anorexia nervosa, diagnosed by DSM-IV criteria. Subjects were evaluated by means of a semistructured interview and self-reported questionnaires, such as the Eating Disorders Inventory and Hopkins Symptom Checklist. A principal component analysis was used to study the dimensionality of different types of self-injurious behavior, including purging. Our findings confirm the distinction between impulsive and compulsive self-injurious behavior. The dimensions appear to be represented as a continuum in both the anorexia nervosa diagnostic subgroups. A third distinct dimension emerged that included self-induced vomiting and laxative/diuretics abuse. Childhood sexual abuse and anxiety significantly predict the presence of impulsive self-injury, whereas obsessionality and age predict compulsive self-injury. The coexistence of a positive score on both dimensions of self-injurious behavior was the strongest predictor of treatment dropout. The present study highlights the importance of self-injurious behavior; it should be given due consideration in future outcome studies on anorexia nervosa     

Habitual binge/purge behavior influences circulating ghrelin levels in eating disorders

Previous studies have reported that fasting plasma ghrelin concentrations play an important role in the pathophysiology of eating disorders. The purpose of this study was to examine the relationship between plasma ghrelin levels and frequency of abnormal eating behaviors, nutritional parameters in eating disorders. Fasting blood samples were obtained in 40 female anorexia nervosa (AN) patients, 21 restricting type (AN-R) and 19 binge-eating/purging type (AN-BP), in 31 bulimia nervosa (BN) patients, 18 purging type (BN-P) and 13 non-purging type (BN-NP), in 15 female healthy volunteers (control) before the initiation of active treatment. The fasting plasma ghrelin concentrations in all subjects were negatively correlated with nutritional parameters such as body mass index, percent body fat and serum cholinesterase concentration. The mean plasma ghrelin level in BN-P was higher than that in both BN-NP and controls despite similar nutritional parameters. The plasma ghrelin levels in both AN-R and AN-BP did not differ from BN-P despite difference of nutritional parameters. For both AN-BP and BN-P patients with habitual binge/purge behavior, there were significant correlations among plasma ghrelin values, frequencies of binge/purge cycles and serum amylase values. In BN-NP, there were no significant correlations among plasma ghrelin values, frequencies of binge-eating episodes and serum amylase values. These results suggest that habitual binge/purge behavior may have some influence on circulating plasma ghrelin levels in both BN-P and AN-BP. Habitual binge/purge cycles with vomiting as opposed to binge-eating episodes without vomiting may have a greater influence on fasting plasma ghrelin concentration in eating disorders.     

Restricters who purge:Implications of purging behavior for psychopathology and classification of anorexia nervosa

The significance of purging behavior that occurs in the absence of binge eating in anorexia nervosa was examined. Fifty-two women with anorexia nervosa were divided into 3 groups: 26 nonpurging or “pure” restricters, 18 purging restricters, and 8 bulimic (or binge-and-purge) individuals. Results demonstrated that purging restricters, compared to nonpurging restricters, exhibited significantly more body distortion on the Body Distortion Questionnaire, weight concern on the Eating Disorder Inventory, external locus of control on the Rotter Locus of Control Scale, depression on the Beck Depression Inventory, and general psychopathology on the Minnesota Multiphasic Personality Inventory-2. There were no significant differences between nonpurging and purging restricters on the Family Environment Scale. Bulimic individuals did not show levels of psychopathology consistently as high as the purging restricter group. It was concluded that purging behavior in and of itself is a salient and valid marker for subtyping anorexia neruosa. Possible dqerences between groups in terms of etiology and tmatrnent approach are discussed.     

Comparison of regional cerebral blood flow in patients with eating disorders

We used single photon emission computed tomography (SPECT) with Tc-99m-HMPAO to examine the characteristics of regional cerebral blood flow (rCBF) in five patients with bulimia nervosa (BN), eight patients with anorexia nervosa (AN), and in nine healthy controls. The SPECT examinations were performed before and attar food intake stimulus, and the values of the corrected ratio (R) for rCBF in 10 cerebral cortical regions before (R_before) and after eating (R_after) were calculated. The asymmetry indices (AI) of the R values for the left and right side of each cortical region and the percent change from R_before to R_after (%change) were computed. In comparison with the other two groups, BN patients showed significantly higher R_before values in the bilateral inferior frontal and left temporal regions. The AN patients showed significantly lower R_before values in the left parietal region than the control group. There were no significant differences in R_after values among the three groups. The %change values in the AN group showed the greatest increase in 9 out of the 10 regions. In contrast to the positive values obtained from the 10 regions observed in the AN group, 5 out of the 10 regions in the BN group showed negative values. Among the three groups, significant differences in %change were observed on both sides of the inferior frontal, temporal, parietal, and occipital regions. These findings indicate that differences in cerebral function of BN and AN patients can be characterized through SPECT imaging.     

Guided self-help for binge eating/purging anorexia nervosa before inpatient treatment

Abstract

The goal of this study was to develop a cognitive–behavioral self-help manual for anorexia nervosa. Patients diagnosed with anorexia nervosa (N=102), binge eating/purging type (AN-B/P), were consecutively assigned to one of two conditions: 6-week manualized guided self-help or a wait-list control. All patients thereafter received inpatient treatment in a hospital for behavioral medicine. The primary outcome variable was the number of days in inpatient treatment. Secondary outcome variables were measures of psychopathology. Results showed that duration of inpatient treatment was significantly shorter (by 5.2 days) among participants receiving guided self-help. Body image, slimness ideal, general psychopathology, and some bulimic symptoms improved significantly during self-help. The authors conclude that, to increase effects of therapist-guided self-help in AN-B/P, additional variants of a self-help manual should be tried in different therapeutic settings.     

Differences in regional grey matter volumes in currently ill patients with anorexia nervosa

Neurobiological findings in anorexia nervosa (AN) are inconsistent, including differences in regional grey matter volumes. Methodological limitations often contribute to the inconsistencies reported. The aim of this study was to improve on these methodologies by utilising voxel‐based morphometry (VBM) analysis with the use of diffeomorphic anatomic registration through an exponentiated lie algebra algorithm (DARTEL), in a relatively large group of individuals with AN. Twenty‐six individuals with AN and 27 healthy controls underwent a T1‐weighted magnetic resonance imaging (MRI) scan. AN participants were found to have reduced grey matter volumes in a number of areas including regions of the basal ganglia (including the ventral striatum), and parietal and temporal cortices. Body mass index (BMI) and global scores on the Eating Disorder Examination Questionnaire (EDE‐Q) were also found to correlate with grey matter volumes in a region of the brainstem (including the substantia nigra and ventral tegmental area) in AN, and predicted 56% of the variance in grey matter volumes in this area. The brain regions associated with grey matter reductions in AN are consistent with regions responsible for cognitive deficits associated with the illness including anhedonia, deficits in affect perception and saccadic eye movement abnormalities. Overall, the findings suggest reduced grey matter volumes in AN that are associated with eating disorder symptomatology.     

Threshold of regional cerebral blood flow for infarction in patients with acute cerebral ischemia

Threshold of regional cerebral blood flow (rCBF) for cerebral tissue survival in relation to time was studied in patients with acute cerebral ischemia with xenon-enhanced computed tomography (XeCT). Case 1: A 58-year-old man with right hemiparesis, total aphasia and a high intensity area of 1 cm 2 in the left insula on diffusion weighted image underwent XeCT CBF study before and after intra-arterial local thrombolytic therapy (IALT) on the occluded middle cerebral artery (MCA) 4 hours and 7 hours after stroke onset, respectively. Case 2: A 65-year-old woman with recurrent transient ischemic attacks (TIAs) caused by severe stenosis of the left MCA underwent XeCT CBF study 5 hours after onset of the last attack. XeCT was conducted by 5-min wash-in method. In Case 1 the rCBF in the pre-IALT MCA territory was 4 to 19 ml/100 g/min. The area where rCBF in the post-IALT increased to above 15 ml/100g/min were saved, but the other area where it remained in the 9 to 14 ml/100 g/min evolved into infarct on subsequent CT scan/MR (magnetic resonance) imaging. The patient was discharged with only mild motor dysphasia. In Case 2 the left corona radiata showed rCBF of 7 ml/100 g/min and this area evolved into infarct on MR imaging. The patient was discharged home with right hemiparesis. Our results showed validity of the rCBF threshold in acute cerebral ischemia reported by Jones et al. Residual rCBF in the acute stage of cerebral ischemic stroke can predict the fate of the lesion.