White matter microstructure in women with acute and remitted anorexia nervosa: an exploratory neuroimaging study

Anorexia nervosa (AN) is a highly heritable psychiatric disorder characterized by starvation and emaciation and associated with changes in brain structure. The precise nature of these changes remains unclear, as does their developmental time course and capacity for reversal with weight restoration. In this exploratory neuroimaging study, we sought to characterize changes in white matter microstructure in women with acute and remitted AN. Diffusion-weighted MRI data was collected from underweight women with a current diagnosis of AN (acAN: n?=?23), weight-recovered women with a past diagnosis of AN (recAN: n?=?23), and age-matched healthy control women (HC: n?=?24). Image processing and analysis were performed with Tract-Based Spatial Statistics, part of FSL, and group differences in voxelwise, brain-wide fractional anisotropy (FA) and mean diffusivity (MD), indices of white matter microstructure, were tested with nonparametric permutation and threshold-free cluster enhancement. No significant main effect of group on FA was identified. A significant main effect of group on MD was observed in a large cluster covering 9.2% of white matter and including substantial portions of the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus, and post hoc analyses revealed similar effects of group on axial diffusivity (AD) and radial diffusivity (RD). Clusterwise MD was significantly higher in acAN participants (+3.8%) and recAN participants (+2.9%) than healthy controls, and the same was true for clusterwise AD and RD. Trait-based increases in diffusivity, changes in which have been associated with atypical myelination and impaired axon integrity, suggest a link between altered white matter microstructure and vulnerability to AN, and evidence of reduced oligodendrocyte density in AN provides further support for this hypothesis. Potential mechanisms of action include atypical neurodevelopment and systemic inflammation.

     

Altered fimbria-fornix white matter integrity in anorexia nervosa predicts harm avoidance

The eating disorder anorexia nervosa (AN) is associated with high anxiety. The brain mechanisms that drive those behaviors are unknown. In this study we wanted to test whether brain white matter (WM) integrity is altered in AN, and related to heightened anxiety. Sixteen adult women with AN (mean age 24 ± 7 years) and 17 healthy control women (CW, mean age 25 ± 4 years) underwent diffusion tensor imaging (DTI) of the brain. The DTI brain images were used to calculate the fractional anisotropy (FA) of WM tracts, which is a measure for WM integrity. AN individuals compared to CW showed clusters of significantly reduced FA (p < 0.05, corrected) in the bilateral fimbria-fornix and the fronto-occipital fasciculus, as well as the posterior cingulum WM. In the AN group, Harm Avoidance was predicted by FA in the left and right fimbria-fornix. Those findings were not due to WM volume deficits in AN. This study indicates that WM integrity is abnormal in AN in limbic and association pathways, which could contribute to disturbed feeding, emotion processing and body perception in AN. The prediction of Harm Avoidance in AN by fimbria-fornix WM integrity suggests that this pathway may be mechanistically involved in high anxiety in AN.     

Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa

Abnormalities in brain metabolism have not been consistently well localized in anorexia nervosa (AN), and effects of specific therapies on these functional abnormalities have not been studied. Androgen replacement therapy improves mood, well-being and cognitive function in men with androgen deficiency. We therefore hypothesized that women with AN and relative androgen deficiency would exhibit regional brain hypometabolism compared with healthy controls, and that low-dose physiologic androgen replacement would attenuate the hypometabolism in some of these brain loci. We used FDG PET and statistical parametric mapping methods to investigate regional brain glucose metabolism in (1) 14 women with AN and 20 healthy control subjects of similar mean age and (2) women with AN after randomization to low-dose replacement testosterone therapy or placebo. Cerebral metabolism was decreased in the posterior cingulate, pregenual anterior cingulate, left middle temporal, right superior temporal, and left dorsolateral prefrontal cortex in the AN group compared with controls. In AN patients receiving testosterone, cerebral metabolism increased in the posterior cingulate, subgenual anterior cingulate, premotor cortex, right caudate and right parietal lobes. In conclusion, our data demonstrate distinct loci of regional brain hypometabolism in women with AN compared with controls. Moreover, abnormalities in one of these regions-the posterior cingulate cortex-were attenuated towards normal with low-dose testosterone replacement therapy. Further study is warranted to replicate these findings, as well as to determine their physiological and clinical significance.     

Sexuality of women with anorexia nervosa

The sexual development and life of 30 adult women with anorexia nervosa and of 50 control women was investigated using a structured interview and 3 sexological questionnaires. Heterosexual development was found to be normal in the initial stages, but psychosexual adaptation in adulthood was impaired. Primary or secondary insufficiencies of sexual life were found for 80% of the anorectic patients. Biological and psychosocial factors may participate in this unfavourable state. Discussion of sexual problems should be part of the process of treating women with anorexia nervosa.     

Temperament and character in women with anorexia nervosa

The present study examined temperament differences among anorexia nervosa (AN) subtypes and community controls, as well as the effect of body weight on personality traits in women with AN. Temperament and Character Inventory (TCI) scores were compared between 146 women with restrictor-type AN (RAN), 117 women with purging-type AN (PAN), 60 women with binge/purge-type AN (BAN), and 827 community control women (CW) obtained from an archival normative database. Women with AN scored significantly higher on harm avoidance and significantly lower on cooperativeness than CW. Subtype analyses revealed that women with RAN and PAN reported the lowest novelty seeking, RAN women the highest persistence and self-directedness, and PAN women the highest harm avoidance. Body mass index had a nominal effect on subgroup differences, suggesting that personality disturbances are independent of body weight. Findings suggest that certain facets of temperament differ markedly between women with AN, regardless of diagnostic subtype, and controls. More subtle temperament and character differences that were independent of body weight emerged that distinguish among subtypes of AN.     

CSF neurochemistry of women with anorexia nervosa and normal women

CSF tyrosine, tryptophan, 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), gamma-aminobutyric acid, choline, and calcium were compared in 33 anorexic and 14 normal women. The only significant difference between groups was a lower tyrosine level in the anorexic patients; their MHPG level was nonsignificantly higher. No significant group differences in body weight or depressive subgroup were found. HVA levels were positively related to body weight, and choline was negatively correlated with anorexia severity. The role of tyrosine requires further research, but these findings do suggest that HVA and choline increase with some recovery measures and MHPG is increased with this illness.     

Autonomic nervous system function in women with anorexia nervosa

Clinical Autonomic Research - Abnormalities in autonomic function have been observed in people with anorexia nervosa. However, the majority of investigations have utilised heart rate variability as...     

Plasma agouti-related protein levels in women with anorexia nervosa

Agouti-related protein (AGRP) is the competitive antagonist of alpha-melanocyte stimulating hormone (alpha-MSH) located at melanocortin receptors 3 and 4 (MC3R and MC4R), and also acts as an MC4R inverse agonist. Hypothalamic AGRP controls food intake and body weight in rodents. It has also been found in human plasma. To study the possibility of disturbances in melanocortin receptor-related peptides in eating disorders, plasma AGRP, alpha-MSH, and leptin levels were measured in 18 female patients with anorexia nervosa (AN) (age, 23.5+/-7.1 yr; body mass index (BMI) 14.5+/-1.8 kg/m(2)) and 17 age-matched female controls (age, 25.8+/-3.9 yr; BMI 20.2+/-1.6 kg/m(2)). Blood samples were collected after overnight fasting, and plasma peptides levels were measured using ELISA. Plasma AGRP levels increased significantly in AN patients when compared with controls (P<0.01) while plasma alpha-MSH levels were not significantly different. Plasma leptin levels decreased significantly in AN patients when compared with controls (P<0.001). In addition, plasma AGRP levels were negatively correlated with leptin (r=-0.41, P<0.01) and BMI (r=-0.40, P<0.05) in all subjects. In conclusion, plasma AGRP elevation may be related to energy homeostasis disturbance in AN, and in addition to leptin, peripheral AGRP levels could be used as a nutritional marker in AN patients.     

Correlates of sexual abuse in women with anorexia nervosa and bulimia nervosa.

Of 184 female outpatients meeting the DSM-III-R criteria, for anorexia nervosa, bulimia nervosa, or anorexia nervosa with bulimia, approximately 25% reported previous sexual abuse. Furthermore, previous sexual abuse was associated with greater psychological disturbance, measured by the Eating Disorder Inventory and Eating Attitudes Test. Sexual functioning did not differ among women who did or did not report sexual abuse. This finding suggests that sexual abuse or its correlates may affect severity rather than type of eating disorder.     

Changes in skeletal muscles of young women with anorexia nervosa

Summary Biopsies from four young women with advanced anorexia nervosa were examined to investigate the effect of malnutrition on skeletal muscles. None of the patients showed signs of neuromuscular disease and all were physically active at the time of examination.Cryostat sections from the vastus lateralis muscle were stained with hematoxylin-azophloxin-safran and with stains for myofibrillar ATP-ase activity. In addition to routine examination of the sections, the size and distribution of the type 1 and type 2 fibres were calculated by means of a Kontron Digiplan MOP 02.Routine stained sections showed a small grouped atrophy in three cases and a more diffuse atrophy in the fourth. Enzyme histochemical stains revealed a distinct type 2 atrophy, a finding which should serve to distinguish the changes of pure malnutrition from those of conventional denervation.Exact measurements confirmed the predominant type 2 atrophy but showed definite atrophy also of the type 1 fibres. Compared with normal controls the type 1 fibres were reduced by 46% and the type 2 fibres by 75%. These findings are largely in agreement with the recent observations by Essén et al. (1981) on anorexia nervosa. However, in contrast to Essén et al. we did not find any change in the numerical distribution of the fibre types, especially no increase in type 1 fibres. Thus, we could not confirm the hypotheses of a conversion of the fibre types in cachexia.     

The possible selves of adult women with anorexia nervosa

Adopting the construct of possible selves, which are conceptions of our selves in future situations, the objective of this study was to investigate how anorexia patients differ from a non-clinical control group in their conceptions of the future on qualitative content, and the four quantitative dimensions positive and negative emotional valence, and beliefs about probability and controllability. The Possible Selves Statements Test was employed. Participants presented 14 possible selves by completing the question "I can see myself …" and rating each possible self on the 4 dimensions. The patients reported a larger number of negative possible selves, with higher negative valence, often seeing future everyday situations as negative, whereas the control group saw similar situations as positive. The anorexia patients also reported negative possible selves with high controllability and high probability in relation to such situations and in some cases rated recovery from anorexia with a negative valence. Clinical implications are discussed.     

Abnormal white matter microstructure along the thalamus fiber pathways in women with primary dysmenorrhea

Brain Imaging and Behavior - Primary dysmenorrhea (PDM) is a cyclic menstrual pain in the absence of pelvic anomalies, and women with PDM have an increased sensitivity to pain than the internal and...     

Bone mineral density and anorexia nervosa in women

OBJECTIVE: A review of reports of reduced bone mineral density in women with anorexia nervosa was undertaken in order to profile specific risk factors, which could then be used as the basis for suggestions for future research and treatment. METHOD: Thirteen research studies and four case studies of reduced bone mineral density and fractures in women with anorexia nervosa were reviewed. The relationships between bone mineral density and amenorrhea, estrogen, calcium intake, physical activity, parathyroid hormone, alkaline phosphatase, 1,25-dihydroxyvitamin D, cortisol, and growth hormone were examined in the reports of these studies and other reports of altered physiology during anorexia nervosa. RESULTS: The average spinal, radial, and femoral bone mineral density in anorexic women was significantly lower than it was in normal control subjects. Concurrent with the low intake of nutrients by individuals with anorexia nervosa, low body weight, early onset and long duration of amenorrhea, low calcium intake, reduced physical activity, and hypercortisolism appeared more likely to contribute to decreased bone mineral density than did other abnormal aspects of the disorder. CONCLUSIONS: Future research needs to address how such factors as amenorrhea and hypercortisolism affect bone mineral density in anorexia nervosa. Since no controlled trials of estrogen replacement or calcium supplementation in anorexia nervosa have been reported, the proper treatment for decreased bone mineral density is not known. However, the most obviously important intervention is to encourage medical stabilization and weight gain.     

Sleep-wake monitoring in women suffering from anorexia nervosa

There is evidence that some Anorexia Nervosa (AN) patients have sleep abnormalities. No studies of their sleep-wake cycles in a natural environment have yet been reported. The purpose of this study was to evaluate an objective and subjective sleep-wake cycle of AN patients compared to a healthy age-equated control group (CON). Twenty-one AN female and sixteen CON female subjects were recruited. Sleep-wake patterns were monitored using ambulatory monitoring mini-actigraphs for one week. Each subject completed self-report questionnaires. The self-report questionnaires revealed significantly more sleep disturbances in AN than CON, whereas the ambulatory sleep data revealed no significant differences between the two groups in sleep-wake cycle.     

Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa

Background: Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. Methods: We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. Results: We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Limitations: Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Conclusion: Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with interoceptive signalling of one's internal state of well-being, with important relations between brain activity and homeostatic and hedonic aspects of appetite. Our findings give novel evidence of disruption in neurobiological circuits and stress the importance of examining both state and trait characteristics in the investigation of brain phenotypes in individuals with anorexia nervosa.     

Preoccupation with detail contributes to poor abstraction in women with anorexia nervosa

The present study investigated preoccupation with detail as a potential mechanism underlying poor abstraction in anorexia nervosa (AN). Abstract thinking performance of 24 women with AN (16-31 years) was compared against that of 24 healthy controls matched for age, education and socio-economic status, using the Object Assembly subtest of the WAIS III. Participants also completed measures of two indices of preoccupation with detail: field dependence-independence (Group Embedded Figures Test) and obsessionality (Leyton Obsessional Inventory). Perfectionism (Perfectionism subscale of the EDI-II) and mental rigidity (Trail Making Test), sub-components of obsessionality, were also measured. Women with AN showed a significant deficit in abstract thinking performance, which could not be explained by a more general intellectual deficit or diminished information processing speed. The AN sample also showed a greater preoccupation with detail relative to the control group. Controlling for preoccupation with detail reduced the group difference in abstract thinking to non-significance. However, only field dependence-independence contributed significantly to the relationship between group membership and abstract thinking performance. Thus, poor abstract thinking in AN appears to be at least partly attributable to a field-independent cognitive style, characterised by a bias towards focusing on detail at the expense of considering the gestalt.     

Equivalent disruption of regional white matter microstructure in ageing healthy men and women

Diffusion tensor imaging was used to measure regional differences in brain white matter microstructure (intravoxel coherence) and macrostructure (intervoxel coherence) and age-related differences between men and women. Neuropsychiatrically healthy men and women, spanning the adult age range, showed the same pattern of variation in regional white matter coherence. The greatest coherence measured was in corpus callosum, where commissural fibers have one primary orientation, lower in the centrum semiovale, where fibers cross from multiple axes, and lowest in pericallosal areas, where fibers weave and interstitial fluid commonly pools. Age-related declines in intravoxel coherence was equally strong and strikingly similar in men and women, with evidence for greater age-dependent deterioration in frontal than parietal regions. Degree of regional white matter coherence correlated with gait, balance, and interhemispheric transfer test scores.     

Sexual dysfunction in women with anorexia nervosa: Nature and treatment

This paper discusses sexual dysfunction in females with anorexia nervosa. The presence of such dysfunction in these patients has been known for a long time. The links between these disorders are reviewed. The possible explanations of these links are commented on. The clinical presentations are described, and therapeutic approaches are explored. The special considerations needed in treatment are highlighted. Some illustrative case examples are given.