Understanding the genetics and epigenetics of bulimia nervosa/bulimia spectrum disorder and comorbid borderline personality disorder (BN/BSD-BPD): a systematic review.
ABSTRACT: PURPOSE:To evaluate and understand the genetic and epigenetic basis of bulimia nervosa/bulimia spectrum disorder and comorbid borderline personality disorder (BN/BSD-BPD). METHODS:The present systematic review was conducted in accordance to PRISMA guidelines. Advanced systematic searches of Medline, EMBASE, PsychINFO, Web of Science, Scopus, CINHAL plus, and the Cochrane Library were conducted using the search terms 'bulimia nervosa', 'bulimia spectrum disorder', 'borderline personality disorder', 'genes', and 'genetics'. The search strategy garnered seven studies for inclusion in the present review. RESULTS:Women with BN/BSD-BPD had significantly lower serotonin and monoamine oxidise activity compared to women with BN/BSD or healthy controls (HC). As well, women with BN/BSD-BPD displayed elevated methylation of the dopamine receptor gene promoter, brain-derived neurotrophic factor, and changes in the methylation of the glucocorticoid receptor gene promoter (NR3C1) compared to women with BN/BSD and HC. The results also demonstrated that rates of childhood sexual abuse and childhood physical abuse are higher in those with BN/BSD-BPD than those with BN/BSD and HC, and that these types of abuse are often correlated with the methylation differences seen in BN/BSD-BPD women. CONCLUSION:Due to the differences observed between individuals with BN/BSD-BPD and those with BN/BSD and HC a genetic/epigenetic aetiological model of BN/BSD-BPD was developed and is proposed in this review. This evidence-based model visually illustrates the current state of the field and draws attention to the need for subsequent research.
Project description:BACKGROUND: Previous fMRI studies show that women with eating disorders (ED) have differential neural activation to viewing food images. However, despite clinical differences in their responses to food, differential neural activation to thinking about eating food, between women with anorexia nervosa (AN) and bulimia nervosa (BN) is not known. METHODS: We compare 50 women (8 with BN, 18 with AN and 24 age-matched healthy controls [HC]) while they view food images during functional Magnetic Resonance Imaging (fMRI). RESULTS: In response to food (vs non-food) images, women with BN showed greater neural activation in the visual cortex, right dorsolateral prefrontal cortex, right insular cortex and precentral gyrus, women with AN showed greater activation in the right dorsolateral prefrontal cortex, cerebellum and right precuneus. HC women activated the cerebellum, right insular cortex, right medial temporal lobe and left caudate. Direct comparisons revealed that compared to HC, the BN group showed relative deactivation in the bilateral superior temporal gyrus/insula, and visual cortex, and compared to AN had relative deactivation in the parietal lobe and dorsal posterior cingulate cortex, but greater activation in the caudate, superior temporal gyrus, right insula and supplementary motor area. CONCLUSIONS: Women with AN and BN activate top-down cognitive control in response to food images, yet women with BN have increased activation in reward and somatosensory regions, which might impinge on cognitive control over food consumption and binge eating.
Project description:Background:A substantial rate of patients with bulimia nervosa (BN) also suffer from Borderline personality disorder (BN?+?BPD). It is widely unknown how these comorbid patients with BN?+?BPD present and respond to inpatient treatment. Aims of the study were to examine (1) specific characteristics of patients with BN?+?BPD at admission, discharge, and during treatment, and (2) differential effects of inpatient treatment for BN vs. BN?+?BPD. Method:We analyzed routine data of inpatients admitted for the treatment of BN between 2013 and 2017 in a specialized hospital for eating disorders. (1) Cross-sectional differences were examined with independent t-tests and ?2-tests; and (2) treatment effects pertaining to eating disorders symptoms, depression, psychosocial functioning and general psychopathology with repeated measures analysis of variance. Results:Of 1298 inpatients (96% female), 13.2% also had a diagnosis of BPD. (1) Patients with BN?+?BPD had more previous inpatient treatments (p =?0.001), had a longer length of stay (p =?0.003), gained more weight during treatment (p =?0.006), and were more often irregularly discharged (p =?0.018) as well as rated as unfit to work at discharge (p =?0.003). (2) Both groups improved in all examined variables (all main effects treatment p <? 0.001). Patients with BN?+?BPD showed worse symptoms aggregated across admission and discharge (all main effects diagnosis p <? 0.05). Patients with BN?+?BPD showed smaller improvements (interaction treatment×discharge) in depressive symptoms (p =?0.018), perfectionism (p =?0.009), and asceticism (p =?0.035) and discharge scores mostly lay in the range of the admission scores of the BN-only group. Conclusion:Patients with BN?+?BPD improve during intense and specialized inpatient treatment, yet, retain pronounced impairment at discharge despite longer treatment. Treatment needs to be improved and should focus on transdiagnostic symptoms of BN and BPD.
Project description:Purging disorder (PD) has been included as a named condition within the DSM-5 category of Other Specified Feeding or Eating Disorder and differs from bulimia nervosa (BN) in the absence of binge-eating episodes. The current study evaluated satiation through behavioral and self-report measures to understand how this construct may explain distinct symptom presentations for bulimia nervosa (BN) and purging disorder (PD). Women (N?=?119) were recruited from the community if they met DSM-5 criteria for BN (n?=?57), PD (n?=?31), or were free of eating pathology (n?=?31 controls). Participants completed structured clinical interviews and questionnaires and an ad lib test meal during which they provided reports of subjective states. Significant group differences were found on self-reported symptoms, ad lib test meal intake, and subjective responses to food intake between individuals with eating disorders and controls and between BN and PD. Further, ad lib intake was associated with self-reported frequency and size of binge episodes. In a multivariable model, the amount of food consumed during binges as reported during clinical interviews predicted amount of food consumed during the ad lib test meal, controlling for other binge-related variables. Satiation deficits distinguish BN from PD and appear to be specifically linked to the size of binge episodes. Future work should expand exploration of physiological bases of these differences to contribute to novel interventions.
Project description:BACKGROUND: Alterations in the resting-state functional connectivity (rs-FC) of several brain networks have been demonstrated in eating disorders. However, very few studies are currently available on brain network dysfunctions in bulimia nervosa (BN). The somatosensory network is central in processing body-related stimuli and it may be altered in BN. The present study therefore aimed to investigate rs-FC in the somatosensory network in bulimic women. METHODS: Sixteen medication-free women with BN (age?=?23?±?5?years) and 18 matched controls (age?=?23?±?3?years) underwent a functional magnetic resonance resting-state scan and assessment of eating disorder symptoms. Within-network and seed-based functional connectivity analyses were conducted to assess rs-FC within the somatosensory network and to other areas of the brain. RESULTS: Bulimia nervosa patients showed a decreased rs-FC both within the somatosensory network (t?=?9.0, df?=?1, P?=?0.005) and with posterior cingulate cortex and two visual areas (the right middle occipital gyrus and the right cuneus) (P?=?0.05 corrected for multiple comparison). The rs-FC of the left paracentral lobule with the right middle occipital gyrus correlated with psychopathology measures like bulimia (r?=?-0.4; P?=?0.02) and interoceptive awareness (r?=?-0.4; P?=?0.01). Analyses were conducted using age, BMI (body mass index), and depressive symptoms as covariates. CONCLUSION: Our findings show a specific alteration of the rs-FC of the somatosensory cortex in BN patients, which correlates with eating disorder symptoms. The region in the right middle occipital gyrus is implicated in body processing and is known as extrastriate body area (EBA). The connectivity between the somatosensory cortex and the EBA might be related to dysfunctions in body image processing. The results should be considered preliminary due to the small sample size.
Project description:Altered inhibitory control has been implicated in the development and maintenance of eating disorders (ED), however it is unclear how different types of inhibitory control are affected across the EDs. We explored whether individuals with bulimia nervosa (BN), binge eating disorder (BED) and anorexia nervosa (AN) differed from healthy individuals (HC) on two types of motor inhibitory control: proactive inhibition (related to the preparation/initiation of a response) and reactive inhibition (withholding a response in reaction to a signal). Ninety-four women (28 AN, 27 BN, 11 BED, 28 HC) completed two neuropsychological tasks (a cued reaction time task and a stop signal task), and questionnaires assessing clinical variables, mood, anxiety, and inhibitory control. Self-reported inhibitory control was poorer in women with BN compared to the HC and AN groups, but greater in women with AN compared to all other groups. However, no group differences in reactive inhibition were observed. Proactive inhibition was augmented in women with AN compared to HC, and this was related to self-reported intolerance of uncertainty. The findings suggest that proactive inhibition may be a relevant target for behavioural interventions for AN, and call for further research into the relationship between intolerance of uncertainty and proactive inhibition.
Project description:There is a paucity of randomized clinical trials (RCTs) for adolescents with bulimia nervosa (BN). Prior studies suggest cognitive-behavioral therapy adapted for adolescents (CBT-A) and family-based treatment for adolescent bulimia nervosa (FBT-BN) could be effective for this patient population. The objective of this study was to compare the relative efficacy of these 2 specific therapies, FBT-BN and CBT-A. In addition, a smaller participant group was randomized to a nonspecific treatment (supportive psychotherapy [SPT]), whose data were to be used if there were no differences between FBT-BN and CBT-A at end of treatment.This 2-site (Chicago and Stanford) randomized controlled trial included 130 participants (aged 12-18 years) meeting DSM-IV criteria for BN or partial BN (binge eating and purging once or more per week for 6 months). Outcomes were assessed at baseline, end of treatment, and 6 and 12 months posttreatment. Treatments involved 18 outpatient sessions over 6 months. The primary outcome was defined as abstinence from binge eating and purging for 4 weeks before assessment, using the Eating Disorder Examination.Participants in FBT-BN achieved higher abstinence rates than in CBT-A at end of treatment (39% versus 20%; p = .040, number needed to treat [NNT] = 5) and at 6-month follow-up (44% versus 25%; p = .030, NNT = 5). Abstinence rates between these 2 groups did not differ statistically at 12-month follow-up (49% versus 32%; p = .130, NNT = 6).In this study, FBT-BN was more effective in promoting abstinence from binge eating and purging than CBT-A in adolescent BN at end of treatment and 6-month follow-up. By 12-month follow-up, there were no statistically significant differences between the 2 treatments.Study of Treatment for Adolescents With Bulimia Nervosa; http://clinicaltrials.gov/; NCT00879151.
Project description:Is starvation in anorexia nervosa (AN) or overeating in bulimia nervosa (BN) a form of addiction? Alternatively, why are individuals with BN more vulnerable and individuals with AN protected from substance abuse? Such questions have been generated by recent studies suggesting that there are overlapping neural circuits for foods and drugs of abuse. To determine whether a shared neurobiology contributes to eating disorders and substance abuse, this review focused on imaging studies that investigated response to tastes of food and tasks designed to characterize reward and behavioral inhibition in AN and BN. BN and those with substance abuse disorders may share dopamine D2 receptor-related vulnerabilities, and opposite findings may contribute to "protection" from substance abuse in AN. Moreover, imaging studies provide insights into executive corticostriatal processes related to extraordinary inhibition and self-control in AN and diminished inhibitory self-control in BN that may influence the rewarding aspect of palatable foods and likely other consummatory behaviors. AN and BN tend to have premorbid traits, such as perfectionism and anxiety that make them vulnerable to using extremes of food ingestion, which serve to reduce negative mood states. Dysregulation within and/or between limbic and executive corticostriatal circuits contributes to such symptoms. Limited data support the hypothesis that reward and inhibitory processes may contribute to symptoms in eating disorders and addictive disorders, but little is known about the molecular biology of such mechanisms in terms of shared or independent processes.
Project description:OBJECTIVE:Recent evidence has suggested an increased rate of comorbid ADHD and subclinical attentional impairments in bulimia nervosa (BN) patients. However, little is known regarding the underlying neural mechanisms of attentional functions in BN. METHOD:Twenty BN patients and twenty age- and weight-matched healthy controls (HC) were investigated using a modified version of the Attention Network Task (ANT) in an fMRI study. This design enabled an investigation of the neural mechanisms associated with the three attention networks involved in alerting, reorienting and executive attention. RESULTS:The BN patients showed hyperactivation in parieto-occipital regions and reduced deactivation of default-mode-network (DMN) areas during alerting compared with HCs. Posterior cingulate activation during alerting correlated with the severity of eating-disorder symptoms within the patient group. Conversely, BN patients showed hypoactivation during reorienting and executive attention in anterior cingulate regions, the temporo-parietal junction (TPJ) and parahippocampus compared with HCs, which was negatively associated with global ADHD symptoms and impulsivity, respectively. DISCUSSION:Our findings demonstrate altered brain mechanisms in BN associated with all three attentional networks. Failure to deactivate the DMN and increased parieto-occipital activation required for alerting might be associated with a constant preoccupation with food or body image-related thoughts. Hypoactivation of executive control networks and TPJ might increase the likelihood of inattentive and impulsive behaviors and poor emotion regulation. Thus, dysfunction in the attentional network in BN goes beyond an altered executive attentional domain and needs to be considered in the diagnosis and treatment of BN.
Project description:OBJECTIVE:Knowledge about physical fitness in women with bulimia nervosa (BN) or binge-eating disorder (BED) is sparse. Previous studies have measured physical activity largely through self-report, and physical fitness variables are mainly restricted to body mass index (BMI) and bone mineral density. We expanded the current knowledge in these groups by including a wider range of physical fitness indicators and objective measures of physical activity, assessed the influence of a history of anorexia nervosa (AN), and evaluated predictive variables for physical fitness. METHOD:Physical activity, blood pressure, cardiorespiratory fitness (CRF), muscle strength, body composition, and bone mineral density were measured in 156 women with BN or BED, with mean (SD) age 28.4 years (5.7) and BMI 25.3 (4.8) kg m-2 . RESULTS:Level of physical activity was higher than normative levels, still <50% met the official physical activity recommendation. Fitness in women with BN were on an average comparable with recommendations or normative levels, while women with BED had lower CRF and higher BMI, VAT, and body fat percentage. We found 10-12% with masked obesity. A history of AN did not predict current physical fitness, still values for current body composition were lower when comparing those with history of AN to those with no such history. DISCUSSION:Overall, participants with BN or BED displayed adequate physical fitness; however, a high number had unfavorable CRF and body composition. This finding calls for inclusion of physical fitness in routine clinical examinations and guided physical activity and dietary recommendations in the treatment of BN and BED.
Project description:Bulimia nervosa (BN) shares central features with substance-related and addictive disorders. The metabotropic glutamate receptor subtype 5 (mGlu5) plays an important role in addiction. Based on similarities between binge eating and substance-related and addictive disorders, we investigated mGlu5 in vivo in 15 female subjects with BN and 15 matched controls. We measured mGlu5 distribution volume ratio (DVR) with positron emission tomography (PET) using [11?C]ABP688. In BN mGlu5 DVR was higher in the anterior cingulate cortex (ACC), subgenual prefrontal cortex, and straight gyrus (p?<?0.05). In BN, higher mGlu5 DVR in various brain regions, including ACC, pallidum, putamen, and caudate, positively correlated with "maturity fears" as assessed using the Eating Disorder Inventory-2 (p?<?0.05). In BN and controls, smokers had globally decreased mGlu5 DVR. We present the first evidence for increased mGlu5 DVR in BN. Our findings suggest that pharmacological agents inhibiting mGlu5 might have a therapeutic potential in BN.