Kamryn T. Eddy

Amygdala–frontal connectivity during emotion regulation

Successful control of affect partly depends on the capacity to modulate negative emotional responses through the use of cognitive strategies (i.e., reappraisal). Recent studies suggest the involvement of frontal cortical regions in the modulation of amygdala reactivity and the mediation of effective emotion regulation. However, within-subject inter-regional connectivity between amygdala and prefrontal cortex in the context of affect regulation is unknown. Here, using psychophysiological interaction analyses of functional magnetic resonance imaging data, we show that activity in specific areas of the frontal cortex (dorsolateral, dorsal medial, anterior cingulate, orbital) covaries with amygdala activity and that this functional connectivity is dependent on the reappraisal task. Moreover, strength of amygdala coupling with orbitofrontal cortex and dorsal medial prefrontal cortex predicts the extent of attenuation of negative affect following reappraisal. These findings highlight the importance of functional connectivity within limbic-frontal circuitry during emotion regulation.

A Longitudinal Investigation of Mortality in Anorexia Nervosa and Bulimia Nervosa

OBJECTIVE Although anorexia nervosa has a high mortality rate, our understanding of the timing and predictors of mortality in eating disorders is limited. The authors investigated mortality in a long-term study of patients with eating disorders. METHOD Beginning in 1987, 246 treatment-seeking female patients with anorexia nervosa or bulimia nervosa were interviewed every 6 months for a median of 9.5 years to obtain weekly ratings of eating disorder symptoms, comorbidity, treatment participation, and psychosocial functioning. From January 2007 to December 2010 (median follow-up of 20 years), vital status was ascertained with a National Death Index search. RESULTS Sixteen deaths (6.5%) were recorded (lifetime anorexia nervosa, N=14; bulimia nervosa with no history of anorexia nervosa, N=2). The standardized mortality ratio was 4.37 (95% CI=2.4-7.3) for lifetime anorexia nervosa and 2.33 (95% CI=0.3-8.4) for bulimia nervosa with no history of anorexia nervosa. Risk of premature death among patients with lifetime anorexia nervosa peaked within the first 10 years of follow-up, resulting in a standardized mortality ratio of 7.7 (95% CI=3.7-14.2). The standardized mortality ratio varied by duration of illness and was 3.2 (95% CI=0.9-8.3) for patients with lifetime anorexia nervosa for 0 to 15 years (4/119 died), and 6.6 (95% CI=3.2-12.1) for those with lifetime anorexia nervosa for >15 to 30 years (10/67 died). Multivariate predictors of mortality included alcohol abuse, low body mass index, and poor social adjustment. CONCLUSIONS These findings highlight the need for early identification and intervention and suggest that a long duration of illness, substance abuse, low weight, and poor psychosocial functioning raise the risk for mortality in anorexia nervosa.

What predicts suicide attempts in women with eating disorders

BACKGROUND Suicide is a common cause of death in anorexia nervosa and suicide attempts occur often in both anorexia nervosa and bulimia nervosa. No studies have examined predictors of suicide attempts in a longitudinal study of eating disorders with frequent follow-up intervals. The objective of this study was to determine predictors of serious suicide attempts in women with eating disorders. METHOD In a prospective longitudinal study, women diagnosed with either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) were interviewed and assessed for suicide attempts and suicidal intent every 6-12 months over 8.6 years. RESULTS Fifteen percent of subjects reported at least one prospective suicide attempt over the course of the study. Significantly more anorexic (22.1%) than bulimic subjects (10.9%) made a suicide attempt. Multivariate analyses indicated that the unique predictors of suicide attempts for anorexia nervosa included the severity of both depressive symptoms and drug use over the course of the study. For bulimia nervosa, a history of drug use disorder at intake and the use of laxatives during the study significantly predicted suicide attempts. CONCLUSIONS Women with anorexia nervosa or bulimia nervosa are at considerable risk to attempt suicide. Clinicians should be aware of this risk, particularly in anorexic patients with substantial co-morbidity.

Depression and Eating Disorders: Treatment and Course

BACKGROUND We examined the course of major depressive disorder (MDD) and predictors of MDD recovery and relapse in a longitudinal sample of women with eating disorders (ED). METHODS 246 Boston-area women with DSM-IV anorexia nervosa-restricting (ANR; n=51), AN-binge/purge (ANBP; n=85), and bulimia nervosa (BN; n=110) were recruited between 1987 and 1991 and interviewed using the Eating Disorders Longitudinal Interval Follow-up Evaluation (LIFE-EAT-II) every 6-12 months for up to 12 years. 100 participants had MDD at study intake and 45 developed MDD during the study. Psychological functioning and treatment were assessed. RESULTS Times to MDD onset (1 week-4.3 years), recovery (8 weeks-8.7 years), and relapse (1 week-5.2 years) varied. 70% recovered from MDD, but 65% subsequently relapsed. ANR patients were significantly less likely to recover from MDD than ANBP patients (p=0.029). Better psychological functioning and history of MDD were associated with higher chance of MDD recovery. Higher baseline depressive severity and full recovery from ED were associated with greater likelihood of MDD relapse; increased weight loss was somewhat protective. Adequate antidepressant treatment was given to 72% of patients with MDD and generally continued after MDD recovery. Time on antidepressants did not predict MDD recovery (p=0.27) or relapse (p=0.26). LIMITATIONS Small ED diagnostic subgroups; lack of non-ED control group. CONCLUSIONS The course of MDD in EDs is protracted; MDD recovery may depend on ED type. Antidepressants did not impact likelihood of MDD recovery, nor protect against relapse, which may impact on treatment strategies for comorbid MDD and EDs.

Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosa.

CONTEXT Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans. OBJECTIVE The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry. DESIGN This was a cross-sectional study. SETTING The study was conducted at a clinical research center. PARTICIPANTS Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC). MEASURES Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal. RESULTS Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in fMRI activation in food motivation brain regions, including the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula. CONCLUSIONS Oxytocin may be involved in the pathophysiology of anorexia.

Leptin Levels Are Associated With Decreased Depressive Symptoms in Women Across the Weight Spectrum, Independent of Body Fat

Objective  Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite‐regulating hormones may have opposing effects on mood and stress pathways. Women with anorexia nervosa (AN), hypothalamic amenorrhoea (HA) and obesity are at increased risk of depression and anxiety. It is unknown whether dysregulation of leptin or ghrelin contributes to the development of depression and/or anxiety in these disorders. We investigated the relationship between leptin and ghrelin levels and symptoms of depression, anxiety and perceived stress in women across the weight spectrum.

Re-examining premature mortality in anorexia nervosa: a meta-analysis redux.

Anorexia nervosa (AN) is reported to have the highest premature mortality of any psychiatric disorder, but recent meta-analyses may have inflated estimates. We sought to re-estimate mortality after methodological corrections and to identify predictors of mortality. We included 41 cohorts from 40 peer-reviewed studies published between 1966 and 2010. Methods included double data extraction, log-linear regression with an over-dispersed Poisson model, and all-cause and suicide-specific standardized mortality ratios (SMRs), with 95% Poisson confidence intervals. Participants with AN were 5.2 [3.7-7.5] times more likely to die prematurely from any cause, and 18.1 [11.5-28.7] times more likely to die by suicide than 15-34 year old females in the general population. Our estimates were 10% and 49% lower, respectively, than previously reported SMRs. Risk of premature mortality was highest in studies with older participants, although confounding by treatment was present. Gender, ascertainment, and diagnostic criteria also impacted risk.

A personality classification system for eating disorders: a longitudinal study

BACKGROUND Studies of eating disorders (EDs) suggest that empirically derived personality subtypes may explain heterogeneity in ED samples that is not captured by the current diagnostic system. Longitudinal outcomes for personality subtypes have not been examined. METHOD In this study, personality pathology was assessed by clinical interview in 213 individuals with anorexia nervosa and bulimia nervosa at baseline. Interview data on EDs, comorbid diagnoses, global functioning, and treatment utilization were collected at baseline and at 6-month follow-up intervals over a median of 9 years. RESULTS Q-factor analysis of the participants based on personality items produced a 5-prototype system, including high-functioning, behaviorally dysregulated, emotionally dysregulated, avoidant-insecure, and obsessional-sensitive types. Dimensional prototype scores were associated with baseline functioning and longitudinal outcome. Avoidant-Insecure scores showed consistent associations with poor functioning and outcome, including failure to show ED improvement, poor global functioning after 5 years, and high treatment utilization after 5 years. Behavioral dysregulation was associated with poor baseline functioning but did not show strong associations with ED or global outcome when histories of major depression and substance use disorder were covaried. Emotional dysregulation and obsessional-sensitivity were not associated with negative outcomes. High-functioning prototype scores were consistently associated with positive outcomes. CONCLUSIONS Longitudinal results support the importance of personality subtypes to ED classification.

Appetite-regulating hormones cortisol and peptide YY are associated with disordered eating psychopathology, independent of body mass index

OBJECTIVE Disordered eating occurs in women at both weight extremes of anorexia nervosa (AN) and obesity. Cortisol, peptide YY (PYY), leptin, and ghrelin are hormones involved in appetite and feeding behavior that vary with weight and body fat. Abnormal levels of these hormones have been reported in women with AN, functional hypothalamic amenorrhea (HA), and obesity. The relationship between appetite-regulating hormones and disordered eating psychopathology is unknown. We therefore studied the relationship between orexigenic and anorexigenic hormones and disordered eating psychopathology in women across a range of weights. DESIGN A cross-sectional study of 65 women, 18-45 years: 16 with AN, 12 normal-weight with HA, 17 overweight or obese, and 20 normal-weight in good health. METHODS Two validated measures of disordered eating psychopathology, the Eating Disorders Examination-Questionnaire (EDE-Q) and Eating Disorders Inventory-2 (EDI-2), were administered. Fasting PYY, leptin, and ghrelin levels were measured; cortisol levels were pooled from serum samples obtained every 20 min from 2000 to 0800 h. RESULTS Cortisol and PYY levels were positively associated with disordered eating psychopathology including restraint, eating concerns, and body image disturbance, independent of body mass index (BMI). Although leptin levels were negatively associated with disordered eating psychopathology, these relationships were not significant after controlling for BMI. Ghrelin levels were generally not associated with EDE-Q or EDI-2 scores. CONCLUSIONS Higher levels of cortisol and PYY are associated with disordered eating psychopathology independent of BMI in women across the weight spectrum, suggesting that abnormalities in appetite regulation may be associated with specific eating disorder pathologies.

Empirical identification and validation of eating disorder phenotypes in a multisite clinical sample.

Identified problems with the classification system of eating disorders (EDs), including its imperfect application to clinical samples, challenge its validity and limit its utility. The present study aimed to empirically identify and validate ED phenotypes in a multisite clinical sample using latent profile analysis (LPA). ED symptom data collected from 687 individuals were included in LPA. Identified latent profiles (LPs) were compared on clinical validators. Five LPs were identified: LP1 (n = 178), objective bingeing and multiple purging methods; LP2 (n = 172), objective bingeing without purging; LP3 (n = 130), objective bingeing and vomiting; LP4 (n = 108), low/normal weight and excessive exercise; LP5 (n = 99), low/normal weight and absence of ED symptoms. Validation analyses demonstrated the most extreme psychopathology/medical morbidity in LP1 and the least in LP5. LP1 and LP3 were most likely to report medication treatment for EDs. Identified LPs imperfectly resembled diagnostic and statistical manual of mental disorders-IV-TR EDs. Multiple purging methods and the absence of ED cognitions marked differences in severity across groups, whereas low weight did not. Clinical differences in psychopathology, medical morbidity, and treatment utilization validated groups. Future research should examine longitudinal stability of empirically-derived phenotypes and incremental validity of alternative classification schema to inform DSM-V.