Biological Aspects of Obesity-Related Eating Disorders: Binge Eating Disorder and the Night Eating Syndrome

1. Biological Aspects of Obesity-Related Eating Disorders: Binge Eating Disorder and the Night Eating Syndrome

Allan Geliebter

New York Obesity Research Center

St. Luke's and Roosevelt Hospitals

Columbia University

Division of Child and Adolescent Psychiatry

Grand Rounds

Columbia University

February 17, 2010

2. Obesity

NIGHT EATING

SYNDROME

BINGE EATING

DISORDER

3. Marx J. Science, 2003; 299: 846-849.

4. Controls of Food Intake

Signals

Initiation

Termination

Differences in BED?

5. Main Criteria for Binge Eating Disorder (BED)

Recurrent episodes of binge eating 2 days/wk for 6 mos.

objectively large amount of food in a discrete time period (2 hours)

sense of loss of control

without purging afterwards

6. Binge Eating Disorder (BED)

* Stomach Capacity

* Gut peptides (leptin, CCK, ghrelin)

* Brain Imaging

7.

* Stomach functions as a food reservoir.

* Stomach capacity could limit meal intake

and influence satiation.

Stomach

8. Gastric Capacity

Estimated by filling a intragastric balloon with water at 100 ml/min through a tube connected to a pump behind the person

based on maximum volume tolerated

based on volume required to produce a

fixed rise in intragastricpressure.

9. Table 1. Characteristics of Overweight Women (M ± SD)

No differences by group.

BODPOD

Geliebter A, Gluck ME, Hashim SA. J Nutr 2005;135:1326-30.

10. *

11. *

12. The two estimates of gastric capacity correlated (r = .60, p = .001) with each other.

13. Test Meal

Participants ingested a liquid meal through a straw from a large opaque cooler to prevent visual feedback until extremely full.

14.

15. Test meal intake correlated significantly

(r = .42, p = .03) with gastric capacity.

16.

17. Binge Eating Disorder (BED)

* Stomach Capacity

* Gut peptides (leptin, CCK, ghrelin)

* Brain Imaging

18. Leptin

* Leptin is secreted primarily by adipose tissue and rises slowly after meals. Leptin administration decreases food intake and weight in animals (Zhang et al., 1994) and modestly inhumans (Heymsfieldet al., 1999).

Hypothesis

* Leptin would rise to a lesser extent postprandially in BED.

19. CCK

* CCK, is secreted primarily by the duodenum, and rises after meals. CCK administration decreases food intake in animals (Gibbs et al., 1973) and humans (Kissileff et al., 1981).

* Evidence that postmeal CCK rises less in Bulimia Nervosa (Devlin et al., 1997), perhaps contributing to larger meal intake.

Hypothesis

* CCK would also rise to a less post meal in BED.

20. Ghrelin

* Ghrelin, is secreted primarily by the stomach and stimulates food intake in animals (Tschöp et al., 2000) and humans (Wren et al., 2001).

* Ghrelin is elevated before meals and falls afterwards (Cummings et al, 2002), unlike other peripheral appetite hormones, which rise after meals.

Hypothesis

Obese individuals with BED would have high ghrelin levels given their excess meal intake.

21. Methods

* After a 12 h overnight fast, an intravenous catheter was inserted at 8 am. Subjects rested for 15 minutes before first blood draw at -15 min.

* Meal was provided at time 0 and consumed at constant rate from graduated beaker in 5 min.

* The breakfast liquid test meal (600 ml diluted Boost) provided 1254 kJ (300 kcal): 24% protein (19 g), 55% carbohydrate (41 g, including 20 g sugar), and 21% fat (6 g).

22. Methods (cont’)

Blood samples were assayed for several peptide

hormones, including leptin, CCK, and ghrelin.

Meal

_________I____I______I______I______I

-15 0 5 15 30 60 90 120

min

23. meal

24. meal

25. meal

26. Ghrelin Findings

BED S’s had lower fasting ghrelin levels than non-BED S’s, contrary to hypothesis.

In BED S’s, ghrelin levels declined less after meal.

Results extend and are consistent with findings of lower ghrelin levels in obese individuals.

Ghrelin may be down-regulated in obese BED S’s due to overeating possibly via stomach capacity.

Geliebter A, Gluck ME, Hashim SA. J Nutr 2005;135:1326-30

27. Binge Eating Disorder (BED)

* Stomach Capacity

* Gut peptides (leptin, CCK, ghrelin)

* Brain Imaging

28. Introduction

Only a few studies have employed functional brain imaging underlying binge eating in humans.

29. Participants

Women (n = 20)

Geliebter A, Logan M, Ladell T, Schneider T, Sharafi M, Hirsh J. Appetite 2006;46:31-5

30.

31. Visual Runs

Stimulation

Baseline

Baseline

Binge

Non-binge

Non-foods

32. Auditory Runs

Stimulation

Baseline

Baseline

Binge

Chocolate

Cookies

Caramel

Sundae

Pepperoni

Pizza

Acorn

Squash

Iceberg

Lettuce

English

Cucumbers

Non-binge

Looseleaf

Binder

Pencil

Sharpener

Letter

Opener

Non-food

33. Individual Analysis (Method 1)

The analysis used an fMRI program, which identifies brain activation areas for each individual.

34. Obese NonBinge Eater

Obese Binge Eater

L

R

Lean Binge Eater

Lean NonBinge Eater

35. Results and Discussion

* The only brain area activated for all members of a group was the premotor area in the obese binge eaters in response to the binge type foods.

* For 80%, it was in the oral premotor region.

* It is unlikely that this was due to swallowing as the primary motor area was not activated.

* The premotor area is involved in planning of motor behavior, and may reflect thoughts about ingesting the binge type foods.

36. Groups Analysis (Method 2)

Another analysis underway is with Statistical Parametric Mapping (SPM), which combines brains from subjects in a group and maps to a reference brain.

37. Controls of Food Intake

Signals Stomach PeptidesStress Hormone

Initiation Ghrelin Cortisol

TerminationCapacity CCK, Leptin

Emptying

Differences found in BED

38. Night Eating Syndrome (NES)

NES was first described by Stunkard(Stunkard, 1955)

39. Night Eating

* Description and Prevalence

* Psychological factors

* Stress

* Sleep Timing

* Treatment

* Diagnosis

40. Background

Night eating syndrome (NES) is characterized by:

morning anorexia

evening hyperphagia

sleep disturbances

awakenings from sleep to eat

41. NES Prevalence

42. NSRED

NES

-

+

Conscious during eating

+

-

Amnesia after eating

+

-

Associated parasomnias

+

-

Consumption of non-food

-

+

Depressed mood

-

+

Evening hyperphagia

Rare

Moderate

Prevalence

Night Eating Syndrome vs. Nocturnal Sleep-Related Eating Disorder

43. Night Eating

* Description and Prevalence

* Psychological factors

* Stress

* Sleep Timing

* Treatment

* Diagnosis

44. Subject Characteristics(mean + SD)

45. Methods

* Following 8 h fast, participants completed psychological scales:

--ZungDepression Self-Rating Scale (Zung, 1965)

--Rosenberg Self-Esteem Scale (Rosenberg, 1966)

--Night Eating Diagnostic Questionnaire (Gluck et al., 2001)

* They then completed ratings of hunger & fullness and ingested a liquid meal until extremely full.

46. Methods (cont’)

They then began the weight loss program:

* 900 kcal, liquid formula diet

* weekly nutritional counseling sessions

* weight recorded weekly

47. 50

45

NES

Normal

p = .04

40

35

30

p = .003

25

20

15

10

5

0

Depression

Low Self-Esteem

48. NES

Normal

50

45

40

p = .005

35

p = .06

30

25

20

15

10

5

0

Hunger

Fullness

49. Test Meal Intake

* Night eaters' test meal intake (979 g +417 SD) did not differ significantly from normals (859 g + 459).

* However, test meal intake was greater later in the day only for the night eaters (F = 11.1, p = .01).

50. Weight Loss (kg)

9

8

7

p = .006

6

5

4

3

2

1

0

NES

Normal

51. Night Eating

* Description and Prevalence

* Psychological factors

* Stress

* Sleep Timing

* Treatment

* Diagnosis

52. Stress & Eating Disorders

* Stress plays a role in initiating eating episodes in:

--Bulimia Nervosa

--Binge Eating Disorder

* Does stress also play a role in Night Eating?

53. Stress & Night Eating

Onset of NES

* Many develop NES following life stress (Stunkard, 2002)

* NES often remits if stress alleviated (Stunkard, 2002)

* Progressive muscle relaxation improves symptoms of NES (Pawlow et al, 2003)

(Allison & Stunkard, 2004)

54. Stress & Cortisol

* Cortisol secretion by adrenal gland is a major component of the stress response

(Ur, 1991).

* Glucocorticoids can increase food intake & body weight in rats (Dallman et al., 2003)and humans(Tataranni et al., 1996).

* Cortisol may be a potential mediator of stress-induced eating episodes.

55. HPA Axis

Yehuda R, N Engl J Med, 346; 2002:108-114.

56. Cortisol in Eating Disorders

* Several studies have examined cortisol in eating disorders after a laboratory stressor:

--Exaggerated plasma cortisol response in AN (Abell et al, 1987), BN (Koo-Loeb et al, 2000), and BED (Gluck et al., 2004)

--Higher 24-h urinary cortisol following a stressor in BN (Koo-Loeb et al, 2000)

* No studies have examined:

--cortisol in response to laboratory stress in NES

--or ghrelin, which has recently been shown to increase in response to a laboratory stressor

57. Hypotheses

NES would have:

* higher basal levels of cortisol

* higher cortisol levels following

Cold Pressor Test (CPT)

* less suppression of cortisol after a

dexamethasone suppression test (DST)

58. Methods

* Recruited obese women with and without NES

* Measured basal plasma cortisol at 8:30 am

* Measured plasma cortisol at 8:30 am in response to dexamethasone the night before

* Cold Pressor Test (CPT) at about 12:30 pm

59. Group Characteristics (M+SD)

60. Basal Cortisol

ns

g/dL

61. Cortisol Following DST

n.s.

g/dl

62. Cold Pressor Test

HAND IMMERSION

HAND

WITHDRAWAL

I

I

I

I

I

I

I

0

2

15

5

30

60

45

-10 min

Blood Draws for Cortisol, Ghrelin, Hunger Ratings

63. Cortisol

g/dL

Main effect, p<.05

Group diff , n.s.

Baseline (mean of

-10 and 0 min) NE > Norm, p<.05

AUC, NE > Norm,p=.02, (n.s. after controlling for baseline.)

64. Ghrelin

pg/mL

Main effect, p<.05

Group diff , n.s.

Baseline (mean of

-10 and 0 min), n.s.

AUC, n.s.

65. Hunger

Main effect, p<.05

Group diff, n.s.

Baseline, n.s.

AUC, n.s.

66. Controls of Food Intake

Signals Stress HormoneTime Cues

Initiation Cortisol Evening/Night

Termination

Differences found in NES

67. Night Eating

* Description and Prevalence

* Psychological factors

* Stress

* Sleep Timing

* Treatment

* Diagnosis

68. Timing of Sleep Onset and Offset

NES Control

Sleep onset time (Lab) 23:38 ± 1:5922:52 ± 1:04

Sleep onset time (home) 23:57 ± 1:3323:32 ±1:06

Sleep offset time (Lab) 7:04 ± 0:48 7:06 ± 0:41

Sleep offset time (home) 7:35 ± 1:11 6:59± 1:12

NES and Control Ss did not differ in sleep periods in the laboratory (Rogers et al., 2006 ) or at home (diary and actigraphy) (O ’Reardon et al., 2004).

69. Food Intake

NES > Controls

Inpatient study reflects night eating (20 h- 08 h) in NES subjects (Allison et al,. 2005)

Outpatient study shows shifted calorie intake curve in NES (O’Reardon et al., 2004)

70. Night Eating

* Description and Prevalence

* Psychological factors

* Stress

* Sleep Timing

* Treatment

* Diagnosis

71. Randomized Controlled Trial of Sertraline

Patients randomized to sertraline(n=17)

or placebo (n = 17) for 8 weeks.

O’Reardon et al., 2006

72. Night Eating Symptom Scale

73. Nocturnal ingestions/week

74. % Caloric Intake after Dinner

75. Weight change

76. Discussion

NES – altered circadian food intake

* SSRIs could be acting on the SCN to synchronize food intake and sleep-wake cycle rhythms

* SSRIs may also act to control the compulsion to eat as they do in BN & BED

77. Control

NES

Lundgren et al., 2008

78. Behavioral Treatment

No Formal Studies

Useful Strategies

* Reduce triggers, e.g., stress that induce eating

* Keep tempting foods out of reach

* Increase breakfast consumption

Recommended Manual

Overcoming Night Eating Syndrome

Kelly Allison, Albert Stunkard, Sarah Tier

New Harbinger, 2004

79. Night Eating

* Description and Prevalence

* Psychological factors

* Stress

* Sleep Timing

* Treatment

* Diagnosis

80. Proposed Research Diagnostic Criteria for NES(First International Night Eating Symposium, April 26, 2008, Minneapolis, MN)

I. The daily pattern of eating demonstrates a significantly increased intake in the

evening and/or nighttime, as manifested by one or both of the following:

A. > 25% of food consumed after the evening meal

B. > 2 episodes of nocturnal eating per week

II. Awareness and recall of evening and nocturnal eating episodes

III. > 3 of the following:

A. Lack of desire to eat in the morning and/or breakfast is omitted on four or more

mornings per week

B. Presence of a strong urge to eat between dinner and sleep onset and/or during

the night

C. Sleep onset and/or sleep maintenance insomnia are present four or more nights

per week

D. Presence of a belief that one must eat in order to initiate or return to sleep

E. Mood is frequently depressed and/or mood worsens in the evening

IV. The disorder is associated with significant distress and/or impairment in functioning.

V. The disordered pattern of eating has been maintained for at least 3 months.

VI. The disorder is not secondary to substance abuse or dependence, medical disorder,

medication, or another psychiatric disorder.

Allison et al, 2009

81. Acknowledgements

Co-Investigators

Marci Gluck, Sami Hashim, Eric Yahav, Dennis Gage, Joy Hirsch, Susan Carnell

Resources

NY Obesity Research Center provided hormone assays and body composition

measurements

Grant Support

NIH Grants RO1 DK 554318, R01 DK074046, R03 DK068392, and MO1 RR0064529