EATING DISORDERS

1
EATING DISORDERS
2
OVERVIEW

• Eating Basic Principles
• Anorexia Nervosa Bulimia Nervosa
• basic overview
• neurochemistry
• neuroanatomy
• Obesity
• neurochemistry

3
FOOD TO ENERGY
CARBOHYDRATES GLUCOSE
FAT FATTY ACIDS
PROTEIN AMINO ACIDS
4
NEUROANATOMY OF EATING
5
EATING BEHAVIOURS

• Continuum?
• chronic dieter
• binge eating
• purger
• subthreshold bulimic
• bulimics and anorexics

6
HISTORICAL VIEW

• Lateral hypothalamus control eating
• Ventromedial hypothalamus controls inhibition of
  eating
• based on lesion data
• BUT MORE COMPLICATED THAN THAT..

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HYPOTHALAMUS

• definitely involved in the control of eating
• Releasing Hormones
• Lesions
• Pathways

http//web.psych.ualberta.ca/msnyder/p104x1/notes
/ch13.html
8
CURRENT VIEWS

• Dopaminergic nigrostriatal pathway
• same effect as LH lesions
• Paraventricular Nucleus (PVN) of the Hypothalamus
• injection of NE

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CNS CUES TO INITIATE EATING

• Glucostatic Theory
• glucose, insulin, glucagon
• Lipostatic Theory
• lipids, fatty free acids
• Hormonal Satiety Cues
• CCK

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EATING DISORDERS
11
AGE OF ONSET?

• age of body hatred decreasing
• worse to be obese than have a physical disability
• restrictive and unhealthy eating at young age
• nutritional deficiencies
• ex. Pica, Rumination Disorder, Feeding Disorders
  in Infancy or Early Childhood

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DSM-IV

• ANOREXIA NERVOSA
• refusal to maintain body weight (less than 85 of
  that expected)
• intense of gaining weight/fat
• disturbance in way weight/shape is viewed
• amenorrhea

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SPECIFIC TYPES

• Restricting Type
• Binge-Eating/Purging Type

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PREVALENCE

• more prevalent in industrialized societies
• 0.5-1 AN 90 are females
• mean onset of 17 years
• highly variable course and outcome

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ASSOCIATED FEATURES

• depressive symptoms
• depressed mood, social withdrawal, irritability,
  insomnia, diminished interest in sex
• obsessive compulsive disorder

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CHARACTERISTICS OF AN

• preoccupied with being food and with not becoming
  fat
• various physiological effects
• mortality rate 5
• genetic predisposition

17
DSM-IV

• BULIMIA NERVOSA
• recurrent episodes of binge eating
• eating in a discrete period a larger amount than
  normal
• lack of control over eating
• recurrent inappropriate compensatory behavior in
  order to prevent weight gain
• at least twice a week for 3 months
• does not occur during episodes of AN

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SPECIFIC TYPES

• Purging Type
• Nonpurging Type

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PREVALENCE

• usually slightly older onset than AN
• usually starts after dieting
• 1-3 AN 90 are females
• may be chronic or intermittent
• 5-30 suicide or self-injurious behaviour
• 18-24 abuse alcohol

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ASSOCIATED FEATURES

• within normal weight range
• more likely to be overweight prior to onset
• between binges, restrict caloric intake
• 30-50 meet criteria for personality disorders
  (Borderline)
• depressive symptoms

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CHARACTERISTICS OF BN

• binging and purging
• various physiological changes
• cannot control diet/food intake (unlike AN)
• few outward physical signs
• experience anxiety with forbidden foods

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WHAT IS THE DIFFERENCE BETWEEN BINGING-EATING/PURG
ING AN AND BN?
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SIMILARITIES AND DIFFERENCES

• SIMILARITIES
• prevalent among young females
• fear of weight gain
• body image distortion disturbance
• comorbidity

• DIFFERENCES
• AN below normal weight denial of disorder
• BN normal weight aware of problem

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CAUSE CONSEQUENCE?

• PSYCHOSOCIAL FACTORS
• VS.
• BIOLOGICAL FACTORS

25
NEUROBIOLOGY
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OVERVIEW

• Genetic Factors
• Biological Set Point
• Neurochemistry
• Neuroanatomy

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SEROTONIN

• changes in the levels of 5-HT activity
• increased 5-HT
• precursors decreased
• lower levels of 5-HT metabolites
• enhances AN characteristics
• antagonist manner in medial hypothalamus
• rebound effect with recovery

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Cont...

• Scenarios
• 1. variations in serotonin receptors
• 2. Abnormalities predisposition
• work with E/NE systems
• abnormalities before and after recovery show
  that may not be caused solely by psychosocial
  factors?

29
EPINEPHRINE

• hypothalamic site dependent effects
• epinephrine vs. norepinephrine
• ?1-adrenergic vs. ?2-adrenergic receptors
• elevated in serum, but not in CSF
• meal size rather than frequency
• effects of recovery?

30
DOPAMINE

• increased dopamine
• amphetamines induce anorexia through action on
  catecholamines
• indirect effect on AN??

31
OPIOIDS

• food intake reward value of food?
• released in response to starvation reward value?
• involved in preference for sweet foods
• opioid antagonist naloxone
• opioids on E/NE system

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THE HPA AXIS
LIMBIC SYSTEM (Hippocampus)
ve
HYPOTHALAMUS
(Paraventricular Nucleus)
-ve
CRH
PITUITARY GLAND
(Anterior Pituitary)
ACTH
ADRENAL GLAND
Glucocorticoid
(Adrenal Cortex)
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PITUITARY GLAND
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HPA AXIS

• CRH increased levels
• ACTH normal
• Cortisol increased levels
• CRH ACTH pituitary?
• ACTH Cortisol adrenal?
• Hypothalamus?

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Cont...

• compensatory reactions?
• decreased feedback sensitivity?
• effects of other hormones that are affected by
  HPA axis
• growth hormone
• thyroid hormone
• reproductive axis
• immune system
• hippocampus

36
ESTROGEN

• amenorrhea
• LH GnRH correlate with body weight
• but amenorrhea precedes weight loss
• opioids dopamine

http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/lhfsh.html
37
GROWTH HORMONE

• Direct effects target receptors in fat protein,
  lipid, carbohydrate metabolism
• Indirect effects mediated by insulin-like growth
  factor-1 (IGF-1) muscle bone growth

GHRH growth hormone-releasing hormone SS
somatostatin
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/gh.html
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Cont...

• GH is increased frequency of secretory pulses
• GHRH
• decrease in binding protein
• normally suppressed by glucose loading
• IGF-1 is decreased protective
• GH resistance

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THYROID GLAND

• Thyroglobulin converted to T3 T4
• almost all cells are target of THs
• calcitonin
• metabolic rate, growth development

TRH Thyroid-releasing hormone
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/tsh.html
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Cont...

• low levels in AN
• increased formation of inactive metabolites
• blunted and delayed TSH response
• weight gain reverses deficits

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OTHERS...

• CCK induced satiety normalizes with weight gain
• LEPTIN solely secreted by fat cells appetite
  suppressive
• NPY increased levels appetite stimulating
  inhibited by CRH

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NEUROANATOMY

• enlarged ventricles, shrinkage of brain tissue
• metabolism of parietal cortex, frontal cortex,
  basal ganglia
• secondary effects
• ex. HPA axis elevated cortisol

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NEUROCHEMISTRY OF BN

• Differences from AN
• reduced PRL response to 5-HT
• depletion of tryptophan
• SSRIs are useful for treating
• seasonal variations in bulimic symptoms as there
  are in mood

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Cont...

• little evidence for addiction model in AN
• ie. no effect of opioids?
• pattern of right-left asymmetries during
  cognitive task

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COMORBIDITY

• depression
• personality disorders
• odd or eccentric
• antisocial, borderline, histronic, narcissistic
• anxious or fearful
• OCD, avoidant, and dependent
• substance abuse

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TREATMENT

• ANOREXIA
• family therapy
• psychotherapy
• drug treatment
• not effective
• 10 starve to death
• gt50 still have problems
• predictors of better prognosis

• BULIMIA
• psychotherapy
• maladaptive tendencies
• more effective than drugs?
• drug treatment
• more effective
• education
• addressing beliefs
• maintaining progress
• intrapersonal therapy

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OBESITY

• childhood obesity one of the fastest growing
  medical problems
• future medial problems ex. diabetes
• imbalance in food intake and energy expenditure
• fat stores accommodate increasing levels
• BMI gt 27 or BMI gt 30 obese

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NEUROPEPTIDES

• CCK reduces food intake
• Glucagon reduces food intake, enhances insulin
  secretion
• NPY knockout mice are not obese
• Leptin injections have led to dose-related
  weight loss

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NTs HORMONES

• Serotonin receptors in PVN reduce fat total
  intake
• Norepinephrine ?2- adrenergic receptors
• Opioids modulate fat intake drugs?
• Melanocortin reduces food intake receptor
  knockouts obese
• Insulin resistance fat storage

50
THYROID GLAND

• Thyroglobulin converted to T3 T4
• almost all cells are target of THs
• calcitonin
• metabolic rate, growth development

TRH Thyroid-releasing hormone
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/tsh.html
51
THYROID HORMONE

• deficiency causes obesity
• affects resting energy expenditure
• some conflicting results
• obese people are either found to have normal or
  elevated levels of T3
• diet sensitive related to with energy
  expenditure metabolism

52
GROWTH HORMONE

• Direct effects target receptors in fat protein,
  lipid, carbohydrate metabolism
• Indirect effects mediated by insulin-like growth
  factor-1 (IGF-1) muscle bone growth

GHRH growth hormone-releasing hormone SS
somatostatin
http//www.vivo.colostate.edu/hbooks/pathphys/endo
crine/hypopit/gh.html
53
GROWTH HORMONE

• decreased levels secretions shorter
  endogeneous clearance
• decrease levels of IGF-1?
• IGF-1 in normal range GH binding protein is
  increased
• mediates effects through IGF-1

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GH, TH, GONADAL STEROIDS

• GH TH work together at puberty
• testosterone lean body mass vs. fat
• estrogen fat vs. lean body mass
• testosterone levels fall increases visceral and
  body fat
• ovariectomies obesity
• estrogen receptor knockouts obesity

55
THE HPA AXIS
LIMBIC SYSTEM (Hippocampus)
ve
HYPOTHALAMUS
(Paraventricular Nucleus)
-ve
CRH
PITUITARY GLAND
(Anterior Pituitary)
ACTH
ADRENAL GLAND
Glucocorticoid
(Adrenal Cortex)
56
GLUCOCORTICOIDS

• critical for the development maintenance
• increased modest obesity
• decreased (adrenalectomized) loss of fat
• enzyme cortisone cortisol
• higher morning levels of cortisol
• greater stress response
• increased CRH CRH activity
• parallel activation of sympathetic system

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CAUSE CONSEQUENCE?

• PSYCHOSOCIAL FACTORS
• VS.
• BIOLOGICAL FACTORS

58
THIS WEEKS READINGS

• Schmidt, I., Fritz, A., Scholch, C., Schneider,
  D., Simon, E., Plageman, A. (2001). The effect
  of leptin treatment on the development of obesity
  in overfed suckling Wistar rats. International
  Journal of Obesity, 25, 1168-1174.

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Cont

• Siegfried, Z., Berry, E.M., Hao, S., Avraham,
  Y. (2003). Animal models in the investigation of
  anorexia. Physiology Behavior, 79, 811-825.

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LAST WEEKS READINGS

• Wolterink, G., Daenen, L.E.W.P.M., Dubbledam, S.,
  Gerrits, M.A.F.M., van Rijn, R., Kruse, C.G., van
  der Heijden, J.A.M., van Ree, J.M. (2001).
  Early amygdala damage in the rat as a model for
  neurodevelopmental psychopathological disorders.
  European Neuropsychopharmacology, 11, 51-59.

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Cont

• Sagvolden, T. (2000). Behavioral validation of
  the spontaneously hypertensive rat (SHR) as an
  animal model of attention-deficit/hyperactivity
  disorder (AD/HD). Neuroscience Biobehavioral
  Reviews, 24, 31-39.