W4-Neurobiology of EDs

• Eating disorders reflect a discrepancy between one's physical needs to eat and the drive to eat
• Homeostatic hunger

  Driven by physiological necessity (e.g., rumblings of empty stomach)
• Hedonic hunger

  Driven by pleasure and motivation
• Control of Feeding Behavior

  1. Homeostatic system communicates to hypothalamus your level of energy

  2. Hedonic/motivation system
• Factors that regulate homeostatic hunger

  • Appetite hormones regulated by hypothalamus
  • Leptin from adipose cells tells hypothalamus to reduce appetite
  • Cholecystokinin and peptide YY from stomach & intestine suppress hunger when food detected
  • Ghrelin from stomach & intestine stimulates hunger when stomach empty and blood glucose low
• Brain regions involved in homeostatic and hedonic hunger

  • Lateral hypothalamus - "Go" (hedonic)
  • Ventromedial hypothalamus - "Stop"
  • Limbic, cognitive circuits; pleasure and motivations > appetite & food intake
  • Hypothalamic-brain stem system; energy balance > appetite & food intake
• Humans can override hypothalamic energy balance signals - obese overeat despite sufficient energy stores, AN restrict eating although emaciated
• Hunger

  Food becomes more pleasurable, increased motivation to eat

  Activates regions associated with reward or reducing top down cognitive inhibitory control

  Enhances preference for immediate rewards

  Enhances sensitivity to drugs of abuse in animals, can lead to purchases of unhealthy, higher-calorie foods when shopping
• Satiety

  Habituate to same foods, food can be aversive
• In controls, hunger activates reward systems more for high-calorie foods
• In AN-R, activation during taste is abnormally low when hungry


  Suggests reduced reward sensitivity, difficulty translating hunger signals into motivated action
• In RBN, activation during taste is abnormally high after eating


  Suggests RBN may not devalue food reward when fed

  The brain is not sending signal that's reducing rewarding value, so one conitnue's to eat to get reward.

  Or not getting the "stop" signal
• Decreased caudate response to taste is associated with increased harm avoidance - avoid punishment by inhibiting or restricting behavior - in AN


  Suggests brain basis for coding food as risky and for successful caloric restriction
• Reward dysfunction extends to non-food reward in AN and BN
• Reduced inhibitory control in BN

  Altered self-regulatory circuitry

  Overreliance in S-R, reward-based learning (hippocampus & amygdala)

  • hunger/urge to binge
  • binge eating
  • compensatory behavior
• In AN, hunger may not sensitize food reward motivation, enabling food restriction
• In BN, food reward may not be appropriately devalued after eating, and coupled with reduced inhibitory control, may contribute to binge eating
• Neurobiological deficits in eating disorders

  • Hunger/satiety (Ghrelin/leptin) cues don't translate to action
  • Anticipatory anxiety
  • Approach/avoid eating to regulate emotions
  • Altered "reward" drive to eat
  • Enhanced/reduced ability to "inhibit" eating
  • Denial, resistance to treatment, lack of insight
  • Can't differentiate biological signals
  • Internal noisy signals create anxiety, avoidance, and/or dysregulated behavior
• Eating Disorders are not well understood and many have a chronic course and poor outcome and may die
• Have to synthesize and integrate theories - Psychosocial, genetics, neurobiology
• Keep patients motivated, work with families
• May be complex and confusing
• AN

  • % prevalence: 0.25
  • % women: 95
  • Weight: Low
  • Eating: Restrict
  • Mood/impulse control: Over control
• AN-BN

  • % prevalence: 0.25
  • % women: 95
  • Weight: Low
  • Eating: Restrict, binge
  • Mood/impulse control: Over/under control
• BN

  • % prevalence: 1-3
  • % women: 90
  • Weight: Normal
  • Eating: Restrict, binge
  • Mood/impulse control: Over/under control
• Symptoms in Eating Disorders

  • Body image distortion
  • Neg affect, perfect, obsessive
  • Exercise
  • Anhedonic
  • Denial, resistance, ego syntonic
  • Drugs, alcohol, poor impulse control

  
• Treatment of Anorexia Nervosa

  • Early Treatment: Parentectomy
  • First Generation: Weight Restoration, Behavior Modification, Antidepressants, neuroleptics unsuccessful/unproven, Successful inpatient weight gain but high relapse
  • Second Generation: Relapse Prevention, Specialized Psychotherapies (Family, CBT, DBT, etc), Control trials - SSRI's, atypicals, etc, Goal: Response w/o hospitalization, reduced relapse
• Maudsley Treatment Approach

  • Agnostic view of cause of illness (No blame)
  • Family made responsible to re-feed child (Empowerment)
  • Non authoritarian therapeutic stance (Joining)
  • Separation of child and illness (Respect for adolescent)
  • Highly focused, staged treatment
  • Emphasis on behavioral recovery rather than insight and understanding
  • Indirect approach to improving family functioning
  • Supports gradually increased independence from therapy
• Family Based (Maudsley) Treatment for Adolescent Anorexia Nervosa

  • Russell et al (1987)—90% improvement in subgroup of with short-duration AN
  • Le Grange et al (1992)—70% improvement
  • Robin et al (1999)—90% improvement with family treatment compared to 65% with individual therapy
  • Eisler et al (2000)—65% improvement in cohort
  • Eisler et al (1997)—five year follow-up on Russel et al (1987) found improvements were maintained
• Maudsley Limitations

  • Adolescents, not adults
  • Not tested in severely underweight AN
  • Does not reverse temperament, personality
  • Family ingredients predicting good outcome ?
• Many women diet in our culture, but relatively few develop AN, BN
• Are there susceptibility factors that make some women vulnerable to dieting, weight loss?
• New Understanding of ED: Genetics and ED

  • ED often occur in families
  • AN and BN cross transmitted in families – shared vulnerability?
  • Increased family risk for ED, mood disorders, OCD and OCPD
  • Twin studies: Approximately 50+% heritable risk of AN
  • ED have significant genetic correlations with other psychiatric disorders
  • Genetic associations with OCD, Major depression, Schizophrenia, anxiety, Neuroticism
  • Linkage studies suggest finding on chromosome 1
  • Some evidence of involvement of serotonin and dopamine genes
• Suggests powerful neurobiology is genetically transmitted
• Childhood Trait Vulnerabilities

  • Anxiety
  • Perfectionism
  • Obsessionality
  • Harm avoidance
  • Negative emotionality
• Anxiety disorder increased risk of subsequent AN, highest risk was OCD – especially in males
• Shared genetic susceptibility of AN and anxiety disorders
• Anxiety associated with GABA gene alterations, benzodiazepine insensitive
• Lifetime and Premorbid Rates of Anxiety Disorders in Eating Disorders

  • Range for AN: 10 - 62%
  • Range for AN BN: 10 - 66%
  • Range for BN: 0 - 43%
• General population rate OCD: 1-3% of adults; 2-4% of children