Non-Substance Addiction

Gambling in Australia

• Estimates suggest that Australians lost approx $25 billion on legal forms of gambling in 2018-19, representing the largest per capita losses in the world

• Australia is home to less than half a percent of the world’s population but has 20% of its pokies

DSM-V Substance-Related and Addictive Disorders

Section II: Diagnostic Criteria and Codes

Substance-Related and Addictive Disorders

• Substance- related disorders

• Non-substance-related disorders

  • Gambling disorder

    • Reflects research findings that gambling disorder is similar to substance-related disorders in clinical expression, brain origin, comorbidity, physiology and treatment

    • Promote treatment of pathological gambling

Section III: Emerging Measures and Models

• Requires further research before consideration as formal disorders

  • Videogame disorder

Gambling Disorder

• Persistent and recurrent problematic gambling behaviour leading to clinically significant impairment or distress, as indicated by the inidividual exhibiting four (or more) of the following in a 12-month period:

  • Needs to gamble with increasing amounts of money in order to achieve the desired excitement. Escalation/Tolerance

  • Is restless or irritable when attempting to cut down or stop gambling. Withdrawal

  • Has made repeated unsuccessful efforts to control, cut back or stop gambling. Loss of control

  • Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past gambling experiences, handicapping or planning the next venture, thinking of ways to get money with which to gamble) Preoccupation

  • Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed). After losing money gambling, often returns another day to get even (”chasing” one’s losses). Escape

  • Lies to conceal the extent of involvement with gambling

  • Has jeopardised or lost a significant relationship, job, or educational or career opportunity because of gambling. Compulsion

  • Relies on others to provide money to relieve desperate financial situations caused by gambling

• Specify current severity:

  • Mild = 4-5 criteria met

  • Moderate = 6-7 criteria met

  • Severe = 8-9 criteria met

Drug Addiction vs Gambling

• Core symptoms overlap

  • Cravings

  • Withdrawal

  • Tolerance

  • Relapse

• Rates of drug use are higher in GD

• GD is higher in drug users

  • Suggests a shared neurobiological mechanism

• May depend on the substance: e.g., more commonalities between GD and alcoholism rather than MDMA

• GD is often co-morbid with life-time drug use, particularly alcohol and tobacco (Cunningham-Williams, Cottler, Compton & Spitznagel)

  • However, it is not clear whether disorders are co-occurring, whether one precedes the other and what influence shared environmental, social and/or genetic risk factors may have among these disorders

• Theories developed to explain drug addiction may also be relevant to GD

• Incentive sensitisation (Robinson et al 2013)

  • If you are exposed to drugs of abuse, then cues can take on conditioning-reinforcing properties

  • Transforms ordinary stimuli, such as cues associated with rewards, into incentive stimuli , making them motivationally attractive and able to trigger an urge to pursue and consume their reward

  • Although wanting and liking of a drug are typically strong linked in the initial phases of drug use, only wanting becomes sensitised and consequently increases as the addiction develops

  • Individuals with GD show increased sensitivity to gambling-associated cues

  • Van Holst et al 2012

    • PGs showed more activation in the left dorsolateral prefrontal cortex, right ventral striatum, and right anterior cingulate following exposure to gambling related cues

• Reward deficiency hypothesis

  • Individuals drawn to gambling due to a developmentally understimulated reward system (reuter et al)

    • Turn over a card - red = win

    • Activation of the ventral striatum is greater in controls than pathological gamblers

      • Brain of PGs does not react in a normal way - they don’t get happy sensation so they continue to gamble in hope of reactivating those reward systems

• IOWA Gambling Task

  • Measures an individual’s approach to risk-taking, impulsivity, and ability to delay short-term gratification to achieve long-term rewards

  • There are 4 card desks - each is associated with a reward or penalty

    • E.g., Deck A = $100, but penalty 1/2 of the time is a $250 penalty

  

  • People with PG perform worse on the IGT than healthy controls

    • Persistence at high risk decisions involving the continued choice of potential large immediate rewards despite experiencing larger punishments

  • High risk selections: PG show greater activation of right caudate and OFC

  • May indicate greater salience for greater rewards, rather than deficit in inhibitory control

    • Discount information about losing money

• Rat Gambling Task

  

  • Same concept as IOWA task, but using food pellets instead

    • 2 pellets with higher penalty chance

    • 1 pellet with lower penalty chance

  • Rats naturally formed three clusters

    • Good, indifferent and poor decision makers

  • Poor decision makers were also risk taking as measured on the emergence test and elevated plus maze

  • Poor decision makers were also more sensitive to reward on a progressive ratio and runway apparatus

Neurobiology

• Dopamine increase with gambling

• Treatments for Parkinson’s disease (DA agonists) have been associated with the developmnt of pathological gambling

• Zeeb et al 2009

  • PG have low levels of serotonin when gambling

    • 5-HT plays a role in emotional responses to aversive events

    • May impair the ability to integrate information about expected losses in decision making - blunted emotional response

  • On the RGT

    • 5-HT1 agonist (replicated low levels 5-HT levels) impairs performance

    • A dopamine agonist impair task performance, a D2 antagonist improved performance

Compulsive Overeating

• Society viewed obesity as being due to a lack of will power or self-control

• Then it was thought to be hormonal - mice lacking leptin overeat (leptin signals satiety)

• However, only a very small number of people have the genetic deficiency of low leptin

  • Obese people have actually higher than normal levels of leptin

    • Leptin resistance

    • Signal-to-noise ratio is out → the signal is not detected because there is so much leptin already

Is it an addiction?

• Kenny 2001; 2013

  • The sensory properties of drugs of abuse can activate the same brain systems as palatable food

  • Furthermore, drugs of abuse penetrate into the CNS and act directly in these brain systems

  • The sites of action of most major classes of addictive drugs on the neurocircuitry controlling food palatability are indicated

1. Food related hormones interact with the brain reward system

   • Leptin from the adipose tissue

   • Insulin and pancreatic enzymes from the pancreas

   • Ghrelin etc from the gastrointestinal tract

2. Peripheral input from the vagus nerve alters neuronal activity in the nucleus tractus solitatrius → hypothalamus

3. Arcuate nucleus in the hypothalamus mediates activity in the secondary neurons that regulate food intake

• When you are hungry, hormones increase the reactivity of reward circuits via endorphins

• As you eat, the release of how hormones reduces how pleasurable the food is

• Modern foods - high in fat or sugar - may override appetite-supressing hormones

The eating cycle

• In an attempt to overcome the effects of these foods, our body responds by increasing the levels of appetite suppressing hormones

• Brains of obese people respond weakly to food, even junk food

• Indicates a muffled reward circuit leading to depressed mood

• Eating delectable food then temporarily overcomes this, but also perpetuates the cycle

• Obesity is therefore not caused by a lack of willpower, nor is it caused by a hormone imbalance

• In some cases, obesity may be caused by hedonic overeating that hijacks the brain reward system

Overeating and Addiction

• Shared features with drug addiction:

  • All drugs release dopamine in the accumbens

  • Appetising food also releases dopamine in the striatum

  • Obese people have low densities of D2 receptors - same as people with drug addiction

• Volkow et al 2008

  • Decreased D2 density in obese individuals supports the hypothesis that obesity involves dysfunction of similar brain pathways as seen in drug addict s

  • The loss of D2 receptors means a reduction in inhibitory control over corticostriatal transmission

  • D2 receptors are coupled to inhibitory G-proteins

• Kenny et al

  • Sensitivity to reward

  • Intracranial Self-Stimulation (ICSS)

    • Cafeteria-style diet (high sugar) for 0,1 or 18-23 hrs/day for 40 days

    • Development of obesity was closely associated with worsening deficit in reward threshold (elevated threshold for reward)

    • Similar to extended access to cocaine or heroin

    • Extended access to highly palatable food induces addiction-like deficits in brain reward function

    • This persisted for more than 2 weeks after the diet was removed, even though their body weight returned to normal

    • Striatal D2R expression

      • Overconsumption might reduce D2 receptor density (as in humans), contributing to reward hyposensitivity

    • D2R viral knock-down - vulnerability?

      • D2Rs knocked-down in the dSTR via infusion of a lenti-virus

      • Increased vulnerability to diet-induced reward hypofunction

    • Compulsive overeating

      • 30 min access to caf diet for 5-7 d in operant chamber

      • Conditioning of light with foot shock

      • Cue light exposure reduced food intake in chow only and short access rats, not extended access rats

      • it also did not influence caf diet intake in D2RKO rats

<aside>

• Ease of access to palatable high-fat food is important risk factor obesity

• Decreased sensitivity may reflect counteradaptation to oppose overstimulation by food

• Hypofunction may contribute to further overconsumption to alleviate this state

• D2R changes may be associated with genetic vulnerability, suggesting predisposition to accelerated development of obesity in some individuals Evidence of food seeking despite adverse consequences

• This supports previous work suggesting that obesity and drug addiction arise from similar neuroadaptive responses in reward circuits:

  • Binge eating

  • Escalation </aside>

• However

  • Others suggest obesity and drug addiction are fundamentally different

    • Tolerance and withdrawal do not occur in obese individuals in the same way

    • Also we would have all been then classified as food addicts as food is essential to our survival

    • But maybe the food today is not what we evolved to eat?