Week 3

Question 1

What is behavioral genetics? (3)

Answer 1

Talking about the heritability of behavior or behavioral conditions

Meant to clarify the role of genetic vs. environmental risk factors in SUDs and addiction

Estimates heritability based on correlations between pairs of relatives, often twins

Question 2

What does the Verhulst et al meta-analysis of studies examining AUD reveal? (2)

Answer 2

Looked at twin and adoption studies to look at the effects of nature (twins raised separately) versus nurture (twins raised together) on the development of AUDs

Found that 50% of the risk is heritable while in 10% of the risk is due to shared environment

Question 3

What is molecular genetics?

Answer 3

Aim is to identify the genetic variants that explain heritability of SUDs and addiction

Question 4

What are different molecular genetic approaches? (3) What is the limitation of these methods? What is the solution?

Answer 4

Linkage analysis looks at a family tree and traces patterns of genes tied/linked to SUDs

Candidate gene approaches want to test a specific polymorphism that could be a factor in SUDs

Genome-wide association studies (GWAS) assess polygenic risk by looking at thousands of people with and without SUDs to look for general and specific genetic risk

They are often insufficient as they only look at one or two genes/factors, which isn’t the full picture

More valid when combined with behavioral genetics studies

Question 5

What two kind of risks did a recent GWAS meta analysis separate genetic liability to SUDs into?

Answer 5

General polygenic risk (multiple causes/sources)

Substance-specific addiction risk (PDE4B gene tied to having risk for smoking, alcohol, opioid and cannabis addiction)

Question 6

What does the study “does polygenic risk for substance-related traits predict ages of onset and progression of symptoms?” demonstrate? (4) What is a limitation?

Answer 6

Found a genetic link to transition points and symptom progression for my people of European and African ancestry

Transition points include age of first substance use, regular use, reporting problems to healthcare professional and DSM SUD diagnosis

Polygenic risk is correlated with all transition points for Europeans whereas findings are mixed for Africans

Demonstrates that certain genes are associated with substance use and transitions/changes to SU

It was a small sample which is a limitation but is a starting point

Question 7

What study discovered the neurobiology of reward?

Answer 7

A McGill study identified the reward centre in the brain by studying the effects of electrical stimulation on certain areas of rat brains

Rats would consistently hit a lever due to the sensations it sent to the brain and prioritized it above all else (parenting, food, sex)

Question 8

How does the neurobiology of reward relate to humans and substance use? (3)

Answer 8

The exact location in the human brain is still subject to death but it is believed to involve the dopamine system and its opioid-releasing neurons

Stimulants and other drugs increase dopamine release in the nucleus accumbens, which is located in the ventral striatum

This led to a general theory of addiction in which addictive psychoactive substances release dopamine but non-addictive psychoactive drugs do not

Question 9

What is dopamine theory? (2)

Answer 9

States that drugs directly or indirectly increase dopamine levels in the brain

The mesolimbic dopamine system is most often associated with and seen as the key to addiction

Question 10

How does the mesolimbic dopamine system work? (2)

Answer 10

Located in the ventral tegmental area

Substances of abuse hijack the MDS because the amount of dopamine is increased so much that natural dopamine releases become insufficient and it is the only thing you want now

Question 11

How does cocaine affect the brain? (2)

Answer 11

It blocks certain paths and transporters designed to recycle and reuptake dopamine

This causes a large buildup of dopamine in the nucleus accumbens which gives you the pleasure/high of cocaine

Question 12

How do amphetamines affect the brain? (2)

Answer 12

Since amphetamines are similar in structure to dopamine, they can move from outside the neuron into the cell via dopamine transporters or through the membrane

Once inside, they force dopamine out of their storage vesicles and expel them into the synapse, creating a high

Question 13

How does dopamine theory relate to addiction? (4)

Answer 13

Addiction is thought to be the result of repeated stimulation of the mesolimbic system, which triggers reorganization in the brain’s neurocircuitry

These changes may mediate positive reinforcement, motivation, craving and relapse for the drug

As people become more driven to use the drug, the drive can also progress to a state of negative reinforcement (using the drug because if you stop, you go into painful withdrawals)

The longer you use the drug, the more so it turns from positive reinforcement to negative

Question 14

What are the two neural mechanisms underlying vulnerability to addiction?

Answer 14

Neuroplasticity and neuroadaptation

Question 15

What is neuroplasticity? (5)

Answer 15

The brain’s ability to reorganize itself by forming new neural connections throughout life

Allows the neurons in the brain to compensate for injury or diseases and the adjust their activities in response to new situations or to changes in their environment

Important for learning and memory

The more you do something, the more your brain will change to accommodate that thing and become more vulnerable/open to it

If you stop the action after the brain is reorganized, it will create a negative result because it has reorganized to need it

Question 16

What is neuroadaptation?

Answer 16

The process whereby the body compensates for the presence of a chemical in the body so that it can continue to function normally

For people who abuse substances, it leads to tolerance and dependence on a substance because it is now your new normal and required to maintain that new functioning normal

Question 17

What is sensitization?

Answer 17

Occurs when repeated administration of a drug elicits escalating effects at a given dose

Question 18

Does dopamine theory apply to substances other than cocaine and amphetamines? (3)

Answer 18

A literature review shows that dopamine is not at the centre of every addiction or SUD

While it is good for stimulants and alcohol, research is not as consistent for nicotine use, ketamine, THC and diamorphine

Dopamine theory does still tend to dominate the field though

Question 19

What are two challenges to dopamine theory?

Answer 19

The lower availability of striatal dopamine receptors is not consistently observed across different drugs (not in cannabis)

Decreased dopamine release in dependence is not consistently observed across different drugs (not in cannabis)

Question 20

What are 4 takeaways from the DA theory of addiction?

Answer 20

Dopamine release seems to apply better to stimulants like cocaine

Mixed results from non-stimulants should have given the field pause for thought

Research has largely focused in the striatum even though decision-making, which is a big part of addiction), mainly takes place in the cortex

DA likely has other roles and we are only beginning to understand

Question 21

What does the insula have to do with craving? (3)

Answer 21

The insula is involved in a network of brain regions that represent bodily states associated with emotion and decision making

If you conceptualize cue-induced craving as an emotion, drug seeking cues activate the insula and craving emotions

Using this logic, lesions in the insula should make it easier to fight addiction and relapse since it should stop cravings

Question 22

What does the Naqvi et al. study look into? (3)

Answer 22

The study started by studying emotions and craving as an emotion, which led to addiction

They looked into 19 patients with insula lesions and 50 comparison patients with lesions adjacent and non-adjacent to the insula, all of them smoking an average of a pack a day at the time of the lesion due to stroke and similar in criteria and background

Found that there was no difference in quit rate between the groups but among patients who did quit, those with insula lesions were more likely to experience a disruption of their smoking addiction

Question 23

What does the Suner-Soler et al. study look at? (4)

Answer 23

A prospective analysis of the link between insula damage and quitting smoking and disruption of addiction over time

Compared regular smokers who had insula and non-insula strokes

Found those with insula strokes were more likely to quit smoking over a 6-month and 1 year follow up period

Also were more likely to experience a disruption of addiction

Question 24

Is cue-induced drug craving linked to activity in the insula among substances others than cigarettes? (2)

Answer 24

Multiple meta analyses have different results, which some saying yes to cocaine, nicotine and alcohol and others saying no

Lots of studies point to the insula relating to nicotine and alcohol dependence

Question 25

What are the 2 kinds of drug-seeking behaviors/modes?

Answer 25

Goal-directed and automatic

Question 26

What is the goal directed mode of drug seeking? How does the insula impact it? (3)

Answer 26

Usually occurs in the earlier phase of addiction There is conflict between drug-taking and alternative goals like avoiding negative consequences and adhering to responsibilities, a decision-making process takes place where one must determine which goal is more important The insula motivates drug seeking behavior motivated by the hedonic value of drug-taking via interoceptive representation (you can taste how good it will be when trying to make that decision)

Question 27

What is the automatic mode of drug seeking? (3)

Answer 27

This is in the later phase of addiction There is no decision or conflict, you just do the addictive behavior Result of neuroplasticity and changes in the brain

Question 28

How does the developing brain relate to addiction according to the Conrod et al. study? (3)

Answer 28

As teenagers, we are younger and our brains are less developed, making us more vulnerable to addiction The study looked at the developing brain and addiction and risk through studying differential rates at which certain brain structures and connections may underlie stereotypical adolescent behaviors contributing to addiction (sensation seeking, impulsive and risky decision making) Addiction relevant subcortical circuitry implicated in reward processing, motivation and emotional reactivity seem to develop early during adolescence

Question 29

Explain the global dual-process models of cognitive control in adolescents and addiction (3)

Answer 29

Increased sensitivity to reward/positive-affect/motivational cues and immature responses lead to risk for the initiation and maintenance of uncontrolled behaviors like SU The neurodevelopmental imbalance in adolescent fronto-basal ganglia limbic circuitry is further prolonged or exaggerated by heavy substance use during this developmental period, resulting in more uncontrolled patterns of substance use and increasing risk of SUD In other words, youths undeveloped and immature brains make them vulnerable to use substances and when they do, it messes up their brain so that they continue using them, putting them at risk of a substance use disorder

Question 30

What overall effects did the study find of substance use on developing minds? (3)

Answer 30

Drug-dependent adolescents demonstrate heightened drug reactivity to reward processing Behavioral task performance and control is still up for debate but fMRI studies show increased behavior inhibition Stress and HPA activity in youth can be a risk factor for SU

Question 31

What does the longitudinal research show according to Conrod? (4)

Answer 31

Few studies have been able to tease apart consequences of SU and neurodevelopmental factors that put them at risk of SU just from being an adolescent For cannabis, heavy use predicted reduced growth in cognitive functioning over time For alcohol, AUDs were predictive of neuropsychological functioning against baseline performance measures Overall, adolescents who use substances earlier in life showed worse executive functioning

Question 32

How does early adverse experiences impact addiction? (2) What are the three brain structures most impacted?

Answer 32

As the number of ACEs rises, so too does the risk of addiction issues and other health issues Early life experiences appear to modify our brain structures and other aspects of our brain The dopamine system (motivation and reward), the oxytocin system (bonding) and the glucocorticoid system (stress)

Question 33

How do early life experiences impact the DA system at 3 different levels?

Answer 33

At the molecular level (in rats), stress in offspring may change the expression and function of DA system and the quality of maternal care received early in life influences development of the DA system in the offspring At the neuroendocrine level (in rats and humans), stress may shift levels of stimulus-evoked DA release At the behavioral level (in rats and humans), young exposed to early maternal deprivation and adversity showed heightened reactivity to novelty in adulthood and novelty/sensation seeking behavior (like addictive substances and behavior) At the behavioral level (in humans),

Question 34

How do early life experiences impact the OT system at 3 levels?

Answer 34

At the molecular level (in rats), low levels of maternal care in early life is directly associated with reduced density of OT receptors and their ability to form connections and bonds with others (more aggressive) At the neuroendocrine level (in rats, monkeys and humans), lower OT levels were found in those exposed to early adversity/stress At the behavioral level (in rats, monkeys and humans), social impairments and attachment issues were observed

Question 35

How do early life experiences impact the GC system at three levels?

Answer 35

At the molecular level (in rats), early deprivation produces long term abnormalities in GC functioning At the neuroendocrine level (in rats, monkeys and humans), found increased reactivity of the HPA axis in response to stress and reactions in humans are mixed At the behavioral level, alterations to the GC diminish the capacity to effectively respond to stress

Question 36

How does repeated exposure to addictive substances affect users? (4)

Answer 36

Results in abnormal DA release due to neuroadaptations Release of GCs and HPA axis gradually decrease In withdrawal, the HPA axis intensifies which can lead to continued substance seeking or relapse OT decreases and neurosynthesis of OT is reduced

Question 37

What is the impact of intergenerational effects? (4)

Answer 37

Impaired maternal care can shape the early life experiences of their offspring Transition to motherhood is associated with neuroadaptations in the DA, OT and GC systems Substance using mothers may be more vulnerable to deregulated functions in those systems These systems are central to maternal care and may be co-opted in maternal substance addiction