Lec 3 - Genetics of Addiction, Psychosocial Explanations for Addiction

Convergence that addiction is a disorder of _____

"*various cycles*" Or patterns of maladaptive *overconsumption* that over T become increasingly *difficult to change*

Psychosocial models: *Personality factors* - "addictive personality" concept

"Addictive personality" perspective - elicited interest but is *controversial* = *weak* empirical support* - IDEA: Folks w addiction have common set of personality traits that make them prone to all sorts of addictions - food, sex, alc, drugs - *NOT SUPPORTED by science*

Developmental psychopathology model: what does it mean to "mature out"? What behavior the model consistent with?

"mature out" process = for many individuals, particularly for *alcohol use* - fostered by *role transition* (work, marriage, etc.) - e.g. drink heavily in college -> mature out/phase out of behavior - *natural recovery* Consistent w *normative exploration/experimentation* in adolescence + young adulthood - young brains = wired to experiment + explore!!

Success stories for candidate gene: ALDHD2 gene - role

*Aldehyde dehydrogenase* - role in *alcohol metabolism* - asians have *flush* = alcohol poison -> discomfort + sedation -> difficult time breaking down alc - Variation gene associated w flushing response - Neg response to alcohol - *Protects you from developing alcoholism

*Level of Response to alcohol* - how is it measured? - what is a low responder? - heritable?

*BEHAVIORAL* Endophenotype for addiction *SRE* = *Self-Rating of Effects of Alc* = measures one's *reponse level* to alc - First 5x you ever drank If need *more drinks* to reach certain levels of intoxications = *low responders* = *higher risk* for developing problems Yes, level of response = *heritable construct* - which means may differ bt ppl due to candidate gene

Cog processes: what can motives and expectancies be thought of as? What is an important complement?

*Explicit reflective* cognitive processes or *declarative "top-down"* process in which individual REPORTS *introspectively available cognitions* about drug - what is available, what can be accessed Important complement: *implicit automatic* cog processes or *unconscious "bottom-up" that reflect *SALIENCE* of drugs -> *cognitive bias*, impulsivity -> so automatic, sometimes not accessible to individuals - e.g. smokers do attention task: spend more time attending to smoking-related stimuli - Cog bias ameliorated to cognitive training, in itself could serve as a *treatment option*

GWAS for alcohol

*Genome Wide Association Studies* - frontier in genetic research; more technology -> look at entire genome Three GWAS for *alcoholism*: - results not conclusive - *WHY*: 1. few genes cross genomewide significance level - when they do, candidate genes advanced have 2. unknown functional significance and biological plausibility - 3. REQUIRE *high significance level* bc we carry thousands and thousands of markers to see if they predict particular phenotype

Endophenotype for alcoholism: Individuals who can *drink others under table" have a ____ risk of developing AUD

*HIGHER* - *Innate tolerance* = individuals from onset of dirnking history can handle more - this is a *risk factor!* - drink more + expose brain to more alc -> experience more neg consequences level of response = behavioral endophenotype for addiction

Patrick sees his hip friend using cocaine at a party and decided to try it too. What kind of peer influence is this?

*Modeling* Not an overt offer Not permissive social network Don't know social norm

Success stories for candidate gene: CHRNA5 gene

*Nicotinic cholinergic receptor* - If you are an occasional smoker, variation in gene determines whether you become *habitual/dependent*

What does the developmental psychopathology model say about a critical developmental window? What is this developmental window similar to?

There is a critical *developmental window* for *addiction* from *adolescence to young adulthood* Similar to: an *etiological "critical period"* - sets stage for healthy AND unhealthy sub use across lifespan Perspective enhanced by UNDERSTANDING *neurocog development*

Psychosocial Models: Reinforcement-Based approach - type of learning - role of drugs - types of reinforcement - recent application of model

- *operant* learning approach Common across substances: - *substance use* = fundamentally a form of instrumental learning Behavior = determined by *consequences* - particularly *reinforcing* prop of drugs - Drugs = *reinforcers*; agents of operant learning - Do it once, feel good, signals to brain "you should do more of it" - *pos + neg reinforcement*: -> positive = do to feel good -> negative = do to alleviate negative symptoms Recent application of model: *Behavioral economics* is a reinforcement-based model - Delay discounting - Purchase tasks - est. money use - how much someone is *willing to pay* for alc/drugs as way to *estimate value of commodities* Part of theory is to *quantify reinforcer value*!!

what we know so far about genetics of addiction: - Family studies - Twin studies

- 1. *Family studies* = provide initial *evidence* of heritability -> some disorders more common in certain families - 2. *Twin studies* = provide heritability *estimates*

Psychological model: *Cognitive processes* - emphasis - define expectancies - how do they affect behavior?

- Attention to people's *thoughts and beliefs* about drugs of abuse - *Mental or information processing mechanisms* - involve *expectancies AND motives* - *Expectancies* = cognitive templates -> 1. *POSITIVE* expectancies can *drive behavior* - e.g. if friend lists more pos cognitions about alc -> more likely to drink "It'll make me more talkative, social, etc" -> 2. Account for *placebo effect* - e.g. Lab: nonalc beer -> lot of ppl cannot tell difference, report feeling drunk; cognitions DRIVE behavior -> 3. do *not* necessarily reflect direct *pharmacological effects* - children before drinking have expectancies about what it'll be like

Main Concepts of Addiction genetics

- Disorder of complex genetics - contribution from genetic + environmental factors - long way to go - large-scale studies, GWAS

Genetic association studies - What approach do they use? - What do they seek to demonstrate?

- Use "*candidate gene*" approach = examine *frequency of genotypes* among CASES (i.e. affected individuals) vs. CONTROLS (i.e. unaffected) - *Case* = individuals affected by disorder - Is candidate more prevalent in cases? Seek to demonstrate that *frequency of candidate* gene of interest = *HIGHER* among cases rel. to control -> supports hypothesis that candidate gene maybe *associated w disorder* of interest

Components of addiction

- genetics - environment - physiology - behavior genetics is the counterpart to environment

What are some normative personality traits consistently associated w addictive behavior (we all have, but in excess may predispose someone to addiction):

1. *Impulsivity*: capacity for self-control of arising impulses 2. *behavioral tasks* - Studies: e.g. gambling tasks, ask them to take *risks* (behave in certain way), then assess behavior 3. *Barrat impulsiveness scale (BIS)*: rarely, occasionally, often, always - items capture *risk-taking and impulsivity* - "plan task carefully" - "save regularly" - "concentrate easily" More impulsive = more *likely to engage w substances* - when seen: at *initiation* AND *continuation* of use

THREE types of peer influences

1. *Over offers* = idea that you'll be given opp to experiment w subs by virtue of peer group (pass joint, offer drink) 2. *Modeling* = see someone you like/resepect smoking joint -> influences you to try it 3. *Social norms* = esp college students, *OVERESTIMATE* norms of use - Intervention: CHALLENGE belief about norms

Which personality trait have been linked to addiction?

1. *impulsivity* = strongest link LATER on, develop *compulsivity*

Heritability estimates for following SUDs - AUD - Cannabis use disorder - Cocaine use disorder - nicotine dependence

1. Alcohol = 0.58 (due to genetic factors) 2. Cannabis = 0.71 3. Cocaine = 0.70 4. Nicotine = 0.73 Average for all substances is 50/50 for genetics/environment (point made in discussion)

Recommendation for GWAS studies

1. Increase sample size 2. Narrow phenotype

Psychosocial models of addiction

1. Reinforcement-based approach 2. Variability in drug effects 3. Cognitive processes 3. Personality factors 4. Developmental psychopathology

Social factors reflect

Influence of *fam, friends, extended social networks* including sociocultural context For PREVENTION: give alternative behaviors or activities

Social models of addiction

1. Social networks 2. Social influences + mechanisms 3. Sociocultural influences

Genetic linkage and association studies - what does linkage analysis involve? - what does it find? - what needs to be significant for there to be genetic linkage? - LOD Score - classical critical LOD score

1. What: examines *family pedigrees* of affect individuals (i.e. *probands*) in order to find *chromosomal regions shared* among *affected* relatives, but NOT among unaffected relatives 2. Finds: *genetic locations in chromo* - shows that a *genetic marker* of known genetic location tends to be TRANSMITTED along w DISEASES w/in fam 3. *Transmission* of marker among affected relatives must be significantly greater than transmission of marker expected *by chance* 4. *LOD scores* = quantitative index of linkage - *higher* scores = *greater evidence* of linkage 5. *Classical critical* LOD score = *3 or higher*

Parent influence when its structure + warmth vs harsh

1.*structure + warmth* are *PROTECTIVE* against misuse/dangerous use 2. *harsh* parenting = *risk factor* -> more likely to externalize, rebel

If cocaine use disorder has a heritability of 70%, what percentage do environmental factors contribute to the development of cocaine use disorder? Impossible to determine 35% 30% 15% 70%

30%

Q: Addiction is a disorder of ____ genetics A. complex B. Mendelian C. single-gene D. high-genetics

A. complex mendelian = another term for single-gene disorders - unlikely to account for addiction altgoether

Social model: Sociocultural influences - 4 factors?

Broaden spectrum Social influences on addiction include: *higher-order factors* within society + culture: 1. *religion* - many AA groups embedded in religion 2. *Economic conditions* 3. *Public policy* - taxation, legal age, density of outlets (applied to legal subs + gambling only) - more expensive cig = less people buy - town regulates how many e.g. liquor stores in particular area 4. *Cost of care + access to ev-based intervention*

Candidate genes in level of response to alc

Candidate genes in *GABA A receptor* = underlie expression of this behavioral "response level" endophenotype Predisposes individuals to have *differential responses* to alcohol

Social model: Classes of social influence and mechanisms - what is considered powerful in adolescence? - what is considered powerful beyond adolescence?

During adolescence + young adulthood, 1. *parental influence* + 2. *peer affiliation* are VERY powerful BEYOND adolescence: addiction occur in *couples/dyads* w more *negative consequences* including *intimate partner violence* - use sub together - meet up in environments conducive to drug/alc use - challenging for individuals to quit together; for one to quite while other doesn't

Definition of heritability

Extent to which *genetic individual differences* contribute to individual differences in *observed behavior* Statistical defn: *proportion of phenotypic variance* attributable to *genetic*

T or F: Experimentation w drugs in young adulthood is maladaptive and not normal part of development

False Chronic use is maladaptive, but experimentation is not

T or F: Your expectations about how a drug will make u feel cannot overpower actual pharmacological effects of drug

False it's called placebo effect

1. What kind of concept is heritability? 2. Heritability estimates for alcoholism

Heritability = *population genetics* concept - est. *risk* for POPULATION, not for a particular individual Divide pie into genetic vs. environmental causation: *Heritability est. for alcoholism* range bt 40-60% of variance = On avg, *40-60%* of risk for developing alcoholism *attributed to genetics* - This is considered a *moderately heritable* disorder *Schizo + bipolar* disorder illness = est of *70-80%* (higher)

Addiction = complex disorder attributed to interaction of _____ and _____ With what framework should we study alc susceptibility?

Interaction of genetic and environmental factors - *Genetic factors* that affect susceptibility to addictive disorder *may* be involved in *only certain components* of spectrum of disorder -> NOT EVERYONE becomes addicted by SAME pathway!!!! *Framework* to study alcoholism susceptibility: focus on *Particular* component of dependence spec = use *endophenotype approach

Why are endophenotypes helpful in understanding the roots of addiction? Endophenotypes reflect the combination of genetic and environmental factors It is easier to identify the genetic basis of endophenotypes The presence of addiction is highly correlated with some endophenotypes Endophenotypes allow researchers to estimate the heritability of different substance use disorders

It is easier to identify the genetic basis of endophenotypes

Etiology of Addiction: what makes a successful addiction model?

It must synthesize pharmacological, experiential, cultural, situational, personality components in fluid description of addiction motivation

Which of the following is a cognitive process that individuals have conscious awareness of? Cognitive bias Bottom up processes Impulsivity Motives

Motives + expectancies no conscious awareness for: cog biases, bottom up processes, impulsivity

Motives in cognitive processes - how assessed - motive for opioid users - motive for several drugs

Motives also cognitive determinants of substance use - motives reflect *reasons* person reports for *WHY* they use drug - typically assessed in *self-report* format e.g. "I feel a strong bond w my cigarettes"; "I'm around smokers much of time" reflects social motive 1. *Pain management* = important motive for opioid users 2. *social enhancement* =motive common across several drugs

Another psychological model: *Variability in ACUTE drug effects* - emphasis - early theory model - effects of alcohol - response component

Not competing, but parallel model to explain fx of alc/drugs 1. Emphasizes: *Variation* in drug's SUBJECTIVE effects as a *determinant* of *use and misuse* - Drink -> feel great -> want to drink more - Drink -> flushing response -> do not want to drink - alc + drus serve a purpose: *individual differences* in how much we experience reinforcing effects of alc + drugs, some due to genetics -> DIFFERENCES determine *whether someone will use it more or not* 2.*Tension-reduction model*: early theory that alc use was *predicted by ability to reduce tension* in given model 3. *Stimulant* AND *Sedative* effects - stimulant effects are risky; sedation is protective 4. Level of response to alcohol

Which kind of learning is tied to addiction in the reinforcement-based approach? Learning through peer modeling Pavlovian learning Experimentation learning Operant learning

Operant/instrumental learning Don't get confused: cues are through pavlovian learning/classical conditioning

Social model: *Social networks model*

Proposes that individuals *self-select into networks* populated w ppl exhibiting *similar levels* of sub use (or lack thereof) - Birds of feather flock together - *Social network analyses*: social media, scientists want to quantify them to study them more systematically *Change* in social networks during *treatment* can *SUPPORT* recovery (i.e. *role of AA*) - escape from permissive environments

Theories most appealed to you

Reinforcement-based approach variability in drug effects

Psychosocial model: *Developmental psychopathology* - what influences does it consider?

Seeks to understand *psychiatric conditions (disorders, including addiction) as maladaptive deviations* from normative development -> aberrations + experiences through environment may *change course of someone's behavior + pathology* Broadened lens to capture influences *PRIOR* to drug use - *Prenatal influences* - babies in utero can show withdrawal! - *Adverse childhood events*

Pedigree

Segments of DNA chromos transferred alongside disorder = GODO for single-gene or Mendelian disorders - Approach ≠ successful for complex disorders (i.e. psychiatric disorders)

Mona, a young adult college student, has an alcohol use disorder. Most of her friends drink heavily. This example is supported by which model of addiction? Social influences and mechanisms Social networks Sociocultural influences Personality factors Developmental psychopathology

Social networks

Which of the following models takes the broadest view on addiction? Social influences and mechanisms Personality factors Social networks Developmental psychopathology Sociocultural influences

Sociocultural influences

What is one weakness of genome-wide association studies? Researchers need to select a candidate gene of interest before beginning the analysis It cannot identify genetic markers for endophenotypes They look at the entire sequence of DNA The threshold to designate a gene as important is very high

Threshold to designate gene as important is very high

____ studies reveal heritability of a trait A. Family B. Twin C. Adoption D. Association

Twin studies - give most precise estimates of heritability *Heritability* = how much given phenotype/trait/disorder is due to genetic facotrs

When Carmen smokes marijuana, she feels relaxed, calm, and in high spirits. When Lena smokes marijuana, by contrast, she feels anxious and paranoid. Which of the following models attempts to explain why Carmen is more likely to develop a cannabis use disorder? Reinforcement-based approach Cognitive processes Variability in drug effects Personality factors Social network perspective

Variability in drug effects

Translational model in genetics of addiction

Want to link behavioral disorder to genes = BIG leap Idea: identify behavioral or brain or cell functions w role in disorder = more tractable to understand

Neurobiological theories emphasize - define neurobiological

drug's ability to hijack ancient brain sys responsible for adaptive motivation, learning, exec control *neurobiological* = brain systems + adaptaions

What is critical in psychological theories?

elevations in *reinforcing value* of drug effects + deficits in *self-regulatory capacity* are critical INCLUDES - reinforcement-based approach: operant conditioning - Variability in drug effects: biological response (innate); paranoid when high - cognitive processes: thoughts + beliefs about drug; top-down (expectancies + motives) - personality factors - developmental psychopathology: critical developmental window; maladaptive deviations from norm development; mature out

Etiology conclusions: - goal of scientific theory - three major sections of biopsychosocial approach

goal: "carve nature at its joints" - etiological models inform treatment development - multidimensional, mult levels of analyses Three major sections: 1. biology 2. psychology 3. social

According to the reinforcement-based approach, a person suffering from an alcohol use disorder would estimate the cost of a bottle of vodka as _________ a person that does not suffer from an alcohol use disorder. higher than lower than the same as

higher than est. money use - how much someone is *willing to pay* for alc/drugs as way to *estimate value of commodities*

If an individual possesses the aldehyde dehydrogenase gene, that individual is... more likely to develop an alcohol use disorder more likely to become a habitual smoker less likely to become a habitual smoker less likely to develop an alcohol use disorder

less likely to develop an AUD

Endophenotype approach

phenotype that is not the disorder per se but *related to the disorder*

Cognitive bias

systematic error in thinking