Genetic and Neuro Factors in Addiction

Attributional Models

**See PPT Slides**

Some Intermediate-Level Factors in SUD Etiology

*Intermediate = factors in-between general and idiosyncratic - Religiosity - Parental and peer influences (e.g., parental monitoring, acculturation) - Early stressors and trauma = parental loss; physical, sexual, and emotional abuse - Parental drug use or dependence - Socioeconomic status - Parental depression - Current stressors

Macro-Level Factors in SUD Etiology

*Macro = general (or generic) influences, affecting or shared by all or many - Alcohol laws - State distribution policies - Drug laws - Outlet density = number of places where alcohol available (e.g., bars, stores) in certain geographical area

Micro-Level Factors in SUD Etiology

*Micro = idiosyncratic (something peculiar to an individual) factors - Psychological factors - Alcohol expectancies and drinking motives - Personality traits (e.g., novelty and sensation seeking) *There is no such thing as an "addictive personality" - Subjective reactions (e.g., flushing response among certain ethnicities) - Genetics --> genotype - Explain 40%-60% of vulnerability to addiction

Half-second Delay

- "Free won't" (healthy decision-making) lags behind the impetus (desire, urge, "decision") to use by half a second

Phenotypes in Addiction

- Addiction = genetic vulnerability or probability, not genetically determined - Environment plays important role in determining whether genetic vulnerability is expressed - Remember: phenotype = interaction between genetic make-up and environment (G X E) - this implies that addictions develop - they are not instant - and therefore they follow certain phases or pathways - presence of substance use, dependence, withdrawal symptoms - severity of alcohol use disorder - Polygenic → no one gene is responsible • Genes not always "active" • A person's genotype modulates his/her responsiveness to environmental • Reciprocal (not linear) interaction between genetic and environmental factors

Drug Effects on Frontal Lobe

- Chronic exposure: - distort functions - reduce blood flow - decisions mading - opposite of tolerance *Ask cl when they first started to use --> 15 yrs old is a critical age

Addiction is a(n)...

- Complex interplay/interaction of biological or genetic influences/factors AND environmental influences/factors

Etiological Distinctions

- How substance use begins ≠ How substance use problems begin: -environmental factors explain initiation of substance use -genetic factors explain escalation or worsening of problems related to substance use - Vast majority of persons who use substances do not develop substance-related problems - Etiology of Addiction? - Complex interplay of macro, intermediate, and micro factors - from "nature vs. nurture" to "nature via nurture"

Dopamine (DA) Cont...

- Most drugs ↑ level of DA in brain regions critical for reward by blocking reuptake or reabsorption - and ↑ levels of DA make neuronal pathway more sensitive, thereby activating reward pathway - Fewer DA receptors may: - Be consequence of drug use (e.g., cocaine) - Predate drug use and therefore represent a vulnerability factor (high DA receptor levels serve to protect against substance use/abuse)

Genetic Vulnerability or Biological Susceptibility vs. Responsibility

- biological constraints = knowledge of these constraints will hopefully lead to treatments

GABA

- brain's chief inhibitory neurotransmitter - stabilizes brain and prevents over-excitation of neurons - alcohol enhances GABA activity

Dopamine (DA)

- can produce both excitatory and inhibitory effects - involved in movement, learning, attention, appetite processing - Parkinson's disease caused by deficiency of DA - overactivity or oversensitivity of DA receptors linked with symptoms of schizophrenia - less DA activity found in specific brain regions of adults with ADHD

norepinephrine (NE)

- excitatory neurotransmitter - involved in maintaining wakefulness and alertness - during panic states (e.g., for person with panic disorder), centers in brain that ordinarily alert an individual to impending danger are "bathed in" NE

epinephrine

- functions to maintain heart rate, blood pressure - Adrenalin

serotonin (5-HT)

- involved in inhibition of activity and behavior - active in mood regulation, control of eating, sleep and arousal, and pain regulation - thought to have an opposing action to excitatory neurotransmitters, e.g., norepinephrine

DA and Substance Use/Addiction

- substance use increases release of DA, similar to other pleasurable activities, e.g., sex - most drugs target the brain's reward system by flooding the circuit with DA - with continued substance use, brain adjusts to surge in DA, resulting in disruption of natural reward process by producing less DA or by reducing number of DA receptors

Neurotransmitters

- two most important types of neural or cellular activity: 1. Arousal - includes regulation of activity and rest 2. Orientation - to time, place, and person (i.e., consciousness) - types of messages relayed by neurotransmitters: 1. Excitatory: increases likelihood that impulse will be relayed 2. Inhibitory: decreases possibility that impulse will be transmitted -all neurons or cells can receive both excitatory and inhibitory impulses simultaneously

Genetics and Addiction

1. Genes and environment jointly determine addiction - genes do not work in isolation - neuroadaptation - environmental factors play a substantial role - may play larger role in initiating and continuing use (beyond experimentation) whereas genetic factors take precedence among persons who move from use to dependence 2. Inherited characteristic(s) = predisposition, susceptibility, vulnerability - NOT inherited disease 3. Heterogeneity among persons with addiction in terms of (extent, type of) genetic and environmental contributions 4. Recognizing role of genetic risk factors does not require that addiction be defined as disease 5. Significant implications for identifying effective prevention and tx strategies 6. Genetic testing will likely gain public acceptance, become popular; usher in new ethical considerations and practice guidelines for helping professionals

Mesolimbic Dopamine Pathway

1. Ventral Tegmental Area (VTA) 2. Amygdala (Pleasure, pain) 3. Nucleus Accumbens (expectation, reward) & Ventral Striatum 4. Frontal Cortex *Involves: memory, reward, and judgement

What accounts for escalation or worsening of substance use problems, including dependence?

Biological, psychological processes

"GO!" - "STOP!" Framework

GO! function in anterior, ancient area of brain STOP! function in newer, more recently developed frontal area of brain

Types of Influences/Factors

RISK: - vulnerability - susceptibility - predispositional - Propensity PROTECTIVE: - safe - reduce - religiosity *being born outside of USA

What accounts for onset or initiation of substance use?

Social, environmental factors