Midterm 1 Flashcards
What are the 4 ways of knowing?
intuition, deduction, authority, observation
What is intuition?
i know its true because it makes sense (ex: logic, street smarts)
what is tenacity?
i know it’s true because it’s always been that way
what is authority?
i know its true because the bible, Koran, President, etc tell me it’ts true
what is science?
it’s true insofar as measurable evidence from reliable instruments verify it repeatedly
what 2 types of science is psychology considered
physical and social science
the 6 core influences in the ecological systems theory
(from outside to in)
1. chronosystem (development, time)
2. macrosystem
(social and cultural values)
3. exosystem
(indirect environment)
4. mesosystem
(connections)
5. microsystem
(immediate environment)
6. person
Invested parties in the macrosystem
political dynamics, economic systems, institutional influences
invested parties in the exosystem
parents’ workplaces, extended family cohesion, neighborhood resources
invested parties in the mesosystem
home and school, peers and family, family and church
invested parties in the microsystem
home, daycare, school, peers, teachers, social workers, therapists, psychologists
invested parties in a person
genetics, temperament, learning abilities, neurologists, pediatricians, psychiatrists, other practitioners
how many pages does DSM-5 devote to substance related addicted disorders
107 pages
how many addictive disorders are in DSM-5
40 different disorders
main categories of addictive disorders
- alcohol related
- caffeine related
- cannabis related
- hallucinogen related
- inhalant related
- opioid related
- sedative, hypotonic, or anxiolytic related
- stimulant related
- tobacco related
- other substance related
- non substance related
- gambling disorder
what do the DSM addiction categories focus on and what do they exclude
they focus on specific substances used but do not consider the etiopathophysiology
What is substance abuse?
Maladaptive use of substances which cause impairment or distress:
-School/job problems
-Family dysfunction
-Criminal problems (e.g., a DUI)
-Recurrent use in hazardous situations (e.g., driving drunk)
what is substance dependence
essential feature of substance dependence is a cluster of cognitive, behavioral, and physiological symptoms indicating that individual use of the substance despite significant substance related problems. there is a pattern of repeated self admin that can result in tolerance, withdrawal, and compulsive drug taking behavior
Tolerance Characteristics
- a need for markedly increased amounts of the substance to achieve intoxication or desired effect
- markedly diminished effect with continued use of the same amount of the substance
withdrawal characteristics
- the characteristic withdrawal syndrome for the substance (ex: for cocaine; increased sadness, fatigue, appetite)
- the same or closely related substance is taken to relieve or avoid withdrawal symptoms (ex: for alcohol; benzodiazepines (ex Xanax) might be substituted)
Although conceptually more sensible, there are no clean lines between_____________________?
1) heavy use
2) abuse
3) dependence
so differential diagnosis is unreliable
In class we focus on the ___________________ approach but what are other factors that play a role in addiction
- neuroscientific approach
- other factors include environments, families, neighborhood context, and sociopolitical influences along with biological vulnerabilities
Lifetime prevalence percentages of drug abuse and dependence
8% for abuse
3% for dependence
what is the ratio for people that will experience some form of substance use disorder in their lifetime?
1 in 7
What would be the total number of people that have some form of substance use disorder
20 million people over age of 12
Average number of people with alcohol related disorder from 2002 to 2013
Around 15.1
Average number of people with illicit drug related disorder from 2002 to 2013
Around 3.95
What drug addiction has increased rapidly over the past decade that is not seen in graphs of overall drug use
opioid addiction
What disorders have increased substantially from 2001-2002 to 2012-2013 across nearly all the demographic groups?
Alcohol use, high risk drinking, and alcohol use disorder
Which age group shows the highest increase in the graphs of alcohol use (AU), high risk drinking (HRD), and alcohol use disorder (AUD) seen in class?
People over sixty five had the highest increase
22.4% AU
65.2% HRD
106.7% AUD
what sex had the highest increase according to the AU, HRD, and AUD graphs
Women had the highest increase in all 3 graphs
15.8 AU
57.9 HRD
83.7 AUD
What two races/ethnicities had the highest increase in the AU, HRD, and AUD graphs
Black or Asian/Pacific Islanders have the highest increase percentages
Black rate include:
24.2 AU
62.4 HRD
92.8 AUD
Asian/Pacific islander rates:
29.1 AU
56.5 HRD
77.8 AUD
What is the single most abused substance
alcohol
What is the annual drag on the US economy due to excessive drinking
250 billion
- 180 billion in workplace productivity
- 28 billion in healthcare costs
- 25 billion in law enforcement costs
- 13 billion in motor vehicle accidents
what percent of males and females have experienced 1+ alcohol adverse events
60% of males and 30% of females
What percentage of intimate partner violence in the US involves alcohol
55% of cases of intimate partner violence
(1) what percent of women are sexually assaulted or raped by adulthood and (2) what percent involve alcohol use by male perpetrators
(1) 25%
(2) 12.5%
what is the leading cause of death among to 8 to 34 yo in the US
alcohol related traffic fatalities
What is the ratio of traffic fatalities that involve alcohol
1 in 3
what age group has the highest percent of alcohol use (heavy, binge, and normal use)
21-25 yo w/ total percent of 69.3
26% normal use
30.2% binge use
13.1% heavy use
From 2002 to 2013 what drug use has decreased
cocaine use has trended down from 1.5 mill to .9 mill
from 2002 to 2013, what drug use has remained the same
marijuana
from 2002 to 2013, what drug use has increased
pain relievers
what drug increases rapidly due to prescriptions
opiate addiction because it starts as pain prescription which leads to addiction, contributing to addiction rates
what myth exists about opioid therapy
myth is that risk of addiction is low during prolonged opioid therapy for pain, esp when controlled release compounds are used, but it is not supported by research
by how much has opioid prescription death increased between 1999 to 2014
increased by six fold
what type of prescriptions have increased from 1999 to 2020
opioid prescriptions with synthetic opioids other than methadone (ex fentanyl)
what drug do people turn to after becoming addicted to prescription opioids and why
heroin because it’s cheaper and easier to get
how much have heroin related deaths increased by since 1999 to 2020
have increased by eight fold (from 1500 to 13,165)
what makes heroin more dangerous than prescription
the purity is unpredictable and can be mixed with stronger opiates such as fentanyl and carfentanil
What is the weakest opioid/analgesic
aspirin (non-opioid)
what is the strongest analgesic/opioid
carfentanil
how strong is carfentanil compared to morphine or codeine
10,000-100,000 stronger than morphine and 100,000-1,000,000 stronger than codeine
what was the leading cause of overdose in the US in 2016
fentanyl
what is carfentanil used for
it is used to take down elephants or rhinoceros
what 2 opiate overdose rates have significantly increased from 2011 to 2016
fentanyl and heroin
what benzodiazepine overdose rates has significantly increased from 2011 to 2016
alprazolam
what 2 stimulant overdose rates have significantly increased from 2011 to 2016
cocaine and methamphetamine
Much of vulnerability to substance used disorders is ________________
inherited
how much does the risk for alcoholism increase if a person has an alcoholic parent
increases by 400%
how much does the risk for alcoholism increase if a person has two alcoholic parents
increases over 600%
what percent of vulnerability to substance abuse is genetic
over 50%
what is age of onset determined by
by environment or opportunity
what is age of onset
age of onset is age one becomes dependent
what is determined largely by environment and what is largely due to heritability
age at first drink is determined by environment but dependence is due to heritability
what two factors discussed in class play a role in substance use disorders besides genetics
culture and environment
what country leads in cannabis use among the adult population
iceland
what country leads in cocaine use among the adult population
scotland
what country leads in ecstasy use among the adult population
austrailia
what country leads in amphetamine type stimulant and prescription stimulant use among the adult population
El Salvador
what country leads in prescription opioid and opioid use among the adult population
US
what country leads in opiate use among the adult population
Afghanistan
what country leads in tobacco use among the adult population
US
who first initiated the “war on drugs” term
Richard Nixon in 1971 when he stated that drug use was “public enemy Number 1”
who described how the war on drugs was invented for subversive political purposes
John Ehrlichman (assistant to Nixon for Domestic affairs) in an interview with Dan Baum
Famous John Ehrlichman quote from interview in 1994
“The Nixon campaign in 1968, and the Nixon White House after that, had 2 enemies: the antiwar left and black people. You understand what I’m saying? We knew we couldn’t make it illegal to be either against the war or Black, but by getting the public to associate the hippies with marijuana and Blacks with heroin, and then CRIMINALIZING BOTH HEAVILY, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did”
________________ played a role in Reagan’s radio campaign
political expediency
what was the probable cause of the increasing crime rates during Reagan’s presidency
crime rates increased due to economic downturn which lead to jobs being scarce
What programs were reduced when Reagan cut the “spider’s web of welfare”
- the Aid to Families with Dependent Children (AFDC) programs by 50%
- the supplemental nutrition assistance program (food stamps)
- Medicaid (all who lost AFDC funding lost Medicaid eligibility too)
what was the result of the cut of “the spider’s web of welfare”
poverty rates in US rose by about 35%
What did Reagan create to establish a stricter federal sentencing guidelines
Reagan created US sentencing commission and implemented the Sentencing Reform Act
Number of people incarcerated and the cost of maintaining that number imprisoned
2.3 million are in US prison system and costs about 80 billion annually
what percent of those incarcerated are there due to drug related crimes
50%
Who gets incarcerated (by race) and at what rates
Blacks use drugs at same rate as whites but are more likely to be arrested and incarcerated
Disproportionality in Incarceration (rates in US population versus prison population)
Latinos make up 12.55% of total US pop but make up 18.26% of prison pop
Blacks make up 12.32% of US pop but make up 43.91% of prison pop (4x more in prison than in US pop)
Blacks comprise _____% of US drug users, but _____% of those arrested for drug violations, _______% of those convicted, and ______% of those sentenced to prison
13; 37; 59; 74
lifetime likelihood of imprisonment for US residents born in 2001 for:
men
white men
black men
latino men
Men: 1 in 9
White men: 1 in 17
Black men: 1 in 3
Latino men: 1 in 6
How did the percentage change for the Blacks being sentenced more than Whites after the federal mandatory minimum sentencing
The average federal sentence was 11% for black than for whites before and after it was 49% higher
What is the significant difference in the mandatory minimum sentencing
the sentencing established a 100:1 ratio for powder versus crack cocaine
why is there a difference in the powder versus crack cocaine minimum sentencing
Based on assumption that crack is more dangerous than powder but in reality is probably due to the fact that people with lower income are more likely to deal with crack cocaine whereas people with more income will deal with powder cocaine
What are the 4 problems with the disparities in mandatory sentencing
- cocaine is cocaine (powder is converted to crack with water and baking soda)
- dealers are more likely to transport and sell powdered cocaine
- blacks are disproportionality poor, and poor people are more likely to use crack
- police (arrests) and judges (convictions) are far harsher on blacks than on whites
Rates of marijuana use and arrests among whites and blacks
Rates bw whites and blacks are the same when it comes to marijuana use but blacks are 2-3 times more likely to be arrested than whites
in poor neighborhoods what percent of black males go to prison and what is the most common crime
50% of black males will go to prison, most for nonviolent drug offenses
what are 3 reasons non violent drug users should NOT be sent to prison
- young men who go to prison, recidivism rates approach 60% over 6 yrs
- felony convictions eliminate opportunities for future employment and higher education
- prison rehabilitation programs have been eliminated
there are just as many black people in _________ as there are in ___________
prison; college
Bottom Line about drug use and criminalization in the US
The war on drugs is still being levied against our most vulnerable members of society, in poor urban neighborhoods that are disproportionately black and do not have resources to cope
Do black and white criminalization disparities pertain to first time offenders?
Yes the do. Statistically, black males are more likely to have previous run ins with the law and are more likely to be convicted when they engage in any form of criminal activity, even on first offense
Might apparent racial biases really be driven by prior offenses?
Priors do play a role but it is limited
Between 2012 and 2016, black men received 19.1% longer sentences than white men, controlling statistically for criminal history and a host of other potential predictors including guilty pleas, age, education, and citizenship
disparities among first time offenders only
-blacks are more likely to have their cases rejected or dismissed by prosecutors
- whites are more likely to be placed on diversion and have charges reduced to misdemeanors
-blacks are more likely than latinos who are more likely than whites to receive a prison term
- when sentenced, blacks and latinos receive longer terms than whites
-some disparities are result from historical difference of sentencing guidelines for possession of crack vs meth and heroin
- even for crack, blacks receive longer sentences than whites
-large disparities in arrests, diversion, and sentencing exist for crack vs opioids
Might apparent racial bias stem from differences in police presence in urban vs rural areas?
yes police is a factor but blacks are more likely than whites who go to urban neighborhoods to buy drugs to be arrested for doing so while in those neighborhoods
What disproportionalities and disparities suggest institutional racism
- disparities in first time offenders
- biases be driven by prior offenses
- differences in police presence in urban vs rural areas
what 2 things are built into structure of social institutions that continue to operate even without active support and maintenance of individuals
policies and practices
what is direct racism
policies that are purposefully designed to have discriminatory effects
example of direct racism
the original motivation for war on drugs as described by John Ehrlichman
What is indirect racism
practices that have disproportionate effects on people of different races without any intent to discriminate
example of indirect racism
increased police presence in poor urban neighborhoods can result in more young black people being arrested than white people who commit similar crimes
in 2013 what were federal prosecutors not allowed to specify
they could not specify the amount of drugs involved when charging low level AND nonviolent drug offenders
What was the result of not specifying the amount of drugs in low level, nonviolent cases
judges could then have more leeway in their sentencing than was required by the mandatory federal punishments
What is significant about US Attorney General Jeff Sessions and did he help or hurt the drug criminalization situation
He was the person who reversed the policy that gave judges the discretion to lower sentences
what is the Neighborhood Safety, Drug treatment, and Rehab amendment initiative that Ohio started in 2018
It is an initiative that would have
1. changed drug possession felonies to misdemeanors
2. prohibited prison sentences for technical probation violations
3. expanded the ability to earn up to 25% off a prison sentence through rehabilitative programning
4. redirected funds saved from reduced incarceration to drug treatment and victims’ services
explain the racial disparities in policing
Stats of police killing disproportionately
Stats of police killing disproportionately
people killed by police
31% black
12% hispanic
People killed while not attacking
39% black
12% hispanic
In how many cities do people kill more black men than the overall US murder rate
13 cities
For unarmed victims killed by police what is the ratio of white versus minorities
Minorities are twice as likely to be killed than whites when unarmed
What is the neural analysis of addiction
Sensitization of brain regions to drug cues (ex: greater DA neural reactivity in the striatum); down-regulation of brain function via allostatic load
Behavioral analysis of addiction
Use of larger amounts or over longer periods of time
Emotional analysis of addiction
Development of craving, a strong emotional urge to use
What are the 4 brain DA systems
- tuberoinfundibular
- nigrostriatal
- mesolimbic
- mesocortical
Tuberoinfundibular pathway
originates in the arcuate nucleus of the hypothalamus and projects to the pituitary gland
function of tuberoinfundibular pathway
releases Dopamine to limit the secretion of Prolactin; important for hormone regulation
Nigrostriatal pathway
originates in the Substantia Nigra, pars compacta and projects to the dorsal striatum
function of nigrostriatal
important for movement but also plays role in addiction
structures found in dorsal striatum
caudate and putamen
Mesolimbic pathway
originates in the ventral tegmental area (VTA) and projects forward to the ventral striatum, the nucleus accumbens, the amygdala, and the bed nucleus stria terminalis
mesolimbic function
implicated in all reward motivated behavior (food, self preservation, sex)
what DA systems are subcortical and phylogenetically old
- tuberoinfundibular
- nigrostriatal
- mesolimbic
mesocortical pathway
projects forward from portions of the mesolimbic system to cortical areas including the dorsolateral PFC, the medial PFC, the anterior cingulate cortex (ACC), and the temporal cortex
What DA systems is largely cortical and what does cortical mean
the mesocortical system; cortical means it is evolved fully in primates
how is mesocortical system regulated
it has a top down regulation over impulses generated by the subcortex
What is associated with mood states
Tonic DA activity is associated with mood states
what are the 2 tonic DA activities
high tonic DA and low tonic DA
what is high tonic DA
it is positive affectivity (affective component of euphoria)
what is low tonic DA
it is negative affectivity, irritability (affective component of craving)
What system activity is experience dependent
mesolimbic DA activity
What does repeated phasic activation produce
it leads to reduced tonic activity and sensitization
What do most drugs of abuse produce
they produce phasic increases in mesolimbic DA that exceed those produced by normal reinforces (Food, sex)
what 3 things is addiction associated with when it comes to DA activity
- reduced tonic neural firing
- sensitized phasic neural firing
- sensitized phasic neural firing that begins with cue exposure
what are two possible ways to induce reduced tonic neural activity
- induced by adaptive recalibration of neural firing (via altered numbers of DA receptors and transporters)
- long term (sometimes permanent) structural damage to DA neurons
what is recalibration of neural systems in response to repeated activation called
allostatic load
How long does it take for DA transporter recovery to occur for meth users
It is only after 14 months that a meth abuser begins to show normal levels of DA transporters
what drugs can lead to permanent damage to midbrain DA neurons
meth and cocaine induced damage
What is addiction defined as
- a compulsion to seek and take a drug
- loss of control in limiting intake
- emergence of negative emotional state (dysphoria, anxiety, irritability) when access to drug is denied
how is addiction subdivided
- occasional, controlled, or social use
- abuse
- depedence/addiction
what drug has the highest probability of abuse/dependence given any use
heroin, it is 3x more likely than the runner up (cocaine)
what are the 11 statements that are currently used to define SUD according to DSM
refer to pg 15 of lecture 3
what kind of disease is addiction known as and what is it characterized by
addiction is a progressive disease, characterized by chronic relapsing
what are the steps leading to addiction and eventually recover
- acute reinforcement/social drug taking
- escalating/compulsive use binge drinking
- dependence
- withdrawal
- protracted withdrawal
5.5 relapse - recovery
what kind of changes does addiction cause that can persist for months/years after quitting
structural and functional changes in brain circuits
what aspects of addiction are not isomorphic
emotional and neural aspects of addiction
how does associative learning play a role in addiction
the experience dependent down regulation of striatal DA activity produces dysphoria, irritability, and anhedonia which induces craving and changes to both structure and function of brain regions that are implicated in associative learning
what are the 2 broad types of genetic studies in psychopathology research
- quantitative behavioral genetics
- molecular genetics
other names for quantitative behavioral genetics
aka behavioral genetics, quantitative genetics, biometrical genetics
objective of quantitative behavioral genetics
parse variance in behavior (trait, phenotype) into heritable (both genetic and non-genetic) and non-heritable (environmental) components using latent variable modeling
how is variance studied in quantitative behavioral genetics studied
variance is studied by using twin, family, and adoption studies
what are the assumptions of basic twin studies
- monozygotic twins have nearly 100% shared genetic polymorphisms
- dizygotic twins have 50% shared genetic polymorphisms
- both monozygotic and dizygotic twins share many features of the environment (intrauterine, development, parenting factors, education, SES, etc)
- non twin sib-sib pairs also share 50% genetic polymorphisms but share fewer features of environment (diff classrooms, fewer common friends, etc)
What is the ace model
uses large groups of twins and other siblings, the attempt is to study percentage of overall variance in phenotype (addiction symptoms) that attribute to heritability (A^2), shared environment (C^2), and unique environment (E^2)
What is shared environment (C)
events shared by both twins
What is non-shared environment (E)
events experienced by only one twin
how many and what are the assumptions about the ace model?
5 total and refer to lecture 5 for specifics
how are environmental effects facilitated into shared versus non shared components?
study includes identical twins who are reared together and identical twins who are reared apart
what is a major limitation of the ACE model
it does not account for GxE interactions or gene-environment correlations (rGE) which are unmeasured and subsumed within A^2, resulting in overestimates of heritability
what accounts for initiation of alcohol use
peer influences
what accounts for quantity and maintenance of alcohol use
heritability
how does behavioral genetics differ from molecular genetics
molecular genetics involves direct assessment of genes
objective of molecular genetics
identify specific genetic polymorphisms that increase vulnerability to psychopathology, including addiction
what are polymorphisms
alleles/variants that are in only about 1% of the 30000 protein coding genese
what is a single base pair
a DNA sequence variation that occurs when a single nucleotide of A, T, C or G in a genome differs between members of a species or between paired chromosomes with an individual
what is a genotype
specific genes underlying a phenotype
phenotype
observable characteristics of an organism that may or may not correspond with a particular genotype
what is mendelian inheritance
inheritance pattern for single gene, dominant/recessive traits
homozygotes vs heterozygotes
DD and dd are homozygotes
Dd and dD are heterzygotes
is human behavior or disorders determined by a single gene
No
what is a three factor cross
a trihybrid phenotype
what is the ratio for inferring the genotype from the phenotype
only 1 in 4 cases
what ratio can be inferred in a trihybrid phenotype
only 1 in 64 cases can the genotype be inferred from the phenotype
what is polygenetic inheritance/determinism
the influence of multiple genes on a physical or behavioral phenotype
what is penetrance
the proportion of individuals who carry genetic vulnerability (often called liability) and express the disorder
what is an example of penetrance
almost 10% of individuals carry at least some genetic vulnerability to schizophrenia but less than 1% develop the disorder
what is incomplete penetrance
Not all individuals with a mutant genotype show the mutant phenotype
what is multifactorial inheritance
Multifactorial inheritance means that many factors are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition.
what are the neurobiological factors that contribute to blunted
- neuro-hormonal modulators
- environmental influences
- genetic liability/burden
what are the 3 levels of analysis in the multifactorial influences on striatal function
neurobiological, emotional, and behavioral
what are the neuro hormonal modulators involved in blunted striatal responding
- testosterone levels
- L-HPA axis function
what are the environmental influences involved in blunted striatal responding
- TBI, hypoxia, teratogen exposure
- epigenetic regulation of receptor function
what are the genetic liabilities/burdens involved in blunted striatal responding
-epigenetic regulation of receptor function
- DAT, DRD, SLC6A4, and CACNA1C (vulnerability alleles)
- 18p11.32, 16p11.2, and CNV burden (heritable CNVs)
- disrupted neuro development (de novo mutations)
what is the behavioral bias associated with striatal function
vulnerability to addiction
what are the 3 approaches used to identify candidate genes for different disorders
- genetic linkage study
- genetic association study
- genome-wide association study
what is genetic linkage
they refer to the tendency of alleles that are near one another on the same chromosome to be inherited together or “linked”
what is done during a linkage study
- obtain large sample of families with two children with a trait or disorder
- collect genetic data from family members
- scan broad sections of genome (by historical standards) in searches for genetic markers with known chromosomal locations that may be linked to a gene for the disorder
- make educated guesses about the location of genes for complex disorders, which may be confirmed/refined in subsequent studies
example of genetic linkage study
gene responsible of CF (cystic fibrosis) was found by linking the disease to genetic variant on long arm chromosome 7 within affected families. Followed by several other studies to find the CFTR (cystic fibrosis transmembrane conductance regulator) gene
Problems with linkage studies
- they are expensive and lead to many false leads, and have not produced strong or replicable results for psychiatric disorders
- linkage studies are best suited for identifying risk loci for monogenic or oligogenic traits, whereas addiction is inherited multifactorially
what is gene association
refers to situations in which specific genes are associated with certain phenotypes. In studies that attempt to identify allelic variants that segregate with the trait of interest in the general population
what is done during gene association studies
begin with a specific candidate gene, and then compare allelic frequencies of the gene among people with and without the disorder (case control design) which provides more statistical power than linkage studies
problem with gene association studies
-scientists have no idea where to look
- association studies indicate that all vulnerability genes combined account for only a few percent of variance any behavioral trait (including addiction) whereas behavioral genetics studies tell us that preponderance of variance in most traits is heritable (this is called missing heritability problem)
what is a genome wide associated study
study where hundreds of thousands of genes are tagged across the genome in very large samples, and searches for associations with psychopathology are conducted using strong corrections for family wise alpha error rates
what has been found due to GWAS studies
found 14 loci and had 8 hits on specific chromosome with 2.3 MB and several alcohol dehydrogenase genes that have previously been implicated in alcohol consumption. This contributes to the idea that alcohol consumption is a complex, multifactorial trait
what number of SNPs explain 50% of population based phenotypic variation in schizophrenia liability
8332
what is gene polymorphism
a DNA sequence variation that is common in the population. Polymorphic variants usually do not cause life threatening diseases directly, but may influence behavioral and other specific phenotypic propensities that interact with environments to confer susceptibility to disease including psychopathology
are gen polymorphism inherited or taught
they are inherited
what is a gene mutation
a change in DNA sequence away from ordinary variation observed in population.
what are de novo mutations
Mutation that is present in a family member as a result of a mutation in a germ cell of one of the parents
how do genes affect complex behavior
certain gene polymorphisms confer behavioral biases that render individuals susceptible to disease in certain environments (GxE)
how do genes code for protein expressions
- transcriptions of DNA into mRNA
- translation of amino acids into proteins by tRNA
who oversimplifies the genes that control complex traits
popular press accounts
how do genes affect neurotransmitter system function
- alter neurotransmitter availability via synthesis and metabolism pathways
- alter efficiency of neurotransmission more directly
what genes are implicated in impulsivity
MAO, COMT, DAT, and DRD4 which all can collectively alter DA function
where are several candidate genes for alcohol and other substance dependencies expressed in
in the liver
which genes are attributable to genetic differences in the alcohol metabolism
ALDH2, ADH1B, ra1693482, 4s698, ADH1C
what gene is responsible for clearing alcohol
ALDH2, one copy of ALDH2 gene is inherited from each parent
which gene variable will clear acetaldehyde slowly
ALDH2^2
2 main components of nervous system
CNS and PNS
Where is the CNS
brain and spinal cord
where is the PNS
the nerves and ganglia outside of the brain and spinal cord
3 subdivisions of the PNS
- sympathetic nervous system
- parasympathetic nervous system
- somatic nervous system
what is the sympathetic nervous system
the excitatory component of PNS (accelerates HR, opens bronchial passage, dilates pupils, etc); largely adrenergic (adrenaline, epinephrine)
What is the parasympathetic nervous system
the inhibitory component of PNS (deaccelerates HR, constricts pupils, aids in digestion); largely cholinergic (acetylcholine)
what is the somatic nervous system
provides voluntary control over skeletal muscles; largely cholinergic
Parts of brain that are part of the CNS
temporal lobe, frontal lobe, parietal lobe, occipital lobe, cerebellum, brain stem (includes midbrain, pons, medulla)
the 2 main divisions of the systems within the PNS are separated into?
- autonomic (subconscious, control systems) 2. somatic (voluntary, muscle movement)
what are the 2 systems found in the autonomic PNS
- parasympathetic (rest and digest)
- sympathetic (fight or flight)
what is the enteric nervous system
it controls function of gastrointestinal tract; uses many transmitters, especially serotonin and dopamine
what parts of the nervous system do drugs of abuse alter
they alter function of all human nervous system components
what are the four major components of a neuron
- cell body
- axon
- dendrites
- synapses
what is the cell body
includes a nucleus which contains the genetic material of the cell (machinery for generating neurotransmitters and action potentials)
what is the axon
conducts action potentials (electrical impulses) to synapse to release neurotransmitters
What are dendrites
receives signals from neurotransmitter release by pre-synaptic neuron
what are synapses
“space between” pre and post synaptic neurons that allow for inter-neuronal communication
what are the 3 major functions of neurons
- inhibition
- excitation
- modulation
what is neuron inhibition
reducing the likelihood of action potentials at post synaptic neurons via release of inhibitory neurotransmitters
what is neuron excitation
increasing likelihood of action potentials at post synaptic neurons via release of excitatory neurotransmitters
what is neuron modulation
influencing neurotransmission of populations of neurons, usually through diffusion of neurotransmitters through tissue
what are the 6 major steps in neurotransmission (NT)
- NT synthesis
- NT storage
- NT release from presynaptic terminal into the synapse
- NT inactivation via removal of the synapse by reuptake or metabolism
- activation of post synaptic receptor
- signal transduction
what occurs in NT synthesis
molecule mechanism of peptide precursors and enzymes for further synthesis or cleavage
what causes NT inactivation
removal from synaptic cleft through reuptake process or NT breakdown by enzyme in the synapse or presynaptic terminal
what triggers postsynaptic cell response
activation of postsynaptic receptor
what responds to NT receptor activation
subsequent signal transduction
what are the support cells of CNS
glia cells
what is the function of glial cells
They support neurons by supplying nutrients along with other functions including myelin synthesis and innate brain defense system against pathology
what are oligodendrocytes
A type of glial cell that forms insulating myelin sheaths around the axons of neurons in the central nervous system.
how does myelin affect NT speed
they increase speed via salutatory conduction where action potential jump across nodes of ranvier
what are 3 types of glial cells
oligodendrocytes, astrocytes, microglia
What are astrocytes?
These are abundant, star-shaped cells that account for nearly half of the neural tissue. These brace neurons and form barrier between capillaries and neurons. These also help control the chemical environment of the brain.
function of astrocytes
form blood brain barrier, help guide neural migration during circuit development, regulate NT and reuptake
what are microglia
immune like cells that do not cross the blood brain barrier
function of microglia
remove waste and foreign material and secrete growth factors and cytokines when activated
how many names does a drug have and what are they
3 names
1. chemcial
2. generic (nonproprietary)
3. trade (proprietary)
how are drugs classified
according to their psychotropic effects and the major NT they affect
what are the main 3 classifications for drugs
behavioral, pharmacodynamic, and legal classification
what are the 5 main categories for drug behavioral classification
- stimulants
- opioids
- sedative hypnotics
- antidepressants
- psychedelics
stimulant behavioral effects
drugs that stimulate/produce arousal and behavioral activation
opioid behavioral effects
natural/syn/semi-syn drugs that bind to opioid receptors and produce analgesia
What is analgesia?
reduction of pain or elevation of pain thresholds
sedative hypnotics behavioral effects
drugs that sedate/decrease arousal, producing anti-anxiety effects, hypnosis, or sleep
antidepressant behavioral effects
drugs used to treat psychosis and include classic antipsychotics and modern 2nd generation drugs
example of anti psych drug
haloperidol
example of 2nd generation drug
olanzapine
psychedelic behavioral effect
drugs that produce psychedelic experiences (mind altering)
example of sedative hypnotic drug
examples include alcohol and benzodiazepines
example of stimulants
examples include cocaine, amphetamines, nicotine, and caffeine
examples of psychedelics
LSD, marijuana, psilocybin
stimulant pharmodynamic effect
stimulants are indirect dopamine agonists
opioid pharmodynamic effect
opioid are direct opioid receptor agonists ( primary pain relieving and secondary anti anxiety effects)
sedative hypnotic pharmodynamic effect
directly/indirectly facilitate gamma-aminobutyric acid (GABA)
antipsychotics pharmodynamic effect
dopamine antagonists and serotonin receptor antagonists
antidepressant pharmodynamic effect
serotonin/norepinephrine reuptake inhibitors or combo of both NT
psychedelic pharmodynamic effect
directly/indirectly facilitate serotonin by increasing serotonin release
what are the 2 categories of drug legal classification
prescription vs nonprescription
what is legal drug classification based on
based on specific criteria for potential of abuse and potential for depednence
what is absorption
the movement of a drug through the bloodstream which is determined by several factors
what are the different types of drug administration routes
-intravenous (IV)
-smoked
-intranasal
-subcutaneous (fatty tissue under skin)
-intramuscular (muscle injection)
-oral
how does faster absorption affect potential for abuse
faster absorption such as IV or smoked means higher likelihood of abuse
why do you get drunk when drinking on empty stomach
on empty stomach the ethanol levels are absorbed by the blood at a quicker rate than a full stomach
what is drug elimination
the process through which drugs are removed from the body including how they are metabolized by the liver and excreted in urine by kidneys
what kinetics does alcohol follow
zero order kinetics which means that the absolute amount of alcohol eliminated over time is constant
what eliminates alcohol from body
alcohol is eliminated primarily by liver metabolism and excretion in urine
what is the half life of alcohol
the amount of time it takes for blood levels to be cut by 50% via metabolism
the half life is about .01 gram percent per hour for a 154 lb. man
what are drug receptors
cellular elements with which a drug interacts to produce its effects
what are the 2 types of drug receptors
agonists vs antagonists
what are agonists
drugs that bind to receptors & produce a stimulatory response like a natural substance such as a hormone would
what are antagonists
drugs that bind to receptors and block effects of agonists, prevent receptor activation, and block a response
restrictive definition of agonism
they can mimic a particular NT, bind to that NT postsynaptic receptor and either activate them or increase the NT effects
restrictive definition of antagonism
they can mimic a particular NT, bind to the NT postsynaptic receptor enough to block NT binding
why is cocaine a DA transporter antagonist according to Koob
cocaine blocks the DA transporter and blocks DA from being recycled by presynaptic neurons
why is cocaine an agonist according to a more broad definition
Cocaine is a DA agonists because it increases availability of DA for neurotransmission
what is dose response function
the relationship between the amount of a drug taken and the intensity and type of the resulting effect
what does the normal dose response function look like
as drug dose increase, effects increase up to a point
what is efficacy
maximal effect a drug can produce (y-axis).
what is potency
amount of drug needed to produce a given effect relative to a standard.
what is the therapeutic ratio
a means of indexing safety of a drug for a specific response
how is therapeutic ratio calculated
divide the LD50/ED50
what is LD50
dose that produces death in 50% of the population
what is ED50
dose that produces desired therapeutic effect in 50% of the population
what is the therapeutic ratio for morphine or alcohol
morphine is 8 and alcohol is 1
why is alcohol not a safe anesthetic
bc the lethal dose is the same as the effective dose for the purpose. Morphine is a safer option for an anesthetic
how do stimulants affect DA transmission in the NAc
they directly increase DA transmission
how do opiates affect DA transmission in NAc
they indirectly increase DA transmission by inhibiting GABA interneurons in the VTA which will disinhibit VTA DA neurons.
They directly act on opioid receptors on NAc neurons
how does nicotine affect VTA
Activates VTA DA neurons directly by stimulating nicotinic cholinergic receptors and indirectly stimulate its receptors on glutamatergic nerve terminals that innervate DA cells
how does alcohol affect VTA and NAc
Alcohol promotes GABA receptor function and inhibits GABAergic terminals in VTA to disinhibit VTA Da neurons. It can also inhibit glutamatergic terminals that innervate NAc neurons
how does cannabinoid mechanisms affect VTA and NAc
activate cannabinoid CB1 receptors on glutamatercig and GABAergic nerve terminals in the NAc and on NAc neurons
PCP effect on VTA and NAc
inhibit NMDA glutamate receptors in NAc
what are the 3 stages of addiction
- binge/intoxication
- withdrawal/negative affect
- preoccupation/anticipation
what occurs during the binge/intoxication stage?
reward (mesolimbic DA) and motor (nigrostriatal DA) systems implicated heavily acute positive reinforcement effects predominate liking emotions (pleasure, contentment, enthusiasm)
What occurs during the withdrawal/negative affect stage
central nucleus of the amygdala and bed nucleus ofthe stria terminalis (BNST) implicated heavily (in addition to reward and motor systems) acute punishment effects predominate aversive (negative) emontions (disgust, fear, malaise) are elicited
what occurs during preoccupation/anticipation stage
prefrontal cortex, orbitofrontal cortex, and hippocampus implicated heavily (in addition to reward, motor, and punishment systems), obsessive effects predominate wanting emotions (craving, desire, preoccupation) are elicited
what is ventral striatum responsible for in the brain
euphoria, reward
what is dorsal striatum responsible for
habits and preservation
what is the thalamus responible for
habits and preservation
what is global pallidus responsible for
habits and preservation
what brain structures are involved in binge/intoxication stage
ventral striatum, dorsal striatum, global pallidus, and thalamus
what are the brain structures involved in the withdrawal/negative effect
amygdala, bed nucleus of the stria terminalis, and ventral striatum
what is the amygdala and BNST responsible for
known as the extended amygdala and responsible for malaise, dysphoria, negative emotional states
what is ventral striatum responsible for in withdrawal stage
decreased reward
what brain structures are invovled in the preoccupation/anticipation stage
anterior cingulate, prefrontal cortex, orbitofrontal cortex, basolateral nucleus of amygdala, and hippocampus
what is the prefrontal cortex, orbitofrontal cortex responsible for
subjective effects of craving, executive function
what is the basolateral nucleus of amygdala responsible for
conditioned cues
what is the hippocampus responsible for
conditioned contextual cues
what is incentive sensitization theory
positive incentive value of drugs increases with repeated use in addiction-prone individuals (positive at first) but overtime become decoupled through neuroplastic changes in brain function. theory is imp bc it accounts for emotional components of addiction
what is motivation
willingness to exert effort/perform work for desired outcome
what is a primary reinforcer
an innately reinforcing stimulus, such as one that satisfies a biological need (food, sex, shelter)
what is a secondary reinforcer
any reinforcer that becomes reinforcing after being paired with a primary reinforcer, such as praise, tokens, or gold stars (money, achievement, prestige, drugs)
in addiction are drugs a primary or secondary reinforcer
they take on primary reinforcing properties
what 2 major motivators play a role in addiction
willingness to exert effort/perform work for a commodity (reward) or a willingness to exert effort/perform work to avoid punishment both play a major role
what is active avoidness
have to physically leave or run away to avoid
what is passive avoidness
to hide under a table
what are the 3 ways animal models quantify motivation
- ammount of food or water consumed
- persistance of operant behaviors to obtain incentives
- intracranial self stimulation (ICSS)
example of amount of food or water consumed quantifying motivation
food deprived animals eat more than non food deprived animals meaning that food deprivation increases motivation to eat
example of persistance of operant behaviors to obtain incentives demonstrating motivation
food deprived animals will work harder for food rewards than satiated animals
what is a breakpoint
maximum number of operant responses (lever presses) a trained animal will engage in for drug delivery
do alcohol dependent or nondependent rats have a higher breaking point
dependent rats will work for alcohol more meaning they will have a higher breakpoint
what is classical conditioning
repeatedly pairing 2 stimuli until the conditioned stimulus elicits the same response as the unconditioned stimulus
what is an unconditioned stimulus
A stimulus that elicits an unconditioned response
ex: cocaine laxative effects bc it it is reflexive
what is a conditioned stimulus
a stimulus that after repeated pairings with the unconditioned stimulus will elicit the unconditioned response
ex: john takes crack and will learn to go to bathroom before consuming drug
why is classical conditioning not a good measure of motivation
bc it does not require work
what is operant conditioning
changing the occurrence, frequency, or magnitude of behavior through use of reinforcement
