Exam 2 Study Guide - Professor Nichea Spillane PDF

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Professor Nichea Spillane...

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● Genetics ● Definitions of ● genotype ○ combination of genes ● phenotype ○ how genes are expressed ● Endophenotype- a genetic epidemiology terms which is used to separate behavioral symptoms into more stable phenotypes with a clear genetic connection ○ Genetically influenced phenotype ○ Identifiable before a disorder develops ○ Associated with high risk of developing a disorder ● polymorphism ○ genetic variation resulting in the occurrence of several different forms or types of individuals among the members of a single species ● What are the 4 known sources of genetic influence on the likelihood of development AUDs? ● Variations in alcohol-metabolizing enzymes ● Low response to alcohol ● § Always able to “hold my liquor” ● § Less cognitive/motor impairment ● § Seen in COAs ● § Ability to drink heavily and develop tolerance ● o Disinhibited, impulsive, externalizing, temperament ● § Nonspecific to drinking ● § Heavier drinking, more problems ● § Early onset of AUDs ● § Gene x environment interaction ● o Psychiatric comorbidity ● § Antisocial personality (adj OR = 1.7, lifetime AD) ● § Bipolar mood disorder (adj OR = 2.1, lifetime AD) ● § Schizophrenia ● · Be familiar with the variations in alcohol – metabolizing enzymes and the effect they have on the alcohol metabolism process AND risk for developing AUD. ● o Variations in alcohol- metabolizing enzymes ● § Beverage alcohol à ADH (ADH1B*2 variant speeds up process) à acetaldehyde(flushing, nausea, vomiting, headache) à ALDHà Acetic acid CO2 H2O ● § Beverage alcohol à ADH (ADH1C*2 variant slows process) à acetaldehyde (lower levels, less aversive) à ALDHà Acetic acid CO2 H2O ● § Beverage alcohol à ADH à acetaldehyde (flushing, nausea, vomiting, headache) à ALDH ( ALDH2*2 variant slows metabolism {may have 1 allele or 2})à Acetic acid CO2 H2O

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· Genes explain 50% vulnerability · AUDS are poly genetic · AUDS are multifactorial · Know what Low Response to Alcohol refers to o o what the implications are § o Are they more or less likely to develop AUD? § more · Which disorders can be viewed as genetically influenced conditions related to an enhanced risk for substance use disorders? o · What are the three types of gene-environment interactions we discussed? o Active o Passive o Evocative § Passive: Environment is not independent of genes • prenatal exposure to alcohol • Parenting, parent/sib role models § Reactive/evocative: certain temperaments precede AUDs and evoke responses from parents, teachers, peers, etc. § high activity level / behavioral under control • emotionality / low soothability / neuroticism • poor attention span / persistence sociability / extraversion § Active (niche seeking): People actively seek environments that complement/support their genotype § self-selection into “partying” social groups § selection of mates § self-selection away from alcohol involvement (e.g., flushing response) · Know how and which NT/NM systems are affected by acute doses of alcohol · édopamine (pleasure, reward, attention) · éendogenous opiates (reward, self‐ administration) · éGABA (sedation, anxiety reduction) · êglutamate (excitation, memory, learning) · éserotonin (motivation, regulation of attention, emotions) · What is the mesolimbic pathway? o Aka “reward center” o Activity stimulated primarily by NT dopamine o Most drug abuse stimulate this pathway o Located mid brain · What else is it called?

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Reward center What role does it play in dependence? There is a disruption in the reward system in individuals with alcohol dependence Other activities that stimulate pathway? Running gambling What is neuroadaptation? ○ Process whereby changes in the reinforcing value of alcohol use and abuse to dependence reflect adaptive neural changes from chronic alcohol exposure to high alcohol doses Neurodegeneration ○ Chronic exposure to high doses of alcohol can result in profound changes in the morphology proliferation and survival of neurons True or false: moderate drinking has been identified as contributing factor to a decreases incidence of several diseases ○ True · What is homeostasis? o The body’s need to reach and maintain a certain state of equilibrium, stable levels · How does alcohol affect NT systems over the short-term and long-term? o The presence of exogenous chemicals can disrupt homeostasis o Synaptic transmission is finely regulated § In synapseà enzyme break down extra NT § At presynaptic membrane extra NT is taken back up via reuptake transporter § At postsynaptic membrane up regulation r down regulation # of receptors § Balance · Benefits of moderate drinking? What are they? Risks of moderate drinking? o Health benefits to moderate drinking § Coronary heart disease § Ischemic stroke § Vasculat dementia § Metabolic syndrome § Type 2 diabetes · Recommendations with regard to drinking and heart disease? o Heavy drinking can make you more likely to get serious health problems like liver disease, cancer, and peptic ulcers, among others. Regular or high alcohol use can hurt your heart and lead to diseases of the heart muscle, called cardiomyopathy. Drinking alcohol regularly also can raise your blood pressure. · Know the statistics for who is more likely to have an AUD – men, women, which countries have the most drinking? o Men are more likely to have an AUD § Europe has the most drinking

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· What drugs are most harmful to us and others? o Alcohol § Cocaine § Heroine § methamphetamine · Know who is more likely to drink and drive – who is more likely to have a serious crash? o o younger drivers are more likely to have a serious crash · How can we make public health messages work better and prevent people from drinking and driving? o Make it relatable o Signs · When are we more likely to intervene? o Had to travel far o Close friend o Partner/ significant other o Having strategies to intervene o Perceived ability to intervene · Know long term effects of drinking alcohol on the liver – cirrhosis. o Heavy drinkers more likely to die from cirrhosis o 12th leading cause of death in the united states in 2002 o function of quality and duration o will develop if you drink an average of 8 standard drinks per day 10-20 years o irreversible o consuming alcohol with food lowers risk o gender effects- as alcohol dose risk increases more rapidly for women o spirits might be more harmful o ethnic differences § blacks and Hispanics have a higher rate of cirrhosis o Alcoholic fatty liver § 20% of heavy drinkers § enlarged liver § reversible § can lead to serious liver disease o alcohol hepatitis § liver degeneration, fibrosis, and other changes to liver cells § swollen liver, nausea, vomiting and abdominal pain § mortality rate in severe cases cause 50% § if heavy drinking continues 40% will develop cirrhosis · What does drinking do to you thinking?

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50% of alcoholic adults show problems with spatial skills planning learning memory IQ and language are ok Recovery Much in 1st month More is 1st year f sober What is korsakoff’s syndrome? Mainly affects chronic alcoholic Brain neurological disorder caused by thiamine or vitamin B1 deficiency Characterized by Inability to form new memories (anterograde amnesia) Loss of memory (retrograde amnesia) Apathy or lack of interest in or concern about emotional, social, or physical life Hallucinations or seeing and hearing things not really present Delirium (restlessness, illusions an incoherence of thought and speech) Who does alcohol lead to aggression for? Antisocial personality Alcohol dependency Previous aggressive episodes Low levels of serotonin in the CNS Impaired cognitive functions Alcohol was a factor for 19-37% of violent crimes in 2008 Increased risk of injury Communities shave more bars and liquor stores per capot experience more assault AUDS increased risk for violent acts by 10x Major mental disorders increased by 3x What is alcohol myopia? ■ Pharmacologically based ■ Alcohol narrows perceptual field to the here-and-now ■ Attention to salient instigating cues, to exclusion of distal considerations (e.g. long-term consequences) ■ Especially under conditions of inhibition conflict ■ Intoxication can increase aggression, risky sexual behavior, tipping ■ Predicts both increases and decreases in negative affect/worry, depending on presence of distracting activity ● According to Alcohol Myopia Theory can predict/affect these: ● Attention deficit ● Impulsive behavior

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● Aggression ● Overeating ● Self-awareness ● Anxiety relief ● Empty promises Which paradigm has been used to study aggression in alcohol studies?

· o · *review the FASD slides. o · Know the statistics for pregnant women drinking. o 1 in 10 women 1/3rd binge drink · What is FASD characterized by? ○ Small eyelid openings ○ Short, upturned nose ○ Long upper lip (from nose to mouth) with a thin red border and deficiency central groove ○ Overall size of the head is smaller ○ Wider set eyes · Many drugs affect the dopamine (DA) system: · Heroin => binds to opiate receptors=> DA release Alcohol=> triggers endorphins, which bind to opiate · receptors => DA release Methamphetamine => direct release of DA Cocaine => prevents reuptake of DA after release · Elevated DA levels activate the brain’s reward pathways, reinforcing the associated behavior • Genetic influences change over life course • Several pathways to development of AUDs Effects of alcohol on the brain ○ Cerebellum- can cause stumbling, falling, and slurred speech (BAC of.16-.30) ○ Cerebral cortex- affect judgment, risk taking, personality changes such as being more outgoing, overconfident, and focusing on present vs future, reaction time starts slowing down (BAC of .01-.08) ○ Midbrain- can result in more intense and changeable moods, aggression, vision, hearing and touch can be disorientated (BAC of .09-.15) Effects of alcohol on the brain ○ Cerebellum- can cause stumbling, falling, and slurred speech (BAC of.16-.30) ○ Cerebral cortex- affect judgment, risk taking, personality changes such as being more outgoing, overconfident, and focusing on present vs future, reaction time starts slowing down (BAC of .01-.08) ○ Midbrain- can result in more intense and changeable moods, aggression, vision,

hearing and touch can be disorientated (BAC of .09-.15) ● ● Fetal Alcohol Syndrome ● When a mother drinks, her unborn child is exposed to alcohol ● A fetus metabolizes alcohol more slowly than an adult dose, its BACs are higher than those of the mother ○ This is what can cause damage ● From animal and human studies we know ● Elimination rate is 3-4% higher than the mothers and the effects will last longer ● 1 in 10 women report alcohol use ○ 3.1% report binge drinking ○ 1/3rd of the women who drink in pregnancy engage in binge drinking ○ Among pregnant women alcohol use is highest among those ages 33-44 ○ College graduated ○ Unmarried women ■ Some may not know they are pregnant ● Alcohol-related birth defects include ○ Fetal alcohol syndrome ■ Introduced in 1973 ■ Which is characterized by ● Central nervous system problems ● Low birth weight and height ● Typical facial features ○ Fetal alcohol effects ■ Introduced in 1978 ■ Results from maternal alcohol abuse but are found in the absence of the full-blown syndrome ● Fetal Alcohol Syndrome cases ○ The U.S. has about 15 cases of FASD per 1,000 children ○ Canada has 8 cases of FASD per 1,000 children ○ The European Region has the highest levels worldwide at nearly 20 cases of FASD per 1,000 children ○ The Eastern Mediterranean region has the lowest FASD prevalence ● The facial features of fetal alcohol syndrome ○ Small eyelid openings ○ Short, upturned nose ○ Long upper lip (from nose to mouth) with a thin red border and deficiency central groove ○ Overall size of the head is smaller ○ Wider set eyes ● FAS

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○ Full-blown fetal alcohol syndrome represents open the “tip of an iceberg” relative to all alcohol-related birth defects (ARBDs) ○ Maternal alcohol abuse is the leading known cause of mental retardation in the western world An individual can be diagnosed with FAS without a history of maternal alcohol exposure ○ True ○ This is because chronic alcohol users who are men could explain how this can happen to the child Individuals can be diagnosed with partial FAS ○ True ○ Some facial abnormalities are not always present Children who alcohol-related birth defects will typically have ○ Attention deficits ○ Language difficulties ○ Learning disabilities ○ Impulsive behavior ○ Poor judgement Prenatal alcohol exposure can permanently damage the brain, affecting important structures such as the cerebellum and corpus callosum, as well as specific cell populations in many other regions of the brain ○ Cerebellum ○ Corpus callosum Visualization of the brain of a normal individual (A) and two with FAS (B,C) shows permanent loss of the tissue indicated by the arrows (portions of the corpus callosum) The amount and timing of maternal alcohol use determine the type and extent of resulting birth defects ○ Specific defects depend on when in pregnancy the fetus was exposed to alcohol Alcohol can cause malformation and brain abnormalities in embryos that are only three to four weeks’ old Alcohol can kill specific brain cells in the developing brain Midline structures of the face and brain are deficient in alcohol exposed mouse embryos and in individuals with FAS The face of a child with full-blown FAS can be caused by damage to midline structures Exposure to alcohol during development can cause damage to organs and regions other than the brain Alcohol related birth defects last a lifetime ○ Poor decision making Alcohol related birth defects are expensive ○ Momentarily for treatment, care and lost productivity costs are between 800,00 to 2 million over a lifetime for each individual with FAS ○ Socially relative to delinquency and other emotional drains on involved families

● How much is too much? ○ Is there a safe amount? ● Avoiding FAS ○ There is little risk when the pregnant woman consumes no more than one drink per day ○ > 1 drink per day increases risk of fetal impairment and or spontaneous abortion ○ Negative effects appear to be related to binge drinking, especially high BAC ○ Recommendations→ women who wish to become pregnant should not drink ● ● ● ● ● ● ●

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alcohol No one knows what a “safe” amount of alcohol consumption during pregnancy may be Alcohol-related birth defects are preventable Alcohol and the Adolescent Brain Increases in social behavior, sensation seeking and risk taking → evolutionary purpose Prepare the adolescent to explore new environments, establish new social networks, and become independent of parents Human adolescents are inclined to seek out reinforcements from new experienced and extreme experiences Adolescents appear to be less sensitive to alcohol's depressant effects (compared to adults) ○ Sedation ○ Motor impairment ○ Hangover effects Adolescent may be more sensitive to ○ Positive rewarding effects (enhanced sensitivity of mesocorticolimbic reward system ○ Social facilitation effects ○ Alcohol related cognitive impairment ■ Alcohol depend teens show deficits in attention and working memory Concerns...