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VULNERABILITY HYPOTHESIS IN ADDICTION MEDICINE

Presenter : Dr Nithin Kondapuram,Chairperson: Dr. Arun K.23-07-2014Clinical case presentation1

VULNERABILITY HYPOTHESIS IN ADDICTION MEDICINE

PRESENTER : Dr. NITHIN KONDAPURAM

CHAIRPERSON : Dr. ARUN K.IntroductionAristotle: Drunken women bring forth children like themselves

Plutarch: Drunkards beget drunkards

IntroductionBenjamin Rush (1787) observed that alcohol dependence runs in families.Not everyone who takes drugs becomes addictedVulnerability is a product of the interaction of a persons biology (including their genes), environment and many small factors. These interactions are complex and difficult to tease apart.Vulnerability FactorsThree factor model

GENETICSENVIRONIMENTALREPEATED EXPOSUREMany studies have shown that children of alcoholics are more likely to use alcohol and drugs and to experience alcohol and drug problems than are children of nonalcoholic parentsIn addition, during early adolescence, Children of Alcoholics are significantly more likely to use alcohol, use illicit drugs, drink more heavily, and experience symptoms of substance dependence than non-Children of Alcoholics

Moreover, during adolescence, Children of alcoholics have been observed to have a more accelerated trajectory of heavy alcohol use and to meet the criteria for substance dependence more often than non-Children of Alcoholics.Types of Three Factor ModelsDeviance proneness modelProposed by Sher KJ, in 1991.Children of Alcoholics have higher levels of disinhibition and impulsivity and lower levels of agreeableness than non-Children of Alcoholics .These temperament characteristics, in turn, have been found to consistently predict delinquent behavior, linked to the onset and frequency of substance use, heavier consumption and substance abuse .

Types of Three Factor ModelsSimilarly, extraversion has been shown to be related to substance-use onset, alcohol consumption, and alcohol problemsDelinquency* plays a key role in the development of substance-use disorders.Temperament characteristics in early childhood also have been found to predict delinquent behavior and substance problems much later in development

* minor crime, especially that committed by young people.Types of Three Factor ModelsNegative affect regulation modelProposed by Sher KJ, in 1991The primary premise of the negative affect regulation model is that alcohol and drug problems occur because people drink to reduce negative affectIt also should be noted that individuals who have certain temperament characteristics (e.g., high levels of neuroticism) are more likely to experience high levels of negative affect.Types of Three Factor ModelsAccordingly, these individuals have an elevated risk of using substances as a means to decrease their negative affect. In addition, experiencing a stressful environment (e.g., living with an alcoholic parent) also has been linked to higher levels of negative affectHowever, it is still unclear whether negative affect is a salient predictor of substance use over time.Types of Three Factor ModelsA comprehensive modelProposed by Chassin and Ritter in 2001, The potential mediating roles that delinquency and negative affect may play in the relationship between paternal alcoholism and the onset of Children of Alcoholic substance use were tested the potential effects that temperament, delinquency, and negative affect may have on substance were examined simultaneously.Types of Three Factor ModelsDeviance proneness model, focusing on temperament and delinquency: Negative affect regulation model. focusing on temperament and negative affect: and Comprehensive model, focusing on temperament, delinquency, and negative affect.Vulnerability FactorsThree factor model

GENETICSENVIRONIMENTALREPEATED EXPOSUREGeneticsFamily studies: Winokur 1970, showed increased incidence of alcoholism in first degree relatives of alcoholic probands*Penick 1978 Alcoholics with high family loading tend to have earlier age of onset of dependence and earlier social, personal problems, poorer long term outcome, more severe forms of alcoholism*The proband is the first affected family member who seeks medical attention for agenetic disorderGeneticsAdoption studies: Schuckit 1972 . biological alcoholic father was greater risk factor than surrogate alcoholic father in developing alcoholism. Twin studies: Kaij 1960 found monozygotic twins were more concordant for alcoholism than dizygotic twins.These studies suggests that genetic risk factors account for up to 60 % of the risk

GeneticsKaji, L. (1960)Alcoholism in Twins: Studies on the Etiology and Sequels of Abuse of Alcohol. Almqvist and Wiksell, StockholmGeneticsThe Collaborative Study on the Genetics of Alcoholism: (Hesselbrock et al 2001) n= 9000 adults , 1500 children and adolescentsChrm 1 & 7 have regions containing genes that increase risk of alcoholism.Chrm 4 protective factor - near ADH type 1 genes.

GeneticsCommon Genetic VulnerabilityStimulants73%Heroin/Opiates30%Psychedelics100%Marijuana67%Sedatives81%

Alcohol 93%GeneticsContemporary research in the neurobiology of addiction points toGenetics as the main contributing factor to addiction vulnerability. One gene in particular, theD2 subtype of Dopamine receptor has been studied at length regarding substance addiction. The D2receptor responds to the chemical dopamine which produces rewarding and pleasurable feelings in the brainGeneticsIndividuals with this genetic deficiency in the D2dopamine receptor may be more likely to seek out these recreational pleasure/reward producing substances as they are less receptive to the natural feel good effects of dopamine.This naturally occurring deficiency is one of the most studied genetic vulnerabilities to substance abuse across the field.Vulnerability FactorsThree factor model

GENETICSENVIRONIMENTALREPEATED EXPOSUREEnvironmentEnvironmental factors can also pose risks to a potential addict. For children and adolescents, lack of parental involvement or supervision can enable risky behaviors or experimentation with alcohol or drugs. Additionally, young people who experience abuse or neglect from parents may begin to use substances or engage in addictive behavior as an emotional coping mechanism.

EnvironmentIn older adolescents and even adults, peer pressure is also a risk factor for addiction. Though it might not be overt or aggressive in nature, the pressure from friends to fit in or be accepted in a particular social circle can often create a breeding ground for addiction to take root and develop.

EnvironmentThe availability of a substance, as in the case of a college student having easy access to drugs or alcohol, may also make it much easier for an individual to become addicted.Environmental factors can be so strong that an addict in recovery usually finds it necessary to avoid certain situations or people that may trigger a craving or a relapse into the addictive behavior.Environment - AgeAge: Rat studies provide behavioral evidence that adolescence is a period of increased vulnerability to drug seeking behavior and onset addictionThe mesolimbic dopamine system of the brain is undergoing reorganization and functional changes during adolescence.

EnvironmentBrown et al (1997) Close friends and romantic partners are influential on attitudes and behaviors. As a result, it is more susceptible to become addicted in the wake of drug use during this developmental period. Overall, social, behavioral and developmental factors in adolescence make individuals more liable to drug seeking behavior, and as a result, addiction.

Environment - StressStress: Everyday stress:People smoke, drink to deal with stress/daily-hasslesStresses could lead to addiction, and add to both maintenance and relapse Traumatic stress: PTSD linked to addiction Driessenet al (2008), found that 30% of drug addicts and 15% of alcoholics suffer from PTSD

Environment - PeersPeers: ASocial Identity Theoryis the portion of an individual'sself concept derived from perceived membership in arelevant social group (Henri Tajfel and John Turner )Social Learning Theory States that social behavior is learned primarily by observing and imitating the actions of others. (Bandura and Walters) Vicarious reinforcement Splits into SIT and SLT (Social Identity Theory) and (Social Learning Theory)EnvironmentEiseret al (1989) Positive rewards such as popularity and social status(smoking),Smokers befriend other smokers (Eiseret al, 1995) SITDuncan et al (1995) Exposure to peers that carry out behavior increase likelihood of smoking (SLT)McAlister et al (1984) Smoke due to increased popularity and peer approval- SLT

Vulnerability FactorsThree factor model

GENETICSENVIRONIMENTALREPEATED EXPOSURERepeated exposureRepeated exposure to drugs of abuse is the third component of the 3-factor model of addiction vulnerability. A repeated exposure to a drug is one of the determining factors in distinguishing recreational substance use from chronic abuse.Repeated exposureExperience dependent neural plasticity is a hallmark of repeated drug exposure and refers to the adaptation of the brain due to increased levels of the drug in the body.Repeated exposureLearning is of crucial importance as there is considerable interaction with the environment and the potential for acquiring new information is greatest. By depending largely upon selective experiences, neural connections are altered and strengthened in a manner that is unique to those experiences.Repeated exposureExperience dependent neural plasticity occurs as a result of experience of a novel stimuli (Substance) and rapidly learning the behavior in response.

Vulnerability FactorsThree factor model

GENETICSENVIRONIMENTALREPEATED EXPOSUREExternalizing factorsOff springs of ASPD parents likely to have severe alcoholic course.ADHD Offspring of ASPD parents likely to have severe alcoholic association with early onset of substance use, drug use disorders and risk of chronic dependence.Externalizing symptoms and substance use disorders share the characteristics of CNS disinhibition/hyperexcitability.It is related to P300, GABA and 5 HT functioning

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