VULNERABILITY HYPOTHESIS IN

ADDICTION MEDICINE

Presenter : Dr Nithin Kondapuram,
Chairperson: Dr. Arun K.
25-07-2014
Clinical case presentation
1
Introduction
Aristotle: Drunken women bring forth children like
themselves

Plutarch: Drunkards beget drunkards

Introduction
Benjamin Rush (1787) observed that alcohol
dependence runs in families.
Not everyone who takes drugs becomes addicted
Vulnerability 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 Factors
Three factor model

GENETICS ENVIRONIMENTAL
REPEATED
EXPOSURE
Many 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 parents
In 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 Models
Deviance proneness model
Proposed 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 Models
Similarly, extraversion has been shown to be related to
substance-use onset, alcohol consumption, and alcohol
problems
Delinquency* 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 Models
Negative affect regulation model
Proposed by Sher KJ, in 1991
The primary premise of the negative affect regulation model is
that alcohol and drug problems occur because people drink to
reduce negative affect
It 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 Models
Accordingly, 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 affect
However, it is still unclear whether negative affect is a
salient predictor of substance use over time.
Types of Three Factor Models
A comprehensive model
Proposed 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 Models
Deviance 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 Factors
Three factor model

GENETICS ENVIRONIMENTAL
REPEATED
EXPOSURE
Genetics
Family 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
a genetic disorder
Genetics
Adoption 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



Genetics
The Collaborative Study on the Genetics of
Alcoholism: (Hesselbrock et al 2001)
n= 9000 adults , 1500 children and adolescents
Chrm 1 & 7 have regions containing genes that
increase risk of alcoholism.
Chrm 4 protective factor - near ADH type 1 genes.


Genetics

Common Genetic Vulnerability
Stimulants
73%
Heroin/
Opiates
30%
Psychedelics
100%
Marijuana
67%
Sedatives
81%
Alcohol
93%
Genetics
Contemporary research in the neurobiology of
addiction points to Genetics as the main contributing
factor to addiction vulnerability.
One gene in particular, the D2 subtype of Dopamine
receptor has been studied at length regarding
substance addiction. The D
2
receptor responds to the
chemical dopamine which produces rewarding and
pleasurable feelings in the brain
Genetics
Individuals with this genetic deficiency in the
D
2
dopamine 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 Factors
Three factor model

GENETICS ENVIRONIMENTAL
REPEATED
EXPOSURE
Environment
Environmental 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.

Environment
In 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.

Environment
The 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 - Age
Age: Rat studies provide behavioral evidence
that adolescence is a period of increased
vulnerability to drug seeking behavior and onset
addiction

The mesolimbic dopamine system of the brain is
undergoing reorganization and functional changes
during adolescence.

Environment
Brown 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 - Stress
Stress: Everyday stress:
People smoke, drink to deal with stress/daily-hassles
Stresses 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 - Peers
Peers: A Social Identity Theory is the portion of an
individual's self concept derived from perceived membership in
a relevant 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)
Environment
Eiseret al (1989) Positive rewards such as popularity
and social status(smoking),
Smokers befriend other smokers (Eiseret al, 1995) SIT
Duncan 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 Factors
Three factor model

GENETICS ENVIRONIMENTAL
REPEATED
EXPOSURE
Repeated exposure
Repeated 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 exposure
Experience 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 exposure
Learning 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 exposure
Experience dependent neural plasticity occurs as a
result of experience of a novel stimuli (Substance)
and rapidly learning the behavior in response.
Vulnerability Factors
Three factor model

GENETICS ENVIRONIMENTAL
REPEATED
EXPOSURE
Externalizing factors
Off 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



GENETIC PREDISPOSITIONS
CNS DISINHIBITION
EXTERNALISING SYMPTOMS
EXPOSURE TO ALCOHOL-INITIAL RELEIF FROM HYPERXECITABILITY
TOLERANCE
WITHDRAWAL SYNDRROME EXACERBATES HYPEREXCITABILITY
DEPENDENCE
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