Addiction vulnerability is an individual's risk of developing an
addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use o ...
during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population.
Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction;
the contribution from epigenetic (inheritable traits) risk factors to the total risk is unknown.
Even in individuals with a relatively low genetic risk, exposure to sufficiently high doses of an addictive drug for a long period of time (e.g., weeks–months) can result in an addiction.
In other words, anyone can become an individual with a substance use disorder under particular circumstances. Research is working toward establishing a comprehensive picture of the neurobiology of addiction vulnerability, including all factors at work in propensity for addiction.
Three-factor model
Accepted research now shows that some people have vulnerabilities to addiction and has established a three-factor standard for vulnerability to drug addiction: genetic factors, environmental factors, and repeated exposure to drugs of use.
Being vulnerable to addiction means there is a factor that makes one individual more likely to develop an addiction than another individual. Additionally, many in the science community agree that addiction is not simply just a result of
desensitized neural receptors but also a corollary of long-term associated memories (or cues) of substance use and
self-administration
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient.
In animal experimentati ...
.
Vulnerability to addiction has both physiological and biological components.
Genetic factors
Contemporary research in neurobiology (a branch of science that deals with the anatomy, physiology, and pathology of nervous system) of addiction points to
genetics
Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
as a major contributing factor to addiction vulnerability. It has been estimated that 40–60% of the vulnerability to developing an addiction is due to genetics.
One gene in particular, the
D2 subtype of
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
receptor, has been studied at length in association to substance addiction. The D
2 receptor responds to the chemical dopamine which produces rewarding and pleasurable feelings in the brain. Through mice studies, agreeing contemporary research has shown that individuals with a deficiency in this dopamine receptor exhibit not only a preference for and increased consumption of alcohol over their genetically normal peers,
but also compensated levels of the
cannabinoid
Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...
receptor type CB1.
This suggests that both of these genetic factors work together in the regulation of alcohol and
cocaine
Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...
in the brain and in the normal regulation of dopamine. 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. Recent studies show that GABA also plays a role in vulnerability to addiction. When alcohol is consumed it affects GABA by mimicking its effects on the brain, such as basic motor functions.
Additionally, genetics play a role on individual traits, which may put one at increased risk for experimentation with drugs, continued use of drugs, addictions, and potential for relapse. Some of these individual personality traits, such as impulsivity, reward-seeking, and response to stress, may lead to increased vulnerability to addiction.
Environmental factors
A major environmental factor that increases vulnerability to developing addiction is availability of drugs. Additionally, socioeconomic status and poor familial relationships have been shown to be contributing factors in the initiation and continued use of alcohol or other drugs.
Neurobiology plays a role in addiction vulnerability when in combination with environmental factors. Chronic
stressor
A stressor is a chemical or biological agent, environmental condition, external stimulus or an event seen as causing stress to an organism. Psychologically speaking, a stressor can be events or environments that individuals might consider demandin ...
s contribute to vulnerability because they can put the brain in a compromised state. External stressors (such as financial concerns and family problems) can, after
repeated exposure, affect the physiology of the brain.
Chronic stress or trauma has been shown to have
neuroadaptive effects. The brain can physically “rewire” itself to accommodate for the increase in
cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
produced by the stressors. Evidence has also shown that a great amount of stress hinders prefrontal functioning and causes an increased limbic-striatal level response. This can lead to low behavioral and cognitive control.
Additionally, when the brain is put under severe stress due to repeated drug use, it has been shown to be physiologically altered.
This compromised neural state plays a large role in perpetuating addiction and in making recovery more difficult.
Repeated exposure
Repeated exposure to a drug is one of the determining factors in distinguishing recreational substance use from chronic abuse. Many neurobiological theories of addiction place repeated or continued use of the drug in the path of addiction development. For example, researchers have theorized that addiction is the result of the shift from goal-directed actions to habits and ultimately, to compulsive drug-seeking and taking.
In other words, repeated, deliberate use of the drug plays a role in the eventual compulsory drug-taking and/or habitual drug-taking associated with addiction. Another theory suggests that through repeated use of the drug, individuals become sensitized to drug-associated stimuli which may result in compulsive motivation and desire for the drug.
Additionally, a third neurobiological theory highlights the changes in brain reward circuitry following repeated drug use that contributes to the development of addiction such that addiction is conceptualized as being a progression of
allostatic changes in which the addicted individual is able to maintain stability but at a pathological set point.
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.
In this sense, repeated exposure falls under both physiological vulnerability and behavioral/psychological vulnerability to addiction.
Although many variables individually contribute to an increased risk of developing a substance use disorder, no single vulnerability guarantees the development of addiction. It is the combination of many factors (e.g. genetics, environmental stressors, initiation and continued use of the drug) that culminates in the development of this disorder.
Adolescence
Previous research has examined the increased risk of early-onset substance use during adolescence. Many factors have been identified as being associated with increased risk of substance use during this period of development including individual differences (e.g., negative affect, decreased harm avoidance, and low motivation for achievement), biological (e.g., genetic predisposition and neurological development), and environmental factors (e.g., high levels of stress, peer influences, availability of substances, etc.)
Rat studies provide behavioral evidence that
adolescence
Adolescence () is a transitional stage of physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with the t ...
is a period of increased vulnerability to drug-seeking behavior and onset addiction.
The mesolimbic
dopamine system
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neur ...
of the brain undergoes reorganization and functional changes during adolescence. Rat studies have shown that adolescents have tendencies and abilities to drink more than adults due to minimal disruption to their motor functions and minimal sensitivity to sedation.
As a result, adolescents are more susceptible to developing substance used disorders.
The social, behavioral, and developmental factors in adolescents encourage drug seeking behavior, and as a result, addiction.
Epigenetic factors
Transgenerational epigenetic inheritance
Epigenetic
In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...
genes and their products (e.g., proteins) are the key components through which environmental influences can affect the genes of an individual;
they also serve as the mechanism responsible for
transgenerational epigenetic inheritance
Transgenerational epigenetic inheritance is the transmission of epigenetic markers from one organism to the next (i.e., from parent to child) that affects the traits of offspring without altering the nucleic acid primary structure, primary structur ...
, a phenomenon in which environmental influences on the genes of a parent can affect the associated traits and
behavioral phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
s of their offspring (e.g., behavioral responses to environmental stimuli).
In addiction, epigenetic mechanisms play a central role in the
pathophysiology
Pathophysiology ( physiopathology) – a convergence of pathology with physiology – is the study of the disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is the ...
of the disease;
it has been noted that some of the alterations to the
epigenome
An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism's offspring via transgenerational stranded epigenetic inheritance. Changes to the epigenome ...
which arise through chronic exposure to addictive stimuli during an addiction can be transmitted across generations, in turn affecting the behavior of one's children (e.g., the child's behavioral responses to addictive drugs and
natural reward
Behavioral addiction is a form of addiction that involves a compulsion to engage in a rewarding non- substance-related behavior – sometimes called a natural reward – despite any negative consequences to the person's physical, mental, social ...
s).
The general classes of epigenetic alterations that have been implicated in transgenerational epigenetic inheritance include
DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
,
histone modification
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn ar ...
s, and
downregulation or upregulation of
microRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...
s.
With respect to addiction, more research is needed to determine the specific
heritable
Heredity, also called inheritance or biological inheritance, is the passing on of traits from parents to their offspring; either through asexual reproduction or sexual reproduction, the offspring cells or organisms acquire the genetic informa ...
epigenetic alterations that arise from various forms of addiction in humans and the corresponding behavioral phenotypes from these epigenetic alterations that occur in human offspring.
Based upon preclinical evidence from
animal research
Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...
, certain addiction-induced epigenetic alterations in rats can be transmitted from parent to offspring and produce behavioral phenotypes that decrease the offspring's risk of developing an addiction.
More generally, the heritable behavioral phenotypes that are derived from addiction-induced epigenetic alterations and transmitted from parent to offspring may serve to either increase or decrease the offspring's risk of developing an addiction.
Notes
References
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Addiction psychiatry