Addiction vulnerability
| Addiction and dependence glossary[1][2][3] | |
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Addiction vulnerability is an individual's risk of developing an addiction during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population.[2][4][5] Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction;[2] the contribution from epigenetic (inheritable traits)[6] risk factors to the total risk is unknown.[4] 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.[2] 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.[7] 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.[8] Vulnerability to addiction has both physiological and biological components.
Genetic factors
Contemporary research in neurobiology (a branch of science that deals with the anatomy,
This suggests that both of these genetic factors work together in the regulation of alcohol and cocaine in the brain and in the normal regulation of dopamine. Individuals with this genetic deficiency in the D2 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.[12] 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.[13]
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.[14]
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.[15] Neurobiology plays a role in addiction vulnerability when in combination with environmental factors. Chronic stressors 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.[16]
Chronic stress or trauma has been shown to have neuroadaptive effects. The brain can physically “rewire” itself to accommodate for the increase in cortisol 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.[16] Additionally, when the brain is put under severe stress due to repeated drug use, it has been shown to be physiologically altered.[8][17] 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.[18][19]
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.[20]
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.[21] 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.[22] 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.) [23][24][25] Rat studies provide behavioral evidence that adolescence is a period of increased vulnerability to drug-seeking behavior and onset addiction.[26]
The mesolimbic
Epigenetic factors
Transgenerational epigenetic inheritance
The general classes of epigenetic alterations that have been implicated in transgenerational epigenetic inheritance include
Notes
- testes, and sperm of cocaine-addicted male rats.[4] These epigenetic alterations in the rat mPFC result in increased BDNF gene expression within the mPFC, which in turn blunts the rewarding properties of cocaine and reduces cocaine self-administration.[4] The male but not female offspring of these cocaine-exposed rats inherited both epigenetic marks (i.e., di-acetylation of lysine residues 9 and 14 on histone 3) within mPFC neurons, the corresponding increase in BDNF expression within mPFC neurons, and the behavioral phenotype associated with these effects (i.e., a reduction in cocaine reward, resulting in reduced cocaine-seeking by these male offspring).[4] Consequently, the transmission of these two cocaine-induced epigenetic alterations (i.e., H3K9ac2 and H3K14ac2) in rats from male fathers to male offspring served to reduce the offspring's risk of developing an addiction to cocaine.[4] As of 2018,[update] neither the heritability of these epigenetic marks in humans nor the behavioral effects of the marks within human mPFC neurons has been established.[4]
References
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Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
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Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder. - ^ PMID 23920159.
However, the components that are responsible for the heritability of characteristics that make an individual more susceptible to drug addiction in humans remain largely unknown given that patterns of inheritance cannot be explained by simple genetic mechanisms (Cloninger et al., 1981; Schuckit et al., 1972). The environment also plays a large role in the development of addiction as evidenced by great societal variability in drug use patterns between countries and across time (UNODC, 2012). Therefore, both genetics and the environment contribute to an individual's vulnerability to become addicted following an initial exposure to drugs of abuse. ... The evidence presented here demonstrates that rapid environmental adaptation occurs following exposure to a number of stimuli. Epigenetic mechanisms represent the key components by which the environment can influence genetics, and they provide the missing link between genetic heritability and environmental influences on the behavioral and physiological phenotypes of the offspring.
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