Genetics play a significant role in addiction but genes don't cause addiction. Instead, a person inherits genes that make him more or less susceptible to fall into addiction, given other internal or external environmental factors. The complex role of genetics in addiction is an ongoing, evolving area of cutting-edge research.
Genetics and Environment
According to a 2012 review in Translational Psychiatry, numerous studies demonstrate that susceptibility to addiction is inherited. However, inheriting the risk genes doesn't inevitably lead to addiction.
Rather, the underlying genetic vulnerability or diathesis lies unknown unless environmental stressors, such as exposure to a drug or social pressures, trigger and interact with the predisposition to cause addiction. This is the basic principle that underpins the complex, multi-layered world of addiction science.
Still, many susceptible people might experiment with addictive substances but don't continue to become addicted. Though environmental factors can unmask a genetic predisposition and some factors can increase addiction susceptibility, others can be protective against addiction.
The interplay between genes and the environment is reciprocal. The environment can modify the genetic vulnerability and determine the role of the genetics and genes can determine the effect of the environment.
The greater the underlying genetic predisposition (inheritance), the easier it is for any environmental factor to induce addiction. The reverse is also true; the more powerful the environmental factors, the more likely they are to influence the underlying susceptibility.
Gene-by-environment refers to the observation that the version (variant) of a gene that is inherited can determine how it interacts with the environment. For example, in a 2007 study reported in Biological Psychiatry, college students who had stressful life events and inherited a particular variant of the gene for the serotonin transporter protein were more susceptible to alcohol and drug use.
The Degree of the Genetic Susceptibility
The National Institute of Drug Abuse notes that overall genetics account for 40-60% of the risk for addiction. According to the Textbook of Substance Abuse Treatment, "some genes act to cause general susceptibility to other substances while others cause specific addictions." The risk for each substance varies, but there is a high degree of overlapping susceptibility.
According to the Translational Psychiatry journal review, the following are the substance-specific genetic susceptibility for addiction:
- Nicotine: 33-71%
- Alcohol: 48-66%
- Marijuana: 51-59%
- Cocaine: 42-70%
- Opiates: 23-54%
Gambling addiction risk is 50-60%, according to a 2012 article in the journal Addiction.
Variations (mutations) in specific genes account, in part, for the range of genetic susceptibilities for each substance and for the differences in genetic vulnerabilities between people.
Overlapping Genetic Susceptibility
An early study published in JAMA Psychiatry in 1998 and a follow-up study, the Harvard Twin Study in 2001 by the same researchers, using data from the Vietnam Era Twin Registry, found that the risk for addiction for one substance overlapped with the risk for others. Heroin had the largest unique susceptibility of 36% and a 16% the smallest shared risk.
- Another study in The American Journal of Psychiatry (2003), using data from the Virginia Twin Registry, showed that genetic and other risks overlapped between cocaine, hallucinogens, marijuana, opiates and other illicit drugs. Opiates were found to have the least overlapping susceptibility.
- A 1999 study in the General Archives of Psychiatry reported that nicotine and alcohol addictions, which usually proceed together, had specific genetic risks for addiction but shared a 68% overlapping risk.
Behavioral addiction is similar to substance addiction on the basis of risks and the pattern of the addiction. A study in JAMA Psychiatry in 2000 showed that genetics also play role in gambling addiction and that the susceptibility overlaps with that for alcohol. There is less research and evidence for other behavioral addictions, such as TV-watching or internet-surfing.
An Individual's Susceptibility
A review in the journal Biochemical (2008) notes that multiple early family, twin and adoption studies, which sort out true gene inheritance from shared social, family and other environmental factors, show substantial evidence that a person's risk for addiction "runs in the family."
- One of the early studies published in 1998 in JAMA Psychiatry found that an individual with addicted family members was eight times more likely to become addicted to one or more substances.
- Another early twin study published in the JAMA Psychiatry (2000) showed that identical twins are more similar in their risk for addiction than are fraternal twins.
- These studies also showed that an adopted substance-dependent person resembles his biologic relatives in his genetic risk for addiction rather than his adoptive relatives.
Influences on Genetic Susceptibility
In addition to environmental stressors and gene variations, other factors that may influence the degree of genetic susceptibility include the stage of addiction and a person's age and gender.
Stage of Addiction
In the early stages of substance initiation and occasional use, genetic susceptibility plays less of a role than that of shared family and social environments or other factors. In later stages of regular use and addiction, genetics have a greater role than non-genetic factors, according to the 2000 JAMA Psychiatry study. However, based on a 2005 study in the journal Behavioral Addictions, there is overlap in the degree of the genetics role in the stages of addiction.
Teens are susceptible to experimenting with addictive substances, some of which is linked to impulsivity. A study in 2008 in the Archives of General Psychiatry concludes that during early adolescence social and shared family environments have a greater influence than genetics on addictive behaviors and addiction. In later adolescence and early adulthood genetic predisposition has a greater influence. This influence may lessen as a person "matures out" of addiction.
The 2012 review in Translational Psychiatry states that studies show inconsistent effects of gender on the role of genetics in addiction. According to a 2003 study on nicotine in the journal the Addiction, there is some evidence that genetics play a bigger role in women for starting to smoke than for continuing and the reverse is true for men
A study published in Drug and Alcohol Dependence (1998) indicates that for several substances, the genetic influence was stronger for men than for women to become addicted than for initiating substance use or for occasional use.
Extent of the Genetic Influence
Whether a person decides to start using an addictive substance is to some degree a matter of choice, as explored in a 2013 article in the Journal of Psychiatry and Neuroscience. However, genetics likely plays a role in all parts of the addiction process. This involves genes that code for aspects such as:
- Impulsivity to seek out and initiate a substance use or behavior
- The initial stage of occasional use
- Later stages of chronic use, abuse and addiction
- The amount of substance a person uses
- Use of multiple substances because of overlapping susceptibilities
- The severity of withdrawal symptoms
- Risk of relapses after quitting or during or after treatment
- Whether treatment will be successful
- The effect on the brain reward centers and dopamine and other mediators of the addiction which imprints the later steps to true dependence
Gene variations and what each gene codes for determine the degree of genetic influence on different parts of the process.
The Science of the Genetics
Researchers look for potential (candidate) "susceptibility genes," or regions on chromosomes that are markers of potential genes. These include genes or regions that might assign or modify genetic addiction susceptibility, or mediate parts of the addiction process in affected versus non-affected people.
Potential Genes and Chromosome Markers
Scientists have identified potential genes that mediate the risk for alcohol, nicotine, cocaine, marijuana, opiates, morphine and gambling addiction in human and lab animal studies. Some of these genes, such as ones for alcoholism, have strong evidence from different independent researchers but others have not.
An example are variants of the genes that code for the alcohol metabolism enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH).
The Nature of the Risk Genes
From these genetics studies conducted on a variety of ethnic groups, the experts conclude that there are no major "addiction genes," nor is addiction a single gene inheritance, like cystic fibrosis or sickle cell anemia, for example. Instead, several affected genes on various chromosomes (polygenic association) confer susceptibility. Together they exert a collective influence on a person's inherited addiction risk.
A Complex Genetics
A 2012 review article in Human Genetics notes that the genetics of addiction is not simply a matter of addiction "susceptibility genes" and environment. Multiple other genes that code for various parts of the process are involved and interact in the complex layers of addiction vulnerability and addiction. This includes genes involved in:
- Addictive substance metabolism
- Brain development and remodeling
- New nerve connections
- Regulation of the stress hormones
- Imparting impulsive and risk-taking behaviors
Brain Reward Centers
The brain is hard-wired for addiction to pleasure and reward, not for addiction to substances and behaviors that came eons after the wiring and genetics were set. However, the same primitive brain reward centers and pathways are involved in addiction. This wiring includes setting the memory of the pleasure and reward and how to seek it out and find it, according to the Journal of Psychiatry.
Substance use and addiction cause complex rewiring of the brain's reward and pleasure centers according to a 2012 review in Neuropsychopharmacology. This neuro-adaptation imprints the memory of an experience and the motivation to repeat it. This includes changes in brain cells, nerve cell signal transmission and in the receptors and actions of serotonin and stress hormones. Genes code for all aspects of these changes.
Once initiated, addictive substances or behaviors alter how genes are expressed in these centers. The genetic-induced changes and rewiring makes it more likely that someone will continue on toward addiction, with repeated and increased quantity of substance use (tolerance). As reviewed in Archives of Neurology, in 2007, genes that code for dopamine receptors and the role of dopamine in addiction are key players in this result.
Environmental factors can act as triggers or protective modifiers of genetic addiction susceptibility for initiating a substance or behavior and for repeated use, abuse and addiction. These factors include developmental, behavioral, social, psychological, physical and other inputs many of which have great influence during adolescence, as reviewed in Psychiatry Clinics of North America in 2010.
Some of these co-factors can help to protect against starting or continuing a substance while others can help sustain the addiction once started.
Important environmental factors that can increase vulnerability or trigger the genetic predisposition and increase the chance of substance dependency include:
- Exposure to the substance in the first place
- First use of the substance or any other substance that might trigger general addiction behavior
- Family dynamics such as domestic violence and family mental health
- Personal mental illnesses such as depression or schizophrenia can increase the risk of addiction and the reverse is true
- Friends or family who use drugs
- Childhood deprivation or abuse
- Psychological, sexual, social or physical abuse
- General daily life stress
- Major work stress or other life stress events, such as a death, divorce or job loss
Protective Modifying Factors
Protective factors that can modify the genetic predisposition and the effect of other environmental factors and prevent a person from falling into addiction include:
- Childhood nurturing
- Strong family and social support
- Positive outlook on life
- Lifestyle choices such exercise and healthy nutrition
- Stress coping mechanisms such as meditation
The Evolving Research
The pioneering evidence for the inheritance of addiction disorders come from the family, twin and adoption human epidemiology studies and lab animal studies, as summarized in the Textbook of Substance Abuse Treatment and in the in-depth Nature journal review.
Major advances in the role of genetics in addiction come from studies of the whole genetic code (genome). This includes genome-wide linkage studies and genome wide association studies (GWAS) in humans and genetic studies in lab animals. These studies compare the frequency of chromosome markers and genes in substance-affected versus non-affected people. Linkage studies identify chromosome regions of that might contain genes of interest and GWAS studies seek to identify specific genes.
Advancing Research Tools
To figure out the role of the potential genes and the mechanisms by which they confer susceptibility, various research groups are collaborating and pooling their results. Scientists are also making use of advances in genome research, imaging studies, computer tools and information analysis to better understand the complicated genetics.
Treatment and Prevention
The role of genetics in addiction is complex, but as research tools become more sophisticated, researchers are able to tease out more of the finer details. As scientists further unravel the genetic complexities and the interaction between genetics and environment factors this should lead to improved strategies to prevent and treat addiction.