e-learningsite.com

free essays
Free essays

Genetic Predisposition to Addictive Disorders

GeneticPredisposition to Addictive Disorders

Abstract

Thepurpose of the present study was to evaluate the issue of geneticpredisposition to dependence disorders. The study identified that theoccurrence of addiction disorders in some people and not in others isaccounted for by the 0.1 % of genetic differences in the humangenome. Transmission of genetic disorders occurs in two types ofmechanism, including the specific and the general effects. Thepresence of loci in the DNA sequence, which has the capacity toinfluence addictive disorders, indicates that these disorders areheritable. However, some disorders have shared causation (caused bythe same genomic alteration) or unshared causation (caused byspecific genomic alteration). Each of dependence disorders consideredin the present study has some genomes associated with its occurrence,but there are several cases of overlap. The knowledge provided in thepresent study is important in the design of effective therapeuticstrategies for addictive disorders and reducing controversy ofwhether genetic alteration predisposes people to addictive disorders.

Keywords: Genetic predisposition, genetic markers, gene expression,dependence disorders, genetic influence.

GeneticPredisposition to Addictive Disorders

Currently,health complications that result from addiction to substance use aremajor causes of global health concerns. Although it is widelyaccepted that environmental conditions play a major role in causingaddiction and its related disorders, genetic predisposition is stillcontroversial. Breining Institute (2006) defined geneticpredisposition as the latent susceptibility of an individual to adisease that is activated under certain conditions. The wordaddiction is used to refer to a large number of maladaptive issues ofcertain behaviors or drug use, which results in clinicallysignificant distress or impairment (Agrawal etal.,2012). The difficulties associated with the genetic study ofaddiction, which involves the molecular analysis of heritable traitscould be the primary cause of the failure to comprehend the aspect ofgenetic predisposition of these disorders. However, scientificresearch shows that 40-60 % of predisposition to addictive disordersis explained by genetics and heredity (Monti, 2012). This means thatfurther research and study of addiction might prove how the geneticpredisposition is better explained in terms of heredity thanenvironmental predisposition. Genetic predisposition of individualsto addictive disorders is the most appropriate approach of explainingthe prevalence of addition to substance use and certain behavior insome people and not in others.

Background

Theuse and addiction to different substances has been a common practicefor centuries. Addictive disorders range from moderate to highlyheritable forms of addiction that are influenced by environment andgenes. The study of genetic predisposition to addictive disordershave been a complex exercise, partly because of the closeinterrelationship between addictive disorders and other types ofpsychiatric disorders (Goldman, Oriszi &amp Ducci, 2006). The highrate prevalence of addictive disorder, which has historically shownno signs of decline, warrants the study to identify the keypredisposing factors. In addition, differences that prevail betweenindividuals and their vulnerability to substance use and addictionhave been an issue of concern to researchers. For example, PrimaryPsychiatry (2009) identified that the vulnerability of male subjectsto alcoholic addiction is double the rate of vulnerability of theirfemale counterparts. In addition, rates of prevalence differ withother factors, including the age and the addictive substance underconsideration.

Althoughthe study of genetic predisposition to addictive disorders has beengoing on for many decades, significant breakthrough was made in the1980s following the maturation of technology that could help indirect manipulation of genomes (Philibin, Wiren &amp Crabbe, 2012).The key factor that drives the scientists’ attention to the studyof genetic influence on addiction is the need to resolve thecontroversy of heritability of addictive disorders. The integrationof modern technology has so far facilitated the identification ofspecific genes that are responsible for the occurrence of differenttypes of addiction. Currently, it is evident that there are manygenetic loci that influence the variation as well as themanifestation of addictive disorders. However, the relationshipbetween genes and the occurrence of addictive disorders is morecomplicated than the study of Mendelian genetics and traits (PrimaryPsychiatry, 2009). This has complicated the understanding of theinteraction between environment by gene interaction and genetic loci,which heightens the debate on the role of genetics in predispositionof individuals to addictive disorders.

Statementof problem

Theavailable knowledge that pertains to genetic predisposition todependence is based on the fact that the chronic and acute use ofdrugs results in significant alterations in gene expression,especially in the central nervous system. Most of these alterationsin gene expression as well as their consequences are enduring andremain for a lifetime (Philibin, Wiren &amp Crabbe, 2012). Thediscovery of this persistence of changes in gene expression leads tothe issue of heritability of these alterations and their propagationto subsequent generations. The heritability of these enduringneuroadaptive alterations in gene expressions means that theoffspring of the carrier of altered genes will be vulnerable to orgenetically predisposed to similar addictive disorders as theirparents. Although there are several studies that have addressed theissue of genetic predisposition to dependence disorders, acomprehensive review of update information in this area of study israre. The present study will fill this gap by evaluating themechanism through which genetic predisposition to dependencedisorders, specific genes that facilitate predisposition to differenttypes of dependence, and interplay between gene and environmentalconditions in causation of dependence disorders. This purpose will beachieved by reviewing the available literature in the areas ofgenetic predisposition to dependence disorders.

Thestructure of this paper consists of six parts. The first sectionfocuses on the genetic effect on addiction. This section addressesthe impact of small genetic differences between human beings as thekey factors that accounts for genetic predisposition of some peopleto dependence disorders. The section also addresses the mechanismsthrough which genetic predisposition occurs.

Thesecond part addresses the issue of heritability of dependencedisorders. This section highlights the key models that explain themode of transmission of addictive disorders through genetic transfer.It also differentiates between the inheritance of shared and unshareddependences.

Thethird section focuses on specific genes that influence individualtypes of addiction. The genes considered in this section includegenes for alcohol addiction, opioid dependence, nicotine addition,cocaine dependence, and cannabis dependence.

Thefourth section addresses the interplay between genetic andenvironmental conditions that influence addictive disordersconcurrently.

Thefifth part provides the implications of the study, which include thedesign of effective therapeutic strategies and reduction in doubts onthe capacity of genetic alteration to predispose individuals toaddictive disorders.

Finally,the paper concludes that genetic predisposition to dependencedisorders provides a better explanation for the occurrence of thesedisorders in some people and not in others.

Geneticeffect of addiction

Thenumbers of molecular studies that focus on the influence of heredityon addiction have been increasing over the years. Researchers in thisfield aim at resolving the controversy surrounding the issue ofgenetic predisposition to addictive disorders. Molecular researchersuse the genes, which are the functional units of Deoxyribonucleicacid (DNA) to identify the differences in the basic cellularactivities in different persons. The DNA sequence of all human beingshas a 99.9 % level of similarity while the remaining proportion (0.1%) accounts for the differences (including addiction, diabetes, andstroke among other disorders) between the nearly identical humanbeings (National Institute on Drug Abuse, 2008). Variation in geneticcomposition is the key factors that contribute to the differences inthe individual’s level of resistance or risk of substance use andaddictive disorders. This is a molecular reason that explains thereason for some people to become addicted to substances while othersdo not.

Apartfrom the effect of the difficulty of conducting molecular studies onthe current controversy, inconsistent findings to prove thedifferences in the nature as well as the magnitude of geneticinfluences could also contribute to the debate. At present, there aretwo major factors that have been found to contribute to differencesin heritability of addictive disorders. First, the liability tosubstance use and behavioral addictions are multi-stage process(Agrawal etal.,2012). Addiction starts with the early steps of substance use, whichis followed by regular as well as chronic use before developing intoaddiction. Early stages of use are highly influenced by environmentalconditions they are less heritable while the chronic stages areinfluenced by genetic factors. Secondly, the developmental coursecontributes to differences in heritability of addiction. Forexample, initiation of substance use often begins in adolescencewhile its related disorder occurs during adulthood. Heritable factorshave a stronger influence on individuals during adulthood whenconsidering the number of drugs used and frequency of use. Duringadolescence, on the other hand, there are some shared environmentalconditions that lead to familial resemblance, but 75 % of variancesare unveiled during the adulthood (Agrawal etal.,2012). However, heritable influences for problem use are consistenteven during adolescence.

Mechanismof action of gene’s effect on addictive disorders

Genesinfluence the liability of substance and behavior addiction in twobroad ways. First, some genes influence addiction through effectsthat are specific to certain substances or drugs. According toAgrawal etal.(2012) genes that regulate the metabolism of psychoactive drugscauses effects that are specific to those substances. For example,the relationship existing between variants in ALDH2 (rs671) and ADH1B(rs1229984) and alcohol consumption is the direct cause of the effectof these SNPs on the metabolism of alcohol (Edenberg, 2007). ADH1Baffects the rate which alcohol is converted acetaldehyde while ALDH2reduces the rate of acetaldehyde to acetate. This leads to theaccumulation of acetaldehyde, which causes the flushing syndrome.This is a common occurrence among the Asian communities and it ischaracterized by dizziness, headaches, nausea, and facial reddening.The increase in social pressure in different countries (such as Koreaand Japan) has induced people with protective ALDH2 and ADH1B allelesto drink.

Secondly,some genes influence the liability to addiction through the generaleffect of externalizing behaviors, which include impulsivity anddisinhibition. This means that the effect of genetic liability tocertain addictive substances of behavior could be overlapping whereaddiction to a group of drugs has a shared hereditary influence. Forexample, a twin research conducted by Kendler, Jacobson, Prescott &ampNeale (2003) revealed that liability to cocaine and alcoholdependence has the same genetic vulnerability. This overlappinginfluences leads to a suggestion that some addiction liabilitiesarise from the relationship between certain genes and generalpredilection to some externalizing behavior. The shared hereditarypathways act as reflections of multiple processes, includingcompulsivity and impulsivity. For an instant, genes that influenceimpulsivity have a general impact on multiple dependencies becauseimpulsivity has many behavioral indices (such as conduct problems)that reduce its specificity (Agrawal etal.,2012). The dopamine reward circuit functions independently, but itcan act interactively with GABA-ergic and glutamatergic signaling toinfluence the development and persistence of addiction. This impliesthat there are genetic predispositions to addictive disorders thatthat are not specific, but bear similarities within a group ofsubstances.

Inboth cases, drug specific impact and the general effects, thepresence or absence of certain mid-region chromosomes along the DNAsequence is the key determinants of individual’s vulnerability toaddictive disorders. The improvement in precision and power ofgenetic mapping makes it possible to establish the associationbetween genetic markers (DNA sequences that are found in specificlocations in genome sequence) and phenotypic traits (Philibin, Wiren&amp Crabbe 2012). The co-occurrence of certain genetic markers withphenotypic traits is a suggestion that the gene in which the marketis located codes for the synthesis of gene products that increasesthe risk of predisposition. For example, the presence of a markerclose to serotonin 5-HT 1Breceptor is an indication of aggressive and impulsive geneticpredisposition to alcoholic addiction (Philibin, Wiren &amp Crabbe2012). This implies that the presence of chromosomal regions thatcontain allelic variants that induce addiction is the key determinantof whether an individual is genetically predisposed to the risk ofaddiction or not.

Heritabilityof substance use disorders

Aclear description of the mode in which addiction is inherited helpsin reducing the controversy of the heritability of addictivedisorders. However, the process of identifying functional loci andspecific genes that regulate vulnerability is challenged by differentfactors, including the presence of incomplete phenocopies, variableexpressivity, penetrance, interaction between gene and environment,epistasis, polygenicity, and genetic heterogeneity (Ducci &ampGoldman, 2012). These challenges can be reduced using various modelsthat explain the mode of inheritance of addictions. For example, theepistatic model shows that the combination of different geneticvariants is the key determinant of phenotypes, which leads to a highration of monozygotic (MZ) / dizygotic (DZ) concordance. This isbecause MZ twins have identical alleles while DZ twins shareapproximately half of all alleles. The gene by gene interaction isanother model that is used to explain the heritability of addictivedisorders, especially in the study of alcoholism. The gene by genemodel has revealed that the protective impact of missense variantsthat occur in ADH1B and ALDH2 are addictive (Ducci &amp Goldman,2012). These models help in the determination of specific locusvariants that can be passed on from parent to off springs. Addictivedisorders are inherited in the form of complex and common diseasesthat fail to show the prototype of Mendelian transmission. Thepolygenic model holds that the expression of a given disease in afamily or an individual requires a simultaneous inheritance ofnumerous genetic variants (Goldman, Oriszi &amp Ducci, 2006). Asingle hereditary variation, on the other hand, determines resiliencyand vulnerability because it is insufficient to induce diseaseexpression. The concordance ratio of monozygotic to dizygotic is usedto determine whether the disorder is polygenic or not.

Thegene effect on heritability of addictive disorders changes across thelifespan. According to Ducci &amp Goldman (2012) the geneticinfluence on nicotine, alcohol, and cannabis addiction is low duringadolescence, but increase gradually during the adulthood. Theenvironmental impact, on the other hand, reduces from childhood toadulthood. These occurrences are explained by the fact that humanbeings increase the latitude to determine their own choices as wellas social environments, which increases the significance of genotypein influencing addictive disorders. In addition, some hereditaryfactors gain significance after undergoing repetitive exposure, whichis more likely to occur in adulthood than in childhood. Moreover,there are some alleles that only change the adults’ brainresponses. For an instant, hereditary variations that occur withinthe CHRNA5-CHRNA3-CHRNB4 cluster leads to a stronger impact onsmoking behavior during adulthood than during adolescence (Ducci &ampGoldman, 2012). This effect also moderates the tendency to developthe pattern of abusing tobacco among individuals who have alreadyinitiated the use of nicotine.

Sharedand unshared dependence inheritance

Someaddictions are closely associated with the occurrence of addictionsof other substances, a situation that is referred to as the sharedcausation. The co-occurrence or shared causation of addictivedisorder increases the significance of considering the genetic modeof transmission as well as the neurobiological aspects of dependence.This implies that some types of dependence are caused by the samegenetic variants, which makes it difficult to distinguish theirindividual causes. For example, a cross comparison study conducted byGoldman, Oriszi &amp Ducci (2006) revealed that nicotine and alcoholhave general genetic risk factors where approximately 85 % of alcoholaddicts smoke, 50 % of the heritable liability to nicotinic addictionhas similar causation with the liability to alcohol dependence, andgenetic liability to alcohol addiction is shared with nicotineaddiction. A broader twin studies also revealed that similar geneticfactors explained the individual’s vulnerability to cocaine andcannabis dependence and similar genetic predisposition to nicotine,alcoholism, and caffeine dependence (Ducci &amp Goldman, 2012). Thismeans that risks for genetic predisposition to certain types ofaddiction can be inherited jointly or individually.

Specificgenes for different types of addiction

Genesfor alcohol metabolism and addiction

Thegenetic implication on alcohol addiction is one of the areas thatinterest many researchers. Most interestingly, genes that areinvolved in the metabolism of alcohol have been shown to have adirect implication in the development of alcohol addiction. Accordingto Primary Psychiatry (2009) alcohol dehydrogenase 1B that takes partin the conversion of alcohol to acetaldehyde and aldehydedehydrogenase 2 that is involved in the conversion of acetaldehyde toacetate increases susceptibility to alcohol dependence. Theoccurrence of polymorphism in genes that regulate alcohol metabolismresults in an increase in the level of acetaldehyde, which has asignificant effect on human drinking behavior. ADH1B*2 allele leadsto rapid oxidation of ethanol, which protects individuals againstalcoholism. For example, the East Asian communities have a highfrequency of this allele, which makes them less likely to becomealcoholism (Dick &amp Agrawal, 2008). The ALDH2*2 allele also leadsto strong protection against alcoholism because it is a dominantnegative with reduced rates of the conversion of acetaldehyde, thusresulting in negative physiologic impact that is linked with the useof alcohol. The gene identification efforts have also shown thatADH3, one of the alcohol dehydrogenase genes leads to alcoholaddiction and abuse of polysubstances. This implies that thepredisposition to alcoholic addictive disorder results fromalterations of genes that are involved in the metabolism of alcohol.

GABAreceptors and alcohol addiction

GABAreceptors control the pharmacological impacts of ethanol in humanbrain. Some of its genes include GABRA2, GABRA4, GABRG1, and GABRB1(Kimura &amp Higuchi, 2011). GABA region has microsatellite markerthat is associated with alcohol dependence. The SNP in GABRA2, a genethat encodes for GABA-A receptor increases the risk for ethanoladdiction. In addition, the SNP found in GABRA2 increases the powerof EEG in beta frequency band, which acts as a reflection of theheritable vulnerability of ethanol addiction. The linkagedisequilibrium that exists between GABRA2 markers GABRG1 genes is themajor cause of alcohol dependence. Other genes of GABRA receptor witha positive association with alcohol, addiction include GABRA6,GABRG2, and GABRB2. The occurrence of polymorphism in the genes ofGABA receptors, especially BABRG1 and GABRA2 is positively associatedwith alcohol addiction and brain oscillation, which is anendophenotype for ethanol addiction (Primary Psychiatry, 2009).However, polymorphism in GABRA2 is also associated with geneticpredisposition to other addictive disorders, including dependence onillicit drugs, conduct disorder, and antisocial personality disorder.The high sensitivity of GABA receptors to alcohol leads to motorimpairment, sedation, and anxiety.

Genesrelated to dopamine

Genesof dopaminergic system are part of the candidate gene for substanceaddiction, which is facilitated by the capacity of dopamine to takepart in the reward pathway. According to Primary Psychiatry (2009) D2 receptors are associated with a wide range of addictions, includingalcohol, cocaine, heroin, methamphetamine dependence, smokingbehavior. The D 2 receptor is also associated with non-drugpsychiatric disorders as well as impulsive behavior. Polymorphism ofthe D2 gene occurs in the form of a missense mutation long the codingregion of kinase domain and ankyrin repeat. DRD4 receptor isassociated with alcohol dependence, smoking behavior, and apioidaddiction. The DRD4 receptor gene has a 48-base pair tandem repeatsequence and seven repeat alleles that lead to an indirectassociation with alcohol craving and binge drinking (Kimura &ampHiguchi, 2011). Polymorphism of the dopamine genes occurs at the geneexpression level and creates an impact on the sensitivity of relevantstimuli and dopaminergic tone.

Genesrelated to serotonin

Serotoninregulates the drinking behavior as well as the alcohol craving.Polymorphism occurs in serotonin through deletion or insertion in thepromoter region of its transporter gene. The shorter allele has alower transcription rate compared to the long allele. Polymorphismthat occurs in serotonin genes can also lead to personality disorders(such as depression) and psychiatric disorders. The frequency of theshort allele is positively associated with the risk of severe alcoholaddiction and comorbid psychopathology. The specific serotonin genesassociated with alcohol addiction include HTR2A (2A receptor genes,5-HT3, and HTR1B (1B receptor gene) (Kimura &amp Higuchi, 2011).

Cholinergicmusarinic receptor-2

Thisreceptor is found on chromosome 7q and it is associated with alcoholaddiction. The occurrence of polymorphism in the CHRM2 genepredisposes an individual to the risk of alcohol dependence as wellas alcohol addiction that is coupled with serious depression (Kimura&amp Higuchi, 2011). In most cases the association betweenpolymorphism in CHRM2 and alcohol dependence is detected in peoplewith comorbid and personality trait disorders. This suggests thatboth the psychiatric disorders and as well as the personality traitsincreases the CHRM2 polymorphism to function as a geneticpredisposing factor of addictive disorders.

NeuropeptideY

NeuropeptideY is expressed in the cortex and it has sedative as well asanti-depressive effects. This binding of this receptor leads toemotional control, which takes part in the development of substanceabuse and dependence (Primary Psychiatry, 2009). The use of the drugis perceived to be an attempt by an individual to self-regulate thesigns of psychopathology. Variants in neuropeptide Y are positivelyassociated with preference for alcohol, polymorphism of a singlenucleotide of NPY2R leads to multiple addiction phenotypes, and NPY5Ris positively associated with alcohol withdrawal. Different receptorsof the neuropeptide (including NPY2R, NPY5R, and NPY1R) are alsoassociated with other types of dependence, including nicotinedependence.

Geneticpredisposition to opioid dependence

Addictionto opioids (such as heroin) is induced by polymorphism that occurs inthe genes encoding for mu-opioid receptor (Agrawal etal.,2012). The mu-opioid receptor genes known as the mu-1 undergoesnon-synonymous polymorphism with predisposition to amino acids thatare generated from the conversion of asparagines to aspartic acid,which provides the functional groups. This type of polymorphism leadsto subjective responses to drinking behavior, including craving aswell as sensitivity. The mechanism of action of most of the genesthat predispose individuals to opioid dependence is the generaleffect as opposed to the drug specific effect. For example,polymorphism that occurs in the µ, δ, and k receptor genes leads toheroin, alcohol, and cocaine dependence (Primary Psychiatry, 2009).However, studies onµ receptor gene are perceived to be moreimportant to researchers because it acts as the site of action formorphine and heroin. These genetic variations in these receptorsresults in subjective response to addictive substances, especiallythe opiates, which subject individuals to the risks of dependence.

Geneticpredisposition to nicotine addiction

Thegenes for nicotine response are involved in pathways that areresponsible for the absorption, transportation, and metabolism ofdrugs that contain nicotine. Nicotine addiction is mainly induced bygenetic variations that occur in the chromosome 15 of the genes(including CHRNA5, CHRNB4, and CHRNA3) that encode the subunits ofacetylcholine receptor (Agrawal etal.,2012). Significant variations in these genes, especially the CHRNA5increase individual are susceptible to nicotine dependence. Inaddition, the CYP2A6 gene, which belongs to the family of P450, has asignificant contribution to nicotine addiction. Genetic variations ofCYP 2A6 determines the rate of nicotine metabolism, which in turninfluences individual’s nicotine dependence. Genetic variations inCYP 2B6 are associated with changes in the process of proteinexpression as well as successful smoking cessation (PrimaryPsychiatry, 2009). Nicotine addiction treatment mechanisms target thegenetic variations of the genes that regulate its metabolism.

Geneticpredisposition to cocaine addiction

Addictionto cocaine is induced by variations in a larger number of genes wherechanges in a single gene between them may not lead to a conclusiveevidence of genetic predisposition. These genes include DRD2 thatundergoes dopaminergic nucleotide polymorphism, opioidergic genes(such as PER 1 and CLOCK) that are responsible for the regulation ofcircadian rhythms, and tryptophan hydroxylase 2 (Agrawal etal.,2012). Recent studies have established the relationship between Camk4genes with cocaine dependence. According to NHS Choices (2014)genetic variation of the Camk4 gene at site rs919334 is a commonoccurrence among people with are addicted to cocaine compared withthe general population. The study showed that about fifty percent ofcocaine addicts have twice the number of Camk4 variant more thanpeople without this type of dependence. This suggests that cocaineaddiction is largely influenced by genetic variations unlike thecommon perception that this addiction is results from environmentalconditions.

Geneticpredisposition to cannabis addiction

Cannabisdependence is influenced by several genes, which include thecannabinoid receptor 1 (CNR 1) and fatty acid amide hydrolase.Cannabis compounds bind putatively to CNR 1, from where it brings itsdependence effect (Agrawal etal.,2012). In most cases, predisposition to cannabis and alcoholicdependence is caused by the same genetic variants. According toDryden (2009) most of the genes that predispose human beings to theuse and dependence on alcohol also subject them to the risk ofmarijuana addiction. However, the ultimate effect is accomplished bya combination of genetic variants that lead to co-occurrence of thetwo forms of addiction. For example, GABRA2 is a gene that encodesthe alpha 2 subunit of GABA and its variation increasessusceptibility to both alcohol and cannabis dependence (Agrawal etal.,2012). This means that the distinction between geneticpredispositions to two forms of addiction may be challenging.

Theinterplay between genetic and environmental conditions

Theconsideration of environmental context in the study of geneticpredisposition to addiction is necessary because environmentalfactors often moderate the genetic influence on dependence. Thismeans that the etiology of dependence should be viewed in two ways,namely the gene-environment correlation and gene-environmentinteraction (Agrawal etal.,2012). The gene-environment correlation is the genetic predispositionto addiction, which influence the probability of an individual beingexposed to some to some environmental conditions. The geneenvironment interaction, on the other hand, is the moderation ofheritable predisposition that results from exposure to certainenvironmental conditions. For an instant, a twin study ofpredisposition to alcohol addiction showed that a restrictedenvironment reduces the opportunity for the expression of geneticpredisposition to alcohol use and abuse. A restricted environmentalcondition can be characterized by a high parental monitoring, whichis significant for genetic contribution towards dependence. A studyof the influence of the level of parental monitoring on geneticpredisposition to dependence correlates the variants of CHRM2 andGABRA2 with externalized or environmental trajectories, where thiscorrelation decreases with the increase in the level of parentalrestriction (Agrawal etal.,2012). This means that environmental conditions can either promote orsuppress the expression of genetic variations that induce people touse and abuse substances.

Animportant aspect of the gene-environment interaction is that itrelates to the correlation between environmental and genetic riskswhere heritable features are not associated with the effects ofenvironmental stress. Instead, these genetic factors increase theopportunity for one’s exposure to negative elements. This meansthat the association between the environment and genes does not leadto real interaction, but it is the relationship between the riskfactors of the two predisposing elements. In addition, the validityof the correlation between environmental and genetic factors isreduced in cases where an individual’s access to substances thatleads to dependence is declining. For example, the decline in casesof tobacco addiction among old women reduce the probability ofconcluding that environmental factors (such as social gaiting) areimportant in the expression of genetic variations (Gorwood, Wohl,Strat &amp Rouillon, 2007). Moreover, the modern approaches oftreating addictive disorder, which is referred to as thepsychopharmacogenetics confirms the significance of addressing boththe environmental as well as the genetic factors concurrently inorder to counter dependence successfully (Gorwood, Wohl, Strat &ampRouillon, 2007).

Theconsideration of the influence of environmental factors afteraccounting for a genetic effect enhance the understanding of whetherexposure to certain environmental conditions have persistent oncegenetic factors are overlapped. Monozygotic twins who are discordantfor exposure to environmental factors show a constant interactionbetween genetic predisposition and environmental exposure. Forexample, a study of monozygotic twins who were exposed to sexualabuse during childhood indicated that the abused twins were morelikely to use and abuse substances in their lifetime compared togenetically identical twins that were not exposed (Agrawal etal.,2012). Although the monozygotic twins have identical geneticbackground, the difference in their epigenetic becomes evident withage. This implies that the discordance of the monozygotic twins is anassumption that is utilized in genetic studies pertaining todependence. Consequently, the consideration of the interplay of boththe genetic and environmental conditions in causing addictivedisorders increase the accuracy of studying genetic predisposition toaddictive disorders.

Implications

Theknowledge that substance abuse and subsequent addiction is caused byenvironmental factors is commonplace. However, the presentadvancement in molecular technology has resulted in a significantbreakthrough and enhanced the understanding of the relationshipbetween genetic polymorphism and heritability of dependence disorders(Primary Psychiatry, 2009). This implies that the stakeholders andresearchers in the area of addictive disorders should conveyconvincing information to the society about the possibility of thesedisorders running in families. However, the influence of theenvironmental conditions should not be ignored. In addition, theinsufficiency of the capacity to calculate an individual’svulnerability to dependence disorder using a single of a few numberof loci calls for further investigation of specific genes thatinfluence individual’s susceptibility to addictive disorders. Thiswill enhance the application of the knowledge of geneticpredisposition to dependence disorders in clinical settings. Inaddition, the knowledge will help in tailoring of pharmacotherapy onthe basis of patient’s genetic make-up.

Thecomprehensive evaluation of genetic predisposition to dependencedisorders will also help in the formulation of effective preventionand management strategies. Research shows that the lack of sufficientinformation pertaining to the influence of genetic variations in thetransmission of genetic disorders has resulted in partial success ofprevention and management strategies for these disorders (Goldman,Oriszi &amp Ducci, 2006). This will be achieved through theindividualization of treatment strategies, which ease the task ofhandling the current cases and new incidences of addiction illnessesthat resulted from genetic predisposition. At present, addictions areclassified as the most under-treated disorders despite their highrate of prevalence in the modern society (Goldman, Oriszi &ampDucci, 2006). However, the knowledge of the interplay of both geneticand environmental conditions in predisposing people to addictivedisorders will facilitate the combined use of psychotherapy andpharmacotherapy in addressing the issue of addictive disorders.

Conclusion

Geneticpredisposition of individuals to addictive disorders is the mostappropriate approach of explaining the prevalence of addition tosubstance use and certain behavior in some people and not in others.Previous studies focused on behavior aspects of the occurrence ofaddictive behavior, but more emphasis is currently given to geneticpredisposition. The advancement of molecular studies on transmissionof addictive disorders has enhanced the human understanding of therelationship between genetic alterations and addictive disorders.This has resulted in the identification of specific genes that encodefor different types of addictive disorders. However, the generaleffect of some genetic alterations that leads to the possibility ofseveral addictions being influenced by similar genes complicates theprocess of specific candidate genes for individual addictions. Thisis more common in the cases of alcohol addiction and nicotinedependence.

Althoughthe present paper focuses on the genetic predisposition to dependencedisorders, it pays attention to the interplay that exist between thetwo factors (genetic and environmental factors) and identifies theyjointly contribute towards addictive disorders. This implies that thetreatment as well as the management strategies designed for thesedisorders should address the two types of causes in order to ensuresuccess. Apart from addressing both types of predisposing factors,there is a need for identification of specific loci that influenceeach form of addiction, which can help in the individualization oftherapeutic and preventive strategies. Although this has beenachieved, the integration of modern technology in molecular studieswill lead to the determination of specific candidate genes for eachdisorder. This will further reduce the controversy and debates onwhether genetic alterations are responsible for transmission ofaddictive disorders.

References

Agrawal,A., Verweij, K., Gillespie, N., Heath, A., Lessov-Schlaggar, Martin,N., Nelson, E., Slutske, W., Whitfield, J. &amp Lynskey, M. (2012).The genetics of addiction-a translational perspective. TranslationalPsychology,(2012), 2, 1-24. doi:10.1038/tp.2012.54

BreiningInstitute (2006). Genetic predisposition: Is the human organismpredisposed to addictive disorders? Journalof Addictive Disorders,1, 1-10.

Dick,M. &amp Agrawal, A. (2008). The genetics of alcohol and other drugdependence. AlcoholResearch &amp Health,31 (2), 111-118.

Dryden,J. (2009). Commongenetic factors contribute to alcohol and marijuana use anddependence.Washington, DC: Washington University.

Ducci,F. &amp Goldman, D. (2012). The genetic basis of addictivedisorders. PsychiatricClinics of North America,35 (2), 495-519. doi:10.1016/j.psc.2012.03.010.

Edenberg,J. (2007). The genetics of alcohol metabolism: Role of alcoholdehydrogenase and aldehyde dehydrogenase variants. TheJournal of the National Institute on Alcohol Abuse and Alcoholism, 30(1), 1-13.

Goldman,D., Oriszi, G. &amp Ducci, F. (2006). The genetics of addictions:Uncovering the genes. Focus,4 (3), 401-415.

Gorwood,P., Wohl, M., Strat, Y. &amp Rouillon, F. (2007). Gene-Environmentinteractions in addictive disorders. ComptesRendus Biologies,330 (4), 329-338.

Kendler,S., Jacobson, C., Prescott, A. &amp Neale, C. (2003). Specificity ofgenetic and environmental risk factors for use and abuse / dependenceof cannabis, cocaine, hallucinogens, sedatives, stimulants, andopiates in male twins. TheAmerican Journal of Psychiatry,160 (4), 687-695. doi: 10.1176/appi.ajp.160.4.687

Kimura,M. &amp Higuchi, S. (2011). Genetics of alcohol dependence.Psychiatryand Clinical Neurosciences,65, 213-225.

Monti,J. (2012, July 20). Riskfactors for addiction.San Francisco: Health Line Networks.

NationalInstitute on Drug Abuse (2008). Genetics: The blueprint of health anddisease. NationalInstitute on Drug Abuse.Retrieved April 1, 2014, fromhttp://www.drugabuse.gov/publications/topics-in-brief/genetics-addiction

NHSChoices (2014). Cocaine addiction and genomes. NHSChoices.Retrieved April 1, 2014, fromhttp://www.nhs.uk/news/2008/11November/Pages/cocainegenes.aspx

Philibin,D., Wiren, M. &amp Crabbe, C. (2012). Geneticbasis of addictive behaviors.Oregon: VA Medical Center.

PrimaryPsychiatry (2009, August 1). Genetic influences on addiction. PrimaryPsychiatry.Retrieved April 1, 2014, fromhttp://primarypsychiatry.com/genetic-influences-on-addiction/