Addiction is a brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences.[8] Despite the involvement of a number of psychosocial factors, a biological process– one which is induced by repeated exposure to an addictive stimulus– is the core pathology that drives the development and maintenance of an addiction.[1][9] The two properties that characterize all addictive stimuli are that they are reinforcing (i.e., they increase the likelihood that a person will seek repeated exposure to them) and intrinsically rewarding (i.e., they are perceived as being inherently positive, desirable, and pleasurable).[1][3][7]
Addiction is a disorder of the brain's reward system which arises through transcriptional and epigenetic mechanisms and develops over time from chronically high levels of exposure to an addictive stimulus (e.g., eating food, the use of cocaine, engagement in sexual activity, participation in high-thrill cultural activities such as gambling, etc.).[1][10][11] ΔFosB, a gene transcription factor, is a critical component and common factor in the development of virtually all forms of behavioral and drug addictions.[10][11][12][13] Two decades of research into ΔFosB's role in addiction have demonstrated that addiction arises, and the associated compulsive behavior intensifies or attenuates, along with the overexpression of ΔFosB in the D1-type medium spiny neurons of the nucleus accumbens.[1][10][11][12] Due to the causal relationship between ΔFosB expression and addictions, it is used preclinically as an addiction biomarker.[1][10][12]  ΔFosB expression in these neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement, while decreasing sensitivity to aversion.[note 1][1][10]
Addiction exacts an "astoundingly high financial and human toll" on individuals and society as a whole.[14][15][16] In the United States, the total economic cost to society is greater than that of all types of diabetes and all cancers combined.[16] These costs arise from the direct adverse effects of drugs and associated healthcare costs (e.g., emergency medical services and outpatient and inpatient care), long-term complications (e.g., lung cancer from smoking tobacco products, liver cirrhosis and dementia from chronic alcohol consumption, and meth mouth from methamphetamine use), the loss of productivity and associated welfare costs, fatal and non-fatal accidents (e.g., traffic collisions), suicides, homicides, and incarceration, among others.[14][15][16][17] Classic hallmarks of addiction include impaired control over substances or behavior, preoccupation with substance or behavior, and continued use despite consequences.[18] Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward), coupled with delayed deleterious effects (long-term costs).[19]
Examples of drug and behavioral addictions include alcoholism, marijuana addiction, amphetamine addiction, cocaine addiction, nicotine addiction, opioid addiction, food addiction, gambling addiction, and sexual addiction. The only behavioral addiction recognized by the DSM-5 and the ICD-10 is gambling addiction.  The term addiction is misused frequently to refer to other compulsive behaviors or disorders, particularly dependence, in news media.[20] An important distinction between drug addiction and dependence is that drug dependence is a disorder in which cessation of drug use results in an unpleasant state of withdrawal, which can lead to further drug use.[21]  Addiction is the compulsive use of a substance or performance of a behavior that is independent of withdrawal. Addiction can occur in the absence of dependence, and dependence can occur in the absence of addiction, although the two often occur together.

Neuropsychology

Cognitive control and stimulus control, which is associated with operant and classical conditioning, represent opposite processes (i.e., internal vs external or environmental, respectively) that compete over the control of an individual's elicited behaviors.[22] Cognitive control, and particularly inhibitory control over behavior, is impaired in both addiction and attention deficit hyperactivity disorder.[23][24] Stimulus-driven behavioral responses (i.e., stimulus control) that are associated with a particular rewarding stimulus tend to dominate one's behavior in an addiction.[24]
Stimulus control of behavior

Cognitive control of behavior

Behavioral addiction

The term behavioral addiction refers to a compulsion to engage in a natural reward – which is a behavior that is inherently rewarding (i.e., desirable or appealing) – despite adverse consequences.[6][11][13] Preclinical evidence has demonstrated that marked increases in the expression of ΔFosB through repetitive and excessive exposure to a natural reward induces the same behavioral effects and neuroplasticity as occurs in a drug addiction.[11][25][26][27]
Reviews of both clinical research in humans and preclinical studies involving ΔFosB have identified compulsive sexual activity – specifically, any form of sexual intercourse – as an addiction (i.e., sexual addiction).[11][25] Moreover, reward cross-sensitization between amphetamine and sexual activity, meaning that exposure to one increases the desire for both, has been shown to occur preclinically and clinically as a dopamine dysregulation syndrome;[11][25][26][27] ΔFosB expression is required for this cross-sensitization effect, which intensifies with the level of ΔFosB expression.[11][26][27]
Reviews of preclinical studies indicate that long-term frequent and excessive consumption of high fat or sugar foods can produce an addiction (food addiction).[11][13]
Gambling is a natural reward which is associated with compulsive behavior and for which clinical diagnostic manuals, namely the DSM-5, have identified diagnostic criteria for an "addiction".[11] In order for a person's gambling behavior to meet criteria of an addiction, it shows certain characteristics, such as mood modification, compulsivity, and withdrawal. There is evidence from functional neuroimaging that gambling activates the reward system and the mesolimbic pathway in particular.[11][28]  Similarly, shopping and playing video games are associated with compulsive behaviors in humans and have also been shown to activate the mesolimbic pathway and other parts of the reward system.[11] Based upon this evidence, gambling addiction, video game addiction, and shopping addiction are classified accordingly.[11][28]
Risk factors

There are a number of genetic and environmental risk factors for developing an addiction that vary across the population.[1][29] Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction;[1] the contribution from epigenetic risk factors to the total risk is unknown.[29] 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.[1]
Genetic factors

It has long been established that genetic factors along with environmental (e.g., psychosocial) factors are significant contributors to addiction vulnerability.[1][29] Epidemiological studies estimate that genetic factors account for 40–60% of the risk factors for alcoholism. Similar rates of heritability for other types of drug addiction have been indicated by other studies.[30] Knestler hypothesized in 1964 that a gene or group of genes might contribute to predisposition to addiction in several ways. For example, altered levels of a normal protein due to environmental factors could then change the structure or functioning of specific brain neurons during development. These altered brain neurons could change the susceptibility of an individual to an initial drug use experience. In support of this hypothesis, animal studies have shown that environmental factors such as stress can affect an animal's genotype.[30]
Overall, the data implicating specific genes in the development of drug addiction is mixed for most genes. One reason for this may be that the case is due to a focus of current research on common variants. Many addiction studies focus on common variants with an allele frequency of greater than 5% in the general population; however, when associated with disease, these only confer a small amount of additional risk with an odds ratio of 1.1–1.3 percent. On the other hand, the rare variant hypothesis states that genes with low frequencies in the population (<1%) confer much greater additional risk in the development of the disease.[31]
Genome-wide association studies (GWAS) are used to examine genetic associations with dependence, addiction, and drug use. These studies employ an unbiased approach to finding genetic associations with specific phenotypes and give equal weight to all regions of DNA, including those with no ostensible relationship to drug metabolism or response. These studies rarely identify genes from proteins previously described via animal knockout models and candidate gene analysis. Instead, large percentages of genes involved in processes such as cell adhesion are commonly identified. This is not to say that previous findings, or the GWAS findings, are erroneous. The important effects of endophenotypes are typically not capable of being captured by these methods. Furthermore, genes identified in GWAS for drug addiction may be involved either in adjusting brain behavior prior to drug experiences, subsequent to them, or both.
[32]
A study that highlights the significant role genetics play in addiction is the twin studies. Twins have similar and sometimes identical genetics. Analyzing these genes in relation to genetics has helped geneticists understand how much of a role genes play in addiction. Studies performed on twins found that rarely did only one twin have an addiction. In most cases where at least one twin suffered from an addiction, both did, and often to the same substance.[33] Cross addiction is when already has a predisposed addiction and then starts to become addicted to something different. If one family member has a history of addiction, the chances of a relative or close family developing those same habits are much higher than one who has not been introduced to addiction at a young age.[34] In a recent study done by the National Institute on Drug Abuse, from 2002 to 2017, overdose deaths have almost tripled amongst male and females. In 2017, 72,306 overdose deaths happened in the U.S. that were reported.[35]
Environmental factors
Environmental risk factors for addiction are the experiences of an individual during their lifetime that interact with the individual's genetic composition to increase or decrease his or her vulnerability to addiction.[1]  A number of different environmental factors have been implicated as risk factors for addiction, including various psychosocial stressors;[1] however, an individual's exposure to an addictive drug is by far the most significant environmental risk factor for addiction.[1] The National Institute on Drug Abuse (NIDA) cites lack of parental supervision, the prevalence of peer substance use, drug availability, and poverty as risk factors for substance use among children and adolescents.[36]
Adverse childhood experiences (ACEs) are various forms of maltreatment and household dysfunction experienced in childhood. The Adverse Childhood Experiences Study by the Centers for Disease Control and Prevention has shown a strong dose–response relationship between ACEs and numerous health, social, and behavioral problems throughout a person's lifespan, including those associated with substance abuse.[37] Children's neurological development can be permanently disrupted when they are chronically exposed to stressful events such as physical, emotional, or sexual abuse, physical or emotional neglect, witnessing violence in the household, or  a parent being incarcerated or suffering from a mental illness. As a result, the child's cognitive functioning or ability to cope with negative or disruptive emotions may be impaired. Over time, the child may adopt substance use as a coping mechanism, particularly during adolescence.[37] A study of 900 court cases involving children who experienced abuse found that a vast amount of them went on to suffer from some form of addiction in their adolescence or adult life.[38] This pathway towards addiction that is opened through stressful experiences during childhood can be avoided by a change in environmental factors throughout an individual's life and opportunities of professional help.[38] If one has friends or peers who engage in drug use favorably, the chances of them developing an addiction increases. Family conflict and home management is also a cause for one to become engaged in drug or alcohol use.[39]

Age
Adolescence represents a period of unique vulnerability for developing an addiction.[40] In adolescence, the incentive-rewards systems in the brain mature well before the cognitive control center. This consequentially grants the incentive-rewards systems a disproportionate amount of power in the behavioral decision-making process. Therefore, adolescents are increasingly likely to act on their impulses and engage in risky, potentially addicting behavior before considering the consequences.[41] Not only are adolescents more likely to initiate and maintain drug use, but once addicted they are more resistant to treatment and more liable to relapse.[42][43]
Statistics have shown that those who start to drink alcohol at a younger age are more likely to become dependent later on. About 33% of the population tasted their first alcohol between the ages of 15 and 17, while 18% experienced it prior to this. As for alcohol abuse or dependence, the numbers start off high with those who first drank before they were 12 and then drop off after that. For example, 16% of alcoholics began drinking prior to turning 12 years old, while only 9% first touched alcohol between 15 and 17. This percentage is even lower, at 2.6%, for those who first started the habit after they were 21.[44]
Most individuals are exposed to and use addictive drugs for the first time during their teenage years.[45] In the United States, there were just over 2.8million new users of illicit drugs in 2013 (~7,800 new users per day);[45] among them, 54.1% were under 18years of age.[45] In 2011, there were approximately 20.6million people in the United States over the age of 12 with an addiction.[46] Over 90% of those with an addiction began drinking, smoking or using illicit drugs before the age of 18.[46]
Comorbid disorders
Individuals with comorbid (i.e., co-occurring) mental health disorders such as depression, anxiety, attention-deficit/hyperactivity disorder (ADHD) or post-traumatic stress disorder are more likely to develop substance use disorders.[47][48][49] The NIDA cites early aggressive behavior as a risk factor for substance use.[36] A study by the National Bureau of Economic Research found that there is a "definite connection between mental illness and the use of addictive substances" and a majority of mental health patients participate in the use of these substances: 38% alcohol, 44% cocaine, and 40% cigarettes.[50]
Epigenetic factors
Transgenerational epigenetic inheritance

Epigenetic genes and their products (e.g., proteins) are the key components through which environmental influences can affect the genes of an individual;[29] they also serve as the mechanism responsible for transgenerational epigenetic inheritance, a phenomenon in which environmental influences on the genes of a parent can affect the associated traits and behavioral phenotypes of their offspring (e.g., behavioral responses to environmental stimuli).[29] In addiction, epigenetic mechanisms play a central role in the pathophysiology of the disease;[1] it has been noted that some of the alterations 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 rewards).[29][51]
The general classes of epigenetic alterations that have been implicated in transgenerational epigenetic inheritance include DNA methylation, histone modifications, and downregulation or upregulation of microRNAs.[29] With respect to addiction, more research is needed to determine the specific heritable 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.[29][51] Based upon preclinical evidence from animal research, 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.[note 2][29] 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.[29][51]
Mechanisms

Chronic addictive drug use causes alterations in gene expression in the mesocorticolimbic projection.[13][59][60]  The most important transcription factors that produce these alterations are ΔFosB, cAMP response element binding protein (CREB), and nuclear factor kappa B (NF-κB).[13] ΔFosB is the most significant biomolecular mechanism in addiction because the overexpression of ΔFosB in the D1-type medium spiny neurons in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and behavioral effects (e.g., expression-dependent increases in drug self-administration and reward sensitization) seen in drug addiction.[13] ΔFosB expression in nucleus accumbens D1-type medium spiny neurons directly and positively regulates drug self-administration and reward sensitization through positive reinforcement while decreasing sensitivity to aversion.[note 1][1][10] ΔFosB has been implicated in mediating addictions to many different drugs and drug classes, including alcohol, amphetamine and other substituted amphetamines, cannabinoids, cocaine, methylphenidate, nicotine, opiates, phenylcyclidine, and propofol, among others.[10][13][59][61][62] ΔJunD, a transcription factor, and G9a, a histone methyltransferase, both oppose the function of ΔFosB and inhibit increases in its expression.[1][13][63] Increases in nucleus accumbens ΔJunD expression (via viral vector-mediated gene transfer) or G9a expression (via pharmacological means) reduces, or with a large increase can even block, many of the neural and behavioral alterations that result from chronic high-dose use of addictive drugs (i.e., the alterations mediated by ΔFosB).[12][13]
ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[13][64] Natural rewards, like drugs of abuse, induce gene expression of ΔFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through ΔFosB overexpression.[11][13][64] Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards (i.e., behavioral addictions) as well;[13][11][64] in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.[64] Research on the interaction between natural and drug rewards suggests that dopaminergic psychostimulants (e.g., amphetamine) and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess bidirectional cross-sensitization effects that are mediated through ΔFosB.[11][26][27]  This phenomenon is notable since, in humans, a dopamine dysregulation syndrome, characterized by drug-induced compulsive engagement in natural rewards (specifically, sexual activity, shopping, and gambling), has also been observed in some individuals taking dopaminergic medications.[11]
ΔFosB inhibitors (drugs or treatments that oppose its action) may be an effective treatment for addiction and addictive disorders.[65]
The release of dopamine in the nucleus accumbens plays a role in the reinforcing qualities of many forms of stimuli, including naturally reinforcing stimuli like palatable food and sex.[66][67] Altered dopamine neurotransmission is frequently observed following the development of an addictive state.[11] In humans and lab animals that have developed an addiction, alterations in dopamine or opioid neurotransmission in the nucleus accumbens and other parts of the striatum are evident.[11] Studies have found that use of certain drugs (e.g., cocaine) affect cholinergic neurons that innervate the reward system, in turn affecting dopamine signaling in this region.[68]
Reward system

Mesocorticolimbic pathway

Understanding the pathways in which drugs act and how drugs can alter those pathways is key when examining the biological basis of drug addiction. The reward pathway, known as the mesolimbic pathway, or its extension, the mesocorticolimbic pathway, is characterized by the interaction of several areas of the brain.
The projections from the ventral tegmental area (VTA) are a network of dopaminergic neurons with co-localized postsynaptic glutamate receptors (AMPAR and NMDAR). These cells respond when stimuli indicative of a reward are present. The VTA supports learning and sensitization development and releases DA into the forebrain.[70] These neurons also project and release DA into the nucleus accumbens,[71] through the mesolimbic pathway. Virtually all drugs causing drug addiction increase the dopamine release in the mesolimbic pathway,[72] in addition to their specific effects.
The nucleus accumbens (NAcc) is one output of the VTA projections.  The nucleus accumbens itself consists mainly of GABAergic medium spiny neurons (MSNs).[73] The NAcc is associated with acquiring and eliciting conditioned behaviors, and is involved in the increased sensitivity to drugs as addiction progresses.[70] Overexpression of ΔFosB in the nucleus accumbens is a necessary common factor in essentially all known forms of addiction;[1] ΔFosB is a strong positive modulator of positively reinforced behaviors.[1]
The prefrontal cortex, including the anterior cingulate and orbitofrontal cortices,[74] is another VTA output in the mesocorticolimbic pathway; it is important for the integration of information which helps determine whether a behavior will be elicited.[75] It is also critical for forming associations between the rewarding experience of drug use and cues in the environment. Importantly, these cues are strong mediators of drug-seeking behavior and can trigger relapse even after months or years of abstinence.[76]
Other brain structures that are involved in addiction include:
The basolateral amygdala projects into the NAcc and is thought to also be important for motivation.[75]
The hippocampus is involved in drug addiction, because of its role in learning and memory. Much of this evidence stems from investigations showing that manipulating cells in the hippocampus alters dopamine levels in NAcc and firing rates of VTA dopaminergic cells.[71]
Role of dopamine and glutamate
Dopamine is the primary neurotransmitter of the reward system in the brain. It plays a role in regulating movement, emotion, cognition, motivation, and feelings of pleasure.[77] Natural rewards, like eating, as well as recreational drug use cause a release of dopamine, and are associated with the reinforcing nature of these stimuli.[77][78] Nearly all addictive drugs, directly or indirectly, act upon the brain's reward system by heightening dopaminergic activity.[79]
Excessive intake of many types of addictive drugs results in repeated release of high amounts of dopamine, which in turn affects the reward pathway directly through heightened dopamine receptor activation. Prolonged and abnormally high levels of dopamine in the synaptic cleft can induce receptor downregulation in the neural pathway. Downregulation of mesolimbic dopamine receptors can result in a decrease in the sensitivity to natural reinforcers.[77]
Drug seeking behavior is induced by glutamatergic projections from the prefrontal cortex to the nucleus accumbens. This idea is supported with data from experiments showing that drug seeking behavior can be prevented following the inhibition of AMPA glutamate receptors and glutamate release in the nucleus accumbens.[74]
Reward sensitization

Reward sensitization is a process that causes an increase in the amount of reward (specifically, incentive salience[note 5]) that is assigned by the brain to a rewarding stimulus (e.g., a drug). In simple terms, when reward sensitization to a specific stimulus (e.g., a drug) occurs, an individual's "wanting" or desire for the stimulus itself and its associated cues increases.[82][81][83] Reward sensitization normally occurs following chronically high levels of exposure to the stimulus. ΔFosB (DeltaFosB) expression in D1-type medium spiny neurons in the nucleus accumbens has been shown to directly and positively regulate reward sensitization involving drugs and natural rewards.[1][10][12]
"Cue-induced wanting" or "cue-triggered wanting", a form of craving that occurs in addiction, is responsible for the majority of compulsive behavior that addicts exhibit.[81][83] During the development of an addiction, the repeated association of otherwise neutral and even non-rewarding stimuli with drug consumption triggers an associative learning process that causes these previously neutral stimuli to act as conditioned positive reinforcers of addictive drug use (i.e., these stimuli start to function as drug cues).[81][84][83] As conditioned positive reinforcers of drug use, these previously neutral stimuli are assigned incentive salience (which manifests as a craving)– sometimes at pathologically high levels due to reward sensitization– which can transfer to the primary reinforcer (e.g., the use of an addictive drug) with which it was originally paired.[81][84][83]
Research on the interaction between natural and drug rewards suggests that dopaminergic psychostimulants (e.g., amphetamine) and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess a bidirectional reward cross-sensitization effect[note 6] that is mediated through ΔFosB.[11][26][27] In contrast to ΔFosB's reward-sensitizing effect, CREB transcriptional activity decreases user's sensitivity to the rewarding effects of the substance. CREB transcription in the nucleus accumbens is implicated in psychological dependence and symptoms involving a lack of pleasure or motivation during drug withdrawal.[1][69][80]
The set of proteins known as "regulators of G protein signaling" (RGS), particularly RGS4 and RGS9-2, have been implicated in modulating some forms of opioid sensitization, including reward sensitization.[85]

Neuroepigenetic mechanisms

Altered epigenetic regulation of gene expression within the brain's reward system plays a significant and complex role in the development of drug addiction.[63][86] Addictive drugs are associated with three types of epigenetic modifications within neurons.[63] These are (1) histone modifications, (2) epigenetic methylation of DNA at CpG sites at (or adjacent to) particular genes, and (3) epigenetic downregulation or upregulation of microRNAs which have particular target genes.[63][13][86]  As an example, while hundreds of genes in the cells of the nucleus accumbens (NAc) exhibit histone modifications following drug exposure – particularly, altered acetylation and methylation states of histone residues[86] – most other genes in the NAc cells do not show such changes.[63]
Summary of addiction-related plasticity

Diagnosis
The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term "Substance Use Disorder" to refer to a spectrum of use-related conditions.  The DSM-5 eliminates the terms "abuse" and "dependence" from diagnostic categories, instead using the specifiers of "mild", "moderate" and "severe" to indicate the extent of disordered use.  Specifiers are determined by the number of diagnostic criteria present in a given case. The manual has never actually used the term "addiction" clinically.[20] Currently, only drug addictions and gambling addiction are listed in the DSM-5.  Past editions have used physical dependence and the associated withdrawal syndrome to identify an addictive state. Physical dependence occurs when the body has adjusted by incorporating the substance into its "normal" functioning – i.e., attains homeostasis – and therefore physical withdrawal symptoms occur upon cessation of use.[87] Tolerance is the process by which the body continually adapts to the substance and requires increasingly larger amounts to achieve the original effects. Withdrawal refers to physical and psychological symptoms experienced when  reducing or discontinuing a substance that the body has become dependent on. Symptoms of withdrawal generally include but are not limited to anxiety, irritability, intense cravings for the substance, nausea, hallucinations, headaches, cold sweats, and tremors.
Medical researchers who actively study addiction have criticized the DSM classification of addiction for being flawed and involving arbitrary diagnostic criteria.[21] Writing in 2013, the director of the United States National Institute of Mental Health discussed the invalidity of the DSM-5's classification of mental disorders:[88]
 While DSM has been described as a "Bible" for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been "reliability" – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever.
Most recently, though, the NIH acknowledged advances in identifying biomarkers, noting they outperform traditional phenomenological categories in identifying types of psychosis.[89][90] As a diagnostic biomarker, ΔFosB expression could be used to diagnose an addiction in humans, but this would require a brain biopsy and therefore is not used in clinical practice.
Treatment

According to a review, "in order to be effective, all pharmacological or biologically based treatments for addiction need to be integrated into other established forms of addiction rehabilitation, such as cognitive behavioral therapy, individual and group psychotherapy, behavior-modification strategies, twelve-step programs, and residential treatment facilities."[7]
Behavioral therapy
A meta-analytic review on the efficacy of various behavioral therapies for treating drug and behavioral addictions found that cognitive behavioral therapy (e.g., relapse prevention and contingency management), motivational interviewing, and a community reinforcement approach were effective interventions with moderate effect sizes.[91]
Clinical and preclinical evidence indicate that consistent aerobic exercise, especially endurance exercise (e.g., marathon running), actually prevents the development of certain drug addictions and is an effective adjunct treatment for drug addiction, and for psychostimulant addiction in particular.[11][92][93][94][95]  Consistent aerobic exercise magnitude-dependently (i.e., by duration and intensity) reduces drug addiction risk, which appears to occur through the reversal of drug induced addiction-related neuroplasticity.[11][93] One review noted that exercise may prevent the development of drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of the reward system.[95] Aerobic exercise decreases drug self-administration, reduces the likelihood of relapse, and induces opposite effects on striatal dopamine receptor D2 (DRD2) signaling (increased DRD2 density) to those induced by addictions to several drug classes (decreased DRD2 density).[11][93] Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction.[11][93][94]
Medication
Alcohol addiction

Alcohol, like opioids, can induce a severe state of physical dependence and produce withdrawal symptoms such as delirium tremens. Because of this, treatment for alcohol addiction usually involves a combined approach dealing with dependence and addiction simultaneously.
Pharmacological treatments for alcohol addiction include drugs like naltrexone (opioid antagonist), disulfiram, acamprosate, and topiramate.[96][97] Rather than substituting for alcohol, these drugs are intended to affect the desire to drink, either by directly reducing cravings as with acamprosate and topiramate, or by producing unpleasant effects when alcohol is consumed, as with disulfiram. These drugs can be effective if treatment is maintained, but compliance can be an issue as alcoholic patients often forget to take their medication, or discontinue use because of excessive side effects.[98][99] According to a Cochrane Collaboration review, the opioid antagonist naltrexone has been shown to be an effective treatment for alcoholism, with the effects lasting three to twelve months after the end of treatment.[100]
Behavioral addictions

Behavioral addiction is a treatable condition. Treatment options include psychotherapy and psychopharmacotherapy (i.e., medications) or a combination of both. Cognitive behavioral therapy (CBT) is the most common form of psychotherapy used in treating behavioral addictions; it focuses on identifying patterns that trigger compulsive behavior and making lifestyle changes to promote healthier behaviors. Currently, there are no medications approved for treatment of behavioral addictions in general, but some medications used for treatment of drug addiction may also be beneficial with specific behavioral addictions.[28] Any unrelated psychiatric disorders should be kept under control, and differentiated from the contributing factors that cause the addiction.
Cannabinoid addiction
As of 2010, there are no effective pharmacological interventions for cannabinoid addiction.[101] A 2013 review on cannabinoid addiction noted that the development of CB1 receptor agonists that have reduced interaction with β-arrestin 2 signaling might be therapeutically useful.[102]
Nicotine addiction

Another area in which drug treatment has been widely used is in the treatment of nicotine addiction, which usually involves the use of nicotine replacement therapy, nicotinic receptor antagonists, or nicotinic receptor partial agonists.[103][104]  Examples of drugs that act on nicotinic receptors and have been used for treating nicotine addiction include antagonists like bupropion and the partial agonist varenicline.[103][104]
Opioid addiction

Opioids cause physical dependence, and treatment typically addresses both dependence and addiction.
Physical dependence is treated using replacement drugs such as suboxone or subutex (both containing the active ingredients buprenorphine) and methadone.[105][106] Although these drugs perpetuate physical dependence, the goal of opiate maintenance is to provide a measure of control over both pain and cravings. Use of replacement drugs increases the addicted individual's ability to function normally and eliminates the negative consequences of obtaining controlled substances illicitly. Once a prescribed dosage is stabilized, treatment enters maintenance or tapering phases. In the United States, opiate replacement therapy is tightly regulated in methadone clinics and under the DATA 2000 legislation. In some countries, other opioid derivatives such as levomethadyl acetate,[107] dihydrocodeine,[108] dihydroetorphine[109] and even heroin[110][111] are used as substitute drugs for illegal street opiates, with different prescriptions being given depending on the needs of the individual patient. Baclofen has led to successful reductions of cravings for stimulants, alcohol, and opioids, and also alleviates alcohol withdrawal syndrome. Many patients have stated they "became indifferent to alcohol" or "indifferent to cocaine" overnight after starting baclofen therapy.[112]
Psychostimulant addiction
As of May 2014, there is no effective pharmacotherapy for any form of psychostimulant addiction.[7][113][114][115] Reviews from 2015 and 2016 indicated that TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions;[116][117] however, as of February 2016, the only compounds which are known to function as TAAR1-selective agonists are experimental drugs.[116][117]
Research

Research indicates that vaccines which utilize anti-drug monoclonal antibodies can mitigate drug-induced positive reinforcement by preventing the drug from moving across the blood–brain barrier;[118] however, current vaccine-based therapies are only effective in a relatively small subset of individuals.[118][119] As of November 2015, vaccine-based therapies are being tested in human clinical trials as a treatment for addiction and preventative measure against drug overdoses involving nicotine, cocaine, and methamphetamine.[118]
Since addiction involves abnormalities in glutamate and GABAergic neurotransmission,[120][121] receptors associated with these neurotransmitters (e.g., AMPA receptors, NMDA receptors, and GABAB receptors) are potential therapeutic targets for addictions.[120][121][122][123] N-acetylcysteine, which affects metabotropic glutamate receptors and NMDA receptors, has shown some benefit in preclinical and clinical studies involving addictions to cocaine, heroin, and cannabinoids.[120] It may also be useful as an adjunct therapy for addictions to amphetamine-type stimulants, but more clinical research is required.[120]
Current medical reviews of research involving lab animals have identified a drug class – class I histone deacetylase inhibitors[note 7] – that indirectly inhibits the function and further increases in the expression of accumbal ΔFosB by inducing G9a expression in the nucleus accumbens after prolonged use.[12][63][124][86]  These reviews and subsequent preliminary evidence which used oral administration or intraperitoneal administration of the sodium salt of butyric acid or other class I HDAC inhibitors for an extended period indicate that these drugs have efficacy in reducing addictive behavior in lab animals[note 8] that have developed addictions to ethanol, psychostimulants (i.e., amphetamine and cocaine), nicotine, and opiates;[63][86][125][126] however, few clinical trials involving human addicts and any HDAC class I inhibitors have been conducted to test for treatment efficacy in humans or identify an optimal dosing regimen.[note 9]
Gene therapy for addiction is an active area of research. One line of gene therapy research involves the use of viral vectors to increase the expression of dopamine D2 receptor proteins in the brain.[128][129][130][131][132]
Epidemiology
Due to cultural variations, the proportion of individuals who develop a drug or behavioral addiction within a specified time period (i.e., the prevalence) varies over time, by country, and across national population demographics (e.g., by age group, socioeconomic status, etc.).[29]
Asia

Australia
The prevalence of substance abuse disorder among Australians was reported at 5.1% in 2009.[133]
Europe

United States
Based upon representative samples of the US youth population in 2011, the lifetime prevalence[note 10] of addictions to alcohol and illicit drugs has been estimated to be approximately 8% and 2–3% respectively.[15]  Based upon representative samples of the US adult population in 2011, the 12 month prevalence of alcohol and illicit drug addictions were estimated at roughly 12% and 2–3% respectively.[15] The lifetime prevalence of prescription drug addictions is currently around 4.7%.[134]
As of 2016, about 22million people in the United States need treatment for an addiction to alcohol, nicotine, or other drugs.[16][135] Only about 10%, or a little over 2million, receive any form of treatments, and those that do generally do not receive evidence-based care.[16][135] One-third of inpatient hospital costs and 20% of all deaths in the US every year are the result of untreated addictions and risky substance use.[16][135] In spite of the massive overall economic cost to society, which is greater than the cost of diabetes and all forms of cancer combined, most doctors in the US lack the training to effectively address a drug addiction.[16][135]
Another review listed estimates of lifetime prevalence rates for several behavioral addictions in the United States, including 1–2% for compulsive gambling, 5% for sexual addiction, 2.8% for food addiction, and 5–6% for compulsive shopping.[11]  A systematic review indicated that the time-invariant prevalence rate for sexual addiction and related compulsive sexual behavior (e.g., compulsive masturbation with or without pornography, compulsive cybersex, etc.) within the United States ranges from 3–6% of the population.[25]
According to a 2017 poll conducted by the Pew Research Center, almost half of US adults know a family member or close friend who has struggled with a drug addiction at some point in their life.[136]
South America

Personality theories of addiction

Personality theories of addiction are psychological models that associate personality traits or modes of thinking (i.e., affective states) with an individual's proclivity for developing an addiction.  Models of addiction risk that have been proposed in psychology literature include an affect dysregulation model of positive and negative psychological affects, the reinforcement sensitivity theory model of impulsiveness and behavioral inhibition, and an impulsivity model of reward sensitization and impulsiveness.[137][138][139][140][141]
See also

Binge drinking
Binge eating disorder
Discrimination against drug addicts
Pavlovian-instrumental transfer
Philosophy of medicine
Notes

Image legend

– a TEDMED 2014 talk by Nora Volkow, the director of the National Institute on Drug Abuse at NIH.

Kyoto Encyclopedia of Genes and Genomes (KEGG) signal transduction pathways:

What percentage of the U.S. population suffers from drug addiction?


Treyarch is an American video game developer, founded in 1996 by Peter Akemann and Doğan Köslü, and acquired by Activision in 2001. Located in Santa Monica, California, it is known for its work for the Call of Duty series, with some other games in the series developed by Infinity Ward and Sledgehammer Games.
History
Treyarch was founded in 1996, the company was acquired by Activision in 2001.
In 2005, Gray Matter Interactive was merged into Treyarch.[2]
As part of the 2007 Leipzig Games Convention, Activision announced that Treyarch would be one of three developers behind their first James Bond based game, 007: Quantum of Solace. The game was released on October 31, 2008 in Europe and November 4, 2008 in North America. Vicarious Visions developed the Nintendo DS version and Eurocom developed the PlayStation 2 version. Treyarch is a major developer in the Call of Duty series.
Call of Duty: Black Ops II held the record for the largest entertainment launch in history in any form of entertainment, breaking the record within 24 hours of its release until it was surpassed by Grand Theft Auto V.[3] Sales from the game worldwide reached US$650million within five days after its release.[4] Treyarch worked on the Wii U version of Call of Duty: Ghosts, in order to optimize it for the console.[5] Treyarch's most recently released video game is Call of Duty: Black Ops 4, which was released on October 12, 2018.[6]
Games developed

Ports

How many video games have been developed by Treyarch?


The Republic of Chile is an overwhelmingly Spanish-speaking country, with the exceptions of isolated native and immigrant communities. According to Ethnologue, Chile has nine living languages and seven extinct.[1]
Spanish
Of the 18 million Chileans, some 17 million speak Chilean Spanish as their first language.[1] It is a Spanish dialect which is sometimes difficult for speakers of the Castilian variant of Spanish to understand. It is very similar to Andalusian Spanish in pronunciation but it does have a lot of local slang.
Native languages
Mapudungun
There are some 1,700,000 Mapuche living in Chile, of whom 114,000 speak Mapudungun.[1] Huilliche dialect or Chesungun is a divergent variety of Mapudungun that had 2,000 speakers in 1982, living in the Los Ríos and Los Lagos regions. As most of those speakers were elderly, it is uncertain if there are any existing speakers today.[1]
Quechua
Chilean Quechua has 8,200 speakers in the far northeast high plains. It is believed to possibly be identical to South Bolivian Quechua or at the very least highly intelligible with it.[1]
Rapa Nui
Rapa Nui, the Polynesian language of Easter Island, is spoken by some 3,400 Chileans, whereof 3,200 live on Easter Island and some 200 live on the mainland.[1]
Other
Central Aymará has 935 speakers in Putre and Arica Province.[1]
Kawésqar has only 7 remaining speakers.[1]
Yámana has Cristina Calderón as a sole speaker and will likely become extinct soon.[2]
Extinct languages
Some indigenous languages of Chile now extinct are Diaguita, Kunza and Selk'nam.[1]
German
Although it is estimated that 150,000 to 200,000 Chileans have some German ancestry, the number who speak German has been in decline since the end of World War II. In the 1980s it was estimated that some 35,000 German Chileans spoke German,[1] but today it is spoken only by some 20,000, most of them living in Los Ríos and Los Lagos Region.[3]
English
Large numbers of Chileans, especially those from higher levels of socio-economic classes speak or understand English to some degree. British English schools are common and some have long histories that derive from English migrants in the 19th century.
Chilean Sign Language
According to the World Federation of the Deaf 2008 survey report for South America, Chile's official number of deaf citizens is 66,500.[4] The number who master Chilean Sign Language is uncertain, but if it follows the general norm of one in four deaf persons having learnt sign language, the number of sign language users in Chile should be around 16,000.
Notes


This page lists the highest-attended concerts of all time. The oldest 100,000-crowd concert reported to Billboard Boxscore is Grateful Dead's gig at the Raceway Park, Englishtown, New Jersey on September 3, 1977. The concert was attended by 107,019 people, which remains the largest ticketed concert in the United States to date. Frank Sinatra, Tina Turner, and Paul McCartney broke the record respectively in Maracanã Stadium. With an audience of over 184,000 people on April 21, 1990, McCartney held the record for 27 years. Italian singer Vasco Rossi surpassed McCartney's record with his solo concert on July 1, 2017. The concert was a celebration of his 40 years of career.
Although the attendance numbers of free concerts are known to be exaggerations,[1] several concerts have been reported to have a million audience or more. According to the Guinness World Records, Rod Stewart's show in Copacabana Beach, Rio de Janeiro, remains the highest-attended free concert with an estimated 3.5 million audience.
Highest-attended concerts

Single-artist concerts
The following are the highest-attended single-artist's ticketed concerts (excluding music festivals) with attendance of 100,000 people or more.

Free concerts
The following are free concerts with reported attendance of one million people or more. It also includes multi-artist festivals which may not be directly comparable with single-artist concerts. Attendance numbers for many of the kinds of events listed here rely on estimations from the promoters and are known to be exaggerations.[1]

See also
List of highest-grossing concert tours

Which rock concert had the largest attendance in history?


Jamaican Patois, known locally as Patois (Patwa or Patwah)  and called Jamaican Creole by linguists, is an English-based creole language with West African influences (a majority of loan words of Akan origin)[4] spoken primarily in Jamaica and the Jamaican diaspora; it is spoken by the majority of Jamaicans as a native language. Patois developed in the 17th century, when slaves from West and Central Africa were exposed to, learned and nativized the vernacular and dialectal forms of English spoken by the slaveholders: British English, Scots and Hiberno-English.  Jamaican Creole exhibits a gradation between more conservative creole forms that are not significantly mutually intelligible with English,[5] and forms virtually identical to Standard English.[6]
Jamaicans refer to their language as patois. The term patois comes from Old French, patois "local or regional dialect"[7]  (earlier "rough, clumsy, or uncultivated speech"), possibly from the verb patoier, "to treat roughly", from patte "paw",[8] from Old Low Franconian *patta "paw, sole of the foot" + -ois, a pejorative suffix. The term may have arisen from the notion of a clumsy or rough manner of speaking. Linguists refer to the language as a creole.[9] Creoles are often stigmatized as the "lesser" language even though the majority of the population speaks Jamaican Creole as their mother tongue.[10]
Jamaican pronunciation and vocabulary are significantly different from English, despite heavy use of English words or derivatives, but their writing system shows commonalities with the English alphabet.[11]
Significant Jamaican Patois-speaking communities exist among Jamaican expatriates in Miami, New York City, Toronto, Hartford, Washington, D.C., Nicaragua, Costa Rica,  and Panama (in the Caribbean coast), also London,[12] Birmingham, Manchester, and Nottingham. A mutually intelligible variety is found in San Andrés y Providencia Islands, Colombia, brought to the island by descendants of Jamaican Maroons (escaped slaves) in the 18th century. Mesolectal forms are similar to very basilectal Belizean Kriol.
Jamaican Patois exists mostly as a spoken language and is also heavily used for musical purposes, especially in reggae and dancehall as well as other genres. Although standard British English is used for most writing in Jamaica, Jamaican Patois has been gaining ground as a literary language for almost a hundred years. Claude McKay published his book of Jamaican poems Songs of Jamaica in 1912. Patois and English are frequently used for stylistic contrast (codeswitching) in new forms of internet writing.[13]
Phonology
Accounts of basilectal Jamaican Patois postulate around 21 phonemic consonants[14] one which can be contrastive in the Western dialect.[15]There are between 9 and 16 vowels.[16] Some vowels are capable of nasalization and others can be lengthened.[15]

 The status of /h/ as a phoneme is dialectal: in western varieties, it is a full phoneme and there are minimal pairs (/hiit/ 'hit' and /iit/ 'eat'); in central and eastern varieties, the presence of [h] in a word is in free variation with no consonant so that the words for 'hand' and 'and' (both underlyingly /an/) may be pronounced [han] or [an].[18]
 The palatal stops [c], [ɟ][19] and [ɲ] are considered phonemic by some accounts[20] and phonetic by others.[21]  For the latter interpretation, their appearance is included in the larger phenomenon of phonetic palatalization.
Examples of palatalization include:[22]
/kiuu/ → [ciuː] → [cuː] ('a quarter quart (of rum)')
/ɡiaad/ → [ɟiaːd] → [ɟaːd] ('guard')
/piaa + piaa/ → [pʲiãːpʲiãː] → [pʲãːpʲãː] ('weak')
Voiced stops are implosive whenever in the onset of prominent syllables (especially word-initially) so that /biit/ ('beat') is pronounced [ɓiːt] and /ɡuud/ ('good') as [ɠuːd].[14]
Before a syllabic /l/, the contrast between alveolar and velar consonants has been historically neutralized with alveolar consonants becoming velar so that the word for 'bottle' is /bakl̩/ and the word for 'idle' is /aiɡl̩/.[23]

Jamaican Patois exhibits two types of vowel harmony; peripheral vowel harmony, wherein only sequences of peripheral vowels (that is, /i/, /u/, and /a/) can occur within a syllable; and back harmony, wherein /i/ and /u/ cannot occur within a syllable together (that is, /uu/ and /ii/ are allowed but * /ui/ and * /iu/ are not).[24]  These two phenomena account for three long vowels and four diphthongs:[25]

Sociolinguistic variation
Jamaican Patois features a creole continuum (or a linguistic continuum):[26][27][28] the variety of the language closest to the lexifier language (the acrolect) cannot be distinguished systematically from intermediate varieties (collectively referred to as the mesolect) or even from the most divergent rural varieties (collectively referred to as the basilect). This situation came about with contact between speakers of a number of Niger–Congo languages and various dialects of English, the latter of which were all perceived as prestigious and the use of which carried socio-economic rewards.[29]  The span of a speaker's command of the continuum generally corresponds to social context.[30]
Grammar
The tense/aspect system of Jamaican Patois is fundamentally unlike that of English. There are no morphological marked past participles; instead, two different participle words exist: en and a. These are not verbs, but simply invariant particles that cannot stand alone like the English to be. Their function also differs from English.
According to Bailey (1966), the progressive category is marked by /a~da~de/.  Alleyne (1980) claims that /a~da/ marks the progressive and that the habitual aspect is unmarked but by its accompaniment with words such as "always", "usually", etc. (i.e. is absent as a grammatical category). Mufwene (1984) and Gibson and Levy (1984) propose a past-only habitual category marked by /juusta/ as in /weɹ wi juusta liv iz not az kuol az iiɹ/ ('where we used to live is not as cold as here').[31]
For the present tense, an uninflected verb combining with an iterative adverb marks habitual meaning as in /tam aawez nuo kieti tel pan im/ ('Tom always knows when Katy tells/has told about him').[32]
en is a tense indicator
a is an aspect marker
(a) go is used to indicate the future
/mi ɹon/
I run (habitually); I ran
/mi a ɹon/ or /mi de ɹon/
I am running
/a ɹon mi dida ɹon/ or /a ɹon mi ben(w)en a ɹon/
I was running
/mi did ɹon/ or /mi ben(w)en ɹon/
I have run; I had run
/mi a ɡo ɹon/
I am going to run; I will run
Like other Caribbean Creoles (that is, Guyanese Creole and San Andrés-Providencia Creole; Sranan Tongo is excluded) /fi/ has a number of functions, including:[33]
Directional, dative, or benefactive preposition
/dem a fait fi wi/ ('They are fighting for us')[34]
Genitive preposition (that is, marker of possession)
/dat a fi mi buk/ ('that's my book')
Modal auxiliary expressing obligation or futurity
/im fi kom op ja/ ('he ought to come up here')
Pre-infinitive complementizer
/unu hafi kiip samtiŋ faɹ de ɡini piipl-dem fi biit dem miuzik/ ('you have to contribute something to the Guinean  People for playing their music')[35]
Pronominal system
The pronominal system of Standard English has a four-way distinction of person, number, gender and case. Some varieties of Jamaican Patois do not have the gender or case distinction, but all varieties distinguish between the second person singular and plural (you).
I, me = /mi/
you, you (singular) = /ju/
he, him = /im/ (pronounced [ĩ] in the basilect varieties)
she, her = /ʃi/ or /im/ (no gender distinction in basilect varieties)
we, us, our = /wi/
you (plural) = /unu/
they, them, their = /dem/
Copula
the Jamaican Patois equative verb is also a
e.g. /mi a di tiitʃa/ ('I am the teacher')
Jamaican Patois has a separate locative verb deh
e.g. /wi de a london/ or /wi de inna london/ ('we are in London')
with true adjectives in Jamaican Patois, no copula is needed
e.g. /mi haadbak nau/ ('I am old now')
This is akin to Spanish in that both have 2 distinct forms of the verb "to be" - ser and estar - in which ser is equative and estar is locative. Other languages, such as Portuguese and Italian, make a similar distinction. (See Romance Copula.)
Negation
/no/ is used as a present tense negator:
/if kau no did nuo au im tɹuotuol tan im udn tʃaans pieɹsiid/ ('If the cow knew that his throat wasn't capable of swallowing a pear seed, he wouldn't have swallowed it')[36]
/kiaan/ is used in the same way as English can't
/it a puoɹ tiŋ dat kiaan maʃ ant/ ('It is a poor thing that can't mash an ant')[37]
/neva/ is a negative past participle.[38]
/dʒan neva tiif di moni/ ('John did not steal the money')
Orthography
Patois has long been written with various respellings compared to English so that, for example, the word "there" might be written ⟨de⟩, ⟨deh⟩, or ⟨dere⟩, and the word "three" as ⟨tree⟩, ⟨tri⟩, or ⟨trii⟩.  Standard English spelling is often used and a nonstandard spelling sometimes becomes widespread even though it is neither phonetic nor standard (e.g. ⟨pickney⟩ for /pikni/, 'child').
In 2002, the Jamaican Language Unit was set up at the University of the West Indies at Mona to begin standardizing the language, with the aim of supporting non-English-speaking Jamaicans according to their constitutional guarantees of equal rights, as services of the state are normally provided in English, which a significant portion of the population cannot speak fluently. The vast majority of such persons are speakers of Jamaican Patois. It was argued that failure to provide services of the state in a language in such general use or discriminatory treatment by officers of the state based on the inability of a citizen to use English violates the rights of citizens. The proposal was made that freedom from discrimination on the ground of language be inserted into the Charter of Rights.[39] They standardized the Jamaican alphabet as follows:[40]

Nasal vowels are written with -hn, as in kyaahn (can't) and iihn (isn't it?)

h is written according to local pronunciation, so that hen (hen) and en (end) are distinguished in writing for speakers of western Jamaican, but not for those of central Jamaican.
Vocabulary

Jamaican Patois contains many loanwords, most of which are African in origin, primarily from Twi (a dialect of Akan).[41]
Many loanwords come from English, but are also borrowed from Spanish, Portuguese, Hindi, Arawak and African languages as well as Scottish and Irish dialects.
Examples from African languages include /se/ meaning that (in the sense of "he told me that..." = /im tel mi se/), taken from Ashanti Twi, and Duppy meaning ghost, taken from the Twi word dupon ('cotton tree root'), because of the African belief of malicious spirits originating in the root of trees (in Jamaica and Ghana, particularly the cotton tree known in both places as "Odom").[42] The pronoun /unu/, used for the plural form of you, is taken from the Igbo language. Red eboe describes a fair-skinned black person because of the reported account of fair skin among the Igbo in the mid 1700s.[43] De meaning to be(at a location) comes from  Yoruba.[44] From the Ashanti-Akan, comes the term Obeah which means witchcraft, from the Ashanti Twi word Ɔbayi which also means "witchcraft".[41]
Words from Hindi include ganja (marijuana), and janga (crawdad). Pickney or pickiney meaning child, taken from an earlier form (piccaninny) was ultimately borrowed from the Portuguese pequenino (the diminutive of pequeno, small) or Spanish pequeño ('small').
There are many words referring to popular produce and food items—ackee, callaloo, guinep, bammy, roti, dal, kamranga.  See Jamaican cuisine.
Jamaican Patois has its own rich variety of swearwords. One of the strongest is blood claat (along with related forms raas claat, bomba claat,   claat and others—compare with bloody in Australian English and British English, which is also considered a profanity).
Homosexual men may be referred to with the pejorative term /biips/[45], fish [46]or batty boys.
Example phrases
/mi aalmuos lik im/ - I nearly hit him[47]
/im caan biit mi, im dʒos loki dat im won/ - He can't beat me, he simply got lucky and won.[48]
/siin/ - Affirmative particle[49]
/papiˈʃuo/ - Foolish exhibition, a person who makes a foolish exhibition of him or herself, or an exclamation of surprise.[50]
/uman/ - Woman[51]
/bwoi/ - Boy[52]
Literature and film
A rich body of literature has developed in Jamaican Patois. Notable among early authors and works are Thomas MacDermot's All Jamaica Library and Claude McKay's Songs of Jamaica (1909), and, more recently, dub poets Linton Kwesi Johnson and Mikey Smith. Subsequently, the life-work of Louise Bennett or Miss Lou (1919–2006) is particularly notable for her use of the rich colorful patois, despite being shunned by traditional literary groups. "The Jamaican Poetry League excluded her from its meetings, and editors failed to include her in anthologies."[53]  Nonetheless, she argued forcefully for the recognition of Jamaican as a full language, with the same pedigree as the dialect from which Standard English had sprung:
Dah language weh yuh proud a,
Weh yuh honour an respec –
Po Mas Charlie, yuh no know se

Dat it spring from dialec!—Bans a Killin

After the 1960s, the status of Jamaican Patois rose as a number of respected linguistic studies were published, by Frederic Cassidy (1961, 1967), Bailey (1966) and others.[54] Subsequently, it has gradually become mainstream to codemix or write complete pieces in Jamaican Patois; proponents include Kamau Brathwaite, who also analyses the position of Creole poetry in his History of the Voice: The Development of Nation Language in Anglophone Caribbean Poetry (1984). However, Standard English remains the more prestigious literary medium in Jamaican literature. Canadian-Caribbean science-fiction novelist Nalo Hopkinson often writes in Trinidadian and sometimes Jamaican Patois. Jean D'Costa penned a series of popular children's novels, including Sprat Morrison (1972; 1990), Escape to Last Man Peak (1976), and Voice in the Wind (1978), which draw liberally from Jamaican Patois for dialogue, while presenting narrative prose in Standard English.[55] Marlon James employs Patois in his novels including A Brief History of Seven Killings (2014). In his science fiction novel Kaya Abaniah and the Father of the Forest (2015), British-Trinidadian author Wayne Gerard Trotman presents dialogue in Trinidadian Creole, Jamaican Patois, and French while employing Standard English for narrative prose.
Jamaican Patois is also presented in some films and other media, for example, the character Tia Dalma's speech from Pirates of the Caribbean: Dead Man's Chest, and a few scenes in Meet Joe Black in which Brad Pitt's character converses with a Jamaican woman. In addition, early Jamaican films like The Harder They Come (1972), Rockers (1978), and many of the films produced by Palm Pictures in the mid-1990s (e.g. Dancehall Queen and Third World Cop) have most of their dialogue in Jamaican Patois; some of these films have even been subtitled in English.
Bible
In December 2011, it was reported that the Bible was being translated into Jamaican Patois. The Gospel of St Luke has already appeared as: Jiizas: di Buk We Luuk Rait bout Im. While the Rev. Courtney Stewart, managing the translation as General Secretary of the West Indies Bible Society, believes this will help elevate the status of Jamaican Patois, others think that such a move would undermine efforts at promoting the use of English. The Patois New Testament was launched in Britain (where the Jamaican diaspora is significant) in October 2012 as "Di Jamiekan Nyuu Testiment", and with print and audio versions in Jamaica in December 2012.[56][57][58]

A comparison of the Lord's Prayer

...as it occurs in Di Jamiekan Nyuu Testiment:[59]
Wi Faada we iina evn,
mek piipl av nof rispek fi yu an yu niem.
Mek di taim kom wen yu ruul iina evri wie.
Mek we yu waahn apm pan ort apm,
jos laik ou a wa yu waahn fi apm iina evn apm
Tide gi wi di fuud we wi niid.
Paadn wi fi aal a di rang we wi du,
siem laik ou wi paadn dem we du wi rang.
An no mek wi fies notn we wi kaaz wi fi sin,
bot protek wi fram di wikid wan.

...as it occurs in English Standard Version:
Our Father in heaven,
hallowed be Your name.
Your kingdom come,
Your will be done,
on earth, as it is in heaven.
Give us this day our daily bread,
and forgive us our debts,
as we also have forgiven our debtors.
And lead us not into temptation,
but deliver us from evil.

See also

African American Vernacular English
English-based creole languages
Jamaican English
Nation language
Rastafarian vocabulary

Bibliography

CS1 maint: multiple names: authors list (link) CS1 maint: extra text: authors list (link)

</ref>

Further reading


Vertebrates /ˈvɜːrtɪbrɪts/ comprise all species of animals within the subphylum Vertebrata /-eɪ/ (chordates with backbones). Vertebrates represent the overwhelming majority of the phylum Chordata, with currently about 69,276 species described.[4] Vertebrates include the jawless fishes and jawed vertebrates, which include the cartilaginous fishes (sharks, rays, and ratfish) and the bony fishes.
Other vertebrates are the tetrapods, which include a bony fish clade known as the lobe-finned fishes, as well as amphibians, reptiles, birds and mammals.
Extant vertebrates range in size from the frog species Paedophryne amauensis, at as little as 7.7mm (0.30in), to the blue whale, at up to 33m (108ft). Vertebrates make up less than five percent of all described animal species; the rest are invertebrates, which lack vertebral columns.
The vertebrates traditionally include the hagfish, which do not have proper vertebrae due to their loss in evolution,[5] though their closest living relatives, the lampreys, do.[6] Hagfish do, however, possess a cranium. For this reason, the vertebrate subphylum is sometimes referred to as "Craniata" when discussing morphology.
Molecular analysis since 1992 has suggested that hagfish are most closely related to lampreys,[7] and so also are vertebrates in a monophyletic sense. Others consider them a sister group of vertebrates in the common taxon of craniata.[8]
Etymology
The word origin of vertebrate derives from the Latin word vertebratus (Pliny), meaning joint of the spine.[9] The Proto-Indo-European language origins are still unclear.
Vertebrate is derived from the word vertebra, which refers to any of the bones or segments of the spinal column.[10]
Anatomy and morphology

All vertebrates are built along the basic chordate body plan: a stiff rod running through the length of the animal (vertebral column and/or notochord),[11] with a hollow tube of nervous tissue (the spinal cord) above it and the gastrointestinal tract below.
In all vertebrates, the mouth is found at, or right below, the anterior end of the animal, while the anus opens to the exterior before the end of the body. The remaining part of the body continuing after the anus forms a tail with vertebrae and spinal cord, but no gut.[12]
Vertebral column
The defining characteristic of a vertebrate is the vertebral column, in which the notochord (a stiff rod of uniform composition) found in all chordates has been replaced by a segmented series of stiffer elements (vertebrae) separated by mobile joints (intervertebral discs, derived embryonically and evolutionarily from the notochord).
However, a few vertebrates have secondarily lost this anatomy, retaining the notochord into adulthood, such as the sturgeon[13] and coelacanth. Jawed vertebrates are typified by paired appendages (fins or legs, which may be secondarily lost), but this trait is not required in order for an animal to be a vertebrate.

Gills

All basal vertebrates breathe with gills. The gills are carried right behind the head, bordering the posterior margins of a series of openings from the pharynx to the exterior. Each gill is supported by a cartilagenous or bony gill arch.[14] The bony fish have three pairs of arches, cartilaginous fish have five to seven pairs, while the primitive jawless fish have seven. The vertebrate ancestor no doubt had more arches than this, as some of their chordate relatives have more than 50 pairs of gills.[12]
In amphibians and some primitive bony fishes, the larvae bear external gills, branching off from the gill arches.[15] These are reduced in adulthood, their function taken over by the gills proper in fishes and by lungs in most amphibians. Some amphibians retain the external larval gills in adulthood, the complex internal gill system as seen in fish apparently being irrevocably lost very early in the evolution of tetrapods.[16]
While the more derived vertebrates lack gills, the gill arches form during fetal development, and form the basis of essential structures such as jaws, the thyroid gland, the larynx, the columella (corresponding to the stapes in mammals) and, in mammals, the malleus and incus.[12]
Central nervous system
The central nervous system of vertebrates is based on a hollow nerve cord running along the length of the animal. Of particular importance and unique to vertebrates is the presence of neural crest cells. These are progenitors of stem cells, and critical to coordinating the functions of cellular components.[17] Neural crest cells migrate through the body from the nerve cord during development, and initiate the formation of neural ganglia and structures such as the jaws and skull.[18][19][20]
The vertebrates are the only chordate group to exhibit cephalisation, the concentration of brain functions in the head. A slight swelling of the anterior end of the nerve cord is found in the lancelet, a chordate, though it lacks the eyes and other complex sense organs comparable to those of vertebrates. Other chordates do not show any trends towards cephalisation.[12]
A peripheral nervous system branches out from the nerve cord to innervate the various systems. The front end of the nerve tube is expanded by a thickening of the walls and expansion of the central canal of spinal cord into three primary brain vesicles: The prosencephalon (forebrain), mesencephalon (midbrain) and rhombencephalon (hindbrain), further differentiated in the various vertebrate groups.[21] Two laterally placed eyes form around outgrowths from the midbrain, except in hagfish, though this may be a secondary loss.[22][23] The forebrain is well developed and subdivided in most tetrapods, while the midbrain dominates in many fish and some salamanders. Vesicles of the forebrain are usually paired, giving rise to hemispheres like the cerebral hemispheres in mammals.[21]
The resulting anatomy of the central nervous system, with a single hollow nerve cord topped by a series of (often paired) vesicles, is unique to vertebrates. All invertebrates with well-developed brains, such as insects, spiders and squids, have a ventral rather than dorsal system of ganglions, with a split brain stem running on each side of the mouth or gut.[12]
Evolutionary history

First vertebrates

Vertebrates originated about 525 million years ago during the Cambrian explosion, which saw the rise in organism diversity. The earliest known vertebrate is believed to be the Myllokunmingia.[1] Another early vertebrate is Haikouichthys ercaicunensis. Unlike the other fauna that dominated the Cambrian, these groups had the basic vertebrate body plan: a notochord, rudimentary vertebrae, and a well-defined head and tail.[24] All of these early vertebrates lacked jaws in the common sense and relied on filter feeding close to the seabed.[25] A vertebrate group of uncertain phylogeny, small-eel-like conodonts, are known from microfossils of their paired tooth segments from the late Cambrian to the end of the Triassic.[26]
From fish to amphibians

The first jawed vertebrates appeared in the latest Ordovician and became common in the Devonian, often known as the "Age of Fishes".[27] The two groups of bony fishes, the actinopterygii and sarcopterygii, evolved and became common.[28] The Devonian also saw the demise of virtually all jawless fishes, save for lampreys and hagfish, as well as the Placodermi, a group of armoured fish that dominated the entirety of that period since the late Silurian. The Devonian also saw the rise of the first labyrinthodonts, which was a transitional form between fishes and amphibians.
Mesozoic vertebrates
Amniotes branched from labyrinthodonts in the subsequent Carboniferous period. The Parareptilia and synapsid amniotes were common during the late Paleozoic, while diapsids became dominant during the Mesozoic. In the sea, the bony fishes became dominant; the birds, a derived form of dinosaurs, evolved in the Jurassic.[29] The demise of the non-avian dinosaurs at the end of the Cretaceous allowed for the expansion of mammals, which had evolved from the therapsids, a group of synapsid amniotes, during the late Triassic Period.
After the Mesozoic
The Cenozoic world has seen great diversification of bony fishes, frogs, birds and mammals.
Over half of all living vertebrate species (about 32,000 species) are fish (non-tetrapod craniates), a diverse set of lineages that inhabit all the world's aquatic ecosystems, from snow minnows (Cypriniformes) in Himalayan lakes at elevations over 4,600 metres (15,100 feet) to flatfishes (order Pleuronectiformes) in the Challenger Deep, the deepest ocean trench at about 11,000 metres (36,000 feet). Fishes of myriad varieties are the main predators in most of the world's water bodies, both freshwater and marine. The rest of the vertebrate species are tetrapods, a single lineage that includes amphibians (with roughly 7,000 species); mammals (with approximately 5,500 species); and reptiles and birds (with about 20,000 species divided evenly between the two classes). Tetrapods comprise the dominant megafauna of most terrestrial environments and also include many partially or fully aquatic groups (e.g., sea snakes, penguins, cetaceans).
Classification
There are several ways of classifying animals. Evolutionary systematics relies on anatomy, physiology and evolutionary history, which is determined through similarities in anatomy and, if possible, the genetics of organisms.[30] Phylogenetic classification is based solely on phylogeny.[31] Evolutionary systematics gives an overview; phylogenetic systematics gives detail. The two systems are thus complementary rather than opposed.[32]
Traditional classification

Conventional classification has living vertebrates grouped into seven classes based on traditional interpretations of gross anatomical and physiological traits. This classification is the one most commonly encountered in school textbooks, overviews, non-specialist, and popular works. The extant vertebrates are:[12]
Subphylum Vertebrata
Class Agnatha (jawless fishes)
Class Chondrichthyes (cartilaginous fishes)
Class Osteichthyes (bony fishes)
Class Amphibia (amphibians)
Class Reptilia (reptiles)
Class Aves (birds)
Class Mammalia (mammals)
In addition to these, there are two classes of extinct armoured fishes, the Placodermi and the Acanthodii.
Other ways of classifying the vertebrates have been devised, particularly with emphasis on the phylogeny of early amphibians and reptiles. An example based on Janvier (1981, 1997), Shu et al. (2003), and Benton (2004)[33] is given here:
Subphylum Vertebrata
Palaeospondylus
Superclass Agnatha or Cephalaspidomorphi (lampreys and other jawless fishes)
Infraphylum Gnathostomata (vertebrates with jaws)
Class †Placodermi (extinct armoured fishes)
Class Chondrichthyes (cartilaginous fishes)
Class †Acanthodii (extinct spiny "sharks")
Superclass Osteichthyes (bony vertebrates)
Class Actinopterygii (ray-finned bony fishes)
Class Sarcopterygii (lobe-finned fishes, including the tetrapods)
Class Amphibia (amphibians, some ancestral to the amniotes)- now a paraphyletic group
Class Synapsida (mammals and the extinct mammal-like reptiles)
Class Sauropsida (reptiles and birds)
While this traditional classification is orderly, most of the groups are paraphyletic, i.e. do not contain all descendants of the class's common ancestor.[33] For instance, descendants of the first reptiles include modern reptiles, as well as mammals and birds. Most of the classes listed are not "complete" (and are therefore paraphyletic) taxa, meaning they do not include all the descendants of the first representative of the group. For example, the agnathans have given rise to the jawed vertebrates; the bony fishes have given rise to the land vertebrates; the traditional "amphibians" have given rise to the reptiles (traditionally including the synapsids, or mammal-like "reptiles"), which in turn have given rise to the mammals and birds. Most scientists working with vertebrates use a classification based purely on phylogeny, organized by their known evolutionary history and sometimes disregarding the conventional interpretations of their anatomy and physiology.
Phylogenetic relationships
In phylogenetic taxonomy, the relationships between animals are not typically divided into ranks, but illustrated as a nested "family tree" known as a phylogenetic tree. The one below is based on studies compiled by Philippe Janvier and others for the Tree of Life Web Project and Delsuc et al.[34][35]

Vertebrata/

Agnatha/

Hyperoartia (lampreys)
MyxiniCyclostomes
?†Euconodontaunnamed

†Pteraspidomorphi
?†Thelodontiunnamed

?†Anaspidaunnamed

†Galeaspidaunnamed

?†Pituriaspida
†OsteostraciGnathostomata

†Placodermi (armoured fishes)unnamed

Acanthodians, incl. Chondrichthyes (cartilaginous fishes)Euteleostomi

Actinopterygii (ray-finned fishes)Sarcopterygii(lobe-finnedfish)

?†Onychodontiformes
Actinistia (coelacanths)unnamed

†Porolepiformes
Dipnoi (lungfishes)unnamed

†Rhizodontimorpha

†Tristichopteridae
TetrapodaCraniata
Number of extant species
The number of described vertebrate species are split evenly between tetrapods and fish. The following table lists the number of described extant species for each vertebrate class as estimated in the IUCN Red List of Threatened Species, 2014.3.[36]

The IUCN estimates that 1,305,075 extant invertebrate species have been described,[36] which means that less than 5% of the described animal species in the world are vertebrates.
Vertebrate species databases
The following databases maintain (more or less) up-to-date lists of vertebrate species:
Fish: Fishbase
Amphibians:
Reptiles: Reptile Database
Birds:
Mammals:
Reproductive systems
Nearly all vertebrates undergo sexual reproduction. They produce haploid gametes by meiosis. The smaller, motile gametes are spermatozoa and the larger, non-motile gametes are ova. These fuse by the process of fertilisation to form diploid zygotes, which develop into new individuals.
Inbreeding
During sexual reproduction, mating with a close relative (inbreeding) often leads to inbreeding depression. Inbreeding depression is considered to be largely due to expression of deleterious recessive mutations.[37] The effects of inbreeding have been studied in many vertebrate species.
In several species of fish, inbreeding was found to decrease reproductive success.[38][39][40]
Inbreeding was observed to increase juvenile mortality in 11 small animal species.[41]
A common breeding practice for pet dogs is mating between close relatives (e.g. between half- and full siblings).[42] This practice generally has a negative effect on measures of reproductive success, including decreased litter size and puppy survival.[43][44][45]
Incestuous matings in birds result in severe fitness costs due to inbreeding depression (e.g. reduction in hatchability of eggs and reduced progeny survival).[46][47][48]
Inbreeding avoidance
As a result of the negative fitness consequences of inbreeding, vertebrate species have evolved mechanisms to avoid inbreeding. Numerous inbreeding avoidance mechanisms operating prior to mating have been described.
Toads and many other amphibians display breeding site fidelity. Individuals that return to natal ponds to breed will likely encounter siblings as potential mates. Although incest is possible, Bufo americanus siblings rarely mate.[49] These toads likely recognize and actively avoid close kins as mates. Advertisement vocalizations by males appear to serve as cues by which females recognize their kin.[49]
Inbreeding avoidance mechanisms can also operate subsequent to copulation. In guppies, a post-copulatory mechanism of inbreeding avoidance occurs based on competition between sperm of rival males for achieving fertilization.[50] In competitions between sperm from an unrelated male and from a full sibling male, a significant bias in paternity towards the unrelated male was observed.[50]
When female sand lizards mate with two or more males, sperm competition within the female's reproductive tract may occur. Active selection of sperm by females appears to occur in a manner that enhances female fitness.[51] On the basis of this selective process, the sperm of males that are more distantly related to the female are preferentially used for fertilization, rather than the sperm of close relatives.[51] This preference may enhance the fitness of progeny by reducing inbreeding depression.
Outcrossing
Mating with unrelated or distantly related members of the same species is generally thought to provide the advantage of masking deleterious recessive mutations in progeny[52] (and see Heterosis). Vertebrates have evolved numerous diverse mechanisms for avoiding close inbreeding and promoting outcrossing[53] (and see Inbreeding avoidance).
Outcrossing as a way of avoiding inbreeding depression, has been especially well studied in birds. For instance, inbreeding depression occurs in the great tit when the offspring are produced as a result of a mating between close relatives. In natural populations of the great tit (Parus major), inbreeding is avoided by dispersal of individuals from their birthplace, which reduces the chance of mating with a close relative.[54]
The purple-crowned fairywren females paired with related males may undertake extra-pair matings that can reduce the negative effects of inbreeding. However, there are ecological and demographic constraints on extra pair matings. Nevertheless, 46% of broods produced by incestuously paired females contained extra-pair young.[48]
Southern pied babblers (Turdoides bicolor) appear to avoid inbreeding in two ways. The first is through dispersal, and the second is by avoiding familiar group members as mates.[55] Although both males and females disperse locally, they move outside the range where genetically related individuals are likely to be encountered. Within their group, individuals only acquire breeding positions when the opposite-sex breeder is unrelated.
Cooperative breeding in birds typically occurs when offspring, usually males, delay dispersal from their natal group in order to remain with the family to help rear younger kin.[56] Female offspring rarely stay at home, dispersing over distances that allow them to breed independently, or to join unrelated groups.
Parthenogenesis
Parthenogenesis is a natural form of reproduction in which growth and development of embryos occur without fertilization.
Reproduction in squamate reptiles is ordinarily sexual, with males having a ZZ pair of sex determining chromosomes, and females a ZW pair. However, various species, including the Colombian Rainbow boa (Epicrates maurus), Agkistrodon contortrix (copperhead snake) and Agkistrodon piscivorus (cotton mouth snake) can also reproduce by facultative parthenogenesis -that is, they are capable of switching from a sexual mode of reproduction to an asexual mode- resulting in production of WW female progeny.[57][58] The WW females are likely produced by terminal automixis.
Mole salamanders are an ancient (2.4-3.8 million year-old) unisexual vertebrate lineage.[59] In the polyploid unisexual mole salamander females, a premeiotic endomitotic event doubles the number of chromosomes. As a result, the mature eggs produced subsequent to the two meiotic divisions have the same ploidy as the somatic cells of the female salamander. Synapsis and recombination during meiotic prophase I in these unisexual females is thought to ordinarily occur between identical sister chromosomes and occasionally between homologous chromosomes. Thus little, if any, genetic variation is produced. Recombination between homeologous chromosomes occurs only rarely, if at all.[60] Since production of genetic variation is weak, at best, it is unlikely to provide a benefit sufficient to account for the long-term maintenance of meiosis in these organisms. However, meiosis may have been maintained during evolution by the efficient recombinational repair of DNA damages that meiosis provides, an advantage that could be realized at each generation.[61]
Self-fertilization
The mangrove killifish (Kryptolebias marmoratus) produces both eggs and sperm by meiosis and routinely reproduces by self-fertilisation. The capacity for selfing in these fishes has apparently persisted for at least several hundred thousand years.[62] Each individual hermaphrodite normally fertilizes itself when an egg and sperm that it has produced by an internal organ unite inside the fish's body.[63] In nature, this mode of reproduction can yield highly homozygous lines composed of individuals so genetically uniform as to be, in effect, identical to one another.[64][65]  Although inbreeding, especially in the extreme form of self-fertilization, is ordinarily regarded as detrimental because it leads to expression of deleterious recessive alleles, self-fertilization does provide the benefit of fertilization assurance (reproductive assurance) at each generation.[64]
See also
Marine vertebrate
Skeletal system of the horse
Taxonomy of the vertebrates (Young, 1962)

Bibliography

 chapter in United States Environmental Protection Agency and University of Florida/Institute of Food and Agricultural Sciences National Public Health Pesticide Applicator Training Manual

 Marc W. Kirschner, iBioSeminars, 2008.