Compare and contrast the biological mechanisms underlying addiction and obsessive compulsive disorder. Refer in your answer to recent experimental studies that have advanced understanding of the underlying causes and the brain pathology of these two disorders.

Compare and contrast the biological mechanisms underlying addiction and obsessive compulsive disorder. Refer in your answer to recent experimental studies that have advanced understanding of the underlying causes and the brain pathology of these two disorders.

This essay aims to compare and contrast the underlying biological mechanisms of both addiction and obsessive-compulsive disorder by examining recent experimental studies that advance our understanding of the disorders. It will focus on the biological mechanisms of learning, reward and motivation and discuss how these compare and contrast in the brains of addicts and in the brains of individuals suffering from obsessive-compulsive disorder. Disorders of inhibitory control will also be examined to discuss whether this could also be responsible for some of the symptomology that lays behind addiction and/or obsessive-compulsive disorder and will argue if this could be the reason as to why many disorders that demonstrate dysfunction of executive function and inhibitory control such as obsessive-compulsive disorder, attention deficit hyperactivity disorder and schizophrenia are also at high risk of suffers developing a co morbid substance misuse disorder. Finally it will discuss why some individuals develop addictions or obsessive-compulsive disorder while others do not.

Addiction is a chronic and relapsing brain disease (Leshner, 1999) that affects an estimated two-million individuals in the UK alone (Godfrey, Stewart & Gossop, 2004). When referring to substance misuse, the term “addiction” implies a pathological and compulsive pattern of drug-seeking or drug-taking behaviour which occupies a large percentage of an individuals’ time and thoughts and persists despite adverse consequences (Hasin, Liu, Alderson & Grant, 2006). This persistent and compulsive pattern of behaviour can also be seen in behavioural addictions such as pathological gambling, sex addictions, shopping addictions for example. It is this persistence to continue to engage in maladaptive behaviour despite adverse consequences that is seen as the defining marker in addiction. Many addicts are unable to stop their addictive behaviour despite wishing to be able to do so and even after successful cessation the likelihood of relapse is high even after a sustained period of abstinence (West, 2013). Although addiction appears to have a clear compulsive component, the compulsive nature of addiction is quite different from the compulsions seen in obsessive-compulsive disorder.  

Obsessive-compulsive disorder is an anxiety disorder characterised by intrusive thoughts, feelings, ideas or images, these are known as obsessions, that lead to an immediate urge to perform a behavioural act or ritual, known as compulsions (Abramowitz & Houts, 2002). The obsessive thoughts and feelings witnessed in patients with obsessive-compulsive disorder cause significant distress and anxiety often adversely impacting on their ability to successfully participate in everyday activities. Compulsions aim to relieve stress and anxiety and often present as behaviours or rituals such as excessive hand-washing, cleaning or checking (Abramowitz & Houts, 2002). The compulsions seen in obsessive-compulsive disorder differ from the compulsive behaviours displayed by addicts. Although addicts may suffer adverse consequences due to the nature of their addiction, the original motivating factor to engage in their addictive behaviours is largely argued to be for hedonic reasons (Kennett, Matthews & Snoek, 2013).  Patients suffering from obsessive-compulsive disorder do not engage in their compulsions for pleasurable gain but to relieve an overwhelming sense of anxiety. It could be argued however that this relief in itself is pleasurable and could be likened to the relief felt by an addict when alleviating withdrawal symptoms? To discuss this argument in more depth it is now necessary to explain the biological mechanisms of learning, reward and motivation and discuss how these mechanisms function in the brains of addicts as well as in individuals suffering from obsessive-compulsive disorder. 

One of the most common misconceptions about the nature of drug addiction concerns its relationship with physical dependence (Pinel, 2014). Much evidence however suggests that addiction occurs due to dysfunction among the neural processes that typically serve reward-related learning (Hyman, Malenka & Nestler, 2006). It is suggested that homeostatic adaptations in the brains of persistent compulsive drug users are not due to dependence and withdrawal effects but rather due to adaptations in long-term associative memory processes occurring in several neural circuits that receive input from midbrain dopamine neurons (Beke & Hyman, 2000; Robbins & Everitt, 2002; Everitt & Robbins, 2005; Hyman, 2005). The investigation of associative learning processes in addiction first stemmed from the observation that drug taking and relapse often follows exposure to drug related cues or drug-associated stimuli (Hyman, Malenka & Nestler, 2006) leading many researchers to believe that classical and operant conditioning principles underlie the compulsiveness of addictive behaviour (Glass & Chandler, 2013). While it is highly likely that individuals engage in recreational drug use for their hedonic effects, positive reinforcement models of addiction fail to explain the ongoing motivation to continue to engage in drug-seeking/drug-taking behaviours when positive effects are minimal or non-existent. This can be further explained by examining the individual structures that make up the brains reward circuitry.

Drugs of abuse produce their reinforcing effects by altering dopaminergic transmission within the limbic system (Volkow, Fowler & Wang, 2004), causing a disruption to many closely interconnected brain structures (Pierce & Kumaresan, 2005). Many studies have consistently shown that drugs of abuse induce large increases of dopamine in the nucleus accumbens, the major component of the ventral striatum. This is interpreted as a sense of pleasure and will often reinforce behaviour, thus increasing the likelihood of it occurring again. For example in animal models, rats will learn how to press a lever to self-administer drugs after repeated exposure. They will also learn quickly drug associated cues that are predictive of reward. For example rats will demonstrate conditioned place preference, preferring a location they received reinforcing drugs over a location where they received a saline injection (Bardo & Bevis, 2000).

 All forms of reward including natural rewards such as food and procreation release dopamine. The nucleus accumbens plays a central role in the cognitive processing of motivation, pleasure, reward and reinforcement learning and therefore plays a large part in addiction (Hyman, Malenka & Nestler, 2006). The incentive-sensitization theory of addiction suggests that increased dopamine within reward system due to compulsive drug use leads to the system becoming over sensitised or over responsive to drugs and drug-associated stimuli (Robinson & Berridge, 2008). The increase in dopamine within the nucleus accumbens causes a large amount of incentive salience to be attributed to the drug responsible (Robinson & Berridge, 2008). In addition to the nucleus accumbens, the amgydala and prefrontal cortex play major roles in the valuation of rewards and the establishment of reward associated memories (Everitt et al. 2003, Kalivas et al. 2005). fMRI studies measuring brain responses towards natural reinforcers between addicted and non-addicted individuals have shown decreased activation in limbic regions in addicts. In contrast addicted individuals showed increased limbic activation when exposed to drug-related stimuli compared to non-addicted individuals (Martin-Soelch et al., 2001). This is suggestive that there is a decreased sensitization for natural rewards in addicted individuals, suggesting that higher incentive salience has been attributed to drugs of abuse indicating an increased sensitivity to those drugs within the reward system (Robinson & Berridge, 2003). There is also evidence to suggest that compulsive drug users become desensitised to the reinforcing properties of natural rewards, perhaps suggesting why addicts become so preoccupied by drug-taking and drug-seeking behaviours they lose interest in everything else.

There is much evidence to suggest that these different brain structures are altered in compulsive drug users when compared to the rest of the population, however despite the vast array of different drugs of abuse; opiates, psychostimulants, cannabinoids etc, symptoms of addiction remain the same regardless of substance. This suggests that the same brain mechanisms are responsible for all types of compulsive behaviours. Although obsessive-compulsive disorder is classified as an anxiety disorder it has also been conceptualized as a behavioural addiction (Heuvel et al., 2004). As discussed previously, like in addiction, individuals with obsessive-compulsive disorder may develop a dependency for compulsive behaviours due to the rewarding effects that reduction of the obsession-induced anxiety brings (Figee et al. 2010).  Recent studies have demonstrated that the Nucleus accumbens is a successful target for deep brain stimulation as a treatment method of obsessive-compulsive disorder (Huff et al., 2010) suggestive that there may be dysfunction in the reward system of obsessive-compulsive patients. When examining the type of compulsive behaviours seen frequently in obsessive-compulsive disorder; washing, cleaning, checking it can be argued that these types of behaviours may have some evolutionary benefit such as to promote reproductive fitness. Therefore these compulsions could be attributed to the same motivational learning and reward system that is argued to be responsible for the cravings and repetitive compulsive pattern of behaviour in addiction. Graybiel & Rauch (2000) proposed that obsessive-compulsive disorder stems from maladaptive habit learning and dysfunction in goal-directed motivation.

Two areas of the frontal cortex, the anterior cingulate cortex and the orbitofrontal cortex, areas involved in inhibitory decision-making processes especially involving reward-related behaviours, have been shown to be affected after chronic compulsive drug use (Volkow et al, 2002). These regions process the reward value of environmental stimuli, assess future consequences of one’s actions (response selection) and inhibit inappropriate behaviours (response inhibition) (Bechara & Damasio, 2002). Dysfunction within these two regions has been associated with both the compulsive nature of both addiction and obsessive-compulsive disorder.  It is expected that dopamine disruption in the orbitofrontal cortex affects n individual’s ability to be able to effectively assign saliency value to a stimulus as a function of its context. Evidence has found that compulsive cocaine users were unable to process the relative value of a non-drug related reward. In a task assessing monetary gain, a majority of addicts were unable to assess the difference in value of hypothetical monetary rewards. fMRI results showed this inability was related to activity in the orbitolfrontal cortex. Brain activation decreased in addicts during the task when compared to healthy controls (Golstein & Volkow, 2005).  Disruption of dopamine in the anterior cingulate cortex affects the process of inhibitory control. In obsessive-compulsive disorder the dysfunction of the anterior cingulate cortex has suggested to be the reason for why individuals are unable to inhibit their intrusive thoughts and compulsions. 

Dysfunction in the anterior cingulated cortex is found in many other disorders of inhibition control such as tourettes and ADHD. Volkow, Fowler & Wang (2004) argue that the disruptions in both the orbitofrontal cortex and anterior cingulate cortex are behind the compulsive drug use and loss of control of addicts when exposed to drugs or drug-related stimuli. When drug-free addicts are presented with drug related memories or stimuli, or if the drug is administered, they show increased activation in the orbitolfrontal cortex and this enhanced activation increased desire for the drug. This suggests that orbitolfrontal cortex and anterior cingulated cortex hypermetabolism may trigger compulsive drug use in addicts just as it contributes to the compulsive behaviour in patients with obsessive-compulsive disorder (Volkow, Fowler & Wang, 2004).

The inhibitory system is an alternative system that may well be responsible for the underlying features of both addiction and obsessive-compulsive disorder. Clinical descriptions of both addiction and obsessive-compulsive disorder highlight an inability to inhibit intrusive thought patterns (obsessions/cravings) and the ritualistic behaviours seen in obsessive-compulsive disorder as compulsions and in addiction as compulsive drug seeking or drug taking. Modell et al (2002) investigated the compulsive nature of cravings in individuals suffering from chronic alcoholism. It was found that alcoholics rated themselves high for obsessive-compulsive behaviours when compared to that of controls. Brain imaging studies of obsessive-compulsive disorder patients show reduced pre-frontal activity and enhanced basal ganglia activity which matches similar findings when looking at the brains of those with chronic alcohol dependence. Modell et. al  (2002) found using the self rated obsessive compulsive scale (based on the Yale-Brown obsessive compulsive scale) to measure cravings, that when alcoholics were given a sip of alcohol, activity in the basal ganglia increased, and  this increased basal ganglia activity directly related with self reported desire to drink. Deficits in inhibitory function may explain the common occurrence of co-morbid substance misuse disorders in disorders involving inhibitory control and executive function such as ADHD, schizophrenia and extending to obsessive-compulsive disorder.  Impulse control disorders are currently where the behavioural addictions are categorized in the DSM-5 which shows that the symptoms overlap. Although it is clear that brain mechanisms responsible for compulsive behaviours are very similar in both addiction and obsessive-compulsive disorder this does not explain why not everyone who recreationally takes addictive substances becomes addicted nor does explain why compulsive symptoms in obsessive-compulsive disorder only extend to rituals such as checking, cleaning and washing and does not result in a whole host of impulsive behaviours such as is the case with tourettes or ADHD.

Lastly genetic components also have a role in addiction and obsessive-compulsive disorder. A recent study has discovered that patients with obsessive-compulsive disorder share a significant association on chromosome 9 near gene “PTPRD”. In animal models this gene has been associated with dysfunction in learning and memory giving more evidence to suggest that aspects of compulsive behaviour does stem from learning processes. The same gene has also been linked to some cases of attention deficit hyperactivity disorder, demonstrating that compulsive behaviour is also related to dysfunction with inhibitory processes and executive function (Hopkins, 2014). In the future further research can be done to discover the relationship and interaction affects between the role of “PTPRD” with the compulsions of addictive behaviour as well as examining the compulsive nature of obsessive-compulsive disorder.

In conclusion it is suggested that brain areas responsible for motivation, reward based learning and inhibitory control all have a part to play in symptoms of compulsive behaviour (Abramowitz & Houts, 2002, Hyman, Malenka & Nestler, 2006, Heuvel et al., 2004 & Golstein & Volkow, 2005). Whether that is the compulsive behaviour or drug seeking or drug taking in addiction, or whether it is the compulsions of obsessive-compulsive disorder. Hypersensitivity of dopamine in the nucleus accumbens is responsible for sensitivity towards drugs and drug related cues in addicts leading to a reinforced desire to continue to use (Robinson & Berridge, 2008, Hyman, Malenka & Nestler, 2006, Volkow, Fowler & Wang, 2004). Associative learning is also seen in obsessive-compulsive disorder and it is argued that obsessive-compulsive symptoms arise from problems with habitual learning processes (Graybiel & Rauch, 2000). Obsessive-compulsive patients also have increased dopamine in the nucleus accumbens and it is argued that this may be responsible for the behavioural compulsions experienced by patients (Huff et al., 2010). Acting on a compulsion to relieve the obsession-related anxiety is rewarded in the brain just like the addict is when they engage in their addictive behaviours of compulsive drug use (Figee et al. 2010).  Dopamine changes also happen in the oribitolfrontal cortex and anterior cingulate cortex in both addiction and obsessive-compulsive disorder (Volkow et al, 2002). Dysfunction in the orbitolfrontal cortex is likely to cause problems with motivation and goal-directed behaviour whereas dysfunction within the anterior cingulate cortex causes problem s with inhibitory control. Dysfunctions with inhibitory control is seen in many patients suffering with addiction and obsessive-compulsive disorder and may explain why substance misuse disorders are often a comorbidity of inhibitory control disorders such as obsessive-compulsive disorder, tourettes, schizophrenia and ADHD for example.

Much of the research cantered around inhibitory control mechanisms is new and current and as this develops it can be expected that as neuro-imaging techniques and technologies improve, more will be learnt about the neural substrates of each disorder and how each structure interacts with the other. 

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