Obsessive+Compulsive+Disorder

//By: Sharita Bobikuganathan// =**General Overview**=

Obsessive Compulsive Disorder (OCD) is a prevalent form of anxiety disorder found in both children and adults, but more commonly in adults. It is seen as a disorder that gives rise to severe functional impairment in individuals. OCD is a disorder with a lifetime prevalence of 2-3%. This disorder is primarily distinguished based on the increase in the frequency of specific repetitive behaviours including washing hands excessively, hoarding, repetitive checking, unwanted thoughts that persist in one’s mind and etc. [2] These symptoms are classified as either obsession or compulsions and can occur as early as adolescence; it is found to be more common among boys than girls during adolescence. These are referred to as compulsions and they act as a way for individuals to relieve the stress that they may be encountering. These compulsions are usually time-consuming and in most cases, individuals are unaware of them. The ability to relieve their stress is often temporary and individuals have a hard time switching from one task to another; indicating inability to be mentally flexible. Also, people with OCD are most often too engaged in their internal mental processes and are more specifically focused on their obsessions. Intense anxiety is faced by individuals who have difficulty overcoming these unwanted thoughts and repetitive behaviour. [2]  OCD is found to be highly co-morbid with other anxiety disorders. Approximately, 79.7% of patients with OCD have other psychiatric conditions as well. [3]  This disorder continues to be widely studied and there is a need for further development to take place in the research field pertaining to this illness.

 **Example of a Hoarder:**  media type="youtube" key="euT0T5GimE0" height="315" width="560" = = =**Symptoms and Behavioural Characteristics**=  toc

**Decline in Cognitive Functioning**
Obsessive Compulsive disorder is primarily known as a disorder involving repetitive behaviour that individuals exhibit in the form of compulsions and obsessions. In some cases of OCD, individuals show a decline in verbal memory and lack of full attention capacity. [4] This poor selective attention capacity explains the inability of individuals with OCD to disregard intrusive internal thoughts that they frequently encounter as well as their inability to adapt to changes in their daily routines.The satisfaction of performing these compulsions and obsessions change over time. This change is often accompanied by a shift in the individual's attention span, resulting in the loss of the reward feeling that's obtained after performing these uncontrollable obsessions. [2]  Cognitive self-consciousness, defined as the tendency to be alert of one's thoughts and mental processes, is found to be elevated in individuals with OCD. [4]  This has been found to be linked to the recurrent symptoms associated with this disorder. Individuals tend to place greater importance to their thoughts and this affects their capacity to adapt in the society. It has also been found to be involved in the decline of non-verbal memory performance and problem solving skills. [4]  Visuo-spatial abilities, executive functioning and motor speed are also some of the cognitive deficits experienced by individuals with OCD.

**Recurrent Behaviours**
The repetitiveness of certain forms of behaviour result when normally occurring thoughts are mis-intrepreted based on the individual's flawed judgement. These symptoms affect all aspects of one's life. Individuals with OCD lack effective learning strategies which result in poor planning and organizational skills. [5]  Common examples of such behaviour include: obsessions with contamination, ordering behaviour, saving obsessions, religious obsessions and etc. [2] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">These recurrent behaviours play a role in the individuals' social interactions and relationships with others. [6] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Even though, the individual may be aware of their symptoms, they are still unable to let go of these persistent thoughts. [2] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> They feel the urge to complete the task to avoid feeling guilt or to avoid the fear of the consequences they may face if task was not completed in a specific way. [2] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> In some severe cases, individuals may spend hours in their obsessive practices and thoughts. [2] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Children diagnosed with OCD are found to only carry compulsions at first; examples include: blinking and breathing routines. [3]

=**Neuroanatomical Aspect**=

**Variations in cortical thickness of temporal gyrus and posterior insular cortex**
<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">There are significant differences in the cortical thickness of the different regions of brain.For example, the reduction in the thickness around the parietal gyri is found to mediate the expression of the "cleaning" symptoms in individuals who have a strong fear towards germs. Some studies have shown the inferior frontal cortex and posterior middle temporal gyrus to be thicker which in turn promotes inhibiton deficits in OCD individuals. Other regions with thinner<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> cortical lining include: the left inferior frontal, left middle frontal, left precentral, left parahippocampal and left orbitofrontal cortices. [8] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Neuronal density and cortical thickness influence each other, especially with myelination, glial cells and vascular factors. [8] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> The cortical thickness also plays a role in the neuronal signaling and transmission. There have also been reports of gray matter volume abnormalities in individuals with OCD. There is less regional gray matter volume mainly in the regions of the medial prefrontal cortex in people with OCD. [1] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Reduction in the gray matter in the orbitofrontal cortex and anterior cingulate cortex has been shown to change the individual's emotional behaviour and ex perience. [2] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> This explains why OCD individuals experience abnormal fears to certain external stimuli. On the other hand, studies show that OCD individuals have an increased amount of gray matter in the ventral putamen and anterior cerebellum. [8]

<span style="display: block; font-family: 'Times New Roman','serif'; font-size: 14.6667px; text-align: center;"> <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> **Neurotransmission within cortical striatal-thalamocortical circuitry**

<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"><span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"><span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">The cortico-striatal thalamocortical network is seen to play a significant role in the prevention of inner impulses, most frequently experienced by individuals with OCD. The increased stability of these neuronal networks found within the cortices displays the inability of individuals with OCD to move out of one motor pattern (behaviour). [2] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> This explains their inability to stop their repetitive behaviour. This abnormal firing of the neurons could be found in the orbitofrontal Cortex, anterior cingulate cortex, dorso-lateral and medial prefrontal cortex and in the caudate nucleus. [5] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"><span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Also, the involvement of the medial prefrontal cortex is significant in OCD cases. This region of the brain is known to inhibit conditioned fear responses and there is a lack of this inhibition in the individuals diagnosed with this disorder. [1] This is explained by the reduced level of connectivity between the brain areas. The lack of inhibition can again be related to the continuous repetition of specific motor behaviours, indicating brain dysfunction. Impairment in the function of the striatum leads to these intrusive thoughts not being readily suppressed, resulting in such recurrent behaviours. [9]

=**Neurochemical Aspect**=

**<span style="font-family: 'Times New Roman','serif'; font-size: 14px;">Dopamine Signaling Pathway **
<span style="display: block; font-family: 'Times New Roman','serif'; font-size: 14.6667px; text-align: center;"> <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Increased levels of dopamine in the synapses have been linked to the repetitive movements found in animals, specifically rats, and this has been related to OCD symptoms. Rats are a good model to differentiate between different brain regions and for detecting activation of these areas prior to performing a compulsion. Rats were found to exhibit compulsive lever-pressing following lesions to the orbito-frontal cortex which results in the decrease of dopamine in the caudate putamen. High extracellular dopamine levels in the nucleus accumbens are also the result after the desensitization of the D2 auto-receptor for dopamine. [10] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> This desensitization leads to a lower inhibition of dopamine release and a decrease in the firing of the dopamine neurons. [11] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">Results obtained from various studies indicate that compulsive behaviours primarily depend on the dorsal but not ventral striatum. [11] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> These brain regions of the rats correspond to the human brain as well.

**<span style="font-family: 'Times New Roman','serif'; font-size: 14px;">Serotonin Levels **
<span style="font-family: 'Times New Roman',Times,serif; font-size: 14.6667px;">Serotonin levels are found to be low in the synapses of individuals diagnosed with OCD. ** [11] ** There is evidence of a lower number of serotonin-binding receptors (5HT2a) which in turn causes decreased levels of serotonin in the orbitofrontal and prefrontal cortex. ** [1] ** These levels are examined via positron emission tomography (PET) or single-photon emission computed tomography (SPECT) studies. The decrease in the serotonin receptors explains why individuals with OCD lose their sensorimotor coordination.** [12] ** Dysfunctional serotonin levels can also be associated with the negative mood some individuals face with respect to their hypothalmic-pituitary-adrenal (HPA) axis. This negative mood arises because individuals aren't able to deal with the environmental stressors that they may experience in an adaptive manner.

**<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">Brain-derived neurotrophic factor plasma levels **
<span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">Brain derived neurotrophic factors (BDNF) are important in the neural development of the brain. They are classified as a member of the neurotrophin superfamily of growth factors, assisting with the growth and stability of the adult brain. It is known to promote neuronal survival, neurogenesis, and synaptic plasticity in humans. Various studies have been performed regarding BDNF levels and OCD but results remain inconsistent. In most cases, BDNF levels were found to be lower in OCD; regardless of drug treatment in comparison to healthy individuals. [14] The BDNF gene has been shown to have strong linkage to to neurotransmitter systems and the synthesis of specific neurotransmitters. These neurotransmitters, in turn, assist with emotional decision-making, learning and memory as well as other higher cognitive processes. [15] Examples of these neurotransmitters include: serotonin, glutamate, and dopamine. [14] Specific coding mutation in the Val66 gene has been associated with OCD. This Met allele of the Val66 gene displays dysfunction in the amygdala activation of fear responses and poor performance on executive functions. [15] Studies indicate that the Met allele in OCD is linked to decreased volumes of the dorso-lateral prefrontral cortex and subcortical regions like the caudate nucleus. [15] This shows why individuals with OCD have poor plannning skills. BDNF is considered a peripheral marker of neurotrophic impairment in OCD and has been associated with other mental illnesses too. [14]

=**Genetics**=

**<span style="font-family: 'Times New Roman','serif'; font-size: 14px;">TNF-alpha gene polymorphisms **
<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">Although not much is known about the genetics with regard to OCD, recent research has shown some linkage to specific genes and OCD in individuals. Polymorphisms in the promoter region of the cytokine tumour necrosis factor-alpha (TNFA) gene was found to be associated with OCD symptoms. TNFA is a pro-inflammatory cytokine and plays a significant role in the brain vasculature and glial cells, resulting in the production and release of secondary messengers. ** [16] **<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Changes in the behaviour of OCD individuals have been related to the levels of the TNFA in the central nervous system and these cytokines are known to cross the blood-brain barrier, passively and actively. ** [16] **<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Cytokines are important in neurochemical changes like the metabolism of serotonin, norephinephrine, and dopamine. ** [16] **<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> There is still the need for research in the mechanisms involved with the TNFA gene (intracellular pathways, apoptotic and oxidative mechanisms) and how it relates to the neuropsychological symptoms encountered by OCD individuals. = = =**Prevention**=

**<span style="font-family: 'Times New Roman','serif'; font-size: 14px;">Cognitive Behavioural Therapy (CBT) **
<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"><span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">Cognitive Behavioural Therapy (CBT) primarily focuses on correcting one's cognitive abnormalities and weakening their natural impulses to participate in anxiety-reducing practices. ** [6] **<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> It is seen as one of the first line treatments for OCD. This form of treatment is more psychologically based and no medication is used. It involves the individual re-evaluating their socially unacceptable behaviour and the consequences that may arise from it. These prevention programs must be continuously reinforced on a weekly basis for a specific period of time (usually 20 weeks) for it to have an effective impact on the individual with OCD. ** [6] **<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> There has been some evidence of metabolic changes in the striatum, thalamus and anterior cingulate cortex following CBT. Initially, in OCD cases, individuals are found with abnormal levels of neurometabolites like the levels of glumatergic proteins. CBT is also found to reduce NMDA activity levels and prevent long-term potentiation (LTP); this inhibits the establishment of dysfunctional neuronal links and decreases OCD symptom severity. ** [17] **<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> Following therapy, it has been reported that individuals are not as troubled by these thoughts and recurrent behaviour. The intensity of this treatment tends to vary based on the degree of OCD in the individual and its cormobidity with other mental illnesses. ** [3] **

**<span style="font-family: 'Times New Roman','serif'; font-size: 14px;">Pharmacotherapy-Selective Serotonin Reuptake Inhibitors **
<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">

<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">Serotonin neurotransmission via selective serotonin reuptake inhibitors (SSRIs) is found to play a role in the neuroplasticity of several cortical and subcortical brain structures as well as modulating the brain volume.** [1] ** SSRIs work by preventing the reuptake of serotonin in the synapes, causing a significant amount of serotonin to remain in the synaptic clefts. OCD individuals are found to have hyperactive 5HT serotonin receptors which prevents serotonin from remaining in the synapses. In OCD cases, the SSRIs play a role in emotional processing by elevating the individual's negative mood causing them to disengage from their dysfunctional thinking patterns and behaviour. [19] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> This in turn, alters their cognitive functions and allows them to engage more effectively in societal norms. SSRIs are known to slowly minimize the OCD symptoms in individuals through the elimination of depressive mood experienced by OCD individuals. Examples of SRIs include: clomipramine (CMI), fluoxetine (FLX), and paroxetine (PAR). [3]

**<span style="font-family: 'Times New Roman','serif'; font-size: 14px;">Psychotherapy-Exposure-Response Treatment **
<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">Exposure-Response Prevention (ERP) treatment is when the patient is faced with their feared stimuli in response to not performing their ritualistic behaviour. For example, an individual who has a fear of germs and is found to constantly be washing their hands will be exposed to sources of contamination for a prolonged time period. [3] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> This form of therapy has been found to be more effective on individuals with milder symptoms and typically carries on for about 15-20 weekly sessions or twice weekly sessions. [3] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> The harder the exposure is to an individual, the more time this treatment will take. Initially, the individual may face a significant amount of distress with first exposure and as therapy continues for several sessions, the level of distress decreases. 55% of patients who have completed 10-20 sessions of ERP therapy have reported a considerable amount of improvement. [3] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;">It has been reported that combined therapy or ERP with medication is found to hasten recovery. Also, ERP in a group setting was found to be effective as well especially in cases where hoarding is an issue. Studies have shown that individuals with sexual and/or religious obsessions are less responsive to this form of therapy. [3] <span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> If obsessions are intangible, it is more difficult to progress efficiently through this treatment since it involves the individual imagining the feared stimuli instead of being directly exposed to it.

<span style="font-family: 'Times New Roman','serif'; font-size: 14.6667px;"> References: