Obsessive-compulsive disorder

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| ICD9 = | ICDO = | OMIM = | MedlinePlus = | eMedicineSubj = med | eMedicineTopic = 1654 | MeshID = D009771 |Obsessive-compulsive disorder (OCD) is a psychiatric anxiety disorder most commonly characterized by a subject's obsessive, distressing, intrusive thoughts and related compulsions (tasks or "rituals") which attempt to neutralize the obsessions.The phrase "obsessive-compulsive" has worked its way into the wider English lexicon, and is often used in an offhand manner to describe someone who is meticulous or absorbed in a cause (see also "anal-retentive"). Such casual references should not be confused with obsessive-compulsive disorder; see clinomorphism. It is also important to distinguish OCD from other types of anxiety, including the routine tension and stress that appear throughout life. Although these signs are often present in OCD, a person who shows signs of infatuation or fixation with a subject/object, or displays traits such as perfectionism, does not necessarily have OCD, a specific and well-defined condition.To be diagnosed with Obsessive-compulsive disorder, one must have either obsessions or compulsions alone, or obsessions and compulsions, according to the DSM-IV-TR diagnostic criteria. The Quick Reference to the diagnostic criteria from DSM-IV-TR (2000) describes these obsessions and compulsions:Quick Reference to the Diagnostic Criteria from DSM-IV-TR. Arlington, VA: American Psychiatric Association, 2000.Obsessions are defined by:
    # Recurrent and persistent thoughts, impulses, or images that are experienced at some time during the disturbance, as intrusive and inappropriate and that cause marked anxiety or distress. # The thoughts, impulses, or images are not simply excessive worries about real-life problems. # The person attempts to ignore or suppress such thoughts, impulses, or images, or to neutralize them with some other thought or action. # The person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind, and are not based in reality.
Compulsions are defined by:
    # Repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly. # The behaviors or mental acts are aimed at preventing or reducing distress or preventing some dreaded event or situation; however, these behaviors or mental acts either are not connected in a realistic way with what they are designed to neutralize or prevent or are clearly excessive.
In addition to these criteria, at some point during the course of the disorder, the sufferer must realize that his/her obsessions or compulsions are unreasonable or excessive. Moreover, the obsessions or compulsions must be time-consuming (taking up more than one hour per day), cause distress, or cause impairment in social, occupational, or school functioning. OCD often causes feelings similar to those of depression.

Causes and related disorders

It was the general belief in 14th, 15th, and 16th century Europe that those who experienced blasphemous, sexual, or other obsessive thoughts were possessed by the Devil. Based on this reasoning, treatment involved banishing the "evil" from the "possessed" person through exorcism.Baer, L.; M. A. Jenike & W. E. Minichiello. Obsessive Compulsive Disorders: Theory and Management. Littleton, MA: PSG Publishing, 1986.Today the community of scientists studying obsessive-compulsive disorder has been split into two factions by a disagreement over the exact cause of the illness. On one side is a group who believe that obsessive-compulsive behavior is a psychological disorder. On the other side are scientists who believe that obsessive-compulsive behavior is caused by abnormalities in the brain. A majority of researchers now believe in this biological hypothesis of OCD.Stanford University School of Medicine OCD web page states that "although the causes of the disorder still elude us, the recent identification of children with OCD caused by an autoimmune response to Group A streptococcal infection promises to bring increased understanding of the disorder's pathogenesis."

Psychological explanations

Freud

In the early 1910s, Sigmund Freud attributed obsessive-compulsive behavior to unconscious conflicts which manifested as symptoms. Freud describes the clinical history of a typical case of 'touching phobia' as follows: p. 29.

Biological explanations

There are many different theories about the cause of obsessive-compulsive disorder. The majority of researchers believe that there is some type of abnormality in the neurotransmitter serotonin, among other possible psychological or biological abnormalities; however, it is possible that this activity is the brain's response to OCD, and not its cause. Serotonin is thought to have a role in regulating anxiety, though it is also thought to be involved in such processes as sleep and memory function. This neurotransmitter travels from one nerve cell to the next via synapses. In order to send chemical messages, serotonin must bind to the receptor sites located on the neighboring nerve cell. It is hypothesized that OCD sufferers may have blocked or damaged receptor sites that prevent serotonin from functioning to its full potential. This suggestion is supported by the fact that many OCD patients benefit from the use of selective serotonin reuptake inhibitors (SSRIs) — a class of antidepressant medications that allow for more serotonin to be readily available to other nerve cells.BBC Science and Nature: Human Body and Mind. Causes of OCD. . Accessed April 15, 2006. For more about this class of drugs, see the section about potential treatments for OCD.Recent research has revealed a possible genetic mutation that could be the cause of OCD. Researchers funded by the National Institutes of Health have found a mutation in the human serotonin transporter gene, hSERT, in unrelated families with OCD. Moreover, in his study of identical twins, Rasmussen (1994) produced data that supported the idea that there is a "heritable factor for neurotic anxiety".Rasmussen, S.A. "Genetic Studies of Obsessive Compulsive Disorder" in Current Insights in Obsessive Compulsive Disorder, eds. E. Hollander; J. Zohar; D. Marazziti & B. Oliver. Chichester, England: John Wiley & Sons, 1994, pp. 105-114. In addition, he noted that environmental factors also play a role in how these anxiety symptoms are expressed. However, various studies on this topic are still being conducted and the presence of a genetic link is not yet definitely established.Another possible genetic cause of OCD was discovered in August 2007 by scientists at Duke University Medical Center in North Carolina. They genetically engineered mice that lacked a gene called SAPAP3. This protein is highly expressed in the striatum, an area of the brain linked to planning and the initiation of appropriate actions. The mice spent three times as much time grooming themselves as ordinary mice, to the point that their fur fell off.Missing gene creates obsessive-compulsive mouse, New Scientist August 2007Technological advancements have allowed for the possibility of brain imaging. Using tools like positron emission tomography (PET scans), it has been shown that those with OCD tend to have brain activity that differs from those who do not have this disorder.Tennen, M. 2005, June. "Causes of OCD Remain a Mystery". . Accessed April 14, 2006. This suggests that brain functioning in those with OCD may be impaired in some way. A popular explanation for OCD is that offered in the book Brain Lock by Jeffrey Schwartz, which suggests that OCD is caused by the part of the brain that is responsible for translating complex intentions (e.g., "I will pick up this cup") into fundamental actions (e.g., "move arm forward, rotate hand 15 degrees, etc.") failing to correctly communicate the chemical message that an action has been completed. This is perceived as a feeling of doubt and incompleteness which then leads the individual to attempt to consciously deconstruct their own prior behavior — a process which induces anxiety in most people, even those without OCD.It has been theorized that a miscommunication between the orbital-frontal cortex, the caudate nucleus, and the thalamus may be a factor in the explanation of OCD. The orbitofrontal cortex (OFC) is the first part of the brain to notice whether or not something is wrong. When the OFC notices that something is wrong, it sends an initial “worry signal” to the thalamus. When the thalamus receives this signal, it in turn sends signals back to the OFC to interpret the worrying event. The caudate nucleus lies between the OFC and the thalamus and it prevents the initial worry signal from being sent back to the thalamus after it has already been received. However, it is suggested that in those with OCD, the caudate nucleus does not function properly, and therefore does not prevent this initial signal from recurring. This causes the thalamus to become hyperactive and creates a virtually never-ending loop of worry signals being sent back and forth between the OFC and the thalamus. The OFC responds by increasing anxiety and engaging in compulsive behaviors in an attempt to relieve this apprehension. This over activity of the OFC is shown to be attenuated in patients who have successfully responded to SSRI medication. The increased stimulation of the serotonin receptors 5-HT2A and 5-HT2C in the OFC is believed to cause this inhibition. [http://neuro.psychiatryonline.org/cgi/content/full/14/1/88]Some research has discovered an association between a type of size abnormality in different brain structures and the predisposition to develop OCD. Through the use of magnetic resonance imaging (MRI), researchers at Cambridge's Brain Mapping Unit were able to discover distinctive patterns in the brain structure of individuals with OCD and their close family members. [http://www.admin.cam.ac.uk/news/dp/2007112601] This is the first instance in which it has been demonstrated that those with a familial risk of developing OCD have anatomical differences when compared with ordinary individuals. The discovery of these structural differences in the area of the brain associated with stopping motor response may ultimately aid researchers who seek to determine which genes contribute to the development of OCD. In the future it might also provide more objective criteria for diagnosing the disorder.

Symptoms and prevalence

OCD is manifested in a variety of forms.Community studies have placed the prevalence between one and three percent, although the prevalence of clinically recognized OCD is much lower, suggesting that many individuals with the disorder are unaccounted for clinically. The fact that many individuals do not seek treatment may be due in part to stigma associated with OCD. Another reason for not seeking treatment is because many sufferers of OCD do not realize that what they are suffering from is OCD, mainly because the typical depiction of the disorder in the media and elsewhere only covers a few of the many symptoms of OCD.The typical OCD sufferer performs tasks (or compulsions) to seek relief from obsession-related anxiety. To others, these tasks may appear odd and unnecessary. But for the sufferer, such tasks can feel critically important, and must be performed in particular ways to ward off dire consequences and to stop the stress from building up. Examples of these tasks: repeatedly checking that one's parked car has been locked before leaving it; turning lights on and off a set number of times before exiting a room; repeatedly washing hands at regular intervals throughout the day.Symptoms may include some, all, or perhaps none of the following:
  • Repeated hand washing.
  • Repeated clearing of the throat, although nothing may need to be cleared.
  • Specific counting systems — e.g., counting in groups of four, arranging objects in groups of three, grouping objects in odd/even numbered groups, etc.
  • One serious symptom which stems from this is "counting" steps — e.g., feeling the necessity to take 12 steps to the car in the morning.
  • Perfectly aligning objects at complete, absolute right angles, or aligning objects perfectly parallel etc. This symptom is shared with OCPD and can be confused with this condition unless it is realized that in OCPD it is not stress-related.
  • Fear of acting out on violent or aggressive impulses, or feeling overly responsible for the safety of others.
  • Sexual obsessions or unwanted sexual thoughts. Two classic examples are fear of being homosexual or fear of being a pedophile. In both cases, sufferers will obsess over whether or not they are genuinely aroused by the thoughts.
  • Strange and chronic worries about certain events such as sleeping, eating, leaving home, etc without proper items. An example would be one who literally can't fall asleep without a metronome.
  • Having to "cancel out" bad thoughts with good thoughts. An example of this would be imagining harming a child and having to imagine a child playing happily to cancel it out.
  • A fear of contamination (see Mysophobia); some sufferers may fear the presence of human body secretions such as saliva, blood, sweat, tears, vomit, or mucus, or excretions such as urine or feces. Some OCD sufferers even fear that the soap they're using is contaminated.
  • A need for both sides of the body to feel even. A person with OCD might walk down a sidewalk and step on a crack with the ball of their left foot, then feel the need to step on another crack with the ball of their right foot. If one hand gets wet, the sufferer may feel very uncomfortable if the other is not. If the sufferer is walking and bumps into something, he/she may hit the object or person back to feel a sense of evenness. These symptoms are also experienced in a reversed manner. Some sufferers would rather things to be uneven, favoring the preferred side of the body.
  • An obsession with numbers (be it in math class, watching TV, or in a room). Some people are obsessed with even numbers and loathe odd numbers (odd numbers cause them a great deal of anxiety and often make the person uncomfortable or even angry) or vice versa.
  • Twisting the head on a toy around, then twisting it all the way back exactly in the opposite direction (see even body section).
  • Fear of transformation. A fear of transforming into someone or something else. Losing ones self or taking on undesired characteristics is what creates the anxiety and fear. Rituals such as counting, blinking, checking, hand washing etc. may eliminate the anxiety when they are done in a way which "feels right" to the sufferer.
  • In some cases, a pattern of uniformity on a bank account may indicate obsessive-compulsive spending. For example, an OCD-affected figure skater may issue a check to his/her coach for a private lesson every week, paying the same amount each time. In addition, the affected person may feel complacent about or invincible against the economic issues.
    • There are many other possible symptoms, and one need not display those above to suffer from OCD. Formal diagnosis is performed by a mental health professional. Furthermore, possessing the symptoms above is not an absolute diagnosis of OCD.OCD sufferers are aware that such thoughts and behavior are not rational, but feel bound to comply with them to fend off feelings of panic or dread. Because sufferers are consciously aware of this irrationality but feel helpless to push it away, untreated OCD is often regarded as one of the most vexing and frustrating of the major anxiety disorders.In an attempt to further relate the immense distress that those afflicted with this condition must bear, Barlow and Durand (2006) use the following example.Barlow, D. H. and V. M. Durand. Essentials of Abnormal Psychology. California: Thomson Wadsworth, 2006. They implore readers not to think of pink elephants. Their point lies in the assumption that most people will immediately create an image of a pink elephant in their minds, even though told not to do so. The more one attempts to stop thinking of these colorful animals, the more one will continue to generate these mental images. This phenomenon is termed the "Thought Avoidance Paradox”, and it plagues those with OCD on a daily basis, for no matter how hard one tries to get these disturbing images and thoughts out of one's mind, feelings of distress and anxiety inevitably prevail. Although everyone may experience unpleasant thoughts at one time or another, these are usually warranted concerns that are short-lived and fade after an adequate time period has lapsed. However, this is not the case for OCD sufferers.Carter, K. "Obsessive-Compulsive Disorder." PSYC 210 lecture: Oxford College of Emory University. Oxford, GA. 14 Feb. 2006.Obsessive-compulsive disorder is often confused with the separate condition obsessive compulsive personality disorder. The two are not the same condition, however. OCD is ego dystonic, meaning that the disorder is incompatible with the sufferer's self-concept. Because disorders that are ego dystonic go against an individual's perception of his/herself, they tend to cause much distress. OCPD, on the other hand, is ego syntonic—marked by the individual's acceptance that the characteristics displayed as a result of this disorder are compatible with his/her self-image. Ego syntonic disorders understandably cause no distress. Persons suffering from OCD are often aware that their behavior is not rational and are unhappy about their obsessions but nevertheless feel compelled by them. Persons with OCPD, by contrast, are not aware of anything abnormal about themselves; they will readily explain why their actions are rational, and it is usually impossible to convince them otherwise. Persons with OCD are ridden with anxiety; persons who suffer from OCPD, by contrast, tend to derive pleasure from their obsessions or compulsions.Carter, K. "Obsessive-Compulsive Personality Disorder." PSYC 210 lecture: Oxford College of Emory University. Oxford, GA. 11 April 2006. This is a significant difference between these disorders.Equally frequently, these rationalizations do not apply to the overall behavior, but to each instance individually; for example, a person compulsively checking their front door may argue that the time taken and stress caused by one more check of the front door is considerably less than the time and stress associated with being robbed, and thus the check is the better option. In practice, after that check, the individual is still not sure, and it is still better in terms of time and stress to do one more check, and this reasoning can continue as long as necessary.Some OCD sufferers exhibit what is known as overvalued ideas. In such cases, the person with OCD will truly be uncertain whether the fears that cause them to perform their compulsions are irrational or not. After some discussion, it is possible to convince the individual that their fears may be unfounded. It may be more difficult to do ERP therapy on such patients, because they may be, at least initially, unwilling to cooperate. For this reason OCD has often been likened to a disease of pathological doubt, in which the sufferer, while not usually delusional, is often unable to fully realize what sorts of dreaded events are reasonably possible and which aren't.OCD is different from behaviors such as gambling addiction and overeating. People with these disorders typically experience at least some pleasure from their activity; OCD sufferers do not actively want to perform their compulsive tasks, and experience no pleasure from doing so.OCD is placed in the anxiety class of mental illness, but like many chronic stress disorders it can lead to clinical depression over time. The constant stress of the condition can cause sufferers to develop a deadening of spirit, a numbing frustration, or sense of hopelessness. OCD's effects on day-to-day life—particularly its substantial consumption of time—can produce difficulties with work, finances and relationships.There is no known cure for OCD as of yet, but there are a number of successful treatment options available.

    Related disorders

    People with OCD may be diagnosed with other conditions, such as anorexia nervosa, social anxiety disorder, bulimia nervosa, Tourette syndrome, compulsive skin picking, body dysmorphic disorder, and trichotillomania. There is some research demonstrating a link between drug addiction and obsessive compulsive disorder as well. Many who suffer from OCD suffer from panic attacks. There is a higher risk of drug addiction among those with any anxiety disorder (possibly as a way of coping with the heightened levels of anxiety), but drug addiction among obsessive compulsive patients may serve as a type of compulsive behavior and not just as a coping mechanism. Depression is also extremely prevalent among sufferers of OCD. One explanation for the high depression rate among OCD populations was posited by Mineka, Watson, and Clark (1998), who explained that people with OCD (or any other anxiety disorder) may feel depressed because of an "out of control" type of feeling.Some cases are thought to be caused at least in part by childhood streptococcal infections and are termed PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The streptococcal antibodies become involved in an autoimmune process. Though this idea is not set in stone, if it does prove to be true, there is cause to believe that OCD can to some very small extent be "caught" via exposure to strep throat (just as one may catch a cold). However, if OCD is caused by bacteria, this provides hope that antibiotics may eventually be used to treat or prevent it.

    Demographics and other statistics

    In a 1980 study of 20,000 adults from New Haven, Baltimore, St. Louis, Durham, and Los Angeles, the lifetime prevalence rate of OCD for both sexes was recorded at 2.5%.Education also appears to be a factor. The lifetime prevalence of OCD is lower for those who have graduated high school than for those who have not (1.9 percent versus 3.4 percent). However, in the case of college education, lifetime prevalence is higher for those who graduate with a degree (3.1 percent) than it is for those who have only some college background (2.4 percent). As far as age is concerned, the onset of OCD usually ranges from the late teenage years until the mid-20s in both sexes, but the age of onset tends to be slightly younger in males than in females.Antony, M. M.; F. Downie & R. P. Swinson. "Diagnostic Issues and Epidemiology in Obsessive-Compulsive Disorder". in Obsessive-Compulsive Disorder: Theory, Research, and Treatment, eds. M. M. Antony; S. Rachman; M. A. Richter & R. P. Swinson. New York: The Guilford Press, 1998, pp. 3-32. Violence is very rare among OCD sufferers, but the disorder is often debilitating to their quality of life. Also, the psychological self-awareness of the irrationality of the disorder can be painful. For people with severe OCD, it may take several hours a day to carry out the compulsive acts. To avoid perceived obsession triggers, they also often avoid certain situations or places altogether.It has been alleged that sufferers are generally of above-average intelligence, as the very nature of the disorder necessitates complicated thinking patterns.

    Treatment

    According to the Expert Consensus Guidelines for the Treatment of obsessive-compulsive disorder, behavioral therapy (BT), cognitive therapy (CT), medications, or any combination of the three, are first-line treatments for OCD. Psychodynamic psychotherapy may help in managing some aspects of the disorder, but there are no controlled studies that demonstrate effectiveness of psychoanalysis or dynamic psychotherapy in OCD.Koran LM, Hanna GL, Hollander E, Nestadt G, Simpson HB; American Psychiatric Association. Am J Psychiatry 2007; 164(7 Suppl): 5-53. PMID 17849776.The specific technique used in BT/CBT is called exposure and ritual prevention (also known as exposure and response prevention) or ERP; this involves gradually learning to tolerate the anxiety associated with not performing the ritual behavior. At first, for example, someone might touch something only very mildly "contaminated" (such as a tissue that has been touched by another tissue that has been touched by the end of a toothpick that has touched a book that came from a "contaminated" location, such as a school.) That is the "exposure." The "ritual prevention" is not washing. Another example might be leaving the house and checking the lock only once (exposure) without going back and checking again (ritual prevention). The person fairly quickly habituates to the (formerly) anxiety-producing situation and discovers that their anxiety level has dropped considerably; they can then progress to touching something more "contaminated" or not checking the lock at all—again, without performing the ritual behavior of washing or checking.Medications as treatment include selective serotonin reuptake inhibitors (SSRIs) such as paroxetine (Seroxat, Paxil), sertraline (Zoloft), fluoxetine (Prozac), and fluvoxamine (Luvox) as well as the tricyclic antidepressants, in particular clomipramine (Anafranil). SSRIs prevent excess serotonin from being pumped back into the original neuron that released it. Instead, the serotonin can then bind to the receptor sites of nearby neurons and send chemical messages or signals that can help regulate the excessive anxiety and obsessive-compulsive thoughts. In some treatment resistant cases, a combination of clomipramine and an SSRI has shown to be effective even when neither drug on its own has been efficacious. Serotonergic antidepressants typically take longer to show benefit in OCD than with most other disorders which they are used to treat, as it is common for 2–3 months to elapse before any tangible improvement is noticed. In addition to this, the treatment usually requires high doses. Fluoxetine for example is usually prescribed in doses of 20 mg per day for clinical depression, whereas with OCD the dose will often range from 20 mg to 80 mg or higher, if necessary. In most cases antidepressant therapy alone will only provide a partial reduction in symptoms, even in cases that are not deemed treatment resistant. Other medications such as riluzole, memantine, gabapentin (Neurontin), lamotrigine (Lamictal), and low doses of the newer atypical antipsychotics olanzapine (Zyprexa), quetiapine (Seroquel) and risperidone (Risperdal) have also been found to be useful as adjuncts in the treatment of OCD. The use of antipsychotics in OCD must be undertaken carefully however, since although there is very strong evidence that at low doses they are beneficial (most likely due to their dopamine receptor antagonism), at high doses these same antipsychotics have proven to cause dramatic obsessive-compulsive symptoms even in those who don't normally have OCD. This is most likely due to the antagonism of 5-HT2A receptors becoming very prominent at these doses and outweighing the benefits of dopamine antagonsim. Another point that must be noted with antipsychotic treatment is that SSRIs inhibit the chief enzyme that is responsible for metabolising antipsychotics — CYP2D6 — so the dose will be effectively higher than expected when these are combined with SSRIs.The naturally occurring sugar inositol may be an effective treatment for OCD. Inositol appears to modulate the actions of serotonin and has been found to reverse desensitisation of the neurotransmitter's receptors.St John's Wort has been claimed to be of benefit due to its (non-selective) serotonin re-uptake inhibiting qualities, and a small number of anecdotal cases have emerged that have shown positive results. However there is so far little scientific evidence to support these claims.Recent research has found increasing evidence that opioids may significantly reduce OCD symptoms, though the addictive property of these drugs likely stands as an obstacle to their sanctioned approval for OCD treatment. Anecdotal reports suggest that some OCD sufferers have successfully self-medicated with opioids such as Ultram and Vicodin, though the off-label use of such painkillers is not widely accepted, again because of their addictive qualities. Tramadol is an atypical opioid that may be a viable option as it has a low potential for abuse and addiction, mild side effects, and shows signs of rapid efficacy in OCD. Tramadol not only provides the anti-OCD effects of an opiate, but also inhibits the re-uptake of serotonin (in addition to norepinephrine). This may provide additional benefits, but should not be taken in combination with antidepressant medication unless under careful medical supervision due to potential serotonin syndrome.Studies have also been done that show nutrition deficiencies may also contribute to OCD and other mental disorders. Certain vitamin and mineral supplements may aid in such disorders and provide the nutrients necessary for proper mental functioning. Research has generally shown that psychotherapy in combination with psychotropic medication is more effective than either option alone.For some, neither medication, support groups nor psychological treatments are helpful in alleviating obsessive-compulsive symptoms. These patients may choose to undergo psychosurgery as a last resort. In this procedure, a surgical lesion is made in an area of the brain (the cingulate bundle). In one study, 30% of participants benefited significantly from this procedure. Deep brain stimulation and vagus nerve stimulation are possible surgical options which do not require the destruction of brain tissue, although their efficacy has not been conclusively demonstrated.Recent studies at the University of Arizona using the tryptamine alkaloid psilocybin have shown promising results. There are reports that other hallucinogens such as LSD and peyote have produced similar benefits. It has been hypothesised that this effect may be due to stimulation of 5-HT2A receptors and less importantly, 5-HT2C receptors. This causes, among many other effects, an inhibitory effect on the orbito-frontal cortex, an area of the brain in which hyperactivity has been strongly associated with OCD.Emerging evidence has suggested that regular nicotine treatment may be helpful in improving symptoms of obsessive-compulsive disorder, although the pharmacodynamical mechanism by which this improvement is achieved is not yet known, and more detailed studies are needed to fully confirm this hypothesis. It should also be noted that there are anecdotal reports of OCD worsening when cigarettes are smoked.

    Neuropsychiatry

    OCD primarily involves the brain regions of the striatum, the orbitofrontal cortex and the cingulate cortex. OCD involves several different receptors, mostly H2, M4, nk1, NMDA, and non-NMDA glutamate receptors. The receptors 5-HT1D, 5-HT2C, and the μ opioid receptor exert a secondary effect. The H2, M4, nk1, and non-NMDA glutamate receptors are active in the striatum, whereas the NMDA receptors are active in the cingulate cortex.The activity of certain receptors is positively correlated to the severity of OCD, whereas the activity of certain other receptors is negatively correlated to the severity of OCD. Those correlations are as follows:Activity positively correlated to severity:
  • H2
  • M4
  • nk1
  • non-NMDA glutamate receptors
    • Activity negatively correlated to severity:
  • NMDA
  • μ opioid
  • 5-HT1D
  • 5-HT2C
    • The central dysfunction of OCD may involve the receptors nk1, non-NMDA glutamate receptors, and NMDA, whereas the other receptors could simply exert secondary modulatory effects.Pharmaceuticals that act directly on those core mechanisms are aprepitant (nk1 antagonist), riluzole (glutamate release inhibitor), and tautomycin (NMDA receptor sensitizer). Also, the anti-Alzheimer's drug memantine is being studied by the OC Foundation in its efficacy in reducing OCD symptoms due to it being a NMDA antagonist. One case study published in The American Journal of Psychiatry suggests that "memantine may be an option for treatment-resistant OCD, but controlled studies are needed to substantiate this observation." The drugs that are popularly used to fight OCD lack full efficacy because they do not act upon what are believed to be the core mechanisms. .

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