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== Overview ==
==Overview==


Different biological and psychological explanations have been put forward to understand the pathophysiology of obsessive-compulsive disorder. It is generally agreed that neurotransmitters play an important role in the pathophysiology of obsessive–compulsive disorder.
Different [[biological]] and [[psychological]] explanations have been put forward to understand the pathophysiology of obsessive-compulsive disorder. It is generally agreed that [[neurotransmitters]] play an important role in the pathophysiology of obsessive–compulsive disorder.


==Pathophysiology==
==Pathophysiology==
===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:


:{{cquote|After it has started, in early childhood, the patient shows a strong '''desire''' to touch, the aim of which is of a far more specialized kind that one would have been inclined to expect. This desire is promptly met with an '''external''' prohibition against carrying out that particular kind of touching. The prohibition is accepted, since it finds support from powerful '''internal''' forces, and proves stronger than the instinct which is seeking to express itself in the touching. In consequence, however, of the child's primitive physical constitution, the prohibition does not succeed in '''abolishing''' the instinct. Its only result is to '''repress''' the instinct (the desire to touch) and banish it into the unconscious. Both the prohibition and instinct persist: the instinct because it has only been repressed and not abolished, and the prohibition because, if it ceased, the instinct would force its way through into consciousness and into actual operation. A situation is created which remains undealt with—a psychical fixation—and everything else follows from the continuing conflict between the prohibition and the instinct.''<ref>{{cite book |last=Freud |first=Sigmund |authorlink=Sigmund Freud |others=trans. Strachey |title=Totem and Taboo:Some Points of Agreement between the Mental Lives of Savages and Neurotics |year=1950 |publisher=W. W. Norton & Company |location=New York |id=ISBN 0-393-00143-1 }} p. 29.</ref>}}
*Obsessive-compulsive disorder is thought to be caused by a variety of factors. Some forms of OCD appear to be [[familial]] and linked to other disorders such as [[tic disorders]], [[depression]], and [[obsessive compulsive personality disorder]], while others appear to be familial but unrelated to other disorders, and even others display no family background.<ref name="pmid7802125">{{cite journal| author=Pauls DL, Alsobrook JP, Goodman W, Rasmussen S, Leckman JF| title=A family study of obsessive-compulsive disorder. | journal=Am J Psychiatry | year= 1995 | volume= 152 | issue= 1 | pages= 76-84 | pmid=7802125 | doi=10.1176/ajp.152.1.76 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7802125  }} </ref><ref name="pmid14593431">{{cite journal| author=Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J et al.| title=Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype. | journal=Mol Psychiatry | year= 2003 | volume= 8 | issue= 11 | pages= 933-6 | pmid=14593431 | doi=10.1038/sj.mp.4001365 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14593431  }} </ref>
*A type of size abnormality has been discovered in various [[brain]] structures, according to some studies. The majority of researchers conclude that there is an abnormality in the neurotransmitter [[serotonin]], as well as other potential [[psychological]] or [[biological]] abnormalities; however, this activity may be the brain's reaction to OCD rather than its trigger.
*[[Serotonin]] is believed to play a role in [[anxiety]] regulation, as well as other processes including [[sleep]] and [[memory]]. [[Synapses]] enable this [[neurotransmitter]] to travel from one [[nerve cell]] to the next. [[Serotonin]] must bind to [[receptor]] sites on neighboring nerve cells in order to transmit chemical messages. It's thought that OCD patients' receptor sites are blocked or impaired, preventing serotonin from reaching its full potential. The fact that many OCD patients benefit from the use of [[selective serotonin reuptake inhibitors]] (SSRIs), a type of [[antidepressant]] medication that allows more serotonin to be readily available to other nerve cells, backs up this theory. (See the section on potential OCD treatments for more information on this class of drugs.)<ref name="bbc">BBC Science and Nature: Human Body and Mind. Causes of OCD. <http://www.bbc.co.uk/science/humanbody/mind/articles/disorders/causesofocd.shtml>. Accessed April 15, 2006.</ref>
*A possible [[genetic mutation]] that causes OCD has been discovered in recent research. In unrelated families with OCD, researchers funded by the [[National Institutes of Health]] discovered a mutation in the human serotonin transporter gene, [[hSERT]]. Furthermore, Rasmussen (1994) produced data in his study of identical twins that supported the idea of a "[[heritable]] factor for neurotic anxiety." He also mentioned that how these anxiety symptoms are expressed is influenced by environmental factors. However, various studies on this topic are still ongoing, and the existence of a [[Genetic linkage|genetic link]] has yet to be proven.<ref>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. </ref>
*In August 2007, scientists at [[Duke University Medical Center]] in North Carolina discovered another possible [[genetic]] cause of OCD. They created mice that were missing a gene called SAPAP3. This protein is abundant in the striatum, a brain region associated with planning and taking appropriate actions. The mice groomed themselves three times as much as normal mice, to the point where their fur fell off.<ref>[http://www.newscientist.com/channel/life/genetics/mg19526183.400-missing-gene-creates-obsessivecompulsive-mouse-.html Missing gene creates obsessive-compulsive mouse], New Scientist August 2007</ref>
*[[Brain imaging]] is now possible thanks to technological advancements. It has been demonstrated using tools such as [[positron emission tomography]] (PET scans) that people with OCD have brain activity that differs from people who do not have the disorder. This suggests that OCD sufferers' brain functioning may be hampered in some way. According to Jeffrey Schwartz's book Brain Lock, 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 coerced. This is experienced as a sense of doubt and incompleteness, prompting the individual to attempt to consciously deconstruct their previous behavior — a process that causes anxiety in most people, even those who do not have OCD.
*A miscommunication between the orbital-frontal cortex, the [[caudate nucleus]], and the [[thalamus]] has been proposed as a possible factor in the explanation of OCD. The [[orbitofrontal cortex]] (OFC) is the first part of the brain to notice if there is a problem. When the OFC detects a problem, it sends a preliminary "worry signal" to the thalamus. When the thalamus receives this signal, it transmits signals to the OFC, which the OFC interprets. Between the OFC and the thalamus is the caudate nucleus, which prevents the initial worry signal from being sent back to the thalamus after it has already been received. However, it is thought that in people with OCD, the caudate nucleus does not function properly, allowing the initial signal to reappear. The thalamus becomes [[hyperactive]] as a result, and a seemingly endless loop of worry signals is sent back and forth between the OFC and the thalamus. In an attempt to alleviate this apprehension, the OFC increases anxiety and engages in compulsive behaviors.[http://neuro.psychiatryonline.org/cgi/content/full/14/1/88]


===Biological explanations===
==Neuropsychiatry==
There are many different theories about the cause of obsessive-compulsive disorder. Some research has discovered a type of size abnormality in different brain structures. 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 [[synapse]]s. 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) &mdash; a class of [[antidepressant]] medications that allow for more serotonin to be readily available to other nerve cells.<ref name="bbc">BBC Science and Nature: Human Body and Mind. Causes of OCD. <http://www.bbc.co.uk/science/humanbody/mind/articles/disorders/causesofocd.shtml>. Accessed April 15, 2006.</ref> (For more about this class of drugs, see the [[OCD#Treatment|section about potential treatments]] for OCD.)
 
*The [[striatum]], [[orbitofrontal cortex]], and [[cingulate cortex]] are the brain regions most affected by OCD. Several receptors including [[glutamate receptors]] (NMDA and non-NMDA), the [[H2]], M4, nk1, are involved in OCD. A secondary effect is mediated by the [[5-HT1D receptor|5-HT1D]], [[5-HT2C receptor|5-HT2C]], and [[opioid receptors]]. The striatum is home to the H2, M4, nk1, and non-NMDA glutamate receptors, while the cingulate cortex is home to the NMDA receptors.
*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:
 
:*[[Histamine receptor|H2]]
:*[[Muscarinic acetylcholine receptor|M4]]
:*[[Tachykinin receptor|nk1]]
:*non-NMDA [[glutamate receptors]]
 
*Activity negatively correlated to severity:
 
:*[[NMDA receptor|NMDA]]
:*[[Mu opioid receptor|μ opioid]]
:*[[5-HT receptor|5-HT1D]]
:*[[5-HT receptor|5-HT2C]]
 
*The receptors nk1, non-NMDA glutamate receptors, and NMDA may be involved in the central dysfunction of OCD, whereas the other receptors may simply have secondary modulatory effects.
*[[Aprepitant]] (nk1 antagonist), [[riluzole]] (glutamate release inhibitor), and [[tautomycin]] are examples of pharmaceuticals that act directly on those core mechanisms (NMDA receptor sensitizer).
*The OC Foundation is also testing the anti-Alzheimer's drug [[memantine]], which is an NMDA antagonist, for its efficacy in reducing OCD symptoms. Memantine may be considered for treatment-resistant OCD, according to a case study published in The [[American Journal of Psychiatry]], but controlled studies are needed to support this assertion. Drugs used to treat the OCD are not fully efficacious as they are not thought to act on the core mechanisms responsible to cause OCD.<ref>{{cite journal |author=Poyurovsky M, Weizman R, Weizman A, Koran L |title=Memantine for treatment-resistant OCD |journal=The American journal of psychiatry |volume=162 |issue=11 |pages=2191-2 |year=2005 |pmid=16263867 |doi=10.1176/appi.ajp.162.11.2191-a |url=http://www.ajp.psychiatryonline.org/cgi/content/full/162/11/2191-a}}</ref>
 
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
==Pathophysiology==
===Physiology===
The normal physiology of [name of process] can be understood as follows:


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 "[[heredity|heritable]] factor for [[neurosis|neurotic]] anxiety".<ref>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. </ref> 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.
===Pathogenesis===


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.<ref>[http://www.newscientist.com/channel/life/genetics/mg19526183.400-missing-gene-creates-obsessivecompulsive-mouse-.html Missing gene creates obsessive-compulsive mouse], New Scientist August 2007</ref>
*The exact pathogenesis of [disease name] is not completely understood.


Technological 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.<ref>Tennen, M. 2005, June. "Causes of OCD Remain a Mystery". <http://www.healthatoz.com/ healthatoz/Atoz/dc/cen/ment/obcd/alert07172003.jsp>. Accessed April 14, 2006.</ref> 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 &mdash; a process which induces anxiety in most people, even those without OCD.
OR


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.<ref name="bbc" /> 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 receptor|5-HT2A]] and [[serotonin receptor|5-HT2C]] in the OFC is believed to cause this inhibition. [[http://neuro.psychiatryonline.org/cgi/content/full/14/1/88]]
*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
==Neuropsychiatry==
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OCD primarily involves the brain regions of the [[striatum]], the [[orbitofrontal cortex]] and the [[cingulate cortex]]. OCD involves several different [[receptor (biochemistry)|receptors]], mostly [[H2 receptor|H2]], [[muscarinic acetylcholine receptor|M4]], [[substance P|nk1]], [[NMDA receptor|NMDA]], and non-NMDA [[glutamate receptor]]s. The receptors [[5-HT receptor|5-HT1D]], [[5-HT receptor|5-HT2C]], and the [[opioid receptor|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.
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*The progression to [disease name] usually involves the [molecular pathway].
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
==Genetics==
[Disease name] is transmitted in [mode of genetic transmission] pattern.
 
OR
 
Genes involved in the pathogenesis of [disease name] include:
 
*[Gene1]
*[Gene2]
*[Gene3]
 
OR
 
The development of [disease name] is the result of multiple genetic mutations such as:
 
*[Mutation 1]
*[Mutation 2]
*[Mutation 3]
 
==Associated Conditions==
Conditions associated with [disease name] include:
 
*[Condition 1]
*[Condition 2]
*[Condition 3]
 
==Gross Pathology==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
 
==Microscopic Pathology==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
==Overview==
The exact pathogenesis of [disease name] is not fully understood.
 
OR
 
It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
 
OR
 
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
 
OR
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
 
OR
 
The progression to [disease name] usually involves the [molecular pathway].
 
OR
 
The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
==Pathophysiology==
===Physiology===
The normal physiology of [name of process] can be understood as follows:
 
===Pathogenesis===
 
*The exact pathogenesis of [disease name] is not completely understood.
 
OR
 
*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
*The progression to [disease name] usually involves the [molecular pathway].
*The pathophysiology of [disease/malignancy] depends on the histological subtype.
 
==Genetics==
[Disease name] is transmitted in [mode of genetic transmission] pattern.
 
OR
 
Genes involved in the pathogenesis of [disease name] include:
 
*[Gene1]
*[Gene2]
*[Gene3]
 
OR
 
The development of [disease name] is the result of multiple genetic mutations such as:


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:
*[Mutation 1]
*[Mutation 2]
*[Mutation 3]


Activity positively correlated to severity:
==Associated Conditions==
*[[Histamine receptor|H2]]
Conditions associated with [disease name] include:
*[[Muscarinic acetylcholine receptor|M4]]
*[[Tachykinin receptor|nk1]]
*non-NMDA [[glutamate receptors]]


Activity negatively correlated to severity:
*[Condition 1]
*[[NMDA receptor|NMDA]]
*[Condition 2]
*[[Mu opioid receptor|μ opioid]]
*[Condition 3]
*[[5-HT receptor|5-HT1D]]
*[[5-HT receptor|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.
==Gross Pathology==
On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].


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."<ref>{{cite journal |author=Poyurovsky M, Weizman R, Weizman A, Koran L |title=Memantine for treatment-resistant OCD |journal=The American journal of psychiatry |volume=162 |issue=11 |pages=2191-2 |year=2005 |pmid=16263867 |doi=10.1176/appi.ajp.162.11.2191-a |url=http://www.ajp.psychiatryonline.org/cgi/content/full/162/11/2191-a}}</ref> 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. .
==Microscopic Pathology==
On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease nam


==References==
==References==

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Priyanka Kumari, M.B.B.S[2]Sonya Gelfand

Overview

Different biological and psychological explanations have been put forward to understand the pathophysiology of obsessive-compulsive disorder. It is generally agreed that neurotransmitters play an important role in the pathophysiology of obsessive–compulsive disorder.

Pathophysiology

  • Obsessive-compulsive disorder is thought to be caused by a variety of factors. Some forms of OCD appear to be familial and linked to other disorders such as tic disorders, depression, and obsessive compulsive personality disorder, while others appear to be familial but unrelated to other disorders, and even others display no family background.[1][2]
  • A type of size abnormality has been discovered in various brain structures, according to some studies. The majority of researchers conclude that there is an abnormality in the neurotransmitter serotonin, as well as other potential psychological or biological abnormalities; however, this activity may be the brain's reaction to OCD rather than its trigger.
  • Serotonin is believed to play a role in anxiety regulation, as well as other processes including sleep and memory. Synapses enable this neurotransmitter to travel from one nerve cell to the next. Serotonin must bind to receptor sites on neighboring nerve cells in order to transmit chemical messages. It's thought that OCD patients' receptor sites are blocked or impaired, preventing serotonin from reaching its full potential. The fact that many OCD patients benefit from the use of selective serotonin reuptake inhibitors (SSRIs), a type of antidepressant medication that allows more serotonin to be readily available to other nerve cells, backs up this theory. (See the section on potential OCD treatments for more information on this class of drugs.)[3]
  • A possible genetic mutation that causes OCD has been discovered in recent research. In unrelated families with OCD, researchers funded by the National Institutes of Health discovered a mutation in the human serotonin transporter gene, hSERT. Furthermore, Rasmussen (1994) produced data in his study of identical twins that supported the idea of a "heritable factor for neurotic anxiety." He also mentioned that how these anxiety symptoms are expressed is influenced by environmental factors. However, various studies on this topic are still ongoing, and the existence of a genetic link has yet to be proven.[4]
  • In August 2007, scientists at Duke University Medical Center in North Carolina discovered another possible genetic cause of OCD. They created mice that were missing a gene called SAPAP3. This protein is abundant in the striatum, a brain region associated with planning and taking appropriate actions. The mice groomed themselves three times as much as normal mice, to the point where their fur fell off.[5]
  • Brain imaging is now possible thanks to technological advancements. It has been demonstrated using tools such as positron emission tomography (PET scans) that people with OCD have brain activity that differs from people who do not have the disorder. This suggests that OCD sufferers' brain functioning may be hampered in some way. According to Jeffrey Schwartz's book Brain Lock, 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 coerced. This is experienced as a sense of doubt and incompleteness, prompting the individual to attempt to consciously deconstruct their previous behavior — a process that causes anxiety in most people, even those who do not have OCD.
  • A miscommunication between the orbital-frontal cortex, the caudate nucleus, and the thalamus has been proposed as a possible factor in the explanation of OCD. The orbitofrontal cortex (OFC) is the first part of the brain to notice if there is a problem. When the OFC detects a problem, it sends a preliminary "worry signal" to the thalamus. When the thalamus receives this signal, it transmits signals to the OFC, which the OFC interprets. Between the OFC and the thalamus is the caudate nucleus, which prevents the initial worry signal from being sent back to the thalamus after it has already been received. However, it is thought that in people with OCD, the caudate nucleus does not function properly, allowing the initial signal to reappear. The thalamus becomes hyperactive as a result, and a seemingly endless loop of worry signals is sent back and forth between the OFC and the thalamus. In an attempt to alleviate this apprehension, the OFC increases anxiety and engages in compulsive behaviors.[3]

Neuropsychiatry

  • The striatum, orbitofrontal cortex, and cingulate cortex are the brain regions most affected by OCD. Several receptors including glutamate receptors (NMDA and non-NMDA), the H2, M4, nk1, are involved in OCD. A secondary effect is mediated by the 5-HT1D, 5-HT2C, and opioid receptors. The striatum is home to the H2, M4, nk1, and non-NMDA glutamate receptors, while the cingulate cortex is home to the NMDA receptors.
  • 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:
  • Activity negatively correlated to severity:
  • The receptors nk1, non-NMDA glutamate receptors, and NMDA may be involved in the central dysfunction of OCD, whereas the other receptors may simply have secondary modulatory effects.
  • Aprepitant (nk1 antagonist), riluzole (glutamate release inhibitor), and tautomycin are examples of pharmaceuticals that act directly on those core mechanisms (NMDA receptor sensitizer).
  • The OC Foundation is also testing the anti-Alzheimer's drug memantine, which is an NMDA antagonist, for its efficacy in reducing OCD symptoms. Memantine may be considered for treatment-resistant OCD, according to a case study published in The American Journal of Psychiatry, but controlled studies are needed to support this assertion. Drugs used to treat the OCD are not fully efficacious as they are not thought to act on the core mechanisms responsible to cause OCD.[6]

Overview

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR


[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Pathophysiology

Physiology

The normal physiology of [name of process] can be understood as follows:

Pathogenesis

  • The exact pathogenesis of [disease name] is not completely understood.

OR

  • It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
  • [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
  • Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
  • [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
  • The progression to [disease name] usually involves the [molecular pathway].
  • The pathophysiology of [disease/malignancy] depends on the histological subtype.

Genetics

[Disease name] is transmitted in [mode of genetic transmission] pattern.

OR

Genes involved in the pathogenesis of [disease name] include:

  • [Gene1]
  • [Gene2]
  • [Gene3]

OR

The development of [disease name] is the result of multiple genetic mutations such as:

  • [Mutation 1]
  • [Mutation 2]
  • [Mutation 3]

Associated Conditions

Conditions associated with [disease name] include:

  • [Condition 1]
  • [Condition 2]
  • [Condition 3]

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Overview

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR


[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Pathophysiology

Physiology

The normal physiology of [name of process] can be understood as follows:

Pathogenesis

  • The exact pathogenesis of [disease name] is not completely understood.

OR

  • It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
  • [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
  • Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
  • [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
  • The progression to [disease name] usually involves the [molecular pathway].
  • The pathophysiology of [disease/malignancy] depends on the histological subtype.

Genetics

[Disease name] is transmitted in [mode of genetic transmission] pattern.

OR

Genes involved in the pathogenesis of [disease name] include:

  • [Gene1]
  • [Gene2]
  • [Gene3]

OR

The development of [disease name] is the result of multiple genetic mutations such as:

  • [Mutation 1]
  • [Mutation 2]
  • [Mutation 3]

Associated Conditions

Conditions associated with [disease name] include:

  • [Condition 1]
  • [Condition 2]
  • [Condition 3]

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease nam

References

  1. ↑ Pauls DL, Alsobrook JP, Goodman W, Rasmussen S, Leckman JF (1995). "A family study of obsessive-compulsive disorder". Am J Psychiatry. 152 (1): 76–84. doi:10.1176/ajp.152.1.76. PMID 7802125.
  2. ↑ Ozaki N, Goldman D, Kaye WH, Plotnicov K, Greenberg BD, Lappalainen J; et al. (2003). "Serotonin transporter missense mutation associated with a complex neuropsychiatric phenotype". Mol Psychiatry. 8 (11): 933–6. doi:10.1038/sj.mp.4001365. PMID 14593431.
  3. ↑ BBC Science and Nature: Human Body and Mind. Causes of OCD. <http://www.bbc.co.uk/science/humanbody/mind/articles/disorders/causesofocd.shtml>. Accessed April 15, 2006.
  4. ↑ 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.
  5. ↑ Missing gene creates obsessive-compulsive mouse, New Scientist August 2007
  6. ↑ Poyurovsky M, Weizman R, Weizman A, Koran L (2005). "Memantine for treatment-resistant OCD". The American journal of psychiatry. 162 (11): 2191–2. doi:10.1176/appi.ajp.162.11.2191-a. PMID 16263867.


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