Obsessive-compulsive disorder pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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

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:

“

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.

”

Biological Explanations

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 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. (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". 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.

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. 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. [[2]]

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. .

References

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