Neurotransmission and Obsessive Compulsive Disorder

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Introduction

This research paper has reviewed several research articles for the topic. It begins with the detailed picture of the neuron which is the basic cell of the brain. What happens in a neurotransmission is next explained. The electrical conduction and the chemical neurotransmission are so explained as to understand how the SSRIs, which form the primary line of treatment of OCD, act at the synapse. The biologic basis of OCD has been detailed using the backing of many studies and papers found in the literature. The paper ends with the therapy of the anxiety disorder, obsessive compulsive disorder, which has been selected from among the many psychiatric disorders for discussion here.

The Neuron

The neuron is the smallest functional unit of the brain (Saleebey, 2001). There are also glial cells in the brain. This neuron has four parts: the cell body, dendrites, axon and cell terminals. The proteins and the other substances that the neuron needs for its function are manufactured by the cell body or soma and the nucleus and the neuron is known as the “manufacturing and recyling plant” (Stufflebeam, 2008). The nucleus contains the DNA. The dendrites, hairlike and many in number, extend from the upper portion of the cell body. They are the primary receptors and they carry neuronal impulses or information or signals from the other neurons to the cell body (Saleebey, 2001). The axon extends from the lower portion of the cell body and transports the impulse that came in through the dendrites to the dendrites of another neuron. The axons vary in length according to the part of the body they are supplying. The terminal buttons or end feet of the axon constitute the fourth part and are named the axon terminals; they contain the neurotransmitters. The neurotransmitters are the chemical media through which signals flow between neurons at chemical synapses (Stufflebeam, 2008). The synapse is the small interval or space between the axon of one neuron and the dendrites of another and is in conjunction with the axon terminal. The synapse is the position where the communication between neurons occur (Saleebey, 2001). A single axon has connections with the dendrites of many neurons. The transfer of information from neuron to neuron becomes smoother with the myelin sheath around the axon.

Conduction of neuronal impulses

The neurons are surrounded by a cell membrane which is formed by a watery solution of chemicals and fatty acids (Saleebey, 2001). These are the chemicals which make possible the transmission across the synapse and within the cell. The passage of impulses within the cell is through the chemical ions or electrically charged molecules found inside the cell and outside. Ion channels in and outside the cell allow the passage of chemical ions of sodium, potassium, calcium and chloride ions. There is a resting potential within the cell and the voltage difference across the cell is one-tenth of a volt. (Saleebey, 2001). The impulse when propagated changes the resting potential. Sodium ions move in to the cell and potassium ions move out. This sodium-potassium pump allows the production of adenosine triphosphate. The voltage change travels from the top of the axon to the end at a speed ranging from a few miles to 200 miles per hour. The calcium ions rush into the cell when the impulse reaches the end of the axon. Neurotransmission

The rushing in of calcium ions causes the migration of chemical vesicles to the axon terminals and subsequent release of the neurotransmitters across the synapse. The neurotransmitters move across the synapse along an ion channel to a receptor site on the dendrites of the next neuron setting up an electrical response (Saleebey, 2001). The action potential will be inhibitory or excitatory depending on which ion channel has been opened by the the summative effect of thousands of molecules. Transmission between cells is chemical and within the cells is electrical. Occasionally the neurotransmitter causes the release of G-proteins inside the cell. They modulate the stimuli or information passing from one cell to another. They produce a cascading flow of stimulus from the outer cell membrane to the innermost portion of the neuron (Saleebey, 2001). The G-proteins also acts upon the effector enzyme and reaches the nucleus of the cell, disturbing it’s structure and function. The type of neurotransmitter and the amount can be changed by the G-proteins which also influences the number and type of enzymes which the cell makes (Saleebey, 2001).

Obsessive Compulsive Disorder

“OCD is a treatable and biologic disease in which serotonin metabolism plays a major role” (Valente, 2002). It is basically an anxiety disorder characterized by persistent thoughts and repetitive behavior. Coping with problems becomes difficult and the individual’s life is disturbed. Statistics show that the number of Americans suffering from anxiety disorders and whose quality of life and performance have been disturbed comes to five million (Valente, 2002).

Biological basis of OCD

The question whether obsessive compulsive disorder or for that matter, any psychiatric illness, has a biological basis is not significant anymore as the omission of the words “organic disorder” in the DSM-IV itself imply that this is so (APA, 1994, p.10). Could it be that all mental illnesses, which were previously described as functional, have a biological basis? (Arben, 1996). Thought and behavior are both considered by many researchers to be a part of the brain activity and must therefore be a biological process. The second reason is that close relatives of patients with schizophrenia and bipolar disease are susceptible to getting the illness themselves or have some minor version of it. Behavioral traits and personality characteristics are more common among relatives (Arben, 1996). Thirdly patients on Prozac which increases the quantity of serotonin, a neurotransmitter, feel better and it does not demonstrate that a lower serotonin level had been the cause. In a study with schizophrenia patients, many were found to have brain irregularities and it became doubtful as to whether it was due to the irregularities or environmental and psychological stressors. The various discussion findings point to more of a biological basis than any other (Arben, 1996). Historically, it has been reported that people who had biological disorders like Von Economo’s Disease (55-74%), war-related injuries and Gilles de la Tourette’s syndrome developed OCD (Valente, 2002). Neuranatomical deviations have been blamed for the OCD. Family and twin studies also demonstrate an increased genetic susceptibility to OCD. 63% of monozygotic twins had OCD and one in 4-5 family members had OCD when there was a family history (Valente, 2002).

The anxiety and the other symptoms of OCD develop due to brain malfunction or existence of some biochemical substances. Mood, movement, blood pressure and neural impulse conduction are carried out by the neurotransmitters norepinephrine, serotonin and dopamine.

Tremors, anxiety, nervousness and changed vital signs are due to the norepinephrine. The symptoms of OCD are relieved by SRIs. Researchers have found that “serotonin (5-HT) modulates cooperative social behavior and latency or impulsivity” (Valente, 2002). The biological basis is also upheld by the fact that clinical improvement has been seen after brain surgery. Patients with cingulotomy in the last 25 years had a 25% benefit, another 25 % were functionally better and 31 % improved markedly (Steketee, 1998 as cited in Valente, 2002).

Patients in England who had a limbic leucotomy were seen to have a clinical improvement in 84 % of them.

Other views

Cognitive theorists feel that patients develop OCD due to “negative thinking and irrational ideas” along with genetic and biochemical causes (Valente, 2002). 62-92% say that their relationships have suffered due to OCD. Academic performance became poor and work performance below par in 58% of people who had the symptoms. 66% of patients had disappointment in their careers and 40 % could not work. 13% tried to commit suicide (Valente, 2002). Some people are of the view that a chemical imbalance has caused the psychiatric illnesses as improvement is seen with drug therapy. Public policy issues are several: whether the insurance coverage should be brought down if it is biological, whether the illnesses should be brought under the Disability provisions like physical disability, and how to distribute funds for research whether for biological or psychological among other debates.

Neurotransmitters

Neurotransmitters are amino acids, monoamines and peptides. The most prevalent excitatory neurotransmitter in the brain is glutamate (Sprenger, 1999). GABA always carries the inhibitory message: it actually is formed from glutamate with one more enzyme and is found more in the areas involved with emotions and thinking. Both function in most information-processing neurotransmissions.

Monoamines are catecholamines and indolamines. Epinephrine (adrenalin), norepinephrine (noradrenalin) and dopamine form the catecholamines while serotonin and melatonin form the indolamines. Epinephrine, which is produced in the adrenal glands, is involved in situations of fear and danger where instant action is required. Noradrenaline is an excitatory neurotransmitter and it makes the brain alert. Dopamine is the inhibitory monoamine neurotransmitter and it controls physical movement making it smooth. It is involved with the regulation of the information flow to the higher levels of the brain. Low levels can affect the working memory of Man. Lack of dopamine causes Parkinsonism (Sprenger, 1999).

Serotonin, the indoleamine, is known as the feel-good neurotransmitter. It helps to send messages all through the brain. Being found in the spaces between the neurons, serotonin has a peculiar phenomenon attached to it. After it helps in sending a message across the synapse to the receiving neuron, it is sucked back by the sending neuron. This is the serotonin reuptake and it is no longer available at the synapse (Sprenger, 1999). Future transmissions can be disturbed by this reuptake of the serotonin.

The lower brain regions at the upper portion of the spinal cord are the regions where serotonin is produced. The neurons producing it possess long axons which reach all over the brain. This is probably why every message to the brain has serotonin involvement (Sprenger, 1999). Circulating serotonin may act longer and allow better transmissions. It is the serotonin level which decides the emotional make-up of a person. Lack of it may cause a person to be depressed always with lack of self-esteem.

SSRIs in the treatment of obsessive compulsive disorder, inhibits the reuptake of serotonin at specific receptors. Essentially then, serotonin is allowed to flow freely through the brain. The SSRIs block the reuptake channels. A free flow of information results and the individual feels better. The SSRIs take a few weeks to produce its full effect.

Management

The patient and family need time to adjust to the illness and find ways to reduce anxiety.

Medication, cognitive behavior therapy and education counseling form the management procedures.

Pharmacological Treatment for OCD

In 1959, drugs that enhance the production of neurotransmitter serotonin were used widely (Joel, 1959 as cited in Menzies, 2003). Iproniazid, an MAO inhibitor, acts on monoamine oxidase to inhibit the metabolism of serotonin. MAO inhibitors are still used but preference is for the serotonin reuptake inhibitors (SRIs). Since late 1960s, clomipramine is the most widely studied SRI. Now the first line of treatment includes the selective serotonin reuptake inhibitors. They are the five selective SRIs or SSRIs which do not have an action on noradrenaline uptake. but act on the axon terminals to inhibit the reuptake of serotonin allowing its free circulation. They produce a reduction of 30-60% in the symptoms which provide great relief to patients. Studies have also been conducted on them: fluoexetine (Prozac), paroxetine (Paxil), fluvoxamine (Luvox), sertraline (Zoloft) and citalopram. A study of 3 systematic reviews indicated that SSRIs definitely had a better effect than placebos (Soomro, 2001 as cited in Valente, 2002). Most studies except for one said that treatment with clomipramine had better outcomes than sertraline. A randomized clinical study suggested that a combination of behavioral therapy with fluvoxamine produced a better effect on the participants than the behavior therapy alone (Soomro, 2001 as cited in Valente, 2002). SSRIs produce a favorable effect only after 8-10 weeks. Drug interactions and toxicity are possible when combined with other anti-psychiatric drugs. The following paragraph indicates the findings of various studies.

Features noted in studies of SSRIs

Forty to sixty per cent of OCD patients show improvement when SRIs are used in treatment (Expert Consensus Guidelines, 1997 as cited in Menzies, 2003). Complete response is rare and residual symptoms are common. If there is no response initially with SRI, other SRIs would have no response. Doses are seen higher than in depression. SRIs are usually tolerated by most patients. Discontinuation by patients can be reduced by starting from a low dosage, gradually increasing it and instructing the patients on the possible side-effects. The benefit continues for a long time in people who respond well. A gradual reduction in dosage is recommended for patients who have responded. Full discontinuation causes relapses (Expert Consensus Guidelines, 1997 as cited in Menzies, 2003).

Choice of SSRI

The choice of the SSRI will depend on the comparison of efficacy, tolerability and safety. Clomipramine is the most efficacious and inexpensive. People with sleep disturbances are advised to use this as it helps overcome insomnia. It is avoided in women of child-bearing age in pregnancy to reduce the risk of neonatal complications: fluoxetine is better as it has only a low risk of terratogenesis and is safe during pregnancy. However clomipramine is the safest drug during breast-feeding. Flouxetine has a low risk following discontinuation. It is avoided in breast feeding. Drug interactions can occur as the liver inhibits enzyme functions. Paroxetine is fairly safe even in overdosage. Highest rate of discontinuation is seen with this drug. Fluvoxamine is safe even if overdosage occurs but drugs interactions occur due to liver enzyme inhibition. Sertraline has similar features of fluvoxamine but is safe in breast feeding. Drug interactions are not seen with Citalopram and it is safe in overdosage (Expert Consensus Guidelines, 1997 as cited in Menzies, 2003).

Nonpharmacological treatment

The patient must be guided to develop skills and information to cope with his illness.

Sharing their concerns would help the families and patients build a relationship and ease out tension as patients are generally unwilling to share their worries. The community scares them and the patients are reluctant to disclose everything to their doctor for fear of ridicule. Educational counseling should solve this problem. The patient must be informed about sources of help in his locality for easy approach, help-seeking and self-management.

Cognitive behavioral therapy

The negative thoughts of OCD patients cause their anxiety. Cognitive behavioral therapy when instituted with a time-bound plan can turn the patient around on his “irrational thoughts including obsessions, overvalued ideas and perfectionistic expectations” (Beck, 1979 as cited in Valente, 2002). If the anxiety is not treated, the patient may opt for suicide. Helping them focus on their own problems, finding solutions for removing them by themselves and thinking rationally would be the advice given. Cognitive self -appraisal is also a part of the treatment. The skills to reduce anxiety and systematic desensitization are taught through behavior strategies.

Discussion

.The neuron is the primary functioning unit of the brain. Neurotransmission is the transfer of chemical ions across the synapse at the axon terminals of the neurons. The transfer of information across the neural network is the method by which the nervous system controls the actions of the body and processes information in the brain. The biologic basis of the OCD has been discussed and it has been found to be the accepted basis. Among the many neurotransmitters serotonin is the one which is significant in the treatment of psychiatric disorders. This neurotransmitter has the characteristic of reuptake by the sender neuron. The treatment of psychiatric disorders like the obsessive compulsive disorder involves the use of the selective serotonin reuptake inhibitors like Prozac and Luvox. These drugs inhibit the serotonin reuptake at the axon terminals. The treatment of the OCD is promising and shows results after 8-10 weeks of start of treatment.

References

American Psychiatric Association, (1994). “Diagnostic and Statistical Manual of Mental Disorders”. 4^th Ed. Washington D.C.

Arben, P.D. (1996). “Are Mental Illnesses Biological Diseases? Some Public Policy Implications”. Journal of Health and Social Work. Volume: 21. Issue: 1. Publication Year: 1996, National Association of Social Workers.

Menzies, R.G. (2003). “Obsessive Compulsive Disorder: Theory, Research, and Treatment”. (Ed.) R.G. Menzies and Padmal de Silva, Published by Wiley: Chichester, England.

Saleebey, D. (2001). “Human Behavior and Social Environments: A Biopsychosocial Approach”. Columbia University Press.

Sprenger, M. (1999). “Learning and Memory: The Brain in Action”. Published by Association for Supervision and Curriculum Development. Place of Publication: Alexandria, VA. Publication Year: 1999.

Stufflebeam, R. (2008). “Neurons, Synapses, Action Potentials, and Neurotransmission”.

Valente, S.M. (2002). “Obsessive Compulsive Disorder”, Perspectives in Psychiatric Care, Vol. 38.

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