Obsessive-compulsive disorder as a 5-HT subsystem-related behavioural disorder

Article Abstract:

A review of the research linking brain serotonin (also called 5-HT) function to obsessive-compulsive disorder (OCD) is presented. Clomipramine is an antidepressant drug that prevents the re-uptake of serotonin, with the result that more serotonin remains active. In the early 1980s, several studies found clomipramine to be more effective than other drugs of its type in reducing symptoms of OCD. Later studies found a relationship between improvement in OCD symptoms and reductions in concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in cerebrospinal fluid (the fluid that bathes the brain and spinal cord). Reduced cerebrospinal levels of 5-HIAA imply a reduction in the re-uptake of serotonin. Studies evaluating the appropriate duration of treatment for OCD found that patients who improved after 5 to 27 months of clomipramine treatment, and were subsequently withdrawn from the drug, experienced a return of OCD symptoms within seven weeks. New, selective serotonin uptake inhibitors that have proven to be effective antidepressants (e.g., fluvoxamine) have also been tested and found to be highly effective in reducing OCD symptoms. Inducing serotonin activity by other means does not always improve OCD symptoms. For example, when OCD patients were administered m-chlorophenylpiperazine (m-CPP), which initiates serotonin activity, they became anxious and depressed, and their OCD symptoms increased. However, when m-CPP was administered to patients treated with clomipramine for several months, the depression, anxiety and OCD symptoms did not significantly increase. These paradoxical findings suggest that there may be a brain abnormality in OCD involving alterations and possible interactions of serotonin and related substances. (Consumer Summary produced by Reliance Medical Information, Inc.)

Obsessive-compulsive disorder, Obsessive compulsive disorder, Serotonin metabolism

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The antidepressant effects of 5-HT uptake inhibitors

Article Abstract:

Serotonin is a neurotransmitter, or chemical messenger, found in the brain. The theory that serotonin deficiency may play a role in the causation of depression is supported by findings of low levels of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin, in the cerebrospinal fluid (which bathes the brain and spinal cord) of depressed patients. Also, low levels of serotonin or 5-HIAA have been found in the post-mortem examination of the brain tissue of suicide victims. Recently, several selective serotonin uptake inhibitors (a type of drug) have been made available for clinical study; when the re-uptake of serotonin is blocked, more serotonin remains active in the brain. Many well-designed studies have demonstrated the clinical efficacy of the serotonin uptake inhibitors (such as zimelidine, fluoxetine, fluvoxamine, sertraline, and citalopram) in treating depression. Like standard antidepressants, these drugs have a two-to-three-week delay in the onset of their action. Since selective serotonin uptake inhibitors are relatively new drugs, therapeutic dose ranges have not been defined. Side effects can include insomnia, gastrointestinal problems, nervousness, anxiety, and headaches, and appear to be partially related to dosage. These drugs demonstrate fewer side-effects (less sedation, and fewer alterations in blood pressure) than standard tricyclic antidepressants, making them more practical than tricyclics in treating elderly patients. Selective serotonin uptake inhibitors have also been shown to be effective in treating anxiety, panic, and obsessive-compulsive disorder. Unlike standard antidepressants, serotonin uptake inhibitors do not lead to weight gain. (Consumer Summary produced by Reliance Medical Information, Inc.)

Innovations, Drug therapy, Depression, Mental, Depression (Mood disorder), Antidepressants

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Evidence for the 5-HT hypothesis of suicide: a review of post-mortem studies

Article Abstract:

Recent research suggests a link between the brain chemical, serotonin, and the risk for suicide. Traditional psychiatric theory claims that low serotonin levels are associated with depression. Serotonin (also called 5-HT) is metabolized by an enzyme to another substance, 5-hydroxyindoleacetic acid (5-HIAA). Initially, post-mortem studies of the levels of serotonin or 5-HIAA in the brains of suicide victims were carried out to study the biochemistry of depression. Most of those studies found moderately low levels of both serotonin and 5-HIAA. Several later studies have found lower levels of 5-HIAA in the cerebrospinal fluid (which bathes the brain and spinal cord) of psychiatric patients who attempted suicide than the levels in non-suicidal psychiatric patients with similar diagnoses. Studies of suicidal and non-suicidal patients with bipolar disorder do not show differences in 5-HIAA in cerebrospinal fluid. This may be because low cerebrospinal fluid levels of 5-HIAA are already associated with bipolar disorder. The degree of violence used to accomplish suicide seems to be unrelated to serotonin or 5-HIAA levels, although violent suicide attempters have been shown to have increased numbers of 5-HT-2 receptors, structures which are thought to mediate the effects of serotonin. It is not clear why violent behavior is directed inwardly by some people, but it has been suggested that changes in other brain chemicals may influence the direction of violent, impulsive acts. (Consumer Summary produced by Reliance Medical Information, Inc.)

Suicide, Self-destructive behavior, Self injurious behavior, Serotonin receptors

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