Epilepsy | The Role of Serotonin in Seizures

Epilepsy research study

What is the primary objective of this study?

This study will investigate the role that a brain chemical called serotonin plays in seizures. Serotonin, present naturally in the brain, helps transmit signals between nerve cells. Glucose is a sugar that is the main fuel of the brain. Studying these two chemicals may help explain why people with epilepsy get seizures and are more likely to be depressed. Healthy volunteers and patients 18 to 60 years of age who have epilepsy with or without depression and whose seizures are not controlled by medication may be eligible for this study. Candidates are screened with a review of their medical history, a physical examination and an electroencephalogram (EEG, brain wave recording). Participants undergo the following procedures: - Positron emission tomography (PET) scans: The first of three PET scans measures brain blood flow and the activity at some of the brain serotonin receptors (the parts of brain cells to which serotonin attaches). A second scan measures the amount of serotonin transported between brain cells. A third scan measures glucose use. The PET scanner is shaped like a doughnut. The subject lies on a bed that slides in and out of the scanner with his or her head inside the opening. A special mask is fitted to the subject s head to help keep it still during the procedure so the images will be clear. For the first scan, catheters (plastic tubes) are placed in an arm vein to inject a radioactive substance and in an artery in the wrist to collect blood samples. The other two scans require only the catheter in the arm. - Magnetic resonance imaging: This test uses a strong magnetic field and radio waves to obtain images of the brain. The scanner is a metal cylinder surrounded by a strong magnetic field. The subject lies on a table that can slide in and out of the cylinder. Most scans last between 45 and 90 minutes. Subjects wear earplugs to muffle loud knocking noises that occur during scanning. - Psychological evaluation: Subjects are interviewed and fill out questionnaires to help study sadness and depression in epilepsy. - Blood draw: Blood tests look for differences in genes between people with epilepsy who are depressed and those who are not.

Who is eligible to participate?

- INCLUSION CRITERIA: - Patients must have seizures documented by appropriate clinical and laboratory studies . This criterion will be established by studies performed by the referring physicians, preliminary screening in the NINDS Clinical Epilepsy Section outpatient clinic, or if necessary, inpatient video-EEG monitoring. - Male and Female subjects aged between 18 and 60 years - Healthy control subjects will also be recruited. - Subjects must be able to give written informed consent prior to participation in this study. EXCLUSION CRITERIA: - Patients younger than 18 or older than 60 years old. There is evidence for reduced 5HT1A receptor binding in patients over 60. - Patients with a known treatable seizure etiology such as neoplastic or infectious disease. - Patients with MRI findings consistent with brain tumors, trauma or AVMs. - Patients with progressive neurologic disorders. - Patients with a history of significant medical disorders, or requiring treatment with drugs that can not be stopped, and would interfere with the study, except for antidepressants. - Patients with cancer. - Patients not capable of giving an informed consent. - Patients who had seizure activity 24 hours prior to the study. - Women who are pregnant or nursing - Subjects who are current smokers, and cannot stop for at least two weeks before the PET scan, as smoking may affect serotonergic neurotransmission. - Healthy subjects must be free from a personal history of seizure disorders - Patients with coagulation abnormalities.

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?



Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Study Status


Start Date: February 20, 2007

Completed Date: June 5, 2015


Type: Observational


Primary Outcome:

Secondary Outcome:

Study sponsors, principal investigator, and references

Principal Investigator: William H Theodore, M.D.

Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)


More information:

Bromfield EB, Altshuler L, Leiderman DB, Balish M, Ketter TA, Devinsky O, Post RM, Theodore WH. Cerebral metabolism and depression in patients with complex partial seizures. Arch Neurol. 1992 Jun;49(6):617-23. Erratum in: Arch Neurol 1992 Sep;49(9):976.

Discuss Serotonin