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fMRI Study of Nicotinic Effect on Neurophysiology of Schizophrenia

30 de junio de 2017 actualizado por: National Institute on Drug Abuse (NIDA)

Background:

  • Individuals who have schizophrenia are significantly more likely to smoke than the general population, which leads to increased smoking-related illnesses and high rates of nicotine dependence. Research suggests that high rates of smoking and nicotine addiction in people with schizophrenia are related to the fact that nicotine temporally improves performance in several cognitive tasks, including sensory gating, long-term memory, and visual tracking-all of which are affected by schizophrenia.
  • Smoking among schizophrenia patients may be a form of self-medication, since nicotine may temporarily treat and improve cognitive deficits caused by schizophrenia. Researchers are interested in studying the effects of nicotine on the brain activity of individuals with schizophrenia to better understand how nicotine affects the brain regions connected to memory, visual tracking, and attention.

Objectives:

  • To identify specific brain regions involved in the anticipatory learning deficits found in schizophrenia patients who smoke.
  • To determine whether and how nicotine enhances performance in these regions.

Eligibility:

- Smokers (at least 10 cigarettes per day) between 18 and 50 years of age who either are healthy volunteers or have been diagnosed with schizophrenia/schizoaffective disorder.

Design:

  • Participants will be asked to avoid consuming alcohol and restrict consuming caffeinated beverages for 24 hours before the study days. Participants will provide urine and breath samples at the start of the study to be tested for chemicals that may interfere with the study.
  • The study will require two to four visits, with two fMRI sessions and other visits for a clinical interview or training.

Participants will have a training session with a possible mock MRI scan to learn how to do tasks that track eye movement and measure ability to pay attention.

  • During the fMRI scanning sessions, participants will receive either a nicotine patch or a placebo patch without nicotine. After the patch is in place, participants will perform tasks while receiving MRI scans. The scans will take up to 2 hours.
  • Participants will provide blood samples after finishing the MRI sessions.

Descripción general del estudio

Descripción detallada

The prevalence rate of smoking among schizophrenia patients is as high as 88 percent. This is associated with a 2-fold increase in deaths due to smoking related diseases-compounded by high rates of nicotine dependence and low abstinence rates following cessation programs. Converging lines of evidence suggest that high rates of smoking and nicotine addiction among schizophrenic patients is influenced by the presence of disease-related abnormalities in brain function. Genetic and post mortem studies show that patients exhibit abnormalities in neuronal nicotinic receptors, which are involved in a number of cognitive functions. Pharmacological studies show that nicotine temporally improves performance in several cognitive tasks including sensory gating, long-term memory, and visual tracking. These data support a growing consensus that smoking among schizophrenic patients is a form of self-medication, and suggest that the success of targeted smoking cessation programs will depend, in part, on finding alternative means of treating the underlying cognitive deficits. One of the most reproducible neurocognitive and biological changes in schizophrenia is abnormal visual tracking, or smooth pursuit eye movements. Preliminary data show that previously reported deficits in visual tracking are related to anticipatory learning deficits and that nicotine enhances performance in patients by temporarily treating this learning deficit. A better understanding of these processes may lead to better behavioral and/or pharmacological therapeutic interventions for excessive nicotine abuse and recidivism in this clinically vulnerable population. In order to identify brain regions underlying this learning deficit we propose to compare brain activations in 30 healthy controls and 30 patients with schizophrenia during anticipation of target motion using functional magnetic resonance imaging (fMRI). In order to identify the brain regions involved in nicotine-induced enhancement of anticipatory learning we will compare activation in patients under conditions of unexpected and anticipated target motion following administration of nicotine and placebo.

Tipo de estudio

De observación

Inscripción (Anticipado)

100

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

    • Maryland
      • Catonsville, Maryland, Estados Unidos, 21228
        • Maryland Psychiatric Research Center (MPRC) 55 Wade Avenue

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 50 años (Adulto)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

  • INCLUSION CRITERIA:

Subjects (schizophrenia patients and healthy control smokers) must be between the ages of 18-50 and in good health based on history and physical exams. Age restrictions are based on age-related declines (usually occurring after age 55-58) in eye tracking performance. Schizophrenia patients are persons with a DSM-IV Axis-I diagnosis for schizophrenia, based on a best-estimate diagnosis by the Structured Clinical Interview for DSM-IV (SCID) supplemented by family informants and medical records, done at the MPRC. Those in nicotine protocols must demonstrate that they are experienced users based upon exhaled CO and must smoke a minimum of 10 cigarettes/day with duration of use of at least 1 year. Subjects may be users of alcohol and/or marijuana but may not meet criteria for dependence on either and may not have used either for at least 24 hours prior to scanning.

EXCLUSION CRITERIA:

Subjects will be excluded if they are unable to undergo MRI scanning due to pregnancy, implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts) or claustrophobia. Subjects will also be excluded if they have 1) any major medical illnesses to include, but not limited to, uncontrolled high blood pressure or high blood sugar, cardiovascular disease, asthma, peripheral vascular diseases, coagulopathies, history of superficial or deep vein thrombosis, HIV, or other infectious diseases (e.g. Hepatitis B), 2) mood or anxiety disorders, or substance-induced psychiatric disorders, 3) neurological illnesses to include, but not limited to, seizure disorders, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS tumor, and other conditions that cause neurocognitive sequelae, 4) significant alcohol or other drug use, other than nicotine dependence, 5) if their T1 weighted images reveal gross structural abnormalities and/or, 6)have a history of syncope. Urine pregnancy tests will be performed on all female volunteers of child-bearing age before each experimental session. Subjects who are positive for any drug other than nicotine or marijuana will be excluded. Subjects in nicotine protocols may not be actively seeking or engaged in smoking cessation treatment. If a subject requires change of antipsychotic medications because of exacerbation of psychotic symptoms, the subject will be considered clinically unstable and his/her participation will be discontinued. Patients with Axis-I mood disorders or substance-induced psychiatric disorders are excluded. We also exclude patients with significant alcohol or other illicit drug use, other than nicotine dependence. This is operationally defined as no SCID/DSM-IV Axis-I substance dependence in the past 6 months, and no current substance abuse. Exceptions are occasional use of marijuana.

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Perspectivas temporales: Otro

Colaboradores e Investigadores

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Publicaciones y enlaces útiles

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Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

8 de febrero de 2005

Finalización del estudio

3 de mayo de 2012

Fechas de registro del estudio

Enviado por primera vez

9 de enero de 2010

Primero enviado que cumplió con los criterios de control de calidad

9 de enero de 2010

Publicado por primera vez (Estimar)

12 de enero de 2010

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

2 de julio de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

30 de junio de 2017

Última verificación

3 de mayo de 2012

Más información

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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