Sensorimotor Gating in Schizophrenia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Erica Duncan, MD, Emory University
ClinicalTrials.gov Identifier:
NCT00561561
First received: November 20, 2007
Last updated: September 29, 2014
Last verified: September 2014
  Purpose

This study is looking at problems people sometimes have taking in information from their senses. Specifically, we are comparing the way in which people diagnosed with schizophrenia process sound information, compared with people who have never been diagnosed with a psychiatric disorder. When people hear a loud sound they sometimes feel startled, and when they feel startled they usually blink their eyes. However, if they hear a softer sound shortly before the loud one they may not blink their eyes - in other words, the eye-blink response is smaller. When this happens it's called prepulse inhibition of startle. In this study, we want to measure the startle response and prepulse inhibition of startle in individuals diagnosed with schizophrenia versus individuals not diagnosed with schizophrenia. We also want to find out whether people show the same amount of prepulse inhibition of startle as other members of their family.


Condition Intervention
Schizophrenia
Procedure: acoustic startle testing

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Sensorimotor Gating in Schizophrenia

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • prepulse inhibition of acoustic startle [ Time Frame: prospective ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood and extracted DNA


Estimated Enrollment: 500
Study Start Date: June 2001
Estimated Study Completion Date: December 2015
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
subjects with schizophrenia
Procedure: acoustic startle testing
recording of eyeblink component of acoustic startle reflex with small surface electrodes during presentation of acoustic stimuli through headphones
2
health controls
Procedure: acoustic startle testing
recording of eyeblink component of acoustic startle reflex with small surface electrodes during presentation of acoustic stimuli through headphones
3
family members of subjects with schizophrenia
Procedure: acoustic startle testing
recording of eyeblink component of acoustic startle reflex with small surface electrodes during presentation of acoustic stimuli through headphones
4
family members of healthy controls
Procedure: acoustic startle testing
recording of eyeblink component of acoustic startle reflex with small surface electrodes during presentation of acoustic stimuli through headphones

Detailed Description:

Patients with schizophrenia have difficulty screening out irrelevant stimuli, and often have the experience of sensory flooding. These "gating deficits" may contribute to the thought disorder, cognitive fragmentation and hallucinations which are so debilitating to these individuals. The acoustic startle response is a reflex contraction of the skeletal muscles in response to a sudden acoustic stimulus. It occurs across mammalian species and can be easily measured. The modulation of this reflex by a preliminary nonstartling stimulus is termed prepulse inhibition of acoustic startle (PPI), a paradigm which is used as an operational measure of sensorimotor gating. In consonance with the schizophrenia symptoms that are suggestive of gating deficits, many patients with schizophrenia have deficits in PPI when compared to healthy controls. The brain regions that modulate PPI include the hippocampus and prefrontal cortex, areas that are implicated as being abnormal in schizophrenia. Our prior work and work from other labs suggests that PPI impairment in schizophrenia does not improve with treatment and hence may be a trait related abnormality. Work from our current funding period supports our original hypothesis, namely that impaired PPI exhibits familial association. Specifically, we are finding that PPI in first degree family members of subjects with schizophrenia is impaired. Further work is needed in order to establish that PPI impairment is heritable.

An endophenotype is a measurable trait or phenotype detectable by a biological test. Using an endophenotype rather than presence or absence of disease is a powerful tool in the study of diseases with complex polygenic etiologies such as schizophrenia. Progress in the genetics of schizophrenia is greatly confounded by the difficulty in identifying individuals who carry genes contributing to schizophrenia. Incomplete penetrance and the fact that both heritable and environmental factors interact to produce the disease add to this difficulty. This means that some individuals carrying vulnerability genes for schizophrenia who fail to exhibit robust symptoms will be classified erroneously as unaffected in genetic studies, confounding attempts to reliably define the heritable phenotype. The phenomenon of incomplete penetrance is exhibited by the finding that the risk of schizophrenia is the same for children of affected and nonaffected monozygotic twins. The polygenic etiology of schizophrenia makes it unlikely that a pooled sample of individuals defined by the presence of schizophrenia will greatly overlap in the vulnerability genes that they carry. The goal of the endophenotype approach is to narrow the defined phenotype so that a more homogeneous genotype is expected, making it much more fruitful and to conduct genetic studies.

We hypothesize that impaired PPI will prove to be a heritable endophenotype in schizophrenia. Based on our work accomplished during the current funding period, we now propose to further develop this line of research by conducting a heritability analysis of PPI. Our field is greatly in need of this work as a prelude to endophenotype-based genetic studies. We will accomplish our important goal by collecting and characterizing a cohort of healthy controls and their families, and by expanding our sample of schizophrenia subjects and their families. We will collect diagnostic, symptom, cognitive, pedigree, and PPI data all subjects, and will collect blood and extract DNA for future genetic analyses. We will use a family based strategy to investigate the pattern and degree of heritability of impaired PPI in families of schizophrenia and control probands.

This project will provide the necessary next step in advancing the use of impaired PPI as a powerful tool for the discovery of vulnerability genes contributing to schizophrenia. Currently available treatments for this devastating disorder are sadly inadequate. Our medications are virtually ineffective for a subset of our patients. The discovery of vulnerability genes and of a method for biological subtyping of patients will allow our field to develop genetically informed new treatments that specifically target particular subtypes of patients. This approach is our best hope for bringing relief to patients suffering from this disease.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

subjects with schizophrenia and their family members; healthy controls and their family members

Criteria

Inclusion Criteria:

  • Diagnosis of a Schizophrenia Spectrum disorder OR no history of Psychiatric Illness

Exclusion Criteria:

  • History of head injury with loss of consciousness of more than 5 minutes
  • History of neurological disease (ex. meningitis, encephalitis)
  • Drug or alcohol abuse within the last 3 months
  • Hearing loss
  • Non-correctable vision problems
  • Current cancer treatment (radiation or chemotherapy currently ongoing)
  • History of Post Traumatic Stress Disorder
  • Diagnosis of HIV or AIDS
  • Uncontrolled diabetes
  • History of seizures
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00561561

Locations
United States, Georgia
Atlanta VA Medical Center
Decatur, Georgia, United States, 30033
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Erica Duncan, MD Atlanta VA Medical Center, Emory University Dept of Psychiatry & Behavioral Sciences
  More Information

No publications provided

Responsible Party: Erica Duncan, MD, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT00561561     History of Changes
Other Study ID Numbers: IRB00021861
Study First Received: November 20, 2007
Last Updated: September 29, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Schizophrenia
Prepulse Inhibition
Acoustic Startle

Additional relevant MeSH terms:
Schizophrenia
Schizophrenia and Disorders with Psychotic Features
Mental Disorders

ClinicalTrials.gov processed this record on October 01, 2014