Cortical Activation and Cognitive Performance During Repetitive Transcranial Magnetic Stimulation in First-Episode Psychosis: A Pilot Study
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Schizophrenia
- Sponsor
- Indiana University
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Cognitive Performance
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (fMRI) at baseline and following the course of rTMS administration.
Detailed Description
Schizophrenia is a chronic and disabling illness that typically begins in the late teen and early adult years.1 This illness is associated with significant impairments in areas such as independent living, social functioning, and vocational functioning.2 Indeed, only 10% of people with schizophrenia are employed, translating into annual lost wages of nearly 15 billion dollars.3,4 Schizophrenia also represents an important societal burden as this illness has been estimated to cost over 40 billion dollars each year in the United States alone.5 Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment for neuropsychiatric illness. A non-invasive intervention, rTMS utilizes the application of a repetitively pulsed magnetic field over the scalp to induce an electric field within a discrete area of the cerebral cortex. This electric field results in altered ion flow across the neuronal cellular membrane and ultimately changes in neuronal polarization. The end result is altered neuronal activity in the area of the cerebral cortex where the rTMS is applied.12 rTMS is a safe and well-tolerated intervention that received FDA approval for treatment refractory major depressive disorder in 2008 and has since become commonly used in clinical practice.13 This study proposes to examine the application of rTMS for the treatment of cognitive dysfunction in FEP. This is an important population for study because if effective, rTMS may represent a preventative treatment for the development of social and vocational impairment that is associated with cognitive dysfunction in schizophrenia. This study will also seek to refine the understanding of the brain circuitry that mediates the potential pro-cognitive effects of rTMS through the use of functional magnetic resonance imaging (fMRI) at baseline and following the course of rTMS administration.
Investigators
Michael Francis
Psychiatrist
Indiana University
Eligibility Criteria
Inclusion Criteria
- •18-40 years of age at study entry
- •Male or female
- •DSM IV-TR Diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder as confirmed by Structured Clinical Interview for DSM-IV-TR (SCID)44
- •Subjects in their first-episode of psychosis, defined as the onset of clinically significant psychotic symptoms within the past five years as determined by first medical record documentation of these conditions
- •BACS composite t-score of 40 or less at baseline assessment
- •Clinical stability as defined by:
- •CGI-S score of less than or equal to 4 (moderately ill) at randomization AND
- •Subjects must not have experienced an exacerbation of their illness within 4 weeks prior to randomization, leading to an intensification of psychiatric care in the opinion of the investigator. Examples of intensification of care include, but are not limited to: inpatient hospitalization, day/partial hospitalization, outpatient crisis management, or psychiatric treatment in an emergency room AND
- •Antipsychotic treatment stability for at least 4 weeks prior to randomization (no change in antipsychotic dosing or addition of any new antipsychotic medication).
- •Able to give informed consent
Exclusion Criteria
- •Life-time history of a seizure, excluding febrile seizures and those induced by substance withdrawal
- •Metallic objects planted in or near the head, including implanted pacemaker, medication pump, vagal stimulator, deep brain stimulator, TENS unit, ventriculoperitoneal shunt, or cochlear implants
- •First degree relative (that is, biological father, mother, brother, sister, or child) with idiopathic epilepsy or other seizure disorder
- •History of significant neurological illness (including stroke, CNS infection with persistent neurologic deficit, or other event deemed significant by PI)
- •History of head trauma as defined by a loss of consciousness or a post-concussive syndrome deemed significant by PI
- •Pregnancy or breast feeding
- •Known IQ \< 70 based on medical history
- •Current DSM-IV-TR diagnosis of alcohol or drug dependence (excluding nicotine or caffeine)
- •Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, COPD, severe hypertriglyceridemia, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, or hepatic, renal gastroenterological, respiratory, endocrine, neurologic, hematologic, or infectious diseases based on medical history or physical examination.
- •Subjects with contraindications to MRI or otherwise unable to tolerate MRI procedure
Outcomes
Primary Outcomes
Cognitive Performance
Time Frame: For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline
rTMS effectiveness in improving cognitive performance as measured by the Brief Assessment of Cognition in Schizophrenia (BACS) composite score. The BACS is a battery specifically designed to measure treatment-related changes in cognition, and has alternate forms, thus minimizing practice effects. The battery includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed, and generates a composite score that is calculated by summing t-scores derived by comparisons with a normative sample of 404 healthy controls. The six brief assessments' t-scores, are summed, and averaged to provide a composite t-score. The composite score min and max are between -43 and 100. A higher score indicating better cognitive performance. The composite score is reported as a change score relative to baseline for both.
Cortical Activation
Time Frame: Change from Baseline (day 1) to Visit 13 (day 15)
effects of rTMS on cortical activation using fMRI during working memory and episodic memory tasks
Secondary Outcomes
- Cognitive Performance(14 days)
- Symptoms(For within-group comparisons, scores at V13 (day 15) and V14 (follow-up two weeks after V13) were compared to baseline)
- Negative Symptoms(Assessed at Baseline (day 0), Midpoint (day 8), and Endpoint (day 15))