Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP)
The early stages of the schizophrenia illness are associated with significant decreases in social and intellectual abilities, with more modest declines seen with chronic disease. Multiple studies have identified a relationship between the longer duration of untreated psychosis (the duration between the onset of positive symptoms and treatment) and worse long term outcomes. However, the neurobiology of this phenomenon and its implications for response to antipsychotic medications remain poorly understood.
Glutamatergic excess altering brain connectivity might provide an explanation for why those with longer duration of untreated psychosis have worse clinical outcomes. The investigators propose to use neuroimaging to study 67 first episode psychosis subjects before and after sixteen weeks of treatment with risperidone, a commonly prescribed antipsychotic. We will measure indices of (1) glutamate and (2) structural and functional brain connectivity and test the hypotheses that glutamatergic abnormalities are present in first episode patients and that longer duration of untreated psychosis is associated with greater connectivity abnormalities that set the stage for poor response to treatment. 67 demographic-matched healthy controls will also be recruited as a comparison group - healthy controls will not be administered antipsychotic medication.
The investigator's previous neuroimaging studies have made progress in the understanding of abnormalities in the glutamate system and brain connectivity in unmedicated patients with schizophrenia and modulation of these by antipsychotic medication. Two indices of glutamatergic dysfunction suggestive of glutamate/ glutamine cycle abnormalities have been identified. While antipsychotic medications appear to modulate glutamate, the disturbance in the correlation between metabolites is not restored with treatment. In addition, the investigators found that both structural and functional connectivity abnormalities in unmedicated patients with schizophrenia predict patients' subsequent response to treatment.
To the investigator's knowledge, no other group has performed a study that uses a combination of complementary neuroimaging techniques that will allow generating a broad characterization of glutamatergic function and brain connectivity in first episode psychosis and their change with treatment. The results of the proposed studies could suggest a mechanism by which the duration of untreated psychosis is associated with poor treatment response which might lead to new interventions to target the illness.
|Study Design:||Observational Model: Case Control
Time Perspective: Prospective
|Official Title:||Glutamate, Brain Connectivity and Duration of Untreated Psychosis|
- Comparison of indices of glutamate as measured by 1H-MRS in unmedicated first episode psychosis patients before and after antipsychotic treatment and with healthy controls. [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Comparison of structural and functional brain connectivity in first episode psychosis patients before and after antipsychotic treatment and healthy controls [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Structural brain connectivity (using diffusion tensor imaging) and functional brain connectivity (using resting state connectivity) will be compared between healthy controls and first episode psychosis patients. Additionally within first episode psychosis patients duration of untreated psychosis (DUP) will be correlated with both structural and functional brain connectivity to determine the impact of DUP on both metrics of brain connectivity.
- Evaluation of the contribution of structural and functional connectivity to eventual antipsychotic treatment response in first episode psychosis patients. [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]The investigators will evaluate the relationship between both structural brain connectivity (using diffusion tensor imaging) and functional brain connectivity (using resting state connectivity) before treatment and treatment response after 16 weeks of risperidone therapy in first episode psychosis patients.
|Study Start Date:||January 2014|
|Estimated Study Completion Date:||November 2018|
|Estimated Primary Completion Date:||November 2018 (Final data collection date for primary outcome measure)|
first episode psychosis
Unmedicated first episode psychosis patients that wish to enroll in a 16 week treatment regimen with the drug risperdal.
Other Name: Risperdal
healthy demographic-matched controls
healthy controls will be matched to patients one to one based on: age, smoking status, parental socio-economic status, and gender. Healthy controls must be free from current or past Axis I mental disorders, 1st degree relative current or past Axis I mental disorders, and any other neurological conditions.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02034253
|Contact: David White, MPH, MPAfirstname.lastname@example.org|
|Contact: Ariel Kidwell, BSemail@example.com|
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|Contact: David White, MPH, MPA 205-996-9813 firstname.lastname@example.org|
|Contact: Ariel Kidwell, BS 205-996-9813 email@example.com|
|Principal Investigator: Adrienne C Lahti, MD|
|Principal Investigator:||Adrienne C. Lahti, MD||University of Alabama at Birmingham, Department of Psychiatry|