Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
Antipsychotic treatment response
Brief summary
The goal of this research project is to develop MRI-based biomarkers to identify patients with schizophrenia who are most likely to benefit from first-line antipsychotic or clozapine treatment. The MRI sequences (NM-MRI, MRS and rsfMRI) will be created by translating the best scientific evidence into a potential clinical product that has the highest chance of being clinically relevant predictor of treatment response. This study has the potential to significantly improve patient outcomes and reduce unnecessary interventions and costs at the Royal's Integrated Schizophrenia Recovery Program.
Detailed description
Currently, we cannot predict who will get better on first-line antipsychotic versus clozapine treatment. Although much evidence shows that dopamine and glutamate function are related to treatment response in schizophrenia, the utility of neuromelanin sensitive MRI (NM-MRI) as a measure of dopamine and magnetic resonance spectroscopy (MRS) as a measure of glutamate & glycine (a co-agonist of glutamate receptors) in predicting response to treatment have never been measured in the same sample. The evidence suggests that the function of these two neurotransmitter systems partially determines the response to antipsychotic medications. Additionally, an emerging type of resting-state functional MRI (rsfMRI), naturalistic movie-watching, has been shown to outperform traditional rsfMRI for functional connectivity-based prediction of behaviour and will be explored in the current study. Given the background information, our hypotheses are: 1.1) First-line antipsychotic users will have higher dopamine turnover resulting in a higher NM-MRI signal in the substantia nigra relative to clozapine users. 1.2) First-line antipsychotic users will have lower glutamate and/or glycine concentration as indicated by the MRS signal in the dorsal anterior cingulate relative to clozapine users.
Interventions
DRUGOlanzapine
Antipsychotic medication
DRUGClozapine
Antipsychotic medication
Sponsors
The Royal's Institute of Mental Health Research
The Royal Ottawa Mental Health Centre
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Are voluntary and competent to consent to the study * Are between the ages of 18-55 * Are English literate * Have a diagnosis of schizophrenia or schizoaffective disorder * Are currently taking primarily olanzapine or clozapine
Exclusion criteria
* Medication for the treatment of schizophrenia or schizoaffective disorder has changed in the past month * Have a significant neurologic, neurodevelopmental, cardiovascular, renal, hepatic, hematological, gastrointestinal, pulmonary, or metabolic-endocrine disorder * Are pregnant or breastfeeding * Acquire positive urine test result for all drugs of abuse including cannabis * Have met DSM-5 criteria for substance use disorder other than tobacco in the last 6 months * Have a history of significant head trauma with loss of consciousness for more than 5 minutes * Have any contraindication to MRI * Have any other condition that in the opinion of the investigator(s) could create a hazard to the subject's safety, endanger the study procedures, or interfere with the interpretation of study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neuromelanin-sensitive magnetic resonance imaging (MRI) contrast-to-noise ratio (CNR) | Will be examined cross-sectionally on an as-recruited basis. | Indexes dopamine function |
| Glutamate/glycine magnetic resonance sptrectroscopy (MRS) | Will be examined cross-sectionally on an as-recruited basis. | Indexes glutamate & glycine concentration |
Countries
Canada
Contacts
Primary ContactLauri Tuominen, MD, PhD
Backup ContactColeka Masama, BSc
Outcome results
None listed