Within the schizophrenia population, there are individuals that respond to first-line antipsychotic treatments while others do not. The availability of muscarinic M4 subtype receptors (M4R) may play a role as to whether a person with schizophrenia is responsive to first-line antipsychotics or not. The goal of this observational study is to compare the availability of M4R in antipsychotic-free patients with schizophrenia and matched healthy controls. In addition, M4R availability in schizophrenia patients will be examined in relation to response to first line antipsychotics and clinical and cognitive measures. This study may help better understand antipsychotic resistance in schizophrenia and lead to the development of new treatment options, particularly for cognitive deficits and negative symptoms.
This study is composed of two participant groups. 1) Antipsychotic-free patients with schizophrenia and 2) healthy matched controls. The healthy controls will be matched as closely as possible for age, sex, cannabis, and nicotine consumption to the patient group. All participants will undergo a positron emission tomography (PET) scan to measure the M4R binding with \[11C\]MK-6884 and examine its relationship with clinical and cognitive measures. Participants who meet the inclusion and exclusion criteria at screening visit (visit 1) will be enrolled into the study. All participants will undergo a PET scan with the novel tracer \[11C\]MK-6884 to examine its binding with M4R. The third visit will consist of a MRI scan and cognitive assessments. Participants with schizophrenia will have visit four, which occurs 6 weeks after the first antipsychotic trial, initiated by their treating physician. If the treating physician starts a second antipsychotic trial, then a visit five occurs 6 weeks after the second trial. Both visits four and five involve clinical and cognitive assessments.
Study Type
OBSERVATIONAL
Enrollment
58
PET scan using the novel \[11C\]MK-6884 tracer to measure M4R during the antipsychotic-free state
Centre for Addiction and Mental Health
Toronto, Ontario, Canada
M4 receptor expression
Regional \[11C\]MK-6884 uptake will be quantified as volume of distribution (VT) and binding potential relative to non-displaceable compartment (BPND), as defined by consensus nomenclature for in vivo imaging of reversibly binding radioligands. Ichise's multilinear analysis (MA1) method will be employed to quantify VT, using arterial blood sampling. The simplified reference tissue model (SRTM) will be used to estimate BPND, using the cerebellum as a reference region.
Time frame: At baseline
Clinical Data Statistical Analysis
Exploratory correlations will be performed between clinical symptoms and whole brain VT within the patient group.
Time frame: At baseline and 6 week Follow-up after antipsychotic trial
Statistical Analysis of Cognitive Data
Correlations will be analyzed between memory performance and dorsal striatal VT within the patient group and healthy control group, respectively. Exploratory correlations will be performed between all other cognitive measures and whole brain VT within each group, separately.
Time frame: At baseline and 6 week Follow-up after antipsychotic trial (only for patient group)
Statistical Analysis of Psychopathological Personality Traits in Health Control Group
Correlations will be performed between trait impulsivity and ventral striatal VT within the healthy control group. Exploratory correlations will be performed between all other personality trait measures and whole brain VT
Time frame: At baseline
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