None listed
Conditions
Brief summary
Psychosis is a debilitating neuropsychiatric syndrome characterized by delusions, hallucinations, disorganized thinking and cognitive and emotional disturbances. It is a defining characteristic of schizophrenia, and occurs frequently in other major mental illnesses such as depression and bipolar disorder. All current treatments for psychosis modulate levels of the neurotransmitter dopamine (DA), and it is thought that DA dysregulation within circuits linking frontal brain regions with a set of subcortical nuclei called the striatum (the so called frontostriatal circuits) is a final common pathway for the emergence of psychotic symptoms. Precisely how this dysregulation arises however, remains a mystery. This study will be the first to combine Positron Emission Technology (PET) measures of striatal DA function with functional Magnetic Resonance Imaging (fMRI) measures of frontostriatal connectivity to investigate the way in which altered subcortical dopamine may give rise to, or arise from, aberrant frontostriatal connectivity. The project has three specific aims: 1. characterise the direct relationship between PET markers of striatal DA function and fMRI measures of frontostriatal functional dysconnectivity; 2. determine whether striatal DA abnormalities are a cause or consequence of frontostriatal dysconnectivity; and 3. investigate the potential of these two phenotypes as clinical biomarkers by determining whether they can predict patients’ 12month clinical outcome. We will recruit 50 First Episode Psychosis (FEP) patients and 50 healthy controls to take part in the study. All participants will complete a clinical and brain imaging assessment at baseline. The brain imaging assessment will involve MRI and PET. FEP patients will additionally complete a clinical assessment after a 12 month followup period. No brain imaging will be conducted at this time. No followup of controls will be performed. During the followup period, the research staff will maintain regular contact with the patients' clinical team. Information on treatments will be acquired, enabling us to account for variations in treatment protocols in our analyses.
Interventions
1. Baseline
All participants will complete a baseline assessment
a. Patients will complete the following over 2 visits ideally within one week:
i. Clinical assessment (3 hours)
ii. PET-MRI imaging (3 hours)
The same protocol will be used for healthy controls, though the clinical assessment will be briefer, involving some questionnaires and a structured diagnostic interview
a. Healthy control participants will complete the following over 2 visits ideally within one week:
i. Clinical assessm
1. Baseline All participants will complete a baseline assessment a. Patients will complete the following over 2 visits ideally within one week: i. Clinical assessment (3 hours) ii. PET-MRI imaging (3 hours) The same protocol will be used for healthy controls, though the clinical assessment will be briefer, involving some questionnaires and a structured diagnostic interview a. Healthy control participants will complete the following over 2 visits ideally within one week: i. Clinical assessment (3 hours) ii. PET-MRI imaging (3 hours) 2. 12-month follow-up Patients only will complete a 12-month follow-up assessment, involving: a. Detailed clinical assessment (3 hours) No brain imaging is required at 12-month follow-up
Sponsors
Monash University
Eligibility
Sex/Gender
All
Age
18 Years to 25 Years
Healthy volunteers
Yes
Inclusion criteria
Patient Inclusion criteria: *Experiencing a first episode of psychosis (one or more psychotic symptoms on a daily basis for at least one week) and meeting diagnostic criteria for one of the following DSM-IV disorders: schizophreniform psychosis, schizophrenia, schizoaffective disorder, delusional disorder, brief psychosis, major depressive disorder or bipolar disorder with psychotic features, or psychosis NOS. *Age range 18-25 years *Within 3 months of commencing regular antipsychotic treatment; or lifetime cumulative exposure of < 3 months; or no antipsychotic treatment for at least one year *Ability to provide informed consent as determined either via the clinical opinion of the treating medical physician, or the administration, by one of the research team, of the MacArthur Competence Assessment Tool for Clinical Research. Healthy Control Participant Inclusion criteria: * Psychiatrically healthy individual aged 18-25 years
Exclusion criteria
Patient Exclusion criteria: * Primary diagnosis of Borderline Personality Disorder or Post-Traumatic Stress Disorder * Intellectual disability * Colour blindedness * Diagnosis of substance dependence * History of neurological disorder, brain injury, or significant loss of consciousness * MRI/PET contraindications (pregnancy, breastfeeding, metal implants) * Contraindications for Carbidopa and Entacapone (treatment with MAO inhibitors, blood/needle phobia, glaucoma, malignant melanoma, phaechromocytoma, rhabdomylosis, history of major medical condition such as diabetes, cardiovascular disease, hepatic/renal failure, etc). Healthy Control Participant Exclusion criteria: *Personal history of psychiatric or neurologic illness *First-degree relatives with psychotic illness *Intellectual disability *History of neurological disorder, brain injury, or significant loss of consciousness * MRI/PET contraindications (pregnancy, breastfeeding, metal implants) * Contraindications for Carbidopa and Entacapone (treatment with MAO inhibitors, blood/needle phobia, glaucoma, malignant melanoma, phaechromocytoma, rhabdomylosis, history of major medical condition such as diabetes, cardiovascular disease, hepatic/renal failure, etc).
Outcome results
None listed