Manchester

You will first take part in an interview with a research worker to find out if the study is suitable for you. If you are eligible and agree to participate, we (the research team), will carry out further checks including reviewing your medical and drug treatment case notes. We will arrange a basic medical examination, routine blood tests and blood pressure to make sure there is no medical reason why you should not take part. This will include a routine test which looks at your heart called an ‘ECG’. This is a quick test and is something you may have experienced if you have had a stay in hospital. We will also ask you some questions about any medical conditions you may have, and about your general physical health. We will take a research blood sample for inflammation measures (called cytokines) and genetic analysis.

During this visit you will also carry out some standard tests of your thinking and reasoning skills. These assessments are widely used and are done at your own pace. We will give full instructions about the tasks before you do them.

If you agree, after the visit we will inform your GP about you taking part in the study and your GP may provide information to us about any relevant medical problems you may have. In the unlikely situation where there is an abnormal test result (i.e. abnormalities in blood tests, or in the brain scans), we would inform your GP/Consultant of these findings.

At your next visit we would like you to complete some standard questionnaires/interviews about some of the experiences you may have. We would like to audio record the interviews. The reason for this is so that we can concentrate on talking to you during the interview instead of writing things down. We can also use the recordings to help the researchers ensure they are conducting the interviews and completing the questionnaires correctly. We will ensure that any identifiable data is removed from the recordings so it will never be possible to identify you. We would also like to video record these interviews to further help us become better at conducting these. The recordings will be kept securely and only members of the research team would be able to view them. Once the study is completed these videos will be destroyed. If you wish not to be filmed, we will respect your wishes and not video record the interview.

During this visit we would also take images of your brain using different imaging techniques. There is no set order in which these scans are done. It may be that the scans will have to take place on separate days, or sometimes on the same day. We will discuss this with you. We briefly describe here each technique we would like to do and what would be involved:

• Proton MRS (magnetic resonance spectroscopy)
  MRS takes place in a magnetic resonance imaging (MRI) scanner. This will enable us to take pictures of your brain and to also measure chemical levels. There are no dangers or side-effects of any kind using this type of scanner. No chemicals, injections, or blood samples are involved, and there is also no radiation. You lie with your head inside a short tunnel in a magnetic field. The machine makes quite a lot of noise so you wear padded earphones and there is a microphone. You can listen to music and hear or speak to the operator.  Very occasionally people find this claustrophobic so you can press a button to come out if you don’t want to continue. The proton MRS will take about 45 minutes in the scanner.

• Glucose MRS

  The Glucose MRS scan will take place in the same scanner as mentioned above (the proton MRS scan), so the procedure will be similar.

  This scan looks at how glucose is used by the brain. It involves giving a glucose infusion (administering glucose into a vein in the arm via a small tube placed in the vein called a cannula). We will closely monitor the levels of glucose in your blood stream during the scan to ensure the procedure is safe. This is done by taking a small sample of blood from another cannula placed in either in your arm, hand or foot. The infusion of glucose and the scan together will take approximately 1-1.5 hours. Once the scan is completed we will provide a meal for you to eat and will take a few more small blood samples to ensure your blood glucose levels have returned to normal levels.

  Because we are giving you an infusion of glucose, it is important that you arrive to this visit without eating anything (fasted) since the previous evening. For this reason, the scan will take place first during a morning visit. We will remind you of this fasting before the scan.

Some people with psychosis have inflammation in their body that shows up on blood tests. However, it is unclear how this relates to the symptoms of psychosis. Measuring inflammation in the brain would help us determine its involvement in developing psychosis. We can measure inflammation in the brain with a type of brain scan called Positron Emission Tomography (‘‘PET’’ for short) using a radioactive marker called 11C-PK1195.

The PET scan will take place on a separate day to the other scanning techniques. It will take place at the Wolfson Molecular Imaging Centre (WMIC) – a University of Manchester research facility.

For this scan you will have a cannula (a small plastic tube) inserted into a vein in your arm through which a blood sample will be taken to measure the level of cytokines (a marker of inflammation) in your blood.  You will then be asked to lie on a bed with your head in a PET camera and the radioactive marker will be injected through the cannula in your arm. The scan will then take place and last about 75 minutes. After the scan we will take the cannula out of your arm.

For patients with psychosis, after 12 months from finishing the study, we would like to see you again. At this visit we will repeat the questionnaires/interviews and the tests of thinking and reasoning skills.