Eligibility criteria
TB, Psychosis, psychotic disorder, traumatic brain injury, uncontrolled gastric/duodenal ulcer, malignancy, hallucinatory, psychiatric, ischaemic heart disease, inflammation, schizophrenia, VZV, autism, psychoses, allergic or anaphylactic reactions, delusions, infection, antisocial personality disorder, TB.Any, Hepatitis B, varicella zoster, eating disorder, neurodevelopmental disorder
DISORDER, DISEASES, UNCONTROLLED HYPERTENSION, VARICELLA ZOSTER, OPPORTUNISTIC INFECTIONS, ISCHAEMIC HEART DISEASE, POSITIVE, INFLAMMATORY BOWEL DISEASE, CHICKEN POX, INFLAMMATION, VIRUS, DIVERTICULITIS, SYNDROME, TUBERCULOSIS, INFECTION, HEPATITIS B, HEPATITIS C
We will recruit participants aged 18–40 years. Patient participants must meet International Classification of Diseases 10th Revision (ICD-10) criteria for a diagnosis of schizophrenia and related psychoses (ICD-10 code F20, F22, F25, F28, F29) at the time of eligibility assessment, be within 3 years of first diagnosis of psychotic disorder, be on a stable treatment regime with no recent (within 2 weeks) initiation, cessation or change in class of antipsychotic medication and have a Positive and Negative Syndrome Scale (PANSS) item score ≥3 on P1 (delusions), P2 (conceptual disorganisation), P3 (hallucinatory behaviour) or P6 (suspiciousness/persecution). Additionally, patients recruited to the interventional arm will be required to have serum IL-6 levels≥0.7 pg/mL and a Temporal Experience of Pleasure Scale (TEPS) anticipatory pleasure score ≤41 (based on item numbers 1, 3, 7, 11, 12, 14, 15, 16, 17 and 8) and consummatory pleasure score ≤36 (based on item numbers 2, 4, 5, 6, 8, 9, 10 and 13). The threshold of serum IL-6≥0.7 pg/mL as evidence of inflammation for this particular trial was chosen based on observations from the Personalised Prognostic Tools for Early Psychosis Management (PRONIA) cohort (HCs will have no current or lifetime history of psychiatric diagnosis, as determined by the Mini-International Neuropsychiatric Interview (MINI). See Psychosis Immune Mechanism Stratified Medicine trial inclusion and exclusion criteriaProvide informed consent.Understand written and spoken English.Able and willing to consent to blood sampling.Willing to abstain from strenuous exercise for 72 hours prior to assessment.Pregnancy (confirmed by urine pregnancy test) or breast feeding.Body mass index>35.Current or lifetime diagnosis of antisocial personality disorder, autism or other neurodevelopmental disorder, major traumatic brain injury.Currently active diagnosed eating disorder likely to compromise ability to take part.History of alcohol or substance use disorder (abuse/dependence) within 6 months prior to eligibility assessment (nicotine and caffeine dependence are not exclusionary).Current use of medication likely to compromise interpretation of immunological data.Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other opportunistic infections.Current infection with VZV, TB, Hepatitis B, Hepatitis C or HIV confirmed by blood test. X-ray of the chest will also be performed to assess for TB.Any major episode of infection requiring hospitalisation or treatment with intravenous antibiotics within 4 weeks of eligibility assessment.Unstable cardiac, pulmonary, renal, hepatic, endocrine, haematologic or active infectious disease, including current or prior malignancy.Diverticulitis, inflammatory bowel disease or uncontrolled gastric/duodenal ulcer.Concomitant autoimmune or autoinflammatory rheumatological disease.Concomitant treatment with any biologic drugs.Current and active ischaemic heart disease.Uncontrolled hypertension defined as systolic blood pressure>170 mm Hg or diastolic blood pressure>110 mm Hg.History of severe allergic or anaphylactic reactions to human, humanised or murine monoclonal antibodies.No history of chicken pox infection or no history of varicella zoster immunity.Able and willing to consent to MRI scanning.Contraindications to MRI.No current or lifetime psychiatric diagnosis.Meet ICD-10 criteria for a diagnosis of schizophrenia and related psychoses (code F20, F22, F25, F28, F29) at the time of eligibility assessment, as determined by the Mini-International Neuropsychiatric Interview.Be within 3 years of first diagnosis of psychotic disorder.On stable treatment regime with no recent (within 2 weeks) initiation, cessation or change in class of antipsychotic medication.No indication or other reason for preclusion into research (eg, significant risk of suicidal behaviour or risk to others) as determined by their clinical team.Positive and Negative Syndrome Scale item score≥3 on P1 (delusions), P2 (conceptual disorganisation), P3 (hallucinatory behaviour) or P6 (suspiciousness/persecution).Serum IL-6 level≥0.7 pg/mL at eligibility and baseline assessment.Temporal Experience of Pleasure Scale anticipatory pleasure score≤41 (based on item numbers 1, 3, 7, 11, 12, 14, 15, 16, 17 and 8) and consummatory pleasure score≤36 (based on item numbers 2, 4, 5, 6, 8, 9, 10 and 13).Evidence of COVID-19 immunity required prior to infusion, confirmed before randomisation using evidence of vaccination and antibody titre test.Serum IL-6 level<0.7 pg/mL at eligibility and baseline assessment.ICD-10, International Classification of Diseases 10th Revision; IL-6, interleukin 6; TB, tuberculosis; VZV, varicella zoster virus.