A study of antipsychotic response and cognition using TMS-EEG V1
Overview
Almost a third of people with schizophrenia/schizoaffective disorder are ‘treatment-resistant’, meaning that their symptoms do not respond to treatment with antipsychotics. This results in people having side effects from trying several antipsychotics without improvement of their symptoms.
The pharmacological treatment for schizophrenia, the antipsychotic medications, work through the reduction of a brain chemical called dopamine. Research suggests that the response to antipsychotics may be associated with an imbalance in other brain neurochemicals, such as GABA and glutamate. A thinking ability called cognitive control may also play a role in the response of the symptoms to antipsychotics and research has shown a link between difficulties in cognitive control and more severe symptoms of schizophrenia.
We will use a brain stimulation technique called Transcranial Magnetic Stimulation (TMS) to activate two brain areas, the left primary motor cortex and the left dorsolateral prefrontal cortex, and we will record the brain activity using electroencephalography (EEG). Previous TMS-EEG studies have shown that the activation of the brain following TMS reflects GABA and glutamate release. We will also study if thinking abilities play a role in the response of people’s symptoms to antipsychotics. Participants will be invited to the research site for 3 visits:
1) Screening visit to establish eligibility for participation in the study
2) During the second visit participants will be asked to complete cognitive tests and
3) During the third visit participants will have a TMS-EEG session as above.
We will recruit 44 responders and 44 non-responders to antipsychotics with schizophrenia/schizoaffective disorder and 25 healthy controls. The study will last three years.
The study will develop our understanding on the brain mechanisms of antipsychotic response and will contribute to the identification of candidate neurophysiological and cognitive predictive biomarkers for response to antipsychotics, which can guide treatment in a more effective and safer, patient-centred manner as soon as possible after the initial diagnosis.
The research is funded by MRC-CARP award to the Principal Investigator, Dr Panagiota Michalopoulou, and will be conducted at the NIHR/Wellcome King's Clinical Research Facility (CRF), 1st floor Cheyne Wing, King’s College Hospital NHS Foundation Trust, Denmark Hill SE5 9RS, London.
Are you interested in taking part in this study?
Conditions
SchizophreniaInclusion Criteria
Inclusion criteria for all participants:
— Males or females
— Aged between 18-55
— Right-handed
— Score< = 20 in Beck Depression Inventory
— Physically healthy based on medical history as per interview at screening visit and medical notes
— Negative urine pregnancy test at screening visit
— Sufficient command of English to complete study-related assessments
— Capacity to give written informed consent
— Additional Inclusion criteria for patients
— Schizophrenia/Schizoaffective Disorder diagnosis as per DSM-5
— Outpatient with no hospitalisation for worsening of schizophrenia/schizoaffective disorder within at least 3 months prior to screening visit
— Stable antipsychotic treatment for at least 3 months prior to screening visit and adherent with treatment, as per self-report and medical notes
— AP monotherapy with either olanzapine, aripiprazole, risperidone or paliperidone for both responder and non-responder groups
— Responders will have a score of 3 or less on all items of the Positive and Negative Symptom Scale (PANSS)
— Non-responders will have: i) a score of at least 4 (moderate) on at least two positive symptom items of the PANSS and ii) at least two prior antipsychotic trials of at least 4-6 weeks duration with inadequate clinical improvement
Additional inclusion criteria for Healthy controls:
— No personal or family history of psychotic disorder
Exclusion Criteria
Exclusion criteria for all participants:
— Diagnosis of alcohol or substance dependence (other than nicotine) in the last 6 months preceding the screening visit as per Mini — International Neuropsychiatric Interview (MINI) and the participant’s medical notes
— Treatment with CNS active medications (other than antipsychotics for patients) that may affect performance on the study-related tasks, such as benzodiazepines, sleep medications or stimulants in the last 3 months prior to screening visit
— Severe/uncontrolled/unstable physical illnesses that may affect participation in the study or pose a risk to the participant’s safety such as, uncontrolled diabetes, hypertension, asthma, cardiac-related problems including syncopal episodes
— Systematic neurological disorder, including stroke, significant traumatic brain injury, epilepsy, multiple sclerosis, Parkinson's disease
— Significant head or spinal cord injury
— Diagnosis of migraine
— Pregnancy or lactation
— Unwillingness or inability to follow the protocol procedures
— Participation in research studies using brain stimulation or cognitive enhancing medications in the last 3
months prior to screening visit
— Contraindications to TMS as per TMS safety guidelines including:
— History of epileptic seizures and/or previous or current diagnosis of epilepsy as per participant’s medical r records
— On medications with seizure threshold lowering potential including imipramine, amitriptyline, doxepine, nortriptyline, maprotiline, chlorpromazine, foscarnet, ganciclovir, ritonavir, theophylline, chloroquine, mefloquine, imipenem, penicillin, ampicillin, cephalosporins, metronidazole, isoniazid, levofloxacin, cyclosporin, chlorambucil, vincristine, methotrexate, cytosine arabinoside, lithium, sympathomimetics.
— Presence of metallic hardware and /or implants that contain magnets on the skull/brain, such as intracranial ferromagnetic metal implants, cochlear implants or medications pumps, implanted neurostimulators, such as Deep Brain Stimulators
— Cardiac pacemaker or intracardiac lines
— Presence of metal in the body
Additional exclusion criteria for patients:
— Current treatment with Clozapine or unsuccessful trial with Clozapine in the last 3 months prior to screening visit
— Electroconvulsive therapy (ECT) in the last 6 months prior to the screening visit