Effects of Ketamine and Risperidone on Cognition

Inclusion Criteria:

5.2.1 General inclusion criteria (healthy and schizophrenia groups)

* Male or female aged 18 to 45 years
* Fluent English speakers, preferably with English as first language.
* Normotensive with sitting (5 minutes) blood pressure of 100 to 140 mmHg systolic, and 60 to 90 mmHg diastolic.
* Negative alcohol breath test.
* Negative urine drug screen.
* Participant must have consumed only their normal intake of coffee or tea on the morning of the assessment day and not consumed any other beverages containing caffeine for 2 hours prior to the assessment visit.
* Willing to follow the protocol prohibitions and restrictions .
* Participant must have signed the informed consent form.
* Those participants willing to participate in the pharmacogenomic components of the study must have signed the appropriate informed consent form.

5.2.2 Inclusion criteria applicable to healthy volunteers only

* SPQ score of 21 to 36.
* BMI of 18 to 30 kg/m².
* Non-smoker or light smoker (less than 5 cigarettes per day).
* Has not smoked in the 2 hours prior to the assessment visit.
* Females should be surgically sterile or abstinent or practising an effective method of birth control; they should have a negative urine pregnancy test.
* Healthy at screening and assessment visits as determined by the study physician, based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs, 12-lead ECG and pre-study psychological tests.

5.2.3 Inclusion criteria applicable to participants with schizophrenia only

* Documented history of a diagnosis of schizophrenia as confirmed by GP or psychiatrist or by previous research diagnostic interview.
* Confirmation of diagnosis of schizophrenia, based on the MINI structured clinical interview, carried out by the study physician.
* In good physical health at screening and assessment visits as determined by the study physician, based on a medical evaluation including medical history, physical examination, laboratory tests and vital signs1.

Exclusion Criteria:

5.3.1 General exclusion criteria (healthy and schizophrenia groups)

* History of alcohol or substance dependence.
* Consumption of large amounts of caffeinated drinks.
* Have received over-the-counter medicine within 48 hours prior to assessment visit (apart from paracetamol) unless it will not interfere with the study procedures or compromise safety.
* History of, or current condition of, migraine headaches.
* Significant hearing impairment which in the opinion of the Investigator may interfere with the performance of the psychological test battery.
* Significant visual impairment or history of ocular treatment or ongoing condition which may interfere with the performance of the psychological test battery.
* Participated in a trial with any drug within 84 days of assessment visit.
* Unable or unwilling to comply with study procedures.

5.3.2 Exclusion criteria applicable to healthy volunteers only

* Known or suspected hypersensitivity or intolerance to risperidone or any of their excipients.
* Known or suspected hypersensitivity or intolerance to ketamine or any previous adverse reaction to anaesthesia.
* If female: are pregnant or are trying to get pregnant or are currently breast feeding.
* Relevant history, or presence upon clinical examination, of cardiac, ophthalmologic, gastro-intestinal, hepatic, or renal disease or other condition known to increase risk of side effects.
* History or presence of neurological or psychiatric conditions.
* Have received prescribed medication within 14 days prior to assessment visit (apart from the contraceptive pill) unless it will not interfere with the study procedures or compromise safety.

5.3.3 Exclusion criteria applicable to participants with schizophrenia only

* Changes to antipsychotic medications within 30 days of assessment visit.
* Admission to hospital, involvement with the home treatment team for psychiatric reasons or documented relapse of psychiatric symptoms within last 3 months.
* History or presence of psychiatric or neurological conditions other than schizophrenia, major depression and generalised anxiety disorder.
* Current extra-pyramidal symptoms and/or adverse effects from antipsychotic medications that, in the opinion of the study physician, will interfere with completion of the study tasks.