Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

A Randomized Control Trial Employing fMRI to Investigate the Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

Antipsychotic medication shows generally good effect sizes when looking at reduction of positive psychotic symptoms of schizophrenia, such as paranoia or delusion. However, social functioning often remains deficient in patients, meaning dopamine-receptor antagonists are not sufficient in treatment of people with schizophrenia.

A naturalistic video-based paradigm, named MASC has been used in the past to model over- and undermentalizing in patients with autism spectrum disorder and schizophrenia, since deficits in mentalizing can be explained by either overinterpreting a social situation (e.g. paranoid thoughts about intentions of others towards self) or by lacking the skill to read intentions of others.

To find out whether experimental manipulation via a non-competetive N-methyl-D-aspartate antagonist can induce difficulties with social cognition similar to those observed in people with schizophrenia, the investigators will conduct a RCT applying either ketamine or a placebo intravenously while participants are completing the above mentioned mentalizing task in the fMRI-scanner.

Potential participants are excluded based on the following criteria:

• history of psychiatric/neurological disorder (self and first-degree relatives)
• learning disabilities, or loss of consciousness for more than 5 minutes
• history of alcohol or drug abuse within the last 12 months
• history of ketamine abuse
• history of complications during anesthesia (self and first-degree relatives)
• serious physical illness
• claustrophobia
• color-blindness
• metalliferous implant
• visual impairments other than corrective lenses
• injury or disease of the inner ear with loss of hearing
• consumption of any prescription or over-the-counter medication 3 days previous to the examination
• pregnancy
• currently breastfeeding a baby
• hypotension (blood pressure < 100/60)
• hypertension (blood pressure > 140/90)
• underweight (BMI <17)
• overweight (BMI ≥30)

Recruited participants are required to meet the following criteria:

• height between 150 and 195 cm
• bodyweight between 50 and 99kg
• male or female
• right-handed
• physically, neurologically and psychiatrically healthy
• non-smoker
• normal or corrected-to-normal eye-sight
• good command of German language