Effects of Ketamine on Mentalizing and Metacognition in Healthy Volunteers

Phase 4

Completed

• Conditions: Ketamine-Induced Psychotic Disorder; Social Cognition; Theory of Mind
• Interventions: Drug: Nacl 0.9%; Drug: Ketamine

• Registration Number: NCT05320991
• Lead Sponsor: University Hospital, Bonn

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-06-15
• Primary Completion: 2020-09-27
• Study Completion: 2020-09-27
• Study First Submitted: 2022-03-14
• Status Verified: 2022-04
• Study First Submitted QC: 2022-04-01
• Study First Posted: 2022-04-11
• Last Update Submitted: 2022-04-11
• Last Update Posted: 2022-04-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Nacl 0.9%	Participants receive a saline-solution intravenously
Ketamine	Ketamine	Participants receive ketamine (Plasma-level 100 ng/ml with an initial bolus administered as a 2 mg/ml solution)

Primary Outcome Measures

Name	Time	Method
Changes in Mentalizing/Theory of Mind	During ketamine/placebo application in MRI	Over- and undermentalizing as characterized by the Movie for the assessment of social cognition (MASC). Higher scores on the "Mentalizing"-scale indicate better performance. Scores are divded between 4 scales (Mentalizing, No Mentalizing, Overmentalizing, Undermentalizing), each ranging from 0 to 27. Higher scores in one of the scales pertaining to "no Mentalizing, Overmentalizing or Undermentalizing mean a deficiency in mentalizing skills.
Neural response to ketamine/placebo during social cognition	During ketamine/placebo application in MRI	fMRI imaging will be performed to measure blood oxygen level-dependent (BOLD) signal in response to mentalizing cues in the MASC-task under ketamine/placebo. BOLD-signal will be measured with T2-weighted images in a 3T MRI. Data will be analyzed using SPM 12 in MATLAB. Deviations in BOLD-activity under ketamine compared to placebo (higher or lower activity of certain voxels/clusters compared all other voxels in the brain) will mean a change in neural response due to the effect of the substance

Secondary Outcome Measures

Name	Time	Method
Psychotic symptom load in PANSS-Questionnaire	10 minutes after cessation of MRI and ketamine/placebo application	Positive and negative symptoms measured with questionnaire used in schizophrenia-research (Positive and Negative Symptom Scale). The PANSS uses a scale ranging from 1 to 7 in three different subscales (positive, 7 items; negative, 7 items; disorganized, 16 items). Higher numbers mean more psychotic symptoms.
Metacognitive-Questionnaire (MCQ)	20 minutes after cessation of MRI and ketamine/placebo application	Metacognitive typology as assessed with the MCQ. The MCQ is a questionnaire containing 30 items, based on a 4-point Likert scale (dont agree - strongly agree) from 1 to 4. It measures metacognitive ability in 5 subscales, each containing 6 items (Uncontrollability and Danger, Cognitive Self-Consciousness, Need to control thoughts, Positive Beliefs, Cognitive Confidence). This is a short form of the widely used Metacognitions Questionnaire that measures individual differences in a selection of metacognitive judgments and monitoring tendencies considered important in the metacognitive model of psychological disorders

Trial Locations

Locations (1)

Department of Psychiatry and Psychotherapy, University Hospital Bonn; 🇩🇪 Bonn, Germany