Ketosis Impact on Signs & Symptoms of Schizophrenia and Bipolar disorderS

Pilot Study on Ketosis Impact on Signs and Symptoms of Schizophrenia and Bipolar Disorders

The goal of this clinical trial is to learn if a ketone drink can improve signs and symptoms of patients with a schizophrenia-spectrum disorder (SSD), or a bipolar-spectrum disorder (BD).

The main questions it aims to answer are:

Does a ketone drink improve information processing in patients with SSD/BD?

Other questions it aims to answer are:

Does a ketone drink improve cognitive functioning in patients with SSD/BD? Does a ketone drink improve metabolism and inflammation in patients with SSD/BD? Does a ketone drink affect circadian rhythm in patients with SSD/BD?

Research will compare the effects of the ketone drink with that of an isocaloric carbohydrate drink in the same patients ('cross-over').

Participants will:

1. drink a ketone drink and (after a wash-out period) an isocaloric control drink (randomized order); after each drink:

   • EEG/EMG to determine information-processing parameters (PPI and P300)
   • cognitive tests
   • visual analog scale of mood, energy levels, ability to focus
   • indirect calorimetry to determine use of energy substrate
   • blood draws

2. for 5 consecutive days:

   • wear a continuous glucose monitor (CGM)
   • wear a non-invasive passive sweat biomarker sensor (EnLiSense device)
   • register a diet and nicotine diary
   • saliva sampling (max. 5x/day)

Inclusion Criteria:

• Patients with a first-episode psychosis (underlying schizophrenia-spectrum disorder), or patients with a (hypo)manic or depressive episode (underlying bipolar disorder)
• Age >= 18 years old
• Receiving standard care (including antipsychotic and mood stabilizing medication)
• Mentally competent to give informed consent:

Exclusion Criteria:

• Substance use as cause of psychosis or (hypo)mania
• Substance use (other than nicotine) in the week prior to study onset
• Intellectual disability
• Diabetes mellitus (type 1 or type 2)
• Metabolic disease impacting ketone metabolism (NB: these are rare disorders diagnosed during childhood)
• Liver disease
• Kidney disease
• Cardiovascular disease
• Pregnancy
• Breastfeeding