We hypothesized that short-term treatment with AP drugs induces insulin resistance through a mechanistic route that is independent of weight gain and that atypical drugs exert stronger effects than typical compounds in this respect. We therefore treated healthy non-obese men with olanzapine (atypical AP) or haloperidol (typical AP) for 8 days, and studied the impact of these interventions on glucose and lipid metabolism by hyperinsulinemic euglycemic clamp, isotope dilution technology and indirect calorimetry.

Inclusion Criteria:

• Healthy men, with and without a positive family history of schizophrenia.
• 20 kg/m2 < BMI < 26 kg/m2
• Age 20-40 years
• Fasting plasma glucose < 6 mmo/L

Exclusion Criteria:

• FPG > 6 mmol/L
• BMI > 26 kg/m2
• Psychiatric disorders and/or use of antipsychotic or antidepressants drugs at present or in the past.
• Any significant chronic disease
• Renal, hepatic or endocrine disease
• Use of medication known to influence lipolysis and/or glucose metabolism
• Total cholesterol > 7mmol/L and/or triglycerides > 2 mmol/L
• Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months)
• Difficulties to insert an intravenous catheter
• Smoking (current)
• Severe claustrophobia (ventilated hood)
• Recent blood donation (within the last 2 months)
• Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
• Extensive sporting activities (more than 10 hours of exercise per week)