Autor:innen:
Irene Graf, Wien (Austria)
Ana Weidenauer, Wien (Austria)
Ulrich Sauerzopf, Wien (Austria)
Irena Dajić, Wien (Austria)
Lukas Nics, Wien (Austria)
Michael Krebs, Wien (Austria)
Thomas Scherer, Wien (Austria)
Nicole Praschak-Rieder, Wien (Austria)
Wolfgang Wadsak, Wien (Austria)
Matthäus Willeit, Wien (Austria)
Up to 69% of patients with schizophrenia develop metabolic syndrome. Antipsychotics impact various metabolic processes. Increasing evidence of abnormal glucose and lipid metabolism in drug-naïve patients suggests an imbalance inherent to the disorder. Meta-analyses show decreased total (TC) and low-density lipoprotein (LDL) cholesterol and elevated triglycerides (TG) in untreated patients. Subcortical presynaptic dopamine metabolism and amphetamine-induced dopamine release are increased in psychotic patients.
To evaluate correlations of lipid profiles with dopamine D2/3 receptor binding potentials (BPND) we performed [11C]-(+)-PHNO positron emission tomography in drug-naïve patients with first episode psychosis (FEP) and healthy volunteers (HV) at baseline (1) and under 0.4 mg/KG oral amphetamine (2). TC, LDL, High density lipoprotein (HDL), HDL/LDL quotient and TG were assessed at baseline. BPND was calculated for regions of interest using simplified reference tissue model and cerebellum as reference. We used Pearson product moment correlation (r) and a two-sided 95% confidence interval with a level of significance of p=0.05.
We included 17 FEP (5f/12m; 25.1±6.3 years) and 13 HV (9f/4m; 26.3±2.6 years). BPND in globus pallidus (GP) and TG (n=16, r1=-0.664, p1=0.005; r2=-0.651, p2=0.006) were correlated significantly in FEP. BPND in putamen (PT) was correlated with TC (n=16, r2=-0.504, p2=0.046) in FEP. LDL was correlated with BPND in PT (n=16, r2=-0.568, p2=0.022) and ventral striatum (VS) (n=16, r2=-0.529, p2=0.035) in FEP. HDL was correlated with BPND in VS (n=10, r2=-0.767, p2=0.010) and GP (n1=11, r1=-0.675, p1=0.023; n2=10, r2=-0.740, p2=0.014) in HV. LDL/HDL quotient was correlated with BPND in GP (n=6, r1=0.858, p1=0.029; r2=0.923, p2=0.009) in HV.
We demonstrate significant correlations of lipid parameters with D2/3 receptor binding in brain regions of key relevance to schizophrenia, supporting the notion of altered lipid metabolism in FEP.