Phospholipase A2 activity in first episode schizophrenia: associations with symptom severity and outcome at week 12.

OBJECTIVES: Intracellular phospholipases A2 (inPLA2) are activated during monoaminergic neurotranismision and act as key enzymes in cell membrane repair and remodelling, neuroplasticity, neurodevelopment, apoptosis, synaptic pruning, neurodegenerative processes and neuroinflammation. Several independent studies found increased inPLA2 activity in drug-naïve first episode and chronic schizophrenia. This study investigates if inPLA2 activity is associated with symptoms severity and treatment response in first episode schizophrenia (FES). METHODS: InPLA2 activity was measured in serum of 35 young FES patients (mean age: 19.36 ± 3.32, mean duration of illness: 7.53 ± 6.28 months, 16 neuroleptic-naïve) before and after 12 weeks of treatment with second-generation antipsychotic medications (olanzapine, quetiapine or risperidone), as well as in 22 healthy controls matched for age. Psychopathology and social functioning were assessed at the same time points. RESULTS: Baseline inPLA2 activity was significantly increased in drug-naïve and treated FES patients compared to healthy controls. Baseline inPLA2 activity was also associated with severity of negative symptoms and lower functioning at baseline. Furthermore, baseline inPLA2 activity was associated with improvement in negative symptoms and functioning within the first 12 weeks of treatment. CONCLUSIONS: Intracellular PLA2 activity is increased in first episode schizophrenia and associated with symptom severity and outcome after 12 weeks of treatment. Future studies should investigate the implications of inPLA2 activity as a potential predictor of treatment response for different antipsychotic agents.

Metabolic mapping using 2D 31P-MR spectroscopy reveals frontal and thalamic metabolic abnormalities in schizophrenia.

(31)Phosphorus magnetic resonance spectroscopy ((31)P-MRS) allows in vivo investigation of cerebral phospholipid and energy metabolism. Using 2D chemical shift imaging, this method can be applied to study multiple brain areas and to assess concentrations of both phospholipids and high-energy phosphates. The purpose of our study was to assess multiregional metabolic profiles in schizophrenia using a 2D-resolved MRS technique, and to assess the intercorrelation of findings. We applied (31)P-MRS chemical shift imaging in 31 schizophrenia patients (12 antipsychotic-naïve first-episode and 19 antipsychotic-free multi-episode patients) and 31 healthy age- and sex-matched controls. Spatially resolved maps were compared for the main metabolites of the (31)P spectrum. Metabolites of phospholipid (PME and PDE) and energy (PCr and Pi) metabolism were significantly reduced in bilateral prefrontal and medial temporal (including hippocampal) brain regions, caudate nucleus, thalamus and anterior cerebellum as compared to controls. Moreover, factor analysis of these changes showed a characteristic spatial pattern of changes, which demonstrates significant associations between alterations of phospholipid and energy metabolism, and between metabolic alterations and severity of symptoms (BPRS total score, but not SANS or SAPS scores). This suggests a pattern of intercorrelated changes of these metabolic markers. Results support the notion of disturbed phospholipid turnover in schizophrenia, probably unrelated to prior pharmacological treatment, and associated with increased energy demand.