Phospholipase A2 activity is associated with structural brain changes in schizophrenia

• Published in: NeuroImage (Orlando, Fla.) Vol. 52; no. 4; pp. 1314 - 1327
• Main Authors: Smesny, Stefan, Milleit, Berko, Nenadic, Igor, Preul, Christoph, Kinder, Daniel, Lasch, Jürgen, Willhardt, Ingo, Sauer, Heinrich, Gaser, Christian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2010; Elsevier Limited
• Subjects: Adult; Attention deficit hyperactivity disorder; Biomarkers - blood; Brain; Brain - pathology; Enzymes; Female; Gray matter; Humans; Imaging; Magnetic Resonance Imaging; Male; Marker; Membrane lipids; Middle Aged; Morphometry; MRI; Oxidative stress; Phospholipases A2 - blood; Phospholipids; Psychotropic drugs; Schizophrenia; Schizophrenia - blood; Schizophrenia - pathology; Studies; White matter; Membrane lipids; MRI; Imaging; Schizophrenia; Phospholipids; Marker; Morphometry; Gray matter; White matter
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2010.05.009

Regional structural brain changes are among the most robust biological findings in schizophrenia, yet the underlying pathophysiological changes remain poorly understood. Recent evidence suggests that abnormal neuronal/dendritic plasticity is related to alterations in membrane lipids. We examined whether serum activity of membrane lipid remodelling/repairing cytosolic phospholipase A2 (PLA2) were related to regional brain structure in magnetic resonance images (MRI). The study involved 24 schizophrenia patients, who were either drug-naïve or off antipsychotic medication, and 25 healthy controls. Using voxel-based morphometry (VBM) analysis of T1-high-resolution MRI-images, we correlated both gray matter and white matter changes with serum PLA2-activity. PLA2 activity was increased in patients, consistent with previous findings. VBM group comparison of patients vs. controls showed abnormalities of frontal and medial temporal cortices/hippocampus, and left middle/superior temporal gyrus in first-episode patients. Group comparison of VBM/PLA2-correlations revealed a distinct pattern of disease-related interactions between gray/white matter changes in patients and PLA2-activity: in first-episode patients (n=13), PLA2-activity was associated with structural alterations in the left prefrontal cortex and the bilateral thalamus. Recurrent-episode patients (n=11) showed a wide-spread pattern of associations between PLA2-activity and structural changes in the left (less right) prefrontal and inferior parietal cortex, the left (less right) thalamus and caudate nucleus, the left medial temporal and orbitofrontal cortex and anterior cingulum, and the cerebellum. Our findings demonstrate a potential association between membrane lipid biochemistry and focal brain structural abnormalities in schizophrenia. Differential patterns in first-episode vs. chronic patients might be related to PLA2-increase at disease-onset reflecting localized regenerative activity, whereas correlations in recurrent-episode patients might point to less specific neurodegenerative aspects of disease progression.