Benefits and Meaning of Lipids Profile in Relation to Oxidative Balance and Brain Morphology in Schizophrenia

Abstract

Schizophrenia is characterized by complex metabolic dysregulations and their consequences. Until now, numerous theories have explained its pathogenesis, using a spectrum of available technologies. We focused our interest on lipid profile-periphery high-density cholesterol level and lipoproteins in the human brain and compared magnetic resonance imaging (MRI) scans of patients with schizophrenia and the healthy group. Detailed analysis of biochemical parameters was performed using magnetic resonance spectroscopy. Our study aimed to reveal correlations between periphery high-density lipoproteins levels and lipoproteins in the brain, depicted in MRI scans, and parameters of peripheral oxidative stress expressed as paraoxonase. Patients with schizophrenia have decreased levels of high-density lipoproteins, low paraoxonase activity, and slightly raised sodium in the blood. Positive significant correlations between serum high-density cholesterol and anterior cingulate cortex, unique brain area for schizophrenia pathophysiology, MR spectroscopy signals, and diffusion have been revealed. To our knowledge, this is the first study to describe the effect of an anterior cingulate disorder on high-density cholesterol levels on the development of schizophrenia.

Keywords: brain morphology; high-density cholesterol (HDL); lipids profile; magnetic resonance; oxidative stress; schizophrenia.

Figure 1

Relationship between the number of neutrophils and the T scale in the study group.

Figure 2

Correlation between LDL level and PON in the study group.

Figure 3

Correlation between triglycerides level and PON in the study group.

Figure 4

VOI location for spectroscopy in the human brain in MRI images. (A) the sagittal midline section; (B) the coronal section; (C) the transverse section.

Figure 5

VOI location for spectroscopy in the human brain in MRI images. (A) the coronal section; (B) the transverse section.

Figure 6

Spectroscopic spectrum in the patient from the study group: the right frontal lobe (A), the left frontal lobe (B) and the anterior cingulate cortex (ACC) (C).

Figure 7

Fractional anisotropy map with marked ROI for measuring FA of patient with schizophrenia in the right and left frontal lobe.

Figure 8

Fractional anisotropy map with marked ROI for measuring FA of patient with schizophrenia in the right and left anterior cingulate cortex.

Figure 9

Central and peripheral actions of HDL in patients with schizophrenia disorders. PON-1 activity is decreased in patients in a psychotic decompensation comparison with healthy people. We hypothesized that PON-1 may be a dysfunctional unit, which has not protected HDL or LDL from oxygenation and thus loses anti-inflammatory effects. Hence, there has been a rise in the intensity of oxidative stress manifestations, adhesion molecules, and cytokines concentrations in the peripheral blood vessels. It has also enhanced cholesterol accumulation in macrophages. Dysfunctional and oxidized HDL may be transported in the human brain (in the anterior cingulate gyrus), where it can contribute to local necrotic reactions, stimulate glutamate reactivity, and impact the breakdown of myelin sheaths and cell density. In summary, the dysregulation of HDL and PON-1 in patients with schizophrenia may result in dysfunctional HDL with impaired protective effects and increased oxidative stress. This can have implications for both peripheral and central processes, potentially contributing to neuroinflammation, myelin disruption, and altered cell density in specific brain regions such as the anterior cingulate gyrus. PON-1—paraxonase 1; HDL—high density lipids; LDL—low density lipids; BBB—blood brain barrier.