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. 2020 Jul 29:14:784.
doi: 10.3389/fnins.2020.00784. eCollection 2020.

Reduced Levels and Disrupted Biosynthesis Pathways of Plasma Free Fatty Acids in First-Episode Antipsychotic-Naïve Schizophrenia Patients

Xiang Zhou  1   2 , Tao Long  1   2 , Gretchen L Haas  2   3 , HuaLin Cai  4   5 , Jeffrey K Yao  1   2   3
Affiliations

Reduced Levels and Disrupted Biosynthesis Pathways of Plasma Free Fatty Acids in First-Episode Antipsychotic-Naïve Schizophrenia Patients

Xiang Zhou et al. Front Neurosci. .

Abstract

Membrane phospholipid deficits have been well-documented in schizophrenia (SZ) patients. Free fatty acids (FFAs) partially come from the hydrolysis of membrane phospholipids and serve as the circulating pool of body fatty acids. These FFAs are involved in many important biochemical reactions such as membrane regeneration, oxidation, and prostaglandin production which may have important implications in SZ pathology. Thus, we compared plasma FFA levels and profiles among healthy controls (HCs), affective psychosis (AP) patients, and first-episode antipsychotic-naïve schizophrenia (FEANS) patients. A significant reduction of total FFAs levels was observed in SZ patients. Specifically, significant reductions of 16:0, 18:2n6c, and 20:4n6 levels were detected in FEANS patients but not in APs when compared with levels in HCs. Also, disrupted metabolism of fatty acids especially in saturated and n-6 fatty acid families were observed by comparing correlations between precursor and product fatty acid levels within each fatty acid family. These findings may suggest an increased demand of membrane regeneration, a homeostatic imbalance of fatty acid biosynthesis pathway and a potential indication of increased beta oxidation. Collectively, these findings could help us better understand the lipid metabolism with regard to SZ pathophysiology.

Keywords: antipsychotic-naïve; fatty acid pathway; first-episode schizophrenia; free fatty acids; plasma.

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Figures

FIGURE 1
FIGURE 1
Tight correlations of fatty acids among healthy control (HC) subjects, affective psychosis (AP) patients, and first-episode antipsychotic-naïve schizophrenia patients (FEANS). Critical p-value after Bonferroni correction: 0.0063.
FIGURE 2
FIGURE 2
Disrupted correlations of fatty acids both shown in affective psychosis (AP) patients and first-episode antipsychotic-naïve patients (FEANS). Critical p-value after Bonferroni correction: for 18:3n6/20:4n6, critical p = 0.005; for 16:1n7c/18:1n7, critical p = 0.0167.
FIGURE 3
FIGURE 3
Disrupted correlations of fatty acids only present in first-episode antipsychotic-naïve patients (FEANS). Critical p-value after Bonferroni correction: for 17:0/17:1, critical p = 0.0063; for 18:3n6/20:4n6, critical p = 0.005.
FIGURE 4
FIGURE 4
Significant reversed correlations between 22:6n3 and assessment of positive symptoms (SAPS) in first-episode antipsychotic-naïve patients (FEANS). Critical p-value after Bonferroni correction: p = 0.125.
FIGURE 5
FIGURE 5
Free fatty acids (FFAs) in lipid metabolism and postulated model of reduced plasma FFA levels and its underlying mechanism in schizophrenia pathophysiology. FFAs come from the lipolysis of membrane phospholipids and serve as an active circulating pool in body. They are involved in many important biochemical reactions including regeneration of membrane phospholipids, beta-oxidation, and production of prostaglandins. In schizophrenia, oxidative stress level was accumulated due to environmental or genetic factors. Consequently, oxidative stress led to membrane phospholipid deficits and increased activity of beta-oxidation of FFAs. Since more FFAs were utilized to regenerate cell membranes and were metabolized through beta-oxidation, levels of plasma FFAs were reduced in SZ patients. PLA2, phospholipase A2.
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