Erythrocyte membrane nervonic acid in drug-naive first-episode psychosis and chronic medicated schizophrenia: Implication for impaired myelination and prognosis

Abstract

BACKGROUND

Nervonic acid (NA, C24: 1, w9) is a monounsaturated fatty acid that plays a crucial role in myelination and motor function. It also regulates cognitive and metabolic functions, suggesting that impaired NA metabolism may contribute to the pathophysiology of schizophrenia. Although several studies have measured erythrocyte membrane NA in first-episode psychosis (FEP), findings are conflicting, and the fate of NA in patients with chronic schizophrenia (CSZ) or under long-term antipsychotic treatment schedules remains unknown.

AIM

To measure erythrocyte membrane NA and determine its association with psychopathology and metabolic parameters in drug-naive patients with FEP and antipsychotic-treated patients with CSZ.

METHODS

In this study, twenty-one drug-naive patients with FEP, twenty patients with CSZ treated with atypical antipsychotics, and fourteen healthy male subjects were analyzed. Erythrocyte membrane NA was measured using ultrathin capillary gas chromatography, plasma leptin was measured using enzyme-linked immunosorbent assay, and body mass index (BMI) was calculated by using the formula: Weight (kg)/height (m²). Psychiatric symptoms were evaluated using the brief psychiatry rating scale and the positive and negative syndrome scale (PANSS). Pearson correlation coefficient (r) was computed to find the association between erythrocyte membrane NA, PANSS scores, plasma leptin, and BMI.

RESULTS

In patients with FEP, erythrocyte NA was non-significantly increased (about 12%) and negatively correlated with negative symptoms (PANSS-negative symptom scores, r = -0.4323, P = 0.023) but not with positive symptoms (PANSS-positive symptom scores, r = -0.2915, P = 0.09). In patients with CSZ, erythrocyte NA was reduced considerably (about 40%, P < 0.001 vs FEP and about 30% vs control (CNT) subjects, P = 0.037) and negatively correlated with both PANSS-negative symptom scores (r = -0.4562, P = 0.013) and PANSS-positive symptom scores (r = -0.3911, P = 0.041). Additionally, in patients with FEP, erythrocyte NA was not significantly correlated either with BMI (r = -0.2532, P = 0.231) or plasma leptin (r = -0.3001, P = 0.102). However, in patients with CSZ, it did negatively correlate with both BMI (r = -0.4721, P = 0.029) and plasma leptin (r = -0.4701, P = 0.031).

CONCLUSION

Erythrocyte membrane NA level could be used for predicting the development of metabolic abnormalities, treatment resistance, and prognosis in schizophrenia.

Keywords: Nervonic acid; First-episode psychosis; Chronic schizophrenia; Demyelination; Metabolic abnormalities

Core Tip: Nervonic acid (NA, C24: 1, w9) is a monounsaturated fatty acid that plays a crucial role in myelination and motor function. It also regulates cognitive and metabolic functions, suggesting that impaired NA metabolism may contribute to the pathophysiology of schizophrenia. Although several studies have measured erythrocyte membrane NA in first-episode psychosis, findings are conflicting, and the fate of NA in patients with chronic schizophrenia or under long-term antipsychotic treatment schedule remains unknown. This study was designed to analyze erythrocyte NA composition and its association with psychopathology and metabolic comorbidities in drug-naive patients with first-episode psychosis and antipsychotic-treated patients with chronic schizophrenia.