Published online Jun 19, 2022. doi: 10.5498/wjp.v12.i6.827
Peer-review started: December 31, 2021
First decision: March 13, 2022
Revised: April 3, 2022
Accepted: May 22, 2022
Article in press: May 22, 2022
Published online: June 19, 2022
Insulin resistance (IR) and impaired energy expenditure (IEE) are irreparable metabolic comorbidities in schizophrenia. Although mechanism(s) underlying IR and IEE remains unclear, leptin and fatty acid signaling, which has profound influence on insulin secretion/sensitivity, glucose metabolism and energy expenditure, could be disrupted. However, no association of plasma leptin with erythrocyte membrane fatty acids, body mass index (BMI), and psychotic symptoms in the same cohort of untreated patients with first-episode psychosis (FEP) or medicated patients with chronic schizophrenia (CSZ) is presented before. These studies are crucial for deciphering the role of leptin and fatty acids in the development of IR and IEE in schizophrenia.
To determine the association between plasma leptin, erythrocyte membrane fatty acids, particularly, saturated fatty acids (SFAs), BMI and psychotic symptoms in patients with FEP and CSZ.
In this study, twenty-two drug naive patients with FEP, twenty-one CSZ patients treated with atypical antipsychotic drugs, and fourteen healthy control (CNT) subjects were analyzed. Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay. Erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography. BMI was calculated by using the formula: weight (kg)/height (m2). Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale (BPRS), and positive and negative syndrome scale (PANSS). The total BPRS scores, positive and negative symptom scores (PANSS-PSS and PANSS-NSS, respectively) were recorded. Pearson correlation coefficient (r) analyses were performed to find the nature and strength of association between plasma leptin, PANSS scores, BMI and SFAs, particularly, palmitic acid (PA).
In patients with FEP, plasma leptin not BMI was significantly lower (P = 0.034), whereas, erythrocyte membrane SFAs were significantly higher (P < 0.005) compared to the CNT subjects. Further, plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA (r = −0.4972, P = 0.001), PANSS-PSS (r = −0.4034, P = 0.028), and PANSS-NSS (r = −0.3487, P = 0.048). However, erythrocyte membrane SFAs-PA showed positive correlation with PANSS-PSS (r = 0.5844, P = 0.0034) and PANSS-NSS (r = 0.5380, P = 0.008). In CSZ patients, plasma leptin, BMI, and erythrocyte membrane SFAs, all were significantly higher (P < 0.05) compared to the CNT subjects. Plasma leptin showed positive correlation with BMI (r = 0.312, P = 0.032) but not with PANSS scores or erythrocyte membrane SFAs-PA. However, erythrocyte membrane SFAs-PA showed positive correlation with PANSS-NSS only (r = 0.4729, P = 0.031). Similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultra-high risk of developing psychosis; therefore, the above findings suggest that leptin-fatty acid biosynthesis could be disrupted before the onset of psychosis in schizophrenia.
Disrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation of metabolic comorbidities in schizophrenia. Large-scale studies are warranted to validate the above findings.
Core Tip: Insulin resistance (IR) and impaired energy expenditure (IEE) are untreatable metabolic comorbidities in schizophrenia. Leptin and fatty acids have profound influence on insulin synthesis, secretion and energy metabolism. Although previous studies have measured plasma leptin and membrane fatty acids in schizophrenia, findings are very heterogeneous, and moreover, no single study has ever measured both plasma leptin and membrane fatty acids together in the same cohort of schizophrenia patients. These studies are crucial not only for analyzing the relationship between leptin and fatty acids in the same cohort of schizophrenia patients, but also for deciphering their role in the development of IR and IEE.