Disrupted leptin-fatty acid biosynthesis is an early manifestation of metabolic abnormalities in schizophrenia

ARTICLE HIGHLIGHTS

Research background

Apart from classical symptoms of psychosis, patients with first-episode psychosis and their first-degree relatives display a range of metabolic comorbidities including insulin resistance and impaired energy expenditure. One of the major hurdles in treating schizophrenia psychosis is that intervention with antipsychotic drugs further exacerbates the severity of metabolic comorbidities, which leads to premature antipsychotic withdrawal, a leading cause of relapse in schizophrenia. Finding the underlying mechanism(s) is crucial for designing effective therapies for minimizing the development or exacerbation of metabolic comorbidities during antipsychotic treatment in schizophrenia.

Research motivation

Finding the mechanism(s) underlying metabolic comorbidities is crucial for enhancing treatment adherence and outcome in schizophrenia. Finding such mechanism(s) will also help in designing effective therapies for minimizing the development or exacerbation of metabolic comorbidities during antipsychotic treatment in schizophrenia.

Research objectives

Since leptin and fatty acids together have profound influence on insulin secretion/sensitivity, and energy homeostasis, this study is directed to determine the association between plasma leptin, body mass index, and erythrocyte membrane fatty acids, particularly, saturated fatty acids (SFAs) in patients with first-episode psychosis (FEP).

Research methods

Plasma leptin was measured using sandwich mode enzyme-linked immunosorbent assay; whereas, erythrocyte membrane SFAs were measured using ultrathin capillary gas chromatography. Body mass index was calculated by using the formula: weight (kg)/height (m²). Psychiatric symptoms were evaluated at baseline using brief psychiatric rating scale, and positive and negative syndrome scale (PANSS). Pearson correlation coefficient (r) analyses were performed to find the nature and strength of association between plasma leptin, PANSS scores, body mass index (BMI) and SFAs, particularly, palmitic acid (PA).

Research results

Plasma leptin not BMI was significantly lower, whereas, erythrocyte membrane SFAs were significantly higher in patients with FEP compared to the healthy control subjects. Further, plasma leptin showed negative correlation with erythrocyte membrane SFAs-PA, and PANSS scores. However, erythrocyte membrane SFAs-PA showed positive correlation with PANSS scores. Since, similar changes in the plasma leptin and erythrocyte membrane SFAs have also been reported in individuals at ultra-high risk of developing psychosis, the above findings suggest that leptin-fatty acid biosynthesis could be disrupted from the early stage of the illness in schizophrenia.

Research conclusions

Disrupted leptin-fatty acid biosynthesis/signaling could be an early manifestation and underlying cause of metabolic comorbidities in patients with FEP.

Research perspectives

Although large-scale studies are needed for validation of the above results, the data presented above will help in developing appropriate therapies for minimizing the development of insulin resistance and other metabolic comorbidities and increasing treatment adherence and outcome in schizophrenia. Since oxidative stress and inflammation are the major risk factors for the disrupted leptin-fatty acid biosynthesis/signaling, supplementation with calcium, anti-oxidant and/or anti-inflammatory agents will be highly effective in reducing the development or exacerbation of preexisting metabolic comorbidities in schizophrenia.