Abstract
First-episode psychosis (FEP) is associated with metabolic alterations. However, it is not known if there is heterogeneity in these alterations beyond what might be expected due to normal individual differences, indicative of subgroups of patients at greater vulnerability to metabolic dysregulation. We employed meta-analysis of variance, indexed using the coefficient of variation ratio (CVR), to compare variability of the following metabolic parameters in antipsychotic naïve FEP and controls: fasting glucose, glucose post-oral glucose tolerance test (OGTT), fasting insulin, insulin resistance, haemoglobin A1c (HbA1c), total-cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides. Standardised mean difference in metabolic parameters between groups was also calculated; meta-regression analyses examined physiological/demographic/psychopathological moderators of metabolic change. Twenty-eight studies were analysed (1716 patients, 1893 controls). Variability of fasting glucose [CVR = 1.32; 95% confidence interval (CI) 1.12-1.55; p = 0.001], glucose post-OGTT (CVR = 1.43; 95% CI 1.10-1.87; p = 0.008), fasting insulin (CVR = 1.31; 95% CI 1.09-1.58; p = 0.01), insulin resistance (CVR = 1.34; 95% CI 1.12-1.60; p = 0.001), HbA1c (CVR = 1.18; 95% CI 1.06-1.27; p < 0.0001), total-cholesterol (CVR = 1.15; 95% CI 1.01-1.31; p = 0.03), LDL-cholesterol (CVR = 1.28; 95% CI 1.09-1.50; p = 0.002), and HDL-cholesterol (CVR = 1.15; 95% CI 1.00-1.31; p < 0.05), but not triglycerides, was greater in patients than controls. Mean glucose, glucose post-OGTT, fasting insulin, insulin resistance, and triglycerides were greater in patients; mean total-cholesterol and HDL-cholesterol were reduced in patients. Increased symptom severity and female sex were associated with worse metabolic outcomes. Patients with FEP present with greater variability in metabolic parameters relative to controls, consistent with a subgroup of patients with more severe metabolic changes compared to others. Understanding determinants of metabolic variability could help identify patients at-risk of developing metabolic syndrome. Female sex and severe psychopathology are associated with poorer metabolic outcomes, with implications for metabolic monitoring in clinical practice.
Highlights
People with psychotic disorders die 15 years earlier than members of the general population (Crump, Winkleby, Sundquist, & Sundquist, 2013)
Our second main finding is that greater symptom severity is associated with increased fasting glucose levels and female sex is associated with worse metabolic outcomes, namely increased insulin resistance, reduced high-density lipoprotein (HDL)-cholesterol levels, and raised triglyceride levels
In contrast to previously less well-powered meta-analyses, we show that First-episode psychosis (FEP) is associated with reductions in HDL-cholesterol levels, and that there is no significant difference between patients and controls for low-density lipoprotein (LDL)-cholesterol levels
Summary
People with psychotic disorders die 15 years earlier than members of the general population (Crump, Winkleby, Sundquist, & Sundquist, 2013). Lifestyle and medication play a key role in the metabolic disturbances seen in individuals with psychosis (Pillinger et al, 2020), meta-analyses have observed glucose and lipid alterations from psychosis onset and in the absence of antipsychotic treatment (Greenhalgh et al, 2017; Perry, McIntosh, Weich, Singh, & Rees, 2016; Pillinger et al, 2017a, 2019a; Pillinger, Beck, Stubbs, & Howes, 2017b) These alterations persist when patients and controls are matched for factors associated with metabolic function e.g. diet, physical activity, and body mass index (BMI) (Pillinger et al, 2017a, 2017b). The factors underlying metabolic alterations are not clear, and between-study inconsistency has been highlighted as a limitation of previous meta-analyses (Reynolds, 2021), so we investigated factors that might underlie effects and explain inconsistency
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