Differences in metabolic biomarkers in people with schizophrenia who are of Mexican descent compared to non-Hispanic Whites

Abstract

<h3>Introduction</h3> Metabolic syndrome, a significant risk factor for cardiovascular-related mortality, is highly prevalent in people with schizophrenia (PwS). It is a leading contributor to the growing mortality gap between PwS and the general population. Hispanics/Latinos/as/x (henceforth Hispanics) with schizophrenia, are more likely to have metabolic dysregulation (e.g.,insulin resistance and abdominal obesity) compared to non-Hispanic Whites (NHW). Yet, little is known about the prevalence of metabolic risk factors in PwS of Mexican descent (Mex) and whether they differ from NHW PwS. Further, metabolic biomarkers such as leptin and adiponectin have not been explored in Hispanic PwS. This study compares metabolic biomarkers between Mex PWS that self-report as Mexican, Mexican-American, or Chicano and NHW PwS. We hypothesized that Mex PwS will have worse biomarker levels compared to NHW PwS. We explored the relative contributions of Mex descent and schizophrenia diagnosis to metabolic biomarker levels. Within PwS, we explored whether biomarker differences observed were related to illness-related group differences (e.g.,antipsychotic doses). <h3>Methods</h3> This cross-sectional study included 95 PwS (37% Mex, 46% women) and 88 non-psychiatric comparison participants (NC; 24% Mex, 56% women), ages 26-68 years. Standardized assessments were administered to evaluate body mass index (BMI) and psychopathology (Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms). Fasting levels of leptin, adiponectin, lipids, hemoglobin A1c, insulin, glucose, and insulin resistance (HOMA) were measured. Antipsychotic defined daily dosage (DDD) was determined using the WHO guidelines. Independent sample <i>t</i>-tests were used to assess sociodemographic and clinical differences between Mex and NHW PwS. Linear regression models were conducted to examine the relative contribution of Mex heritage to biomarker levels, including the interaction of Mex heritage and schizophrenia diagnosis as well as controlling for age and sex. Follow-up linear regression models within PwS examined whether biomarker differences were associated with antipsychotic DDD. <h3>Results</h3> Mex and NHW PwS had comparable severity of positive and negative symptoms. Mex PwS reported higher antipsychotic DDD compared to NHW PwS (M=2.42,SD=1.7 and M=1.66,SD=1.6, respectively). Mex NCs had higher mean BMI compared to NHW NCs, but Mex PwS and NHW PwS had similar mean BMI. In the whole sample, there were no significant Mex descent by schizophrenia diagnosis interactions for any of the biomarkers. Mexican descent and having schizophrenia were associated with higher insulin resistance (B=0.16, SE=.05, <i>p</i>=.003, η_p²=0.05 and B=0.24,SE=0.05, <i>p</i><.001, η_p²=0.13, respectively). Mexican descent, female sex, and having schizophrenia were associated with higher leptin levels (B=0.20, SE=0.08, p=0.007, η_p²=0.04; B=0.57, SE=.07, <i>p</i><.001, η_p²=0.29 and B=0.33,SE=0.07, <i>p</i><.001, η_p²=0.12, respectively). The remaining metabolic biomarkers (adiponectin, lipids, hemoglobin, A1c, insulin, and glucose) were not significantly associated with Mexican descent. In the PwS group alone, higher insulin resistance was associated with Mexican descent (B=0.22,SE=0.08,p=.009,η_p²=0.08), but not with antipsychotic DDD (B=-0.02,SE=0.02,p=0.42,η_p²=0.008). Among the PwS group, higher leptin levels were associated with female gender (B=0.62,SE=0.09,p=<.001,η_p²=0.35), but not with Mexican descent or antipsychotic DDD. <h3>Conclusions</h3> PwS of Mexican origin reported higher antipsychotic doses than NHW PwS. Consistent with other studies, we found worse insulin resistance in Mex PwS compared to NHW PwS, despite similar mean BMI. These findings highlight the importance of examining biomarker differences in Hispanic subgroups with schizophrenia, as they may illuminate specific underlying mechanisms in the development of metabolic dysregulation. The current study strengths include its focus on Mexico as the country origin and examining multiple metabolic biomarkers, though limitations include lack of statistical control of dietary intake and acculturation. Future studies of Hispanic PwS should examine antipsychotic dosing, which can be influenced by systemic prescribing practices and symptom severity, as well as the impact of culturally focused interventions to improve metabolic health. In order to improve health outcomes for Hispanic PwS, a deeper understanding of biological, cultural, and medical influences is warranted. <h3>This research was funded by</h3> This work was supported, in part, by the Veterans Affairs Pala Pilot Grant(PI: Ellen E. Lee, MD), NARSAD Young Investigator grant from the Brain & Behavior Research Foundation(PI: Ellen E. Lee, MD), National Institute of Mental Health grants T32 Geriatric Mental Health Program MH019934(PI: Dilip V. Jeste), R01MH094151(PI: Dilip V. Jeste), K23 MH119375(PI: Ellen E. Lee), National Institutes of Health CTSA grant UL1TR001442 (PI: Gary Firestein, MD), and Stein Institute for Research on Aging at the University of California San Diego.