ASSOCIATION BETWEEN ALLOSTATIC LOAD AND CARDIAC STRUCTURE IN ADULT PATIENTS WITH SCHIZOPHRENIA

Abstract Background The pathophysiological consequences of uncompensated adaptation to chronic stress are conceptualized as the allostatic load [1]. Despite the evidence that allostatic load is elevated in individuals with schizophrenia [2-4] and associated with medical comorbidities [5,6], few studies have investigated whether allostatic load adversely affects cardiac health in patients with schizophrenia. Aims & Objectives This exploratory study aimed to evaluate the associations between allostatic load index and echocardiographic metrics in adult patients diagnosed with schizophrenia. Methods We recruited patients who received a DSM-V diagnosis of schizophrenia and aged over 20 years to undergo transthoracic echocardiography, blood biochemistry analysis, and physical examination. Patients were excluded if they had a history of stroke, myocardial infarction, peripheral artery disease, or substance use disorder except for tobacco use. The allostatic load index was computed based on 12 measures representing metabolic, inflammatory, and cardiovascular mediators, including the body mass index, fasting glucose, insulin, triglyceride, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, fibrinogen, high sensitivity C- reactive protein, systolic blood pressure, diastolic blood pressure, and heart rate. Clinical data were obtained through the interview and chart review. Results A total of 27 patients (9 males and 18 females) at mean ages of 37.2 ± 9.3 years old were enrolled in this study. The mean durations of schizophrenia illness and antipsychotics treatment were 14.5 ± 8.1 years and 7.2 ± 6.2 years, respectively. The mean chlorpromazine-equivalent doses were 303.2 ± 218.3 mg per day. Significantly, the allostatic load index was positively correlated with the interventricular septal thickness at end-diastole in patients with schizophrenia (r = 0.415, p = 0.044). In addition, the allostatic load index was negatively correlated to the left ventricular internal diameter at end-diastole (r = –0.452, p = 0.027). Regarding the correlations between allostatic load and antipsychotics treatment, there was a marginally significant correlation between allostatic load index and duration of antipsychotics exposure (r = 0.351, p = 0.072). No significant correlation was found between allostatic load index and current chlorpromazine-equivalent dose (r = -0.059, p = 0.779). Discussion & Conclusion This present study found that the allostatic load index was associated with the increased wall thickness and decreased chamber diameter of left ventricle in patients with schizophrenia. Because the increased wall thickness and decreased chamber diameter of left ventricle are the risk markers predicting heart failure [7,8], the results of this exploratory study suggested that allostatic load may impair cardiovascular health in patients diagnosed with schizophrenia. For a better understanding of the benefit and risk of antipsychotics treatment on allostatic load and cardiac health in patients with schizophrenia, future studies with the prospective design and adequate sample size are required. References 1.Guidi J, Lucente M, Sonino N, Fava GA. Allostatic load and its impact on health: A systematic review. Psychother Psychosom. 2021;90(1):11-27. 2.Nugent KL, Chiappelli J, Rowland LM, Hong LE. Cumulative stress pathophysiology in schizophrenia as indexed by allostatic load. Psychoneuroendocrinology. 2015;60:120-129. 3.Savransky A, Chiappelli J, Fisseha F, Wisner KM, Xiaoming D, Mirmomen SM, Jones AD, Adhikari BM, Bruce HA, Rowland LM, Hong LE. Elevated allostatic load early in the course of schizophrenia. Transl Psychiatry. 2018;8(1):246. 4.Zhou Y, Huang J, Zhang P, Tong J, Fan F, Gou M, Cui Y, Luo X, Tan S, Wang Z, Feng W, Yang F, Tian B, Tian L, Savransky A, Hare S, Ryan MC, Goldwaser E, Chiappelli J, Chen S, Kochunov P, Kvarta M, Tan Y, Hong LE. Allostatic load effects on cortical and cognitive deficits in essentially normotensive, normoweight patients with schizophrenia. Schizophr Bull. 2021;47(4):1048-1057. 5.Bizik G, Picard M, Nijjar R, Tourjman V, McEwen BS, Lupien SJ, Juster RP. Allostatic load as a tool for monitoring physiological dysregulations and comorbidities in patients with severe mental illnesses. Harv Rev Psychiatry. 2013;21(6):296-313. 6.Misiak B, Frydecka D, Zawadzki M, Krefft M, Kiejna A. Refining and integrating schizophrenia pathophysiology - relevance of the allostatic load concept. Neurosci Biobehav Rev. 2014;45:183-201. 7.Dini FL, Galeotti GG, Terlizzese G, Fabiani I, Pugliese NR, Rovai I. Left ventricular mass and thickness: Why does it matter? Heart Fail Clin. 2019;15(2):159-166. 8. Stewart MH, Lavie CJ, Shah S, Englert J, Gilliland Y, Qamruddin S, Dinshaw H, Cash M, Ventura H, Milani R. Prognostic implications of left ventricular hypertrophy. Prog Cardiovasc Dis. 2018;61(5- 6):446-455.