Abstract: Background: The proxies used to compose cognitive reserve (CR) in first episode of psychosis (FEP) have varied in the literature. The development of FEP is linked to the peripheral pathways of the central nervous system [1], but despite this knowledge, no research has considered the introduction of biomarkers as proxies for CR. Furthermore, we know that schizophrenia has been linked to the metabolic system, indicating that alterations in the levels of biological parameters, in particular high-density lipoproteins (HDL), cause worse global functioning and cognitive impairment [2-4]. For these reasons, the present study aimed to create a quantifiable and objective CR index that adjusts for the multifactorial nature of FEP. Methods: We included 668 patients who had FEP and 217 healthy controls, who were assessed for sociodemographic information, years of education, employment status, premorbid IQ and levels of biological parameters: waist circumference, hypertension and levels of HDL, triglycerides and glucose. We performed Pearson correlations to explore whether there is a relationship between CR proxies and biological parameters. Subsequently, multiple regression analyses were performed to search for the causes of the relationships between CR and biological parameters at baseline. In the final step and in line with the methodology used in recent years in CR research, the following were carried out principal component analyses (PCA) and exploratory factor analysis (EFA) to create a ?composite CR score? [5] for each participant, which we will refer to as biological CR. Results: Years of education proxy showed correlational and higher relationship with HDL levels for both FEP patients (r=0.23, b= 0.185) and controls (r= 0.31, b= 0.342). The regressions indicate that the Model 2 formed by the proxies years of education and unemployment had a higher predictive power explaining 5.4% of HDL levels and with a stronger F-statistic (F= 11.80). After several attempts combining all possible components, exploratory analyses showed that the most optimal variables for the composite CR score were years of education and HDL levels. The biological CR would have a greater explanatory power for the phenomenon than classical CR in both groups of participants. In the patients group, classical CR explained 51.79% of the variance, while biological CR explained 59.06%. This percentage increase also occurred in the control group, where classical CR explained 51.04%, while biological CR increased to 67.12%. The years of education proxy was the one that provided the largest information to the CR (>0.70). Conclusion: The main objective of the present study was to explore a possible objective and quantifiable CR, taking into account endogenous and exogenous factors. Following this line of work, it is interesting to note that, in both groups of participants, the results found that the proposed biological CR has a greater explanatory value of the phenomenon than the classical CR consolidated by the literature. Therefore, we can affirm that introducing HDL levels, as a biological proxy, together with the years of education proxy, is a way of obtaining a CR adjusted to the multifactorial nature of psychosis.

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