Chattopadhyay and Das: Statistical Validation of LENS 71 Indian Journal of Mental Health 2022; 9(1) Original Research Article Statistical Validation of LENS: A Smartphone-based Empty Nest Syndrome Screening and Monitoring Biomarker Tool Subhagata Chattopadhyay 1 ,Rupam Das 2 1,2 Dept. of Research and Development (Digital Health) , Acculi Labs Pvt. Ltd. Bangalore 560098, Karnataka, India Corresponding author: Subhagata Chattopadhyay Email – subhagata.chattopadhyay2017@gmail.com ABSTRACT Background: Empty Nest Syndrome (ENS) is a complex grief state, observed in the affected parents when their children leave home. Studies show ENS may progress to clinical-grade depression and anxiety if left uncared for. Methodology: In this double-blind case-control cross-sectional study, 80 subjects are recruited by a panel of psychologists and psychiatrists. Subjects are divided into two equal groups – case (with ENS symptoms) and control (without symptoms). Three instruments are applied – a) ENS interpretation by the psychologists based on the symptoms, b) Lyfas smartphone-based biomedical application to capture the cardiovascular optical biomarkers (COB) from the index finger non-invasively with the help of arterial photoplethysmography technique, and c) Hamilton’s depression scales (HAM-D), which psychiatrists have used to check the mental health of the subjects. The COB (e.g., SD1/SD2, LF/HF, HRVScore, and ENERGY) and a set of physical parameters (e.g., Body mass index or BMI, Heart rate or HR, Systolic blood pressure or SBP, Diastolic blood pressure or DBP, Glycosylated hemoglobin or HbA1c, Cholesterol, Triglyceride, Thyroid-stimulating hormone or TSH, Estradiol or E2, and Testosterone or TST) consist the independent variables, while ENS scores interpreted by the psychologists and HAM-D scores interpreted by the psychiatrists are the dependent variables. Spearman’s rank correlation and Bland Altman’s reliability tests are performed to mine the significant independent variables and reliability of Lyfas ENS (LENS) application. Results: The study observes that SD1/SD2, LF/HF, HRVScore, ENERGY, DBP, BMI, HR, HbA1c, TSH, and Estradiol have significant roles in ENS. Bland Altman's reliability measure shows that LENS (novel instrument under trial) has a high agreement of 92.85% and 93.86%, respectively with ENS scoring done by senior psychologists (champion instrument1) and HAM-D grading performed by psychiatrists (champion instrument2). Conclusions: LENS can be used as a clinical-graded pocket application for screening and monitoring ENS. Keywords: Lyfas; Empty Nest Syndrome; Cardiovascular Optical Biomarkers; Hamilton Depression Scale (Paper received – 31 st March 2022, Peer review completed – 25 th April 2022, Accepted – 28 th April 2022) INTRODUCTION ENS is not a clinical entity under the Diagnostic and Statistical Manual – V (DSM-V), however, it is listed in the International Classification of Diseases (ICD)-11 under “Other Associated Problems with Social or Cultural Environment” (Code: QE0Y) [1]. However, it is a well-observed psychological phenomenon among the parents in society for five decades, mostly in the developing nations [2], when their children leave home for a job or higher educational purposes or marriage [3]. In recent days, offices and institutions are opening in India and overseas, causing children to move out to chase their dreams. It is a sudden disjoint in the family that enjoyed the togetherness during working from home, attending online classes, and so forth. The sudden news of the expectant departure of the children poses to be psychologically shocking to the parents. Some are trapped within the ENS, a term applicable for the parent birds’ mental grief when their grown-up chicks leave the nest [4]. The grief is mostly distributed around the loneliness due to the