Heart Rate Variability and Cognitive Function as Potential Endophenotypes in Schizophrenia: A Cross-Sectional Observational Study Using First-Degree Relatives

Background Heart rate variability (HRV) represents beat-to-beat fluctuations in heart rate arising from the dynamic balance between sympathetic and parasympathetic nervous system activity. Altered HRV reflects autonomic dysregulation and has been reported across several psychiatric disorders, including schizophrenia, where it may contribute to cardiovascular risk and cognitive dysfunction. Aim The aim of this study was to compare the time-domain and frequency-domain heart rate variability parameters between patients with schizophrenia and their first-degree relatives and to analyze the correlation between heart rate variability indices and cognitive performance within an endophenotypic framework. Methods This healthcare-based cross-sectional observational study was performed at the Kalinga Institute of Medical Sciences in Bhubaneswar, India, from October 2023 to October 2024. Fifteen clinically stable subjects diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria and fifteen age- and gender-matched first-degree relatives without schizophrenia were included. 5-minute resting HRV was assessed once at a single time point using a standardized three-lead electrocardiogram (ECG) after a 10-minute adaptation period. Time-domain parameters measured overall variability, whereas frequency-domain parameters analyzed sympathetic and parasympathetic modulation. Cognitive functioning was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). To compare the groups, we used the Mann-Whitney U test, and to look for associations, we used Spearman's rank correlation. Results Time-domain heart rate variability parameters were comparable between patients with schizophrenia and first-degree relatives (p > 0.05). In the frequency domain, the low frequency (LF) to high frequency (HF) ratio (LF/HF) was significantly higher in patients with schizophrenia than in their relatives (median 1.57 vs. 0.79; p = 0.041), indicating relative sympathetic predominance. Absolute LF, HF, and very-low-frequency (VLF) power values did not differ significantly between groups (p > 0.05). Within the schizophrenia group, the LF/HF ratio showed a significant positive correlation with WASI scores (r = 0.701, p = 0.004). Conclusion Schizophrenia is associated with altered autonomic regulation characterized by an increased LF/HF ratio, suggesting sympathovagal imbalance, while time-domain HRV measures remain comparable to those of first-degree relatives. The observed association between autonomic modulation and cognitive performance supports the relevance of HRV as a potential physiological marker linked to cognitive functioning in schizophrenia. Further longitudinal and genetic studies are required to clarify its role as a potential endophenotypic trait.