Heart rate variability: A primer for alcohol researchers.

Problem alcohol drinking remains a major cost and burden for society. Also, rates of problem drinking in women have dramatically increased in recent decades, and women are at risk for more alcohol problems and comorbidities. The purpose of this commentary is to discuss the potential utility of cardiac measures, including heart rate (HR) and HR variability (HRV), as markers of individual and sex differences in the drive to drink alcohol. We recently used cardiac telemetry in female and male adult rats to determine whether different cardiac markers, including HR and HRV, would differently predict alcohol and anxiety-like behavior across the sexes. Indeed, female behaviors related to HRV measures that indicate more parasympathetic (PNS) influence (the "rest and digest" system). In contrast, male behaviors are associated more with sympathetic (SNS) indicators (the activation system). Remarkably, similar sex differences in PNS versus SNS engagement under challenge are seen in several human studies, suggesting strong cross-species convergence in differential autonomic regulation in females and males. Here, we describe the larger challenges that alcohol addiction presents, and how HRV measures may provide new biomarkers to help enhance development of more individualized and sex-specific treatments. We briefly explain the physiological systems underlying cardiac PNS and SNS states, and how specific HRV metrics are defined and validated, especially why particular HRV measures are considered to reflect more PNS versus SNS influence. Finally, we describe hormonal influences and sex differences in brain circuits related to cardiac autonomic regulation. Together, these findings show that HR and HRV have potential for uncovering key underlying mechanisms of sex and individual differences in autonomic drivers, which could guide more personalized treatment.