Reduced heart rate variability (HRV) is proposed to mediate the relation between depressive symptoms and cardiovascular health problems. Yet, several studies have found that in women depression is associated with higher HRV levels, whereas in men depression is associated with lower HRV levels. So far, these studies have only examined gender differences in HRV levels using a single assessment. This study aimed to test the interactive effects of gender and sadness on ambulatory-assessed HRV levels. A sample of 60 (41 women) employees participated in an ambulatory study. HRV levels (mean of successive differences; MSD) were continuously measured for 24 h. During the daytime, hourly assessments of sadness and other mood states were taken, while depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale (CES-D). Gender differences were observed when examining the impact of average daily sadness on MSD. In women, but not in men, the total amount of sadness experienced during the day was associated with higher circadian MSD levels. These findings suggest that researchers need to take gender differences into account when examining the relation between sadness, HRV, and cardiovascular problems.

Introduction
Women face greater challenges quitting smoking and higher health risks than men, yet gender remains understudied in tobacco use disorder (TUD). This study investigates gender differences in subjective craving and heart rate variability (HRV) following tobacco cue exposure in abstinent smokers. Unlike heart rate, HRV reflects parasympathetic modulation, critical for understanding risk and resilience in addiction, but has rarely been studied as a cue-reactivity biomarker.
Methods
Data from 41 men and 40 women who smoked cigarettes for more than 10 years were analyzed. Participants underwent a cue-exposure paradigm consisting of a relaxation phase (75s), exposure to smoking videos (150s) and pictures (150s), and handling tobacco paraphernalia (120s). Relief craving (the urge to use nicotine to alleviate negative emotions) and reward craving (the urge to use nicotine for its pleasurable effects) were measured pre/post cue exposure via the brief Questionnaire on Smoking Urges. HRV was continuously measured as root mean square of successive differences (RMSSD).
Results
Cue exposure increased relief and reward craving and reduced HRV across participants (p<.001) without gender differences. Significant craving-HRV associations emerged only in women: those with higher exposure-induced reward craving showed the largest HRV reductions and recovery during paraphernalia handling (p<0.01), whereas those with higher exposure-induced relief craving had smaller HRV declines and weaker recovery (p<0.01). Conclusion These findings reinforce HRV as a clinically relevant biomarker for tobacco cue reactivity and highlight gender differences in the autonomic nervous system’s role in craving among individuals with TUD, suggesting stronger involvement in women.