Sex Differences in Loneliness-Moderated Physiological Associations with Suicidal Ideation: Age-Dependent Attenuation Across Midlife

Loneliness is a well-established risk factor for suicidal ideation (SI), yet the physiological pathways linking social disconnection to SI remain unclear. Using a stress-reactivity framework, we examined two biomarkers: sleep onset latency (an indicator of nocturnal hyperarousal or sympathetic dysregulation) and low-frequency heart rate variability (LF-HRV) during a cognitive stress task (an index of acute autonomic balance). We tested whether loneliness moderates associations between these biomarkers and SI, whether effects differ by sex, and whether sex differences diminish with age. Cross-sectional data from the MIDUS study (N = 863; mean age 50.8 years; 52.1% female; ages 25–76) were analyzed. Measures included loneliness (UCLA-3), self-reported sleep onset latency, LF-HRV across laboratory conditions, and SI. Multiple imputation (MICE, 30 datasets) and pooled standardized OLS moderation models were used, stratified by sex and age decade, with three-way interactions testing age-related attenuation. Results showed male-specific associations, strongest in younger men. Longer sleep onset latency was associated with higher SI in men (β =.206, p <.001) but not women (β =.065, p >.05), with the largest sex difference in ages 25–34 and convergence by older adulthood. Similarly, LF-HRV was associated with SI in men (β =.172, p =.001) but not women, again concentrated in younger men. A significant loneliness × sleep × age interaction confirmed that the male-specific effect weakened with age. These findings suggest physiological hyperarousal may serve as biomarkers for SI risk linked to loneliness, particularly among younger men.