The causal nature of the association between resting pulse in late adolescence and risk for internalizing and externalizing disorders: a co-relative analysis in a national male Swedish sample

Abstract

Background: Resting pulse is robustly and inversely associated with the risk for externalizing disorders and may be positively associated with internalizing disorders. We know little about the causal nature of these associations. Methods: We examined resting pulse at conscription examination in 369 301 males born 1960–80 with a mean (s.d.) follow-up of 29.1 (7.7) years. From pulse rates, we predicted, using Cox models, the risk for criminal behavior (CB), drug abuse (DA), alcohol use disorder (AUD), major depression (MD), and anxiety disorders (AD), assessed from medical, criminal, and pharmacy registries. Co-relative analyses were conducted on the general population, cousin, half-sibling, full-sibling, and monozygotic pairs discordant for the outcome. Twin/sibling modeling for pulse was performed using OpenMX. Results: Familial resemblance for pulse resulted entirely from genetic factors. In the general population, the risk for externalizing disorders (CB, DA, and AUD) and internalizing disorders (MD and AD) were, respectively, significantly associated with low and high resting pulse rate. For CB, DA, and AUD, co-relative analyses showed that the inverse association with pulse resulted entirely from familial common causes (aka ‘confounders’). By contrast, co-relative analyses found that the association between higher pulse and MD and AD resulted from direct causal effects. Conclusions: Resting pulse has a negative and positive association with, respectively, the risk for externalizing and for internalizing disorders. Co-relative analyses indicate that the nature of these associations differ, suggesting that elevated pulse appears to directly increase the risk for internalizing disorders while the reduced pulse is a risk index for underlying traits that predispose to externalizing disorders.