Blunted Heart Rate Response as a Potential Endophenotype of Substance Use Disorders: Evidence from High-Risk Youth.

Brittany E Evans,Anja S Euser,Anja C Huizink,Tess Koning,Kirstin Greaves-Lord,Ingmar H A Franken,Joke H M Tulen

doi:10.3389/fped.2015.00066

Abstract

Children of parents with a substance use disorder (CPSUD) are at increased risk for developing problematic substance use later in life. Endophenotypes may help to clarify the mechanism behind this increased risk. However, substance use and externalizing symptoms may confound the relation between dysregulated physiological stress responding and familial risk for substance use disorders (SUDs). We examined whether heart rate (HR) responses differed between CPSUDs and controls. Participants (aged 11-20 years) were CPSUDs (N = 75) and controls (N = 363), semi-matched on the basis of sex, socioeconomic status, and ethnicity. HR was measured continuously during a psychosocial stress procedure. Substance use and externalizing symptoms were self-reported and mother-reported, respectively. A piecewise, mixed-effects model was fit for HR across the stress procedure, with fixed effects for HR reactivity and HR recovery. CPSUDs showed a blunted HR recovery. CPSUDs reported drinking more frequently, were more likely to use tobacco daily, were more likely to report ever use of cannabis and used cannabis more frequently, and exhibited more externalizing symptoms. These variables did not confound the relation between familial risk for SUDs and a blunted HR recovery. Our findings suggest dysregulated autonomic nervous system (ANS) responding in CPSUDs and contribute to the accumulating evidence for ANS dysregulation as a potential endophenotype for SUDs.

Highlights

Starting with adoption studies in the 1970s, several studies have demonstrated that the risk for developing substance use disorders (SUDs) is substantially higher in the children of parents with a substance use disorder [CPSUDs; e.g., Ref. [1,2,3,4,5,6,7]]
We included a random effect for the slope across the entire stress procedure (TestSlope) in order to control for within-individual variation in heart rate (HR)
Considering that risky substance use [23] and externalizing symptoms [24] have both been associated with a blunted HR response, we examined whether substance use and number of externalizing symptoms confounded our finding of a blunted HR recovery in CPSUDs compared to youth from the general population

Summary

Introduction

Starting with adoption studies in the 1970s, several studies have demonstrated that the risk for developing substance use disorders (SUDs) is substantially higher in the children of parents with a substance use disorder [CPSUDs; e.g., Ref. [1,2,3,4,5,6,7]]. Starting with adoption studies in the 1970s, several studies have demonstrated that the risk for developing substance use disorders (SUDs) is substantially higher in the children of parents with a substance use disorder [CPSUDs; e.g., Ref. In genetically complex psychiatric disorders, such as SUDs, endophenotypes or biomarkers may help to explain risk for SUDs in CPSUDs. One potential endophenotype is dysregulation of the physiological response to stress. Physiological recovery from the stressor entails deactivation of the SNS and activation of the PNS in order to return to homeostasis [9, 10]. Children of parents with a substance use disorder (CPSUD) are at increased risk for developing problematic substance use later in life. Substance use and externalizing symptoms may confound the relation between dysregulated physiological stress responding and familial risk for substance use disorders (SUDs)

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