Salivary cortisol responses in prepubertal boys: the effects of parental substance abuse and association with drug use behavior during adolescence

Abstract

Background: The purpose of this investigation was threefold. First, we extended our original observation of decreased cortisol reactivity to an anticipated stressor in sons of fathers with a substance use disorder (SUD). Second, we examined the hypothesis that salivary cortisol underresponsivity in these high-risk prepubertal boys is an adaptation to the stress associated with having a father with a current, rather than remitted, SUD. Third, we tested the hypothesis that prepubertal cortisol underreactivity might be associated with subsequent drug use behavior during adolescence.

Methods: Preadolescent salivary cortisol responses were examined in the context of risk-group status, paternal substance abuse offsets, and subsequent adolescent drug use behavior.

Results: The results confirmed a decreased salivary cortisol response to an anticipated stressor among sons of SUD fathers in our expanded sample. In addition, sons of fathers with a current SUD and boys whose fathers had a SUD offset from their 3rd to 6th birthdays had lower anticipatory stress cortisol levels compared with sons of control fathers. Finally, lower preadolescent anticipatory cortisol responses were associated with regular monthly cigarette smoking and regular monthly marijuana use during adolescence.

Conclusions: Hyporeactivity as an adaptation to chronic stress may be salient to the intergenerational transmission of substance abuse liability.

Introduction

Acute exposure to threat or stress generally activates the hypothalamic–pituitary–adrenal cortical axis (HPA), whereas chronic exposure to stressors tends to invoke adaptational mechanisms reducing the reactivity of this neuroendocrine system to acute stress. Individuals with chronic job stress have been shown to have reduced reactivity of the HPA (Caplan et al 1979). Combat veterans Mason et al 1986, Yehuda et al 1990 and Holocaust survivors (Yehuda et al 1995) with posttraumatic stress disorder are also reported to show diminished activity of the HPA axis. Civilians exposed to chronic wartime stress during the Gulf War have demonstrated diminished responsivity of the HPA axis to acute stressors as a consequence of adaptation to protracted chronic stress (Weizman et al 1994). Similarly, rape victims with a history of a prior assault victimization had a reduced mean cortisol response, suggesting that prior traumatization may attenuate subsequent responses to trauma (Resnick et al 1995).

We have previously reported the observation that in anticipation of a modest stressor, prepubertal sons of fathers with a substance use disorder (SUD) demonstrated a diminished salivary cortisol response, and that this psychoneuroendocrine response was mediated by the magnitude of problem behaviors in the children (Moss et al 1995a). Salivary cortisol determinations are a useful, nontraumatic method to assess the dynamics of cortisol responsivity that is of particular utility in children (Wolston et al 1983). Other studies in children have found reduced basal cortisol concentrations associated with aggressivity (Tennes et al 1986), hostility (Tennes and Kreye 1985), and conduct disorder severity (Vanyukov et al 1993); however, some studies reported the absence of these findings Kruesi et al 1989, McBurnett et al 1991. Conversely, shy and behaviorally inhibited children were found to have higher resting salivary cortisol concentrations (Kagan et al 1988).

The heritability of total plasma cortisol and the unbound fraction have been reported as 50.6% and 57.8%, respectively (Meikle et al 1988). Thus, environmental factors are nearly equally important as heritable factors in accounting for the variations in plasma cortisol concentrations. Taken together, these observations suggest that the responsivity of the HPA axis to a given stressor may result from adaptation to ambient stress levels, behavioral disposition, and the genetic regulation of the HPA axis.

One of the hypotheses addressing our prior observation of diminished HPA reactivity in offspring of SUD fathers was that these children had adapted to the chronically stressful home environments evoked by their substance-abusing parents. In this study, we have examined the sons’ salivary cortisol response to a defined stressor within the developmental context of their fathers’ SUD offsets in an expanded sample. Typically, SUD offsets are due to either spontaneous remission or successful treatment episodes. We have previously used this developmental strategy to examine the occurrence of internalizing and externalizing psychopathology in sons of drug-dependent fathers (Moss et al 1997).

The purpose of this investigation was threefold. First, we attempted to extend our original observation of decreased cortisol reactivity to an anticipated stressor in sons of drug-dependent fathers. Second, we examined the hypothesis that salivary cortisol underresponsivity in these high-risk prepubertal boys is an adaptation to the stress produced by having a father with a current, rather than remitted, SUD. Additionally, we explored developmental periods for the child when a paternal SUD has impact on the boy’s cortisol responsivity to stress. Third, we tested the hypothesis that prepubertal cortisol reactivity might be associated with subsequent drug use behavior during adolescence, thereby suggesting a mechanism for intergenerational transmission of substance abuse liability. Consequently, we examined the boys’ prepubertal salivary cortisol responses to an anticipated stressor in the context of regular monthly alcohol, marijuana, and tobacco use at follow-up 4 years later.