Having a family history of a substance use disorder increases a person’s statistical risk for developing an alcohol or drug problem (Merikangas et al., 1998
). One possible explanation for the increased risk is an inherited alteration in brain mechanisms that respond during emotional states. It would be desirable to identify physiological response markers sensitive to a person’s risk for alcoholism and other substance use disorders. A candidate marker is the cortisol response to stress, reflecting activity in the hypothalamic–pituitary–adrenocortical axis (HPA). In healthy individuals, cortisol is secreted in a diurnal pattern exhibiting a morning peak and a nighttime nadir. Cortisol is also regulated in response to a range of stressors (Lovallo, 2005
; Munck et al., 1984
). Cortisol’s response to psychological stress reflects the actions of extrahypothalamic regions of the brain, including the limbic system acting on the HPA. As a result, variations in cortisol’s secretion to psychological stress may reflect individual differences in affective processes, including alterations in neurobiological mechanisms as well as differences in appraisal and coping processes.
Alcoholic patients show a persisting cortisol hyporeactivity to a wide range of stressors (Adinoff et al., 2005a,b), including insulin-induced hypoglycemia (Costa et al., 1996
), as well as psychological stressors, including mental arithmetic plus a cold pressor test (Errico et al., 1993
), mental arithmetic plus isometric handgrip in males (Bernardy et al., 1996
), and simulated public speaking plus isometric handgrip in females (Bernardy, 1995
). These findings raise the question of whether the HPA in alcoholics has been damaged by prolonged exposure to high levels of ethanol. However, later studies demonstrated that patient groups were hyporesponsive to combined mental arithmetic and public speaking stress, although they had a normal diurnal pattern of cortisol secretion (Lovallo et al., 2000
). The normal diurnal pattern suggested intact HPA function, while the patients’ stress cortisol hyporesponsiveness may have reflected a difference in stress-related neural inputs to the hypothalamus that are needed for a psychological stress reaction. In parallel with these HPA findings, we observed that the same patients had an attenuated heart rate response to public speaking stress, although their reflex heart rate and blood pressure changes to orthostatic stress were normal (Panknin et al., 2002
). These HPA and cardiovascular findings are in agreement that the abstinent alcohol and polysubstance abusing patients had normal homeostatic regulation of visceral function, but that the neurological response to psychological stress was blunted. This led us to ask if these patients had a preexisting alteration in neural systems that regulate HPA responses to stress (Lovallo et al., 2000
A family history (FH) of alcoholism also appears to be associated with autonomic and endocrine hyporesponsiveness to stress. In comparison to FH− controls, boys, 10 to 12 years of age, whose fathers had been diagnosed with alcohol and psychoactive substance use disorders were found to exhibit a lower level of salivary cortisol secretion when anticipating a novel stressor task (Dawes et al., 1999
; Moss et al., 1995b
) and when faced with an unfamiliar electroencephalographic study in a hospital laboratory (Moss et al., 1995a
). During a 3–5 year follow-up, the boys most likely to have begun using tobacco and experimenting with drugs were those with the smallest cortisol responses, regardless of family history (Moss et al., 1999
). Adult children of alcoholics also have been found to exhibit a significantly lower plasma cortisol levels to an alcohol challenge in comparison to controls, which is noteworthy because alcohol stimulates the HPA axis under normal circumstances (Croissant and Olbrich, 2004
). Additionally, compared to FH− controls, nonalcoholic men with a high-density family history of alcoholism demonstrated smaller skin conductance responses to a tone signaling delivery of an electric shock (Finn et al., 1994
). These results raise the question of whether the stress hyporesponsivity of FH+ may signify elevated risk of future substance use disorders.
Personality variables have been shown to distinguish between FH+ and FH− groups, suggesting that certain personality traits may serve as markers of a person’s risk for development of a substance abuse problem (Elkins et al., 2004
). Personality variables measuring behavioral disinhibition and negative emotionality are often associated with substance abuse (Sher et al., 1999
). Studies of FH+ children show a clustering of temperamental, behavioral, and biochemical changes that are consistent with a hypothesis that genetic risk factors for alcoholism may be accompanied by altered functioning of the limbic system of the brain and that these alterations may be seen in emotionally or motivationally relevant situations (Blackson et al., 1996
; Cloninger et al., 1981
). Interestingly, antisocial behavior by adolescent boys has been associated with low cortisol responses and this effect was larger in those whose fathers displayed antisocial characteristics (Vanyukov, 1993
The goal of the Oklahoma Family Health Patterns project is to study healthy non-alcohol dependent FH+ and FH− individuals across three laboratory visits to identify markers of high risk in the domains of temperament, cognition and behavior, and psychophysiological function, with an emphasis on probes of emotional response systems. The purpose of this paper is to report on cortisol and autonomic responses to combined social and cognitive stressors in persons at risk of future alcoholism by virtue of a positive family history and their behavioral disinhibition characteristics. The primary hypothesis was that a family history of alcoholism would predict reduced salivary cortisol response to a psychological stressor, but that this reduction would be explained in whole or in part by the temperament characteristics of these persons.