Elsevier

Biological Psychiatry

Volume 60, Issue 8, 15 October 2006, Pages 850-855
Biological Psychiatry

Original article
Cortisol and Adrenocorticotropic Hormone Responses to Naloxone in Subjects With High and Low Neuroticism

https://doi.org/10.1016/j.biopsych.2006.03.049Get rights and content

Background

Neuroticism is a highly heritable personality trait that is a risk factor for certain affective and anxiety disorders. Studies link neuroticism with alterations in the Hypothalamic–Pituitary–Adrenal (HPA) stress response. We interrogated HPA axis dynamics as a function of neuroticism, employing the opioid receptor antagonist, naloxone.

Methods

Subjects were assigned to either high or low neuroticism groups on the basis of Revised Neuroticism, Extraversion, Openness Personality Inventory (NEO-PI-R) scores and received naloxone hydrochloride (0, 125 μg/kg, and 375 ug/kg). Serum adrenocorticotropic hormone (ACTH) and cortisol levels were monitored.

Results

Significant, dose-dependent differences in cortisol response were observed between neuroticism groups, whereas no differences were observed in ACTH. The low neuroticism group demonstrated a dose-dependent cortisol response with a plateau at the 125 μg/kg dose of naloxone. In contrast, the high neuroticism group demonstrated a graded cortisol response to all doses of naloxone.

Conclusions

These findings show that neuroticism is associated with altered cortisol responses to opioid receptor blockade, suggesting that alterations in HPA axis function already exist in persons at increased risk for certain depressive and anxiety disorders.

Section snippets

Subjects

Thirty-five male and female participants, 18–25 years old, without an Axis I psychiatric diagnosis (including past or present alcohol dependence or current abuse) and without a family history of alcoholism, were recruited from the community as part of an ongoing study of cortisol responses to naloxone. Psychiatric diagnostic status was assessed with the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA; Bucholz et al 1994). Participants were assessed for neuroticism with the

Demographic Data

Demographic characteristics of the 35 subjects (high neuroticism group: n = 18; low neuroticism group: n = 17) included in our sample are shown in Table 1. Subjects ranged in age from 18 to 25 years, with an average age of 21 years, completed at least 2 years of college, and were Caucasian. Amount of alcohol consumption was low to moderate, and none of the subjects smoked cigarettes. The two subject groups did not differ on levels of cortisol binding globulin (see Table 2), age, gender (men: n

Discussion

We blocked endogenous opioid activity directed at hypothalamic CRF neurons to assess the possible role of suprapituitary elements in the dysregulations of HPA axis activity associated with neuroticism. This approach involved the administration of two incremental doses of naloxone, a nonselective opioid receptor antagonist, to induce a rise in ACTH and cortisol (Bujdoso et al 2001, Chrousos and Gold 1992, Tsagarakis et al 1990, Yajima et al 1986).

Our findings show that although ACTH responses

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