Dehydroepiandrosterone sulfate, cortisol, mood state and smoking cessation: Relationship to relapse status at 4-week follow-up Natalie A. Ceballos a , Mustafa al'Absi a,b,c, ⁎ a Department of Behavioral Sciences, 1035 University Drive, 236 Medical School Building, University of Minnesota Medical School, Duluth, MN 55812-3031, USA b Department of Family Medicine, 1035 University Drive, 236 Medical School Building, University of Minnesota Medical School, Duluth, MN 55812-3031, USA c Department of Physiology and Pharmacology, 1035 University Drive, 236 Medical School Building, University of Minnesota Medical School, Duluth, MN 55812-3031, USA Received 21 October 2005; received in revised form 24 April 2006; accepted 30 June 2006 Abstract It has been hypothesized that increased baseline dehydroepiandrosterone sulfate (DHEAS) levels may act as a natural antidepressant to attenuate negative affect during cocaine withdrawal and abstinence, decreasing the probability of relapse. The current study extends this model to assess factors related to risk of relapse in a sample of 68 nicotine dependent participants. Repeated measures ANOVAs were used to examine mood state, salivary DHEAS and cortisol levels across three assessment periods in participants who had relapsed over a 4-week follow-up period (n =51, 23 women) compared to those who maintained abstinence (n = 17, 8 women). Total scores on the Profile of Mood States differed between those who had relapsed and those who maintained abstinence (p = 0.008). However, DHEAS and cortisol levels, as well as the ratio of cortisol to DHEAS, did not differ significantly between groups. These findings suggest that, although DHEAS-related enhancement of resiliency to withdrawal may occur, the extent of this protective effect may be modulated by additional factors that warrant further research. © 2006 Elsevier Inc. All rights reserved. Keywords: Dehydroepiandrosterone sulfate; Cortisol; Mood; Smoking; Relapse 1. Introduction Chronic cigarette smoking is a well known and preventable cause of serious illness and death. However, although various smoking cessation treatments exist, relapse rates remain relatively high. According to the National Institutes of Health, less than 7% of the nearly 35 million individuals per year who attempt unaided smoking cessation will maintain abstinence for more than 1 year (National Institutes on Drug Abuse, 2001). Clearly, additional research is needed to determine factors that may predict treatment success and/or recommend additional approaches to smoking cessation. Psychosocial stressors, as well as increased negative and decreased positive mood, have been shown to contribute to risk for smoking relapse (Shiffman and Waters, 2004). A potential biological marker of such subjective characteristics was recently examined in the context of addiction to another stimulant drug, cocaine. Alterations in activity of the hypothalamic–pitutiary– adrenal (HPA) axis have been observed in the early phases of cocaine abstinence. Buydens-Branchey et al. (2002) assessed changes in cortisol and the neuroexcitatory adrenal steroid hor- mone, dehydroepiandrosterone sulfate (DHEAS) in hospitalized cocaine abusers after 6, 9, 18 and 21 days of abstinence. Results indicated a decrease in cortisol and increase in DHEAS over the 3 weeks of abstinence, suggesting a gradual return to the indi- viduals' pre-drug state. More recently, Wilkins et al. (2005) examined the relationship between DHEAS and relapse to co- caine use in a population of treatment-seeking cocaine users. DHEAS has been described as an index of physical and mental well being and may positively impact health by antagonizing glucocorticoids, as many disease states are characterized by high cortisol levels with correspondingly low levels of DHEAS (Wolf and Kirschbaum, 1999). The results of Wilkins et al. suggest that Pharmacology, Biochemistry and Behavior xx (2006) xxx – xxx + MODEL PBB-69974; No of Pages 6 www.elsevier.com/locate/pharmbiochembeh ⁎ Corresponding author. Tel.: +1 218 726 7144; fax: +1 218 726 7559. E-mail address: malabsi@umn.edu (M. al'Absi). 0091-3057/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.pbb.2006.06.021 ARTICLE IN PRESS