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Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers

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Abstract

Rationale

Nicotine administration alters neuroactive steroids in rodent models, and serum levels of the neuroactive steroid DHEAS (dehydroepiandrosterone sulfate) appear to be higher in smokers. These molecules may be relevant to tobacco addiction and affective symptoms.

Objectives

This study aims to investigate DHEAS, allopregnanolone, pregnenolone, and other steroids in male smokers to determine potential associations with nicotine dependence severity and negative affect.

Materials and methods

Allopregnanolone and pregnenolone serum levels were determined by gas chromatography/mass spectrometry, while DHEAS and other steroid levels were determined by radioimmunoassay in 28 male smokers. Correlational analyses were performed to determine potential associations with rating measures, including the Fagerstrom Test for Nicotine Dependence (FTND), the addiction subscale of the Ikard Smoking Motivation Questionnaire (ISMQ), the craving item on the Reasons to Smoke (RTS) Questionnaire, and the negative affect and craving subscales of the Shiffman–Jarvik Withdrawal Questionnaire.

Results

DHEAS levels were inversely correlated with the negative affect subscale of the Shiffman–Jarvik Withdrawal Questionnaire (r=−0.60, p=0.002) and the RTS craving item (r=−0.43, p=0.03), and tended to be inversely correlated with the FTND scores (r=−0.38, p=0.067) and the ISMQ addiction subscale (r=−0.38, p=0.059), adjusting for age. Allopregnanolone levels were positively correlated with cotinine levels (r=0.57, p=0.006); pregnenolone levels tended to be positively correlated with cotinine levels (r=0.40, p=0.066).

Conclusions

DHEAS levels were inversely correlated with negative affect and craving measures, and may predict nicotine dependence severity. Allopregnanolone levels were positively correlated with cotinine levels, suggesting that this neuroactive steroid may be upregulated in smokers. Neuroactive steroids may represent novel smoking cessation agents.

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Acknowledgements

Support for this research was provided by the following sources: K23 MH 65080 (CEM), T32 MH70448 (WTT; PI Dan G. Blazer, M.D. Ph.D.), MIRECC VISN 6 (PI Gregory McCarthy, Ph.D.), Durham VA REAP (PI Roger Madison, Ph.D.), and a grant from Phillip Morris USA (JER). We thank Gillian J. Parke for her excellent assistance in the preparation of this manuscript.

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  1. Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27710, USA

    Christine E. Marx, William T. Trost, Lawrence Shampine, Frederique M. Behm, Louis A. Giordano & Jed E. Rose

  2. Durham Veterans Affairs Medical Center, Mental Health Service Line 116A, 508 Fulton Street, Durham, NC, 27705, USA

    Christine E. Marx, William T. Trost, Louis A. Giordano & Mark W. Massing

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  1. Christine E. Marx
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Correspondence to Christine E. Marx.

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Marx, C.E., Trost, W.T., Shampine, L. et al. Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers. Psychopharmacology 186, 462–472 (2006). https://doi.org/10.1007/s00213-005-0226-x

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