Psychopharmacology

, 186:473 | Cite as

A decrease in the plasma DHEA to cortisol ratio during smoking abstinence may predict relapse: a preliminary study

  • Ann M. Rasmusson
  • Ran Wu
  • Prashni Paliwal
  • George M. Anderson
  • Suchitra Krishnan-Sarin
Original Investigation
First Online:
Received:
Accepted:

Abstract

Rationale

Increases in depressive symptoms during smoking cessation have been associated with risk for relapse. Several studies have linked plasma levels of cortisol and dehydroepiandrosterone (DHEA) or DHEA-sulfate (DHEAS) to depressive symptoms.

Objectives

To determine whether changes in plasma cortisol, DHEA, or DHEAS levels and emergence of depressive symptoms during smoking cessation are associated with smoking relapse.

Materials and methods

Subjects were healthy non-medicated men and women, aged 39±12 years, who smoked, on average, 22 cigarettes per day. Depressive symptoms, smoking withdrawal symptoms, and plasma steroid levels were measured before and after 8 days of verified smoking abstinence. Relapse status at day 15 was then determined.

Results

In the full sample (n=63), there was a trend for changes in depressive symptoms to be associated with relapse. In the subset of 25 subjects with plasma neuroactive steroid data, there was a significant interaction between the change in the plasma DHEA/cortisol ratio from day 0 to day 8 and relapse status at day 15. This ratio was similar before abstinence, but lower at day 8 in relapsed, compared to abstinent, subjects. Changes in the DHEA/cortisol ratio tended to predict changes in depressive symptoms in the women only.

Conclusion

A decrease in the plasma DHEA/cortisol ratio during 8 days of smoking abstinence was associated with relapse over the following week. Further research is needed to fully characterize sex-specific relationships between abstinence-induced changes in neuroactive steroid levels, depressive or withdrawal symptoms, and relapse. Such research may lead to new interventions for refractory smoking dependence.

Keywords

Smoking cessation Smoking relapse Cortisol Dehydroepiandrosterone DHEA DHEAS Sex differences Depression Nicotine Men Women 
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Notes

Acknowledgements

This work was supported by the Yale Interdisciplinary Research Scholar Program on Women and Drug Abuse via the NIH Office of Research on Women’s Health (ORWH) and NIDA 1K12DA14038-01, the Yale Transdisciplinary Tobacco Use Research Center: P50DA13334, and a VA Merit Award to Dr. Rasmusson.

References

  1. Aston-Jones G, Chen S, Zhu Y, Oshinsky ML (2001) A neural circuit for circadian regulation of arousal. Nat Neuroscience 4:732–738CrossRefGoogle Scholar
  2. Araneo BA, Shelby J, Li G-Z, Ku W, Daynes RA (1993) Administration of dehydroepiandrosterone to burned mice preserves normal immunologic competence. Arch Surg 128:318–325PubMedGoogle Scholar
  3. al’Absi M, Hatsukami D, Davis GL, Wittmers LE (2004) Prospective examination of effects of smoking abstinence on cortisol and withdrawal symptoms as predictors of early smoking relapse. Drug Alcohol Depend 73:267–78CrossRefPubMedGoogle Scholar
  4. Arlt W, Callies F, vanVlumen JC, Koehler I, Reincke M, Bidlingmaier M et al (1999) Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med 341:1013–1020PubMedCrossRefGoogle Scholar
  5. Bastianetto S, Ramassamy C, Poirier J, Quirion R (1999) Dehydroepiandrosterone (DHEA) protects hippocampal cells from oxidative stress-induced damage. Mol Brain Res 66:35–41CrossRefPubMedGoogle Scholar
  6. Baulieu EE, Robel P (1998) Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids. Proc Natl Acad Sci 95:4089–4091CrossRefPubMedGoogle Scholar
  7. Benediktsson R, Magnusdottir EM, Seckl JR (1997) Lack of effect of nicotine or ethanol on the activity of 11beta-hydroxysteroid dehydrogenase type 2. J. Steroid Biochem Mol Biol 63:303–307CrossRefPubMedGoogle Scholar
  8. Blauer KL, Poth M, Rogers W, Bernton E (1991) DHEA antagonizes the suppressive effects of dexamethasone on lymphocyte proliferation. Endocrinology 129: 3174–3179PubMedCrossRefGoogle Scholar
  9. Browne ES, Wright BE, Porter JR, Svec F (1992) Dehydroepiandrosterone: antiglucocorticoid action in mice. Am J Med Sci 303:366–371PubMedCrossRefGoogle Scholar
  10. Cam GR, Bassett JR (1984) Effect of prolonged exposure to nicotine and stress on the pituitary-adrenocortical response; the possibility of cross-adaptation. Pharm Biochem Beh 20:221–226CrossRefGoogle Scholar
  11. Chakravarti I, Laha R, Roy J (1967) Handbook of methods of applied statistics, vol 1. Wiley, New York, pp 392–394Google Scholar
  12. Compagnone NA, Mellon SH (2000) Neurosteroids: biosynthesis and function of these novel neuromodulators. Front Neuroendocrinol 21:1–56CrossRefPubMedGoogle Scholar
  13. Cruess DG, Antoni MH, Kumar M, Ironson G, McCabe P, Fernandez JB et al (1999) Cognitive-behavioral stress management buffers decreases in dehydroepiandrosterone sulfate (DHEA-S) and increases in the cortisol/DHEA-S ratio and reduces mood disturbance and perceived stress among HIV-seropositive men. Psychoneuroendocrinology 24:537–549CrossRefPubMedGoogle Scholar
  14. Daynes RA, Dudley DJ, Araneo BA (1990) Regulation of murine lymphokine production in vivo, II: Dehydroepiandrosterone is a natural enhancer of IL-2 synthesis by helper T cells. Eur J Immunol 19:2319–2325CrossRefGoogle Scholar
  15. Duman RS (2004) Depression: a case of neuronal life and death? Biol Psychiatry 56(3):140–145CrossRefPubMedGoogle Scholar
  16. First MB, Spitzer RL, Gibbon M, Williams JB (1995a) Structured Clinical Interview for the DSM-IV Axis I Disorders—NonPatient Edition (SCID-I/NP, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New York, NYGoogle Scholar
  17. First MB, Spitzer RL, Gibbon M, Williams JB (1995b) Structured Clinical Interview for the DSM-IV Axis I Disorders—Patient Edition (SCID-I/P, Version 2.0). Biometrics Research Department, New York State Psychiatric Institute, New York, NYGoogle Scholar
  18. Fitzpatrick J, Ripp SL, Smith NB, Pierce WM, Prough RA (2001) Metabolism of DHEA by cytochromes P450 in rat and human liver microsomal fractions. Arch Biochem Biophysics 389:278–287CrossRefGoogle Scholar
  19. Frye RF, Kroboth PD, Kroboth FK, Stone RA, Folan M, Salek SF, Pollock BG, Linares AM, Hakala C (2000) Sex differences in the pharmacokinetics of dehydroepiandrosterone (DHEA) after single and multiple dose administration in healthy older adults. J Clin Pharmacol 40:596–605CrossRefPubMedGoogle Scholar
  20. Gilbert DG, McClernon J, Rabinovich NE, Dibb WD, Plath LC, Hiyane S, Jensen RA, Meliska CJ, Estes SL, Gehlbach BA (1999) EEG, physiology, and task-related mood fail to resolve across 31 days of smoking abstinence: relations to depressive traits, nicotine exposure, and dependence. Exp Clin Psychopharmacol 7:427–443CrossRefPubMedGoogle Scholar
  21. Goodyer IM, Herbert J, Altham PME (1998) Adrenal steroid secretion and major depression in 8- to 16-year-olds, III. Influence of cortisol/DHEA ratio at presentation on subsequent rates of disappointing life events and persistent major depression. Psychol Med 28:265–273CrossRefPubMedGoogle Scholar
  22. Goto Y, Grace AA (2005) Dopaminergic modulation of limbic and cortical drive of nucleus accumbens in goal-directed behavior. Nat Neuroscience. 8:805–812CrossRefGoogle Scholar
  23. Gritz ER, Carr CR, Marcus AC (1991) The tobacco withdrawal syndrome in unaided quitters. Br J Addiction 86:57–69CrossRefGoogle Scholar
  24. Grundemann D, Schechinger B, Rappold GA, Schomig E (1998) Molecular identification of the cortisone-sensitive extraneuronal catecholamine transporter. Nat Neurosci 1:349–351CrossRefPubMedGoogle Scholar
  25. Hariharan M, VanNoord T, G JF (1988) A high performance liquid chromatographic technique for routine simultaneous determination of nicotine and cotinine in plasma. Clin Chem 34:724–729PubMedGoogle Scholar
  26. Hatsukami D (1994) Effects of nicotine gum on withdrawal symptoms in females vs males. Paper presented at the American Psychological Association, Psychosocial and Behavioral Factors in Women’s Health: Creating an Agenda for the 21st century, Washington, DCGoogle Scholar
  27. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom KO (1991) The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom tolerance questionnaire. Br J Addict 86:1119–1127PubMedCrossRefGoogle Scholar
  28. Heinz A, Weingartner H, George D, Hommer D, Wolkowitz OM, Linnoila M (1999) Severity of depression in abstinent alcoholics is associated with monoamine metabolites and dehydroepiandrosterone-sulfate concentrations. Psychiatry Res 89:97–106CrossRefPubMedGoogle Scholar
  29. Heninger GR (1997) Serotonin, sex, and psychiatric illness. Proc Natl Acad Sci U S A 94:4823–4824CrossRefPubMedGoogle Scholar
  30. Higgins ST, Delaney DD, Budney AJ, Bickel WK, Hughes Foerg F (1991) A behavioral approach to achieving initial cocaine abstinence. Am J Psychiatr 148:1218–1224PubMedGoogle Scholar
  31. Hornsby PJ (1995) Biosynthesis of DHEAS by the human adrenal cortex and its age-related decline. Ann NY Acad Sci 774:29–46PubMedCrossRefGoogle Scholar
  32. Kaminska M, Harris J, Gilsbers K, Dubrovsky B (2000) Dehydroepiandrosterone sulfate (DHEAS) counteracts decremental effects of corticosterone on dentate gyrus LTP. Implications for depression. Brain Res Bull 52:229–234CrossRefPubMedGoogle Scholar
  33. Karishma KK, Herbert J (2002) Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression. Eur J Neurosci 16:445–453CrossRefPubMedGoogle Scholar
  34. Kessler RC (2003) Epidemiology of women and depression. J Affect Disord 74:5–13CrossRefPubMedGoogle Scholar
  35. Kimonides VG, Khatibi NH, Svendsen CN, Sofroniew MV, Herbert J (1998) Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS) protect hippocampal neurons against excitatory amino acid-induced neurotoxicity. Proc Natl Acad Sci U S A 95:1852–1857CrossRefPubMedGoogle Scholar
  36. Kirschbaum C, Scherer G, Strasburger CJ (1994) Pituitary and adrenal hormone responses to pharmacological, physical, and psychological stimulation in habitual smokers and nonsmokers. Clin Investig 72:804–810CrossRefPubMedGoogle Scholar
  37. Koenen KC, Hitsman B, Lyons MJ, Niaura R, McCaffery J, Goldberg J, Eisen SA, True W, Tsuang M (2005) A twin registry study of the relationship between posttraumatic stress disorder and nicotine dependence in men. Arch Gen Psychiatry 62:1258–1265CrossRefPubMedGoogle Scholar
  38. Krishnan-Sarin S, Rosen MI, O’Malley S (1999) Naloxine challenge in smokers. Preliminary evidence of an opioid component in nicotine dependence. Arch Gen Psychiatry 56:663–668CrossRefPubMedGoogle Scholar
  39. Kroboth PD, Amico JA, Stone RA, Folan M, Frye RF, Kroboth FJ, Bigos KL, Fabian TJ, Linares AM, Pollock BG, Hakala C (2003) Influence of DHEA administration on 24-hour cortisol concentrations. J Clin Psychopharmacol 23:96–99CrossRefPubMedGoogle Scholar
  40. Lamba V, Yasuda K, Lamba JK, Assem M, Davila J, Strom S, Schutetz EG (2004) PXR (NR112) splice variants in human tissues, including brain, and identification of neurosteroids and nicotine as PXR activators. Toxicol Appl Pharmacol 199:251–265CrossRefPubMedGoogle Scholar
  41. Leibenluft E, Fiero PL, Rubinow DR (1994) Effects of the menstrual cycle on dependent variables in mood disorder research. Arch Gen Psychiatry 51:761–781PubMedGoogle Scholar
  42. Lisman JE, Grace AA (2005) The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron 46:703–713CrossRefPubMedGoogle Scholar
  43. Littell RC, Milliken GA, Stroup WW, Wolfinger RD (1996) SAS system for mixed models. SAS Institute, Cary, North CarolinaGoogle Scholar
  44. Malaiyandi V, Sellers EM, Tyndale RF (2005) Implications of CYP2A6 genetic variation for smoking behaviors and nicotine dependence. Clin Pharmacol Ther 77:145–158CrossRefPubMedGoogle Scholar
  45. Maser E, Richter E, Friebertshauser J (1996) The identification of 11 beta-hydroxysteroid dehydrogenase as carbonyl reductase of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Eur J Biochem 238(2):484–9CrossRefPubMedGoogle Scholar
  46. Mattson MP, Maudsley S, Martin B (2004) BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends Neurosci 27:589–594CrossRefPubMedGoogle Scholar
  47. Michael A, Jenaway A, Paykel ES, Herbert J (2000) Altered salivary dehydroepiandrosterone levels in major depression in adults. Biol Psychiatry 48:989–995CrossRefPubMedGoogle Scholar
  48. Morgan CA III, Southwick S, Hazlett G, Rasmusson A, Hoyt G, Zimolo Z, Charney D (2004) Relationships among plasma DHEA(S), cortisol, symptoms of dissociation and objective performance in humans exposed to acute stress. Arch Gen Psychiatry 61:812–819CrossRefGoogle Scholar
  49. Morfin R, Starka L (2001) Neurosteroid 7-hydroxylation products in the brain. Int Rev Neurobiol 46:79–95PubMedGoogle Scholar
  50. Prasad A, Imamura M, Prasad C (1997) Dehydroepiandrosterone decreases behavioral despair in high- but not low-anxiety rats. Physiol Behav 62:1053–1057CrossRefPubMedGoogle Scholar
  51. Radloff LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401CrossRefGoogle Scholar
  52. Rajkowski J, Majczynski H, Clayton E, Aston-Jones G (2004) Activation of monkey locus coeruleus neurons varies with difficulty and performance in a target detection task. J Neurophysiol 92:361–371CrossRefPubMedGoogle Scholar
  53. Rasmusson AM, Vythilingam M, Morgan, CA III (2003) The neuroendocrinology of PTSD—new directions. CNS Spectr 8:651–667PubMedGoogle Scholar
  54. Rasmusson AM, Vasek J, Lipschitz DS, Vojvoda D, Mustone ME, Shi Q, Gudmundsen G, Morgan CA, Wolfe J, Charney DS (2004) An increased capacity for adrenal DHEA release is associated with decreased avoidance and negative mood symptoms in women with PTSD. Neuropsychopharmacology 29:1546–1557CrossRefPubMedGoogle Scholar
  55. Rasmusson A, Picciotto M, Krishnan-Sarin S (2006) Smoking as a critical but complex covariate in studies of HPA axis adaptation in PTSD. A review. J Psychopharmacol (in press)Google Scholar
  56. Roll JM, Higgins ST, Badger GJ (1996) An experimental comparison of three different schedules of reinforcement of drug abstinence using cigarette smoking as an exemplar. J Appl Behav Anal 29:495–504CrossRefPubMedGoogle Scholar
  57. Rose KA, Stapleton G, Dott K, Kieny MP, Best R, Schwarz M (1997) Cyp7b, a novel brain cytochrome P450, catalyzes the synthesis of neurosteroids 7α-hydroxy-dehydroepiandrosterone and 7α-hydroxy-pregnenolone. Proc Natl Acad Sci U S A 94:4925–4930CrossRefPubMedGoogle Scholar
  58. Rosenfeld RS, Hellman L, Roffwarg H, Weitzman ED, Fukushima DK, Gallagher TF (1971) Dehydroisoandrosterone is secreted episodically and synchronously with cortisol by normal man. J Clin Endocrinol 33:87–92Google Scholar
  59. Schmidt PJ, Daly RC, Bloch M, Smith MJ, Danaceau MA, Simpson St, Clair L, Murphy JH, Haq N, Rubinow DR (2005) Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry 62:154–162CrossRefPubMedGoogle Scholar
  60. Sellini M, Sartori MP, Baccarini S, Bassi R, Dimitriadis E (1989) ACTH and cortisol after cigarette smoke exposure during the dexamethasone suppression test in smokers and non-smokers. Biologia Sperimentale 65:377–380Google Scholar
  61. Shiffman S (1982) Relapse following smoking cessation: a situational analysis. J Consult Clin Psychol 50:71–86CrossRefPubMedGoogle Scholar
  62. Sobell M, Sobell L (1992) Timeline followback: a technique for assessing self-reported alcohol consumption. In: Measuring alcohol consumption; psychosocial and biochemical methods, Humana, New Jersey, pp 41–72Google Scholar
  63. Strous R, Maayan R, Lapidus R, Stryjer R, Lustig M, Kotler M et al (2003) Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia. Arch Gen Psychiatry 60:133–141CrossRefPubMedGoogle Scholar
  64. Svikis DS, Hatsukami DK, Hughes JR, Caroll KM, Pickens RW (1986) Sex differences in tobacco withdrawal syndrome. Addict Behav 11:459–462Google Scholar
  65. Tobler PN, Fiorillo CD, Schultz W (2005) Adaptive coding of reward value by dopamine neurons. Science 307:1642–1645CrossRefPubMedGoogle Scholar
  66. Tsuda A, Steptoe A, West R, Fieldman G, Kirschbaum C (1996) Cigarette smoking and psychophysiological stress responsiveness effects of recent smoking and temporary abstinence. Psychopharmacology 126:226–233CrossRefPubMedGoogle Scholar
  67. Van Haarst AD, Oitzl MS, Workel JO, De Kloet ER (1996) Chronic brain glucocorticoid receptor blockade enhances the rise in circadian and stress-induced pituitary-adrenal activity. Endocrinology 137:4935–4943CrossRefPubMedGoogle Scholar
  68. Wang H, Napoli KL, Strobel HW (2000) Cytochrome P450 3A9 catalyzes the metabolism of progesterone and other steroid hormones. Mol Cell Biochem 213:127–135CrossRefPubMedGoogle Scholar
  69. Wolkowitz OM, Reus VI, Keebler A, Nelson N, Friedland M, Brizendine L et al (1999) Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry 156:646–649PubMedGoogle Scholar
  70. Yaffe K, Ettinger B, Pressman A, Seeley D, Whooley M, Schaefer C et al (1998) Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry 43:694–700CrossRefPubMedGoogle Scholar
  71. Young AH, Gallagher P, Porter RJ (2002) Elevation of the cortisol dehydroepiandrosterone ratio in drug-free depressed patients. Am J Psychiatry 159:1237–1239CrossRefPubMedGoogle Scholar
  72. Young EA, Carlson NE, Brown MB (2001) Twenty-four-hour ACTH and cortisol pulsatility in depressed women. Neuropsychopharmacology 25:267–276CrossRefPubMedGoogle Scholar
  73. Zhang L, Li B, Ma W, Barker JL, Chang YH, Zhao W (2002) Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) regulate apoptosis during neurogenesis by triggering the Akt signaling pathway in opposing ways. Brain Res Mol Brain Res 98:58–66CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Ann M. Rasmusson
    • 1
    • 2
    • 6
  • Ran Wu
    • 1
    • 3
  • Prashni Paliwal
    • 1
    • 4
  • George M. Anderson
    • 3
    • 5
  • Suchitra Krishnan-Sarin
    • 1
    • 3
  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA
  2. 2.Clinical Neuroscience DivisionVA National Center for PTSDWest HavenUSA
  3. 3.Department of Laboratory Medicine and Transdisciplinary Tobacco Use Research CenterYale University School of MedicineNew HavenUSA
  4. 4.Division of Women’s Behavioral HealthYale University School of MedicineNew HavenUSA
  5. 5.Child Study CenterYale UniversityNew HavenUSA
  6. 6.Psychiatry Service/116AVA Connecticut Healthcare SystemWest HavenUSA

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