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Psychological stress and cortisol secretion in anhedonic alcoholic men
European Psychiatry 18 (2003) 415–417 www.elsevier.com/locate/eurpsy
Short communication
Psychological stress and cortisol secretion in anhedonic alcoholic men D. Marra a, D. Warot a,*, I. Berlin a, E. Hispard b, S. Dally b a
Département de Pharmacologie, Hôpital Pitié-Salpêtrière, 47, Bd de l’Hôpital, 75634 Paris cedex 13, France b Service Médecine Interne, Hôpital Fernand Widal, 200, rue du Fg St Denis, 75010 Paris, France Received 23 October 2001; received in revised form 24 October 2002; accepted 11 June 2003
Abstract We investigated plasma cortisol in a psychological stress paradigm in seven weaned anhedonic alcoholics in comparison with seven age-matched healthy controls. Alcoholics had significantly higher mean plasma cortisol at baseline and no increase following a psychological stress paradigm. Anhedonic alcoholics judged the experimental situation less agreeable than controls. Anhedonic alcoholics may have blunted cortisol response to psychological stress. © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Cortisol; Alcoholism; Anhedonia; Psychological stress
1. Introduction Increased plasma cortisol has consistently been observed in alcoholics [1,7]. Some alcoholics have previously been found to be anhedonic [14]. Anhedonic subjects may need intense pleasurable stimulations to compensate for their low emotional reactivity [13,16]. We hypothesized that anhedonic alcoholics may drink to increase their emotional reactivity.
Controls were seven paid male age-matched nonalcoholics. None of the controls had histories of mental illness, current substance abuse or dependence (except nicotine) or sleep disturbance. All subjects gave their written informed consent and the study was approved by the Ethics Committee of the Pitié-Salpêtrière Hospital, Paris. 3. Standardized psychological stresses 3.1. Delayed auditory feedback (DAF) [3]
2. Subjects and methods Seven male alcoholic patients participated in the study. They all met DSM-VI criteria for alcohol dependence [11]. The duration of alcoholism ranged from 6 to 30 years. Reasons for noninclusion were diagnosis of primary affective disorder with secondary alcoholism [15], schizophrenia, treatment by antidepressants, or neuroleptics, severe somatic illness or no fixed address. To be considered as anhedonic all alcoholic subjects must score 13 or more on Chapman’s Social Anhedonia Scale (SAS) and 18 or more on Chapman’s Physical Anhedonia Scale (PAS) [5]. The cut-offs were chosen according to the results obtained in a French population [2]. * Corresponding author. E-mail address: [email protected] (D. Warot). © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. doi:10.1016/j.eurpsy.2003.06.007
The participant was reading a standard text during 5 min into a microphone. The spoken text was recorded in a speech delayer (Zak, Sembach/Inn, Germany) and transferred back to the test subject via earphones with a delay of 180 ms. 3.2. Arithmetical mental task [9,10] The subject had to subtract 13 as quickly and accurately as possible starting at 1022. The stress procedure lasted 15 min. 4. Dependent measures Hundred millimeter-line Visual Analogue Scales (VAS) were used to record unpleasantness, agreeableness and feeling stressed, at baseline, just after and 105 min after the stress procedure. Plasma concentrations of cortisol were measured by radioimmunologic assay.
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D. Marra et al. / European Psychiatry 18 (2003) 415–417
5. Study design The patients were tested at the end of the second week of abstinence. They had to be free of psychotropic drugs for at least 48 h administered for the withdrawal program. Blood samples (10 ml) were obtained at baseline, and 15, 30, 40, 50, 60, 75, 90 and 120 min after the stress procedure. 6. Statistical analysis Pairwise comparisons were performed by the Mann– Whitney test. Repeated measures ANOVA with factors group and time was used to test overall between- and within-subject effects. 7. Results The mean (±S.D.) age of the anhedonic alcoholics and controls was similar (43 ± 7.8 vs. 42 ± 6.8 years). Anhedonic alcoholics scored higher on both Physical (20.3 ± 3.3 vs. 10 ± 4.7, P < 0.001) and Social Anhedonia Scales (20 ± 7.1 vs. 9.7 ± 4, P < 0.001) than controls. Anhedonic alcoholics had significantly higher baseline plasma cortisol concentration than controls (12.6 ± 3.4 vs. 8.1 ± 2.8 µg/dl, P < 0.02). Baseline plasma cortisol significantly correlated with Physical Anhedonia Scale score (r = 0.58, P = 0.03). Change from baseline to peak plasma cortisol following psychological stress was significantly higher in controls than in anhedonic alcoholics (2.8 ± 4.3 vs. –0.4 ± 3, P = 0.04). The evolution of plasma cortisol concentration in controls indicates an increase following the psychological stress (Fig. 1). In anhedonic alcoholics, mean plasma cortisol concentration shows only a downward trend and no stress induced plasma cortisol increase. A two-way
Fig. 2. Visual Analog Scales (VAS) before (T0), just after (T15) psychological stress exposure and at 120 min after the beginning of psychological stress exposure in anhedonic alcoholics (filled squares) and healthy controls (open squares). Data are means ± S.D.
ANOVA showed no group effect (F1,12 = 1.74, P = 0.212), a significant time effect (F9,108 = 8.65, P < 0.001) and a significant time by group interaction (F9,108 = 2.3, P = 0.02). For the both VAS “stressed” and “unpleasant”, only a significant effect of the psychological stress (F2,24 = 13, P = 0.002 and F2,24 = 5.921, P = 0.014) was shown. For the VAS “agreeable”, a significant group effect (F1,12 = 11.6, P = 0.005) stress effect (F2,24 = 7.95, P = 0.002) were observed with no significant group by stress interaction (Fig. 2).
8. Discussion
Fig. 1. Mean (±S.D.) plasma cortisol concentration before, during and after psychological stress in anhedonic alcoholics (filled squares) and healthy controls (open squares).
In this study, anhedonic alcoholic men had significantly higher baseline plasma cortisol concentration, showed no increase in plasma cortisol in response to psychological stress when compared to age-matched nonalcoholic nonan-
D. Marra et al. / European Psychiatry 18 (2003) 415–417
hedonic subjects. Anhedonic alcoholics rated less agreeable than controls the experimental paradigm, which was equally stressful for both groups. Overall, anhedonic alcoholics could be characterized by blunted plasma cortisol response and attenuated subjective responses to psychological stress. The mean plasma cortisol baseline of alcoholics and controls is similar to those found in other studies of alcoholics and controls [6,7,12]. The increased cortisol level observed in anhedonic alcoholics can reflect an activation of the HPA axis associated with ethanol withdrawal [1,7,8]. Lack of augmentation of plasma cortisol in response to psychological stress was observed in alcoholics abstinent from alcohol up to 4 weeks [4,6]. The subjective sensation of stress perceived by the subjects was statistically similar in the two groups, however, visual inspection of data (Fig. 2) may suggest that even 2 h after stress exposure, anhedonic alcoholics remain stressed while controls returned to the pre-stress level. Anhedonic alcoholics’ scoring on VAS “agreeable” was flat while controls’ response can be considered as normal. This “emotional flatness” which is a characteristic feature of anhedonia, parallels with the observed lack of increase in plasma cortisol. This study has several limitations. The number of the subjects is small, a third group composed of nonanhedonic alcoholic with short term abstinence could have been included.
Acknowledgements We are indebted to S. Guillemant for the plasma cortisol determinations. This study was supported by the Assistance Publique-Hôpitaux de Paris.
References [1]
Adinoff B, Risher-Flowers D, De Jong J, Ravitz B, Bone GHA, Nutt DJ, et al. Disturbances of hypothalamic-pituitary-adrenal axis functioning during ethanol withdrawal in six men. Am J Psychiatry 1991;148:1023–5.
[2]
[3]
[4]
[5]
417
Assouly-Besse F, Dollfus S, Petit M. Traduction française des questionnaires d’anhédonie sociale et physique de Chapman: validation de la traduction française à partir de témoins et de patients schizophrènes. Encephale 1995;XXI:273–84. Badian M, Appel E, Palm D, Rupp W, Sittig W, Tauber K. Standardized mental stress in healthy volunteers induced by delayed auditory feedback (DAF). Eur J Clin Pharmacol 1979;16:171–6. Bernardy NC, King AC, Parsons OA, Lovallo WR. Altered cortisol response in sober alcoholics: an examination of contributing factors. Alcohol 1996;13:493–8. Chapman LJ, Chapman JP, Raulin MI. Scales for physical and social anhedonia. J Abnormal Psychol 1976;85:374–82.
[6]
Ehrenreich H, Schuck J, Stender N, Pilz J, Gefeller O, Schilling L, et al. Endocrine and hemodynamic effects of stress versus systemic CRF in alcoholics during early and medium term abstinence. Alcohol Clin Exp Res 1997;21:1285–93.
[7]
Fonzi S, Solinas GP, Costelli P, Parodi C, Murialdo G, Bo P, et al. Melatonin and cortisol circadian secretion during ethanol withdrawal in chronic alcoholics. Chronobiologia 1994;21:109–12.
[8]
Iranmanesh A, Veldhuis JD, Johnson ML, Lizzaralde G. 24-hour pulsatile and circadian patterns of cortisol secretion in alcoholic men. J Androl 1989;10:54–63.
[9]
Kirschbaum C, Wüst S, Faig HG, Hellhammer DH. Heritability of cortisol responses to human corticotrophin-releasing hormone, ergometry, and psychological stress in humans. J Clin Endocrinol Metab 1992;75:1526–30.
[10] Kirschbaum C, Strasburger CJ, Langkrär J. Attenuated cortisol response to psychological stress but not to CRF or ergometry in young habitual smokers. Pharmacol Biochem Behav 1993;44:527–31. [11] Lecrubier Y, Sheehan DV, Weiller E, Amorim P, Bonora I, Sheehan KH, et al. The Mini International Neuropsychiatric Interview (MINI). A short diagnosis structured interview: reliability and validity according to the CIDI. Euro Psychiatry 1997;12:224–31. [12] Marchesi C, Chiodera P, Ampollini P, Volpi R, Coiri V. Betaendorphin, adrenocorticotropic hormone and cortisol secretion in abstinent alcoholics. Psychiatry Res 1997;72:187–94. [13] Marin RS. Differential diagnosis and classification of apathy. Am J Psychiatry 1990;147:22–30. [14] Marra D, Warot D, Payan C, Hispard E, Dally AJ, Puech AJ. Anhedonia and relapse in alcoholism. Psychiatry Res 1998;80:187–96. [15] Schuckit MA, Hesselbrock V. Alcohol dependence and anxiety disorders: what is the relationship? Am J Psychiatry 1994;151:1723– 34. [16] Quay HC. Psychopathic personality as pathological stimulation seeking. Am J Psychiatry 1965;122:180–3.
Short communication
Psychological stress and cortisol secretion in anhedonic alcoholic men D. Marra a, D. Warot a,*, I. Berlin a, E. Hispard b, S. Dally b a
Département de Pharmacologie, Hôpital Pitié-Salpêtrière, 47, Bd de l’Hôpital, 75634 Paris cedex 13, France b Service Médecine Interne, Hôpital Fernand Widal, 200, rue du Fg St Denis, 75010 Paris, France Received 23 October 2001; received in revised form 24 October 2002; accepted 11 June 2003
Abstract We investigated plasma cortisol in a psychological stress paradigm in seven weaned anhedonic alcoholics in comparison with seven age-matched healthy controls. Alcoholics had significantly higher mean plasma cortisol at baseline and no increase following a psychological stress paradigm. Anhedonic alcoholics judged the experimental situation less agreeable than controls. Anhedonic alcoholics may have blunted cortisol response to psychological stress. © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. Keywords: Cortisol; Alcoholism; Anhedonia; Psychological stress
1. Introduction Increased plasma cortisol has consistently been observed in alcoholics [1,7]. Some alcoholics have previously been found to be anhedonic [14]. Anhedonic subjects may need intense pleasurable stimulations to compensate for their low emotional reactivity [13,16]. We hypothesized that anhedonic alcoholics may drink to increase their emotional reactivity.
Controls were seven paid male age-matched nonalcoholics. None of the controls had histories of mental illness, current substance abuse or dependence (except nicotine) or sleep disturbance. All subjects gave their written informed consent and the study was approved by the Ethics Committee of the Pitié-Salpêtrière Hospital, Paris. 3. Standardized psychological stresses 3.1. Delayed auditory feedback (DAF) [3]
2. Subjects and methods Seven male alcoholic patients participated in the study. They all met DSM-VI criteria for alcohol dependence [11]. The duration of alcoholism ranged from 6 to 30 years. Reasons for noninclusion were diagnosis of primary affective disorder with secondary alcoholism [15], schizophrenia, treatment by antidepressants, or neuroleptics, severe somatic illness or no fixed address. To be considered as anhedonic all alcoholic subjects must score 13 or more on Chapman’s Social Anhedonia Scale (SAS) and 18 or more on Chapman’s Physical Anhedonia Scale (PAS) [5]. The cut-offs were chosen according to the results obtained in a French population [2]. * Corresponding author. E-mail address: [email protected] (D. Warot). © 2003 Éditions scientifiques et médicales Elsevier SAS. All rights reserved. doi:10.1016/j.eurpsy.2003.06.007
The participant was reading a standard text during 5 min into a microphone. The spoken text was recorded in a speech delayer (Zak, Sembach/Inn, Germany) and transferred back to the test subject via earphones with a delay of 180 ms. 3.2. Arithmetical mental task [9,10] The subject had to subtract 13 as quickly and accurately as possible starting at 1022. The stress procedure lasted 15 min. 4. Dependent measures Hundred millimeter-line Visual Analogue Scales (VAS) were used to record unpleasantness, agreeableness and feeling stressed, at baseline, just after and 105 min after the stress procedure. Plasma concentrations of cortisol were measured by radioimmunologic assay.
416
D. Marra et al. / European Psychiatry 18 (2003) 415–417
5. Study design The patients were tested at the end of the second week of abstinence. They had to be free of psychotropic drugs for at least 48 h administered for the withdrawal program. Blood samples (10 ml) were obtained at baseline, and 15, 30, 40, 50, 60, 75, 90 and 120 min after the stress procedure. 6. Statistical analysis Pairwise comparisons were performed by the Mann– Whitney test. Repeated measures ANOVA with factors group and time was used to test overall between- and within-subject effects. 7. Results The mean (±S.D.) age of the anhedonic alcoholics and controls was similar (43 ± 7.8 vs. 42 ± 6.8 years). Anhedonic alcoholics scored higher on both Physical (20.3 ± 3.3 vs. 10 ± 4.7, P < 0.001) and Social Anhedonia Scales (20 ± 7.1 vs. 9.7 ± 4, P < 0.001) than controls. Anhedonic alcoholics had significantly higher baseline plasma cortisol concentration than controls (12.6 ± 3.4 vs. 8.1 ± 2.8 µg/dl, P < 0.02). Baseline plasma cortisol significantly correlated with Physical Anhedonia Scale score (r = 0.58, P = 0.03). Change from baseline to peak plasma cortisol following psychological stress was significantly higher in controls than in anhedonic alcoholics (2.8 ± 4.3 vs. –0.4 ± 3, P = 0.04). The evolution of plasma cortisol concentration in controls indicates an increase following the psychological stress (Fig. 1). In anhedonic alcoholics, mean plasma cortisol concentration shows only a downward trend and no stress induced plasma cortisol increase. A two-way
Fig. 2. Visual Analog Scales (VAS) before (T0), just after (T15) psychological stress exposure and at 120 min after the beginning of psychological stress exposure in anhedonic alcoholics (filled squares) and healthy controls (open squares). Data are means ± S.D.
ANOVA showed no group effect (F1,12 = 1.74, P = 0.212), a significant time effect (F9,108 = 8.65, P < 0.001) and a significant time by group interaction (F9,108 = 2.3, P = 0.02). For the both VAS “stressed” and “unpleasant”, only a significant effect of the psychological stress (F2,24 = 13, P = 0.002 and F2,24 = 5.921, P = 0.014) was shown. For the VAS “agreeable”, a significant group effect (F1,12 = 11.6, P = 0.005) stress effect (F2,24 = 7.95, P = 0.002) were observed with no significant group by stress interaction (Fig. 2).
8. Discussion
Fig. 1. Mean (±S.D.) plasma cortisol concentration before, during and after psychological stress in anhedonic alcoholics (filled squares) and healthy controls (open squares).
In this study, anhedonic alcoholic men had significantly higher baseline plasma cortisol concentration, showed no increase in plasma cortisol in response to psychological stress when compared to age-matched nonalcoholic nonan-
D. Marra et al. / European Psychiatry 18 (2003) 415–417
hedonic subjects. Anhedonic alcoholics rated less agreeable than controls the experimental paradigm, which was equally stressful for both groups. Overall, anhedonic alcoholics could be characterized by blunted plasma cortisol response and attenuated subjective responses to psychological stress. The mean plasma cortisol baseline of alcoholics and controls is similar to those found in other studies of alcoholics and controls [6,7,12]. The increased cortisol level observed in anhedonic alcoholics can reflect an activation of the HPA axis associated with ethanol withdrawal [1,7,8]. Lack of augmentation of plasma cortisol in response to psychological stress was observed in alcoholics abstinent from alcohol up to 4 weeks [4,6]. The subjective sensation of stress perceived by the subjects was statistically similar in the two groups, however, visual inspection of data (Fig. 2) may suggest that even 2 h after stress exposure, anhedonic alcoholics remain stressed while controls returned to the pre-stress level. Anhedonic alcoholics’ scoring on VAS “agreeable” was flat while controls’ response can be considered as normal. This “emotional flatness” which is a characteristic feature of anhedonia, parallels with the observed lack of increase in plasma cortisol. This study has several limitations. The number of the subjects is small, a third group composed of nonanhedonic alcoholic with short term abstinence could have been included.
Acknowledgements We are indebted to S. Guillemant for the plasma cortisol determinations. This study was supported by the Assistance Publique-Hôpitaux de Paris.
References [1]
Adinoff B, Risher-Flowers D, De Jong J, Ravitz B, Bone GHA, Nutt DJ, et al. Disturbances of hypothalamic-pituitary-adrenal axis functioning during ethanol withdrawal in six men. Am J Psychiatry 1991;148:1023–5.
[2]
[3]
[4]
[5]
417
Assouly-Besse F, Dollfus S, Petit M. Traduction française des questionnaires d’anhédonie sociale et physique de Chapman: validation de la traduction française à partir de témoins et de patients schizophrènes. Encephale 1995;XXI:273–84. Badian M, Appel E, Palm D, Rupp W, Sittig W, Tauber K. Standardized mental stress in healthy volunteers induced by delayed auditory feedback (DAF). Eur J Clin Pharmacol 1979;16:171–6. Bernardy NC, King AC, Parsons OA, Lovallo WR. Altered cortisol response in sober alcoholics: an examination of contributing factors. Alcohol 1996;13:493–8. Chapman LJ, Chapman JP, Raulin MI. Scales for physical and social anhedonia. J Abnormal Psychol 1976;85:374–82.
[6]
Ehrenreich H, Schuck J, Stender N, Pilz J, Gefeller O, Schilling L, et al. Endocrine and hemodynamic effects of stress versus systemic CRF in alcoholics during early and medium term abstinence. Alcohol Clin Exp Res 1997;21:1285–93.
[7]
Fonzi S, Solinas GP, Costelli P, Parodi C, Murialdo G, Bo P, et al. Melatonin and cortisol circadian secretion during ethanol withdrawal in chronic alcoholics. Chronobiologia 1994;21:109–12.
[8]
Iranmanesh A, Veldhuis JD, Johnson ML, Lizzaralde G. 24-hour pulsatile and circadian patterns of cortisol secretion in alcoholic men. J Androl 1989;10:54–63.
[9]
Kirschbaum C, Wüst S, Faig HG, Hellhammer DH. Heritability of cortisol responses to human corticotrophin-releasing hormone, ergometry, and psychological stress in humans. J Clin Endocrinol Metab 1992;75:1526–30.
[10] Kirschbaum C, Strasburger CJ, Langkrär J. Attenuated cortisol response to psychological stress but not to CRF or ergometry in young habitual smokers. Pharmacol Biochem Behav 1993;44:527–31. [11] Lecrubier Y, Sheehan DV, Weiller E, Amorim P, Bonora I, Sheehan KH, et al. The Mini International Neuropsychiatric Interview (MINI). A short diagnosis structured interview: reliability and validity according to the CIDI. Euro Psychiatry 1997;12:224–31. [12] Marchesi C, Chiodera P, Ampollini P, Volpi R, Coiri V. Betaendorphin, adrenocorticotropic hormone and cortisol secretion in abstinent alcoholics. Psychiatry Res 1997;72:187–94. [13] Marin RS. Differential diagnosis and classification of apathy. Am J Psychiatry 1990;147:22–30. [14] Marra D, Warot D, Payan C, Hispard E, Dally AJ, Puech AJ. Anhedonia and relapse in alcoholism. Psychiatry Res 1998;80:187–96. [15] Schuckit MA, Hesselbrock V. Alcohol dependence and anxiety disorders: what is the relationship? Am J Psychiatry 1994;151:1723– 34. [16] Quay HC. Psychopathic personality as pathological stimulation seeking. Am J Psychiatry 1965;122:180–3.