- Email: [email protected]
Serum prolactin and smoking status in chronic antipsychotic-treated male patients with schizophrenia
Psychiatry Research 209 (2013) 239–241
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Serum prolactin and smoking status in chronic antipsychotic-treated male patients with schizophrenia Xiaobin Zhang a,n, Ru Bu a, Weiwei Sha a, Xin Wang a,b, Jinwen Liu a, Xin Chu a, Jijiang Li a, Hui Dong a, Yaping Liu a, Jie Qing a a b
Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China Department of Tradition Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210009, PR China
art ic l e i nf o
a b s t r a c t
Article history: Received 26 August 2012 Received in revised form 12 March 2013 Accepted 25 April 2013
We investigated the effects of smoking status on the serum prolactin levels in schizophrenia. The serum prolactin concentration was significantly higher in nonsmokers compared with smokers. Moreover, smoking was an independent predictor of prolactin concentration. These findings suggest that smoking has an impact on prolactin concentration in male schizophrenic patients. & 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Prolactin Smoking status Schizophrenia
1. Introduction There has been a longstanding awareness that hyperprolactinemia is a common consequence of antipsychotic treatment, although the potential long-term sequelae of chronically elevated prolactin have only recently been fully recognized (Bushe et al., 2008a). Smoking is more prevalent in schizophrenic patients than in the general population (Sagud et al., 2009). Several studies have demonstrated that cigarette smoking status influences the hormonal regulation of prolactin, but the relationship between cigarette smoking and prolactin secretion seems to be complex, and there appear to be important interspecies differences (Xue et al., 2010). Some studies have suggested that cigarette smoking increases prolactin secretion (Kirschbaum et al., 1994; Mendelson et al., 2003), while others have reported lower prolactin levels in smokers (Trummer et al., 2002; Corona et al., 2005; Glintborg et al., 2012). Moreover, two recent studies reported that current smoking status is a significant predictor of lower prolactin levels and the plasma concentrations of prolactin negatively correlate with smoking status in schizophrenic patients (Mackin et al., 2011 and Ohta et al., 2011). Based on these findings, we hypothesized that smoking status would contribute to the variability in blood prolactin concentrations induced by antipsychotics. Therefore, in this study, we
examined the effect of smoking status on the elevation of plasma prolactin concentrations induced by antipsychotic treatment of chronic schizophrenia inpatients.
2. Methods 2.1. Subject recruitment Recruited male subjects with schizophrenia were all chronic inpatients in the Department of Psychiatry of Yang Zhou Wu Tai Shan Hospital in China. Nonsmokers were defined as subjects who had never smoked before. Smokers were defined as subjects who reported regular smoking of two or more cigarettes a day for at least 2 years. A total of 154 patients (83 smokers and 71 nonsmokers) met the criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (American Psychiatric Association, 2000). The average number of cigarettes per day in the smokers was 8.86 7 5.7. All patients had complete medical records from first admission. Clinical and demographic information was obtained from medical records and interview with patients. All patients had been treated with antipsychotic drugs for longer than 1 year (mean 15.317 9.93 years; range 1–45 years). The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale (PANSS). Fifty healthy males were studied as control subjects, age-matched to the schizophrenia group. The inclusion criteria for control subjects were that they had never smoked, were in good physical health and had no history of mental disorders, neurological disease or drug abuse. The study was approved by the local Institutional Ethics Committee. Written informed consent was obtained after a full written and verbal explanation of the study.
n
Corresponding author. Tel.: +86 51487207382. E-mail addresses: [email protected] (X. Zhang), [email protected] (R. Bu), [email protected] (W. Sha), [email protected] (X. Wang), [email protected] (J. Liu), [email protected] (X. Chu), [email protected] (J. Li), [email protected] (H. Dong), [email protected] (Y. Liu), [email protected] (J. Qing). 0165-1781/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2013.04.026
2.2. Prolactin assay Following an overnight fast, serum samples from the patients and healthy controls were collected between 8:00 and 9:00 a.m and stored at −80 1C until used for assay. Prolactin concentration was analysed in the local hospital biochemistry
240
X. Zhang et al. / Psychiatry Research 209 (2013) 239–241
laboratories using an Access immunoassay analyser and manufacturer's reagents (Beckman-Coulter Inc., USA). The lowest limit of detection was 0.25 ng/ml, and the intra- and inter-assay coefficients of variation were o4% and o 5%, respectively.
2.3. Statistical analysis For statistical analysis, the data were expressed as the means 7 S.D. and were analyzed with the statistical analysis software, SPSS, version 10.0 (SPSS, Inc., Chicago, IL, USA). Chi-squared analysis was performed on categorical data, such as family history, and study groups were compared for continuous variables by two-tailed t-test and analysis of variance (ANOVA). The relationship between serum prolactin levels and clinical variables was examined using Pearson's correlation coefficient. Stepwise linear regression was used to identify independent predictors of prolactin concentration after controlling for potentially confounding variables. Because prolactin was not normally distributed, we examined logtransformed prolactin in the analyses. Statistical significance is indicated by P values less than 0.05.
correlation between serum prolactin concentration (r ¼−0.18, Po 0.1), current daily antipsychotic dose in chlorpromazine equivalents (r ¼0.03, Po 0.8), severity of psychotic symptoms (total PANSS scores) (r ¼−0.19, P o0.1) and the average number of cigarettes per day in smokers. After adjusting for age, BMI, duration of illness, length of antipsychotic treatment, current daily antipsychotic dose in chlorpromazine equivalents and severity of psychotic symptoms (total PANSS scores), linear regression revealed that being a smoker was an independent predictor of lower serum prolactin concentrations (β¼−0.213, t ¼−2.690, P ¼0.008). This was also true in those patients not receiving clozapine monotherapy, in whom smoking was related to lower serum prolactin (25.7 719.8 ng/ml and 35.6 724.8 ng/ml, respectively, P o0.05).
4. Discussion 3. Results The demographic and clinical characteristics of schizophrenic patients and controls are summarized in Table 1. All clinical features between the smokers and nonsmokers were well matched. There were no significant differences in terms of age, body-mass index (BMI), age of illness onset, duration of illness, length of antipsychotic treatment, current daily antipsychotic dose in chlorpromazine equivalents, severity of psychotic symptoms (total PANSS scores) and family history of mental disorders between the two groups. Compared with the healthy controls, schizophrenic patients (smokers and nonsmokers) had significantly higher prolactin levels (27.27 722.45 ng/ml vs. 10.12 7 4.29 ng/ml, P o0.001). The serum prolactin levels were lower in healthy controls as compared with the smokers and nonsmokers groups (22.85 718.56 ng/ml and 32.43725.46 ng/ml, respectively, P o0.001 for both smokers and nonsmokers vs. controls). The serum prolactin concentration was significantly higher in nonsmokers compared with smokers (P ¼0.008). No significant correlation was found between serum prolactin concentration and age in smokers and nonsmokers (r ¼ 0.01, P ¼0.9 and r ¼0.05, P o0.7), in the total schizophrenic group (r ¼0.05, P o0.6) and controls (r ¼0.03, Po 0.8). Moreover, neither BMI (r ¼0.09, Po 0.4 and r¼ 0.17, Po0.2) nor duration of illness (r ¼ −0.12, P o0.3 and r ¼0.13, P o0.3) correlated significantly with serum prolactin in smokers and nonsmokers. No significant correlation was observed between length of antipsychotic treatment (r ¼0.13, P o0.2 and r ¼ −0.16, P o0.2), current daily antipsychotic dose in chlorpromazine equivalents (r ¼ −0.07, P o0.5 and r¼ −0.19, P o0.1), severity of psychotic symptoms (total PANSS scores) (r ¼0.09, P o0.4 and r ¼0.20, P o0.1) and serum prolactin levels in smokers and nonsmokers. There was no significant
We found a robust statistical association between cigarette smoking and serum prolactin concentration in the chronically hospitalized male patients with schizophrenia who had received continuous antipsychotic drug treatment for periods of at least 1 year. Moreover, after investigation of potential confounding variables, only smoking status was associated with prolactin concentration. The regulation of prolactin secretion by the pituitary gland is complex, and clinical studies investigating the relationship between cigarette smoking and prolactin secretion in populations without mental illness have yielded inconsistent results (Trummer et al., 2002; Mendelson et al., 2003; Corona et al., 2005; Xue et al., 2010; Glintborg et al., 2012; Blanco-Muñoz et al., 2012). This may be due, at least in part, to the different populations studied, and differing acute and chronic effects of cigarette smoking on prolactin secretion. The present results are consistent with the findings of a recent study in which both current and ex-cigarette smokers in community antipsychotic-treated patients from across the diagnostic spectrum had significantly lower mean prolactin levels (Mackin et al., 2011). Further, Ohta et al. (2011) reported that the plasma concentration of prolactin positively correlated with gender and negatively correlated with age and smoking status in schizophrenic patients during risperidone treatment. Our study involved a range of different antipsychotic drug treatments, which may be associated with different effects on prolactin secretion. It is conceivable that this is also associated with differences in smoking behavior, which could confound the findings. Notable is that a proportion of the patients received clozapine monotherapy; this generally has relatively small effects on blood prolactin concentrations. However, after removing this group, the remaining patients on prolactin-raising drugs also demonstrated a strong negative association between serum prolactin and smoking.
Table 1 Characteristics of schizophrenic patients and healthy controls (mean 7 SD). Control group (n ¼50)
Age (years) Body-mass index (kg/m2) Age of illness onset (years) Duration of illness (years) Length of antipsychotic treatment (years) Current antipsychotic dose/day (mg chlorpromazine equivalents) Family history of mental disorders Severity of psychotic symptoms: PANSS total Serum prolactin levels (ng/ml)
50.22 7 9.45 – – – – – – – 10.137 4.29
Schizophrenic patients Smokers (n ¼83)
Nonsmokers (n ¼71)
51.63 7 10.42 24.987 3.21 27.65 7 7.60 23.96 7 13.06 14.23 7 8.56 408.59 7 194.00 Y/N: 16/65 60.43 7 19.62 22.85 7 18.56
53.117 9.64 24.107 3.07 28.45 77.71 24.5812.18 16.56 7 11.25 469.707 212.08 Y/N: 14/57 64.89 7 21.21 32.43 725.46
Abbreviations: PANSS, Positive and Negative Syndrome Scale; SD, standard deviations. a
P
One-way ANOVA test with Tukey post-test, serum prolactin levels (ng/ml) in nonsmokers 4 smokers 4 controls.
0.283 0.084 0.519 0.765 0.146 0.07 0.764 0.178 0.0001a
X. Zhang et al. / Psychiatry Research 209 (2013) 239–241
Some further limitations should be taken into consideration. First, the patient sample size was small and it would therefore be unwise to generalize from these results. Another limitation was that our patients are all male in the study. Although it has been reported that the difference in mean prolactin level between males and females who received antipsychotic treatment was not statistically significant (Mackin et al., 2011), some researchers have found gender differences in prolactin levels before or after antipsychotic treatment (Sawamura et al., 2006; Garcia-Rizo et al., 2012). The impact of smoking cessation on prolactin levels in antipsychotic-treated patients is unknown and also requires further investigation. Future studies will need to confirm the association between smoking status and higher prolactin concentration-related adverse effects. Although many studies found prolactin levels are increased in antipsychotic-treated patients, smoking data are rarely reported and not considered when measuring prolactin levels (Bushe et al., 2008b). In conclusion, smoking was associated with lower prolactin levels in the schizophrenic patients. Future studies should explore the mechanism by which tobacco smoking modulates prolactin secretion in patients treated with antipsychotic drugs. Acknowledgments This study was partially supported by Jiangsu Province Natural Science Foundation (BK2011434) and Yangzhou Municipal key technology problems Foundation (YZ2010089). These funding sources had no further role in study design, data collection, analysis and manuscript writing. We thank the patients in Yangzhou Wu Tai Shan Hospital and healthy volunteers for their support and participation. References American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders IV-TR. APA, Washington, DC. Blanco-Muñoz, J., Lacasaña, M., Aguilar-Garduño, C., 2012. Effect of current tobacco consumption on the male reproductive hormone profile. Science of the Total Environment 426, 100–105.
241
Bushe, C., Shaw, M., Peveler, R.C., 2008a. A review of the association between antipsychotic use and hyperprolactinaemia. Journal of Psychopharmacology 22, 46–55. Bushe, C., Yeomans, D., Floyd, T., Smith, S.M., 2008b. Categorical prevalence and severity of hyperprolactinaemia in two UK cohorts of patients with severe mental illness during treatment with antipsychotics. Journal of Psychopharmacology 22, 56–62. Corona, G., Mannucci, E., Petrone, L., Ricca, V., Mansani, R., Cilotti, A., Balercia, G., Chiarini, V., Giommi, R., Forti, G., Maggi, M., 2005. Psychobiological correlates of smoking in patients with erectile dysfunction. International Journal of Impotence Research 17, 527–534. Garcia-Rizo, C., Fernandez-Egea, E., Oliveira, C., Justicia, A., Parellada, E., Bernardo, M., Kirkpatrick, B., 2012. Prolactin concentrations in newly diagnosed, antipsychotic-naïve patients with nonaffective psychosis. Schizophrenia Research 134, 16–19. Glintborg, D., Mumm, H., Hougaard, D.M., Ravn, P., Andersen, M., 2012. Smoking is associated with increased adrenal responsiveness, decreased prolactin levels and a more adverse lipid profile in 650 white patients with polycystic ovary syndrome. Gynecological Endocrinology 28, 170–174. Kirschbaum, C., Scherer, G., Strasburger, C.J., 1994. Pituitary and adrenal hormone responses to pharmacological, physical, and psychological stimulation in habitual smokers and nonsmokers. The Clinical Investigator 72, 804–810. Mackin, P., Waton, A., Nulkar, A., Watkinson, H.M., 2011. Prolactin and smoking status in antipsychotic-treated patients. Journal of Psychopharmacology 25, 698–703. Mendelson, J.H., Sholar, M.B., Mutschler, N.H., Jaszyna-Gasior, M., Goletiani, N.V., Siegel, A.J., Aello, N.K., 2003. Effects of intravenous cocaine and cigarette smoking on luteinizing hormone, testosterone, and prolactin in men. The Journal of Pharmacology and Experimental Therapeutics 307, 339–348. Ohta, C., Yasui-Furukori, N., Furukori, H., Tsuchimine, S., Saito, M., Nakagami, T., Yoshizawa, K., Kaneko, S., 2011. The effect of smoking status on the plasma concentration of prolactin already elevated by risperidone treatment in schizophrenia patients. Progress in Neuropsychopharmacology and Biological Psychiatry 35, 573–576. Sagud, M., Mihaljević-Peles, A., Mück-Seler, D., Pivac, N., Vuksan-Cusa, B., Brataljenović, T., Jakovljević, M., 2009. Smoking and schizophrenia. Psychiatria Danubina 21, 371–375. Sawamura, K., Suzuki, Y., Fukui, N., Sugai, T., Someya, T., 2006. Gender differences in prolactin elevation induced by olanzapine in Japanese drug-naïve schizophrenic patients. Progress in Neuropsychopharmacology and Biological Psychiatry 30, 1511–1514. Trummer, H., Habermann, H., Haas, J., Pummer, K., 2002. The impact of cigarette smoking on human semen parameters and hormones. Human Reproduction 17, 1554–1559. Xue, Y., Morris, M., Ni, L., Guthrie, S.K., Zubieta, J.K., Gonzalez, K., McConneII, D.S., Domino, E.F., 2010. Venous plasma nicotine correlates of hormonal effects of tobacco smoking. Pharmacology, Biochemistry and Behavior 95, 209–215.
Contents lists available at ScienceDirect
Psychiatry Research journal homepage: www.elsevier.com/locate/psychres
Brief report
Serum prolactin and smoking status in chronic antipsychotic-treated male patients with schizophrenia Xiaobin Zhang a,n, Ru Bu a, Weiwei Sha a, Xin Wang a,b, Jinwen Liu a, Xin Chu a, Jijiang Li a, Hui Dong a, Yaping Liu a, Jie Qing a a b
Department of Psychiatry, Affiliated WuTaiShan Hospital of Medical College of Yangzhou University, Yangzhou 225003, PR China Department of Tradition Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210009, PR China
art ic l e i nf o
a b s t r a c t
Article history: Received 26 August 2012 Received in revised form 12 March 2013 Accepted 25 April 2013
We investigated the effects of smoking status on the serum prolactin levels in schizophrenia. The serum prolactin concentration was significantly higher in nonsmokers compared with smokers. Moreover, smoking was an independent predictor of prolactin concentration. These findings suggest that smoking has an impact on prolactin concentration in male schizophrenic patients. & 2013 Elsevier Ireland Ltd. All rights reserved.
Keywords: Prolactin Smoking status Schizophrenia
1. Introduction There has been a longstanding awareness that hyperprolactinemia is a common consequence of antipsychotic treatment, although the potential long-term sequelae of chronically elevated prolactin have only recently been fully recognized (Bushe et al., 2008a). Smoking is more prevalent in schizophrenic patients than in the general population (Sagud et al., 2009). Several studies have demonstrated that cigarette smoking status influences the hormonal regulation of prolactin, but the relationship between cigarette smoking and prolactin secretion seems to be complex, and there appear to be important interspecies differences (Xue et al., 2010). Some studies have suggested that cigarette smoking increases prolactin secretion (Kirschbaum et al., 1994; Mendelson et al., 2003), while others have reported lower prolactin levels in smokers (Trummer et al., 2002; Corona et al., 2005; Glintborg et al., 2012). Moreover, two recent studies reported that current smoking status is a significant predictor of lower prolactin levels and the plasma concentrations of prolactin negatively correlate with smoking status in schizophrenic patients (Mackin et al., 2011 and Ohta et al., 2011). Based on these findings, we hypothesized that smoking status would contribute to the variability in blood prolactin concentrations induced by antipsychotics. Therefore, in this study, we
examined the effect of smoking status on the elevation of plasma prolactin concentrations induced by antipsychotic treatment of chronic schizophrenia inpatients.
2. Methods 2.1. Subject recruitment Recruited male subjects with schizophrenia were all chronic inpatients in the Department of Psychiatry of Yang Zhou Wu Tai Shan Hospital in China. Nonsmokers were defined as subjects who had never smoked before. Smokers were defined as subjects who reported regular smoking of two or more cigarettes a day for at least 2 years. A total of 154 patients (83 smokers and 71 nonsmokers) met the criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (American Psychiatric Association, 2000). The average number of cigarettes per day in the smokers was 8.86 7 5.7. All patients had complete medical records from first admission. Clinical and demographic information was obtained from medical records and interview with patients. All patients had been treated with antipsychotic drugs for longer than 1 year (mean 15.317 9.93 years; range 1–45 years). The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale (PANSS). Fifty healthy males were studied as control subjects, age-matched to the schizophrenia group. The inclusion criteria for control subjects were that they had never smoked, were in good physical health and had no history of mental disorders, neurological disease or drug abuse. The study was approved by the local Institutional Ethics Committee. Written informed consent was obtained after a full written and verbal explanation of the study.
n
Corresponding author. Tel.: +86 51487207382. E-mail addresses: [email protected] (X. Zhang), [email protected] (R. Bu), [email protected] (W. Sha), [email protected] (X. Wang), [email protected] (J. Liu), [email protected] (X. Chu), [email protected] (J. Li), [email protected] (H. Dong), [email protected] (Y. Liu), [email protected] (J. Qing). 0165-1781/$ - see front matter & 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.psychres.2013.04.026
2.2. Prolactin assay Following an overnight fast, serum samples from the patients and healthy controls were collected between 8:00 and 9:00 a.m and stored at −80 1C until used for assay. Prolactin concentration was analysed in the local hospital biochemistry
240
X. Zhang et al. / Psychiatry Research 209 (2013) 239–241
laboratories using an Access immunoassay analyser and manufacturer's reagents (Beckman-Coulter Inc., USA). The lowest limit of detection was 0.25 ng/ml, and the intra- and inter-assay coefficients of variation were o4% and o 5%, respectively.
2.3. Statistical analysis For statistical analysis, the data were expressed as the means 7 S.D. and were analyzed with the statistical analysis software, SPSS, version 10.0 (SPSS, Inc., Chicago, IL, USA). Chi-squared analysis was performed on categorical data, such as family history, and study groups were compared for continuous variables by two-tailed t-test and analysis of variance (ANOVA). The relationship between serum prolactin levels and clinical variables was examined using Pearson's correlation coefficient. Stepwise linear regression was used to identify independent predictors of prolactin concentration after controlling for potentially confounding variables. Because prolactin was not normally distributed, we examined logtransformed prolactin in the analyses. Statistical significance is indicated by P values less than 0.05.
correlation between serum prolactin concentration (r ¼−0.18, Po 0.1), current daily antipsychotic dose in chlorpromazine equivalents (r ¼0.03, Po 0.8), severity of psychotic symptoms (total PANSS scores) (r ¼−0.19, P o0.1) and the average number of cigarettes per day in smokers. After adjusting for age, BMI, duration of illness, length of antipsychotic treatment, current daily antipsychotic dose in chlorpromazine equivalents and severity of psychotic symptoms (total PANSS scores), linear regression revealed that being a smoker was an independent predictor of lower serum prolactin concentrations (β¼−0.213, t ¼−2.690, P ¼0.008). This was also true in those patients not receiving clozapine monotherapy, in whom smoking was related to lower serum prolactin (25.7 719.8 ng/ml and 35.6 724.8 ng/ml, respectively, P o0.05).
4. Discussion 3. Results The demographic and clinical characteristics of schizophrenic patients and controls are summarized in Table 1. All clinical features between the smokers and nonsmokers were well matched. There were no significant differences in terms of age, body-mass index (BMI), age of illness onset, duration of illness, length of antipsychotic treatment, current daily antipsychotic dose in chlorpromazine equivalents, severity of psychotic symptoms (total PANSS scores) and family history of mental disorders between the two groups. Compared with the healthy controls, schizophrenic patients (smokers and nonsmokers) had significantly higher prolactin levels (27.27 722.45 ng/ml vs. 10.12 7 4.29 ng/ml, P o0.001). The serum prolactin levels were lower in healthy controls as compared with the smokers and nonsmokers groups (22.85 718.56 ng/ml and 32.43725.46 ng/ml, respectively, P o0.001 for both smokers and nonsmokers vs. controls). The serum prolactin concentration was significantly higher in nonsmokers compared with smokers (P ¼0.008). No significant correlation was found between serum prolactin concentration and age in smokers and nonsmokers (r ¼ 0.01, P ¼0.9 and r ¼0.05, P o0.7), in the total schizophrenic group (r ¼0.05, P o0.6) and controls (r ¼0.03, Po 0.8). Moreover, neither BMI (r ¼0.09, Po 0.4 and r¼ 0.17, Po0.2) nor duration of illness (r ¼ −0.12, P o0.3 and r ¼0.13, P o0.3) correlated significantly with serum prolactin in smokers and nonsmokers. No significant correlation was observed between length of antipsychotic treatment (r ¼0.13, P o0.2 and r ¼ −0.16, P o0.2), current daily antipsychotic dose in chlorpromazine equivalents (r ¼ −0.07, P o0.5 and r¼ −0.19, P o0.1), severity of psychotic symptoms (total PANSS scores) (r ¼0.09, P o0.4 and r ¼0.20, P o0.1) and serum prolactin levels in smokers and nonsmokers. There was no significant
We found a robust statistical association between cigarette smoking and serum prolactin concentration in the chronically hospitalized male patients with schizophrenia who had received continuous antipsychotic drug treatment for periods of at least 1 year. Moreover, after investigation of potential confounding variables, only smoking status was associated with prolactin concentration. The regulation of prolactin secretion by the pituitary gland is complex, and clinical studies investigating the relationship between cigarette smoking and prolactin secretion in populations without mental illness have yielded inconsistent results (Trummer et al., 2002; Mendelson et al., 2003; Corona et al., 2005; Xue et al., 2010; Glintborg et al., 2012; Blanco-Muñoz et al., 2012). This may be due, at least in part, to the different populations studied, and differing acute and chronic effects of cigarette smoking on prolactin secretion. The present results are consistent with the findings of a recent study in which both current and ex-cigarette smokers in community antipsychotic-treated patients from across the diagnostic spectrum had significantly lower mean prolactin levels (Mackin et al., 2011). Further, Ohta et al. (2011) reported that the plasma concentration of prolactin positively correlated with gender and negatively correlated with age and smoking status in schizophrenic patients during risperidone treatment. Our study involved a range of different antipsychotic drug treatments, which may be associated with different effects on prolactin secretion. It is conceivable that this is also associated with differences in smoking behavior, which could confound the findings. Notable is that a proportion of the patients received clozapine monotherapy; this generally has relatively small effects on blood prolactin concentrations. However, after removing this group, the remaining patients on prolactin-raising drugs also demonstrated a strong negative association between serum prolactin and smoking.
Table 1 Characteristics of schizophrenic patients and healthy controls (mean 7 SD). Control group (n ¼50)
Age (years) Body-mass index (kg/m2) Age of illness onset (years) Duration of illness (years) Length of antipsychotic treatment (years) Current antipsychotic dose/day (mg chlorpromazine equivalents) Family history of mental disorders Severity of psychotic symptoms: PANSS total Serum prolactin levels (ng/ml)
50.22 7 9.45 – – – – – – – 10.137 4.29
Schizophrenic patients Smokers (n ¼83)
Nonsmokers (n ¼71)
51.63 7 10.42 24.987 3.21 27.65 7 7.60 23.96 7 13.06 14.23 7 8.56 408.59 7 194.00 Y/N: 16/65 60.43 7 19.62 22.85 7 18.56
53.117 9.64 24.107 3.07 28.45 77.71 24.5812.18 16.56 7 11.25 469.707 212.08 Y/N: 14/57 64.89 7 21.21 32.43 725.46
Abbreviations: PANSS, Positive and Negative Syndrome Scale; SD, standard deviations. a
P
One-way ANOVA test with Tukey post-test, serum prolactin levels (ng/ml) in nonsmokers 4 smokers 4 controls.
0.283 0.084 0.519 0.765 0.146 0.07 0.764 0.178 0.0001a
X. Zhang et al. / Psychiatry Research 209 (2013) 239–241
Some further limitations should be taken into consideration. First, the patient sample size was small and it would therefore be unwise to generalize from these results. Another limitation was that our patients are all male in the study. Although it has been reported that the difference in mean prolactin level between males and females who received antipsychotic treatment was not statistically significant (Mackin et al., 2011), some researchers have found gender differences in prolactin levels before or after antipsychotic treatment (Sawamura et al., 2006; Garcia-Rizo et al., 2012). The impact of smoking cessation on prolactin levels in antipsychotic-treated patients is unknown and also requires further investigation. Future studies will need to confirm the association between smoking status and higher prolactin concentration-related adverse effects. Although many studies found prolactin levels are increased in antipsychotic-treated patients, smoking data are rarely reported and not considered when measuring prolactin levels (Bushe et al., 2008b). In conclusion, smoking was associated with lower prolactin levels in the schizophrenic patients. Future studies should explore the mechanism by which tobacco smoking modulates prolactin secretion in patients treated with antipsychotic drugs. Acknowledgments This study was partially supported by Jiangsu Province Natural Science Foundation (BK2011434) and Yangzhou Municipal key technology problems Foundation (YZ2010089). These funding sources had no further role in study design, data collection, analysis and manuscript writing. We thank the patients in Yangzhou Wu Tai Shan Hospital and healthy volunteers for their support and participation. References American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders IV-TR. APA, Washington, DC. Blanco-Muñoz, J., Lacasaña, M., Aguilar-Garduño, C., 2012. Effect of current tobacco consumption on the male reproductive hormone profile. Science of the Total Environment 426, 100–105.
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