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Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy: Response to a biochemical evaluation
Epilepsy & Behavior 41 (2014) 312–313
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Letter to the Editor Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy: Response to a biochemical evaluation
To the Editor We appreciate the interest of Agilli and colleagues in their Letter to the Editor regarding our recent article entitled “Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy — A pilot cross-sectional fMRI study” [1]. We agree with them that there are many important factors that need to be considered when interpreting our results including the presence of chronic medical conditions (e.g., autoimmune disease), medication use, and nicotine use. However, these and many other factors are inherent to human subject research, and while investigators do their best to account for many of these potential confounders, it is virtually impossible to do so for all of them. With these considerations, we will discuss the concerns put forth by the authors of the letter. One concern put forward by Agilli et al. in their letter was regarding the possible presence of chronic medical conditions and their putative effect on cortisol response in our subjects. This issue was already addressed in the paper, as described in the Methods section where we have indicated that all subjects were physically healthy with no premorbid history of neurological (other than epilepsy) or psychiatric illness (with the exception of depression). Thus, although not explicitly stated, persons with autoimmune and chronic inflammatory disorders were excluded from study participation based on these criteria. Further, the authors of the letter were also concerned with drugs that could potentially affect salivary cortisol levels (e.g., psychiatric drugs). We did not expect the use of psychiatric medications other than antidepressants in our sample, given that persons with psychiatric illness other than depression were excluded, and as stated in the Discussion section of our paper, no subjects reported a diagnosis of depression. We did record the number of antiepileptic drugs (AEDs) currently being taken by patients with left temporal lobe epilepsy (LTLE), which was not significantly different between patients with well-controlled epilepsy and those without well-controlled epilepsy. However, because of the small sample size and preliminary nature of the study, we were not able to covary the number of AEDs in our analyses. Further, we did not collect information on the numerous other drugs that may potentially have an effect on salivary cortisol and were listed in the Granger et al. study referenced by the authors of the letter [2], but all our subjects were generally healthy outside of epilepsy; thus, the expectation was that they were not taking medications other than AEDs and, possibly, antidepressants. We agree with Granger et al. that the issue surrounding medication effects on salivary cortisol is extremely complex, as evidenced in their own study in which they did not account for the directional effects (i.e., potentially lowering or increasing levels) of individual medications on salivary cortisol or for possible interactive effects of multiple medications [2].
http://dx.doi.org/10.1016/j.yebeh.2014.08.018 1525-5050/© 2014 Elsevier Inc. All rights reserved.
The issues surrounding the influence of nicotine use and smoking status on salivary cortisol are just as complicated as the medication effects. While we are aware of the possible effects of nicotine and smoking on cortisol levels, there can be ambiguity in the data presented in the literature since it is difficult to account for all factors. For example, the Badrick et al. [3] and Kumari et al. [4] studies cited by the authors of the letter reported increased levels of diurnal salivary cortisol in active smokers. However, in these and similar other studies where participants were instructed to not brush their teeth or eat/drink anything for 15 min prior to saliva collection but were not instructed to avoid nicotine use, there remains the potential for acute nicotine effects [3,4]. Having the abovementioned data in mind, we do not feel that acute nicotine effects are particularly relevant to our study results because the collection of our saliva samples was separated in all subjects who smoked for at least 1 h prior to their last nicotine use (first saliva sample) and at least 2.5 h prior to the first poststress saliva sample; this allowed us to minimize, if not alleviate, the acute effects of nicotine on cortisol levels. Furthermore, studies referenced by Agilli and colleagues describing baseline diurnal salivary cortisol are not directly comparable with studies investigating nicotine effects on salivary cortisol response to acute stress, which report that current smokers/ nicotine users have an attenuated salivary cortisol stress response [5–7]. Since the effects of nicotine on fMRI signals may need to be considered as well, we collected data on current nicotine use in all subjects participating in our study. Analysis of these data (not reported in the initial publication) shows that the proportion of current smokers in our healthy control subjects (8/22) and in patients with LTLE (6/23) is not significantly different (p = 0.46). Given that the proportions of smokers in both groups were similar, we would not expect the effect of smoking status on salivary cortisol stress response to be different between the healthy group and the group with epilepsy. Thus, even if present, the effects of nicotine/smoking status on cortisol were expected to be comparable in both groups and not affect the final results of the study.
Conflict of interest Jane B. Allendorfer, in the last 12 months, received research funding and salary support from NIH, Charles Shor Foundation for Epilepsy Research, and the University of Alabama at Birmingham. Jerzy P. Szaflarski, in the last 12 months, received research funding (and salary support) from NIH (NINDS and NICHD), Epilepsy Foundation of America, the U.S. Food and Drug Administration (FDA), Charles Shor Foundation for Epilepsy Research, and the University of Alabama at Birmingham.
References [1] Allendorfer JB, Heyse H, Mendoza L, Nelson EB, Eliassen JC, Storrs JM, et al. Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy — a pilot cross-sectional fMRI study. Epilepsy Behav 2014;36C:115–23.
Letter to the Editor [2] Granger DA, Hibel LC, Fortunato CK, Kapelewski CH. Medication effects on salivary cortisol: tactics and strategy to minimize impact in behavioral and developmental science. Psychoneuroendocrinology 2009;34(10):1437–48. [3] Badrick E, Kirschbaum C, Kumari M. The relationship between smoking status and cortisol secretion. J Clin Endocrinol Metab 2007;92(3):819–24. [4] Kumari M, Badrick E, Chandola T, Adler NE, Epel E, Seeman T, et al. Measures of social position and cortisol secretion in an aging population: findings from the Whitehall II study. Psychosom Med 2010;72(1):27–34. [5] Childs E, de Wit H. Hormonal, cardiovascular, and subjective responses to acute stress in smokers. Psychopharmacology (Berl) 2009;203(1):1–12. [6] Roy MP, Steptoe A, Kirschbaum C. Association between smoking status and cardiovascular and cortisol stress responsivity in healthy young men. Int J Behav Med 1994; 1(3):264–83. [7] Tsuda A, Steptoe A, West R, Fieldman G, Kirschbaum C. Cigarette smoking and psychophysiological stress responsiveness: effects of recent smoking and temporary abstinence. Psychopharmacology (Berl) 1996;126(3):226–33.
Jane B. Allendorfer Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, USA
313
Corresponding author at: Department of Neurology, Division of Epilepsy, 312 Civitan International Research Center, 1719 6th Avenue South, Birmingham, AL 35294, USA. Tel.: +1 205 975 3372; fax: +1 205 975 6255. E-mail address: [email protected]. Jerzy P. Szaflarski Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, USA Department of Psychiatry, University of Cincinnati Academic Health Center, Cincinnati, OH, USA 6 August 2014
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Letter to the Editor Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy: Response to a biochemical evaluation
To the Editor We appreciate the interest of Agilli and colleagues in their Letter to the Editor regarding our recent article entitled “Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy — A pilot cross-sectional fMRI study” [1]. We agree with them that there are many important factors that need to be considered when interpreting our results including the presence of chronic medical conditions (e.g., autoimmune disease), medication use, and nicotine use. However, these and many other factors are inherent to human subject research, and while investigators do their best to account for many of these potential confounders, it is virtually impossible to do so for all of them. With these considerations, we will discuss the concerns put forth by the authors of the letter. One concern put forward by Agilli et al. in their letter was regarding the possible presence of chronic medical conditions and their putative effect on cortisol response in our subjects. This issue was already addressed in the paper, as described in the Methods section where we have indicated that all subjects were physically healthy with no premorbid history of neurological (other than epilepsy) or psychiatric illness (with the exception of depression). Thus, although not explicitly stated, persons with autoimmune and chronic inflammatory disorders were excluded from study participation based on these criteria. Further, the authors of the letter were also concerned with drugs that could potentially affect salivary cortisol levels (e.g., psychiatric drugs). We did not expect the use of psychiatric medications other than antidepressants in our sample, given that persons with psychiatric illness other than depression were excluded, and as stated in the Discussion section of our paper, no subjects reported a diagnosis of depression. We did record the number of antiepileptic drugs (AEDs) currently being taken by patients with left temporal lobe epilepsy (LTLE), which was not significantly different between patients with well-controlled epilepsy and those without well-controlled epilepsy. However, because of the small sample size and preliminary nature of the study, we were not able to covary the number of AEDs in our analyses. Further, we did not collect information on the numerous other drugs that may potentially have an effect on salivary cortisol and were listed in the Granger et al. study referenced by the authors of the letter [2], but all our subjects were generally healthy outside of epilepsy; thus, the expectation was that they were not taking medications other than AEDs and, possibly, antidepressants. We agree with Granger et al. that the issue surrounding medication effects on salivary cortisol is extremely complex, as evidenced in their own study in which they did not account for the directional effects (i.e., potentially lowering or increasing levels) of individual medications on salivary cortisol or for possible interactive effects of multiple medications [2].
http://dx.doi.org/10.1016/j.yebeh.2014.08.018 1525-5050/© 2014 Elsevier Inc. All rights reserved.
The issues surrounding the influence of nicotine use and smoking status on salivary cortisol are just as complicated as the medication effects. While we are aware of the possible effects of nicotine and smoking on cortisol levels, there can be ambiguity in the data presented in the literature since it is difficult to account for all factors. For example, the Badrick et al. [3] and Kumari et al. [4] studies cited by the authors of the letter reported increased levels of diurnal salivary cortisol in active smokers. However, in these and similar other studies where participants were instructed to not brush their teeth or eat/drink anything for 15 min prior to saliva collection but were not instructed to avoid nicotine use, there remains the potential for acute nicotine effects [3,4]. Having the abovementioned data in mind, we do not feel that acute nicotine effects are particularly relevant to our study results because the collection of our saliva samples was separated in all subjects who smoked for at least 1 h prior to their last nicotine use (first saliva sample) and at least 2.5 h prior to the first poststress saliva sample; this allowed us to minimize, if not alleviate, the acute effects of nicotine on cortisol levels. Furthermore, studies referenced by Agilli and colleagues describing baseline diurnal salivary cortisol are not directly comparable with studies investigating nicotine effects on salivary cortisol response to acute stress, which report that current smokers/ nicotine users have an attenuated salivary cortisol stress response [5–7]. Since the effects of nicotine on fMRI signals may need to be considered as well, we collected data on current nicotine use in all subjects participating in our study. Analysis of these data (not reported in the initial publication) shows that the proportion of current smokers in our healthy control subjects (8/22) and in patients with LTLE (6/23) is not significantly different (p = 0.46). Given that the proportions of smokers in both groups were similar, we would not expect the effect of smoking status on salivary cortisol stress response to be different between the healthy group and the group with epilepsy. Thus, even if present, the effects of nicotine/smoking status on cortisol were expected to be comparable in both groups and not affect the final results of the study.
Conflict of interest Jane B. Allendorfer, in the last 12 months, received research funding and salary support from NIH, Charles Shor Foundation for Epilepsy Research, and the University of Alabama at Birmingham. Jerzy P. Szaflarski, in the last 12 months, received research funding (and salary support) from NIH (NINDS and NICHD), Epilepsy Foundation of America, the U.S. Food and Drug Administration (FDA), Charles Shor Foundation for Epilepsy Research, and the University of Alabama at Birmingham.
References [1] Allendorfer JB, Heyse H, Mendoza L, Nelson EB, Eliassen JC, Storrs JM, et al. Physiologic and cortical response to acute psychosocial stress in left temporal lobe epilepsy — a pilot cross-sectional fMRI study. Epilepsy Behav 2014;36C:115–23.
Letter to the Editor [2] Granger DA, Hibel LC, Fortunato CK, Kapelewski CH. Medication effects on salivary cortisol: tactics and strategy to minimize impact in behavioral and developmental science. Psychoneuroendocrinology 2009;34(10):1437–48. [3] Badrick E, Kirschbaum C, Kumari M. The relationship between smoking status and cortisol secretion. J Clin Endocrinol Metab 2007;92(3):819–24. [4] Kumari M, Badrick E, Chandola T, Adler NE, Epel E, Seeman T, et al. Measures of social position and cortisol secretion in an aging population: findings from the Whitehall II study. Psychosom Med 2010;72(1):27–34. [5] Childs E, de Wit H. Hormonal, cardiovascular, and subjective responses to acute stress in smokers. Psychopharmacology (Berl) 2009;203(1):1–12. [6] Roy MP, Steptoe A, Kirschbaum C. Association between smoking status and cardiovascular and cortisol stress responsivity in healthy young men. Int J Behav Med 1994; 1(3):264–83. [7] Tsuda A, Steptoe A, West R, Fieldman G, Kirschbaum C. Cigarette smoking and psychophysiological stress responsiveness: effects of recent smoking and temporary abstinence. Psychopharmacology (Berl) 1996;126(3):226–33.
Jane B. Allendorfer Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, USA
313
Corresponding author at: Department of Neurology, Division of Epilepsy, 312 Civitan International Research Center, 1719 6th Avenue South, Birmingham, AL 35294, USA. Tel.: +1 205 975 3372; fax: +1 205 975 6255. E-mail address: [email protected]. Jerzy P. Szaflarski Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA Department of Neurology, University of Cincinnati Academic Health Center, Cincinnati, OH, USA Department of Psychiatry, University of Cincinnati Academic Health Center, Cincinnati, OH, USA 6 August 2014