G Model
AJP-693; No. of Pages 4 Asian Journal of Psychiatry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Short communication
The cortisol response to social stress in social anxiety disorder Oriana Vaccarino a,c, Robert Levitan a,b,c, Arun Ravindran a,b,c,* a
Centre for Addiction and Mental Health, 100 Stokes St., Toronto, ON, Canada M6 J 1H4 University of Toronto, Department of Psychiatry, 250 College Street, 8th Floor, Toronto, ON, Canada M5 T 1R8 c University of Toronto, Institute of Medical Science, 1 King’s College Circle, Room 2374, Toronto, ON, Canada M5S 1A8 b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 28 October 2014 Received in revised form 13 March 2015 Accepted 18 March 2015 Available online xxx
This study evaluated the cortisol stress response (CSR) following the Trier Social Stress Test in Social Anxiety Disorder (SAD) and control participants, to determine whether individual differences in CSR associate more (11 with SAD) diagnosis or dimensional characteristics [i.e. childhood trauma (CT)]. Twenty-one participants had full data available for both CT-scores and cortisol area-under-the-curve (AUC). Linear-regression produced significant results: predicting AUCG with study group, emotional abuse (EA) scores and their interaction (F = 3.14, df = 5,15; p = .039); of note, the study group by EA interaction was significant at p = .015, driven by a strong positive association between EA and cortisol AUCG in the control group and a negative association between these variables in the SAD group. This suggests that EA in SAD patients is associated with altered CSR, highlighting need to measure dimensional characteristics. ß 2015 Elsevier B.V. All rights reserved.
Keywords: Social anxiety disorder Cortisol Social stress Childhood trauma Emotional abuse
1. Introduction Social Anxiety Disorder (SAD) is a common disorder defined by an intense fear of being negatively evaluated by others, and fear of embarrassment in social situations (Antony and Stein, 2009; Woody and Nosen, 2009). The estimated lifetime prevalence of SAD is 10 percent (Kessler, 2003; Stein and Stein, 2008). Individuals with SAD often experience negative self-focused cognitions that tend to worsen anxiety when social threat is anticipated (Schulz, 2008). Given the fundamental role of impaired social evaluation in the pathophysiology of SAD, it would be important to determine whether SAD patients exhibit any unique pattern of stress responsivity to a social challenge. This can be studied empirically using standardized social stress protocols measuring neurohormonal changes. The literature to date examining the cortisol stress response (CSR) following a social challenge in SAD has reported mixed results (Beaton et al., 2006; Condren et al., 2002; Furlan
Abbreviations: SAD, social anxiety disorder; CSR, cortisol stress response; CT, childhood trauma; EA, emotional abuse; CAMH, Centre for Addiction and Mental Health; SCID, structured clinical interview for DSM disorders; TSST, trier social stress test; CTQ, Childhood Trauma Questionnaire; AUC, area under the curve. * Corresponding author at: Centre for Addiction and Mental Health, 100 Stokes St., Toronto, ON, Canada M6 J 1H4. Tel.: +1 416 979 6933; fax: +1 416 595 6728. E-mail address: [email protected] (A. Ravindran).
et al., 2001; Levin, 1993; Martel et al., 1999; Roelofs et al., 2009; Shirotsuki et al., 2009; van West et al., 2008; Yoon, 2012). One possible explanation for this inconsistency is that moderating factors such as childhood trauma (CT) have a greater influence on social stress responses and/or overall cortisol secretion than does the condition, itself. For example, Elzinga et al. (2010) showed that individuals with SAD and a history of childhood abuse had greatly enhanced cortisol reactivity to a psychosocial stress task in comparison to those with SAD alone. Similarly, van der Vegt et al. (2010) examined awakening cortisol levels in anxiety disorders, and stressed the effects of early childhood adversity on cortisol reactivity in these conditions. This is in keeping with the notion that emotional abuse (EA), more so than physical or sexual abuse, may be associated with the pathophysiology of SAD (Asher and Coie, 1990; Lochner et al., 2010). More recently, a study has found that different forms of CT are associated with different CSR (Kuhlman et al., 2015). Failure to assess and control for such moderating factors could help explain previous heterogeneous findings. The goal of the current study was to examine the relationship between the CSR and CT, as well as its subcomponent childhood EA. To this end, the present study examined cortisol responses in SAD and control participants in response to the TSST. It further evaluated whether individual differences in the experience of CT were associated with the CSR in this context. Thus, it was hypothesized that individual differences in early adversity would
http://dx.doi.org/10.1016/j.ajp.2015.03.004 1876-2018/ß 2015 Elsevier B.V. All rights reserved.
Please cite this article in press as: Vaccarino, O., et al., The cortisol response to social stress in social anxiety disorder. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.03.004
G Model
AJP-693; No. of Pages 4 O. Vaccarino et al. / Asian Journal of Psychiatry xxx (2015) xxx–xxx
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be a strong predictor of the CSR following the TSST, whether or not SAD participants differed from controls overall. 2. Methods and materials The study sample consisted of 24 participants (12 SAD, 12 controls) aged 18 to 65. Of those 24 participants, 8 were female and 16 were male. SAD was established as the primary diagnosis by a psychiatrist at CAMH then confirmed by a trained interviewer using the SCID (First et al., 1995). Control participants had no current or past history of Axis I or II disorders. Exclusion criteria for both groups included recent major life stressors, pregnancy, breastfeeding, and chronic medical disease. Controls were matched to SAD participants by gender and age. Participants underwent an informed consent process and signed a consent form prior to enrolment. This study received CAMH Research Ethics Board approval and complied with the Code of Ethics of the World Medical Association. The study consisted of two visits. During visit 1, all participants underwent a diagnostic interview (SCID) (First et al., 1995) to confirm the diagnosis of SAD and rule out other Axis I and II disorders. Demographic and current treatment information, medical and psychiatric history were obtained. Participants completed questionnaires including standardized measures of anxiety, depression, and the CTQ (Bernstein and Fink, 1998). The CTQ is a self-report questionnaire assessing CT with subscales examining emotional, physical, and sexual childhood abuse and neglect. During visit 2, The TSST (Kirschbaum et al., 1993) was administered in the early afternoon (to account for diurnal variations). Based on the procedures developed by Kirschbaum et al., (1993), social stress was induced by placing participants in a novel situation where they believed they were being socially evaluated. This study followed the same protocol reported in Roelofs et al. (2009). Based on Roelofs et al. (2009), TSST modifications were available to participants who felt unable to
complete the TSST. Participants were reminded that they could stop participating at any time. Serial plasma cortisol samples were taken two minutes after arrival, immediately prior to TSST, and ten, thirty, forty-five, and sixty minutes post-TSST using an indwelling line connected to a blood pump. A total of 21 participants [11 with SAD including 4 females, and 10 controls including 4 females] had full data available for both CT scores and cortisol area under the curve (AUC). To examine the influence of study group, CT scores and their interaction on cortisol responses during the TSST, we used linear regression including each of these three independent predictors while controlling for age and BMI. Separate models were examined for AUCG (AUC with respect to ground) and AUCI (AUC with respect to increase) (Pruessner et al., 2003). Based on (1) the high rates of emotional abuse reported by patients with SAD (Asher and Coie, 1990; Lochner et al., 2010) and (2) recent evidence suggesting that different forms of childhood adversity are associated with different cortisol stress responses (Kuhlman et al., 2015), we performed one set of analyses based on total CTQ scores and another based on childhood EA scores only. 3. Results When total CTQ scores were included in the models, no significant effects were noted. In contrast, a significant result was produced when predicting cortisol AUCG with study group, emotional abuse scores and their interaction, controlling for age and BMI (F = 3.14, df = 5.15; p = .039). Of particular interest was the finding of a highly significant study group by emotional abuse interaction in predicting AUCG (standardized beta = 1.56, t = 2.75, p = .015). As shown in Fig. 1, this was driven by a very strong positive relationship between emotional abuse scores and AUCG in the control group (r2 = 49) and a moderately strong negative relationship between emotional abuse scores and AUCG in the
Participant Group
3000.00
Social Anxiety Control Social Anxiety Control
2500.00
AUC_G5
2000.00
1500.00
1000.00 R Sq Linear = 0.177 R Sq Linear = 0.498
500.00 6.00
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10.00
12.00
14.00
16.00
18.00
20.00
Emotional Abuse Score Fig. 1. Relationship between emotional abuse scores and cortisol (AUCG) in response to TSST in SAD patients and controls.
Please cite this article in press as: Vaccarino, O., et al., The cortisol response to social stress in social anxiety disorder. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.03.004
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AJP-693; No. of Pages 4 O. Vaccarino et al. / Asian Journal of Psychiatry xxx (2015) xxx–xxx
social anxiety group (r2 = .177). When we removed the single outlier with an unusually high AUCG in the social anxiety group, the group by emotional abuse interaction was significant at p = .002, with the correlation between emotional abuse and AUCG in the SAD group now at r2 = .33. No significant findings related to AUCI were noted. 4. Discussion The primary goal of the current study was to determine whether individual differences in CSR relate more to the specific condition of SAD or are more influenced by moderating factors such as the presence of CT. The main finding was a significant study group by emotional abuse score interaction in predicting cortisol AUCG (a measure of total cortisol secretion) during the TSST. This finding was driven by a negative association between emotional abuse scores and cortisol AUCG in the SAD group, which strongly contrasted the marked positive relationship between emotional abuse scores and AUCG in the control group. Past research has shown that individuals with SAD report higher rates of CT, and in particular EA, compared to healthy individuals (Asher and Coie, 1990; Lochner et al., 2010). The present findings suggest that EA in SAD patients is associated with an altered cortisol stress response, in particular total cortisol exposure in response to a social challenge as reflected in the AUCG. CT, including EA, has been previously reported to be associated with an altered stress response in several clinical populations. Commonly, this manifests as a blunted cortisol response (Bergen et al., 2012; Carpenter et al., 2007, 2009; van der Vegt et al., 2010), which has been proposed as an adaptive compensatory response that may have beneficial effects (Fries et al., 2005). This notion is supported by previous findings showing that there is initial HPA axis activation and increased cortisol reactivity with the onset of trauma, but over time and as the stressor becomes chronic, a compensatory blunted response occurs (Miller et al., 2007). The findings from the current investigation are similar to these previous results, showing an inverse relationship between childhood EA and total cortisol response in the SAD group only. The present findings showing that certain behavioural characteristics of the SAD population may influence their cortisol reactivity pattern could have implications for future research on this topic, in particular, the need to consider the influence of factors such as CT and more specifically childhood emotional abuse. Contributors This study was conducted and designed by Oriana Vaccarino for her M.Sc. thesis work, with the guidance and support of her supervisor Dr. Arun Ravindran. Oriana Vaccarino conducted the analysis and interpretation of the data, with the help of both Dr. Robert Levitan and Dr. Arun Ravindran. Dr. Robert Levitan was a committee member for Oriana’s M.Sc. work who helped refine the design of the study, and give guidance and suggestions throughout the study. All three authors played a large role in the drafting and revising of this manuscript, and have approved this manuscript for submission. Financial disclosure and role of funding source There are no financial conflicts of interests to disclose. No financial support was received from any commercial entity for this study.
3
Acknowledgements We would like to acknowledge the help and support of our team at the Centre for Addiction and Mental Health, including: Martha McKay, Tricia da Silva, Jessica Grummitt, Tracy Bhikram, Vanessa Ballarino, as well as the volunteers who helped make this study possible. We would also like to acknowledge the support of the Institute of Medical Science and the Department of Psychiatry at the University of Toronto.
References Antony, M.M., Stein, M.B., 2009. Oxford Handbook of Anxiety and Related Disorders. Oxford University Press, New York, NY. Asher, S.R., Coie, J.D., 1990. Peer Rejection in Childhood. Cambridge University Press, New York, NY. Beaton, E.A., Schmidt, L.A., Ashbaugh, A.R., et al., 2006. Low salivary cortisol levels among socially anxious young adults: preliminary evidence from a selected and a non-selected sample. Pers. Individ. Diff. 41 (7), 1217–1228, http://dx.doi.org/ 10.1016/j.paid.2006.02.020. Bergen, A.W., Mallick, A., Nishita, D., et al., 2012. Chronic psychosocial stressors and salivary biomarkers in emerging adults. Psychoneuroendocrinology 37 (8), 1158–1170, http://dx.doi.org/10.1016/j.psyneuen.2011.11.010. Bernstein, D., Fink, L., 1998. Childhood Trauma Questionnaire: A Retrospective SelfReport. Harcourt Brace & Company, Austin, Texas. Carpenter, L., Carvalho, J.P., Tyrka, A.R., et al., 2007. Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biol. Psychiatry 62 (10), 1080–1087, http:// dx.doi.org/10.1016/j.biopsych.2007.05.002. Carpenter, L., Tyrka, A., Ross, N., et al., 2009. Effect of childhood emotional abuse and age on cortisol responsivity in adulthood. Biol. Psychiatry 66 (1), 69–75, http:// dx.doi.org/10.1016/j.biopsych.2009.02.030. Condren, R.M., O’Neill, A., Ryan, M.C.M., et al., 2002. HPA axis response to a psychological stressor in generalized social phobia. Psychoneuroendocrinology 27 (6), 693–703, http://dx.doi.org/10.1016/S0306-4530(01)00070-1. Elzinga, B.M., Spinhoven, P., Berretty, E., et al., 2010. The role of childhood abuse in HPA-axis reactivity in social anxiety disorder: a pilot study. Biol. Psychol. 83 (1), 1–6, http://dx.doi.org/10.1016/j.biopsycho.2009.09.006. First, M., Frances, A., Pincus, H., 1995. DSM–IV handbook of differential diagnosis. American Psychiatric Press, Inc., Washington, DC. Fries, E., Hesse, J., Hellhammer, J., et al., 2005. A new view on hypocortisolism. Psychoneuroendocrinology 30 (10), 1010, http://dx.doi.org/10.1016/j.psyneuen.2005.04.006. Furlan, P.M., DeMartinis, N., Schweizer, E., et al., 2001. Abnormal salivary cortisol levels in social phobic patients in response to acute psychological but not physical stress. Biol. Psychiatry 50 (4), 254–259, http://dx.doi.org/10.1016/ S0006-3223(00)01126-4. Kessler, R.C., 2003. The impairments caused by social phobia in the general population: implications for intervention. Acta Psychiatr. Scand. 108 (Suppl. 417), 19–27. Kirschbaum, C., Pirke, K.M., Hellhammer, D.H., 1993. The ‘Trier social stress test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28 (1–2), 78. Kuhlman, K.R., Geiss, E.G., Vargas, I., Lopez-Duran, N.L., 2015. Differential associations between childhood trauma subtypes and adolescent HPA-axis functioning. Psychoneuroendocrinology 54, 103–114. Levin, A.P., 1993. Responses of generalized and discrete social phobics during public speaking. J. Anxiety Dis. 7 (3), 207, http://dx.doi.org/10.1016/08876185(93)90003-4. Lochner, C., Seedat, S., Allgulander, C., et al., 2010. Childhood trauma in adults with social anxiety disorder and panic disorder: a cross-national study. Afr. J. Psychiatry 13, 376–381. Martel, F.L., Hayward, C., Lyons, D.M., et al., 1999. Salivary cortisol levels in socially phobic adolescent girls. Depress. Anxiety 10 (1), 25–27, 10.1002/(SICI)15206394(1999)10:13.0.CO;2-O. Miller, G.E., Chen, E., Zhou, E.S., 2007. If it goes up, must it come down? Chronic stress and the hypothalamic–pituitary–adrenocortical axis in humans. Psychol. Bull. 133 (1), 25–45, http://dx.doi.org/10.1037/00332909.133.1.25. Pruessner, J.C., Kirschbaum, C., Meinlschmid, G., et al., 2003. Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28 (7), 916–931, http://dx.doi.org/10.1016/S0306-4530(02)001087. Roelofs, K., van Peer, J., Berretty, E., et al., 2009. Hypothalamus–pituitary–adrenal axis hyperresponsiveness is associated with increased social avoidance behavior in social phobia. Biol. Psychiatry 65 (4), 336–343, http://dx.doi.org/10.1016/ j.biopsych.2008.08.022. Schulz, S.M., 2008. Negative self-focused cognitions mediate the effect of trait social anxiety on state anxiety. Behav. Res. Ther. 46 (4), 438, http://dx.doi.org/ 10.1016/j.brat.2008.01.008.
Please cite this article in press as: Vaccarino, O., et al., The cortisol response to social stress in social anxiety disorder. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.03.004
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Shirotsuki, K., Izawa, S., Sugaya, N., et al., 2009. Salivary cortisol and DHEA reactivity to psychosocial stress in socially anxious males. Int. J. Psychophysiol. 72 (2), 198–203, http://dx.doi.org/10.1016/j.ijpsycho.2008.12.010. Stein, M.B., Stein, D.J., 2008. Social anxiety disorder. Lancet 371 (9618), 1115–1125, http://dx.doi.org/10.1016/S0140-6736(08)60488-2. van der Vegt, E.J.M., van der Ende, J., Huizink, A.C., et al., 2010. Childhood adversity modifies the relationship between anxiety disorders and cortisol secretion. Biol. Psychiatry 68 (11), 1048–1054, http://dx.doi.org/10.1016/j.biopsych.2010. 07.027.
van West, D., Claes, S., Sulon, J., et al., 2008. Hypothalamic–pituitary–adrenal reactivity in prepubertal children with social phobia. J. Affect. Dis. 111 (2–3), 281–290, http://dx.doi.org/10.1016/j.jad.2008.03.006. Woody, S.R., Nosen, E., 2009. Psychological models of phobic disorders and panic. In: Antony, M.M., Stein, M.B. (Eds.), Oxford Handbook of Anxiety and Related Disorders. Oxford University Press, New York, NY, pp. 209–224. Yoon, K.L., 2012. Stress reactivity in social anxiety disorder with and without comorbid depression. J. Abnorm. Psychol. 121 (1), 250, http://dx.doi.org/10. 1037/a0025079.
Please cite this article in press as: Vaccarino, O., et al., The cortisol response to social stress in social anxiety disorder. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.03.004
AJP-693; No. of Pages 4 Asian Journal of Psychiatry xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Asian Journal of Psychiatry journal homepage: www.elsevier.com/locate/ajp
Short communication
The cortisol response to social stress in social anxiety disorder Oriana Vaccarino a,c, Robert Levitan a,b,c, Arun Ravindran a,b,c,* a
Centre for Addiction and Mental Health, 100 Stokes St., Toronto, ON, Canada M6 J 1H4 University of Toronto, Department of Psychiatry, 250 College Street, 8th Floor, Toronto, ON, Canada M5 T 1R8 c University of Toronto, Institute of Medical Science, 1 King’s College Circle, Room 2374, Toronto, ON, Canada M5S 1A8 b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 28 October 2014 Received in revised form 13 March 2015 Accepted 18 March 2015 Available online xxx
This study evaluated the cortisol stress response (CSR) following the Trier Social Stress Test in Social Anxiety Disorder (SAD) and control participants, to determine whether individual differences in CSR associate more (11 with SAD) diagnosis or dimensional characteristics [i.e. childhood trauma (CT)]. Twenty-one participants had full data available for both CT-scores and cortisol area-under-the-curve (AUC). Linear-regression produced significant results: predicting AUCG with study group, emotional abuse (EA) scores and their interaction (F = 3.14, df = 5,15; p = .039); of note, the study group by EA interaction was significant at p = .015, driven by a strong positive association between EA and cortisol AUCG in the control group and a negative association between these variables in the SAD group. This suggests that EA in SAD patients is associated with altered CSR, highlighting need to measure dimensional characteristics. ß 2015 Elsevier B.V. All rights reserved.
Keywords: Social anxiety disorder Cortisol Social stress Childhood trauma Emotional abuse
1. Introduction Social Anxiety Disorder (SAD) is a common disorder defined by an intense fear of being negatively evaluated by others, and fear of embarrassment in social situations (Antony and Stein, 2009; Woody and Nosen, 2009). The estimated lifetime prevalence of SAD is 10 percent (Kessler, 2003; Stein and Stein, 2008). Individuals with SAD often experience negative self-focused cognitions that tend to worsen anxiety when social threat is anticipated (Schulz, 2008). Given the fundamental role of impaired social evaluation in the pathophysiology of SAD, it would be important to determine whether SAD patients exhibit any unique pattern of stress responsivity to a social challenge. This can be studied empirically using standardized social stress protocols measuring neurohormonal changes. The literature to date examining the cortisol stress response (CSR) following a social challenge in SAD has reported mixed results (Beaton et al., 2006; Condren et al., 2002; Furlan
Abbreviations: SAD, social anxiety disorder; CSR, cortisol stress response; CT, childhood trauma; EA, emotional abuse; CAMH, Centre for Addiction and Mental Health; SCID, structured clinical interview for DSM disorders; TSST, trier social stress test; CTQ, Childhood Trauma Questionnaire; AUC, area under the curve. * Corresponding author at: Centre for Addiction and Mental Health, 100 Stokes St., Toronto, ON, Canada M6 J 1H4. Tel.: +1 416 979 6933; fax: +1 416 595 6728. E-mail address: [email protected] (A. Ravindran).
et al., 2001; Levin, 1993; Martel et al., 1999; Roelofs et al., 2009; Shirotsuki et al., 2009; van West et al., 2008; Yoon, 2012). One possible explanation for this inconsistency is that moderating factors such as childhood trauma (CT) have a greater influence on social stress responses and/or overall cortisol secretion than does the condition, itself. For example, Elzinga et al. (2010) showed that individuals with SAD and a history of childhood abuse had greatly enhanced cortisol reactivity to a psychosocial stress task in comparison to those with SAD alone. Similarly, van der Vegt et al. (2010) examined awakening cortisol levels in anxiety disorders, and stressed the effects of early childhood adversity on cortisol reactivity in these conditions. This is in keeping with the notion that emotional abuse (EA), more so than physical or sexual abuse, may be associated with the pathophysiology of SAD (Asher and Coie, 1990; Lochner et al., 2010). More recently, a study has found that different forms of CT are associated with different CSR (Kuhlman et al., 2015). Failure to assess and control for such moderating factors could help explain previous heterogeneous findings. The goal of the current study was to examine the relationship between the CSR and CT, as well as its subcomponent childhood EA. To this end, the present study examined cortisol responses in SAD and control participants in response to the TSST. It further evaluated whether individual differences in the experience of CT were associated with the CSR in this context. Thus, it was hypothesized that individual differences in early adversity would
http://dx.doi.org/10.1016/j.ajp.2015.03.004 1876-2018/ß 2015 Elsevier B.V. All rights reserved.
Please cite this article in press as: Vaccarino, O., et al., The cortisol response to social stress in social anxiety disorder. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.03.004
G Model
AJP-693; No. of Pages 4 O. Vaccarino et al. / Asian Journal of Psychiatry xxx (2015) xxx–xxx
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be a strong predictor of the CSR following the TSST, whether or not SAD participants differed from controls overall. 2. Methods and materials The study sample consisted of 24 participants (12 SAD, 12 controls) aged 18 to 65. Of those 24 participants, 8 were female and 16 were male. SAD was established as the primary diagnosis by a psychiatrist at CAMH then confirmed by a trained interviewer using the SCID (First et al., 1995). Control participants had no current or past history of Axis I or II disorders. Exclusion criteria for both groups included recent major life stressors, pregnancy, breastfeeding, and chronic medical disease. Controls were matched to SAD participants by gender and age. Participants underwent an informed consent process and signed a consent form prior to enrolment. This study received CAMH Research Ethics Board approval and complied with the Code of Ethics of the World Medical Association. The study consisted of two visits. During visit 1, all participants underwent a diagnostic interview (SCID) (First et al., 1995) to confirm the diagnosis of SAD and rule out other Axis I and II disorders. Demographic and current treatment information, medical and psychiatric history were obtained. Participants completed questionnaires including standardized measures of anxiety, depression, and the CTQ (Bernstein and Fink, 1998). The CTQ is a self-report questionnaire assessing CT with subscales examining emotional, physical, and sexual childhood abuse and neglect. During visit 2, The TSST (Kirschbaum et al., 1993) was administered in the early afternoon (to account for diurnal variations). Based on the procedures developed by Kirschbaum et al., (1993), social stress was induced by placing participants in a novel situation where they believed they were being socially evaluated. This study followed the same protocol reported in Roelofs et al. (2009). Based on Roelofs et al. (2009), TSST modifications were available to participants who felt unable to
complete the TSST. Participants were reminded that they could stop participating at any time. Serial plasma cortisol samples were taken two minutes after arrival, immediately prior to TSST, and ten, thirty, forty-five, and sixty minutes post-TSST using an indwelling line connected to a blood pump. A total of 21 participants [11 with SAD including 4 females, and 10 controls including 4 females] had full data available for both CT scores and cortisol area under the curve (AUC). To examine the influence of study group, CT scores and their interaction on cortisol responses during the TSST, we used linear regression including each of these three independent predictors while controlling for age and BMI. Separate models were examined for AUCG (AUC with respect to ground) and AUCI (AUC with respect to increase) (Pruessner et al., 2003). Based on (1) the high rates of emotional abuse reported by patients with SAD (Asher and Coie, 1990; Lochner et al., 2010) and (2) recent evidence suggesting that different forms of childhood adversity are associated with different cortisol stress responses (Kuhlman et al., 2015), we performed one set of analyses based on total CTQ scores and another based on childhood EA scores only. 3. Results When total CTQ scores were included in the models, no significant effects were noted. In contrast, a significant result was produced when predicting cortisol AUCG with study group, emotional abuse scores and their interaction, controlling for age and BMI (F = 3.14, df = 5.15; p = .039). Of particular interest was the finding of a highly significant study group by emotional abuse interaction in predicting AUCG (standardized beta = 1.56, t = 2.75, p = .015). As shown in Fig. 1, this was driven by a very strong positive relationship between emotional abuse scores and AUCG in the control group (r2 = 49) and a moderately strong negative relationship between emotional abuse scores and AUCG in the
Participant Group
3000.00
Social Anxiety Control Social Anxiety Control
2500.00
AUC_G5
2000.00
1500.00
1000.00 R Sq Linear = 0.177 R Sq Linear = 0.498
500.00 6.00
8.00
10.00
12.00
14.00
16.00
18.00
20.00
Emotional Abuse Score Fig. 1. Relationship between emotional abuse scores and cortisol (AUCG) in response to TSST in SAD patients and controls.
Please cite this article in press as: Vaccarino, O., et al., The cortisol response to social stress in social anxiety disorder. Asian J. Psychiatry (2015), http://dx.doi.org/10.1016/j.ajp.2015.03.004
G Model
AJP-693; No. of Pages 4 O. Vaccarino et al. / Asian Journal of Psychiatry xxx (2015) xxx–xxx
social anxiety group (r2 = .177). When we removed the single outlier with an unusually high AUCG in the social anxiety group, the group by emotional abuse interaction was significant at p = .002, with the correlation between emotional abuse and AUCG in the SAD group now at r2 = .33. No significant findings related to AUCI were noted. 4. Discussion The primary goal of the current study was to determine whether individual differences in CSR relate more to the specific condition of SAD or are more influenced by moderating factors such as the presence of CT. The main finding was a significant study group by emotional abuse score interaction in predicting cortisol AUCG (a measure of total cortisol secretion) during the TSST. This finding was driven by a negative association between emotional abuse scores and cortisol AUCG in the SAD group, which strongly contrasted the marked positive relationship between emotional abuse scores and AUCG in the control group. Past research has shown that individuals with SAD report higher rates of CT, and in particular EA, compared to healthy individuals (Asher and Coie, 1990; Lochner et al., 2010). The present findings suggest that EA in SAD patients is associated with an altered cortisol stress response, in particular total cortisol exposure in response to a social challenge as reflected in the AUCG. CT, including EA, has been previously reported to be associated with an altered stress response in several clinical populations. Commonly, this manifests as a blunted cortisol response (Bergen et al., 2012; Carpenter et al., 2007, 2009; van der Vegt et al., 2010), which has been proposed as an adaptive compensatory response that may have beneficial effects (Fries et al., 2005). This notion is supported by previous findings showing that there is initial HPA axis activation and increased cortisol reactivity with the onset of trauma, but over time and as the stressor becomes chronic, a compensatory blunted response occurs (Miller et al., 2007). The findings from the current investigation are similar to these previous results, showing an inverse relationship between childhood EA and total cortisol response in the SAD group only. The present findings showing that certain behavioural characteristics of the SAD population may influence their cortisol reactivity pattern could have implications for future research on this topic, in particular, the need to consider the influence of factors such as CT and more specifically childhood emotional abuse. Contributors This study was conducted and designed by Oriana Vaccarino for her M.Sc. thesis work, with the guidance and support of her supervisor Dr. Arun Ravindran. Oriana Vaccarino conducted the analysis and interpretation of the data, with the help of both Dr. Robert Levitan and Dr. Arun Ravindran. Dr. Robert Levitan was a committee member for Oriana’s M.Sc. work who helped refine the design of the study, and give guidance and suggestions throughout the study. All three authors played a large role in the drafting and revising of this manuscript, and have approved this manuscript for submission. Financial disclosure and role of funding source There are no financial conflicts of interests to disclose. No financial support was received from any commercial entity for this study.
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Acknowledgements We would like to acknowledge the help and support of our team at the Centre for Addiction and Mental Health, including: Martha McKay, Tricia da Silva, Jessica Grummitt, Tracy Bhikram, Vanessa Ballarino, as well as the volunteers who helped make this study possible. We would also like to acknowledge the support of the Institute of Medical Science and the Department of Psychiatry at the University of Toronto.
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