- Email: [email protected]
P.8.b.001 Interaction of acetylcholinesterase reactivators with albumin
P.8.b. Other topics (basic) distress (r = 0.418), emotional (r = 0.564), physical (r = 0.469), and practical problems (r = 0.356). Other Hwa-byung related symptom categories showed moderate correlation with distress (r = 0.447) and physical problems (r = 0.532). Conclusions: Assessing the diverse psychological symptoms including distress and proper emotional interventions across phases of cancer treatment is very important. Hwa-byung, i.e. culture-specific syndrome, showed very strong association with distress and life problems among Korean women cancer patients. Hwa-byung scale might be one of the proper early psychological screening tools and help provide interventions especially for Korean women cancer patients. References [1] Holland, J.C., Andersen, B., Breitbart, W.S., Compas, B., Dudley, M.M., Fleishman, S., et al., 2010. Distress management. J Natl Compr Canc Netw 8, 448–485. [2] SK. Min., 2008. Clinical correlates of hwa-byung and aproposal for a new anger disorder. Psychiatry Investig 5, 125–141.
P.8.a.004 Depersonalisation/derealisation symptoms in social phobia versus controls during acute social stress S. Crawcour1 ° , D. Braeuer1 , E. Klumbies2 , K. Kirschbaum2 , J. Hoyer1 1 Technische Universitaet Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany; 2 Technische Universitaet Dresden, Institute of Bio-Psychology, Dresden, Germany Current psychological models of social phobia emphasize the role of cognitive factors for the development and maintenance of social phobia (SP). Though typical for many anxiety disorders (e.g. post-traumatic stress disorder and during panic attacks), depersonalisation and derealisation (DP/DR) have to date received little consideration in models of SP. Our current study aimed at investigating how frequently and intensely DP/DR symptoms occur during a stressful performance (Trier Social Stress Test; TSST) in social phobia patients and healthy controls. Hypotheses about the psychological predictors and consequences of these symptoms were tested. To the best of our knowledge, this is the first study to test DP/DR symptoms during acute social stress. N = 54 patients with social phobia and N = 34 control participants without mental disorders were examined before, during, and after a TSST. An adapted state version of the Cambridge Depersonalisation Scale was applied along with measures of social anxiety, depression, personality, participants’ subjective appraisal, safety behaviours, and post-event processing. Dissociative symptoms were more frequent in SP patients (92%) than in controls (52%). Dissociative symptoms were moderately associated with clinical variables, but specifically in patients they were highly positively correlated with safety behaviours and postevent-processing, even after controlling for social anxiety. The results demonstrate that dissociative symptoms are typical during intense states of social anxiety. The role of these symptoms in the maintenance of social anxiety should be more thoroughly explored and conceptualized. Hence, we provide strong evidence for the integration of DP/DR into models of social phobia. Given that DP/DR are seldom experienced and are rather ‘exceptional’ in nature, social phobia patients may attempt to avoid situations provoking DP/DR to the largest possible extent.
S439
In future research endeavours, it may prove useful to understand how DP/DR are related to avoidance and safety behaviours in social phobia patients; whether DP/DR are linked to (potential) sub-types of SP; and how susceptible DP/DR are to specific variants of treatment. Attention training would offer itself as an appropriate intervention to help counteract the experience of acute DP/DR symptoms. In spite of the fact that cognitive-behavioral therapy based on the model of Clark and Wells is highly efficacious in the treatment of social phobia, some patients fail to show a clinical significant response to treatment. It is unlikely that a single variable would explain why some patients cannot benefit from treatment. However, it could be hypothesized that patients with a strong tendency to experience DP/DR symptoms during role play and behavioural experiments would be prone to experience a definitive psychological barrier that prevents treatment success. Role plays and behavioural experiments in social situations are an integral part of the procedures proposed by Clark and Wells. The notion that patients fear experiencing DP/DR during role plays and/or behaviour experiments would explain why they cannot fully, i.e., without open or implicit safety behaviours, engage in such interventions. Further research should therefore specifically explore the possibility that fear of DP/DR defines a specific hindrance to benefit from CBT treatment. References [1] Clark, D.M., Ehlers, A., McManus, F., Hackman, A., Fennell, M., Campbell, H., et al. (2003). Cognitive therapy versus Fluoxetine in generalized social phobia: a randomized placebo-controlled trial. Journal of Consulting and Clinical Psychology, 71(6), 1058–1067. [2] Clark, D.M., Ehlers, A., Hackmann, A., McManus, F., Fennell, M., Grey, N., et al. (2006). Cognitive therapy versus exposure and applied relaxation in social phobia: a randomized controlled trial. Journal of Consulting and Clinical Psychology, 74(3), 568–578. [3] Clark, D., & Wells, A. (1995). A cognitive model of social phobia. In R. Heimberg, M. Liebowitz, D. Hope, F. Schneier (Eds.), Social phobia: Diagnosis, assessment, and treatment (pp. 69−93). New York: Guilford.
P.8.b. Other topics (basic) P.8.b.001 Interaction of acetylcholinesterase reactivators with albumin F. Zemek1 ° , V. Sepsova1 , L. Drtinova1 , J. Korabecny1 , M. Pohanka2 , J. Zdarova Karasova3 , K. Kuca2 1 Faculty of Military Health Sciences, Department of Toxicology, Hradec Kr´alov´e, Czech Republic; 2 Faculty of Military Health Sciences, Centre of Advance Studies, Hradec Kr´alov´e, Czech Republic; 3 Faculty of Military Health Sciences, Department of Public Health, Hradec Kr´alov´e, Czech Republic Interactions between drugs and proteins abundant in human serum especially albumin and alpha 1-acid glycoprotein are known for many decades. The importance of mentioned interactions is underlined by compulsory experimental determination as part of the drug registration process. Numerous examples of widely prescribed drugs (warfarin, valproate, digoxin etc.) and risks that can arise when protein binding is not previously considered and subsequent treatment complications are listed in vast number of manuscripts. Moreover, variables such as age, personal health status and/or concomitant medication also play a vital role and have to be taken into consideration in plasma protein binding
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P.8.b. Other topics (basic)
studies. Plasmatic proteins and their interactions with drugs play an important role especially in elimination process and also concerning drugs acting in the central nervous system, which are prone to concentration deviations that can negatively affect ongoing treatment. Reactivators of acetylcholinesterase (briefly named oximes), that should be used in the treatment of nerve agent and pesticide poisoning, are presumed to exert maximum protein binding of five per cent however experimental verification is absent, at least to the authors’ best knowledge. A set of six newly synthesized reactivators (K027, K203, K282, K075, K108, K127) were selected for In Vitro testing. Obidoxime, trimedoxime and oxime HI-6 were used as standards for comparison. Design of the study was to imitate physiological environment of human blood vessels (temperature, real blood concentration of albumin, achieved maximal plasma concentration of tested compounds after therapeutic doses application). Special Centrifree® Ultrafiltration Devices were used for separation of the unbound fraction of tested compounds from the solution of albumin and phosphate buffer with pH around 7.4. Gained ultrafiltrate did not undergo any more treatments and was immediately analyzed by HPLC system Agilent 1260 Infinity (Palo Alto, CA, USA). Majority of tested acetylcholinesterase reactivators exhibited binding capacity ranging between 2−3% of plasma concentration, obidoxime was between 4−5% of plasma concentration, trimedoxime displayed binding of 7−8% and oxime HI-6 only 1% of plasma concentration [1]. Acquired data are in coherence with expectations based on the analysis of pharmacokinetic data measured beforehand. AUC showed relatively quick clearance from plasma suggesting that these compounds did not form any depots by binding on plasmatic proteins. Related pharmacokinetic data were published previously [2,3]. Unfortunately, the binding of tested compounds did not display significant differences that may explain significant changes in clearance. According to the known structures of acetylcholinesterase reactivators it was proposed that these substances will not bind to any of the main albumin sites (Sudlow I and Sudlow II). Proposed assumptions were the basis for the design of the presented study. Understandably, additional measurements with different method are needed to validate these results. Detailed description of the method used and results will be discussed within our contribution. References [1] Zemek, F., Karasova, J.Z., Musilek, K., Kuca, K., 2011. Method optimization for acetylcholinesterase modulators–albumin interactions. Mil Med Sci Lett 80, 58−64. [2] Karasova, J.Z., Hnidkova, D., Pohanka, M., Musilek, K., Chilcott, R.P., Kuca, K., 2012. Pharmacokinetics of acetylcholinesterase reactivator K203 and consequent evaluation of low molecular weight antioxidants/ markers of oxidative stress. J Appl Biomed 10, 71−78. [3] Karasova, J.Z., Novotny, L., Antos, K., Zivna, H., Kuca, K., 2010. Time-dependent changes in concentration of two clinically used acetylcholinesterase reactivators (HI-6 and obidoxime) in rat plasma determined by HPLC techniques after in vivo administration. Anal Sci 26, 63−67. Disclosure statement: This paper is financially supported by an educational grant from Ministry of Education, Youth and Sports, Czech RepublicMinistry of Education, Youth and Sports, Czech Republic. Specific research of Faculty of Military Health Sciences (Establishment of biochemical and pharmacokinetic parameters selected acetylcholinesterase inhibitors).
P.8.b.002 The Global Alliance of Mental Illness Advocacy Networks (GAMIAN-Europe) pan European adherence to treatment P. Montellano1 , P. Arteel1 , M. De Hert2 , K. Alptekin3 , D. Gauci1 ° 1 GAMIAN-Europe, patients association, Brussels, Belgium; 2 KULeuven, UPC St Jozef, Kortenberg, Belgium; 3 Univ Izmir, Psychiatry, Izmir, Turkey Purpose of the study: Up to now to treatment adherence has been assessed by psychiatrists, nurses and other health professionals. GAMIAN-Europe wants to add the patients’ view to this debate. The primary objective of this study is to establish the adherence to treatment reported by a European sample of participants with a diagnosis of schizophrenia, aged 18 years or older. Secondary aims include the assessment of the adherence to treatment as seen by patients and the examination of differences by countries. In the questionnaire, adherence to treatment is not restricted to adherence to medication, but includes adherence to psychotherapy/counselling, psycho-education and self-help. Methodology: The study has a cross-sectional design where participants will be asked to complete a survey measuring their reported adherence to treatment. Data will be collected from GAMIAN-Europe member organisations in European Countries (WHO definition). There will be no open questions thereby removing any likelihood of pharmacovigilance issues. GAMIAN-Europe member organisations in all European countries (WHO definition of Europe) were invited to take part. The survey is published on the Gamian-Europe website (http:// www.gamian.eu/adherence_to_treatment.htm). In non-English speaking countries, a consistent translation and cross-cultural adaptation procedure was be adopted to ensure that the survey packs used in each country are as comparable as possible. Participants can react online or download a printable PDF version of the questionnaire and send it to the GAMIANEurope secretariat. The aim will be to recruit a total of 200 responses and an incentive will be paid to each collaborating patient organisation. By May 1st , a total of 150 valid responses from 10 countries were received. The Questionnaire is online for a period of three months from 1 April 2012 to 30 June 2012. This survey has been supported by Janssen EMEA. Data analysis: The data arising from this study will be analysed quantitatively by an academic research institute. These analyses will focus on establishing the reliability and validity of the study measures, as well as establishing any cross-cultural and betweencountry differences. Results: Results will be available by the end of August 2012 and will be presented at the GAMIAN convention (12th and 13th October 2012 in Utrecht, Netherlands) and at a meeting of the European Parliament Interest Group on Mental health, Well being and Brain Disorders scheduled for end November 2012. Disclosure statement: This paper is financially supported by an educational grant from Janssen EMEA.
P.8.a.004 Depersonalisation/derealisation symptoms in social phobia versus controls during acute social stress S. Crawcour1 ° , D. Braeuer1 , E. Klumbies2 , K. Kirschbaum2 , J. Hoyer1 1 Technische Universitaet Dresden, Institute of Clinical Psychology and Psychotherapy, Dresden, Germany; 2 Technische Universitaet Dresden, Institute of Bio-Psychology, Dresden, Germany Current psychological models of social phobia emphasize the role of cognitive factors for the development and maintenance of social phobia (SP). Though typical for many anxiety disorders (e.g. post-traumatic stress disorder and during panic attacks), depersonalisation and derealisation (DP/DR) have to date received little consideration in models of SP. Our current study aimed at investigating how frequently and intensely DP/DR symptoms occur during a stressful performance (Trier Social Stress Test; TSST) in social phobia patients and healthy controls. Hypotheses about the psychological predictors and consequences of these symptoms were tested. To the best of our knowledge, this is the first study to test DP/DR symptoms during acute social stress. N = 54 patients with social phobia and N = 34 control participants without mental disorders were examined before, during, and after a TSST. An adapted state version of the Cambridge Depersonalisation Scale was applied along with measures of social anxiety, depression, personality, participants’ subjective appraisal, safety behaviours, and post-event processing. Dissociative symptoms were more frequent in SP patients (92%) than in controls (52%). Dissociative symptoms were moderately associated with clinical variables, but specifically in patients they were highly positively correlated with safety behaviours and postevent-processing, even after controlling for social anxiety. The results demonstrate that dissociative symptoms are typical during intense states of social anxiety. The role of these symptoms in the maintenance of social anxiety should be more thoroughly explored and conceptualized. Hence, we provide strong evidence for the integration of DP/DR into models of social phobia. Given that DP/DR are seldom experienced and are rather ‘exceptional’ in nature, social phobia patients may attempt to avoid situations provoking DP/DR to the largest possible extent.
S439
In future research endeavours, it may prove useful to understand how DP/DR are related to avoidance and safety behaviours in social phobia patients; whether DP/DR are linked to (potential) sub-types of SP; and how susceptible DP/DR are to specific variants of treatment. Attention training would offer itself as an appropriate intervention to help counteract the experience of acute DP/DR symptoms. In spite of the fact that cognitive-behavioral therapy based on the model of Clark and Wells is highly efficacious in the treatment of social phobia, some patients fail to show a clinical significant response to treatment. It is unlikely that a single variable would explain why some patients cannot benefit from treatment. However, it could be hypothesized that patients with a strong tendency to experience DP/DR symptoms during role play and behavioural experiments would be prone to experience a definitive psychological barrier that prevents treatment success. Role plays and behavioural experiments in social situations are an integral part of the procedures proposed by Clark and Wells. The notion that patients fear experiencing DP/DR during role plays and/or behaviour experiments would explain why they cannot fully, i.e., without open or implicit safety behaviours, engage in such interventions. Further research should therefore specifically explore the possibility that fear of DP/DR defines a specific hindrance to benefit from CBT treatment. References [1] Clark, D.M., Ehlers, A., McManus, F., Hackman, A., Fennell, M., Campbell, H., et al. (2003). Cognitive therapy versus Fluoxetine in generalized social phobia: a randomized placebo-controlled trial. Journal of Consulting and Clinical Psychology, 71(6), 1058–1067. [2] Clark, D.M., Ehlers, A., Hackmann, A., McManus, F., Fennell, M., Grey, N., et al. (2006). Cognitive therapy versus exposure and applied relaxation in social phobia: a randomized controlled trial. Journal of Consulting and Clinical Psychology, 74(3), 568–578. [3] Clark, D., & Wells, A. (1995). A cognitive model of social phobia. In R. Heimberg, M. Liebowitz, D. Hope, F. Schneier (Eds.), Social phobia: Diagnosis, assessment, and treatment (pp. 69−93). New York: Guilford.
P.8.b. Other topics (basic) P.8.b.001 Interaction of acetylcholinesterase reactivators with albumin F. Zemek1 ° , V. Sepsova1 , L. Drtinova1 , J. Korabecny1 , M. Pohanka2 , J. Zdarova Karasova3 , K. Kuca2 1 Faculty of Military Health Sciences, Department of Toxicology, Hradec Kr´alov´e, Czech Republic; 2 Faculty of Military Health Sciences, Centre of Advance Studies, Hradec Kr´alov´e, Czech Republic; 3 Faculty of Military Health Sciences, Department of Public Health, Hradec Kr´alov´e, Czech Republic Interactions between drugs and proteins abundant in human serum especially albumin and alpha 1-acid glycoprotein are known for many decades. The importance of mentioned interactions is underlined by compulsory experimental determination as part of the drug registration process. Numerous examples of widely prescribed drugs (warfarin, valproate, digoxin etc.) and risks that can arise when protein binding is not previously considered and subsequent treatment complications are listed in vast number of manuscripts. Moreover, variables such as age, personal health status and/or concomitant medication also play a vital role and have to be taken into consideration in plasma protein binding
S440
P.8.b. Other topics (basic)
studies. Plasmatic proteins and their interactions with drugs play an important role especially in elimination process and also concerning drugs acting in the central nervous system, which are prone to concentration deviations that can negatively affect ongoing treatment. Reactivators of acetylcholinesterase (briefly named oximes), that should be used in the treatment of nerve agent and pesticide poisoning, are presumed to exert maximum protein binding of five per cent however experimental verification is absent, at least to the authors’ best knowledge. A set of six newly synthesized reactivators (K027, K203, K282, K075, K108, K127) were selected for In Vitro testing. Obidoxime, trimedoxime and oxime HI-6 were used as standards for comparison. Design of the study was to imitate physiological environment of human blood vessels (temperature, real blood concentration of albumin, achieved maximal plasma concentration of tested compounds after therapeutic doses application). Special Centrifree® Ultrafiltration Devices were used for separation of the unbound fraction of tested compounds from the solution of albumin and phosphate buffer with pH around 7.4. Gained ultrafiltrate did not undergo any more treatments and was immediately analyzed by HPLC system Agilent 1260 Infinity (Palo Alto, CA, USA). Majority of tested acetylcholinesterase reactivators exhibited binding capacity ranging between 2−3% of plasma concentration, obidoxime was between 4−5% of plasma concentration, trimedoxime displayed binding of 7−8% and oxime HI-6 only 1% of plasma concentration [1]. Acquired data are in coherence with expectations based on the analysis of pharmacokinetic data measured beforehand. AUC showed relatively quick clearance from plasma suggesting that these compounds did not form any depots by binding on plasmatic proteins. Related pharmacokinetic data were published previously [2,3]. Unfortunately, the binding of tested compounds did not display significant differences that may explain significant changes in clearance. According to the known structures of acetylcholinesterase reactivators it was proposed that these substances will not bind to any of the main albumin sites (Sudlow I and Sudlow II). Proposed assumptions were the basis for the design of the presented study. Understandably, additional measurements with different method are needed to validate these results. Detailed description of the method used and results will be discussed within our contribution. References [1] Zemek, F., Karasova, J.Z., Musilek, K., Kuca, K., 2011. Method optimization for acetylcholinesterase modulators–albumin interactions. Mil Med Sci Lett 80, 58−64. [2] Karasova, J.Z., Hnidkova, D., Pohanka, M., Musilek, K., Chilcott, R.P., Kuca, K., 2012. Pharmacokinetics of acetylcholinesterase reactivator K203 and consequent evaluation of low molecular weight antioxidants/ markers of oxidative stress. J Appl Biomed 10, 71−78. [3] Karasova, J.Z., Novotny, L., Antos, K., Zivna, H., Kuca, K., 2010. Time-dependent changes in concentration of two clinically used acetylcholinesterase reactivators (HI-6 and obidoxime) in rat plasma determined by HPLC techniques after in vivo administration. Anal Sci 26, 63−67. Disclosure statement: This paper is financially supported by an educational grant from Ministry of Education, Youth and Sports, Czech RepublicMinistry of Education, Youth and Sports, Czech Republic. Specific research of Faculty of Military Health Sciences (Establishment of biochemical and pharmacokinetic parameters selected acetylcholinesterase inhibitors).
P.8.b.002 The Global Alliance of Mental Illness Advocacy Networks (GAMIAN-Europe) pan European adherence to treatment P. Montellano1 , P. Arteel1 , M. De Hert2 , K. Alptekin3 , D. Gauci1 ° 1 GAMIAN-Europe, patients association, Brussels, Belgium; 2 KULeuven, UPC St Jozef, Kortenberg, Belgium; 3 Univ Izmir, Psychiatry, Izmir, Turkey Purpose of the study: Up to now to treatment adherence has been assessed by psychiatrists, nurses and other health professionals. GAMIAN-Europe wants to add the patients’ view to this debate. The primary objective of this study is to establish the adherence to treatment reported by a European sample of participants with a diagnosis of schizophrenia, aged 18 years or older. Secondary aims include the assessment of the adherence to treatment as seen by patients and the examination of differences by countries. In the questionnaire, adherence to treatment is not restricted to adherence to medication, but includes adherence to psychotherapy/counselling, psycho-education and self-help. Methodology: The study has a cross-sectional design where participants will be asked to complete a survey measuring their reported adherence to treatment. Data will be collected from GAMIAN-Europe member organisations in European Countries (WHO definition). There will be no open questions thereby removing any likelihood of pharmacovigilance issues. GAMIAN-Europe member organisations in all European countries (WHO definition of Europe) were invited to take part. The survey is published on the Gamian-Europe website (http:// www.gamian.eu/adherence_to_treatment.htm). In non-English speaking countries, a consistent translation and cross-cultural adaptation procedure was be adopted to ensure that the survey packs used in each country are as comparable as possible. Participants can react online or download a printable PDF version of the questionnaire and send it to the GAMIANEurope secretariat. The aim will be to recruit a total of 200 responses and an incentive will be paid to each collaborating patient organisation. By May 1st , a total of 150 valid responses from 10 countries were received. The Questionnaire is online for a period of three months from 1 April 2012 to 30 June 2012. This survey has been supported by Janssen EMEA. Data analysis: The data arising from this study will be analysed quantitatively by an academic research institute. These analyses will focus on establishing the reliability and validity of the study measures, as well as establishing any cross-cultural and betweencountry differences. Results: Results will be available by the end of August 2012 and will be presented at the GAMIAN convention (12th and 13th October 2012 in Utrecht, Netherlands) and at a meeting of the European Parliament Interest Group on Mental health, Well being and Brain Disorders scheduled for end November 2012. Disclosure statement: This paper is financially supported by an educational grant from Janssen EMEA.