- Email: [email protected]
P.4.b.023 An updated meta-analysis of classical fear conditioning in the anxiety disorders
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P.4.b. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (clinical)
GAD associated disability (SDS-social and family) between two groups. Results: Sociodemographics and clinical characteristics of the groups are compared in Table 1. 51% (24/47) of the Turkish GAD patients and 88.6% (31/35) of the Turkish immigrants with GAD had comorbid major depression. Table 1. GAD patients Turkish (n = 47) Age Sex Education HAM-D HAM-A PSWQ GADSS SDS-social SDS-family
43.6±8.9 F/M:40/7 9±3.8 14.5±5.5 26.6±7 62.9±9.5 14.5±3.1 5.2±2 5.2±1.9
Turkish immigrants (n = 35) 45.1±8 F/M: 27/8 8.9±3.6 24.3±7.1 36.9±7.9 65.6±8.7 17±2.6 7.7±1.1 6.9±1.6
Statistics F or c2
p-value
F = 0.62 c2 = 0.58 F = 0.03 F = 48.68 F = 38.96 F = 1.71 F = 14.29 F = 44.81 F = 18.49
>0.1 >0.1 >0.1 <0.001* <0.001* >0.1 <0.001* <0.001* <0.001*
*p < 0.05.
When HAM-D score was taken as a covariate; GADSS, PSWQ, SDS-family scores were similar in two groups (p > 0.05 for all), only SDS-social life score was found to be higher in Turkish immigrants with GAD (F = 7.952, p = 0.006*). HAM-D X GADSS, HAM-D X PSWQ, HAM-D X SDS-social, HAM-D X SDS-family interactions were all found statistically significant (p < 0.001 for all). Conclusions: The results of the study presented that when depression was controlled, there was no difference in terms of GAD severity between native and immigrant groups. Depression which was much more common in Turkish immigrants had interactions with worry, GAD severity and GAD associated disability. Furthermore, only disability in social life was higher in immigrants with GAD independent of depression. These preliminary results may suggest that lack of social support which also leads to higher depression rates in Turkish immigrants with GAD living in Germany. References [1] Lindert, J., Ehrenstein, O.S., Priebe, S., Mielck, A., Br¨ahler, E., 2009. Depression and anxiety in labor migrants and refugees--a systematic review and meta-analysis. Soc Sci Med 69(2):246–257. [2] Levecque, K., Lodewyckx, I., Vranken, J., 2007. Depression and generalised anxiety in the general population in Belgium: a comparison between native and immigrant groups. J Affect Disord. 97(1−3):229– 239. [3] Bermejo, I., Kriston, L., H¨olzel, L.P., H¨arter M., 2012. P-585 − Depression and anxiety in elderly immigrants in Germany − a transcultural analysis. European Psychiatry, 27(Supp1):1.
P.4.b.023 An updated meta-analysis of classical fear conditioning in the anxiety disorders P. Duits1 ° , S. Lissek2 , D.C. Cath1 , J.J.C.M. Hox3 , A.O. Hamm4 , I.M. Engelhard1 , M.A. Van den Hout1 , J.M.P. Baas5 1 Utrecht University, Clinical and Health Psychology, Utrecht, The Netherlands; 2 University of Minnesota, Psychology, Minnesota, USA; 3 Utrecht University, Social Science Methodology, Utrecht, The Netherlands; 4 Greifswald University, Physiological and Clinical Psychology, Greifswald, Germany; 5 Utrecht University, Experimental Psychology, Utrecht, The Netherlands Background: Individual differences in aversive associative learning (i.e., enhanced acquisition and reduced extinction of fear) are thought to play an important role in the development and maintenance of anxiety disorders. These can be measured with fear conditioning paradigms in which a conditioned stimulus (CS+) is paired with an aversive outcome (unconditioned stimulus; US), while another stimulus (CS−) is not paired with the US. Eventually, the CS+ (relative to the CS−) will itself evoke a conditioned fear response in the absence of the US (fear acquisition). The conditioned fear response tends to extinguish after presentation of the CS+ only (fear extinction), which is a process that may be facilitated by the use of pharmacotherapeutic approaches. The aim of the current study was twofold: (1) to systematically examine differences in fear conditioning between anxiety patients and healthy controls using meta-analytic methods, and (2) to examine the extent to which study characteristics may account for the variability in findings across studies. Method: Thirty-five patient–control studies (published between 1920 and 2013) were obtained through Pubmed and Psychinfo, as well as from a previous meta-analysis on fear conditioning [1]. The final data-set represented conditioning scores for 932 patients with anxiety disorders and 1199 healthy controls. All studies used classical fear conditioning paradigms and included psychophysiological (e.g. startle reflex, skin conductance response) and/or subjective outcome measures (e.g. US expectancy ratings, fear ratings). A series of meta-analyses was carried out using Hierarchical Linear Modeling to obtain multivariate multilevel random effects models. Results: During acquisition, robustly increased fear responses to the CS− were demonstrated in anxiety patients compared to controls. This effect may represent an impaired ability to inhibit fear when a CS− is presented and/or may signify a tendency of anxiety disordered patients to generalize fear responses more easily to other previously neutral stimuli. During extinction, enhanced fear responses to the CS+ were found in patients compared to controls, indicating delayed and/or reduced extinction of fear in anxiety patients. Finally, anxiety patients compared to controls tended to show dysfunctional discrimination learning during extinction (p = 0.057), i.e. patients persisted to discriminate between CS+ and CS−, when the CS+ was no longer predicting the aversive outcome. With respect to our second aim, type of US (disorder specific versus non-specific) seems to influence the final outcome. Conclusion: Taken together, the current meta-analysis demonstrates increased fear responses in anxiety patients compared to healthy controls with respect to the CS− during acquisition, as well as increased fear responses to the CS+ during extinction. Further research is needed to investigate the predictive value of fear extinction on treatment outcome, as extinction processes are thought to underlie the beneficial effects of exposure treat-
P.4.b. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (clinical) ment in anxiety disorders [2]. The results of this meta-analysis demonstrate that anxiety disordered patients may indeed benefit from improvements of the extinction process during exposure therapy with pharmacotherapeutic approaches, such as the use of D-cycloserine, a partial agonist of the NMDA receptor that may facilitate fear extinction [3]. References [1] Lissek, S., Powers, A.S., McClure, E.B., Phelps, E.A., Woldehawariat, G., Grillon, C., & Pine, D.S. (2005). Classical fear conditioning in the anxiety disorders: A meta-analysis. Behaviour Research and Therapy, 43(11), 1391–1424. [2] Hofmann, S.G. (2008). Cognitive processes during fear acquisition and extinction in animals and humans: Implications for exposure therapy of anxiety disorders. Clinical Psychology Review, 28(2), 199–210. [3] Davis, M. (2011). NMDA receptors and fear extinction: implications for cognitive behavioral therapy. Dialogues in Clinical Neuroscience, 13(4), 463−74.
P.4.b.024 Too much deliberation? Cautious decision making in obsessive–compulsive disorder P. Banca1 ° , M.D. Vestergaard2 , V. Rankov1 , M. Mitchell1 , M. Irvine1 , T. Lapis1 , M. Castelo-Branco3 , V. Voon1 1 University of Cambridge, Psychiatry, Cambridge, United Kingdom; 2 University of Cambridge, Physiology Development and Neuroscience, Cambridge, United Kingdom; 3 University of Coimbra, Institute for Biomedical Imaging and Life Sciences, Coimbra, Portugal Introduction: Compulsive behaviours are typical symptoms of Obsessive Compulsive Disorder (OCD) that reflect difficulties to commit to ultimate decisions. They may be conceptualized as a means to accumulate sufficient evidence prior to a decision. Here we investigate the process of evidence accumulation in OCD in perceptual discrimination and probabilistic reasoning, hypothesizing impairments in both decision types. Methods: Twenty-eight OCD patients (16F/12M) and 35 healthy control (20F/15M) subjects were tested with a low-level visual perceptual task (random dot motion task), whereby different coherent levels for motion were defined to measure high and low uncertainty, a probabilistic reasoning task (jumping to conclusions task) and two response conflict tasks as control tasks (Flanker task and reinforcement learning conflict task). Logistic regression analysis across all coherence levels (which accounted for visual detection threshold) and hierarchical drift diffusion modeling (HDDM) [1] were used to characterize response strategies between patients with OCD and healthy controls in the random dot motion task. Results: OCD patients compared to healthy volunteers were more cautious in weighing the alternatives and accumulated more evidence particularly to high uncertainty in the visual perceptual but not probabilistic reasoning task: longer reaction time for high uncertainty trials [F(1,59) = 179.7, p < 0.0001] and response time intercept (OCD 2.29 s; HV 1.88 s; t = 2.054, df = 59, p = 0.044). This behaviour was consistent across behavioural and computational approaches and was more evident in patients with higher compulsivity scores. The HDDM analysis further showed higher decision boundaries, or evidence needed to make a decision in high uncertainty (OCD: M = 3.04; SD = 0.036, HV: M = 2.70; SD = 0.028, p < 0.0001) and slower drift rate, reflecting poorer quality of evidence, in low uncertainty in OCD subjects (OCD: M = 1.14; SD = 0.037; HV: M = 1.33; SD = 0.035,
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p = 0.0002) (for explanation of these constructs, see [2]). With a penalty cost for speed, OCD subjects lost the previous effect of uncertainty on reaction time and reversed the difference in decision boundaries (OCD: M = 1.74; SD = 0.041; HV: M = 1.85; SD = 0.051, p = 0.04), accumulating less evidence in low uncertainty trials compared to healthy volunteers, without compromising accuracy. There were no significant differences between groups in the confidence ratings and in the reaction time after receiving positive or negative feedback in the random dots task. There were also no significant differences between groups on accuracy and reaction time measured by the control tasks. Our findings in the perceptual task were unrelated to high-level visual perceptual deficits and response conflict. Conclusions: This study extends the assessment of evidence gathering in OCD from probabilistic to perceptual decisions. We highlight the convergence and divergence of behavioural and computational approaches to evidence accumulation in OCD demonstrating a differential influence of high and low uncertainty contexts on evidence accumulation and on the quality of evidence. We further emphasize that OCD subjects are sensitive to an explicit salient penalty cost on evidence accumulation without compromising accuracy, possibly by influencing internal costbenefit ratios. Finally, our lack of sensitivity to external feedback in OCD subjects highlights the differential role of implicit cost and external feedback in decision formation in OCD. These findings may have relevance for therapeutic approaches. References [1] Wiecki, T.V., Sofer, I., Frank, M.J., 2013 HDDM: Hierarchical Bayesian estimation of the Drift-Diffusion Model in Python. Frontiers in neuroinformatics, 7:14. [2] Ratcliff, R., McKoon, G., 2008 The diffusion decision model: theory and data for two-choice decision tasks. Neural computation 20, 873– 922. Disclosure statement: This work was supported by the Wellcome trust and the Portuguese Foundation for Science and Technology.
P.4.b.025 Association between symptoms of posttraumatic stress disorder and blood pressure in the elderly T.Y. Kim1 ° , H.K. Chung1 , J.H. Choi1 , S.H. Kang1 , T.K. Choi2 , Y.J. Bang1 , H.S. So1 1 VHS Medical Center, Neuropsychiatry, Seoul, South-Korea; 2 CHA University, Neuropsychiatry, Seongnam Kyounggi, South-Korea Posttraumatic stress disorder (PTSD) is a complex, often chronic and debilitating mental disorder that develops in response to traumatic events. Physiological response to victims of the trauma is a part of the DSM definition of PTSD. The common physiological responses include increase in heart rate, blood pressure, tremor and other symptoms to autonomic arousal. Several studies have reported the association between posttraumatic stress disorder and the risk of hypertension. Specific symptoms of PTSD also have been reported to be associated with hypertension. Moreover, use of specific antihypertensive medications (e.g. angiotensin converting enzyme inhibitor, angiotensin receptor blocker) are supposed to be associated with decrease in reexperience and hyperarousal symptoms. The aim of this study was to evaluate the impact of PTSD symptoms on blood pressure in the elderly Korean veterans of the Vietnam War.
P.4.b. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (clinical)
GAD associated disability (SDS-social and family) between two groups. Results: Sociodemographics and clinical characteristics of the groups are compared in Table 1. 51% (24/47) of the Turkish GAD patients and 88.6% (31/35) of the Turkish immigrants with GAD had comorbid major depression. Table 1. GAD patients Turkish (n = 47) Age Sex Education HAM-D HAM-A PSWQ GADSS SDS-social SDS-family
43.6±8.9 F/M:40/7 9±3.8 14.5±5.5 26.6±7 62.9±9.5 14.5±3.1 5.2±2 5.2±1.9
Turkish immigrants (n = 35) 45.1±8 F/M: 27/8 8.9±3.6 24.3±7.1 36.9±7.9 65.6±8.7 17±2.6 7.7±1.1 6.9±1.6
Statistics F or c2
p-value
F = 0.62 c2 = 0.58 F = 0.03 F = 48.68 F = 38.96 F = 1.71 F = 14.29 F = 44.81 F = 18.49
>0.1 >0.1 >0.1 <0.001* <0.001* >0.1 <0.001* <0.001* <0.001*
*p < 0.05.
When HAM-D score was taken as a covariate; GADSS, PSWQ, SDS-family scores were similar in two groups (p > 0.05 for all), only SDS-social life score was found to be higher in Turkish immigrants with GAD (F = 7.952, p = 0.006*). HAM-D X GADSS, HAM-D X PSWQ, HAM-D X SDS-social, HAM-D X SDS-family interactions were all found statistically significant (p < 0.001 for all). Conclusions: The results of the study presented that when depression was controlled, there was no difference in terms of GAD severity between native and immigrant groups. Depression which was much more common in Turkish immigrants had interactions with worry, GAD severity and GAD associated disability. Furthermore, only disability in social life was higher in immigrants with GAD independent of depression. These preliminary results may suggest that lack of social support which also leads to higher depression rates in Turkish immigrants with GAD living in Germany. References [1] Lindert, J., Ehrenstein, O.S., Priebe, S., Mielck, A., Br¨ahler, E., 2009. Depression and anxiety in labor migrants and refugees--a systematic review and meta-analysis. Soc Sci Med 69(2):246–257. [2] Levecque, K., Lodewyckx, I., Vranken, J., 2007. Depression and generalised anxiety in the general population in Belgium: a comparison between native and immigrant groups. J Affect Disord. 97(1−3):229– 239. [3] Bermejo, I., Kriston, L., H¨olzel, L.P., H¨arter M., 2012. P-585 − Depression and anxiety in elderly immigrants in Germany − a transcultural analysis. European Psychiatry, 27(Supp1):1.
P.4.b.023 An updated meta-analysis of classical fear conditioning in the anxiety disorders P. Duits1 ° , S. Lissek2 , D.C. Cath1 , J.J.C.M. Hox3 , A.O. Hamm4 , I.M. Engelhard1 , M.A. Van den Hout1 , J.M.P. Baas5 1 Utrecht University, Clinical and Health Psychology, Utrecht, The Netherlands; 2 University of Minnesota, Psychology, Minnesota, USA; 3 Utrecht University, Social Science Methodology, Utrecht, The Netherlands; 4 Greifswald University, Physiological and Clinical Psychology, Greifswald, Germany; 5 Utrecht University, Experimental Psychology, Utrecht, The Netherlands Background: Individual differences in aversive associative learning (i.e., enhanced acquisition and reduced extinction of fear) are thought to play an important role in the development and maintenance of anxiety disorders. These can be measured with fear conditioning paradigms in which a conditioned stimulus (CS+) is paired with an aversive outcome (unconditioned stimulus; US), while another stimulus (CS−) is not paired with the US. Eventually, the CS+ (relative to the CS−) will itself evoke a conditioned fear response in the absence of the US (fear acquisition). The conditioned fear response tends to extinguish after presentation of the CS+ only (fear extinction), which is a process that may be facilitated by the use of pharmacotherapeutic approaches. The aim of the current study was twofold: (1) to systematically examine differences in fear conditioning between anxiety patients and healthy controls using meta-analytic methods, and (2) to examine the extent to which study characteristics may account for the variability in findings across studies. Method: Thirty-five patient–control studies (published between 1920 and 2013) were obtained through Pubmed and Psychinfo, as well as from a previous meta-analysis on fear conditioning [1]. The final data-set represented conditioning scores for 932 patients with anxiety disorders and 1199 healthy controls. All studies used classical fear conditioning paradigms and included psychophysiological (e.g. startle reflex, skin conductance response) and/or subjective outcome measures (e.g. US expectancy ratings, fear ratings). A series of meta-analyses was carried out using Hierarchical Linear Modeling to obtain multivariate multilevel random effects models. Results: During acquisition, robustly increased fear responses to the CS− were demonstrated in anxiety patients compared to controls. This effect may represent an impaired ability to inhibit fear when a CS− is presented and/or may signify a tendency of anxiety disordered patients to generalize fear responses more easily to other previously neutral stimuli. During extinction, enhanced fear responses to the CS+ were found in patients compared to controls, indicating delayed and/or reduced extinction of fear in anxiety patients. Finally, anxiety patients compared to controls tended to show dysfunctional discrimination learning during extinction (p = 0.057), i.e. patients persisted to discriminate between CS+ and CS−, when the CS+ was no longer predicting the aversive outcome. With respect to our second aim, type of US (disorder specific versus non-specific) seems to influence the final outcome. Conclusion: Taken together, the current meta-analysis demonstrates increased fear responses in anxiety patients compared to healthy controls with respect to the CS− during acquisition, as well as increased fear responses to the CS+ during extinction. Further research is needed to investigate the predictive value of fear extinction on treatment outcome, as extinction processes are thought to underlie the beneficial effects of exposure treat-
P.4.b. Anxiety disorders, OCD, stress related disorders and treatment − Anxiety disorders (clinical) ment in anxiety disorders [2]. The results of this meta-analysis demonstrate that anxiety disordered patients may indeed benefit from improvements of the extinction process during exposure therapy with pharmacotherapeutic approaches, such as the use of D-cycloserine, a partial agonist of the NMDA receptor that may facilitate fear extinction [3]. References [1] Lissek, S., Powers, A.S., McClure, E.B., Phelps, E.A., Woldehawariat, G., Grillon, C., & Pine, D.S. (2005). Classical fear conditioning in the anxiety disorders: A meta-analysis. Behaviour Research and Therapy, 43(11), 1391–1424. [2] Hofmann, S.G. (2008). Cognitive processes during fear acquisition and extinction in animals and humans: Implications for exposure therapy of anxiety disorders. Clinical Psychology Review, 28(2), 199–210. [3] Davis, M. (2011). NMDA receptors and fear extinction: implications for cognitive behavioral therapy. Dialogues in Clinical Neuroscience, 13(4), 463−74.
P.4.b.024 Too much deliberation? Cautious decision making in obsessive–compulsive disorder P. Banca1 ° , M.D. Vestergaard2 , V. Rankov1 , M. Mitchell1 , M. Irvine1 , T. Lapis1 , M. Castelo-Branco3 , V. Voon1 1 University of Cambridge, Psychiatry, Cambridge, United Kingdom; 2 University of Cambridge, Physiology Development and Neuroscience, Cambridge, United Kingdom; 3 University of Coimbra, Institute for Biomedical Imaging and Life Sciences, Coimbra, Portugal Introduction: Compulsive behaviours are typical symptoms of Obsessive Compulsive Disorder (OCD) that reflect difficulties to commit to ultimate decisions. They may be conceptualized as a means to accumulate sufficient evidence prior to a decision. Here we investigate the process of evidence accumulation in OCD in perceptual discrimination and probabilistic reasoning, hypothesizing impairments in both decision types. Methods: Twenty-eight OCD patients (16F/12M) and 35 healthy control (20F/15M) subjects were tested with a low-level visual perceptual task (random dot motion task), whereby different coherent levels for motion were defined to measure high and low uncertainty, a probabilistic reasoning task (jumping to conclusions task) and two response conflict tasks as control tasks (Flanker task and reinforcement learning conflict task). Logistic regression analysis across all coherence levels (which accounted for visual detection threshold) and hierarchical drift diffusion modeling (HDDM) [1] were used to characterize response strategies between patients with OCD and healthy controls in the random dot motion task. Results: OCD patients compared to healthy volunteers were more cautious in weighing the alternatives and accumulated more evidence particularly to high uncertainty in the visual perceptual but not probabilistic reasoning task: longer reaction time for high uncertainty trials [F(1,59) = 179.7, p < 0.0001] and response time intercept (OCD 2.29 s; HV 1.88 s; t = 2.054, df = 59, p = 0.044). This behaviour was consistent across behavioural and computational approaches and was more evident in patients with higher compulsivity scores. The HDDM analysis further showed higher decision boundaries, or evidence needed to make a decision in high uncertainty (OCD: M = 3.04; SD = 0.036, HV: M = 2.70; SD = 0.028, p < 0.0001) and slower drift rate, reflecting poorer quality of evidence, in low uncertainty in OCD subjects (OCD: M = 1.14; SD = 0.037; HV: M = 1.33; SD = 0.035,
S601
p = 0.0002) (for explanation of these constructs, see [2]). With a penalty cost for speed, OCD subjects lost the previous effect of uncertainty on reaction time and reversed the difference in decision boundaries (OCD: M = 1.74; SD = 0.041; HV: M = 1.85; SD = 0.051, p = 0.04), accumulating less evidence in low uncertainty trials compared to healthy volunteers, without compromising accuracy. There were no significant differences between groups in the confidence ratings and in the reaction time after receiving positive or negative feedback in the random dots task. There were also no significant differences between groups on accuracy and reaction time measured by the control tasks. Our findings in the perceptual task were unrelated to high-level visual perceptual deficits and response conflict. Conclusions: This study extends the assessment of evidence gathering in OCD from probabilistic to perceptual decisions. We highlight the convergence and divergence of behavioural and computational approaches to evidence accumulation in OCD demonstrating a differential influence of high and low uncertainty contexts on evidence accumulation and on the quality of evidence. We further emphasize that OCD subjects are sensitive to an explicit salient penalty cost on evidence accumulation without compromising accuracy, possibly by influencing internal costbenefit ratios. Finally, our lack of sensitivity to external feedback in OCD subjects highlights the differential role of implicit cost and external feedback in decision formation in OCD. These findings may have relevance for therapeutic approaches. References [1] Wiecki, T.V., Sofer, I., Frank, M.J., 2013 HDDM: Hierarchical Bayesian estimation of the Drift-Diffusion Model in Python. Frontiers in neuroinformatics, 7:14. [2] Ratcliff, R., McKoon, G., 2008 The diffusion decision model: theory and data for two-choice decision tasks. Neural computation 20, 873– 922. Disclosure statement: This work was supported by the Wellcome trust and the Portuguese Foundation for Science and Technology.
P.4.b.025 Association between symptoms of posttraumatic stress disorder and blood pressure in the elderly T.Y. Kim1 ° , H.K. Chung1 , J.H. Choi1 , S.H. Kang1 , T.K. Choi2 , Y.J. Bang1 , H.S. So1 1 VHS Medical Center, Neuropsychiatry, Seoul, South-Korea; 2 CHA University, Neuropsychiatry, Seongnam Kyounggi, South-Korea Posttraumatic stress disorder (PTSD) is a complex, often chronic and debilitating mental disorder that develops in response to traumatic events. Physiological response to victims of the trauma is a part of the DSM definition of PTSD. The common physiological responses include increase in heart rate, blood pressure, tremor and other symptoms to autonomic arousal. Several studies have reported the association between posttraumatic stress disorder and the risk of hypertension. Specific symptoms of PTSD also have been reported to be associated with hypertension. Moreover, use of specific antihypertensive medications (e.g. angiotensin converting enzyme inhibitor, angiotensin receptor blocker) are supposed to be associated with decrease in reexperience and hyperarousal symptoms. The aim of this study was to evaluate the impact of PTSD symptoms on blood pressure in the elderly Korean veterans of the Vietnam War.