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Depersonalization Experiences in Undergraduates Are Related to Heightened Stress Cortisol Responses Timo Giesbrecht, PhD, Tom Smeets, MSc, Harald Merckelbach, PhD, and Marko Jelicic, PhD vealed clinically highly relevant findings, relatively little is Abstract: The relationship between dissociative tendencies, as mea-
known about the more proximal mechanisms involved in sured with the Dissociative Experiences Scale and its amnesia, absorption/imaginative involvement, and depersonalization/dereal- One line of research that might shed light on proximal ization subscales, and HPA axis functioning was studied in 2 mechanisms involved in dissociation is the one directed at samples of undergraduate students (N ⫽ 58 and 67). Acute stress hypothalamic-pituitary-adrenal (HPA) axis functioning in de- was induced by means of the Trier Social Stress Test. Subjective and personalization disorder (DPD; Simeon et al., 2001; Stanton physiological stress (i.e., cortisol) responses were measured. Indi- et al., 2001). Unfortunately, the 2 studies that investigated the viduals high on the depersonalization/derealization subscale of the matter yielded conflicting results. Stanton et al. (2001) found Dissociative Experiences Scale exhibited more pronounced cortisol a trend toward lower basal cortisol levels of patients with responses, while individuals high on the absorption subscale showed DPD when compared with individuals with major depressive attenuated responses. Interestingly, subjective stress experiences, as disorder. However, the authors acknowledge that HPA axis indicated by the Tension-Anxiety subscale of the Profile of Mood dysfunction "may be more sensitively detected by examining States, were positively related to trait dissociation. The present of the response of the HPA axis to provocation challenge" findings illustrate how various types of dissociation (i.e., deperson- (Stanton et al., 2001, p. 88). In line with this suggestion, alization/derealization, absorption) are differentially related to cor- Simeon et al. (2001) evaluated HPA axis functioning in DPD tisol stress responses.
by means of a low-dose dexamethasone administration.
Key Words: Dissociation, acute stress, cortisol response, Trier
These authors showed that DPD is associated with HPA axis Social Stress Test.
dysregulation. More specifically, DPD was found to be re-lated to diminished negative feedback control of cortisol. The (J Nerv Ment Dis 2007;195: 282–287) authors also found that DPD patients have elevated levels ofplasma cortisol. Interestingly, these findings are in starkcontrast to the dysregulations encountered in individuals Dissociative experiences include subjective phenomena suffering from posttraumatic stress disorder (PTSD). In like derealization, absorption, and memory complaints.
PTSD, such dysregulations are often characterized by In their mild form, such experiences are quite common in the enhanced negative feedback (Stein et al., 1997; Yehuda et normal population (e.g., Ross et al., 1991). Yet, they are particularly pronounced in certain diagnostic categories (e.g., Findings of Simeon et al. (2001) suggest that persistent depersonalization disorder, borderline personality disorder; post- dissociation, and especially the depersonalization component traumatic stress disorder; schizophrenia; see, e.g., Holmes et al., of dissociation, should be associated with diminished nega- 2005; Merckelbach et al., 2005). Although there is an im- tive feedback control of cortisol. Therefore, we expect dis- pressive amount of literature on the topic of dissociation, sociative tendencies to be related to heightened levels of researchers in this domain have primarily focused on the cortisol following a stressor. However, their study did not alleged traumatic etiology of dissociative experiences (see for include a stressor. The goal of the present study was therefore a review, Giesbrecht and Merckelbach, 2005; Kihlstrom, to investigate the relationship between dissociative tenden- 2005). Although research on distal antecedents (i.e., dysfunc- cies and HPA axis functioning in a nonclinical sample under tional family environment) related to dissociation has re- conditions of acute stress. Given that the dissociative symp-toms typical for clinical groups have their low-intensitycounterparts in the general population (Bernstein and Put- Department of Experimental Psychology, Maastricht University, The Neth- nam, 1986; Leonard et al., 1999), we recruited a nonclinical sample. In doing so, we hoped to exclude the confounding This study was supported by a grant from the Netherlands Organization for Scientific Research (to N.W.O., grant number 402-01-088-D).
influence of comorbidity on HPA axis functioning. To induce Send reprint requests to Timo Giesbrecht, PhD, Department of Experimental stress, we exposed undergraduate students to the Trier Social Psychology, Maastricht University, PO Box 616, 6200 MD, Maastricht, Stress Test (TSST; Kirschbaum et al., 1993). With this The Netherlands. E-mail: [email protected].
laboratory task, acute stress can be induced in a reliable way.
Copyright 2007 by Lippincott Williams & Wilkins On the basis of the Simeon et al. (2001) results, we expected higher levels of trait dissociation generally, and the deper- The Journal of Nervous and Mental Disease • Volume 195, Number 4, April 2007


The Journal of Nervous and Mental Disease • Volume 195, Number 4, April 2007 Dissociation and Acute Stress sonalization/derealization subscale of the Dissociative Expe- "annoyed," "angry," and "grumpy" for the subscale Anger- riences Scale (DES) in particular, to go along with heightened Hostility and "nervous," "tensed," and "panicky" for the levels of cortisol following the stressor. The relationship Tension-Anxiety subscale. Total scores for the 2 subscales between the cortisol response and pathological dissociation, were calculated by adding up all item scores. The POMS has as measured by the Dissociative Experiences Scale Taxon excellent psychometric properties (Lezak, 2004; Wald and (Waller et al., 1996), and the other facets of dissociative Mellenberg, 1990).
experiences, notably absorption and amnesia, will also beinvestigated.
Trier Social Stress Test
The TSST (Kirschbaum et al., 1993) combines both social and cognitive stress. It consists of 3 stages, each lasting 5 minutes: a preparation period, a free speech, and a mental arithmetic task. Thus, participants are first told to prepare aspeech for a job interview, which they subsequently have to give. After the speech, a mental arithmetic task is adminis- Participants were 58 undergraduate students enrolled at tered. Every time the participant makes an error, she/he has to Maastricht University. Twenty-nine of them were women.
Their mean age was 19.93 years (SD ⫽ 3.33; range, 17– 41 start over. The participants are aware of the fact that both the years). Participants suffering from cardiovascular diseases, speech and the mental arithmetic task are videotaped and endocrine disorders, or who were taking medication were observed by the experimenter. The participant has to remain excluded from the study. Participants gave written consent standing during these 2 last stages. The TSST is a reliable prior to taking part and were compensated through a small method to induce psychological stress in the laboratory (see amount of money. Participants were asked to refrain from Kirschbaum and Hellhammer, 1994) and was found to pro- eating, drinking, and smoking for at least 1 hour prior to the voke the most pronounced physiological (cortisol) reaction as beginning of the testing session. The study was approved by compared with other stress induction procedures (Dickerson the standing ethical committee of the Faculty of Psychology, and Kemeny, 2004).
Participants were tested individually in our laboratory Dissociative Experiences Scale (Bernstein and Putnam, with the experimenter present. All experimental sessions took 1986, Cronbach's alpha ⫽ 0.92). The DES is a self-report place in the afternoon (between 14:00 and 17:00 hours) to scale asking respondents to indicate on 100 mm Visual- reduce variability in the cortisol response due to fluctuations Analogue Scales to what extent they experience 28 dissocia- of cortisol levels over the day (Kirschbaum and Hellhammer, tive phenomena in daily life. Examples of such phenomena 1994). Participants first completed the DES. Next, prema- include feelings of depersonalization, derealization, and psy- nipulation cortisol levels were sampled and participants com- chogenic amnesia. In their meta-analytic study, van IJzen- pleted the first POMS. Then, participants were exposed to the doorn and Schuengel (1996) provided evidence for the sound TSST (Kirschbaum et al., 1993). Immediately after the TSST, psychometric properties of the DES. A subset of 8 DES items a second cortisol sample was obtained, and the POMS was forms the Dissociative Experiences Scale Taxon (DES-T; readministered. A third and fourth cortisol sample were taken Cronbach's alpha ⫽ 0.67; Waller et al., 1996). This taxon is 20 and 40 minutes after the TSST, respectively (see e.g., thought to be especially sensitive to pathological dissociation.
Smeets et al., in press).
DES-T scores can be obtained by averaging across DES items3, 5, 7, 8, 12, 13, 22, and 27 (e.g., Eisen and Carlson, 1998).
Saliva Sampling and Free Cortisol Analysis
In addition to the DES-T, separate subscale scores Cortisol data were obtained using Salivettes (Sarstedt, were also calculated following the 3-factor solution pro- Nu¨mbrecht, Germany). Salivettes are small cotton swabs on posed by Ross et al. (1995), Sanders and Green (1994), and which participants gently chew for a 1-minute period. Next, Carlson et al. (1991). These were amnesia (Cronbach's the swab is put into a small plastic tube. Immediately upon alpha ⫽ 0.81), absorption and imaginative involvement(Cronbach's alpha ⫽ 0.83), and depersonalization and collection, the uncentrifuged saliva samples were stored at derealization (Cronbach's alpha ⫽ 0.66).
⫺40°C. Salivary-free cortisol levels were determined in du-plicate by direct radioimmunoassay, including a competition Profile of Mood States
reaction between 125iodohistamine-cortisol and anticortisol The Profile of Mood States (POMS; McNair et al., serum made against the 3-CMO-BSA conjugate. Via a con- 1992) is a widely used self-report measure to quantify typical ventional "second antibody" method, separation of free and and persistent mood reactions to current life situations. In the antibody-bound 125iodohistamine9 cortisol was performed present study, subjective stress experiences were assessed after overnight incubation of 100 ␮L saliva at 4°C. To using its Anger-Hostility and Tension-Anxiety subscales.
reduce sources of variability, all 4 samples from an indi- Participants indicate to what extent they agree with adjectives vidual were analyzed in the same assay. Mean intra- and describing their current mood or feelings on 5-point scales interassay coefficients of variation ranged from 4.3% to (anchors: 0 ⫽ not at all, 4 ⫽ extremely). Adjectives include 8.3%, respectively.
2007 Lippincott Williams & Wilkins


Giesbrecht et al. The Journal of Nervous and Mental Disease • Volume 195, Number 4, April 2007 Pearson Product-Moment Correlations Among the Dissociative Experiences Scale (DES), the Dissociative Experiences Scale Taxon Total Score (DES-T), theAmnesia, Absorption, and Depersonalization Subscale of the DES, the Pre- andPostmanipulation Scores on the Anger-Hostility and the Tension Anxiety Scale of theProfile of Mood States (POMS) for an Undergraduate Sample (N ⫽ 58)* *Only relevant correlations are shown.
†Correlation is significant at the 0.05 level (2-tailed).
scores and the DES absorption subscale. This DES subscaleaccounted for 16.97% of the variance.
The mean DES score was 16.6 (SD ⫽ 9.8). This score corresponds to values previously reported for student samples Cortisol responses of 1 participant were identified as (Merckelbach et al., 2002). Mean scores for the DES-T, the outliers and were omitted from all subsequent analyses. Mean amnesia, absorption, and depersonalization/derealization sub- baseline cortisol level was 3.99 nmol/L (SD ⫽ 1.82). Re- scale were 9.1 (SD ⫽ 8.1), 11.8 (SD ⫽ 10.1), 24.1 (SD ⫽ peated measures ANOVA with the 4 measurement times as 13.6), and 7.2 (SD ⫽ 7.5), respectively.
within-subject factor revealed a significant main effect oftime 关F(3,54) ⫽ 11.48, p ⬍ 0.01兴 indicating that our manip- Subjective Stress Experiences
ulation elicited significant physiological stress reactions (i.e., Mean scores on the Anger-Hostility and the Tension- increased cortisol levels) in participants.
Anxiety POMS subscales were 1.0 (SD ⫽ 2.9) and 5.2 (SD ⫽ To quantify the cortisol response, we calculated the 2.5) obtained prior to the TSST and 2.5 (SD ⫽ 3.3) and 9.0 area under the curve with respect to increase (AUC ). This (SD ⫽ 3.0), after the TSST, respectively. Paired samples t parameter was calculated following the recommendations of tests indicated that for both Anger-Hostility and Tension- Pruessner et al. (2003). All correlations between DES and its Anxiety, postmanipulation scores were higher than prema- subscales, and cortisol stress response parameters fell short of nipulation scores 关t(57) ⫽ 3.24, p ⬍ 0.01 and t(57) ⫽ 8.95, significance (r ⬍ 0.10, p ⬎ 0.47). In addition, baseline p ⬍ 0.01, respectively兴. This shows that our TSST manipu- cortisol levels were unrelated to dissociation scores (r ⬍ 0.16, lation was successful in inducing psychological stress.
p ⬎ 0.22).
Table 1 presents Pearson product–moment correlations between DES, DES-T, and the subscales of the DES and the POMS subscales. Dissociation was related neither to thePOMS Anger-Hostility nor to the Tension-Anxiety subscales Our finding that dissociation is not related an attenuated prior to the manipulation (i.e., at baseline). However, disso- cortisol response during acute stress, i.e., TSST, is in sharp ciation correlated positively with the Tension-Anxiety and contrast with the proposed HPA axis dysfunction. However, the Anger-Hostility subscale after the manipulation.
Through stepwise regression, we explored to what extent subjective stress experiences after the TSST, as mea- Summary of Stepwise Multiregressions on the sured by the POMS Anger-Hostility and the Tension-Anxiety POMS Anger-Hostility and Tension-Anxiety Subscale (Study 1; subscales, were predicted by dissociative tendencies (DES and its subscales, DES-T), while controlling for the respec- tive POMS subscale prior to the TSST, age, and gender. Forthe POMS Anger-Hostility subscale, this analysis resulted in POMS Anger-Hostility a model that accounted for 27% (R2) of the variance (Table POMS Anger-Hostility 2). The model included the POMS premanipulation scores and the DES depersonalization/derealization subscale. This DES depersonalization subscale subscale of the DES accounted for 12.53% of the variance.
POMS Tension-Anxiety For the POMS Tension-Anxiety subscale, this analysis re- DES absorption subscale sulted in a model that accounted for 25% (R2) of the variance POMS Tension-Anxiety (Table 2). The model included the POMS premanipulation 2007 Lippincott Williams & Wilkins


The Journal of Nervous and Mental Disease • Volume 195, Number 4, April 2007 Dissociation and Acute Stress due to our relatively small sample size, the aforementioned Pearson Product-Moment Correlations Among null findings have to be interpreted with caution and require the Dissociative Experiences Scale (DES), the Dissociative replication. Therefore, we conducted a second study, which Experiences Scale Taxon Total Score (DES-T), the Amnesia, parallels the procedure of study 1, while employing a modi- Absorption, and Depersonalization Subscale of the DES, fied version of the TSST.
Cortisol Baseline Levels, and Area Under the Curve withRespect to Increase (AUC ) for an Undergraduate Samples (Study 2; N ⫽ 67) A sample of 67 (33 woman) undergraduate students enrolled at Maastricht University participated in our second study. Their mean age was 19.70 years (SD ⫽ 1.76; range: 18 –27 years). After completion of the DES, they all under- went our slightly modified version of the TSST. This time we made the TSST even more stressful. During this TSST, the job interview was replaced by a speech about their personal- ity to make this task more personally relevant. Furthermore, *Only relevant correlations are shown.
the difficulty of the arithmetic task was increased by having †Correlation is significant at the 0.05 level (2-tailed).
participants solve a number of difficult subtractions. Themodified TSST was of the exact same duration as the TSSTduring study 1. Our cortisol sampling procedure closely Summary of the Stepwise Multiple Regression on mirrored the one employed during study 1. Subjective stress the Glucocorticoid Stress Response, as Indexed by the Area experiences were not measured during study 2.
Under the Curve for an Undergraduate Sample (Study 2:N ⫽ 67) Area Under the Curve
The mean DES, DES-T, amnesia, absorption, and de- personalization/derealization subscale scores were 22.3 (SD ⫽ 11.0), 13.2 (SD ⫽ 9.3), 15.0 (SD ⫽ 11.0), 33.1 (SD ⫽ 14.9), DES depersonalization and 11.5 (SD ⫽ 10.7), respectively.
Mean baseline cortisol levels were 7.4 nmol/L (SD ⫽ 5.9). Repeated measures ANOVA with the 4 measurementtimes as within-subject factor revealed a significant main response, while experiences of absorption exhibited a nega- effect 关F(3,64) ⫽ 21.51, p ⬍ 0.01兴, indicating that our manipulation significantly increased cortisol levels.
During study 2, the cortisol responses were quantified in the same way as in study 1. Overall, cortisol responses in The main findings of our 2 studies can be catalogued as study 2, as indexed by the area under the curve with respect follows. The elevated levels of both subjective distress (study to increase, were significantly higher than those in study 1 1) and physiological stress (both studies) showed that we 关t(122) ⫽ 3.01, p ⬍ 0.01兴. Unlike in study 1, the more were effective in inducing acute stress by means of the TSST pathological manifestations of dissociation, notably the procedure used in both studies. Interestingly, individuals high DES-T and the depersonalization/derealization subscale of on dissociation experienced a pronounced increase in sub- the DES, were related to the cortisol stress response, as jective stress as measured with the Tension-Anxiety and the indexed by the area under the curve with respect to increase Anger-Hostility subscale of the POMS. These increases were (Table 3). In addition, the more benign manifestation of mainly carried by individual differences in absorption and dissociation, absorption, was related to lowered baseline depersonalization/derealization, respectively. Our findings cortisol levels.
concerning the cortisol response were less straightforward. In To index the unique influence of the various facets of study 1, dissociation was unrelated to the cortisol stress dissociation on the cortisol stress response, we conducted a response. However, in study 2, which was designed to be forward stepwise multiple regression analyses. In these anal- more stressful than study 1, heightened levels of DES-T and yses, the stress response, as indexed by the area under the the depersonalization/derealization subscale of the DES were curves served as dependent variable, while gender, age, and positively related to the cortisol response. The subsequent baseline cortisol levels were controlled for. Table 4 presents regression analysis implied that this finding was due to the summary of the multiple regressions. The analyses re- individual differences in the frequency of depersonalization/ sulted in a model consisting of baseline cortisol levels, derealization experiences. Moreover, this analysis signifies gender, depersonalization/derealization, and absorption. This that the benign manifestation of dissociation (i.e., absorption) model accounted for 31% (R2) of the variance in the cortisol was negatively related to the cortisol response.
stress response. Interestingly, the depersonalization/dereal- Thus, HPA axis dysregulation is not limited to individ- ization subscale was positively related to the cortisol stress uals suffering from DPD (Simeon et al., 2001) but does also 2007 Lippincott Williams & Wilkins


Giesbrecht et al. The Journal of Nervous and Mental Disease • Volume 195, Number 4, April 2007 occur, albeit in a milder form and under acute stress condi- conducted along these lines might broaden our understanding tions, in healthy individuals who report a high frequency of of the different processes implicated in dissociation. Also our depersonalization/derealization experiences. Interestingly, the samples exhibited rather homogenous (i.e., low) dissociation absorption subscale of the DES exhibited an opposite rela- levels. Therefore, a replication of our findings in clinical tionship with the cortisol response. Thus, while a malign groups exhibiting severe dissociative symptoms would be manifestation of dissociation, i.e., depersonalization/dereal- highly informative, although ethical issues arise when using ization, was found to be related to heightened cortisol re- the TSST in such groups. Second, we focused on the rela- sponses, possibly due to diminished negative HPA axis feed- tionship between dissociative tendencies and HPA axis func- back, absorption appeared to be related to a suppression of tioning. Future research in this area might benefit from cortisol responses. The finding that absorption goes along quantifying acute (i.e., peritraumatic) dissociative responses with a suppression of cortisol responses is in line with that of as a response to acute stress and how it overlaps with Morgan et al. (2004, 2001), who investigated peritraumatic dissociation as a trait. On a related note, 2 studies have dissociation and stress-related hormones in a sample of investigated how peritraumatic dissociation during actual trauma healthy military personnel participating in survival school relates to subsequent physiological reactions to trauma narra- training. Their data suggested that individuals who dissociate tives. Griffin et al. (1997) reported reduced physiological extensively during this extremely stressful experience dampen arousal in female victims of recent rape who experienced their peripheral stress-related physiology during acute stress heightened levels of peritraumatic dissociation. On the con- (see, for similar findings, Koopman et al., 2003).
trary, Nixon et al. (2005) found heightened levels of peritrau- In study 1, we found that dissociative experiences, matic dissociation being related to heightened responsivity in notably their absorption and depersonalization/derealization victims of a motor vehicle accident or physical assault (see, components, are positively correlated with subjective distress for similar results, Giesbrecht et al., in press; Ladwig et al., during acute stress, a finding which replicates the findings of 2002). Thus, both studies yielded conflicting findings. More- Griffin et al. (1997) in their sample of traumatized women.
over, these studies did not investigate dissociation as a trait.
However, this pattern is difficult to reconcile with "the To conclude, we found that individuals with raised ‘shut-down' symptomatology typically characteristic of dis- dissociative levels report more subjective stress. Moreover,the benign manifestation of dissociation (i.e., absorption) was sociative states" (Simeon et al., 2003, p. 93). Thus, the related to decreased cortisol responses, while the malign one, findings of Griffin et al (1997) appear not to be limited to notably depersonalization and derealization, was related to clinical samples, but probably represent a more general ten- increased levels of cortisol. In more general terms, our results dency of high dissociators to experience stressful events as highlight the importance of HPA axis dysregulations in de- more distressing than low dissociators. Germane to this issue personalization and derealization experiences. In keeping is previous research (e.g., Mulder et al., 1998) showing that with recent work (Holmes et al., 2005), they also illustrate dissociation levels are related to current mental disorders in that it is important to differentiate between various types of the general population. Thus, it might also be the case that the dissociation because types might differentially related to link between dissociation and subjective distress during acute stress responses.
stress is not due to dissociation levels per se (i.e., direct), butis mediated by current psychiatric disorders (i.e., indirect).
However, as we did not quantify general psychopathology in study 1, neither possibility can be ruled out.
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Source: http://haraldmerckelbach.nl/artikelen_engels/2007/Depersonalization_Experiences_In_Undergraduates_Are_Related_To.pdf

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Gemeinsame Stellungnahme zur Nutzenbewertung gemäß § 35a SGB V von Projektnummer IQWiG A15-60 IQWiG Bericht Nr. 379 vom 30. März 2016 Vorgangsnummer 2016-01-01-D-207 1. Einleitung 2. Stand des Wissens 3. Dossier und Bewertung von Sacubitril/Valsartan bei symptomatischer chronischer Herzinsuffizienz mit reduzierter Ejektionsfraktion 3.1 Zweckmäßige Vergleichstherapie 3.2 Studien 3.3 Endpunkte 3.4 Übertragbarkeit der Studiendaten auf Deutschland 3.5 Bericht des IQWiG 3.6 Ausmaß des Zusatznutzens

The community-reinforcement approach

Reinforcement Approach William R. Miller, Ph.D., and Robert J. Meyers, M.S., with Susanne Hiller-Sturmhöfel, Ph.D. The community-reinforcement approach (CRA) is an alcoholism treatment approach thataims to achieve abstinence by eliminating positive reinforcement for drinking and enhancingpositive reinforcement for sobriety. CRA integrates several treatment components, includingbuilding the client's motivation to quit drinking, helping the client initiate sobriety, analyzingthe client's drinking pattern, increasing positive reinforcement, learning new copingbehaviors, and involving significant others in the recovery process. These components can beadjusted to the individual client's needs to achieve optimal treatment outcome. In addition,treatment outcome can be influenced by factors such as therapist style and initial treatmentintensity. Several studies have provided evidence for CRA's effectiveness in achievingabstinence. Furthermore, CRA has been successfully integrated with a variety of othertreatment approaches, such as family therapy and motivational interviewing, and has beentested in the treatment of other drug abuse. KEY WORDS: AODU (alcohol and other drug use)treatment method; reinforcement; AOD (alcohol and other drug) abstinence; motivation; AODuse pattern; AODD (alcohol and other drug dependence) recovery; treatment outcome;cessation of AODU; professional client relations; family therapy; motivational interviewing;spouse or significant other; literature review