Publications by authors named "Christoph Mueller-Pfeiffer"

27 Publications

  • Page 1 of 1

Interfering with fear memories by eye movement desensitization and reprocessing.

Int J Psychophysiol 2021 Aug 24;166:9-18. Epub 2021 Apr 24.

Department of Consultation- Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address:

Objective: Pharmacologic and behavioral interventions that block reconsolidation of reactivated fear memory have demonstrated only limited success in modifying stronger and long-standing fear memories. Given the efficacy of Eye Movement Desensitization and Reprocessing (EMDR) in treating PTSD, pursuit eye movements are a promising and novel intervention for studies of human memory reconsolidation. Here, we examined the efficacy of pursuit eye movements in interfering with reconsolidation of conditioned fear memories.

Methods: We conducted a 3-day differential Pavlovian fear conditioning procedure in healthy adults, using videos of biologically prepared stimuli (tarantulas), partly reinforced with electrical shocks while recording skin conductance response (SCR) as a measure of autonomic conditioned responses. Fear conditioning was performed on Day 1. On Day 2, 38 participants were randomized into groups performing pursuit eye movements either immediately after fear memory reactivation, when the fear memory was stable, or 10 min later, when the fear memory was assumed to be more labile. On Day 3, fear memory strength was assessed by SCR to both reactivated and nonreactivated fear memories.

Results: Strong differential conditioning to the spider stimuli were observed during both fear acquisition and fear memory reactivation. Reactivated fear memory conditioned responses of participants performing pursuit eye movements after a 10-min delay were significantly smaller in the reinstatement phase (0.16 μS; 95% CI [0.02, 0.31]).

Conclusions: Pursuit eye movements were effective in reducing fear-conditioned SCR in reinstatement. This result supports the theoretical proposition that EMDR can interfere with reactivated fear memory reconsolidation.
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http://dx.doi.org/10.1016/j.ijpsycho.2021.04.006DOI Listing
August 2021

Increased Reward-Related Activation in the Ventral Striatum During Stress Exposure Associated With Positive Affect in the Daily Life of Young Adults With a Family History of Depression. Preliminary Findings.

Front Psychiatry 2020 18;11:563475. Epub 2021 Jan 18.

Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Being the offspring of a parent with major depression disorder (MDD) is a strong predictor for developing MDD. Blunted striatal responses to reward were identified in individuals with MDD and in asymptomatic individuals with family history of depression (FHD). Stress is a major etiological factor for MDD and was also reported to reduce the striatal responses to reward. The stress-reward interactions in FHD individuals has not been explored yet. Extending neuroimaging results into daily-life experience, self-reported ambulatory measures of positive affect (PA) were shown to be associated with striatal activation during reward processing. A reduction of self-reported PA in daily life is consistently reported in individuals with current MDD. Here, we aimed to test (1) whether increased family risk of depression is associated with blunted neural and self-reported reward responses. (2) the stress-reward interactions at the neural level. We expected a stronger reduction of reward-related striatal activation under stress in FHD individuals compared to HC. (3) the associations between fMRI and daily life self-reported data on reward and stress experiences, with a specific interest in the striatum as a crucial region for reward processing. Participants were 16 asymptomatic young adults with FHD and 16 controls (HC). They performed the Fribourg Reward Task with and without stress induction, using event-related fMRI. We conducted whole-brain analyses comparing the two groups for the main effect of reward (rewarded > not-rewarded) during reward feedback in control (no-stress) and stress conditions. Beta weights extracted from significant activation in this contrast were correlated with self-reported PA and negative affect (NA) assessed over 1 week. Under stress induction, the reward-related activation in the ventral striatum (VS) was higher in the FHD group than in the HC group. Unexpectedly, we did not find significant group differences in the self-reported daily life PA measures. During stress induction, VS reward-related activation correlated positively with PA in both groups and negatively with NA in the HC group. As expected, our results indicate that increased family risk of depression was associated with specific striatum reactivity to reward in a stress condition, and support previous findings that ventral striatal reward-related response is associated with PA. A new unexpected finding is the negative association between NA and reward-related ventral striatal activation in the HC group.
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http://dx.doi.org/10.3389/fpsyt.2020.563475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873952PMC
January 2021

Functional impairment in Posttraumatic Stress Disorder: A systematic review and meta-analysis.

J Psychiatr Res 2021 04 25;136:14-22. Epub 2021 Jan 25.

Department of Consultation-Psychiatry and Psychosomatics, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Posttraumatic Stress Disorder (PTSD) is a serious and debilitating condition often associated with significant impairments in daily functioning. To date, research on the complexity of functional impairment in individuals with PTSD is scarce and only limited. Yet, a quantitative synthesis and comprehensive review of existing evidence is needed to better characterize the magnitude of functional impairment in PTSD in distinct domains. We conducted a systematic literature search including observational studies comparing functioning of individuals with and without PTSD. Random effects meta-analyses were performed for the different functional domains according to the WHO International Classification of Functioning, Disability and Health (ICF). The protocol followed the MOOSE guidelines for systematic reviews. A total of thirty-four studies comprising 14 206 participants were included in the study. Compared to healthy individuals, subjects with PTSD showed significant (ps < 0.001) impairments with large to very large effect sizes (ds > 1) in all domains. Subjects with, compared to without, PTSD showed significant (ps < 0.001) impairments with medium to large effect sizes (ds > 0.5) in the domains General Tasks and Demands, Mobility, Self Care, Domestic Life, Interpersonal Interactions and Relationships, Major Life Areas and Community, Social and Civic Life. Significant impairments with small to medium effect sizes in the same domains were observed comparing PTSD to other mental disorders. In conclusion, PTSD has a significant impact on most areas of daily functioning as conceptualized in the International Classification of Functioning, Disability and Health (ICF) of the WHO. Early detection and targeted treatment of functional deficits is warranted in this patient population.
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http://dx.doi.org/10.1016/j.jpsychires.2021.01.039DOI Listing
April 2021

Striatal reactivity to reward under threat-of-shock and working memory load in adults at increased familial risk for major depression: A preliminary study.

Neuroimage Clin 2020 22;26:102193. Epub 2020 Jan 22.

IReach Lab, Unit of Clinical and Health Psychology, Department of Psychology, University of Fribourg, Fribourg, Switzerland.

Introduction: Anhedonia, a core symptom of Major Depressive Disorder (MDD), manifests as a lack or loss of motivation as reflected by decreased reward responsiveness, at both behavioral and neural (i.e., striatum) levels. Exposure to stressful life events is another important risk factor for MDD. However, the mechanisms linking reward-deficit and stress to MDD remain poorly understood. Here, we explore whether the effects of stress exposure on reward processing might differentiate between Healthy Vulnerable adults (HVul, i.e., positive familial MDD) from Healthy Controls (HCon). Furthermore, the well-described reduction in cognitive resources in MDD might facilitate the stress-induced decrease in reward responsiveness in HVul individuals. Accordingly, this study includes a manipulation of cognitive resources to address the latter possibility.

Methods: 16 HVul (12 females) and 16 gender- and age-matched HCon completed an fMRI study, during which they performed a working memory reward task. Three factors were manipulated: reward (reward, no-reward), cognitive resources (working memory at low and high load), and stress level (no-shock, unpredictable threat-of-shock). Only the reward anticipation phase was analyzed. Imaging analyses focused on striatal function.

Results: Compared to HCon, HVul showed lower activation in the caudate nucleus across all conditions. The HVul group also exhibited lower stress-related activation in the nucleus accumbens, but only in the low working memory (WM) load condition. Moreover, while stress potentiated putamen reactivity to reward cues in HVul when the task was more demanding (high WM load), stress blunted putamen reactivity in both groups when no reward was at stake.

Conclusion: Findings suggest that HVul might be at increased risk of developing anhedonic symptoms due to weaker encoding of reward value, higher difficulty to engage in goal-oriented behaviors and increased sensitivity to negative feedback, particularly in stressful contexts. These findings open new avenues for a better understanding of the mechanisms underlying how the complex interaction between the systems of stress and reward responsiveness contribute to the vulnerability to MDD, and how cognitive resources might modulate this interaction.
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http://dx.doi.org/10.1016/j.nicl.2020.102193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011085PMC
March 2021

Behavioral Responses to Uncertainty in Weight-Restored Anorexia Nervosa - Preliminary Results.

Front Psychol 2019 5;10:2492. Epub 2019 Nov 5.

Unit of Clinical and Health Psychology, University of Fribourg, Fribourg, Switzerland.

Impaired decision-making under conditions of uncertainty seems to contribute to the expression and maintenance of anorexia nervosa (AN), but it is not clear whether this impairment is a disease state that would remit with treatment, or a persisting trait in patients with AN. To examine this question, a longitudinal study was conducted in 12 female inpatients with AN (age = 22.2, SE = 1.36), before (Time-1) and after reaching a body mass index of >17.5 kg/m (Time-2). Intolerance of uncertainty (IU) was assessed via a decision-making task, the wheel of fortune (WOF). Weight gain at Time-2 was accompanied with significant changes in uncertainty-related performance compared to Time-1 [(Time × Uncertainty), < 0.05]. At Time-1, reaction times (RTs) varied in function of uncertainty, while at Time-2, uncertainty did not modulate RTs. These findings support a change in decision-making under uncertainty with successful weight-rehabilitation in AN. While IU was present in underweight patients, it became non-significant after weight restoration.
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http://dx.doi.org/10.3389/fpsyg.2019.02492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848854PMC
November 2019

Striatal responsiveness to reward under threat-of-shock and working memory load: A preliminary study.

Brain Behav 2019 10 26;9(10):e01397. Epub 2019 Sep 26.

IReach Lab, Unit of Clinical and Health Psychology, Department of Psychology, University of Fribourg, Fribourg, Switzerland.

Introduction: Reward and stress are important determinants of motivated behaviors. Striatal regions play a crucial role in both motivation and hedonic processes. So far, little is known on how cognitive effort interacts with stress to modulate reward processes. This study examines how cognitive effort (load) interacts with an unpredictable acute stressor (threat-of-shock) to modulate motivational and hedonic processes in healthy adults.

Materials And Methods: A reward task, involving stress with unpredictable mild electric shocks, was conducted in 23 healthy adults aged 20-37 (mean age: 24.7 ± 0.9; 14 females) during functional magnetic resonance imaging (fMRI). Manipulation included the use of (a) monetary reward for reinforcement, (b) threat-of-shock as the stressor, and (c) a spatial working memory task with two levels of difficulty (low and high load) for cognitive load. Reward-related activation was investigated in a priori three regions of interest, the nucleus accumbens (NAcc), caudate nucleus, and putamen.

Results: During anticipation, threat-of-shock or cognitive load did not affect striatal responsiveness to reward. Anticipated reward increased activation in the ventral and dorsal striatum. During feedback delivery, both threat-of-shock and cognitive effort modulated striatal activation. Higher working memory load blunted NAcc responsiveness to reward delivery, while stress strengthened caudate nucleus reactivity regardless reinforcement or load.

Conclusions: These findings provide initial evidence that both stress and cognitive load modulate striatal responsiveness during feedback delivery but not during anticipation in healthy adults. Of clinical importance, sustained stress exposure might go along with dysregulated arousal, increasing therefore the risk for the development of maladaptive incentive-triggered motivation. This study brings new insight that might help to build a framework to understand common stress-related disorders, given that these psychiatric disorders involve disturbances of the reward system, cognitive deficits, and abnormal stress reactivity.
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http://dx.doi.org/10.1002/brb3.1397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790302PMC
October 2019

Psychiatric Symptom Profiles Predict Functional Impairment.

Front Psychiatry 2019 13;10:37. Epub 2019 Feb 13.

Department of Consultation-Liaison-Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Mental illness often interferes with daily functioning and an individual's pattern of psychiatric signs and symptoms may predict risk of future disability. Understanding the linkage between psychiatric symptoms and impaired functioning is critical for accurate rehabilitation planning and legal assessment. Here, we investigated the stability of functional impairment measures over 18 months and their association with psychiatric symptoms. Moreover, we developed a clinical self-report measure that allows estimation of functional impairment levels over 18 month observation periods. Consecutively treated outpatients and daycare patients ( = 155) from several psychiatric units in Switzerland completed the Dissociative Experiences Scale, Somatoform Dissociation Questionnaire, Multidimensional Inventory for Dissociation, Beck Depression Inventory, Brief Symptom Inventory, and WHO Disability Assessment Schedule at baseline, 6, 12, and 18 month follow-up examinations. The association between symptoms functional impairment over time was investigated using longitudinal linear mixed models. Penalized regression was used to identify questionnaire items that best predicted functional impairment. We found high stability in the extent of functional impairment over 18 months. Fear of negative evaluation, fatigue, concentration problems, negative alterations in mood, and dissociative symptoms showed the strongest association with functional impairment measures. The empirically derived scale for functional impairment prediction explained between 0.62 and 0.77 of the variance in disability across various life domains. Given the capability for somatic and mental symptoms associated with social anxiety, depression, and dissociation to predict future disability, these symptoms have strong potential for guiding rehabilitation planning and prognostic evaluation in insurance medicine. The Functional Impairment Prediction Scale may serve as a valuable, empirical-based extension in legal assessments of how work capacity is affected by psychological factors.
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http://dx.doi.org/10.3389/fpsyt.2019.00037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396718PMC
February 2019

Impaired Recognition of Positive Emotions in Individuals with Posttraumatic Stress Disorder, Cumulative Traumatic Exposure, and Dissociation.

Psychother Psychosom 2018 1;87(2):118-120. Epub 2018 Mar 1.

Department of Psychiatry and Psychotherapy, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

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http://dx.doi.org/10.1159/000486342DOI Listing
October 2018

Locus Coeruleus Activity Mediates Hyperresponsiveness in Posttraumatic Stress Disorder.

Biol Psychiatry 2018 02 7;83(3):254-262. Epub 2017 Sep 7.

Department of Psychiatry and Psychotherapy, University Hospital Zurich, University of Zurich, Zurich, Switzerland. Electronic address:

Background: Patients with posttraumatic stress disorder (PTSD) are hyperresponsive to unexpected or potentially threatening environmental stimuli. Research in lower animals and humans suggests that sensitization of the locus coeruleus-norepinephrine system may underlie behavioral and autonomic hyperresponsiveness in PTSD. However, direct evidence linking locus coeruleus system hyperactivity to PTSD hyperresponsiveness is sparse.

Methods: Psychophysiological recording and functional magnetic resonance imaging were used during passive listening to brief, 95-dB sound pressure level, white noise bursts presented intermittently to determine whether behavioral and autonomic hyperresponsiveness to sudden sounds in PTSD is associated with locus coeruleus hyperresponsiveness.

Results: Participants with PTSD (n = 28) showed more eye-blink reflexes and larger heart rate, skin conductance, and pupil area responses to loud sounds (multivariate p = .007) compared with trauma-exposed participants without PTSD (n = 26). PTSD participants exhibited larger responses in locus coeruleus (t = 2.60, region of interest familywise error corrected), intraparietal sulcus, caudal dorsal premotor cortex, and cerebellar lobule VI (t ≥ 4.18, whole-brain familywise error corrected). Caudal dorsal premotor cortex activity was associated with both psychophysiological response magnitude and levels of exaggerated startle responses in daily life in PTSD participants (t ≥ 4.39, whole-brain familywise error corrected).

Conclusions: Behavioral and autonomic hyperresponsiveness in PTSD may arise from a hyperactive alerting/orienting system in which processes related to attention and motor preparation localized to lateral premotor cortex, intraparietal sulcus, and posterior superior cerebellar cortex are modulated by atypically high phasic noradrenergic influences originating in the locus coeruleus.
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http://dx.doi.org/10.1016/j.biopsych.2017.08.021DOI Listing
February 2018

How fat will it make me? Estimation of weight gain in anorexia nervosa.

Appetite 2017 07 6;114:368-373. Epub 2017 Apr 6.

Unit of Clinical and Health Psychology, Department of Psychology, University of Fribourg, Switzerland.

This study investigates the subjective estimation of weight gain in patients with anorexia nervosa (AN) when being confronted with food cues both in a general (self-unrelated) and in an intent-to-eat (self-related) condition. Looking at the presentation of different snack pictures with different nutrition values (high-low calories), AN patients (N = 24) and age-matched healthy women (N = 27) estimated the weight gain when they imagined eating the presented portions of snack pictures once a day in addition to the normal daily nutrition in the following two conditions: 1) a general condition without specific additional instruction, 2) an intent-to-eat condition, in which they were instructed to imagine that they would eat the snack themselves. Compared to healthy women, patients with AN estimated a higher weight gain only in the intent-to-eat condition, i.e. when they imagined eating the snacks themselves, but not in the general, not self-related condition. In the patient group, mean estimations of weight gain were associated with the "drive for thinness". This study suggests cognitive abnormalities related to the effects of food intake on the weight gain in AN, and that these cognitive anomalies could be related to the fear of gaining weight, one central symptom of AN. It appears that the self-reflective disturbed cognition, rather than the general cognition, could be the main driver underlying anorexia and that the overestimation of the energetic content of food is related to the drive for thinness.
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http://dx.doi.org/10.1016/j.appet.2017.04.002DOI Listing
July 2017

Altered Pain Perception and Fear-Learning Deficits in Subjects With Posttraumatic Stress Disorder.

J Pain 2016 12 15;17(12):1325-1333. Epub 2016 Sep 15.

University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.

There is growing evidence that fear-learning abnormalities are involved in the development of posttraumatic stress disorder (PTSD) and chronic pain. More than 50% of PTSD patients suffer from chronic pain. This study aimed to examine the role of fear-learning deficits in the link between pain perception and PTSD. We included 19 subjects with PTSD and 21 age- and sex-matched healthy control subjects in a fear-conditioning experiment. The conditioned stimulus (CS) consisted of visual signs flashed upon a screen in front of each subject. The unconditioned stimulus was either a low or high temperature impulse delivered through a thermal contact thermode on the subjects' hand. A designation of 'CS-' was assigned to CS always followed by nonpainful low-temperature stimuli; a designation of 'CS+' was given to CS that were randomly followed by either a low or a more painful high temperature. Skin conductance was used as a physiological marker of fear. In healthy control subjects, CS+ induced more fear than CS-, and a low-temperature stimulus induced less subjective pain after CS- than after CS+. PTSD subjects failed to demonstrate such adaptive conditioning. Fear ratings after CS presentation were significantly higher in the PTSD group than in the control group. There were significant interaction effects between group and the type of CS on fear and pain ratings. Fear-learning deficits are a potentially promising, specific psychopathological factor in altered pain perception associated with PTSD. Deficits in safety learning may increase fear and, consequently, pain sensations. These findings may contribute to elucidating the pathogenesis behind the highly prevalent comorbidity that exists between PTSD and pain disorders, and to developing new treatments.

Perspective: This study provides new insights into the pathogenesis of chronic pain in patients with PTSD. The findings may help to develop new treatment strategies for this highly prevalent comorbidity in PTSD.
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http://dx.doi.org/10.1016/j.jpain.2016.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5580085PMC
December 2016

Effects of Posture and Stimulus Spectral Composition on Peripheral Physiological Responses to Loud Sounds.

PLoS One 2016 1;11(9):e0161237. Epub 2016 Sep 1.

Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland.

In the "loud-tone" procedure, a series of brief, loud, pure-tone stimuli are presented in a task-free situation. It is an established paradigm for measuring autonomic sensitization in posttraumatic stress disorder (PTSD). Successful use of this procedure during fMRI requires elicitation of brain responses that have sufficient signal-noise ratios when recorded in a supine, rather than sitting, position. We investigated the modulating effects of posture and stimulus spectral composition on peripheral psychophysiological responses to loud sounds. Healthy subjects (N = 24) weekly engaged in a loud-tone-like procedure that presented 500 msec, 95 dB sound pressure level, pure-tone or white-noise stimuli, either while sitting or supine and while peripheral physiological responses were recorded. Heart rate, skin conductance, and eye blink electromyographic responses were larger to white-noise than pure-tone stimuli (p's < 0.001, generalized eta squared 0.073-0.076). Psychophysiological responses to the stimuli were similar in the sitting and supine position (p's ≥ 0.082). Presenting white noise, rather than pure-tone, stimuli may improve the detection sensitivity of the neural concomitants of heightened autonomic responses by generating larger responses. Recording in the supine position appears to have little or no impact on psychophysiological response magnitudes to the auditory stimuli.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161237PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008836PMC
August 2017

Delayed extinction fails to reduce skin conductance reactivity to fear-conditioned stimuli.

Psychophysiology 2016 09 17;53(9):1343-51. Epub 2016 Jun 17.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

A brief 10-min time delay between an initial and subsequent exposure to extinction trials has been found to impair memory reconsolidation in fear-conditioned rodents and humans, providing a potential means to reduce fearfulness in anxiety disorders and posttraumatic stress disorder (PTSD). The present study used videos of biologically prepared, conditioned stimuli (tarantulas) to test the efficacy of delayed extinction in blocking reconsolidation of conditioned fear in healthy young adults. Strong differential conditioning, measured by skin conductance, was observed among a screened subset of participants during acquisition. However, the delayed-extinction intervention failed to reduce reactivity to the conditioned stimulus paired with the extinction delay. These results are partially consistent with other recent, mixed findings and point to a need for testing other candidate interventions designed to interfere with the reconsolidation process.
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http://dx.doi.org/10.1111/psyp.12687DOI Listing
September 2016

Discriminative evaluative conditioning in the long-term after severe accidental injury.

Psychiatry Res 2016 06 14;240:144-150. Epub 2016 Apr 14.

Department of Psychology, Division of Clinical and Health Psychology, University Fribourg, Switzerland.

Impairments in classical fear conditioning and deficits in discriminative learning are observed in posttraumatic stress disorder (PTSD). However, it is unknown whether similar impairments can be found with types of discriminative learning other than classical conditioning, such as evaluative conditioning (EC), in which the valence of a stimulus can be transferred to other stimuli. In this study, we investigated whether EC is also influenced by traumatic experiences independently of presence of PTSD. We tested 14 accident survivors with remitted PTSD, 14 survivors without PTSD, and 16 non-trauma controls. We used behavioral measures, psychophysiological indicators, and subjective ratings for tasks. General effects of learning were observed across groups and conditioning/extinction. Trauma controls had slower reaction times (RTs) to the aversive conditioned stimulus compared to appetitive conditioned and neutral stimuli, as well as slower RTs and increased accuracy during conditioning than during extinction. Remitted PTSD participants showed opposite results, demonstrating decreased accuracy and slower RTs during conditioning as compared to during extinction. No discriminative effect was found in the non-trauma controls and the remitted PTSD participants. These results suggest that a traumatic experience influences EC, and that this influence differs between individuals who have and have not developed PTSD after traumatic exposure.
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http://dx.doi.org/10.1016/j.psychres.2016.04.022DOI Listing
June 2016

Blunted responses to reward in remitted post-traumatic stress disorder.

Brain Behav 2015 Aug 11;5(8):e00357. Epub 2015 Jun 11.

Division of Clinical and Health Psychology, Department of Psychology, University of Fribourg Fribourg, Switzerland.

Background: Recent evidence suggests blunted responses to rewarding stimuli in patients with post-traumatic stress disorder (PTSD). However, it is not clear whether these alterations in reward processing normalize in remitted PTSD patients.

Methods: We tested behavioral and physiological responses to monetary reward in a spatial memory task in 13 accident survivors with remitted PTSD, 14 accident survivors who never had PTSD, and 16 nontrauma-exposed subjects. All accident survivors were recruited from two samples of severely physically injured patients, who had participated in previous prospective studies on the incidence of PTSD after accidental injury approximately 10 years ago. Reaction time, accuracy, skin conductance responses, and self-reported mood were assessed during the task.

Results: Accident survivors who never had PTSD and nontrauma exposed controls reported significantly higher positive mood in the reinforced versus nonreinforced condition (P < 0.045 and P < 0.001, respectively), while there was no effect of reinforcement in remitted PTSD subjects.

Conclusions: Our findings suggest an alteration of the reward system in remitted PTSD. Further research is needed to investigate whether altered reward processing is a residual characteristic in PTSD after remission of symptoms or, alternatively, a preexisting risk factor for the development of PTSD after a traumatic event.
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http://dx.doi.org/10.1002/brb3.357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559020PMC
August 2015

Testing the "Sexually Abused-Abuser Hypothesis" in Adolescents: A Population-Based Study.

Arch Sex Behav 2015 Nov 16;44(8):2189-99. Epub 2015 May 16.

Institute of Social and Preventive Medicine, University of Zurich, Zurich, Switzerland.

A long-standing belief in the literature on sex offenders is that sexually victimized youths are at increased risk of becoming sex offenders themselves. The present study tested the link between past sexual abuse, either with or without contact, and sexually offending behavior in a representative sample of male and female adolescents while controlling for other types of abuse, mental health problems, substance use, and non-sexual violent behaviors. Self-reported data were collected from a nationally representative sample of 6,628 students attending 9th grade public school in Switzerland (3,434 males, 3,194 females, mean age = 15.50 years, SD = 0.66 years). Exposure to contact and non-contact types of sexual abuse was assessed using the Child Sexual Abuse Questionnaire and sexually offending behavior by the presence of any of three behaviors indicating sexual coercion. Two-hundred-forty-five males (7.1 %) and 40 females (1.2 %) reported having sexually coerced another person. After controlling for non-sexual abuse, low parent education, urban versus rural living, mental health problems, substance use, and non-sexual violent behavior, male adolescents who were victims of contact sexual abuse and non-contact sexual abuse were significantly more likely to report coercive sexual behaviors. Females who experienced contact or non-contact sexual abuse were also found at increased risk of committing sexual coercion after controlling for covariates. The present findings demonstrate a strong relationship between past sexual abuse, with and without physical contact, and sexual-offending behavior in male and female adolescents. Reducing exposure to non-contact sexual abuse (like Internet-based sexual exploitation) should become a new area of sexual violence prevention in youths.
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http://dx.doi.org/10.1007/s10508-014-0440-xDOI Listing
November 2015

Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: preliminary findings.

Psychiatry Res 2014 Dec 28;224(3):288-95. Epub 2014 Sep 28.

Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; Center of Education and Research (COEUR), Psychiatric Services of the County of St. Gallen-North, Wil, Switzerland.

Although posttraumatic stress disorder (PTSD) is associated with a variety of structural and functional brain changes, the molecular pathophysiological mechanisms underlying these macroscopic alterations are unknown. Recent studies support the existence of an altered excitation-inhibition balance in PTSD. Further, there is preliminary evidence from blood-sample studies suggesting heightened oxidative stress in PTSD, potentially leading to neural damage through excessive brain levels of free radicals. In this study we investigated PTSD (n=12) and non-PTSD participants (n=17) using single-voxel proton magnetic resonance spectroscopy (MRS) in dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). We found significantly higher levels of γ-amino butyric acid (GABA) (a primary inhibitory neurotransmitter) and glutathione (a marker for neuronal oxidative stress) in PTSD participants. Atypically high prefrontal inhibition as well as oxidative stress may be involved in the pathogenesis of PTSD.
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http://dx.doi.org/10.1016/j.pscychresns.2014.09.007DOI Listing
December 2014

Prereactivation propranolol fails to reduce skin conductance reactivity to prepared fear-conditioned stimuli.

Psychophysiology 2015 Mar 16;52(3):407-15. Epub 2014 Sep 16.

Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Pharmacologic blockade of memory reconsolidation has been demonstrated in fear-conditioned rodents and humans and may provide a means to reduce fearfulness in anxiety disorders and posttraumatic stress disorder. Studying the efficacy of potential interventions in clinical populations is challenging, creating a need for paradigms within which candidate reconsolidation-blocking interventions can be readily tested. We used videos of biologically prepared conditioned stimuli (tarantulas) to test the efficacy of propranolol in blocking reconsolidation of conditioned fear in healthy young adults. Strong differential conditioning, measured by skin conductance, was observed among a screened subset of participants during acquisition. However, subsequent propranolol failed to reduce reactivity to the reactivated conditioned stimulus. These results are consistent with other recent findings and point to a need for testing other candidate drugs.
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http://dx.doi.org/10.1111/psyp.12326DOI Listing
March 2015

Atypical visual processing in posttraumatic stress disorder.

Neuroimage Clin 2013 29;3:531-8. Epub 2013 Aug 29.

Psychiatric University Hospital, University of Bern, Bern, Switzerland.

Background: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies.

Method: Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task.

Results: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures.

Conclusions: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits, whose origins may be related to dysfunctional attention processes.
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http://dx.doi.org/10.1016/j.nicl.2013.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871398PMC
December 2013

Cortical and cerebellar modulation of autonomic responses to loud sounds.

Psychophysiology 2014 Jan 9;51(1):60-9. Epub 2013 Sep 9.

Department of Psychiatry and Psychotherapy, University Hospital Zurich, Zurich, Switzerland; Center of Education and Research (COEUR), Psychiatric Services of the County of St. Gallen-North, Wil, Switzerland; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Detecting unexpected environmental change causes modulation of autonomic activity essential for survival. Understanding the neural mechanisms associated with responses to loud sounds may provide insights into the pathophysiology of posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit heightened autonomic responses to unexpected loud sounds. We combined fMRI with autonomic psychophysiological assessment to investigate central and peripheral reactivity to loud tones in 20 healthy participants. Activity in anterior insula, pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated with both tones and concomitant skin conductance responses. Since regions signaling unexpected external events modulate autonomic activity, heightened loud tone autonomic responses in PTSD may reflect sensitization of this "salience" network.
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http://dx.doi.org/10.1111/psyp.12142DOI Listing
January 2014

Startle reactivity in the long-term after severe accidental injury: preliminary data.

Psychiatry Res 2013 Dec 17;210(2):570-4. Epub 2013 Jul 17.

Department of Psychiatry and Psychotherapy, University Hospital Zurich, Switzerland. Electronic address:

An exaggerated startle response is one of the core hyperarousal symptoms of posttraumatic stress disorder (PTSD). Heightened startle eye-blink magnitude and reduced habituation of this response in PTSD patients have been reported in several studies. However, it is unclear whether this is an enduring characteristic of individuals vulnerable for PTSD or to which degree trauma-exposed individuals who do not develop PTSD also show exaggerated startle. Thirteen accident survivors with remitted PTSD, 12 trauma controls, and 16 non-trauma controls were examined. Four measures of startle reactivity were analyzed in response to 15 bursts of white noise (95 dB, 50 ms): eye-blink magnitude, eye-blink onset latency, skin conductance response, and heart rate response. The eye-blink reflex was measured over the left musculus orbicularis oculi. Reactivity and habituation were analyzed using linear mixed models. Remitted PTSD subjects did not differ from non-trauma controls regarding any of the startle reactivity or habituation measures. Unexpectedly, trauma controls showed larger eye-blink magnitude than non-trauma controls. These results suggest that the exaggerated startle response disappears after remission from PTSD. Further, they suggest that psychologically resilient trauma survivors might show a PTSD-like pattern of exaggerated physiological startle even many years after a traumatic event.
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http://dx.doi.org/10.1016/j.psychres.2013.06.034DOI Listing
December 2013

Characteristics of child maltreatment and their relation to dissociation, posttraumatic stress symptoms, and depression in adult psychiatric patients.

J Nerv Ment Dis 2013 Jun;201(6):471-7

Department of Psychiatry and Psychotherapy, University Hospital, Zurich, Switzerland.

Little is known about the influence of particular characteristics of childhood maltreatment, such as developmental stage, relationship to the perpetrator, and nature of the trauma, on adult psychopathology. The effects of childhood maltreatment were assessed in adult psychiatric patients (N = 287) using self-rating scales and diagnostic checklists. Maltreatment was strongly associated with dissociation. This relationship was observed for all childhood developmental stages and was strongest when the perpetrator was outside the family. Dissociation was more strongly correlated with childhood emotional abuse and sexual harassment than with sexual or physical abuse. Childhood sexual abuse was found to be associated with symptoms of posttraumatic stress. The findings suggest that dissociation is a relatively specific consequence of childhood maltreatment that is largely independent of the familial relationship to the perpetrator or the child's developmental stage.
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http://dx.doi.org/10.1097/NMD.0b013e3182948096DOI Listing
June 2013

How much should I eat? Estimation of meal portions in anorexia nervosa.

Appetite 2013 Apr 28;63:42-7. Epub 2012 Dec 28.

Department of Psychiatry and Psychotherapy, University Hospital of Zurich, Zurich, Switzerland.

Pathological concern regarding one's weight and weight gain is a crucial feature of anorexia nervosa. Consequently, anorexia nervosa patients often claim that they are uncertain regarding the amount of food they should eat. The present study investigated whether individuals with anorexia nervosa show an altered estimation of meal portion sizes and whether this estimation is modulated by an intent-to-eat instruction (where patients are asked to imagine having to eat the presented meal), meal type and meal portion size. Twenty-four women with anorexia nervosa and 27 healthy women estimated, using a visual analogue scale, the size of six different portions of three different meals, with and without intent-to-eat instructions. Subjects with anorexia nervosa estimated the size of small and medium meal portions (but not large meal servings) as being significantly larger, compared to estimates of healthy controls. The overestimation of small meal portions by anorexia nervosa subjects was significantly greater in the intent-to-eat, compared to general, condition. These findings suggest that disturbed perceptions associated with anorexia nervosa not only include interoceptive awareness (i.e., body weight and shape), but also extend to external disorder-related objects such as meal portion size. Specific therapeutic interventions, such as training regarding meal portion evaluation, could address these difficulties.
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http://dx.doi.org/10.1016/j.appet.2012.12.016DOI Listing
April 2013

Global functioning and disability in dissociative disorders.

Psychiatry Res 2012 Dec 10;200(2-3):475-81. Epub 2012 May 10.

Department of Psychiatry and Psychotherapy, University Hospital of Zurich, Culmannstrasse 8, 8091 Zurich, Switzerland.

Dissociative disorders are frequent comorbid conditions of other mental disorders. Yet, there is controversy about their clinical relevance, and little systematic research has been done on how they influence global functioning. Outpatients and day care patients (N=160) of several psychiatric units in Switzerland were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Axis I Disorders, Structured Clinical Interview for DSM-IV Dissociative Disorders, Global Assessment of Functioning Scale, and World Health Organization Disability Assessment Schedule-II. The association between subjects with a dissociative disorder (N=30) and functional impairment after accounting for non-dissociative axis I disorders was evaluated by linear regression models. We found a proportion of 18.8% dissociative disorders (dissociative amnesia=0%, dissociative fugue=0.6%, depersonalization disorder=4.4%, dissociative identity disorder=7.5%, dissociative disorder-not-otherwise-specified=6.3%) across treatment settings. Adjusted for other axis I disorders, subjects with a comorbid dissociative identity disorder or dissociative disorder-not-otherwise-specified had a median global assessment of functioning score that was 0.86 and 0.88 times, respectively, the score of subjects without a comorbid dissociative disorder. These findings support the hypothesis that complex dissociative disorders, i.e., dissociative identity disorder and dissociative disorder-not-otherwise-specified, contribute to functional impairment above and beyond the impact of co-existing non-dissociative axis I disorders, and that they qualify as "serious mental illness".
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http://dx.doi.org/10.1016/j.psychres.2012.04.028DOI Listing
December 2012

The validity and reliability of the German version of the Somatoform Dissociation Questionnaire (SDQ-20).

J Trauma Dissociation 2010 ;11(3):337-57

Clinic for Psychiatry and Psychotherapy, University Hospital, Zurich, Switzerland.

The present study investigated the validity of the German version of the Somatoform Dissociation Questionnaire (SDQ-20), a scale designed to measure somatoform dissociative symptoms. Somatoform dissociation involves physical manifestations of a dissociation of the personality and is considered a unique entity in the phenomenological spectrum of dissociation. The validity and reliability of the German version of the SDQ-20 was examined using a sample of 225 patients with (n = 39) and without dissociative disorders who were recruited from several in- and outpatient psychiatric clinics. Patients were assessed using structured diagnostic interviews; diagnostic checklists; and self-rating scales for dissociation, and posttraumatic stress. Patients with dissociative disorders reported significantly more (p < .001) somatoform dissociative symptoms than patients without dissociative disorders (criterion validity). Significant correlations (p < .001) were found between scores of somatoform dissociation, psychoform dissociation, posttraumatic stress symptoms, and traumatic childhood experiences (construct validity). Reliability was corroborated by a Cronbach's alpha coefficient of .91 and a test-retest correlation of .89. A component factor analysis suggested unidimensionality of the SDQ-20. In conclusion, the psychometric properties and cross-cultural validity of the German version of the SDQ-20 are excellent. Our results form the basis for the further study of somatoform dissociation in German-speaking populations.
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http://dx.doi.org/10.1080/15299731003793450DOI Listing
October 2010

Impact of alexithymia on treatment outcome: a naturalistic study of short-term cognitive-behavioral group therapy for panic disorder.

Psychopathology 2010 27;43(3):170-9. Epub 2010 Feb 27.

Department of Psychiatry, University Hospital of Zürich, Switzerland.

Background: It is often suggested in the literature that alexithymic patients are less responsive to psychotherapy than nonalexithymic patients. However, few empirical studies have examined this issue. Furthermore, it is unclear whether or not alexithymia itself may improve during psychotherapy.

Methods: Fifty-five consecutive outpatients with panic disorder received short-term cognitive-behavioral group therapy (CBGT) and were followed up 6 months later. Nineteen patients (35%) were on concomitant antidepressant medication. Alexithymia was measured using the 20-item Toronto Alexithymia Scale (TAS-20). Both completers and intention-to-treat analyses were calculated, taking into consideration the potentially confounding effect of comorbid conditions.

Results: Baseline alexithymia did not predict outcome of CBGT, neither at posttreatment nor at follow-up. The presence of comorbid axis I disorders predicted nonresponse at posttreatment but not at follow-up. TAS-20 total scores decreased over time, with the TAS-20 factors 1 (difficulty identifying feelings) and 2 (difficulty describing feelings) decreasing significantly, while factor 3 (externally oriented thinking) remained largely stable.

Conclusions: These findings are encouraging for cognitive-behavioral therapists working with patients with alexithymia who suffer from panic disorder: CBGT outcome does not appear to be negatively affected by alexithymia, and some alexithymic characteristics may even be reduced following CBGT. Assessing alexithymia at treatment onset may be useful for individually tailoring therapeutic interventions.
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http://dx.doi.org/10.1159/000288639DOI Listing
July 2010
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