Early Affective Processing in Patients with Acute Posttraumatic Stress Disorder: Magnetoencephalographic Correlates

Background: In chronic PTSD, a preattentive neural alarm system responds rapidly to emotional information, leading to increased prefrontal cortex (PFC) activation at early processing stages (<100 ms). Enhanced PFC responses are followed by a reduction in occipito-temporal activity during later processing stages. However, it remains unknown if this neuronal pattern is a result of a long lasting mental disorder or if it represents changes in brain function as direct consequences of severe trauma.Methodology: The present study investigates early fear network activity in acutely traumatized patients with PTSD. It focuses on the question whether dysfunctions previously observed in chronic PTSD patients are already present shortly after trauma exposure. We recorded neuromagnetic activity towards emotional pictures in seven acutely traumatized PTSD patients between one and seven weeks after trauma exposure and compared brain responses to a balanced healthy control sample. Inverse modelling served for mapping sources of differential activation in the brain.Principal Findings: Compared to the control group, acutely traumatized PTSD patients showed an enhanced PFC response to high-arousing pictures between 60 to 80 ms. This rapid prefrontal hypervigilance towards arousing pictorial stimuli was sustained during 120–300 ms, where it was accompanied by a reduced affective modulation of occipito-temporal neural processing.Conclusions: Our findings indicate that the hypervigilance-avoidance pattern seen in chronic PTSD is not necessarily a product of an endured mental disorder, but arises as an almost immediate result of severe traumatisation. Thus, traumatic experiences can influence emotion processing strongly, leading to long-lasting changes in trauma network activation and expediting a chronic manifestation of maladaptive cognitive and behavioral symptoms

Reliability and validity of the German version of the Structured Interview of Personality Organization (STIPO)

Background: The assessment of personality organization and its observable behavioral manifestations, i.e. personality functioning, has a long tradition in psychodynamic psychiatry. Recently, the DSM-5 Levels of Personality Functioning Scale has moved it into the focus of psychiatric diagnostics. Based on Kernberg's concept of personality organization the Structured Interview of Personality Organization (STIPO) was developed for diagnosing personality functioning. The STIPO covers seven dimensions: (1) identity, (2) object relations, (3) primitive defenses, (4) coping/rigidity, (5) aggression, (6) moral values, and (7) reality testing and perceptual distortions. The English version of the STIPO has previously revealed satisfying psychometric properties. Methods: Validity and reliability of the German version of the 100-item instrument have been evaluated in 122 psychiatric patients. All patients were diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) and were assessed by means of the STIPO. Moreover, all patients completed eight questionnaires that served as criteria for external validity of the STIPO. Results: Interrater reliability varied between intraclass correlations of .89 and 1.0, Crohnbach's a for the seven dimensions was .69 to .93. All a priori selected questionnaire scales correlated significantly with the corresponding STIPO dimensions. Patients with personality disorder (PD) revealed significantly higher STIPO scores (i.e. worse personality functioning) than patients without PD; patients cluster B PD showed significantly higher STIPO scores than patients with cluster C PD. Conclusions: Interrater reliability, Crohnbach's a, concurrent validity, and differential validity of the STIPO are satisfying. The STIPO represents an appropriate instrument for the assessment of personality functioning in clinical and research settings

Reliability and validity of the German version of the Structured Interview of Personality Organization (STIPO)

Background: The assessment of personality organization and its observable behavioral manifestations, i.e. personality functioning, has a long tradition in psychodynamic psychiatry. Recently, the DSM-5 Levels of Personality Functioning Scale has moved it into the focus of psychiatric diagnostics. Based on Kernberg's concept of personality organization the Structured Interview of Personality Organization (STIPO) was developed for diagnosing personality functioning. The STIPO covers seven dimensions: (1) identity, (2) object relations, (3) primitive defenses, (4) coping/rigidity, (5) aggression, (6) moral values, and (7) reality testing and perceptual distortions. The English version of the STIPO has previously revealed satisfying psychometric properties. Methods: Validity and reliability of the German version of the 100-item instrument have been evaluated in 122 psychiatric patients. All patients were diagnosed according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) and were assessed by means of the STIPO. Moreover, all patients completed eight questionnaires that served as criteria for external validity of the STIPO. Results: Interrater reliability varied between intraclass correlations of .89 and 1.0, Crohnbach's a for the seven dimensions was .69 to .93. All a priori selected questionnaire scales correlated significantly with the corresponding STIPO dimensions. Patients with personality disorder (PD) revealed significantly higher STIPO scores (i.e. worse personality functioning) than patients without PD; patients cluster B PD showed significantly higher STIPO scores than patients with cluster C PD. Conclusions: Interrater reliability, Crohnbach's a, concurrent validity, and differential validity of the STIPO are satisfying. The STIPO represents an appropriate instrument for the assessment of personality functioning in clinical and research settings

Stress-Induced Allodynia – Evidence of Increased Pain Sensitivity in Healthy Humans and Patients with Chronic Pain after Experimentally Induced Psychosocial Stress

Background: Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia. Methods: Multiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min) and after (10 and 90 min) inducing psychological stress with a standardized psychosocial stress test (“Trier Social Stress Test”). Results: Both healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain. Conclusions: Our results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions

Sex Differences in Itch Perception and Modulation by Distraction – an fMRI Pilot Study in Healthy Volunteers

Background: Even though itch is a common syndrome of many diseases there is only little knowledge about sex and gender differences in pruritus, especially in central itch perception and modulation. To our knowledge, this is the first fMRI study examining sex differences in perception and its modulation by distraction. Methods: Experimental itch was induced by application of histamine (0.1 mM) via microdialysis fibers twice at the left forearm and twice at the left lower leg in 33 healthy volunteers (17 females, 16 males). The brain activation patterns were assessed by fMRI during itch without and with distraction (Stroop task). Between the various conditions, subjects were asked to rate itch intensity, desire to scratch and pain intensity. In a second experiment in 10 of the 33 volunteers histamine was replaced by saline solution to serve as control for the ‘Stroop’ condition. Results: Women generally presented higher itch intensities compared to men during itch over the course of the experiment. A more specific analysis revealed higher itch intensities and desire to scratch in women during experimental induced itch that can be reduced by distraction at the lower legs when itch is followed by ‘Stroop’. In contrast, men depicted significant reduction of ‘itch’ by ‘Stroop’ at the forearms. Women depicted higher brain activation of structures responsible for integration of sensory, affective information and motor integration/planning during ‘itch’ and ‘Stroop’ condition when compared to men. No sex differences were seen in the saline control condition. Conclusion: Women and men exhibited localisation dependent differences in their itch perception with women presenting higher itch intensities and desire to scratch. Our findings parallel clinical observations of women reporting higher itch intensities depending on itch localisation and suffering more from itch as compared to men

Association of Leptin Gene DNA Methylation With Diagnosis and Treatment Outcome of Anorexia Nervosa

Epigenetic alterations are increasingly implicated in the pathophysiology of anorexia nervosa (AN) but are as yet poorly understood. We investigated possible associations between the leptin gene (LEP) and the leptin receptor gene (LEPR) DNA promoter methylation and (1) a diagnosis of AN and (2) outcome after a 10 months psychotherapeutic outpatient treatment. 129 (LEPR: n = 135) patients with AN were investigated during the large scale psychotherapeutic Anorexia Nervosa Treatment Outpatient Study (ANTOP) trial, compared to 117 (LEPR: n = 119) age and height matched, normal-weight healthy controls. Blood samples were taken at baseline, the end of therapy (40 weeks) and the 12-months follow-up and compared to controls. Methylation was measured in whole blood via bisulfite sequencing. Within the promoter region 32 (LEP) and 39 CpG sites (LEPR) were analyzed. Two key findings were observed. First, LEP and LEPR methylation at baseline were lower in patients compared to controls (LEP: [%] AN: 30.94 ± 13.2 vs. controls: 34.53 ± 14.6); LEPR ([%] AN: 3.73 ± 5.4 vs. controls: 5.22 ± 8.3, mixed linear models: both P &lt; 0.001). Second, lower DNA methylation of the LEP promoter, with a dynamic upregulation during treatment, was associated with a full recovery in AN patients (% change from baseline to follow-up in full recovery patients: +35.13% (SD: 47.56); mixed linear model: P &lt; 0.0001). To test for potential predictive properties of mean LEP DNA methylation a LEP DNA methylation cut-off (31.25% DNA methylation) was calculated, which significantly discriminated full recovery vs. full syndrome AN patients. This cut-off was then tested in a group of previously unclassified patients (missing follow-up data of the Structured Interview for Anorexic and Bulimic disorders; n = 33). Patients below the cut-off (31.25% LEP DNA methylation) showed an increase in BMI over time, while those above the cut-off had a decrease in BMI (ANOVA at the 12-months follow-up: P = 0.0142). To our knowledge, this is the first study investigating epigenetic alterations in AN over time. Our findings indicate that LEP DNA methylation might be involved in the disease course of AN

Factors and processes shaping the population structure and distribution of genetic variation across the species range of the freshwater snail radix balthica (Pulmonata, Basommatophora)

Background: Factors and processes shaping the population structure and spatial distribution of genetic diversity across a species' distribution range are important in determining the range limits. We comprehensively analysed the influence of recurrent and historic factors and processes on the population genetic structure, mating system and the distribution of genetic variability of the pulmonate freshwater snail Radix balthica. This analysis was based on microsatellite variation and mitochondrial haplotypes using Generalised Linear Statistical Modelling in a Model Selection framework. Results: Populations of R. balthica were found throughout North-Western Europe with range margins marked either by dispersal barriers or the presence of other Radix taxa. Overall, the population structure was characterised by distance independent passive dispersal mainly along a Southwest-Northeast axis, the absence of isolation-by-distance together with rather isolated and genetically depauperated populations compared to the variation present in the entire species due to strong local drift. A recent, climate driven range expansion explained most of the variance in genetic variation, reducing at least temporarily the genetic variability in this area. Other factors such as geographic marginality and dispersal barriers play only a minor role. Conclusions: To our knowledge, such a population structure has rarely been reported before. It might nevertheless be typical for passively dispersed, patchily distributed taxa (e.g. freshwater invertebrates). The strong local drift implied in such a structure is expected to erode genetic variation at both neutral and coding loci and thus probably diminish evolutionary potential. This study shows that the analysis of multiple factors is crucial for the inference of the processes shaping the distribution of genetic variation throughout species ranges. Additional files Additional file 1: Distribution of Radix taxa. Spatial distribution of the Radix MOTU as defined in Pfenninger et al. 2006 plus an additional, newly discovered taxon. This map is the basis for the inference of the species range of R. balthica. Additional file 2: Sampling site table and spatial distribution of diversity indices, selfing estimates and inferred population bottlenecks for R. balthica. Table of sampling site code, geographical position in decimal degrees latitude and longitude, number of individuals analysed with microsatellites (Nnuc), expected heterozygosity (HE) and standard deviation across loci, mean rarefied number of alleles per microsatellite locus (A) and their standard deviation, number of individuals analysed for mitochondrial variation (Nmt), rarefied number of mitochondrial COI haplotypes (Hmt), number of individuals measured for body size (Nsize). Figures A1 - A3 show a graphical representation of the spatial distribution of He, Hmt and, s, respectively. Additional file 3: Assessment of environmental marginality. PCA (principle component analysis) on 35 climatic parameters for the period from 1960 - 2000 from publicly availableWorldClim data. Additional file 4: Inference of a recent climate driven range expansion in R. balthica. Analysis of the freshwater benthos long term monitoring data of the Swedish national monitoring databases at the Swedish University of Agricultural Sciences SLU with canonical correspondence analysis

Impact of pressure as a tactile stimulus on working memory in healthy participants.

Studies on cross-modal interaction have demonstrated attenuated as well as facilitated effects for both neural responses as well as behavioral performance. The goals of this pilot study were to investigate possible cross-modal interactions of tactile stimulation on visual working memory and to identify possible neuronal correlates by using functional magnetic resonance imaging (fMRI). During fMRI, participants (n = 12 females, n = 12 males) performed a verbal n-back task (0-back and 2-back tasks) while tactile pressure to the left thumbnail was delivered. Participants presented significantly lower behavioral performances (increased error rates, and reaction times) during the 2-back task as compared to the 0-back task. Task performance was independent of pressure in both tasks. This means that working memory performance was not impacted by a low salient tactile stimulus. Also in the fMRI data, no significant interactions of n-back x pressure were observed. In conclusion, the current study found no influence of tactile pressure on task-related brain activity during n-back (0-back and 2-back) tasks

Cerebral Activation and Catastrophizing During Pain Anticipation in Patients With Fibromyalgia

Objective: Anticipation of pain influences its cerebral processing and dysfunctional cognitive style like catastrophizing correlates with the severity of pain. Patients with fibromyalgia syndrome (FMS) exhibit higher levels of catastrophizing, increased attention to pain, and augmented cerebral pain processing. Therefore, alteration in cerebral processing during anticipation of experimental pain and its relation to catastrophizing are the main focus of the study. Methods: Functional magnetic resonance imaging of the brain was acquired during the time of pain anticipation with announcement of its intensity or not in 12 patients with FMS and 14 healthy controls. Within a two-factorial model (factors group'' and session''), the main effect of group and the interaction effect were tested in a whole-brain analysis. In addition, activation of the periaqueductal gray (PAG) was analyzed in a region-of-interest analysis. Results: Patients with FMS generally displayed greater catastrophizing behavior (p = .003) but not during the anticipation of the experimental pain (p > 9.16). Furthermore, patients showed greater activation of the dorsolateral prefrontal cortex (p = .05), the PAG (p = .04), and the posterior parietal cortex (p = .03) during the anticipation of pain, independent of the pain coping behavior during anticipation. Conclusions: The lack of difference in catastrophizing during the experimental pain suggests independent coping mechanisms during experimental and clinical pain. Regarding the importance of the frontal cortex and the PAG in the descending pain modulation system, it seems reasonable to assume that these functional changes related to the context of stimulus presentation may contribute to central sensitization in FMS