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sessive-compulsive disorder (HR = 10.7, 95% CI = 1.7-66.1), bipolar disorder (HR = 7.7, 95% CI = 2.8-20.8), pain disorder (HR = 3.5, 95% CI = 1.3-9.1), and alcohol dependence (HR = 4.7, 95% CI = 1.7-12.4). Increased hazard rates for PDAG (HR = 4.2, 95% CI = 1.4-12.1), bipolar disorder type II (HR = 8.1, 95% CI = 2.3-27.4), pain disorder (HR = 1.9, 95% CI = 1.01-3.5), and alcohol dependence (HR = 2.1, 95% CI = 1.1-4.) were also found for subjects fulfi lling subthreshold SAD. Conclusions: Although revealing a strong association between SAD and PDAG, our results argue against a specifi c SAD-PDAG relationship. PDAG was neither a specifi c outcome nor a complete mediator variable of SAD

Fax +41 61 306 12 34 E-Mail karger@karger

sessive-compulsive disorder (HR = 10.7, 95% CI = 1.7-66.1), bipolar disorder (HR = 7.7, 95% CI = 2.8-20.8), pain disorder (HR = 3.5, 95% CI = 1.3-9.1), and alcohol dependence (HR = 4.7, 95% CI = 1.7-12.4). Increased hazard rates for PDAG (HR = 4.2, 95% CI = 1.4-12.1), bipolar disorder type II (HR = 8.1, 95% CI = 2.3-27.4), pain disorder (HR = 1.9, 95% CI = 1.01-3.5), and alcohol dependence (HR = 2.1, 95% CI = 1.1-4.) were also found for subjects fulfi lling subthreshold SAD. Conclusions: Although revealing a strong association between SAD and PDAG, our results argue against a specifi c SAD-PDAG relationship. PDAG was neither a specifi c outcome nor a complete mediator variable of SAD

Acute Stress-Induced Coagulation Activation in Patients With Remitted Major Depression Versus Healthy Controls and the Role of Stress-Specific Coping

Background: Depressed patients have an increased risk of myocardial infarction, for which acute stress is a frequent trigger. Prothrombotic changes could be one involved mechanism that can be modulated by psychological coping. Purpose: We examined the effects of remitted major depression and situation-specific coping strategies on stress-induced coagulation activation. Methods: Forty patients with remitted depression and 23 healthy controls underwent the Trier Social Stress Test, rating applied coping strategies thereafter. Blood was sampled at baseline and 15 and 45 min poststress to measure fibrinogen, von Willebrand factor (VWF) and D-dimer. Coagulation activation over time was quantified as area under the curve (AUC) with respect to baseline activity. Standardized z-scores of individual coagulation AUC measures were added up to a prothrombotic index. Results: Stress provoked significant VWF (p = .024) and D-dimer (p = .002) responses. Remitted depressed patients used positive distraction coping more frequently than controls did (p = .030). Coagulation AUC measures were similar in both groups. In all participants, higher positive coping total (p = 0.009), driven by devaluation/defense (p = .022) and distraction (p = .004) coping, was associated with a lower prothrombotic index. In controls, but not in remitted depressed patients, higher positive coping total (p = .008), driven by higher devaluation/defense (p = .010) and distraction (p = .023) coping, was associated with lower VWF AUC. Conclusions: Despite the use of favorable coping strategies in a specific stress situation, remitted depressed patients may benefit less from a positive effect of positive situational coping on coagulation activation than controls. Such a mechanism could partially explain the increased risk of myocardial infarction in depressed individuals

<em>FKBP5</em> Gene Expression Predicts Antidepressant Treatment Outcome in Depression

Adverse experiences and chronic stress are well-known risk factors for the development of major depression, and an impaired stress response regulation is frequently observed in acute depression. Impaired glucocorticoid receptor (GR) signalling plays an important role in these alterations, and a restoration of GR signalling appears to be a prerequisite of successful antidepressant treatment. Variants in genes of the stress response regulation contribute to the vulnerability to depression in traumatized subjects. Consistent findings point to an important role of FKBP5, the gene expressing FK506-binding protein 51 (FKBP51), which is a strong inhibitor of the GR, and thus, an important regulator of the stress response. We investigated the role of FKBP5 and FKB51 expression with respect to stress response regulation and antidepressant treatment outcome in depressed patients. This study included 297 inpatients, who participated in the Munich Antidepressant Response Signature (MARS) project and were treated for acute depression. In this open-label study, patients received antidepressant treatment according to the attending doctor’s choice. In addition to the FKBP5 genotype, changes in blood FKBP51 expression during antidepressant treatment were analyzed using RT-PCR and ZeptoMARKTM reverse phase protein microarray (RPPM). Stress response regulation was evaluated in a subgroup of patients using the combined dexamethasone (dex)/corticotropin releasing hormone (CRH) test. As expected, increased FKBP51 expression was associated with an impaired stress response regulation at baseline and after six weeks was accompanied by an elevated cortisol response to the combined dex/CRH test. Further, we demonstrated an active involvement of FKBP51 in antidepressant treatment outcome. While patients responding to antidepressant treatment had a pronounced reduction of FKBP5 gene and FKBP51 protein expression, increasing expression levels were observed in nonresponders. This effect was moderated by the genotype of the FKBP5 single nucleotide polymorphism (SNP) rs1360780, with carriers of the minor allele showing the most pronounced association. Our findings demonstrate that FKBP5 and, specifically, its expression product FKBP51 are important modulators of antidepressant treatment outcome, pointing to a new, promising target for future antidepressant drug development

The 'Early Developmental Stages of Psychopathology (EDSP) study' : a 20-year review of methods and findings

The "Early Developmental Stages of Psychopathology (EDSP)" study is a prospective-longitudinal study program in a community sample (Munich, Germany) of adolescents and young adults. The program was launched in 1994 to study the prevalence and incidence of psychopathological syndromes and mental disorders, to describe the natural course and to identify vulnerability and risk factors for onset and progression as well as psychosocial consequences. This paper reviews methods and core outcomes of this study program.; The EDSP is based on an age-stratified random community sample of originally N = 3021 subjects aged 14-24 years at baseline, followed up over 10 years with up to 3 follow-up waves. The program includes a family genetic supplement and nested cohorts with lab assessments including blood samples for genetic analyses. Psychopathology was assessed with the DSM-IV/M-CIDI; embedded dimensional scales and instruments assessed vulnerability and risk factors.; Beyond the provision of age-specific prevalence and incidence rates for a wide range of mental disorders, analyses of their patterns of onset, course and interrelationships, the program identified common and diagnosis-specific distal and proximal vulnerability and risk factors including critical interactions.; The EDSP study advanced our knowledge on the developmental pathways and trajectories, symptom progression and unfolding of disorder comorbidity, highlighting the dynamic nature of many disorders and their determinants. The results have been instrumental for defining more appropriate diagnostic thresholds, led to the derivation of symptom progression models and were helpful to identify promising targets for prevention and intervention

Domain propagation in He-ion-bombarded magnetic wires with opposite exchange bias

McCord J, Schäfer R, Theis-Bröhl K, et al. Domain propagation in He-ion-bombarded magnetic wires with opposite exchange bias. In: Journal of Applied Physics. JOURNAL OF APPLIED PHYSICS. Vol 97. AMER INST PHYSICS; 2005.Exchange-biased IrMn/CoFe full films are magnetically structured with He-ion bombardment into stripes with antiparallel-aligned loop shift. The patterning results in a two-step magnetization loop corresponding to two regions of oppositely aligned exchange bias. The longitudinal magnetization reversal through head-on domain-wall motion and partial penetration of magnetization from neighboring strips is highly asymmetric involving ripplelike domain structures and incoherent rotation of magnetization. In addition, Neel-wall-like structures with a preferred sense of rotation are formed at the edges of the strips. Along the transverse direction the reversal is dominated by the switching of the magnetic border structures between the strips. Complicated domain patterns are generated under other external field angles. (c) 2005 American Institute of Physics

Data-driven pupil response profiles as transdiagnostic readouts for the detection of neurocognitive functioning in affective and anxiety disorders.

INTRODUCTION Neurocognitive functioning is a relevant transdiagnostic dimension in psychiatry. As pupil size dynamics track cognitive load during a working memory task, we aimed to explore if this parameter allows to identify psychophysiological subtypes in healthy participants and patients with affective and anxiety symptomatology. METHODS Our sample consisted of 226 participants who completed the N-back task during simultaneous fMRI and pupillometry measurements. We used Latent Class Growth Modeling to identify clusters based on pupil size in response to cognitive load. In a second step, these clusters were compared on affective and anxiety symptom levels, performance in neurocognitive tests, and fMRI activity. RESULTS The clustering analysis resulted in two distinct pupil response profiles: one with a stepwise increasing pupil size with increasing cognitive load (reactive group), the other one with a constant pupil size across conditions (non-reactive group). A larger increase in pupil size was significantly associated with better performance in neurocognitive tests in executive functioning and sustained attention. Statistical maps of parametric modulation of pupil size during the N-back task showed the frontoparietal network in the positive and the default mode network in the negative contrast. The pupil response profile of the reactive group was associated with more thalamic activity, likely reflecting better arousal upregulation, and less deactivation of the limbic system. CONCLUSION To conclude, pupil measurements have the potential to serve as a highly sensitive psychophysiological readout for detection of neurocognitive deficits in the core domain of executive functioning adding to the development of valid transdiagnostic constructs in psychiatry

The utility of wearable headband electroencephalography and pulse photoplethysmography to assess cortical and physiological arousal in individuals with stress-related mental disorders.

Several stress-related mental disorders are characterised by disturbed sleep, but objective sleep biomarkers are not routinely examined in psychiatric patients. We examined the use of wearable-based sleep biomarkers in a psychiatric sample with headband electroencephalography (EEG) including pulse photoplethysmography (PPG), with an additional focus on microstructural elements as especially the shift from low to high frequencies appears relevant for several stress-related mental disorders. We analysed 371 nights of sufficient quality from 83 healthy participants and those with a confirmed stress-related mental disorder (anxiety-affective spectrum). The median value of macrostructural, microstructural (spectral slope fitting), and heart rate variables was calculated across nights and analysed at the individual level (N = 83). The headbands were accepted well by patients and the data quality was sufficient for most nights. The macrostructural analyses revealed trends for significance regarding sleep continuity but not sleep depth variables. The spectral analyses yielded no between-group differences except for a group × age interaction, with the normal age-related decline in the low versus high frequency power ratio flattening in the patient group. The PPG analyses showed that the mean heart rate was higher in the patient group in pre-sleep epochs, a difference that reduced during sleep and dissipated at wakefulness. Wearable devices that record EEG and/or PPG could be used over multiple nights to assess sleep fragmentation, spectral balance, and sympathetic drive throughout the sleep-wake cycle in patients with stress-related mental disorders and healthy controls, although macrostructural and spectral markers did not differ between the two groups.info:eu-repo/semantics/publishe

Pupil Dilation during Reward Anticipation Is Correlated to Depressive Symptom Load in Patients with Major Depressive Disorder.

Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions

Pupil Dilation during Reward Anticipation Is Correlated to Depressive Symptom Load in Patients with Major Depressive Disorder

Depression is a debilitating disorder with high prevalence and socioeconomic cost, but the brain-physiological processes that are altered during depressive states are not well understood. Here, we build on recent findings in macaques that indicate a direct causal relationship between pupil dilation and anterior cingulate cortex mediated arousal during anticipation of reward. We translated these findings to human subjects with concomitant pupillometry/fMRI in a sample of unmedicated participants diagnosed with major depression and healthy controls. We could show that the upregulation and maintenance of arousal in anticipation of reward was disrupted in patients in a symptom-load dependent manner. We could further show that the failure to maintain reward anticipatory arousal showed state-marker properties, as it tracked the load and impact of depressive symptoms independent of prior diagnosis status. Further, group differences of anticipatory arousal and continuous correlations with symptom load were not traceable only at the level of pupillometric responses, but were mirrored also at the neural level within salience network hubs. The upregulation and maintenance of arousal during reward anticipation is a novel translational and well-traceable process that could prove a promising gateway to a physiologically informed patient stratification and targeted interventions