Tilo Kircher

Philipps University of Marburg, Marburg, Hesse, Germany

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Publications (375)1374.66 Total impact

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    ABSTRACT: Background. Previous studies of the dimensional structure of panic attack symptoms have mostly identified a respiratory and a vestibular/mixed somatic dimension. Evidence for additional dimensions such as a cardiac dimension and the allocation of several of the panic attack symptom criteria is less consistent. Clarifying the dimensional structure of the panic attack symptoms should help to specify the relationship of potential risk factors like anxiety sensitivity and fear of suffocation to the experience of panic attacks and the development of panic disorder. Method. In an outpatient multicentre study 350 panic patients with agoraphobia rated the intensity of each of the ten DSM-IV bodily symptoms during a typical panic attack. The factor structure of these data was investigated with nonlinear confirmatory factor analysis (CFA). The identified bodily symptom dimensions were related to panic cognitions, anxiety sensitivity and fear of suffocation by means of nonlinear structural equation modelling (SEM). Results. CFA indicated a respiratory, a vestibular/mixed somatic and a cardiac dimension of the bodily symptom criteria. These three factors were differentially associated with specific panic cognitions, different anxiety sensitivity facets and suffocation fear. Conclusions. Taking into account the dimensional structure of panic attack symptoms may help to increase the specificity of the associations between the experience of panic attack symptoms and various panic related constructs.
    Psychological Medicine 12/2015; 45(8):1675-1685. DOI:10.1017/S0033291714002803 · 5.43 Impact Factor
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    ABSTRACT: Aldosterone and mineralocorticoid receptor (MR)-function have been related to depression. We examined central and peripheral parameters of MR-function in order to characterize their relationship to clinical treatment outcome after six weeks in patients with acute depression. 30 patients with a diagnosis of major depression were examined 3 times over a 6 week period. Aldosterone and cortisol salvia samples were taken at 7.00 a.m. before patients got out of bed. Easy to use e-devices were used to measure markers of central MR function, i.e. slow wave sleep (SWS) and heart-rate variability (HRV). Salt-taste intensity (STI) and salt pleasantness (SP) of a 0.9% salt solution were determined by a newly developed scale. In addition, systolic blood pressure (SBP) and plasma electrolytes were determined as markers for peripheral MR activity. The relationship between the levels of these biomarkers at baseline and the change in clinical outcome parameters (Hamilton depression rating scale (HDRS)-21, anxiety, QIDS and BDI) after 6 weeks of treatment was investigated. A higher aldosterone/cortisol ratio (Aldo/Cort) (n = 17 due to missing values; p < 0.05) and lower SBP (n = 24; p < 0.05) at baseline predicted poor outcome, as measured with the HDRS, independent of gender. Only in male patients higher STI, lower SP, lower SWS (all n = 13) and higher HRV (n = 11) at baseline predicted good outcome p < 0.05). Likewise, in male patients low baseline sodium appears to be predictive for a poor outcome (n = 12; p = 0.05; based on HDRS-6). In conclusion, correlates of higher central MR-activation are associated with poorer clinical improvement, particularly in men. This contrasts with the finding of a peripheral MR-desensitization in more refractory patients. As one potential mechanism to consider, sodium loss on the basis of dysfunctional peripheral MR function and additional environmental factors may trigger increased aldosterone secretion and consequently worse outcome. These markers deserve further study as potential biological correlates for therapy refractory depression. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Journal of Psychiatric Research 04/2015; DOI:10.1016/j.jpsychires.2015.04.012 · 4.09 Impact Factor
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    ABSTRACT: One of the key features of human interpersonal communication is our ability to integrate information communicated by speech and accompanying gestures. However, it is still not fully understood how this essential combinatory process is represented in the human brain. Functional magnetic resonance imaging (fMRI) studies have unanimously attested the relevance of activation in the posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG), while electroencephalography (EEG) studies have shown oscillatory activity in specific frequency bands to be associated with multisensory integration. In the current study, we used fMRI and EEG to separately investigate the anatomical and oscillatory neural signature of integrating intrinsically meaningful gestures (IMG; e.g. "Thumbs-up gesture") and corresponding speech (e.g., "The actor did a good job"). In both the fMRI (n=20) and EEG (n=20) study, participants were presented with videos of an actor either: performing IMG in the context of a German sentence (GG), IMG in the context of a Russian (as a foreign language) sentence (GR), or speaking an isolated German sentence without gesture (SG). The results of the fMRI experiment confirmed that gesture-speech processing of IMG activates the posterior MTG (GG>GR∩GG>SG). In the EEG experiment we found that the identical integration process (GG>GR∩GG>SG) is related to a centrally-distributed alpha (7-13Hz) power decrease within 700-1400ms post onset of the critical word. These new findings suggest that BOLD response increase in the pMTG and alpha power decrease represent the neural correlates of integrating intrinsically meaningful gestures with their corresponding speech. Copyright © 2015. Published by Elsevier Ltd.
    Neuropsychologia 04/2015; DOI:10.1016/j.neuropsychologia.2015.04.018 · 3.45 Impact Factor
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    ABSTRACT: Regulator of G-protein Signaling 2 (RGS2) is a key regulator of G-protein-coupled signaling pathways involved in fear and anxiety. Data from rodent models and genetic analysis of anxiety-related traits and disorders in humans suggest down-regulation of RGS2 expression to be a risk factor for anxiety. Here we investigated, whether genetic variation in microRNAs mediating posttranscriptional down-regulation of RGS2 may be a risk factor for anxiety as well. 75 microRNAs predicted to regulate RGS2 were identified by four bioinformatic algorithms and validated experimentally by luciferase reporter gene assays. Specificity was confirmed for six microRNAs (hsa-miR-1271-5p, hsa-miR-22-3p, hsa-miR-3591-3p, hsa-miR-377-3p, hsa-miR-4717-5p, hsa-miR-96-5p) by disrupting their seed sequence at the 3' untranslated region of RGS2. Hsa-miR-4717-5p showed the most robust effect on RGS2 and regulated two other candidate genes of anxiety disorders (CNR1 and IKBKE) as well. Two SNPs (rs150925, rs161427) within and 1,000 bp upstream of the hostgene of hsa-miR-4717-5p (MIR4717) show a minor allele frequency greater than 0.05. Both were in high linkage disequilibrium (r(2) = 1, D' = 1) and both major (G) alleles showed a trend for association with panic disorder with comorbid agoraphobia in one of two patient/control samples (combined npatients = 497). Dimensional anxiety traits, as described by Anxiety Sensitivity Index (ASI) and Agoraphobic Cognitions Questionnaire (ACQ) were significantly higher among carriers of both major (G) alleles in a combined patient/control sample (ncombined = 831). Taken together, data indicate that MIR4717 regulates human RGS2 and contributes to the genetic risk towards anxiety-related traits. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2015; DOI:10.1002/ajmg.b.32312 · 3.27 Impact Factor
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    Dataset: BAG German
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    ABSTRACT: See: Nagels, A., Kircher, T., Steines, M., Grosvald, M. & Straube, B. A brief self-rating scale for the assessment of individual differences in gesture perception and production. Learn. Individ. Differ. (2015). doi:10.1016/j.lindif.2015.03.008
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    ABSTRACT: Genome-wide association studies have reported an association between NCAN rs1064395 genotype and bipolar disorder. This association was later extended to schizophrenia and major depression. However, the neurobiological underpinnings of these associations are poorly understood. NCAN is implicated in neuronal plasticity and expressed in subcortical brain areas, such as the amygdala and hippocampus, which are critically involved in dysfunctional emotion processing and -regulation across diagnostic boundaries. We hypothesized that the NCAN risk variant is associated with reduced gray matter volumes in these areas. Gray matter structure was assessed by voxel-based morphometry on structural MRI-data in two independent German samples (healthy subjects, n=512; depressed inpatients, n=171). All participants were genotyped for NCAN rs1064395. Hippocampal and amygdala region-of-interest analyses were performed within each sample. Additionally, whole-brain data from the combined sample were analyzed. Risk (A)-allele carriers showed reduced amygdala and hippocampal gray matter volumes in both cohorts with a remarkable spatial overlap. In the combined sample, genotype effects observed for the amygdala and hippocampus survived correction for entire brain volume. Further effects were also observed in the left orbitofrontal cortex and the cerebellum/fusiform gyrus. We conclude that NCAN genotype is associated with limbic gray matter alterations in healthy and depressed subjects in brain areas implicated in emotion perception and -regulation. The present data suggest that NCAN forms susceptibility to neuro-structural deficits in the amygdala, hippocampus, and prefrontal areas independent of disease, which might lead to disorder onset in the presence of other genetic or environmental risk factors.Neuropsychopharmacology accepted article preview online, 24 March 2015. doi:10.1038/npp.2015.86.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 03/2015; DOI:10.1038/npp.2015.86 · 7.83 Impact Factor
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    ABSTRACT: Gesture production and comprehension have a strong impact on speech comprehension and social communicative functioning. To facilitate research in this area, we created the ‘Brief Assessment of Gesture’ (BAG) tool, a set of 12 subjective statements relating to gesture production and perception in everyday life. Two hundred and twenty German native speakers were asked to rate each statement. Individual differences in empathy were assessed, to disentangle sensitivity to gesture production and perception from general empathic/social functioning. A principal component analysis revealed a four-factor solution, reflecting a production factor and a perception factor, each occurring with and without an empathy component. The current investigation yielded good psychometric results with a high reliability and internal consistency. Our findings suggest that BAG is a straightforward and useful tool to assess individual differences in gesture production and comprehension, as well as related social/empathic functioning. The BAG may serve as an important instrument for research in speech comprehension, cognitive development, language learning and social communicative functioning.
    Learning and Individual Differences 03/2015; DOI:10.1016/j.lindif.2015.03.008 · 1.58 Impact Factor
  • Yunbo Yang, Tilo Kircher, Benjamin Straube
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    ABSTRACT: Psychotherapy changes symptoms through neuroplastic processes in the brain. Neurobiological Models of cognitive behavioral therapy (CBT) effects postulate that the therapeutic changes could be a result of a direct inhibition of bottom-up neural processes and/or enhancement of top-down regulatory brain systems. The current review summarizes recent findings about the neural correlates of CBT in panic disorder, partly supporting and substantially modifying these models. Furthermore, this review focuses on neural biomarkers of therapy response and the neural correlates of genetic moderators of therapy effects. These findings might potentially be useful for person- alized treatment in the future. Finally, we will discuss some future perspectives of the neurosciences in psychotherapy research.
    Zeitschrift für Psychiatrie Psychologie und Psychotherapie 03/2015; 63:79-87. DOI:10.1024/1661-4747/a000226 · 1.99 Impact Factor
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    ABSTRACT: Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2015; DOI:10.1002/ajmg.b.32299 · 3.27 Impact Factor
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    ABSTRACT: During face-to-face communication, body orientation and coverbal gestures influence how information is conveyed. The neural pathways underpinning the comprehension of such nonverbal social cues in everyday interaction are to some part still unknown. During fMRI data acquisition, 37 participants were presented with video clips showing an actor speaking short sentences. The actor produced speech-associated iconic gestures (IC) or no gestures (NG) while he was visible either from an egocentric (ego) or from an allocentric (allo) position. Participants were asked to indicate via button press whether they felt addressed or not. We found a significant interaction of body orientation and gesture in addressment evaluations, indicating that participants evaluated IC-ego conditions as most addressing. The anterior cingulate cortex (ACC) and left fusiform gyrus were stronger activated for egocentric versus allocentric actor position in gesture context. Activation increase in the ACC for IC-ego>IC-allo further correlated positively with increased addressment ratings in the egocentric gesture condition. Gesture-related activation increase in the supplementary motor area, left inferior frontal gyrus and right insula correlated positively with gesture-related increase of addressment evaluations in the egocentric context. Results indicate that gesture use and body-orientation contribute to the feeling of being addressed and together influence neural processing in brain regions involved in motor simulation, empathy and mentalizing. Hum Brain Mapp, 2015. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 01/2015; 36(5). DOI:10.1002/hbm.22746 · 6.92 Impact Factor
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    ABSTRACT: Adaption to changing environments is evolutionarily advantageous. Studies that link genetic and phenotypic expression of flexible adjustment to one's context are largely lacking. In this study, we tested the importance of psychological flexibility, or goal-related context sensitivity, in an interaction between psychotherapy outcome for panic disorder with agoraphobia (PD/AG) and a genetic polymorphism. Given the established role of the 5HTT-LPR polymorphism in behavioral flexibility, we tested whether this polymorphism (short group vs. long group) impacted therapy response as a function of various endophenotypes (i.e., psychological flexibility, panic, agoraphobic avoidance, and anxiety sensitivity). Patients with PD/AG were recruited from a large multicenter randomized controlled clinical trial on cognitive-behavioral therapy. Pre- to post-treatment changes by 5HTT polymorphism were analyzed. 5HTT polymorphism status differentiated pre- to post-treatment changes in the endophenotype psychological flexibility (effect size difference d = 0.4, p < 0.05), but none of the specific symptom-related endophenotypes consistently for both the intent-to-treat sample (n = 228) and the treatment completers (n = 194). Based on the consistency of these findings with existing theory on behavioral flexibility, the specificity of the results across phenotypes, and the consistency of results across analyses (i.e., completer and intent to treat), we conclude that 5HTT polymorphism and the endophenotype psychological flexibility are important variables for the treatment of PD/AG. The endophenotype psychological flexibility may help bridge genetic and psychological literatures. Despite the limitation of the post hoc nature of these analyses, further study is clearly warranted.
    European Archives of Psychiatry and Clinical Neuroscience 01/2015; DOI:10.1007/s00406-015-0575-3 · 3.36 Impact Factor
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    ABSTRACT: Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n=185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n=245; after CBT: n=171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n=39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders.
    Translational Psychiatry 12/2014; 4:e490. DOI:10.1038/tp.2014.130 · 4.36 Impact Factor
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    ABSTRACT: Alterations of eye movements in schizophrenia patients have been widely described for laboratory settings. For example, gain during smooth tracking is reduced, and fixation patterns differ between patients and healthy controls. The question remains, whether such results are related to the specifics of the experimental environment, or whether they transfer to natural settings. Twenty ICD-10 diagnosed schizophrenia patients and 20 healthy age-matched controls participated in the study, each performing four different oculomotor tasks corresponding to natural everyday behavior in an indoor environment: (I) fixating stationary targets, (II) sitting in a hallway with free gaze, (III) walking down the hallway, and (IV) visually tracking a target on the floor while walking straight-ahead. In all conditions, eye movements were continuously recorded binocularly by a mobile lightweight eye tracker (EyeSeeCam). When patients looked at predefined targets, they showed more fixations with reduced durations than controls. The opposite was true when participants were sitting in a hallway with free gaze. During visual tracking, patients showed a significantly greater root-mean-square error (representing the mean deviation from optimal) of retinal target velocity. Different from previous results on smooth-pursuit eye movements obtained in laboratory settings, no such difference was found for velocity gain. Taken together, we have identified significant differences in fundamental oculomotor parameters between schizophrenia patients and healthy controls during natural behavior in a real environment. Moreover, our data provide evidence that in natural settings, patients overcome some impairments, which might be present only in laboratory studies, by as of now unknown compensatory mechanisms or strategies.
    European Archives of Psychiatry and Clinical Neuroscience 12/2014; DOI:10.1007/s00406-014-0567-8 · 3.36 Impact Factor
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    ABSTRACT: Importance: Although neuroimaging research has made substantial progress in identifying the large-scale neural substrate of anxiety disorders, its value for clinical application lags behind expectations. Machine-learning approaches have predictive potential for individual-patient prognostic purposes and might thus aid translational efforts in psychiatric research. Objective: To predict treatment response to cognitive behavioral therapy (CBT) on an individual-patient level based on functional magnetic resonance imaging data in patients with panic disorder with agoraphobia (PD/AG). Design, Setting, and Participants: We included 49 patients free of medication for at least 4 weeks and with a primary diagnosis of PD/AG in a longitudinal study performed at 8 clinical research institutes and outpatient centers across Germany. The functional magnetic resonance imaging study was conducted between July 2007 and March 2010. Interventions: Twelve CBT sessions conducted 2 times a week focusing on behavioral exposure. Main Outcomes and Measures: Treatment response was defined as exceeding a 50% reduction in Hamilton Anxiety Rating Scale scores. Blood oxygenation level-dependent signal was measured during a differential fear-conditioning task. Regional and whole-brain gaussian process classifiers using a nested leave-one-out cross-validation were used to predict the treatment response from data acquired before CBT. Results: Although no single brain region was predictive of treatment response, integrating regional classifiers based on data from the acquisition and the extinction phases of the fear-conditioning task for the whole brain yielded good predictive performance (accuracy, 82%; sensitivity, 92%; specificity, 72%; P < .001). Data from the acquisition phase enabled 73% correct individual-patient classifications (sensitivity, 80%; specificity, 67%; P < .001), whereas data from the extinction phase led to an accuracy of 74% (sensitivity, 64%; specificity, 83%; P < .001). Conservative reanalyses under consideration of potential confounders yielded nominally lower but comparable accuracy rates (acquisition phase, 70%; extinction phase, 71%; combined, 79%). Conclusions and Relevance: Predicting treatment response to CBT based on functional neuroimaging data in PD/AG is possible with high accuracy on an individual-patient level. This novel machine-learning approach brings personalized medicine within reach, directly supporting clinical decisions for the selection of treatment options, thus helping to improve response rates.
    JAMA Psychiatry 11/2014; 72(1). DOI:10.1001/jamapsychiatry.2014.1741 · 12.01 Impact Factor
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    ABSTRACT: Formal thought disorder (FTD) is a core syndrome of schizophrenia. However, patients with other diagnoses, such as mania and depression amongst others, also present with FTD. We introduce a novel, comprehensive clinical rating scale, capturing the full variety of FTD phenomenology including subjective experiences.The 30-item Thought and Language Disorder (TALD) scale is based on a detailed review of the literature, encompassing all formal thought disorder symptoms reported from the early 20th century onwards. Objectively observable symptoms as well as subjective phenomena were included. Two hundred and ten participants (146 patients ICD-10 diagnoses: depression n = 63, schizophrenia n = 63, mania n = 20; 64 healthy control subjects) were interviewed and symptoms rated with the TALD, TLC, HAMD, YMRS and SAPS/SANS. A principal component analyses was performed for the TALD to differentiate sub-syndromes.The principal component analysis revealed four FTD factors; objective and subjective as well as positive and negative factor dimensions. The correlation analyses with the TLC and the SAPS/SANS FTD sub-scores demonstrated the factor validity for the objective factors. The different diagnoses showed a distinct pattern of symptom severity in each of the factors, with mania patients exhibiting the highest value in the positive, objective dimension.The scale showed good psychometric results, which makes it a practicable, nosologically-open instrument for the detailed assessment of all FTD dimensions. The results strengthen the importance of subjective symptom assessment reported by the patient.
    Schizophrenia Research 11/2014; 160(1-3). DOI:10.1016/j.schres.2014.10.024 · 4.43 Impact Factor
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    ABSTRACT: Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hippocampus, a structure crucially implicated in the pathogenesis of Alzheimer's disease (AD). The main aim of this study was to compare neural correlates of associative memory in healthy aging and mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to investigate differences in brain activation and connectivity between young controls (n = 20), elderly controls (n = 32) and MCI patients (n = 21) during associative memory retrieval. We observed lower hippocampal activation in MCI patients than control groups during a face-name recognition task, and the magnitude of this decrement was correlated with lower associative memory performance. Further, increased activation in precentral regions in all older adults indicated a stronger involvement of the task positive network (TPN) with age. Finally, functional connectivity analysis revealed a stronger link of hippocampal and striatal components in older adults in comparison to young controls, regardless of memory impairment. In elderly controls, this went hand-in-hand with a stronger activation of striatal areas. Increased TPN activation may be linked to greater reliance on cognitive control in both older groups, while increased functional connectivity between the hippocampus and the striatum may suggest dedifferentiation, especially in elderly controls.
    Brain Imaging and Behavior 11/2014; DOI:10.1007/s11682-014-9335-7 · 3.39 Impact Factor
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    ABSTRACT: Major depression (MDE) has metabolic and neuroendocrine correlates, which point to a biological overlap between MDE and cardiovascular diseases. Whereas the hypothalamic-pituitary-adrenocortical axis has long been recognized for its involvement in depression, the focus was mostly on cortisol/corticosterone, whereas aldosterone appears to be the 'forgotten' stress hormone. Part of the reason for this is that the receptors for aldosterone, the mineralocorticoid receptors (MR), were thought to be occupied by glucocorticoids in most parts of the brain. However, recently it turned out that aldosterone acts selectively in relevant mood-regulating brain areas, without competing with cortisol/corticosterone. These areas include the nucleus of the solitary tract (NTS), the amygdala and the paraventricular nucleus of the hypothalamus. These regions are intimately involved in the close relationship between emotional and vegetative symptoms. Genetic analysis supports the role of aldosterone and of MR-related pathways in the pathophysiology of depression. Functional markers for these pathways in animal models as well as in humans are available and allow an indirect assessment of NTS function. They include heart rate variability, baroreceptor reflex sensitivity, blood pressure, salt taste sensitivity and slow-wave sleep. MR activation in the periphery is related to electrolyte regulation. MR overactivity is a risk factor for diabetes mellitus and a trigger of inflammatory processes. These markers can be used not only to assist the development of new treatment compounds, but also for a personalized approach to treat patients with depression and related disorders by individual dose titration with an active medication, which targets this system. © 2014 S. Karger AG, Basel.
    Nephron Physiology 11/2014; 128(1-2). DOI:10.1159/000368265 · 1.55 Impact Factor
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    ABSTRACT: Patients with schizophrenia (SZ) often make aberrant cause and effect inferences in non-social and social situations. Likewise, patients may perceive cause-and-effect relationships abnormally as a result of an alteration in the physiology of perception. The neural basis for dysfunctions in causality judgements in the context of both physical motion and social motion is unknown. The current study used functional magnetic resonance imaging (fMRI) to investigate a group of patients with SZ and a group of control subjects performing judgements of causality on animated collision sequences (launch-events, Michotte, 1963) and comparable “social” motion stimuli. In both types of animations, similar motion trajectories of the affected object were configured, using parametrical variations of space (angle deviation) and time (delay). At the behavioural level, SZ patients made more physical and less social causal judgements than control subjects, and their judgements were less influenced by motion attributes (angle/time delay). In the patients group, fMRI revealed greater BOLD-responses, during both physical and social causality judgements (group × task interaction), in the left inferior frontal gyrus (L.IFG). Across conditions (main effect), L.IFG-interconnectivity with bilateral occipital cortex was reduced in the patient group. This study provides the first insight into the neural correlates of altered causal judgements in SZ. Patients with SZ tended to over-estimate physical and under-estimate social causality. In both physical and social contexts, patients are influenced less by motion parameters (space and time) than control subjects. Imaging findings of L.IFG-disconnectivity and task-related hyper-activation in the patient group could indicate common dysfunctions in the neural activations needed to integrate external cue-information (space/time) with explicit (top–down) cause–effect judgements of object motions in physical and social settings.
    Schizophrenia Research 11/2014; DOI:10.1016/j.schres.2014.11.007 · 4.43 Impact Factor
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    ABSTRACT: The potentially detrimental effects of safety behaviors during exposure therapy are still subject to debate. Empirical findings are inconsistent, and few studies have investigated effects of idiosyncratic safety behavior manifestations during exposure or in everyday life. These limitations might be due to a lack of appropriate measures that address individual safety behaviors. We examined psychometric properties and predictive value of the Texas Safety Maneuver Scale (TSMS), a questionnaire specifically targeting safety behaviors in panic disorder and agoraphobia. Effects of safety behavior use, both during everyday life and during therapy, were examined using data from a multicenter RCT of N = 268 patients that aimed at evaluating efficacy and mechanism of action of two variants of an exposure-based therapy. The TSMS total score demonstrated good internal consistency (α = .89), and it showed significant correlations with selected measures of baseline anxiety and impairment. The proposed factor structure could not be replicated. Frequent safety behavior use at baseline was associated with actual safety behavior during exposure exercises. Pronounced in-situ safety behavior, but not baseline safety behavior was associated to detrimental treatment outcome. The results underline the relevance of a rigorous safety behavior assessment in therapy. The actual relationship between safety behavior use and treatment outcome is yet to determine.
    Journal of Anxiety Disorders 10/2014; 28(8). DOI:10.1016/j.janxdis.2014.09.010 · 2.96 Impact Factor

Publication Stats

6k Citations
1,374.66 Total Impact Points


  • 2007–2015
    • Philipps University of Marburg
      • • Institute for German Linguistics
      • • Fachbereich Psychologie
      Marburg, Hesse, Germany
    • Ruhr-Universität Bochum
      • Arbeitsgruppe Klinische Psychologie und Psychotherapie
      Bochum, North Rhine-Westphalia, Germany
    • University of Wuerzburg
      • Department of Psychiatry, Psychosomatics, and Psychotherapy
      Würzburg, Bavaria, Germany
    • Universität des Saarlandes
      • Klinische Neuropsychologie
      Homburg, Saarland, Germany
    • Psychiatrische Universitätsklinik Zürich
      Zürich, Zurich, Switzerland
    • LWL-Klinik Marsberg
      Marsberg, North Rhine-Westphalia, Germany
    • Universität Ulm
      • Klinik für Psychiatrie und Psychotherapie III (Ulm)
      Ulm, Baden-Wuerttemberg, Germany
    • Otto-Friedrich-Universität Bamberg
      Bamberg, Bavaria, Germany
    • University of Cambridge
      Cambridge, England, United Kingdom
    • Humboldt University of Berlin
      • Department of Psychology
      Berlin, Land Berlin, Germany
    • Universität Heidelberg
      • Department of General Psychiatry
      Heidelburg, Baden-Württemberg, Germany
  • 2011–2014
    • Technische Universität Dresden
      • Department of Psychology
      Dresden, Saxony, Germany
    • Durham University
      • Department of Psychology
      Durham, ENG, United Kingdom
  • 2005–2013
    • RWTH Aachen University
      • Department of Psychiatry, Psychotherapy and Psychosomatics
      Aachen, North Rhine-Westphalia, Germany
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
    • Hertie-Institute for Clinical Brain Research
      Tübingen, Baden-Württemberg, Germany
  • 2009
    • The University of York
      • Department of Psychology
      York, ENG, United Kingdom
  • 2005–2009
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 1997–2009
    • University of Tuebingen
      • • Department of Psychiatry and Psychotherapy
      • • Department of Neurology
      Tübingen, Baden-Wuerttemberg, Germany
  • 2006–2007
    • University of Cologne
      • Department of Psychiatry and Psychotherapy
      Köln, North Rhine-Westphalia, Germany
    • University of Birmingham
      Birmingham, England, United Kingdom
  • 2004
    • Max Planck Society
      München, Bavaria, Germany
  • 2002
    • University of Nottingham
      Nottigham, England, United Kingdom
  • 2000
    • London Research Institute
      Londinium, England, United Kingdom