Tilo Kircher

Technische Universität Dresden, Dresden, Saxony, Germany

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Publications (332)1103.15 Total impact

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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; · 2.67 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;
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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; · 2.96 Impact Factor
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    KogWis 2014; 10/2014
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    ABSTRACT: Variation in the 5'-flanking promoter region of the serotonin transporter gene SLC6A4, the 5-HTT-linked polymorphic region (5-HTTLPR) has been inconclusively associated with response to cognitive-behavioural therapy (CBT). As genomic functions are stronger related to neural than to behavioural markers, we investigated the association of treatment response, 5-HTTLPR and functional brain connectivity in patients with panic disorder with agoraphobia (PD/AG). Within the national research network PANIC-NET 231 PD/AG patients who provided genetic information underwent a manualized exposure-based CBT. A subset of 41 patients participated in a functional magnetic resonance imaging (fMRI) add-on study prior to treatment applying a differential fear conditioning task. Neither the treatment nor the reduced fMRI sample showed a direct effect of 5-HTTLPR on treatment response as defined by a reduction in the Hamilton Anxiety Scale score ≥50 % from baseline to post assessment. On a neural level, inhibitory anterior cingulate cortex (ACC)-amygdala coupling during fear conditioning that had previously been shown to characterize treatment response in this sample was driven by responders with the L/L genotype. Building upon conclusive evidence from basic and preclinical findings on the association of the 5-HTTLPR polymorphism with emotion regulation and related brain connectivity patterns, present findings translate these to a clinical sample of PD/AG patients and point towards a potential intermediate connectivity phenotype modulating response to exposure-based CBT.
    Journal of Neural Transmission 09/2014; · 3.05 Impact Factor
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    ABSTRACT: The A allele of the single nucleotide polymorphism (SNP) rs1064395 in the NCAN gene has recently been identified as a susceptibility factor for bipolar disorder and schizophrenia. NCAN encodes neurocan, a brain-specific chondroitin sulfate proteoglycan that is thought to influence neuronal adhesion and migration. Several lines of research suggest an impact of NCAN on neurocognitive functioning. In the present study, we investigated the effects of rs1064395 genotype on neural processing and cognitive performance in healthy subjects. Brain activity was measured with functional magnetic resonance imaging (fMRI) during an overt semantic verbal fluency task in 110 healthy subjects who were genotyped for the NCAN SNP rs1064395. Participants additionally underwent comprehensive neuropsychological testing. Whole brain analyses revealed that NCAN risk status, defined as AA or AG genotype, was associated with a lack of task-related deactivation in a large left lateral temporal cluster extending from the middle temporal gyrus to the temporal pole. Regarding neuropsychological measures, risk allele carriers demonstrated poorer immediate and delayed verbal memory performance when compared to subjects with GG genotype. Better verbal memory performance was significantly associated with greater deactivation of the left temporal cluster during the fMRI task in subjects with GG genotype. The current data demonstrate that common genetic variation in NCAN influences both neural processing and cognitive performance in healthy subjects. Our study provides new evidence for a specific genetic influence on human brain function. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2014; · 6.88 Impact Factor
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    ABSTRACT: Hierarchical predictive coding has been hailed a possible unifying principle of brain function (Friston, 2010). Here, we use syntactic and semantic cues to manipulate discourse prominence and thus predictability of the upcoming topic. Subjects are default topics and passive voice modulates topic prediction by realising a non-default (undergoer) argument as subject (Givon, 1994). Event type also influences prominence: highly causal verbs (e.g. “hit”) foreground both sentence participants by emphasising the prototypicality of actor and undergoer, while low causality verbs (e.g. “see”) foreground neither participant (Pyykkönen, Matthews, & Järvikivi, 2010). For highly causal events, passive voice thus signals intentional topicalization of the less prominent undergoer. In low causality events passive voice is less motivated because actor and undergoer are more closely aligned in prominence. In a naturalistic fMRI study, we examined the hypotheses that (a) passive increases future predictability of the subject; (b) this is modulated by the event-internal motivation for a passive (lower event-internal motivation equals higher discourse predictability); (c) predictions are encoded hierarchically. We obtained images (3T) of 20 healthy right-handed German monolinguals (9 male), employing a 2x2 design: voice (active vs. passive) x causality (high vs. low). Conditions were embedded in 20 two-minute long stories. Act/Pass-high: event[“Then the clown pushed the princess/Then the clown was pushed by the princess] and the teddy bear appeared again from under the dress." reference[“The clown] …“, Act/Pass-low: event[“The professor agitated his assistant/The professor was agitated by his assistant] because the papers had been reporting about an unstable roof construction.” reference[“The professor] …“. Subjects were instructed to listen carefully and were asked two comprehension questions after each story. Analyses included position of measurement (event vs. reference) resulting in a 2x2x2 model. We report clusters of p<.005 and volumes of at least 72 voxels (Monte Carlo corrected). Voice, causality and position interacted in bilateral dorsal stream regions, including the left posterior STG, bilateral Rolandic operculum, premotor cortex and postcentral gyri. All interactions resulted from effects for the target referent as opposed to the context and to higher activation for act-low/pass-high versus act-high/pass-low. Two-way interactions of voice and position due to higher activation for active versus passive conditions at the referent were observed in left frontomedian regions (ACC and SMA). Position and causality interacted in the left angular gyrus, with higher activation for low vs. high causality on the referent. The elevated activation for less predicted topics may reflect prediction error or increased effort associated with processing a non-predicted referent. Our data thus support the assumption that topicality-related discourse predictions are processed in the dorsal stream (Bornkessel-Schlesewsky & Schlesewsky, 2013). They provide initial evidence for a hierarchical organisation, with frontomedial cortex encoding predictions for passive versus active subjects, the angular gyrus encoding higher predictions for participants in causal events, and the posterior STG encoding highly specific predictions for a particular referent based on both voice and causality. Importantly, our data cannot be explained purely by syntactic differences between active and passive sentences since the crucial effects were observed on referents rather than events.
    Society of the Neurobiology of Language, Amsterdam; 08/2014
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    ABSTRACT: G72 (syn. DAOA, D-amino acid oxidase activator) is a susceptibility gene for both schizophrenia and bipolar disorder. Diffusion tensor imaging studies hint at changes in fiber tract integrity in both disorders. We aimed to investigate whether a G72 susceptibility haplotype causes changes in fiber tract integrity in young healthy subjects. We compared fractional anisotropy in 47 subjects that were either homozygous for the M23/M24 risk haplotype (n = 20) or homozygous for M23(rs3918342)/M24(rs1421292) wild type (n = 27) using diffusion tensor imaging with 3 T. Tract-based spatial statistics, a method especially developed for diffusion data analysis, was used to delineate the major fiber tracts. We found clusters of increased FA values in homozygous risk haplotype carriers in the right periinsular region and in the right inferior parietal lobe (IPL). We did not find clusters indicating decreased FA values. The insula and the IPL have been implicated in both schizophrenia and bipolar pathophysiology. Increased FA values might reflect changes in dendritic morphology as previously described by in vitro studies. These findings further corroborate the hypothesis that a shared gene pool between schizophrenia and bipolar disorder might lead to neuroanatomic changes that confer an unspecific vulnerability for both disorders.
    European Archives of Psychiatry and Clinical Neuroscience 07/2014; · 3.36 Impact Factor
  • Yunbo Yang, Tilo Kircher, Benjamin Straube
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    ABSTRACT: Cognitive behavioral therapy (CBT) is an evidence-based treatment for mental disorders. Several meta-analytical reviews supported its efficacy and effectiveness in the treatment of panic disorder with agoraphobia (PD/AG). Recently, it has been shown that neurobiological changes are associated with the process and outcome of CBT. However, the general and specific neurobiological effects of CBT are still widely unknown. Therefore, the potential of applying neuroscience to clinical practice and optimizing CBT is still limited. The current review summarizes recent findings about the neural correlates of CBT in PD/AG measured with fMRI. Furthermore, the current review will focus on neural activation patterns predicting and moderating therapeutic success of CBT, due to its potential application in personalized treatment in the future. Finally, we will discuss some future perspectives of the neurosciences in CBT research.
    Behaviour Research and Therapy 07/2014; · 3.85 Impact Factor
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    Human Brain Mapping, Hamburg; 06/2014
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    ABSTRACT: Theoretical models postulate an important role of attributional style (AS) in the formation and maintenance of persecutory delusions and other positive symptoms of schizophrenia. However, current research has gathered conflicting findings. In a cross-sectional design, patients with persistent positive symptoms of schizophrenia (n = 258) and healthy controls (n = 51) completed a revised version of the Internal, Personal and Situational Attributions Questionnaire (IPSAQ-R) and assessments of psychopathology. In comparison to controls, neither patients with schizophrenia in general nor patients with persecutory delusions (n = 142) in particular presented an externalizing and personalizing AS. Rather, both groups showed a "self-blaming" AS and attributed negative events more toward themselves. Persecutory delusions were independently predicted by a personalizing bias for negative events (beta = 0.197, P = .001) and by depression (beta = 0.152, P = .013), but only 5% of the variance in persecutory delusions could be explained. Cluster analysis of IPSAQ-R scores identified a "personalizing" (n = 70) and a "self-blaming" subgroup (n = 188), with the former showing slightly more pronounced persecutory delusions (P = .021). Results indicate that patients with schizophrenia and patients with persecutory delusions both mostly blamed themselves for negative events. Nevertheless, still a subgroup of patients could be identified who presented a more pronounced personalizing bias and more severe persecutory delusions. Thus, AS in patients with schizophrenia might be less stable but more determined by individual and situational characteristics that need further elucidation.
    Schizophrenia Bulletin 04/2014; · 8.80 Impact Factor
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    ABSTRACT: Speech-associated gesturing leads to memory advantages for spoken sentences. However, unexpected or surprising events are also likely to be remembered. With this study we test the hypothesis that different neural mechanisms (semantic elaboration and surprise) lead to memory advantages for iconic and unrelated gestures. During fMRI-data acquisition participants were presented with video clips of an actor verbalising concrete sentences accompanied by iconic gestures (IG; e.g., circular gesture; sentence: "The man is sitting at the round table"), unrelated free gestures (FG; e.g., unrelated up down movements; same sentence) and no gestures (NG; same sentence). After scanning, recognition performance for the three conditions was tested. Videos were evaluated regarding semantic relation and surprise by a different group of participants. The semantic relationship between speech and gesture was rated higher for IG (IG>FG), whereas surprise was rated higher for FG (FG>IG). Activation of the hippocampus correlated with subsequent memory performance of both gesture conditions (IG+FG>NG). For the IG condition we found activation in the left temporal pole and middle cingulate cortex (MCC; IG>FG). In contrast, for the FG condition posterior thalamic structures (FG>IG) as well as anterior and posterior cingulate cortices were activated (FG>NG). Our behavioral and fMRI-data suggest different mechanisms for processing related and unrelated co-verbal gestures, both of them leading to enhanced memory performance. Whereas activation in MCC and left temporal pole for iconic co-verbal gestures may reflect semantic memory processes, memory enhancement for unrelated gestures relies on the surprise response, mediated by anterior/posterior cingulate cortex and thalamico-hippocampal structures.
    Brain research 04/2014; · 2.46 Impact Factor
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    ABSTRACT: Background: Changes in fiber tract architecture have gained attention as a potentially important aspect of schizophrenia neuropathology. Although the exact pathogenesis of these abnormalities yet remains to be elucidated, a genetic component is highly likely. Neuregulin-1 (NRG1) is one of the best-validated schizophrenia susceptibility genes. We here report the impact of the Neuregulin-1 rs35753505 variant on white matter structure in healthy young individuals with no family history of psychosis. Methods: We compared fractional anisotropy in 54 subjects that were either homozygous for the risk C allele carriers (n = 31) for rs35753505 or homozygous for the T allele (n = 23) using diffusion tensor imaging with 3T. Tract-Based Spatial Statistics (TBSS), a method especially developed for diffusion data analysis, was used to improve white matter registration and to focus the statistical analysis to major fiber tracts. Results: Statistical analysis showed that homozygous risk C allele carriers featured elevated fractional anisotropy (FA) in the right perihippocampal region and the white matter proximate to the left area 4p as well as the right hemisphere of the cerebellum. We found three clusters of reduced FA values in homozygous C allele carriers: in the left superior parietal region, the right prefrontal white matter and in the deep white matter of the left frontal lobe. Conclusion: Our results highlight the importance of Neuregulin-1 for structural connectivity of the right medial temporal lobe. This finding is in line with well known neuropathological findings in this region in patients with schizophrenia.
    Brain and behavior. 03/2014; 4(2):215-26.
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    ABSTRACT: Memory impairments are common in major depression. Neural processing during non-emotional episodic memory in depressed patients has only sparsely been investigated, since the majority of studies have focused on emotional stimuli. The aim of this study was to explore neural correlates of episodic memory in depressive patients and to assess brain regions related to subsequent memory performance. Forty-six participants (23 depressed patients) performed a non-emotional episodic memory encoding and retrieval task while brain activation was measured with functional magnetic resonance imaging. Patients with depression showed decreased activation in the right prefrontal cortex and right cingulate cortex during memory encoding, but increased activation in the right inferior frontal gyrus (IFG) during recognition memory. While a strong association between hippocampal and parahippocampal activation during memory encoding with subsequent memory performance became evident in healthy controls, this relationship was absent in patients with depression. Taken together, these findings demonstrate that memory related brain regions are affected in their appropriate functioning during memory encoding in depressed patients. Therefore, patients with depression may rely to a greater degree on other brain regions such as the IFG during episodic memory retrieval. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 03/2014; · 6.88 Impact Factor
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    ABSTRACT: Major depression is associated with impairments in semantic verbal fluency (VF). However, the neural correlates underlying dysfunctional cognitive processing in depressed subjects during the production of semantic category members still remain unclear. In the current study, an overt and continuous semantic VF paradigm was used to examine these mechanisms in a representative sample of 33 patients diagnosed with a current episode of unipolar depression and 33 statistically matched healthy controls. Subjects articulated words in response to semantic category cues while brain activity was measured with functional magnetic resonance imaging (fMRI). Compared to controls, patients showed poorer task performance. On the neural level, a group by condition interaction analysis, corrected for task performance, revealed a reduced task-related deactivation in patients in the right parahippocampal gyrus, the right fusiform gyrus, and the right supplementary motor area. An additional and an increased task-related activation in patients were observed in the right precentral gyrus and the left cerebellum, respectively. These results indicate that a failure to suppress potentially interfering activity from inferior temporal regions involved in default-mode network functions and visual imagery, accompanied by an enhanced recruitment of areas implicated in speech initiation and higher-order language processes, may underlie dysfunctional cognitive processing during semantic VF in depression. The finding that patients with depression demonstrated both decreased performance and aberrant brain activation during the current semantic VF task demonstrates that this paradigm is a sensitive tool for assessing brain dysfunctions in clinical populations.
    European Archives of Psychiatry and Clinical Neuroscience 02/2014; · 3.36 Impact Factor
  • Schizophrenia Bulletin 02/2014; in press. · 8.80 Impact Factor
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    ABSTRACT: Panic disorder with agoraphobia (PD/AG) is a prevalent mental disorder featuring a substantial complex genetic component. At present, only a few established risk genes exist. Among these, the gene encoding monoamine oxidase A (MAOA) is noteworthy given that genetic variation has been demonstrated to influence gene expression and monoamine levels. Long alleles of the MAOA-uVNTR promoter polymorphism are associated with PD/AG and correspond with increased enzyme activity. Here, we have thus investigated the impact of MAOA-uVNTR on therapy response, behavioral avoidance and brain activity in fear conditioning in a large controlled and randomized multicenter study on cognitive behavioral therapy (CBT) in PD/AG. The study consisted of 369 PD/AG patients, and genetic information was available for 283 patients. Carriers of the risk allele had significantly worse outcome as measured by the Hamilton Anxiety scale (46% responders vs 67%, P=0.017). This was accompanied by elevated heart rate and increased fear during an anxiety-provoking situation, that is, the behavioral avoidance task. All but one panic attack that happened during this task occurred in risk allele carriers and, furthermore, risk allele carriers did not habituate to the situation during repetitive exposure. Finally, functional neuroimaging during a classical fear conditioning paradigm evidenced that the protective allele is associated with increased activation of the anterior cingulate cortex upon presentation of the CS+ during acquisition of fear. Further differentiation between high- and low-risk subjects after treatment was observed in the inferior parietal lobes, suggesting differential brain activation patterns upon CBT. Taken together, we established that a genetic risk factor for PD/AG is associated with worse response to CBT and identify potential underlying neural mechanisms. These findings might govern how psychotherapy can include genetic information to tailor individualized treatment approaches.Molecular Psychiatry advance online publication, 15 January 2013; doi:10.1038/mp.2012.172.
    Molecular Psychiatry 01/2014; 19(1):122-128. · 15.15 Impact Factor
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    ABSTRACT: Panic disorder with agoraphobia is characterized by panic attacks and anxiety in situations where escape might be difficult. However, neuroimaging studies specifically focusing on agoraphobia are rare. Here we used functional magnetic resonance imaging (fMRI) with disorder-specific stimuli to investigate the neural substrates of agoraphobia. We compared the neural activations of 72 patients suffering from panic disorder with agoraphobia with 72 matched healthy control subjects in a 3-T fMRI study. To isolate agoraphobia-specific alterations we tested the effects of the anticipation and perception of an agoraphobia-specific stimulus set. During fMRI, 48 agoraphobia-specific and 48 neutral pictures were randomly presented with and without anticipatory stimulus indicating the content of the subsequent pictures (Westphal paradigm). During the anticipation of agoraphobia-specific pictures, stronger activations were found in the bilateral ventral striatum and left insula in patients compared with controls. There were no group differences during the perception phase of agoraphobia-specific pictures. This study revealed stronger region-specific activations in patients suffering from panic disorder with agoraphobia in anticipation of agoraphobia-specific stimuli. Patients seem to process these stimuli more intensively based on individual salience. Hyperactivation of the ventral striatum and insula when anticipating agoraphobia-specific situations might be a central neurofunctional correlate of agoraphobia. Knowledge about the neural correlates of anticipatory and perceptual processes regarding agoraphobic situations will help to optimize and evaluate treatments, such as exposure therapy, in patients with panic disorder and agoraphobia.
    Psychological Medicine 01/2014; · 5.59 Impact Factor
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    ABSTRACT: Neurosteroids are synthesized both in brain and peripheral steroidogenic tissue from cholesterol or steroidal precursors. Neurosteroids have been shown to be implicated in neural proliferation, differentiation, and activity. Preclinical and clinical studies also suggest a modulatory role of neurosteroids in anxiety-related phenotypes. However, little is known about the contribution of genetic variants in genes relevant for the neurosteroidogenesis to anxiety disorders. We performed an association analysis of single nucleotide polymorphisms (SNPs) in five genes related to the neurosteroidal pathway with emphasis on progesterone and allopregnanolone biosynthesis (steroid-5-alpha-reductase 1A (SRD5A1), aldo-keto reductase family 1 C1-C3 (AKR1C1-AKR1C3) and translocator protein 18 kDA (TSPO) with panic disorder (PD) and dimensional anxiety in two German PD samples (cases N = 522, controls N = 1,115). Case-control analysis for PD and SNPs in the five selected genes was negative in the combined sample. However, we detected a significant association of anticipatory anxiety with two intronic SNPs (rs3930965, rs41314625) located in the gene AKR1C1 surviving correction for multiple testing in PD patients. Stratification analysis for gender revealed a female-specific effect of the associations of both SNPs. These results suggest a modulatory effect of AKR1C1 activity on anxiety levels, most likely through changes in progesterone and allopregnanolone levels within and outside the brain. In summary, this is the first evidence for the gender-specific implication of the AKR1C1 gene in the expression of anticipatory anxiety in PD. Further analyses to unravel the functional role of the SNPs detected here and replication analyses are needed to validate our results.
    Depression and Anxiety 01/2014; · 4.61 Impact Factor
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    ABSTRACT: BACKGROUND: Although several neurophysiological models have been proposed for panic disorder with agoraphobia (PD/AG), there is limited evidence from functional magnetic resonance imaging (fMRI) studies on key neural networks in PD/AG. Fear conditioning has been proposed to represent a central pathway for the development and maintenance of this disorder; however, its neural substrates remain elusive. The present study aimed to investigate the neural correlates of fear conditioning in PD/AG patients. Method The blood oxygen level-dependent (BOLD) response was measured using fMRI during a fear conditioning task. Indicators of differential conditioning, simple conditioning and safety signal processing were investigated in 60 PD/AG patients and 60 matched healthy controls. RESULTS: Differential conditioning was associated with enhanced activation of the bilateral dorsal inferior frontal gyrus (IFG) whereas simple conditioning and safety signal processing were related to increased midbrain activation in PD/AG patients versus controls. Anxiety sensitivity was associated positively with the magnitude of midbrain activation. CONCLUSIONS: The results suggest changes in top-down and bottom-up processes during fear conditioning in PD/AG that can be interpreted within a neural framework of defensive reactions mediating threat through distal (forebrain) versus proximal (midbrain) brain structures. Evidence is accumulating that this network plays a key role in the aetiopathogenesis of panic disorder.
    Psychological Medicine 01/2014; 44(2):381–394. · 5.59 Impact Factor

Publication Stats

4k Citations
1,103.15 Total Impact Points


  • 2011–2014
    • Technische Universität Dresden
      • Department of Psychology
      Dresden, Saxony, Germany
    • Durham University
      • Department of Psychology
      Durham, ENG, United Kingdom
    • University of Pennsylvania
      • Center for Cognitive Neuroscience
      Philadelphia, PA, United States
  • 2007–2014
    • Philipps University of Marburg
      • • Institute for German Linguistics
      • • Fachbereich Psychologie
      Marburg, Hesse, Germany
    • University of Wuerzburg
      • Department of Psychiatry, Psychosomatics, and Psychotherapy
      Würzburg, Bavaria, Germany
    • University of Cologne
      • Department of Psychiatry and Psychotherapy
      Köln, North Rhine-Westphalia, Germany
    • University Hospital Essen
      • Klinik für Psychiatrie und Psychotherapie
      Essen, North Rhine-Westphalia, Germany
    • Universität Hamburg
      • Department of Psychiatry and Psychotherapy
      Hamburg, Hamburg, Germany
    • Ruhr-Universität Bochum
      • Arbeitsgruppe Klinische Psychologie und Psychotherapie
      Bochum, North Rhine-Westphalia, Germany
    • Psychiatrische Universitätsklinik Zürich
      Zürich, Zurich, Switzerland
    • Universität des Saarlandes
      • Klinische Neuropsychologie
      Homburg, Saarland, Germany
    • LWL-Klinik Marsberg
      Marsberg, North Rhine-Westphalia, Germany
    • University of Bonn
      • Department of Neurobiology
      Bonn, North Rhine-Westphalia, Germany
    • Universität Ulm
      • Klinik für Psychiatrie und Psychotherapie III (Ulm)
      Ulm, Baden-Wuerttemberg, Germany
    • University of Cambridge
      Cambridge, England, United Kingdom
    • Otto-Friedrich-Universität Bamberg
      Bamberg, Bavaria, Germany
    • Humboldt University of Berlin
      • Department of Psychology
      Berlin, Land Berlin, Germany
    • Universität Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2013
    • University of Queensland 
      • School of Psychology
      Brisbane, Queensland, Australia
  • 2012–2013
    • King's College London
      • • Institute of Psychiatry
      • • Department of Psychosis Studies
      Londinium, England, United Kingdom
    • Universität Osnabrück
      • Institute of Cognitive Science
      Osnabrück, Lower Saxony, Germany
    • University of Greifswald
      • Institute of Psychology
      Griefswald, Mecklenburg-Vorpommern, Germany
  • 2005–2013
    • RWTH Aachen University
      • Department of Psychiatry, Psychotherapy and Psychosomatics
      Aachen, North Rhine-Westphalia, Germany
    • Korea Advanced Institute of Science and Technology
      Sŏul, Seoul, South Korea
    • Hertie-Institute for Clinical Brain Research
      Tübingen, Baden-Württemberg, Germany
    • Universitätsklinikum Tübingen
      Tübingen, Baden-Württemberg, Germany
  • 2009–2011
    • University of Münster
      • Department of Psychiatry
      Münster, North Rhine-Westphalia, Germany
    • The University of York
      • Department of Psychology
      York, ENG, United Kingdom
    • University of Newcastle
      • Centre for Rural and Remote Mental Health
      Newcastle, New South Wales, Australia
  • 2005–2008
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 1997–2007
    • University of Tuebingen
      • • Institute of Medical Psychology and Behavioral Neurobiology
      • • Department of Psychiatry and Psychotherapy
      • • Group of Clinical Psychology and Psychotherapy
      Tübingen, Baden-Württemberg, Germany
  • 2006
    • University of Birmingham
      Birmingham, England, United Kingdom
  • 2004
    • Max Planck Society
      München, Bavaria, Germany
  • 2001
    • Heinrich-Heine-Universität Düsseldorf
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie der HHU, Rheinische Kliniken Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany