Publications by authors named "Peter Zwanzger"

141 Publications

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes.

J Neural Transm (Vienna) 2020 Nov 29;127(11):1527-1537. Epub 2020 May 29.

Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Margarete-Höppel Platz 1, 97080, Würzburg, Germany.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.
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http://dx.doi.org/10.1007/s00702-020-02206-xDOI Listing
November 2020

Extending the vulnerability-stress model of mental disorders: three-dimensional × environment × coping interaction study in anxiety.

Br J Psychiatry 2020 11;217(5):645-650

Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, and Center for Basics in Neuromodulation, Faculty of Medicine, University of Freiburg, Germany.

Background: The general understanding of the 'vulnerability-stress model' of mental disorders neglects the modifying impact of resilience-increasing factors such as coping ability.

Aims: Probing a conceptual framework integrating both adverse events and coping factors in an extended 'vulnerability-stress-coping model' of mental disorders, the effects of functional neuropeptide S receptor gene (NPSR1) variation (G), early adversity (E) and coping factors (C) on anxiety were addressed in a three-dimensional G × E × C model.

Method: In two independent samples of healthy probands (discovery: n = 1403; replication: n = 630), the interaction of NPSR1 rs324981, childhood trauma (Childhood Trauma Questionnaire, CTQ) and general self-efficacy as a measure of coping ability (General Self-Efficacy Scale, GSE) on trait anxiety (State-Trait Anxiety Inventory) was investigated via hierarchical multiple regression analyses.

Results: In both samples, trait anxiety differed as a function of NPSR1 genotype, CTQ and GSE score (discovery: β = 0.129, P = 3.938 × 10-8; replication: β = 0.102, P = 0.020). In A allele carriers, the relationship between childhood trauma and anxiety was moderated by general self-efficacy: higher self-efficacy and childhood trauma resulted in low anxiety scores, and lower self-efficacy and childhood trauma in higher anxiety levels. In turn, TT homozygotes displayed increased anxiety as a function of childhood adversity unaffected by general self-efficacy.

Conclusions: Functional NPSR1 variation and childhood trauma are suggested as prime moderators in the vulnerability-stress model of anxiety, further modified by the protective effect of self-efficacy. This G × E × C approach - introducing coping as an additional dimension further shaping a G × E risk constellation, thus suggesting a three-dimensional 'vulnerability-stress-coping model' of mental disorders - might inform targeted preventive or therapeutic interventions strengthening coping ability to promote resilient functioning.
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http://dx.doi.org/10.1192/bjp.2020.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589989PMC
November 2020

Drug-Induced Liver Injury (DILI) in Patients with Depression Treated with Antidepressants: A Retrospective Multicenter Study.

Pharmacopsychiatry 2020 Mar 20;53(2):60-64. Epub 2020 Jan 20.

Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, LWL-Klinik Dortmund, Dortmund, Germany.

Introduction: Drug-induced liver injury (DILI) is the 4th most common cause of liver damage in Western countries and can be caused by antidepressants.

Methods: Against the background of increasing antidepressant prescriptions and increasing use of polypharmacy, we analyzed administered antidepressants and other pharmacological substances, liver toxicity, comorbid somatic secondary diseases together with the occurrence of DILI in a patient population of 6 centers throughout Germany.

Results: The majority of the enrolled 329 patients received polypharmacological treatment in an inpatient setting. During antidepressant treatment 5.1% of the patients had elevated serum transaminase levels, whereby exactly and not more than 1 criterion proposed to be indicative for DILI, was fulfilled by 3 patients (0.9%).

Discussion: During patient characterization it becomes clear that a sensitization for relevant risk constellations causing liver injury in MDD patients is relevant to prevent further serious adverse events.
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http://dx.doi.org/10.1055/a-1071-8028DOI Listing
March 2020

Affective temperaments (TEMPS-A) in panic disorder and healthy probands: Genetic modulation by variation.

World J Biol Psychiatry 2020 12 31;21(10):790-796. Epub 2020 Jan 31.

Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objectives: Temperamental traits as ascertained by the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-Questionnaire (TEMPS-A) have been suggested as promising intermediate phenotypes of mental disorders. In anxiety disorders, however, TEMPS scales and their genetic underpinnings are still understudied.

Methods: TEMPS-A scores in 109 patients with panic disorder (PD) were compared to a sample of 536 healthy probands. All participants were genotyped for serotonin transporter gene variation (LPR/rs25531).

Results: PD patients displayed significantly increased scores on the dysthymic, cyclothymic, irritable and anxious subscales, and lower scores on the hyperthymic subscale, respectively (all ps < 0.001) compared to healthy probands. In the total sample, the less active LPR/rs25531 S/L alleles were associated with higher scores on the dysthymic, cyclothymic, irritable and anxious temperaments (all ps < 0.01), but not the hyperthymic subscale. Mediation analyses revealed anxious temperament in particular to mediate the relationship between genotype and PD.

Conclusions: Dysthymic, cyclothymic, irritable and notably anxious temperament could serve as valuable intermediate phenotypes in efforts to unravel neurobiological, particularly serotonin system related genetic pathomechanisms associated with PD and potentially contribute to a panel of vulnerability markers guiding early targeted preventive interventions.
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http://dx.doi.org/10.1080/15622975.2019.1705999DOI Listing
December 2020

Copeptin in CCK-4-induced panic in healthy man: Sexual dimorphisms in secretion pattern and panic response, but no correlation of copeptin with panic symptoms.

Psychoneuroendocrinology 2019 12 5;110:104433. Epub 2019 Sep 5.

University Medical Center Hamburg-Eppendorf, Dept. of Psychiatry and Psychotherapy, Hamburg, Germany.

Copeptin, the C-terminal part of the hypothalamic arginine vaspopressin (AVP) precursor, closely mirrors the production of AVP and was proposed as an easily measured novel marker of the individual stress level in man. First data in male volunteers proposed copeptin as a potential endocrine surrogate marker of cholecystokinin-tetrapeptide (CCK-4)-induced panic. We tried to replicate these pilot data and to extend them to the other sex. 46 healthy human subjects (29 men, 17 women) were given an intravenous bolus of 50 μg CCK-4. Basal and stimulated plasma copeptin was measured and panic symptoms were assessed using the Acute Panic Inventory (API). Basal copeptin was significantly lower in women vs. men, while men showed a significantly higher CCK-4-induced increase of copeptin. In contrast, female subjects displayed a signifcantly higher increase of API ratings by CCK-4. No significant correlations of panic symptoms and copeptin release induced by CCK-4 could be found, neither in man, nor in women, nor in the total sample. A sexual dimorphism in copeptin secretion and in panic response was demonstrated. Prior unexpected findings of copeptin release as an objective read-out of panic could not be replicated. The role of the vasopressinergic system in panic anxiety needs further study in panic patients and in healthy man, using also other panic provocation paradigms.
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http://dx.doi.org/10.1016/j.psyneuen.2019.104433DOI Listing
December 2019

Hypermethylation of the serotonin transporter gene promoter in panic disorder-Epigenetic imprint of comorbid depression?

Eur Neuropsychopharmacol 2019 10 26;29(10):1161-1167. Epub 2019 Jul 26.

Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Germany; Center for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Germany. Electronic address:

Panic disorder (PD) is frequently comorbid with major depressive disorder (MDD), which has been associated with impaired treatment response and recovery rates. Alterations in the serotonergic system may play a crucial role in the pathogenesis of PD and MDD and might constitute a shared biological trunk of both disorders. Epigenetic patterns such as hypermethylation of the serotonin transporter gene (SLC6A4) have been associated with various mental disorders including MDD, but, to date, no association with PD has been reported. In the present study, SLC6A4 promoter methylation was investigated in two independent samples of PD patients in a case-control design (sample 1: N = 120; sample 2: N = 118), while - given the reported high comorbidity of both disorders - taking into account the effect of comorbid MDD. The functional relevance of altered SLC6A4 promoter methylation was investigated by means of luciferase-based reporter gene assays. SLC6A4 promoter hypermethylation in PD patients relative to healthy controls was driven by comorbid diagnosis of MDD (p = 9 × 10), whereas no altered methylation levels were observed in patients without comorbid MDD. This held true not only in comparison to healthy controls, but also in direct comparison between PD patients with and without comorbid MDD (p = .009). Functional analyses revealed increased methylation of the investigated region to confer decreased reporter gene activity. The present results suggest functionally relevant SLC6A4 promoter hypermethylation as a possibly specific epigenetic marker of MDD, but not of PD itself, and thus might constitute a selective biomarker informing differential diagnosis based on individual epigenetic profiles.
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http://dx.doi.org/10.1016/j.euroneuro.2019.07.131DOI Listing
October 2019

Social Defeat Modulates T Helper Cell Percentages in Stress Susceptible and Resilient Mice.

Int J Mol Sci 2019 Jul 17;20(14). Epub 2019 Jul 17.

Department of Psychiatry, University of Münster, 48149 Münster, Germany.

Altered adaptive immunity involving T lymphocytes has been found in depressed patients and in stress-induced depression-like behavior in animal models. Peripheral T cells play important roles in homeostasis and function of the central nervous system and thus modulate behavior. However, the T cell phenotype and function associated with susceptibility and resilience to depression remain largely unknown. Here, we characterized splenic T cells in susceptible and resilient mice after 10 days of social defeat stress (SDS). We found equally decreased T cell frequencies and comparably altered expression levels of genes associated with T helper (Th) cell function in resilient and susceptible mice. Interleukin (IL)-17 producing CD4 and CD8 T cell numbers in the spleen were significantly increased in susceptible mice. These animals further exhibited significantly reduced numbers of regulatory T cells (T) and decreased gene expression levels of TGF-β. Mice with enhanced Th17 differentiation induced by conditional deletion of PPARγ in CD4 cells (CD4-PPARγ), an inhibitor of Th17 development, were equally susceptible to SDS when compared to CD4-PPARγ controls. These data indicate that enhanced Th17 differentiation alone does not alter stress vulnerability. Thus, SDS promotes Th17 cell and suppresses T cell differentiation predominantly in susceptible mice with yet unknown effects in immune responses after stress exposure.
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http://dx.doi.org/10.3390/ijms20143512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678569PMC
July 2019

Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes.

Transl Psychiatry 2019 02 4;9(1):75. Epub 2019 Feb 4.

Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Preclinical studies point to a pivotal role of the orexin 1 (OX) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10), particularly in the female subsample (p = 9.8 × 10). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.
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http://dx.doi.org/10.1038/s41398-019-0415-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361931PMC
February 2019

The causal role of prefrontal hemispheric asymmetry in valence processing of words - Insights from a combined cTBS-MEG study.

Neuroimage 2019 05 1;191:367-379. Epub 2019 Feb 1.

Department of Otorhinolaryngology, Jena University Hospital, Friedrich Schiller University, Stoystr. 3, D-07743, Jena, Germany.

Hemispheric asymmetries play an important role in multiple cerebral functions. Asymmetries in prefrontal cortex (PFC) function have been suggested to regulate emotional processing in that right-hemispheric dominance biases towards negative affect, whereas left PFC dominance favors positive affect. This study used transcranial magnetic stimulation to test the causal role of prefrontal asymmetries in the processing of emotional stimuli. To experimentally induce hemispheric asymmetries, 21 healthy volunteers underwent two separate sessions of inhibitory continuous theta burst stimulation (cTBS) to the left versus right dorsolateral prefrontal cortex. Each stimulation was followed by magnetoencephalographic (MEG) recordings of event-related fields elicited by visually presented emotional words in a silent reading task and a subsequent behavioral emotion categorization task. The asymmetry manipulation influenced valence processing of words in early, mid-latency and late time intervals in right occipitotemporal and parietal brain regions. Left-sided cTBS (inducing right-hemispheric dominance) consistently resulted in enhanced brain responses to negative words, while right-sided cTBS (inducing left-hemispheric dominance) enhanced responses to positive words. On a behavioral level, right-hemispheric dominance resulted in more categorization matches of negative compared to positive words, while left-hemispheric dominance resulted in reverse effects. These results provide direct evidence that bottom-up valence processing is influenced by prefrontal hemispheric asymmetry.
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http://dx.doi.org/10.1016/j.neuroimage.2019.01.057DOI Listing
May 2019

[Development of virtual reality as an exposure technique].

Nervenarzt 2019 Jul;90(7):715-723

kbo-Inn-Salzach-Klinikum, Gabersee 7, 83512, Wasserburg am Inn, Deutschland.

Background: Virtual reality (VR) has been investigated as a medium for exposure therapy of anxiety disorders for 20 years. Various meta-analyses have provided convincing evidence of the therapeutic efficacy of exposure therapy in VR.

Objective: In recent years VR technology and its applications have considerably improved. Therefore, the current state of the art of VR exposure therapy is presented.

Material And Methods: This article provides a narrative review of current research on VR exposure therapy for anxiety disorders and major directions of development in this area.

Results: After an almost exclusive focus on specific phobias in the early days, research on more complex anxiety disorders (particularly on social anxiety disorder) is increasing. In addition, VR has become established as an experimental method to probe psychopathological processes and to elucidate the mechanism of action of (VR) exposure therapy.

Conclusion: There is still a need for more research into VR exposure therapy, especially in complex anxiety disorders (e. g. panic disorder, agoraphobia and social anxiety disorder) and trauma-related disorders. Furthermore, VR has become established as a research tool. The rapid technological development gives reason to expect a continuing increase in VR research, in clinical as well as basic research.
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http://dx.doi.org/10.1007/s00115-019-0678-6DOI Listing
July 2019

Electroconvulsive therapy induced gray matter increase is not necessarily correlated with clinical data in depressed patients.

Brain Stimul 2019 Mar - Apr;12(2):335-343. Epub 2018 Dec 4.

Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany.

Background: Electroconvulsive therapy (ECT) and depression have been associated with brain volume changes, especially in the hippocampus and the amygdala.

Methods: In this retrospective study we collected data from individual pre-post ECT whole brain magnetic resonance imaging scans of depressed patients from six German university hospitals. Gray matter volume (GMV) changes were quantified via voxel-based morphometry in a total sample of 92 patients with major depressive episodes (MDE). Additionally, 43 healthy controls were scanned twice within a similar time interval.

Results: Most prominently longitudinal GMV increases occurred in temporal lobe regions. Within specific region of interests we detected significant increases of GMV in the hippocampus and the amygdala. These results were more pronounced in the right hemisphere. Decreases in GMV were not observed. GMV changes did not correlate with psychopathology, age, gender or number of ECT sessions. We ruled out white matter reductions as a possible indirect cause of the detected GMV increase.

Conclusion: The present findings support the notion of hippocampus and amygdala modulation following an acute ECT series in patients with MDE. These results corroborate the hypothesis that ECT enables primarily unspecific and regionally dependent neuroplasticity effects to the brain.
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http://dx.doi.org/10.1016/j.brs.2018.11.017DOI Listing
June 2019

[Treatment of anxiety disorders].

Authors:
Peter Zwanzger

MMW Fortschr Med 2018 10;160(17):48-54

kbo-Inn-Salzach-Klinikum, Gabersee 7, D-83512, Wasserburg am Inn, Deutschland.

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http://dx.doi.org/10.1007/s15006-018-0025-zDOI Listing
October 2018

[Evaluation of a neuropsychological test battery with psychiatric and psychosomatic patients].

Fortschr Neurol Psychiatr 2018 06 28;86(6):348-355. Epub 2018 Jun 28.

kbo-Inn-Salzach-Klinikum.

Neuropsychological assessment should be an integral component of clinical psychiatric diagnostics. Yet, the commonly used tests have not been investigated adequately for this population so far. The current study evaluated a clinically approved neuropsychological test battery by analyzing data on 226 mentally ill patients using factor and regression analyses. The extraction of three factors (Speed, Memory, and Executive Functions) proved to be adequate as the tests could be allocated properly. Regression analysis revealed an economical basis assessment consisting of three tests (TAP Alertness, VLMT, and Matrices Test). Based on acceptance, economy, and factorial structure aspects, we recommend the investigated test battery for neuropsychological assessment of psychiatric and psychosomatic patients.
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http://dx.doi.org/10.1055/s-0043-119796DOI Listing
June 2018

Violent aggression predicted by multiple pre-adult environmental hits.

Mol Psychiatry 2019 10 24;24(10):1549-1564. Epub 2018 May 24.

Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.

Early exposure to negative environmental impact shapes individual behavior and potentially contributes to any mental disease. We reported previously that accumulated environmental risk markedly decreases age at schizophrenia onset. Follow-up of matched extreme group individuals (≤1 vs. ≥3 risks) unexpectedly revealed that high-risk subjects had >5 times greater probability of forensic hospitalization. In line with longstanding sociological theories, we hypothesized that risk accumulation before adulthood induces violent aggression and criminal conduct, independent of mental illness. We determined in 6 independent cohorts (4 schizophrenia and 2 general population samples) pre-adult risk exposure, comprising urbanicity, migration, physical and sexual abuse as primary, and cannabis or alcohol as secondary hits. All single hits by themselves were marginally associated with higher violent aggression. Most strikingly, however, their accumulation strongly predicted violent aggression (odds ratio 10.5). An epigenome-wide association scan to detect differential methylation of blood-derived DNA of selected extreme group individuals yielded overall negative results. Conversely, determination in peripheral blood mononuclear cells of histone-deacetylase1 mRNA as 'umbrella mediator' of epigenetic processes revealed an increase in the high-risk group, suggesting lasting epigenetic alterations. Together, we provide sound evidence of a disease-independent unfortunate relationship between well-defined pre-adult environmental hits and violent aggression, calling for more efficient prevention.
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http://dx.doi.org/10.1038/s41380-018-0043-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756097PMC
October 2019

Modulating Emotion Perception: Opposing Effects of Inhibitory and Excitatory Prefrontal Cortex Stimulation.

Biol Psychiatry Cogn Neurosci Neuroimaging 2018 04 29;3(4):329-336. Epub 2017 Dec 29.

Institute for Biomagnetism and Biosignal Analysis and Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Muenster, Muenster, Germany. Electronic address:

Background: Excitatory repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (dlPFC) is approved by the U.S. Food and Drug Administration for the treatment of adult patients with treatment-resistant major depressive disorder (MDD). This stimulation is supposed to restore excitability of prefrontal cortex regions that exhibit diminished regulation of emotion-generative systems in MDD. Based on the valence lateralization hypothesis, inhibitory rTMS of the right dlPFC has also been applied in MDD. This approach has proved to be effective, although meta-analyses of emotional perception and affective regulation in healthy control subjects and patients with depression do not support functional asymmetries within dlPFC regions.

Methods: To shed more light on this discrepancy, the effects of excitatory and inhibitory rTMS of the right dlPFC on visual emotional perception were compared in two groups of 41 healthy participants overall. Before and after rTMS stimulation, participants viewed fearful and neutral faces while whole-head magnetoencephalography was recorded and supplemented by behavioral tests.

Results: Visual sensory processing of fearful facial expressions, relative to neutral facial expressions, was reduced after excitatory stimulation and was increased after inhibitory stimulation within right occipital and right temporal regions. Correspondingly, after excitatory rTMS compared with inhibitory rTMS, participants displayed relatively reduced reaction times in an emotion discrimination task and showed reduced emotional arousal.

Conclusions: These results support the hypothesis that excitatory rTMS compared with inhibitory rTMS of the right dlPFC strengthens top-down control of aversive stimuli in healthy control subjects, which should encourage more research on mechanisms of excitatory/inhibitory dlPFC-rTMS protocols in general and on neuromodulatory treatment of MDD.
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http://dx.doi.org/10.1016/j.bpsc.2017.12.007DOI Listing
April 2018

Neurobiological and clinical effects of fNIRS-controlled rTMS in patients with panic disorder/agoraphobia during cognitive-behavioural therapy.

Neuroimage Clin 2017 22;16:668-677. Epub 2017 Sep 22.

Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, Albert-Schweitzer-Campus 1, University of Muenster, Muenster, Germany.

Background: A relevant proportion of patients with panic disorder (PD) does not improve even though they receive state of the art treatment for anxiety disorders such as cognitive-behavioural therapy (CBT). At the same time, it is known, that from a neurobiological point of view, PD patients are often characterised by prefrontal hypoactivation. Intermittent Theta Burst Stimulation (iTBS) is a non-invasive type of neurostimulation which can modulate cortical activity and thus has the potential to normalise prefrontal hypoactivity found in PD. We therefore aimed at investigating the effects of iTBS as an innovative add-on to CBT in the treatment for PD.

Methods: In this double-blind, bicentric study, 44 PD patients, randomised to sham or verum stimulation, received 15 sessions of iTBS over the left prefrontal cortex (PFC) in addition to 9 weeks of group CBT. Cortical activity during a cognitive as well as an emotional (Emotional Stroop) paradigm was assessed both at baseline and post-iTBS treatment using functional near-infrared spectroscopy (fNIRS) and compared to healthy controls.

Results: In this manuscript we only report the results of the emotional paradigm; for the results of the cognitive paradigm please refer to Deppermann et al. (2014). During the Emotional Stroop test, PD patients showed significantly reduced activation to panic-related compared to neutral stimuli for the left PFC at baseline. Bilateral prefrontal activation for panic-related stimuli significantly increased after verum iTBS only. Clinical ratings significantly improved during CBT and remained stable at follow-up. However, no clinical differences between the verum- and sham-stimulated group were identified, except for a more stable reduction of agoraphobic avoidance during follow-up in the verum iTBS group.

Limitations: Limitations include insufficient blinding, the missing control for possible state-dependent iTBS effects, and the timing of iTBS application during CBT.

Conclusion: Prefrontal hypoactivity in PD patients was normalised by add-on iTBS. Clinical improvement of anxiety symptoms was not affected by iTBS.
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http://dx.doi.org/10.1016/j.nicl.2017.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5650598PMC
June 2018

Prefrontal brain responsiveness to negative stimuli distinguishes familial risk for major depression from acute disorder.

J Psychiatry Neurosci 2017 Sep;42(5):343-352

From the Department of Psychiatry, University of Münster, Münster, Germany (Opel, Redlich, Grotegerd, Dohm, Zaremba, Meinert, Bürger, Plümpe, Alferink, Arolt, Dannlowski); the Cluster of Excellence EXC 1003, Cells in Motion, University of Münster, Münster, Germany (Alferink); the Department of Clinical Radiology, University of Münster, Münster, Germany (Heindel, Kugel); the kbo-Inn-Salzach-Klinikum, Wasserburg am Inn, Germany (Zwanzger); the Department of Psychiatry, Ludwig-Maximilian-University, Munich, Germany (Zwanzger); and the Department of Psychiatry, University of Marburg, Marburg, Germany (Dannlowski).

Background: Identifying reliable trait markers of familial risk for major depressive disorder (MDD) is a challenge in translational psychiatric research. In individuals with acute MDD, dysfunctional connectivity patterns of prefrontal areas have been shown repeatedly. However, it has been unclear in which neuronal networks functional alterations in individuals at familial risk for MDD might be present and to what extent they resemble findings previously reported in those with acute MDD.

Methods: We investigated differences in blood oxygen level-dependent (BOLD) response of the medial orbitofrontal cortex (OFC) and dorsolateral prefrontal cortex (DLPFC) to aversive stimuli between acute MDD and familial risk for the disorder in healthy first-degree relatives of acutely depressed patients with MDD (HC-FH+), healthy age- and sex-matched controls without any family history of depression (HC-FH-), and acutely depressed patients with MDD with (MDD-FH+) and without a family history of depression (MDD-FH-) during a frequently used emotional face-matching paradigm. Analyses of task-specific network connectivity were conducted in terms of psychophysiological interactions (PPI).

Results: The present analysis included a total of 100 participants: 25 HC-FH+, 25 HC-FH-, 25 MDD-FH+ and 25 MDD-FH-. Patients with MDD exhibited significantly increased activation in the medial OFC to negative stimuli irrespective of familial risk status, whereas healthy participants at familial risk and patients with MDD alike showed significant hypoactivation in the DLPFC compared with healthy participants without familial risk. The PPI analyses revealed significantly enhanced task-specific coupling between the medial OFC and differing cortical areas in individuals with acute MDD and those with familial risk for the disorder.

Limitations: The main limitation of our study is its cross-sectional design.

Conclusion: Whereas hypoactivation during negative emotion processing in the DLPFC appears as a common feature in both healthy high-risk individuals and acutely depressed patients, activation patterns of the medial OFC and its underlying connectivity seem to distinguish familial risk from acute disorder.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573576PMC
http://dx.doi.org/10.1503/jpn.160198DOI Listing
September 2017

Commonalities and differences in the neural substrates of threat predictability in panic disorder and specific phobia.

Neuroimage Clin 2017 20;14:530-537. Epub 2017 Feb 20.

Institute for Biogmagnetism and Biosignalanalysis, University of Muenster, Germany.

Different degrees of threat predictability are thought to induce either phasic fear or sustained anxiety. Maladaptive, sustained anxious apprehension is thought to result in overgeneralization of anxiety and thereby to contribute to the development of anxiety disorders. Therefore, differences in threat predictability have been associated with pathological states of anxiety with specific phobia (SP) representing phasic fear as heightened response to predictable threat, while panic disorder (PD) is characterized by sustained anxiety (unpredictable threat) and, as a consequence, overgeneralization of fear. The present study aimed to delineate commonalities and differences in the neural substrates of the impact of threat predictability on affective processing in these two anxiety disorders. Twenty PD patients, 20 SP patients and 20 non-anxious control subjects were investigated with an adapted NPU-design (no, predictable, unpredictable threat) using whole-head magnetoencephalography (MEG). Group independent neural activity in the right dlPFC increased with decreasing threat predictability. PD patients showed a sustained hyperactivation of the vmPFC under threat and safety conditions. The magnitude of hyperactivation was inversely correlated with PDs subjective arousal and anxiety sensitivity. Both PD and SP patients revealed decreased parietal processing of affective stimuli. Findings indicate overgeneralization between threat and safety conditions and increased need for emotion regulation via the vmPFC in PD, but not SP patients. Both anxiety disorders showed decreased activation in parietal networks possibly indicating attentional avoidance of affective stimuli. Present results complement findings from fear conditioning studies and underline overgeneralization of fear, particularly in PD.
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http://dx.doi.org/10.1016/j.nicl.2017.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345973PMC
November 2017

Prefrontal transcranial direct current stimulation (tDCS) as treatment for major depression: study design and methodology of a multicenter triple blind randomized placebo controlled trial (DepressionDC).

Eur Arch Psychiatry Clin Neurosci 2017 Dec 28;267(8):751-766. Epub 2017 Feb 28.

Department of Psychiatry and Psychotherapy, Charité-Campus Benjamin Franklin, Berlin, Germany.

Transcranial direct current stimulation (tDCS) has been proposed as novel treatment for major depressive disorder (MDD) based on clinical pilot studies as well as randomized controlled monocentric trials. The DepressionDC trial is a triple-blind (blinding of rater, operator and patient), randomized, placebo controlled multicenter trial investigating the efficacy and safety of prefrontal tDCS used as additive treatment in MDD patients who have not responded to selective serotonin reuptake inhibitors (SSRI). At 5 study sites, 152 patients with MDD receive a 6-weeks treatment with active tDCS (anode F3 and cathode F4, 2 mA intensity, 30 min/day) or sham tDCS add-on to a stable antidepressant medication with an SSRI. Follow-up visits are at 3 and 6 months after the last tDCS session. The primary outcome measure is the change of the Montgomery-Asberg Depression Rating Scale (MADRS) scores at week 6 post-randomisation compared to baseline. Secondary endpoints also cover other psychopathological domains, and a comprehensive safety assessment includes measures of cognition. Patients undergo optional investigations comprising genetic testing and functional magnetic resonance imaging (fMRI) of structural and functional connectivity. The study uses also an advanced tDCS technology including standard electrode positioning and recording of technical parameters (current, impedance, voltage) in every tDCS session. Aside reporting the study protocol here, we present a novel approach for monitoring technical parameters of tDCS which will allow quality control of stimulation and further analysis of the interaction between technical parameters and clinical outcome. The DepressionDC trial will hopefully answer the important clinical question whether prefrontal tDCS is a safe and effective antidepressant intervention in patients who have not sufficiently responded to SSRIs.

Trial Registry: ClinicalTrials.gov Identifier NCT0253016.
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http://dx.doi.org/10.1007/s00406-017-0769-yDOI Listing
December 2017

CRHR1 promoter hypomethylation: An epigenetic readout of panic disorder?

Eur Neuropsychopharmacol 2017 04 21;27(4):360-371. Epub 2017 Feb 21.

Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany; Department of Psychiatry, University of Freiburg, Freiburg, Germany. Electronic address:

The corticotropin releasing hormone receptor 1 (CRHR1) is crucially involved in the hypothalamic-pituitary-adrenal axis and thus a major regulator of the stress response. CRHR1 gene variation is associated with several mental disorders including anxiety disorders. Studies in rodents have demonstrated epigenetic regulation of CRHR1 gene expression to moderate response to stressful environment. In the present study, we investigated CRHR1 promoter methylation for the first time regarding its role in panic disorder applying a case-control approach (N=131 patients, N=131 controls). In an independent sample of healthy volunteers (N=255), CRHR1 methylation was additionally analyzed for association with the Beck Anxiety Inventory (BAI) score as a dimensional panic-related intermediate phenotype. The functional relevance of altered CRHR1 promoter methylation was investigated by means of luciferase-based reporter gene assays. In panic disorder patients, a significantly decreased CRHR1 methylation was discerned (p<0.001). Accordingly, healthy controls with high BAI scores showed significantly decreased CRHR1 methylation. Functional analyses revealed an increased gene expression in presence of unmethylated as compared to methylated pCpGl_CRHR1 reporter gene vectors. The present study identified a potential role of CRHR1 hypomethylation - conferring increased CRHR1 expression - in panic disorder and a related dimensional intermediate phenotype. This up-regulation of CRHR1 gene expression driven by de-methylation might constitute a link between the stress response and panic disorder risk.
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http://dx.doi.org/10.1016/j.euroneuro.2017.01.005DOI Listing
April 2017

State of Acute Agitation at Psychiatric Emergencies in Europe: The STAGE Study.

Clin Pract Epidemiol Ment Health 2016 27;12:75-86. Epub 2016 Oct 27.

Ferrer International, Barcelona, Spain.

Background: Agitation is an array of syndromes and types of behaviors that are common in patients with psychiatric disorders. In Europe, the estimation of prevalence of agitation has been difficult due to the lack of standard studies or systematic data collection done on this syndrome.

Objective: An observational, cross-sectional, multicenter study aimed to assess the prevalence of agitation episodes in psychiatric emergencies in different European countries.

Method: For 1 week, all episodes of acute agitation that were attended to at the psychiatric emergency room (ER) or Acute Inpatient Unit (AIU) in the 27 participating centers were registered. The clinical characteristics and management of the agitation episode were also described. A descriptive analysis was performed.

Results: A total of 334 agitation episodes out of 7295 psychiatric emergencies were recorded, giving a prevalence rate of 4.6% (95% CI: 4.12-5.08). Of them, 172 [9.4% (95% CI: 8.2-10.9)] were attended at the ER and 162 [2.8% (95% CI: 2.4-3.3)] at AIU. Only data from 165 episodes of agitation (those with a signed informed consent form) was registered and described in this report. The most common psychiatric conditions associated with agitation were schizophrenia, bipolar disorder and personality disorder. The management of agitation included from non-invasive to more coercive measures (mechanical, physical restraint or seclusion) that were unavoidable in more than half of the agitation episodes (59.5%).

Conclusion: The results show that agitation is a common symptom in the clinical practice, both in emergency and inpatient psychiatric departments. Further studies are warranted to better recognize (using a standardized definition) and characterize agitation episodes.
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http://dx.doi.org/10.2174/1745017901612010075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5084082PMC
October 2016

"Torpedo" for the brain: perspectives in neurostimulation.

J Neural Transm (Vienna) 2016 10;123(10):1119-20

Department of Psychiatry and Medical Psychology, Ghent University, Ghent, Belgium.

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http://dx.doi.org/10.1007/s00702-016-1613-7DOI Listing
October 2016

Biological markers for anxiety disorders, OCD and PTSD: A consensus statement. Part II: Neurochemistry, neurophysiology and neurocognition.

World J Biol Psychiatry 2017 04 15;18(3):162-214. Epub 2016 Jul 15.

j Department of Psychiatry Psychosomatics and Psychotherapy , University of Wuerzburg , Wuerzburg , Germany.

Objective: Biomarkers are defined as anatomical, biochemical or physiological traits that are specific to certain disorders or syndromes. The objective of this paper is to summarise the current knowledge of biomarkers for anxiety disorders, obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD).

Methods: Findings in biomarker research were reviewed by a task force of international experts in the field, consisting of members of the World Federation of Societies for Biological Psychiatry Task Force on Biological Markers and of the European College of Neuropsychopharmacology Anxiety Disorders Research Network.

Results: The present article (Part II) summarises findings on potential biomarkers in neurochemistry (neurotransmitters such as serotonin, norepinephrine, dopamine or GABA, neuropeptides such as cholecystokinin, neurokinins, atrial natriuretic peptide, or oxytocin, the HPA axis, neurotrophic factors such as NGF and BDNF, immunology and CO hypersensitivity), neurophysiology (EEG, heart rate variability) and neurocognition. The accompanying paper (Part I) focuses on neuroimaging and genetics.

Conclusions: Although at present, none of the putative biomarkers is sufficient and specific as a diagnostic tool, an abundance of high quality research has accumulated that should improve our understanding of the neurobiological causes of anxiety disorders, OCD and PTSD.
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http://dx.doi.org/10.1080/15622975.2016.1190867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341771PMC
April 2017

Hypermethylation of FOXP3 Promoter and Premature Aging of the Immune System in Female Patients with Panic Disorder?

PLoS One 2016 30;11(6):e0157930. Epub 2016 Jun 30.

Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany.

Immunological abnormalities associated with pathological conditions, such as higher infection rates, inflammatory diseases, cancer or cardiovascular events are common in patients with panic disorder. In the present study, T cell receptor excision circles (TRECs), Forkhead-Box-Protein P3 gene (FOXP3) methylation of regulatory T cells (Tregs) and relative telomere lengths (RTLs) were investigated in a total and subsamples of 131 patients with panic disorder as compared to 131 age- and sex-matched healthy controls in order to test for a potential dysfunction and premature aging of the immune system in anxiety disorders. Significantly lower TRECs (p = 0.004) as well as significant hypermethylation of the FOXP3 promoter region (p = 0.005) were observed in female (but not in male) patients with panic disorder as compared to healthy controls. No difference in relative telomere length was discerned between patients and controls, but significantly shorter telomeres in females, smokers and older persons within the patient group. The presently observed reduced TRECs in panic disorder patients and FOXP3 hypermethylation in female patients with panic disorder potentially reflect impaired thymus and immunosuppressive Treg function, which might partly account for the known increased morbidity and mortality of anxiety disorders conferred by e.g. cancer and cardiovascular disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157930PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928917PMC
July 2017

Healthy individuals maintain adaptive stimulus evaluation under predictable and unpredictable threat.

Neuroimage 2016 Aug 18;136:174-85. Epub 2016 May 18.

Institute for Biomagnetism and Biosignalanalysis, University Hospital Muenster, D-48149 Muenster, Germany; Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Muenster, Muenster, Germany.

The anxiety inducing paradigms such as the threat-of-shock paradigm have provided ample data on the emotional processing of predictable and unpredictable threat, but little is known about the processing of aversive, threat-irrelevant stimuli in these paradigms. We investigated how the predictability of threat influences the neural visual processing of threat-irrelevant fearful and neutral faces. Thirty-two healthy individuals participated in an NPU-threat test, consisting of a safe or neutral condition (N) and a predictable (P) as well as an unpredictable (U) threat condition, using audio-visual threat stimuli. In all NPU-conditions, we registered participants' brain responses to threat-irrelevant faces via magnetoencephalography. The data showed that increasing unpredictability of threat evoked increasing emotion regulation during face processing predominantly in dorsolateral prefrontal cortex regions during an early to mid-latency time interval. Importantly, we obtained only main effects but no significant interaction of facial expression and conditions of different threat predictability, neither in behavioral nor in neural data. Healthy individuals with average trait anxiety are thus able to maintain adaptive stimulus evaluation processes under predictable and unpredictable threat conditions.
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http://dx.doi.org/10.1016/j.neuroimage.2016.05.041DOI Listing
August 2016

Emotional processing and rTMS: does inhibitory theta burst stimulation affect the human startle reflex?

J Neural Transm (Vienna) 2016 10 13;123(10):1121-31. Epub 2016 May 13.

Department of Psychiatry and Psychotherapy, University of Muenster, Albert-Schweitzer-Campus 1, Gebaeude A9, 48149, Muenster, Germany.

Repetitive transcranial magnetic stimulation (rTMS) enables the local and non-invasive modulation of cortical activity and has proved to achieve antidepressant effects. To a lesser extent, rTMS is investigated as a treatment option for anxiety disorders. As the prefrontal cortex and the amygdala represent key components of human emotion regulation, we investigated how prefrontally applied rTMS affects the responsiveness of the subcortical amygdala during a fear-relevant study paradigm to examine potential cortico-limbic effects. Sham-controlled, randomised inhibitory rTMS (continuous theta burst stimulation, TBS) was applied to 102 healthy subjects (female = 54) over the right dorsolateral prefrontal cortex. Subsequently, the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) acoustic startle response was investigated. Subjective anxiety ratings (anxiety sensitivity, trait and state anxiety) were considered. Picture category affected the startle magnitude as expected for both TBS intervention groups (highest startle response for unpleasant, lowest for pleasant pictures). However, no modulatory effects of TBS on startle potentiation were discerned. No significant interaction effects of TBS intervention, subjective anxiety ratings, and gender were identified. Interestingly, startle habituation was influenced by TBS intervention on a trend-level, with verum TBS leading to an accelerated habituation. We found no evidence for the hypothesis that prefrontal inhibitory TBS affects the responsiveness of the amygdala during the presentation of emotionally relevant stimuli in healthy subjects. Instead, we found accelerated habituation under verum TBS on a statistical trend-level. Hence, some preliminary hints for modulatory effects of inhibitory TBS on basic learning mechanisms could be found.
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http://dx.doi.org/10.1007/s00702-016-1568-8DOI Listing
October 2016

Influence of 5-HTT variation, childhood trauma and self-efficacy on anxiety traits: a gene-environment-coping interaction study.

J Neural Transm (Vienna) 2016 08 4;123(8):895-904. Epub 2016 May 4.

Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstrasse 15, 97080, Würzburg, Germany.

Environmental vulnerability factors such as adverse childhood experiences in interaction with genetic risk variants, e.g., the serotonin transporter gene linked polymorphic region (5-HTTLPR), are assumed to play a role in the development of anxiety and affective disorders. However, positive influences such as general self-efficacy (GSE) may exert a compensatory effect on genetic disposition, environmental adversity, and anxiety traits. We, thus, assessed childhood trauma (Childhood Trauma Questionnaire, CTQ) and GSE in 678 adults genotyped for 5-HTTLPR/rs25531 and their interaction on agoraphobic cognitions (Agoraphobic Cognitions Questionnaire, ACQ), social anxiety (Liebowitz Social Anxiety Scale, LSAS), and trait anxiety (State-Trait Anxiety Inventory, STAI-T). The relationship between anxiety traits and childhood trauma was moderated by self-efficacy in 5-HTTLPR/rs25531 LALA genotype carriers: LALA probands maltreated as children showed high anxiety scores when self-efficacy was low, but low anxiety scores in the presence of high self-efficacy despite childhood maltreatment. Our results extend previous findings regarding anxiety-related traits showing an interactive relationship between 5-HTT genotype and adverse childhood experiences by suggesting coping-related measures to function as an additional dimension buffering the effects of a gene-environment risk constellation. Given that anxiety disorders manifest already early in childhood, this insight could contribute to the improvement of psychotherapeutic interventions by including measures strengthening self-efficacy and inform early targeted preventive interventions in at-risk populations, particularly within the crucial time window of childhood and adolescence.
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http://dx.doi.org/10.1007/s00702-016-1564-zDOI Listing
August 2016

Prediction of Individual Response to Electroconvulsive Therapy via Machine Learning on Structural Magnetic Resonance Imaging Data.

JAMA Psychiatry 2016 Jun;73(6):557-64

Department of Psychiatry, University of Muenster, Muenster, Germany5Department of Psychiatry, University of Marburg, Marburg, Germany.

Importance: Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, biomarkers that accurately predict a response to ECT remain unidentified.

Objective: To investigate whether certain factors identified by structural magnetic resonance imaging (MRI) techniques are able to predict ECT response.

Design, Setting, And Participants: In this nonrandomized prospective study, gray matter structure was assessed twice at approximately 6 weeks apart using 3-T MRI and voxel-based morphometry. Patients were recruited through the inpatient service of the Department of Psychiatry, University of Muenster, from March 11, 2010, to March 27, 2015. Two patient groups with acute major depressive disorder were included. One group received an ECT series in addition to antidepressants (n = 24); a comparison sample was treated solely with antidepressants (n = 23). Both groups were compared with a sample of healthy control participants (n = 21).

Main Outcomes And Measures: Binary pattern classification was used to predict ECT response by structural MRI that was performed before treatment. In addition, univariate analysis was conducted to predict reduction of the Hamilton Depression Rating Scale score by pretreatment gray matter volumes and to investigate ECT-related structural changes.

Results: One participant in the ECT sample was excluded from the analysis, leaving 67 participants (27 men and 40 women; mean [SD] age, 43.7 [10.6] years). The binary pattern classification yielded a successful prediction of ECT response, with accuracy rates of 78.3% (18 of 23 patients in the ECT sample) and sensitivity rates of 100% (13 of 13 who responded to ECT). Furthermore, a support vector regression yielded a significant prediction of relative reduction in the Hamilton Depression Rating Scale score. The principal findings of the univariate model indicated a positive association between pretreatment subgenual cingulate volume and individual ECT response (Montreal Neurological Institute [MNI] coordinates x = 8, y = 21, z = -18; Z score, 4.00; P < .001; peak voxel r = 0.73). Furthermore, the analysis of treatment effects revealed a increase in hippocampal volume in the ECT sample (MNI coordinates x = -28, y = -9, z = -18; Z score, 7.81; P < .001) that was missing in the medication-only sample.

Conclusions And Relevance: A relatively small degree of structural impairment in the subgenual cingulate cortex before therapy seems to be associated with successful treatment with ECT. In the future, neuroimaging techniques could prove to be promising tools for predicting the individual therapeutic effectiveness of ECT.
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http://dx.doi.org/10.1001/jamapsychiatry.2016.0316DOI Listing
June 2016

Prepare for scare-Impact of threat predictability on affective visual processing in spider phobia.

Behav Brain Res 2016 07 29;307:84-91. Epub 2016 Mar 29.

Institute for Biogmagnetism and Biosignalanalysis, University of Muenster, Germany. Electronic address:

The visual processing of emotional faces is influenced by individual's level of stress and anxiety. Valence unspecific affective processing is expected to be influenced by predictability of threat. Using a design of phasic fear (predictable threat), sustained anxiety (unpredictable threat) and safety (no threat), we investigated the magnetoencephalographic correlates and temporal dynamics of emotional face processing in a sample of phobic patients. Compared to non-anxious controls, phobic individuals revealed decreased parietal emotional attention processes during affective processing at mid-latency and late processing stages. While control subjects showed increasing parietal processing of the facial stimuli in line with decreasing threat predictability, phobic subjects revealed the opposite pattern. Decreasing threat predictability also led to increasing neural activity in the orbitofrontal and dorsolateral prefrontal cortex at mid-latency stages. Additionally, unpredictability of threat lead to higher subjective discomfort compared to predictability of threat and no threat safety condition. Our findings indicate that visual processing of emotional information is influenced by both stress induction and pathologic anxiety.
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http://dx.doi.org/10.1016/j.bbr.2016.03.045DOI Listing
July 2016

Impact of electroconvulsive therapy on magnetoencephalographic correlates of dysfunctional emotional processing in major depression.

Eur Neuropsychopharmacol 2016 Apr 8;26(4):684-92. Epub 2016 Feb 8.

Institute for Biogmagnetism and Biosignal Analysis, University of Münster, Germany; Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Münster, D-48151 Münster, Germany. Electronic address:

In major depressive disorder (MDD), electrophysiological and imaging studies provide evidence for a reduced neural activity in parietal and dorsolateral prefrontal regions. In the present study, neural correlates and temporal dynamics of visual affective perception have been investigated in patients with unipolar depression in a pre/post treatment design using magnetoencephalography (MEG). Nineteen in-patients and 19 balanced healthy controls passed MEG measurement while passively viewing pleasant, unpleasant and neutral pictures. After a 4-week treatment with electroconvulsive therapy or 4-week waiting period without intervention respectively, 16 of these patients and their 16 corresponding controls participated in a second MEG measurement. Before treatment neural source estimations of magnetic fields evoked by the emotional scenes revealed a general bilateral parietal hypoactivation in depressed patients compared to controls predominately at early and mid-latency time intervals. Successful ECT treatment, as reflected by a decline in clinical scores (Hamilton Depression Scale; HAMD) led to a normalization of this distinct parietal hypoactivation. Effective treatment was also accompanied by relatively increased neural activation at right temporo-parietal regions. The present study indicates dysfunctional parietal information processing and attention processes towards emotional stimuli in MDD patients which can be returned to normal by ECT treatment. Since convergent neural hypoactivations and treatment effects have recently been shown in MDD patients before and after pharmacological therapy, this electrophysiological correlate might serve as a biomarker for objective treatment evaluation and thereby potentially advance treatment options and support the prediction of individual treatment responses.
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http://dx.doi.org/10.1016/j.euroneuro.2016.02.005DOI Listing
April 2016