Publications by authors named "Ulrike Lueken"

67 Publications

Behavioral and Magnetoencephalographic Correlates of Fear Generalization are Associated with Responses to Later Virtual Reality Exposure Therapy in Spider Phobia.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Jul 26. Epub 2021 Jul 26.

Institute for Biomagnetism and Biosignalanalysis, University of Münster, Germany.

Background: As overgeneralization of fear is a pathogenic marker of anxiety disorders, we investigated whether pre-treatment levels of fear generalization in spider-phobic patients are related to their response to exposure-based treatment, in order to identify pre-treatment moderators of treatment success.

Methods: Ninety patients with spider phobia completed pre-treatment clinical and magnetoencephalography (MEG) assessments, one session of virtual reality exposure therapy, and a post-treatment clinical assessment. Based on the primary outcome (30% symptom reduction in self-reported symptoms) they were categorized as responders or non-responders. In a pre-treatment MEG fear generalization paradigm involving fear conditioning with two unconditioned stimuli (UCS), we obtained fear ratings, UCS-expectancy ratings, and event-related fields to conditioned stimuli (CS-, CS+) and 7 different generalization stimuli (GS) on a perceptual continuum from CS- to CS+.

Results: Prior to treatment, non-responders showed behavioral overgeneralization indicated by more linear generalization gradients in fear ratings. Analyses of MEG source estimations revealed that non-responders showed a decline of their (inhibitory) frontal activations to safety-signaling CS- and GS compared to CS+ over time, while responders maintained these activations at early (<300ms) and late processing stages.

Conclusions: Results provide initial evidence that pre-treatment differences of behavioral and neural markers of fear generalization may act as moderators of later responses to behavioral exposure. Stimulating further research on fear generalization as a potential predictive marker, our findings are an important first step in the attempt to identify patients who may not profit from ET, and to personalize and optimize treatment strategies for this vulnerable patient group.
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http://dx.doi.org/10.1016/j.bpsc.2021.07.006DOI Listing
July 2021

Clinical predictors of treatment response towards exposure therapy in virtuo in spider phobia: A machine learning and external cross-validation approach.

J Anxiety Disord 2021 Oct 10;83:102448. Epub 2021 Jul 10.

Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

While being highly effective on average, exposure-based treatments are not equally effective in all patients. The a priori identification of patients with a poor prognosis may enable the application of more personalized psychotherapeutic interventions. We aimed at identifying sociodemographic and clinical pre-treatment predictors for treatment response in spider phobia (SP). N = 174 patients with SP underwent a highly standardized virtual reality exposure therapy (VRET) at two independent sites. Analyses on group-level were used to test the efficacy. We applied a state-of-the-art machine learning protocol (Random Forests) to evaluate the predictive utility of clinical and sociodemographic predictors for a priori identification of individual treatment response assessed directly after treatment and at 6-month follow-up. The reliability and generalizability of predictive models was tested via external cross-validation. Our study shows that one session of VRET is highly effective on a group-level and is among the first to reveal long-term stability of this treatment effect. Individual short-term symptom reductions could be predicted above chance, but accuracies dropped to non-significance in our between-site prediction and for predictions of long-term outcomes. With performance metrics hardly exceeding chance level and the lack of generalizability in the employed between-site replication approach, our study suggests limited clinical utility of clinical and sociodemographic predictors. Predictive models including multimodal predictors may be more promising.
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http://dx.doi.org/10.1016/j.janxdis.2021.102448DOI Listing
October 2021

Efficacy of temporally intensified exposure for anxiety disorders: A multicenter randomized clinical trial.

Depress Anxiety 2021 Jul 22. Epub 2021 Jul 22.

Institute of Clinical Psychology & Psychotherapy, Technische Universität Dresden, Dresden, Germany.

Background: The need to optimize exposure treatments for anxiety disorders may be addressed by temporally intensified exposure sessions. Effects on symptom reduction and public health benefits should be examined across different anxiety disorders with comorbid conditions.

Methods: This multicenter randomized controlled trial compared two variants of prediction error-based exposure therapy (PeEx) in various anxiety disorders (both 12 sessions + 2 booster sessions, 100 min/session): temporally intensified exposure (PeEx-I) with exposure sessions condensed to 2 weeks (n = 358) and standard nonintensified exposure (PeEx-S) with weekly exposure sessions (n = 368). Primary outcomes were anxiety symptoms (pre, post, and 6-months follow-up). Secondary outcomes were global severity (across sessions), quality of life, disability days, and comorbid depression.

Results: Both treatments resulted in substantial improvements at post (PeEx-I: d  = 1.50, PeEx-S: d  = 1.78) and follow-up (PeEx-I: d  = 2.34; PeEx-S: d  = 2.03). Both groups showed formally equivalent symptom reduction at post and follow-up. However, time until response during treatment was 32% shorter in PeEx-I (median = 68 days) than PeEx-S (108 days; TR  = 0.68). Interestingly, drop-out rates were lower during intensified exposure. PeEx-I was also superior in reducing disability days and improving quality of life at follow-up without increasing relapse.

Conclusions: Both treatment variants focusing on the transdiagnostic exposure-based violation of threat beliefs were effective in reducing symptom severity and disability in severe anxiety disorders. Temporally intensified exposure resulted in faster treatment response with substantial public health benefits and lower drop-out during the exposure phase, without higher relapse. Clinicians can expect better or at least comparable outcomes when delivering exposure in a temporally intensified manner.
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http://dx.doi.org/10.1002/da.23204DOI Listing
July 2021

Neural processing of emotional facial stimuli in specific phobia: An fMRI study.

Depress Anxiety 2021 08 5;38(8):846-859. Epub 2021 Jul 5.

Institute for Translational Psychiatry, University of Münster, Münster, Germany.

Background: Patients with specific phobia (SP) show altered brain activation when confronted with phobia-specific stimuli. It is unclear whether this pathogenic activation pattern generalizes to other emotional stimuli. This study addresses this question by employing a well-powered sample while implementing an established paradigm using nonspecific aversive facial stimuli.

Methods: N = 111 patients with SP, spider subtype, and N = 111 healthy controls (HCs) performed a supraliminal emotional face-matching paradigm contrasting aversive faces versus shapes in a 3-T magnetic resonance imaging scanner. We performed region of interest (ROI) analyses for the amygdala, the insula, and the anterior cingulate cortex using univariate as well as machine-learning-based multivariate statistics based on this data. Additionally, we investigated functional connectivity by means of psychophysiological interaction (PPI).

Results: Although the presentation of emotional faces showed significant activation in all three ROIs across both groups, no group differences emerged in all ROIs. Across both groups and in the HC > SP contrast, PPI analyses showed significant task-related connectivity of brain areas typically linked to higher-order emotion processing with the amygdala. The machine learning approach based on whole-brain activity patterns could significantly differentiate the groups with 73% balanced accuracy.

Conclusions: Patients suffering from SP are characterized by differences in the connectivity of the amygdala and areas typically linked to emotional processing in response to aversive facial stimuli (inferior parietal cortex, fusiform gyrus, middle cingulate, postcentral cortex, and insula). This might implicate a subtle difference in the processing of nonspecific emotional stimuli and warrants more research furthering our understanding of neurofunctional alteration in patients with SP.
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http://dx.doi.org/10.1002/da.23191DOI Listing
August 2021

Neural adaptation of cingulate and insular activity during delayed fear extinction: A replicable pattern across assessment sites and repeated measurements.

Neuroimage 2021 08 19;237:118157. Epub 2021 May 19.

Department of Psychiatry and Psychotherapy and Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Germany.

Adapting threat-related memories towards changing environments is a fundamental ability of organisms. One central process of fear reduction is suggested to be extinction learning, experimentally modeled by extinction training that is repeated exposure to a previously conditioned stimulus (CS) without providing the expected negative consequence (unconditioned stimulus, US). Although extinction training is well investigated, evidence regarding process-related changes in neural activation over time is still missing. Using optimized delayed extinction training in a multicentric trial we tested whether: 1) extinction training elicited decreasing CS-specific neural activation and subjective ratings, 2) extinguished conditioned fear would return after presentation of the US (reinstatement), and 3) results are comparable across different assessment sites and repeated measures. We included 100 healthy subjects (measured twice, 13-week-interval) from six sites. 24 h after fear acquisition training, extinction training, including a reinstatement test, was applied during fMRI. Alongside, participants had to rate subjective US-expectancy, arousal and valence. In the course of the extinction training, we found decreasing neural activation in the insula and cingulate cortex as well as decreasing US-expectancy, arousal and negative valence towards CS+. Re-exposure to the US after extinction training was associated with a temporary increase in neural activation in the anterior cingulate cortex (exploratory analysis) and changes in US-expectancy and arousal ratings. While ICCs-values were low, findings from small groups suggest highly consistent effects across time-points and sites. Therefore, this delayed extinction fMRI-paradigm provides a solid basis for the investigation of differences in neural fear-related mechanisms as a function of anxiety-pathology and exposure-based treatment.
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http://dx.doi.org/10.1016/j.neuroimage.2021.118157DOI Listing
August 2021

Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis.

Eur Neuropsychopharmacol 2021 Mar 20;44:105-120. Epub 2021 Jan 20.

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany; Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Germany.

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.
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http://dx.doi.org/10.1016/j.euroneuro.2021.01.004DOI Listing
March 2021

Identifying CBT non-response among OCD outpatients: A machine-learning approach.

Psychother Res 2021 01 11;31(1):52-62. Epub 2020 Nov 11.

Faculty of Life Sciences, Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

Machine learning models predicting treatment outcomes for individual patients may yield high clinical utility. However, few studies tested the utility of easy to acquire and low-cost sociodemographic and clinical data. In previous work, we reported significant predictions still insufficient for immediate clinical use in a sample with broad diagnostic spectrum. We here examined whether predictions will improve in a diagnostically more homogeneous yet large and naturalistic obsessive-compulsive disorder (OCD) sample. We used sociodemographic and clinical data routinely acquired during CBT treatment of  = 533 OCD subjects in a specialized outpatient clinic. Remission was predicted with 65% ( = 0.001) balanced accuracy on unseen data for the best model. Higher OCD symptom severity predicted non-remission, while higher age of onset of first OCD symptoms and higher socioeconomic status predicted remission. For dimensional change, prediction achieved  = 0.31 ( = 0.001) between predicted and actual values. The comparison with our previous work suggests that predictions within a diagnostically homogeneous sample, here OCD, are not per se superior to a more diverse sample including several diagnostic groups. Using refined psychological predictors associated with disorder etiology and maintenance or adding further data modalities as neuroimaging or ecological momentary assessments are promising in order to further increase prediction accuracy.
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http://dx.doi.org/10.1080/10503307.2020.1839140DOI Listing
January 2021

Psychological Predictors of Cognitive-Behavioral Therapy Outcomes for Anxiety and Depressive Disorders in Children and Adolescents: A Systematic Review and Meta-Analysis.

J Affect Disord 2021 01 30;278:614-626. Epub 2020 Sep 30.

Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

Background: By understanding specific differences between responders to a treatment and non-responders, treatment modalities may be fitted to the individual in order to increase effectiveness, a concept known as "precision medicine". This systematic review and meta-analysis investigated which pretreatment patient and family characteristics may predict the outcome of cognitive-behavioral therapy (CBT) in clinically anxious and/or depressed youth. In particular, higher symptom severity, more severe co-occurring anxiety or depression and more severe parental psychopathology were hypothesized to predict a worse CBT outcome.

Methods: The databases PubMed, PsycINFO and Cochrane Library were searched; 73 publications were included in the review from which 23 studies were used for the meta-analysis.

Results: Higher symptom severity represented a clinically relevant predictor of a worse CBT outcome, with large effects estimated by meta-analysis. Further, parental psychopathology was significant and detrimental for CBT outcome in anxious but not depressed youth, while the effects for co-occurring anxiety and depression remained unclear. The additional results of the review show that only few characteristics seemed to be clearly associated with a worse CBT outcome, namely worse coping skills and, restricted to depressed patients, more non-suicidal self-injury.

Limitations: The available evidence was of only moderate quality in general, further high-quality research with more transparent reporting is needed.

Conclusions: The patient characteristics identified as being relevant for CBT outcome may represent important candidates for use in single patient prediction models for precision medicine in the field of child and adolescent psychotherapy. The review was preregistered on PROSPERO (ID: CRD42018116881).
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http://dx.doi.org/10.1016/j.jad.2020.09.092DOI Listing
January 2021

The modulating impact of cigarette smoking on brain structure in panic disorder: a voxel-based morphometry study.

Soc Cogn Affect Neurosci 2020 10;15(8):849-859

Department of Psychology, Humboldt-Universität zu Berlin, Berlin 10117, Germany.

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. In total, 143 PD patients (71 smokers) and 178 healthy controls (62 smokers) participated in a multicenter magnetic resonance imaging (MRI) study. T1-weighted images were used to examine brain structural alterations using voxel-based morphometry in a priori defined regions of the defensive system network. PD was associated with gray matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations.
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http://dx.doi.org/10.1093/scan/nsaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543937PMC
October 2020

ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders.

Hum Brain Mapp 2020 Jul 3. Epub 2020 Jul 3.

Department of Psychiatry & Mental Health, University of Cape Town, Cape Town, South Africa.

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.
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http://dx.doi.org/10.1002/hbm.25100DOI Listing
July 2020

Mega-analysis methods in ENIGMA: The experience of the generalized anxiety disorder working group.

Hum Brain Mapp 2020 Jun 29. Epub 2020 Jun 29.

Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.
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http://dx.doi.org/10.1002/hbm.25096DOI Listing
June 2020

Neural correlates of NOS1 ex1f-VNTR allelic variation in panic disorder and agoraphobia during fear conditioning and extinction in fMRI.

Neuroimage Clin 2020 23;27:102268. Epub 2020 Apr 23.

Department of Psychiatry and Psychotherapy & Center for Mind, Brain and Behavior - CMBB, Philipps-Universität Marburg, Marburg, Germany.

Neuronal nitric oxide synthase (NOS-I) impacts on fear/anxiety-like behavior in animals. In humans, the short (S) allele of a functional promotor polymorphism of NOS1 (NOS1 ex1f-VNTR) has been shown to be associated with higher anxiety and altered fear conditioning in healthy subjects in the amygdala and hippocampus (AMY/HIPP). Here, we explore the role of NOS1 ex1f-VNTR as a pathophysiological correlate of panic disorder and agoraphobia (PD/AG). In a sub-sample of a multicenter cognitive behavioral therapy (CBT) randomized controlled trial in patients with PD/AG (n = 48: S/S-genotype n=15, S/L-genotype n=21, L/L-genotype n=12) and healthy control subjects, HS (n = 34: S/S-genotype n=7, S/L-genotype n=17, L/L-genotype=10), a differential fear conditioning and extinction fMRI-paradigm was used to investigate how NOS1 ex1f-VNTR genotypes are associated with differential neural activation in AMY/HIPP. Prior to CBT, L/L-allele carriers showed higher activation than S/S-allele carriers in AMY/HIPP. A genotype × diagnosis interaction revealed that the S-allele in HS was associated with a pronounced deactivation in AMY/HIPP, while patients showed contrary effects. The interaction of genotype × stimulus type (CS+, conditioned stimulus associated with an aversive stimulus vs. CS-, unassociated) showed effects on differential learning in AMY/HIPP. All effects were predominately found during extinction. Genotype associated effects in patients were not altered after CBT. Low statistical power due to small sample size in each subgroup is a major limitation. However, our findings provide first preliminary evidence for dysfunctional neural fear conditioning/extinction associated with NOS1 ex1f-VNTR genotype in the context of PD/AG, shedding new light on the complex interaction between genetic risk, current psychopathology and treatment-related effects.
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http://dx.doi.org/10.1016/j.nicl.2020.102268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200443PMC
March 2021

Correction: Augmenting extinction learning with D-cycloserine reduces return of fear: a randomized, placebo-controlled fMRI study.

Neuropsychopharmacology 2020 06;45(7):1242

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41386-020-0658-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413253PMC
June 2020

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Transl Psychiatry 2020 03 20;10(1):100. Epub 2020 Mar 20.

Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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http://dx.doi.org/10.1038/s41398-020-0705-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083923PMC
March 2020

Predicting cognitive behavioral therapy outcome in the outpatient sector based on clinical routine data: A machine learning approach.

Behav Res Ther 2020 01 16;124:103530. Epub 2019 Dec 16.

Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany; Zentrum für Psychotherapie, Humboldt-Universität zu Berlin, Berlin, Germany. Electronic address:

The availability of large-scale datasets and sophisticated machine learning tools enables developing models that predict treatment outcomes for individual patients. However, few studies used routinely available sociodemographic and clinical data for this task, and many previous investigations used highly selected samples. This study aimed to investigate cognitive behavioral therapy (CBT) outcomes in a large, naturalistic and longitudinal dataset. Routine data from a university-based outpatient center with n = 2.147 patients was analyzed. Only baseline data including sociodemographics, symptom measures and functional impairment ratings was used for prediction. Different competing classification and regression models were compared to each other; the best models were then applied to previously unseen validation data. Applied on the validation set, the best performing classification model for remission achieved a balanced accuracy of 59% (p < 0.001) and the best performing regression model for dimensional change achieved r = 0.27 (p < 0.001). Age, sex, functional impairment, symptom severity, and axis II comorbidity were among the most important features. Predictor performances significantly exceeded chance level but were far from clinical utility. Neither applying more sophisticated approaches nor restricting the sample to homogeneous subgroups resulted in considerable performance gains. Adding hypotheses-based, more specific clinical constructs and deep (e.g. neurobiological) to digital phenotypes may increase prediction performance.
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http://dx.doi.org/10.1016/j.brat.2019.103530DOI Listing
January 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

Effect of CBT on Biased Semantic Network in Panic Disorder: A Multicenter fMRI Study Using Semantic Priming.

Am J Psychiatry 2020 03 16;177(3):254-264. Epub 2019 Dec 16.

Department of Psychiatry and Psychotherapy and Marburg Center for Mind, Brain, and Behavior, Philipps-University Marburg, Marburg, Germany (Yang, Konrad, Straube, Kircher); Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany (Lueken, Herrmann, Deckert); Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany (Lueken); Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany (Richter, Hamm); Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany (Wittmann, Ströhle); Department of Psychiatry, Agaplesion Diakonieklinikum Rotenburg (Wümme), Germany (Konrad); Department of Clinical Radiology, University of Münster, Münster, Germany (Pfleiderer); Christoph-Dornier-Foundation for Clinical Psychology, Bremen, Germany (Lang); Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany (Lang); Functional Imaging Unit, Institute for Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald, Germany (Lotze); Department of Psychiatry, University of Münster, Münster, Germany (Arolt); and Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany (Wittchen).

Objective: Cognitive-behavioral therapy (CBT) has been hypothesized to act by reducing the pathologically enhanced semantic, anxiety-related associations of patients with panic disorder. This study investigated the effects of CBT on the behavioral and neural correlates of the panic-related semantic network in patients with panic disorder.

Methods: An automatic semantic priming paradigm specifically tailored for panic disorder, in which panic symptoms (e.g., "dizziness") were primed by panic triggers (e.g., "elevator") compared with neutral words (e.g., "bottle"), was performed during functional MRI scanning with 118 patients with panic disorder (compared with 150 healthy control subjects) before and 42 patients (compared with 52 healthy control subjects) after an exposure-based CBT. Neural correlates were investigated by comparing 103 pairs of matched patients and control subjects at the baseline (for patients) or T1 (for control subjects) assessment and 39 pairs at the posttreatment or T2 assessment.

Results: At baseline or T1, patients rated panic-trigger/panic-symptom word pairs with higher relatedness and higher negative valence compared with healthy control subjects. Patients made faster lexical decisions to the panic-symptom words when they were preceded by panic-trigger words. This panic-priming effect in patients (compared with control subjects) was reflected in suppressed neural activation in the left and right temporal cortices and insulae and enhanced activation in the posterior and anterior cingulate cortices. After CBT, significant clinical improvements in the patient group were observed along with a reduction in relatedness and negative valence rating and attenuation of neural activation in the anterior cingulate cortex for processing of panic-trigger/panic-symptom word pairs.

Conclusions: The findings support a biased semantic network in panic disorder, which is normalized after CBT. Attenuation of anterior cingulate cortex activation for processing of panic-related associations provides a potential mechanism for future therapeutic interventions.
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http://dx.doi.org/10.1176/appi.ajp.2019.19020202DOI Listing
March 2020

Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.

Neuroimage Clin 2019 21;24:102029. Epub 2019 Oct 21.

Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany.

Introduction: The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network". We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during the anticipation and perception of agoraphobia-specific stimuli.

Method: 121 patients with PD/AG and 77 healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) using the disorder specific "Westphal-Paradigm". It consists of neutral and agoraphobia-specific pictures, half of the pictures were cued to induce anticipatory anxiety.

Results: Risk allele carriers showed significantly higher amygdala activation during the perception of agoraphobia-specific stimuli than A/A homozygotes. A linear group x genotype interaction during the perception of agoraphobia-specific stimuli showed a strong trend towards significance. Patients with the one or two T alleles displayed the highest and HC with the A/A genotype the lowest activation in the inferior orbitofrontal cortex (iOFC).

Discussion: The study demonstrates an association of the NPSR1rs324981 genotype and the perception of agoraphobia-specific stimuli. These results support the assumption of a fronto-limbic dysfunction as an intermediate phenotype of PD/AG.
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http://dx.doi.org/10.1016/j.nicl.2019.102029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854061PMC
September 2020

Augmenting extinction learning with D-cycloserine reduces return of fear: a randomized, placebo-controlled fMRI study.

Neuropsychopharmacology 2020 02 21;45(3):499-506. Epub 2019 Oct 21.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.

D-cycloserine (DCS), a partial NMDA-receptor agonist, seems to be a promising enhancer for exposure therapy in anxiety disorders. It has been tested successfully in animal models of fear extinction, where DCS enhanced extinction learning. Applied in clinical studies, results of DCS-augmented exposure therapy remain ambiguous, calling for a deeper understanding of the underlying mechanisms of DCS and its exact effect on extinction learning and return of fear (ROF) in humans. In the present study, we investigated the effect of DCS-augmented extinction learning on behavioral, psychophysiological, and neural indices of ROF during a 24-h delayed recall test. Thirty-seven participants entered a randomized, placebo-controlled, double-blind, 3-day fear conditioning and delayed extinction fMRI design. One hour before extinction training, participants received an oral dose of 50 mg of DCS or a placebo. Behavioral arousal ratings revealed a generalized ROF during extinction recall in the placebo but not DCS group. Furthermore, participants receiving DCS compared to placebo showed attenuated differential BOLD responses in left posterior hippocampus and amygdala from extinction learning to extinction recall, due to increased hippocampal recruitment in placebo and trendwise decreased amygdala responding in DCS subjects. Our finding that DCS reduces ROF in arousal ratings and neural structures subserving defensive reactions support a role for NMDA receptors in extinction memory consolidation and encourage further translational research.
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http://dx.doi.org/10.1038/s41386-019-0552-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6969173PMC
February 2020

Association of rs7688285 allelic variation coding for GLRB with fear reactivity and exposure-based therapy in patients with panic disorder and agoraphobia.

Eur Neuropsychopharmacol 2019 10 20;29(10):1138-1151. Epub 2019 Aug 20.

Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior (CMBB), University of Marburg and Justus Liebig University Giessen, Germany.

The gene coding for glycine receptor β subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk») in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.
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http://dx.doi.org/10.1016/j.euroneuro.2019.07.133DOI Listing
October 2019

Corrigendum to "Fear Processing in Dental Phobia during Crossmodal Symptom Provocation: An fMRI Study".

Biomed Res Int 2018 6;2018:6497672. Epub 2018 Nov 6.

Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Chemnitzer Straße 46, 01187 Dresden, Germany.

[This corrects the article DOI: 10.1155/2014/196353.].
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http://dx.doi.org/10.1155/2018/6497672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247727PMC
November 2018

The impact of depressive comorbidity on neural plasticity following cognitive-behavioral therapy in panic disorder with agoraphobia.

J Affect Disord 2019 02 4;245:451-460. Epub 2018 Nov 4.

Center of Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital Würzburg, Würzburg, Germany; Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.

Background: Depressive disorders are a frequent comorbidity of panic disorder with agoraphobia (PD/AG). Cognitive-behavioral therapy (CBT) for PD/AG effectively reduces anxiety and depressive symptoms, irrespective of comorbidities. However, as depressive comorbidities can confound fear circuitry activation (i.e. amygdalae, insulae, anterior cingulate cortex) in PD/AG, we investigated whether comorbid depressive disorders alter neural plasticity following CBT.

Methods: Within a randomized, controlled clinical trial on exposure-based CBT, forty-two PD/AG patients including fifteen (35.7%) with a comorbid depressive disorder (PD/AG + DEP) participated in a longitudinal functional magnetic resonance imaging (fMRI) study. A differential fear conditioning task was used as probe of interest. A generalized psycho-physiological interaction analysis (gPPI) served to study functional connectivity patterns.

Results: After CBT, only PD/AG patients without comorbid depressive disorders (PD/AG-DEP) showed reduced activation in the left inferior frontal gyrus (IFG) extending to the insula. While PD/AG-DEP patients showed enhanced functional connectivity (FC) between the left IFG and subcortical structures (anterior cingulate cortex, thalamus and midbrain), PD/AG + DEP patients exhibited increased FC between the left IFG and cortical structures (prefrontal, parietal regions). In both groups, FC decreased following CBT.

Limitations: Primary depressed and medicated patients were excluded. Major depression and dysthymia were collapsed.

Conclusions: Reduced activation in the left IFG, as previously shown in PD/AG, appears to be a specific substrate of CBT effects in PD/AG-DEP patients only. Differential patterns of FC pertaining to fear circuitry networks in patients without depression vs. cognitive networks in patients with comorbid depression may point towards different pathways recruited by CBT as a function of comorbidity.
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http://dx.doi.org/10.1016/j.jad.2018.11.026DOI Listing
February 2019

Translational machine learning for psychiatric neuroimaging.

Prog Neuropsychopharmacol Biol Psychiatry 2019 04 2;91:113-121. Epub 2018 Oct 2.

Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Germany.

Despite its initial promise, neuroimaging has not been widely translated into clinical psychiatry to assist in the prediction of diagnoses, prognoses, and optimal therapeutic strategies. Machine learning approaches may enhance the translational potential of neuroimaging because they specifically focus on overcoming biases by optimizing the generalizability of pipelines that measure complex brain patterns to predict targets at a single-subject level. This article introduces some fundamentals of a translational machine learning approach before selectively reviewing literature to-date. Promising initial results are then balanced by the description of limitations that should be considered in order to interpret existing research and maximize the possibility of future translation. Future directions are then presented in order to inspire further research and progress the field towards clinical translation.
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http://dx.doi.org/10.1016/j.pnpbp.2018.09.014DOI Listing
April 2019

Effects of Cognitive Behavioral Therapy on Neural Processing of Agoraphobia-Specific Stimuli in Panic Disorder and Agoraphobia.

Psychother Psychosom 2018 28;87(6):350-365. Epub 2018 Sep 28.

Department of Psychiatry and Psychotherapy, Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: Patients suffering from panic disorder and agoraphobia are significantly impaired in daily life due to anxiety about getting into a situation due to apprehension about experiencing a panic attack, especially if escape may be difficult. Dysfunctional beliefs and behavior can be changed with cognitive behavioral therapy; however, the neurobiological effects of such an intervention on the anticipation and observation of agoraphobia-specific stimuli are unknown.

Methods: We compared changes in neural activation by measuring the blood oxygen level-dependent signal of 51 patients and 51 healthy controls between scans before and those after treatment (group by time interaction) during anticipation and observation of agoraphobia-specific compared to neutral pictures using 3-T fMRI.

Results: A significant group by time interaction was observed in the ventral striatum during anticipation and in the right amygdala during observation of agoraphobia-specific pictures; the patients displayed a decrease in ventral striatal activation during anticipation from pre- to posttreatment scans, which correlated with clinical improvement measured with the Mobility Inventory. During observation, the patients displayed decreased activation in the amygdala. These activational changes were not observed in the matched healthy controls.

Conclusions: For the first time, neural effects of cognitive behavioral therapy were shown in patients suffering from panic disorder and agoraphobia using disorder-specific stimuli. The decrease in activation in the ventral striatum indicates that cognitive behavioral therapy modifies anticipatory anxiety and may ameliorate abnormally heightened salience attribution to expected threatening stimuli. The decreased amygdala activation in response to agoraphobia-specific stimuli indicates that cognitive behavioral therapy can alter the basal processing of agoraphobia-specific stimuli in a core region of the fear network.
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http://dx.doi.org/10.1159/000493146DOI Listing
December 2018

Psychometric Properties of an Abbreviated Version of the Apathy Evaluation Scale for Parkinson Disease (AES-12PD).

Am J Geriatr Psychiatry 2018 10 30;26(10):1079-1090. Epub 2018 Jun 30.

Institute of Clinical Psychology and Psychotherapy, Department of Psychology, Technische Universität Dresden, Dresden, Germany; Department of Clinical Epidemiology, Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Bremen, Germany.

Background: Apathy is a frequent symptom in Parkinson's disease (PD), substantially aggravating the course of PD. Regarding the accumulating evidence of the key role of apathy in PD, time-efficient assessments are useful for fostering progress in research and treatment. The Apathy Evaluation Scale (AES) is widely used for the assessment of apathy across different nosologies.

Objective: To facilitate the application of the AES in PD, we reduced the AES to two-thirds its length and validated this abbreviated version.

Design: Data sets of 339 PD patients of the DEMPARK/LANDSCAPE study without dementia and depression were randomly split into two samples. Data of sample 1 were used to develop a brief version of the AES (AES-12PD). A cross-validation was conducted in sample 2 and in a subsample of 42 PD patients with comorbid dementia and depressive symptomatology. Receiver operating characteristic analysis was applied to determine the optimal cutoff of the AES-12PD as an indicator of apathy.

Results: The AES-12PD featured high internal consistency that was better compared to the AES. The abbreviated scale was well differentiated from motor impairment and cognitive deficits. The AES-12PD cutoff of 27/28 was the optimal cutoff for apathy in PD patients without dementia and depression. The cutoff of 25/26 indicated apathy in PD patients with comorbid dementia and depression.

Conclusion: Results confirm a high internal consistency and good discriminant validity of the AES-12PD. The AES-12PD represents a reliable tool for the efficient assessment of apathy that can be applied in PD patients with and without dementia and depression.
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http://dx.doi.org/10.1016/j.jagp.2018.06.012DOI Listing
October 2018

Networks of phobic fear: Functional connectivity shifts in two subtypes of specific phobia.

Neurosci Lett 2018 Jan 18;662:167-172. Epub 2017 Oct 18.

Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080 Würzburg, Germany; Neuroimaging Center, Technische Universität Dresden, Chemnitzer Straße 46a, 01187 Dresden, Germany; Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Chemnitzer Straße 46, 01187 Dresden, Germany. Electronic address:

Anxiety disorders can be conceptualized by an abnormal interplay of emotion-processing brain circuits; however, knowledge of brain connectivity measures in specific phobia is still limited. To explore functional interactions within selected fear-circuitry structures (anterior cingulate cortex (ACC), amygdala, insula), we re-examined three task-based fMRI studies using a symptom provocation approach (n=94 subjects in total) on two different phobia subtypes (animal subtype as represented by snake phobia (SP) and blood-injection-injury subtype as represented by dental phobia (DP)), and a non-phobic healthy control group (HC). Functional connectivity (FC) analyses detected a negative coupling between the amygdala and the ACC in HC for both classes of phobic stimuli, while SP and DP lacked this inhibitory relationship during visual stimulus presentation. However, a negative FC between the insula and the amygdala was observed in DP during visual symptom provocation, which reversed to a positive FC under auditory symptom provocation pointing to effects depending on stimulus modality in DP. SP showed significantly higher FC towards snake-anxiety eliciting stimuli than HC on an average measure of FC, while DP showed a similar pattern under auditory stimulation only. These findings altogether indicate FC shifts during symptom provocation in specific phobia possibly reflecting impaired emotion regulation processes within fear-circuitry networks. FC hence could represent a prime target for neuroscience-informed augmentation strategies when treating pathological forms of fear.
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http://dx.doi.org/10.1016/j.neulet.2017.10.031DOI Listing
January 2018

Support Vector Machine Analysis of Functional Magnetic Resonance Imaging of Interoception Does Not Reliably Predict Individual Outcomes of Cognitive Behavioral Therapy in Panic Disorder with Agoraphobia.

Front Psychiatry 2017 9;8:99. Epub 2017 Jun 9.

Department of Clinical Radiology, University Hospital Münster, Münster, Germany.

Background: The approach to apply multivariate pattern analyses based on neuro imaging data for outcome prediction holds out the prospect to improve therapeutic decisions in mental disorders. Patients suffering from panic disorder with agoraphobia (PD/AG) often exhibit an increased perception of bodily sensations. The purpose of this investigation was to assess whether multivariate classification applied to a functional magnetic resonance imaging (fMRI) interoception paradigm can predict individual responses to cognitive behavioral therapy (CBT) in PD/AG.

Methods: This analysis is based on pretreatment fMRI data during an interoceptive challenge from a multicenter trial of the German PANIC-NET. Patients with DSM-IV PD/AG were dichotomized as responders ( = 30) or non-responders ( = 29) based on the primary outcome (Hamilton Anxiety Scale Reduction ≥50%) after 6 weeks of CBT (2 h/week). fMRI parametric maps were used as features for response classification with linear support vector machines (SVM) with or without automated feature selection. Predictive accuracies were assessed using cross validation and permutation testing. The influence of methodological parameters and the predictive ability for specific interoception-related symptom reduction were further evaluated.

Results: SVM did not reach sufficient overall predictive accuracies (38.0-54.2%) for anxiety reduction in the primary outcome. In the exploratory analyses, better accuracies (66.7%) were achieved for predicting interoception-specific symptom relief as an alternative outcome domain. Subtle information regarding this alternative response criterion but not the primary outcome was revealed by univariate comparisons.

Conclusion: In contrast to reports on other neurofunctional probes, SVM based on an interoception paradigm was not able to reliably predict individual response to CBT. Results speak against the clinical applicability of this technique.
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http://dx.doi.org/10.3389/fpsyt.2017.00099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465291PMC
June 2017

Psychometric properties of the apathy evaluation scale in patients with Parkinson's disease.

Int J Methods Psychiatr Res 2017 12 18;26(4). Epub 2017 Apr 18.

Institute of Clinical Psychology and Psychotherapy, Department of Psychology, Technische Universität Dresden, Dresden, Germany.

Parkinson's disease (PD) frequently entails non-motor symptoms, worsening the course of the disease. Apathy is one of the core neuropsychiatric symptoms that has been investigated in recent years; research is however hampered by the limited availability of well-evaluated apathy scales for these patients. We evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a sample of PD patients. Psychometric properties, convergent and discriminant validity and sensitivity/specificity were evaluated in patients with (n = 582) or without dementia/depression (n = 339). Internal consistency was high in the entire sample as well as in patients without dementia/depression. Correlations were moderate for convergent validity (UPDRS I item 4: motivation). While apathy could be differentiated from cognitive decline, it was related to depression (Geriatric Depression Scale, GDS-15). The overall classification accuracy based on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits good psychometric properties in PD patients with and without dementia and/or depression. Commonly used screenings on the presence of apathy had low detection rates compared to the AES and reflected both apathetic and depressive symptoms. Psychometric evaluation of available instruments will support further research on the clinical relevance of apathy for disease progression and treatment approaches in PD patients.
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http://dx.doi.org/10.1002/mpr.1564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6877280PMC
December 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
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