Publications by authors named "Paul Pauli"

234 Publications

A Common Variant Is Associated with Low Agreeableness and Neural Responses to Working Memory Tasks in ADHD.

Genes (Basel) 2021 Aug 29;12(9). Epub 2021 Aug 29.

Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, 97080 Würzburg, Germany.

The cell-cell signaling gene is associated with a wide spectrum of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), autism, and major depression. regulates axonal outgrowth and synapse formation, substantiating its relevance for neurodevelopmental processes. Several studies support the influence of on personality traits, behavior, and executive functions. However, evidence for functional effects of common gene variation in the gene in humans is sparse. Therefore, we tested for association of a functional intronic SNP rs2199430 with ADHD in a sample of 998 adult patients and 884 healthy controls. The Big Five personality traits were assessed by the NEO-PI-R questionnaire. Assuming that altered neural correlates of working memory and cognitive response inhibition show genotype-dependent alterations, task performance and electroencephalographic event-related potentials were measured by n-back and continuous performance (Go/NoGo) tasks. The rs2199430 genotype was not associated with adult ADHD on the categorical diagnosis level. However, rs2199430 was significantly associated with agreeableness, with minor G allele homozygotes scoring lower than A allele carriers. Whereas task performance was not affected by genotype, a significant heterosis effect limited to the ADHD group was identified for the n-back task. Heterozygotes (AG) exhibited significantly higher N200 amplitudes during both the 1-back and 2-back condition in the central electrode position Cz. Consequently, the common genetic variation of is associated with personality traits and impacts neural processing during working memory tasks. Thus, might contribute to symptomatic core dysfunctions of social and cognitive impairment in ADHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12091356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471784PMC
August 2021

Social cognitive factors outweigh negative emotionality in predicting COVID-19 related safety behaviors.

Prev Med Rep 2021 Dec 16;24:101559. Epub 2021 Sep 16.

Department of Psychology, University of Würzburg, Germany.

Emotion-motivation models propose that behaviors, including health behaviors, should be predicted by the same variables that also predict negative affect since emotional reactions should induce a motivation to avoid threatening situations. In contrast, social cognitive models propose that safety behaviors are predicted by a different set of variables that mainly reflect cognitive and socio-structural aspects. Here, we directly tested these opposing hypotheses in young adults ( = 4134) in the context of COVID-19-related safety behaviors to prevent infections. In each participant, we collected measures of negative affect as well as cognitive and socio-structural variables during the lockdown in the first infection wave in Germany. We found a negative effect of the pandemic on emotional responses. However, this was not the main predictor for young adults' willingness to comply with COVID-19-related safety measures. Instead, individual differences in compliance were mainly predicted by cognitive and socio-structural variables. These results were confirmed in an independent data set. This study shows that individuals scoring high on negative affect during the pandemic are not necessarily more likely to comply with safety regulations. Instead, political measures should focus on cognitive interventions and the societal relevance of the health issue. These findings provide important insights into the basis of health-related concerns and feelings as well as behavioral adaptations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pmedr.2021.101559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450590PMC
December 2021

Impaired psychological well-being of healthcare workers in a German department of anesthesiology is independent of immediate SARS-CoV-2 exposure - a longitudinal observational study.

Ger Med Sci 2021 1;19:Doc11. Epub 2021 Sep 1.

Department of Anesthesiology, Würzburg University Hospital, Würzburg, Germany.

The study aimed to assess the mental well-being of healthcare professionals at a German department of anesthesiology and critical care with a specialized ICU for treatment of COVID-19 patients during the first two peaks of the 2020 pandemic, and identifying risk and protective factors. A single-center longitudinal, online-based survey was conducted in healthcare workers from a department of anesthesiology and critical care in Bavaria, the most affected federal state in Germany at the time of assessment. Validated scores for depression, anxiety, somatic disorders, burnout, resilience, and self-management were used and complemented by questions about perceived COVID-19-related stressors. In parallel, patient characteristics in the ICU were collected. 24 and 23 critically ill COVID-19 patients were treated during both observation periods in April/May and November/December 2020, respectively. 87.5% and 78.2% of patients had moderate to severe acute respiratory distress syndrome. From March 6, 2020 onwards, the hospital had switched to a command and control-based hospital incident command system (HICS) and increased work forces. Point prevalence of depression-like symptoms (13.6% and 12.8%) and burnout (21.6% and 17.4%) in the department's healthcare professionals was high. Exposure to SARS-CoV-2 did not increase psychological burden. Consequences of the lockdown were rated as highly distressing by a majority of all ICU personnel. High self-reported trait resilience was protective against signs of depression, generalized anxiety, and burnout. During the pandemic, healthcare professionals have been suffering from increased psychological distress compared to reference data for both the general population and ICU personnel. General effects of the lockdown appear more relevant than actual COVID-19 patient contact. High trait resilience has a protective effect, yet vulnerable individuals may require specific support. Prevention against potential after effects of the lockdown, and in particular measures allowing to avoid another lockdown, appear warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3205/000298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422798PMC
September 2021

Observing physicians acting with different levels of empathy modulates later assessed pain tolerance.

Br J Health Psychol 2021 Aug 10. Epub 2021 Aug 10.

Department of Psychology I, Biological Psychology, Clinical Psychology and Psychotherapy, University of Würzburg, Germany.

Objectives: The patient-physician relationship is essential for treatment success. Previous studies demonstrated that physicians who behave empathic in their interaction with patients have a positive effect on health outcomes. In this study, we investigated if the mere perception of physicians as empathic/not empathic modulates pain despite an emotionally neutral interaction with the patients.

Methods: N = 60 women took part in an experimental study that simulated a clinical interaction. In the paradigm, each participant watched two immersive 360° videos via a head-mounted display from a patient's perspective. The physicians in the videos behaved either empathic or not empathic towards a third person. Importantly, these physicians remained emotionally neutral in the subsequent virtual interaction with the participants. Finally, participants received a controlled, painful pressure stimulus within the narratives of the videos.

Results: The physicians in the high compared with the low empathy videos were rated as more empathic and more likable, indicating successful experimental manipulation. In spite of later neutral behaviour of physicians, this short observation of physicians' behaviour towards a third person was sufficient to modulate pain tolerance of the participants.

Conclusions: The finding of this study that the mere observation of physicians' behaviour towards a third person modulates pain, despite a neutral direct interaction with the participants, has important clinical implications. Further, the proposed paradigm enables investigating aspects of patient-physician communication that are difficult to examine in a clinical setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjhp.12553DOI Listing
August 2021

Associative learning shapes visual discrimination in a web-based classical conditioning task.

Sci Rep 2021 08 3;11(1):15762. Epub 2021 Aug 3.

Department of Psychology, Education, and Child Studies, Erasmus University Rotterdam, Rotterdam, The Netherlands.

Threat detection plays a vital role in adapting behavior to changing environments. A fundamental function to improve threat detection is learning to differentiate between stimuli predicting danger and safety. Accordingly, aversive learning should lead to enhanced sensory discrimination of danger and safety cues. However, studies investigating the psychophysics of visual and auditory perception after aversive learning show divergent findings, and both enhanced and impaired discrimination after aversive learning have been reported. Therefore, the aim of this web-based study is to examine the impact of aversive learning on a continuous measure of visual discrimination. To this end, 205 participants underwent a differential fear conditioning paradigm before and after completing a visual discrimination task using differently oriented grating stimuli. Participants saw either unpleasant or neutral pictures as unconditioned stimuli (US). Results demonstrated sharpened visual discrimination for the US-associated stimulus (CS+), but not for the unpaired conditioned stimuli (CS-). Importantly, this finding was irrespective of the US's valence. These findings suggest that associative learning results in increased stimulus salience, which facilitates perceptual discrimination in order to prioritize attentional deployment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-95200-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333260PMC
August 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/da.23204DOI Listing
July 2021

Reducing Generalization of Conditioned Fear: Beneficial Impact of Fear Relevance and Feedback in Discrimination Training.

Front Psychol 2021 1;12:665711. Epub 2021 Jun 1.

Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), Center of Mental Health, University of Würzburg, Würzburg, Germany.

Anxiety patients over-generalize fear, possibly because of an incapacity to discriminate threat and safety signals. Discrimination trainings are promising approaches for reducing such fear over-generalization. Here we investigated the efficacy of a fear-relevant vs. a fear-irrelevant discrimination training on fear generalization and whether the effects are increased with feedback during training. Eighty participants underwent two fear acquisition blocks, during which one face (conditioned stimulus, CS+), but not another face (CS-), was associated with a female scream (unconditioned stimulus, US). During two generalization blocks, both CSs plus four morphs (generalization stimuli, GS1-GS4) were presented. Between these generalization blocks, half of the participants underwent a fear-relevant discrimination training (discrimination between CS+ and the other faces) with or without feedback and the other half a fear-irrelevant discrimination training (discrimination between the width of lines) with or without feedback. US expectancy, arousal, valence ratings, and skin conductance responses (SCR) indicated successful fear acquisition. Importantly, fear-relevant vs. fear-irrelevant discrimination trainings and feedback vs. no feedback reduced generalization as reflected in US expectancy ratings independently from one another. No effects of training condition were found for arousal and valence ratings or SCR. In summary, this is a first indication that fear-relevant discrimination training and feedback can improve the discrimination between threat and safety signals in healthy individuals, at least for learning-related evaluations, but not evaluations of valence or (physiological) arousal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2021.665711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203828PMC
June 2021

Fear conditioning and stimulus generalization in association with age in children and adolescents.

Eur Child Adolesc Psychiatry 2021 May 13. Epub 2021 May 13.

Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.

The aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8-17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS-) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS-): four generalization stimuli depicting gradual morphs from CS+ to CS- in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS-, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00787-021-01797-4DOI Listing
May 2021

Immersive virtual reality during gait rehabilitation increases walking speed and motivation: a usability evaluation with healthy participants and patients with multiple sclerosis and stroke.

J Neuroeng Rehabil 2021 04 22;18(1):68. Epub 2021 Apr 22.

Department of Psychology I, Biological Psychology, Clinical Psychology And Psychotherapy, University of Würzburg, Marcusstraße 9-11, 97070, Würzburg, Germany.

Background: The rehabilitation of gait disorders in patients with multiple sclerosis (MS) and stroke is often based on conventional treadmill training. Virtual reality (VR)-based treadmill training can increase motivation and improve therapy outcomes. The present study evaluated an immersive virtual reality application (using a head-mounted display, HMD) for gait rehabilitation with patients to (1) demonstrate its feasibility and acceptance and to (2) compare its short-term effects to a semi-immersive presentation (using a monitor) and a conventional treadmill training without VR to assess the usability of both systems and estimate the effects on walking speed and motivation.

Methods: In a within-subjects study design, 36 healthy participants and 14 persons with MS or stroke participated in each of the three experimental conditions (VR via HMD, VR via monitor, treadmill training without VR).

Results: For both groups, the walking speed in the HMD condition was higher than in treadmill training without VR and in the monitor condition. Healthy participants reported a higher motivation after the HMD condition as compared with the other conditions. Importantly, no side effects in the sense of simulator sickness occurred and usability ratings were high. No increases in heart rate were observed following the VR conditions. Presence ratings were higher for the HMD condition compared with the monitor condition for both user groups. Most of the healthy study participants (89%) and patients (71%) preferred the HMD-based training among the three conditions and most patients could imagine using it more frequently.

Conclusions: For the first time, the present study evaluated the usability of an immersive VR system for gait rehabilitation in a direct comparison with a semi-immersive system and a conventional training without VR with healthy participants and patients. The study demonstrated the feasibility of combining a treadmill training with immersive VR. Due to its high usability and low side effects, it might be particularly suited for patients to improve training motivation and training outcome e. g. the walking speed compared with treadmill training using no or only semi-immersive VR. Immersive VR systems still require specific technical setup procedures. This should be taken into account for specific clinical use-cases during a cost-benefit assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12984-021-00848-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061882PMC
April 2021

Thigmotaxis in a virtual human open field test.

Sci Rep 2021 03 23;11(1):6670. Epub 2021 Mar 23.

Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.

Animal models are used to study neurobiological mechanisms in mental disorders. Although there has been significant progress in the understanding of neurobiological underpinnings of threat-related behaviors and anxiety, little progress was made with regard to new or improved treatments for mental disorders. A possible reason for this lack of success is the unknown predictive and cross-species translational validity of animal models used in preclinical studies. Re-translational approaches, therefore, seek to establish cross-species translational validity by identifying behavioral operations shared across species. To this end, we implemented a human open field test in virtual reality and measured behavioral indices derived from animal studies in three experiments ([Formula: see text], [Formula: see text], and [Formula: see text]). In addition, we investigated the associations between anxious traits and such behaviors. Results indicated a strong similarity in behavior across species, i.e., participants in our study-like rodents in animal studies-preferred to stay in the outer region of the open field, as indexed by multiple behavioral parameters. However, correlational analyses did not clearly indicate that these behaviors were a function of anxious traits of participants. We conclude that the realized virtual open field test is able to elicit thigmotaxis and thus demonstrates cross-species validity of this aspect of the test. Modulatory effects of anxiety on human open field behavior should be examined further by incorporating possible threats in the virtual scenario and/or by examining participants with higher anxiety levels or anxiety disorder patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85678-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988123PMC
March 2021

Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets.

J Child Psychol Psychiatry 2021 Oct 22;62(10):1202-1219. Epub 2021 Mar 22.

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.

Objective: Some studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here, we performed the largest ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.

Methods: We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.

Results: There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen's d from -0.18 to 0.18) and would not survive study-wide correction for multiple testing.

Conclusion: Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpp.13396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455726PMC
October 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Impaired fear learning and extinction, but not generalization, in anxious and non-anxious depression.

J Psychiatr Res 2021 03 21;135:294-301. Epub 2021 Jan 21.

Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Margarete-Höppel-Platz 1, 97080, Würzburg, Germany; Interdisciplinary Center for Clinical Research, University Hospital of Würzburg, Josef-Schneider-Str. 2, 97080, Würzburg, Germany; Comprehensive Heart Failure Center (CHFC), University Hospital of Würzburg, Am Schwarzenberg 15, 97078, Würzburg, Germany; Medical Park Chiemseeblick, Department of Psychosomatic Medicine and Psychotherapy, Rasthausstr. 25, 83233, Bernau am Chiemsee, Germany.

Fear conditioning and generalization are well-known mechanisms in the pathogenesis of anxiety disorders. Extinction of conditioned fear responses is crucial for the psychotherapeutic treatment of these diseases. Anxious depression as a subtype of major depression shares characteristics with anxiety disorders. We therefore aimed to compare fear learning mechanisms in patients with anxious versus non-anxious depression. Fear learning mechanisms in patients with major depression (n = 79; for subgroup analyses n = 41 patients with anxious depression and n = 38 patients with non-anxious depression) were compared to 48 healthy participants. We used a well-established differential fear conditioning paradigm investigating acquisition, generalization, and extinction. Ratings of valence, arousal and probability of expected threat were assessed as well as skin conductance response as an objective psychophysiological measure. Patients with major depression showed impaired acquisition of conditioned fear. In addition, depressed patients showed impaired extinction of conditioned fear responses after successful fear conditioning. Generalization was not affected. However, there was no difference between patients with anxious and non-anxious depression. Results differed between objective and subjective measures. Our findings show altered fear acquisition and extinction in major depression as compared to healthy controls, but they do not favor differential fear learning and extinction mechanisms in the pathogenesis of anxious versus non-anxious depression. The results of impaired extinction warrant future studies addressing extinction learning elements in the treatment of depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2021.01.034DOI Listing
March 2021

Subsequent memory effects on event-related potentials in associative fear learning.

Soc Cogn Affect Neurosci 2021 05;16(5):525-536

Institute of Psychology (Biological Psychology Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.

Studies of human fear learning suggest that a reliable discrimination between safe and threatening stimuli is important for survival and mental health. In the current study, we applied the subsequent memory paradigm in order to identify neurophysiological correlates of successful threat and safety learning. We recorded event-related potentials, while participants incidentally learned associations between multiple neutral faces and an aversive outcome [unconditioned stimulus (US)/conditioned stimulus (CS)+] or no outcome (noUS/CS-). We found that an enhanced late positive potential (LPP) to both CS+ and CS- during learning predicted subsequent memory. A quadratic relationship between LPP and confidence in memory indicates a possible role in both correct and false fear memory. Importantly, the P300 to the omission of the US (following CS-) was enhanced for remembered CS-, while there was a positive correlation between P300 amplitude to both US occurrence and omission and individual memory performance. A following re-exposure phase indicated that memory was indeed related to subjective fear of the CS+/CS-. These results highlight the importance of cognitive resource allocation to both threat and safety for the acquisition of fear and suggest a potential role of the P300 to US omission as an electrophysiological marker of successful safety learning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/scan/nsab015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094998PMC
May 2021

Relevance of Religiosity for Coping Strategies and Disability in Patients with Fibromyalgia Syndrome.

J Relig Health 2021 Jan 23. Epub 2021 Jan 23.

Department of Neurology, University of Würzburg, Josef-Schneider-Straße 11, 97080, Würzburg, Germany.

Coping strategies are essential for the outcome of chronic pain. This study evaluated religiosity in a cohort of patients with fibromyalgia syndrome (FMS), its effect on pain and other symptoms, on coping and FMS-related disability. A total of 102 FMS patients were recruited who filled in questionnaires, a subgroup of 42 patients participated in a face-to-face interview, and data were evaluated by correlation and regression analyses. Few patients were traditionally religious, but the majority believed in a higher existence and described their spirituality as "transcendence conviction". The coping strategy "praying-hoping" and the ASP dimension "religious orientation" (r = 0.5, P < 0.05) showed a significant relationship independent of the grade of religiosity (P < 0.05). A high grade of belief in a higher existence was negatively associated with the choice of ignoring as coping strategy (r = - 0.4, P < 0.05). Mood and affect-related variables had the highest impact on disability (b = 0.5, P < 0.05). In this cohort, the grade of religiosity played a role in the choice of coping strategies, but had no effects on health and mood outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10943-020-01177-3DOI Listing
January 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euroneuro.2021.01.004DOI Listing
March 2021

Can Religiosity and Social Support Explain Effects of Trait Emotional Intelligence on Health-Related Quality of Life: A Cross-Cultural Study.

J Relig Health 2021 Jan 7. Epub 2021 Jan 7.

Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.

Religion and social support along with trait emotional intelligence (EI) help individuals to reduce stress caused by difficult situations. Their implications may vary across cultures in reference to predicting health-related quality of life (HRQoL). A convenience sample of N = 200 chronic heart failure (CHF) patients was recruited at cardiology centers in Germany (n = 100) and Pakistan (n = 100). Results indicated that trait-EI predicted better mental component of HRQoL in Pakistani and German CHF patients. Friends as social support appeared relevant for German patients only. Qualitative data indicate an internal locus of control in German as compared to Pakistani patients. Strengthening the beneficial role of social support in Pakistani patients is one example of how the current findings may inspire culture-specific treatment to empower patients dealing with the detrimental effects of CHF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10943-020-01163-9DOI Listing
January 2021

Clustering fibromyalgia patients: A combination of psychosocial and somatic factors leads to resilient coping in a subgroup of fibromyalgia patients.

PLoS One 2020 28;15(12):e0243806. Epub 2020 Dec 28.

Department of Neurology, University of Würzburg, Würzburg, Germany.

Background: Coping strategies and their efficacy vary greatly in patients suffering from fibromyalgia syndrome (FMS).

Objective: We aimed to identify somatic and psychosocial factors that might contribute to different coping strategies and resilience levels in FMS.

Subjects And Methods: Standardized questionnaires were used to assess coping, pain, and psychological variables in a cohort of 156 FMS patients. Quantitative real-time polymerase chain reaction (qRT-PCR) determined gene expression of selected cytokines in white blood cells of 136 FMS patients and 25 healthy controls. Data of skin innervation, functional and structural sensory profiles of peripheral nociceptive nerve fibers of a previous study were included into the statistics. An exploratory factor analysis was used to define variance explaining factors, which were then included into cluster analysis.

Results: 54.9% of the variance was explained by four factors which we termed (1) affective load, (2) coping, (3) pain, and (4) pro-inflammatory cytokines (p < 0.05). Considering differences in the emerged factors, coping strategies, cytokine profiles, and disability levels, 118 FMS patients could be categorized into four clusters which we named "maladaptive", "adaptive", "vulnerable", and "resilient" (p < 0.05). The adaptive cluster had low scores in disability and in all symptom categories in contrast to the vulnerable cluster, which was characterized by high scores in catastrophizing and disability (p < 0.05). The resilient vs. the maladaptive cluster was characterized by better coping and a less pro-inflammatory cytokine pattern (p < 0.05).

Conclusion: Our data suggest that problem- and emotion-focused coping strategies and an anti-inflammatory cytokine pattern are associated with reduced disability and might promote resilience. Additional personal factors such as low anxiety scores, ability of acceptance, and persistence further favor a resilient phenotype. Individualized therapy should take these factors into account.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243806PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769259PMC
January 2021

Greater male than female variability in regional brain structure across the lifespan.

Hum Brain Mapp 2020 Oct 12. Epub 2020 Oct 12.

FIDMAG Germanes Hospitalàries Research Foundation, Barcelona, Spain.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25204DOI Listing
October 2020

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

JAMA Psychiatry 2021 Jan;78(1):47-63

Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University, the Netherlands.

Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.

Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.

Design, Setting, And Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.

Main Outcomes And Measures: Interregional profiles of group difference in cortical thickness between cases and controls.

Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.

Conclusions And Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapsychiatry.2020.2694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450410PMC
January 2021

The genetic architecture of human brainstem structures and their involvement in common brain disorders.

Nat Commun 2020 08 11;11(1):4016. Epub 2020 Aug 11.

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.

Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17376-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421944PMC
August 2020

Acceptance-Based Emotion Regulation Reduces Subjective and Physiological Pain Responses.

Front Psychol 2020 30;11:1514. Epub 2020 Jun 30.

Department of Biological Psychology, Clinical Psychology, and Psychotherapy, Institute of Psychology, University of Würzburg, Würzburg, Germany.

Acceptance-based regulation of pain, which focuses on the allowing of pain and pain related thoughts and emotions, was found to modulate pain. However, results so far are inconsistent regarding different pain modalities and indices. Moreover, studies so far often lack a suitable control condition, focus on behavioral pain measures rather than physiological correlates, and often use between-subject designs, which potentially impede the evaluation of the effectiveness of the strategies. Therefore, we investigated whether acceptance-based strategies can reduce subjective and physiological markers of acute pain in comparison to a control condition in a within-subject design. To this end, participants ( = 30) completed 24 trials comprising 10 s of heat pain stimulation. Each trial started with a cue instructing participants to welcome and experience pain (acceptance trials) or to react to the pain as it is without employing any regulation strategies (control trials). In addition to pain intensity and unpleasantness ratings, heart rate (HR) and skin conductance (SC) were recorded. Results showed significantly decreased pain intensity and unpleasantness ratings for acceptance compared to control trials. Additionally, HR was significantly lower during acceptance compared to control trials, whereas SC revealed no significant differences. These results demonstrate the effectiveness of acceptance-based strategies in reducing subjective and physiological pain responses relative to a control condition, even after short training. Therefore, the systematic investigation of acceptance in different pain modalities in healthy and chronic pain patients is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2020.01514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338768PMC
June 2020

Context-dependent generalization of conditioned responses to threat and safety signals.

Int J Psychophysiol 2020 09 17;155:140-151. Epub 2020 Jun 17.

Department of Psychology (Biological Psychology, Clinical Psychology and Psychotherapy), University of Würzburg, Würzburg, Germany; Center for Mental Health, University of Würzburg, Würzburg, Germany.

Contextual information can modulate the conditioned response to a threat signal (conditioned stimulus, CS+): fear responses are either potentiated or attenuated depending on whether the context is threatening or safe. In this study, we investigated the influence of context on conditioned fear as well as on generalization of conditioned fear. Thirty-two participants underwent a cue-in-context learning protocol in virtual reality (VR). On Day 1 (acquisition), participants received a mild painful electric shock (unconditioned stimulus, US) in one virtual room (fear context, CTX+) at the offset of one colored light (CS+), but never at the offset of another colored light (CS-). In a second room (safety context, CTX-), the two lights were also presented, but not the US. Successful cue conditioning was indicated by aversive ratings and startle potentiation but not skin conductance responses (SCR) to CS+ versus CS- in CTX+ and not in CTX-. On Day 2 (generalization), participants re-visited both fear and safety contexts plus a generalization context (G-CTX), which was an equal mix of CTX+ and CTX-. The two CSs were shown again in all three contexts. Generalization of conditioned fear was revealed in affective ratings (CS+ was rated more aversive than CS- in G-CTX), but not in physiological measures (equal startle potentiation to CS+ versus CS- in all contexts). In sum, contextual information modulates the responses to a threat signal such that a safety context can inhibit conditioned fear. Interestingly, generalization processes also depend on contextual information.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijpsycho.2020.06.006DOI Listing
September 2020

Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups.

Am J Psychiatry 2020 09 16;177(9):834-843. Epub 2020 Jun 16.

The full list of authors in the ENIGMA working groups, author affiliations, author disclosures, and acknowledgments are provided in online supplements.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.

Methods: Structural T-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).

Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.

Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1176/appi.ajp.2020.19030331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296070PMC
September 2020

Social aversive generalization learning sharpens the tuning of visuocortical neurons to facial identity cues.

Elife 2020 06 9;9. Epub 2020 Jun 9.

Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Würzburg, Germany.

Defensive system activation promotes heightened perception of threat signals, and excessive attention to threat signals has been discussed as a contributory factor in the etiology of anxiety disorders. However, a mechanistic account of attentional modulation during fear-relevant processes, especially during fear generalization remains elusive. To test the hypothesis that social fear generalization prompts sharpened tuning in the visuocortical representation of social threat cues, 67 healthy participants underwent differential fear conditioning, followed by a generalization test in which participants viewed faces varying in similarity with the threat-associated face. We found that generalization of social threat sharpens visuocortical tuning of social threat cues, whereas ratings of fearfulness showed generalization, linearly decreasing with decreasing similarity to the threat-associated face. Moreover, individuals who reported greater anxiety in social situations also showed heightened sharpened tuning of visuocortical neurons to facial identity cues, indicating the behavioral relevance of visuocortical tuning during generalization learning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.55204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311168PMC
June 2020

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 11 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00702-020-02206-xDOI Listing
November 2020

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Hum Brain Mapp 2020 May 18. Epub 2020 May 18.

Division of Psychological & Social Medicine and Developmental Neurosciences, Faculty of Medicine, Technischen Universität Dresden, Dresden, Germany.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hbm.25029DOI Listing
May 2020

Memory Retrieval-Extinction Combined With Virtual Reality Reducing Drug Craving for Methamphetamine: Study Protocol for a Randomized Controlled Trial.

Front Psychiatry 2020 29;11:322. Epub 2020 Apr 29.

Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.

Background: Relapse, often precipitated by drug-associated cues that evoke craving, is a key problem in the treatment of methamphetamine use disorder (MUD). Drug-associated memories play a major role in the maintenance of relapse. Extinction training is a common method for decreasing drug craving by suppressing drug-associated memories. However, the effects are often not permanent, which is evident in form of spontaneous recovery or renewal of cue-elicited responses. Based on memory reconsolidation theory, the retrieval-extinction (R-E) paradigm may be more effective in decreasing spontaneous recovery or renewal responses than extinction. After the original memory reactivated to a labile state, extinction will be introduced within the reconsolidation window, thereby updating drug-associated memories. However, there are still some controversial results, which suggest that the reactivation of drug-associated memories and the 10 min-6 h of limited time window are two main elements in the R-E protocol. Virtual reality (VR) is supposed to promote memory reactivation by providing vivid drug-related stimuli when compared with movies.

Objective: The aim of this study is to examine the effectiveness of R-E training combined with VR on reducing spontaneous recovery or renewal of cue-elicited responses, in comparison to extinction, R-E training provided outside the time window of 6 h and R-E training retrieved using videos, in methamphetamine abusers.

Methods: The study is a parallel matched controlled study including 95 participants with MUD. Participants will be randomly assigned to either a R-10 min-E group (methamphetamine-related cues retrieval in VR followed by extinction after 10 min) or a NR-10 min-E group (neutral cues retrieval in VR followed by extinction after 10 min) or a R-6 h-E group (methamphetamine-related cues retrieval in VR followed by extinction after 6 h) or a RV-10 min-E group (methamphetamine-related cues retrieval in videos followed by extinction after 10 min). Cue-evoked craving and reactivity will be assessed at pre-test and at 1 day, 1 week, 1 month, and 6-month post-tests.

Discussion: To our knowledge, this study will probably be the first study to examine the efficacy of R-E training combined with VR to reduce cue-evoked responses in people with MUD. This innovative non-pharmacological intervention targeting drug-associated memories may provide significant clinical implications for reducing relapse, providing the study confirms its efficacy.

Clinical Trial Registration: The trial is registered with Chinese Clinical Trial Registry at 17 October 2018, number: ChiCTR1800018899, URL: http://www.chictr.org.cn/showproj.aspx?proj=30854.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2020.00322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202246PMC
April 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1192/bjp.2020.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589989PMC
November 2020
-->