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Sonstige beteiligte Institutionen
Fractal phenomena can be found in numerous scientific areas including neuroscience. Fractals are structures, in which the whole has the same shape as its parts. A specific structure known as pink noise (also called fractal or 1/f noise) is one key fractal manifestation, exhibits both stability and adaptability, and can be addressed via the Hurst exponent (H). FMRI studies using H on regional fMRI time courses used fractality as an important characteristic to unravel neural networks from artificial noise. In this fMRI-study, we examined 103 healthy male students at rest and while performing the 5-choice serial reaction time task. We addressed fractality in a network associated with waiting impulsivity using the adaptive fractal analysis (AFA) approach to determine H. We revealed the fractal nature of the impulsivity network. Furthermore, fractality was influenced by individual impulsivity in terms of decreasing fractality with higher impulsivity in regions of top-down control (left middle frontal gyrus) as well as reward processing (nucleus accumbens and anterior cingulate cortex). We conclude that fractality as determined via H is a promising marker to quantify deviations in network functions at an early stage and, thus, to be able to inform preventive interventions before the manifestation of a disorder.
Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated.
Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e. g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (-174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = -10, z = -15; F(2,286) = 8.54, p(uncorrected) = 0.0002; p(AlphaSim-corrected) = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses.
Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.
Background:
In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation.
Methods:
Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale.
Results:
Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy.
Conclusions:
The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.
Background:
In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation.
Methods:
Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale.
Results:
Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy.
Conclusions:
The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.
Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.
Anxious depression represents a subtype of major depressive disorder and is associated with increased suicidality, severity, chronicity and lower treatment response. Only a few studies have investigated the differences between anxious depressed (aMDD) and non-anxious depressed (naMDD) patients regarding treatment dosage, serum-concentration and drug-specific treatment response. In our naturalistic and prospective study, we investigated whether the effectiveness of therapy including antidepressants (SSRI, SNRI, NaSSA, tricyclics and combinations) in aMDD patients differs significantly from that in naMDD patients. In a sample of 346 patients, we calculated the anxiety somatization factor (ASF) and defined treatment response as a reduction (≥50%) in the Hamilton Depression Rating Scale (HDRS)-21 score after 7 weeks of pharmacological treatment. We did not observe an association between therapy response and the baseline ASF-scores, or differences in therapy outcomes between aMDD and naMDD patients. However, non-responders had higher ASF-scores, and at week 7 aMDD patients displayed a worse therapy outcome than naMDD patients. In subgroup analyses for different antidepressant drugs, venlafaxine-treated aMDD patients showed a significantly worse outcome at week 7. Future prospective, randomized-controlled studies should address the question of a worse therapy outcome in aMDD patients for different psychopharmaceuticals individually.
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 (N = 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.
Background: Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment.
Methods: We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples.
Results: In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (\(P_{corr}\) = .018, \(P_{corr}\) = .015 and \(P_{corr}\) = .004, respectively). We observed an across-gene BDNF-NTRK2 SNP interaction for rs4923468 and rs1387926. No robust interaction of associated SNPs was found in an analysis of BDNF serum protein levels as a predictor for treatment outcome in a subset of 93 patients.
Conclusions/Limitations: Although not all associations in the discovery analysis could be unambiguously replicated, the findings of the present study identified single nucleotide variations in the BDNF and NTRK2 genes that might be involved in antidepressant treatment outcome and that have not been previously reported in this context. These new variants need further validation in future association studies.
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.
The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.